杂环合成（英文版pdf参考资料）：Recent developments in indole ring synthesis—methodology and applications

1
PER
KI
N
REVIEW
DOI,10.1039/a909834h J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1045
This journal is? The Royal Society of Chemistry 2000
Recent developments in indole ring synthesis—methodology and
applications
Gordon W,Gribble
Department of Chemistry,Dartmouth College,Hanover,NH 03755,USA
Received (in Cambridge,UK) 14th December 1999
Covering,1994–1999,Previous review,Contemp,Org,Synth.,1994,1,145.
1 Introduction
2 Sigmatropic rearrangements
2.1 Fischer indole synthesis
2.1.1 Methodology
2.1.2 Applications
2.1.3 Mechanism
2.2 Gassman indole synthesis
2.3 Bartoli indole synthesis
2.4 Thyagarajan indole synthesis
2.5 Julia indole synthesis
2.6 Miscellaneous sigmatropic rearrangements
3 Nucleophilic cyclization
3.1 Madelung indole synthesis
3.2 Schmid indole synthesis
3.3 Wender indole synthesis
3.4 Couture indole synthesis
3.5 Smith indole synthesis
3.6 Kihara indole synthesis
3.7 Nenitzescu indole synthesis
3.8 Engler indole synthesis
3.9 Bailey–Liebeskind indole synthesis
3.10 Wright indoline synthesis
3.11 Saegusa indole synthesis
3.12 Miscellaneous nucleophilic cyclizations
4 Electrophilic cyclization
4.1 Bischler indole synthesis
4.2 Nordlander indole synthesis
4.3 Nitrene cyclization
4.3.1 Cadogan–Sundberg indole synthesis
4.3.2 Sundberg indole synthesis
4.3.3 Hemetsberger indole synthesis
4.4 Quéguiner azacarbazole synthesis
4.5 Iwao indole synthesis
4.6 Magnus indole synthesis
4.7 Feldman indole synthesis
4.8 Miscellaneous electrophilic cyclizations
5 Reductive cyclization
5.1 o,afii9826-Dinitrostyrene reductive cyclization
5.2 Reissert indole synthesis
5.3 Leimgruber–Batcho indole synthesis
5.4 Makosza indole synthesis
6 Oxidative cyclization
6.1 Watanabe indole synthesis
6.2 Kn?lker indole-carbazole synthesis
7 Radical cyclization
7.1 Tin-mediated cyclization
7.2 Samarium-mediated cyclization
7.3 Murphy indole-indoline synthesis
7.4 Miscellaneous radical cyclizations
8 Metal-catalyzed indole syntheses
8.1 Palladium
8.1.1 Hegedus–Mori–Heck indole synthesis
8.1.2 Yamanaka–Sakamoto indole synthesis
8.1.3 Larock indole synthesis
8.1.4 Buchwald indoline synthesis
8.1.5 Miscellaneous
8.2 Rhodium and ruthenium
8.3 Titanium
8.3.1 Fürstner indole synthesis
8.3.2 Miscellaneous
8.4 Zirconium
8.5 Copper
8.5.1 Castro indole synthesis
8.5.2 Miscellaneous
8.6 Chromium
8.7 Molybdenum
9 Cycloaddition and electrocyclization
9.1 Diels–Alder cycloaddition
9.2 Photocyclization
9.2.1 Chapman photocyclization
9.2.2 Miscellaneous photochemical reactions
9.3 Dipolar cycloaddition
9.4 Miscellaneous
10 Indoles from pyrroles
10.1 Electrophilic cyclization
10.1.1 Natsume indole synthesis
10.1.2 Miscellaneous
10.2 Palladium-catalyzed cyclization
10.3 Cycloaddition routes
10.3.1 From vinylpyrroles
10.3.2 From pyrrole-2,3-quinodimethanes
10.3.3 Miscellaneous
10.4 Radical cyclization
11 Aryne intermediates
11.1 Aryne Diels–Alder cycloaddition
11.2 Nucleophilic cyclization of arynes
12 Miscellaneous indole syntheses
12.1 Oxidation of indolines
12.2 From oxindoles,isatins and indoxyls
12.3 Miscellaneous
13 Acknowledgements
14 References
1 Introduction
Indole and its myriad derivatives continue to capture the
attention of synthetic organic chemists,and a large number of
original indole ring syntheses and applications of known
methods to new problems in indole chemistry have been
reported since the last review by this author in 1994.
1,2
1046 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
Although most of the examples herein involve the indole ring
system,a few novel syntheses of indolines,oxindoles,? isatins,?
indoxyls,? carbazoles,and related ring systems are included in
this review,The organization follows that adopted earlier,
1
albeit with the inclusion of several additional classi?cations.
Unfortunately,space limitations preclude detailed discussions
of these reactions.
2 Sigmatropic rearrangements
2.1 Fischer indole synthesis
The venerable Fischer indole synthesis
3,4
has maintained its
prominent role as a route to indoles,both new and old,and to
the large-scale production of indole pharmaceutical intermedi-
ates,Furthermore,new methodologies have been developed
and new mechanistic insights have been gleaned for the Fischer
indole reaction since the last review.
2.1.1 Methodology
A one-pot synthesis of indoles from phenylhydrazine hydro-
chloride and ketones in acetic acid with microwave irradiation
shows improvement in many cases (higher yields and reaction
times of less than a minute) over the conventional thermal
reaction conditions.
5,6
Microwave irradiation in a pressurized
reactor with water as solvent (220 H11034C,30 min) gives 2,3-dimethyl-
indole in 67% yield from phenylhydrazine and butan-2-one.
7
The use of montmorillonite clay and ZnCl
2
under microwave
conditions a?ords 2-(2-pyridyl)indoles at much lower temper-
atures and with solvent-free acid (Scheme 1).
8
The use of
natural clays (bentonite) and infrared irradiation also furnishes
indoles in high yield from phenylhydrazine and ketones.
9
For
example,acetone a?ords 2-methylindole in 85% yield.
Zeolites in the Fischer indole synthesis are highly shape-
selective catalysts and can reverse the normal regiochemistry
seen with unsymmetrical ketones.
10,11
For example,1-phenyl-
butan-2-one furnishes 2-benzyl-3-methylindole as the major
isomer (83:17) in the presence of zeolite beta,whereas with
no zeolite present this is the minor isomer and the major
isomer is 2-ethyl-3-phenylindole (24:76).
10
The solid phase
Fischer indole synthesis of spiroindolines using substituted
arylhydrazines and polymer-bound piperidine-4-carbaldehyde
has been reported.
12
This research group has described the
preparation of 2-arylindoles on a solid support
13
and the
synthesis of an indole combinatorial library using dendrimer
supports.
14
The thermal cyclization of N-tri?uoroacetyl enehydrazines
leads to indoles (or indolines) under relatively mild conditions
(Scheme 2),apparently due to a lowering of the LUMO energy
level of the tri?uoroacetyl-substituted ole?n that facilitates
the [3,3]-sigmatropic rearrangement of the enehydrazine.
15
A
new catalyst,diethylaluminium 2,2,6,6-tetramethylpiperidinide
(DATMP),provides excellent regioselectivity in the Fischer
indole synthesis of 2,3-dialkylindoles from unsymmetrical
ketones via the isomeric (Z)- and (E)-hydrazones.
16
For
example,(E)-N-methyl-N-phenylhydrazone of 5-methylheptan-
Scheme 1
The IUPAC name for oxindole is indolin-2-one,for indoxyl is indol-3-
ol and for isatin is indoline-2,3-dione.
3-one gives 3-sec-butyl-2-ethyl-1-methylindole as the only
isolable product,and the Z-isomer yields 1,3-dimethyl-2-(2-
methylbutyl)indole with high regioselectivity,The results are
ascribed to regioselective enehydrazine formation by preferen-
tial proton abstraction by the hindered base DATMP.
Buchwald and co-workers have utilized the palladium-
catalyzed coupling of hydrazones with aryl bromides as an
entry to N-arylhydrazones for use in the Fischer indolization.
17
Subsequent hydrolysis and trapping with a ketone under acidic
conditions leads to indoles (Scheme 3).
2.1.2 Applications
The Fischer indole synthesis was used extensively during the
past?ve years to access a wide range of indoles and derivatives.
Examples include 5-methoxy-2-phenylindole used in a
photolysis study,
18
2-ethoxycarbonyl-5-chloro-3-methylindole,
19
2-ethoxycarbonyl-6-chloro-5-methoxy-3-methylindole,
19
and 2-
ethoxycarbonyl-6-methoxy-3-methylindole
20
for use in indole
alkaloid synthesis,
19,20
and 2-ethoxycarbonyl-7-methoxy-
4-nitroindole,
21
2-ethoxycarbonyl-7-methoxy-5-nitroindole,
21
2-ethoxycarbonyl-4-methoxy-7-nitroindole,
21
and 2-ethoxy-
carbonyl-5-methoxy-7-nitroindole
22
for use in the synthesis
of coenzyme PQQ (pyrroloquinoline quinone) analogs.
21,22
The last studies
19–22
utilize the Japp–Klingemann reaction of
an aryl diazonium salt with α-substituted ethyl acetoacetate to
obtain the requisite arylhydrazone,The Japp–Klingemann
reaction was also used with malonates to prepare 2-alkoxy-
carbonyl-5-methoxyindoles on an industrial scale in high yields
and with little waste.
23
The reaction of 1,5-di(p-tolyl)pentane-
1,3,5-trione with 2 equivalents of phenylhydrazine gives rise
to 3-[1-phenyl-5-(p-tolyl)pyrazol-3-yl]-2-(p-tolyl)indole,
24
and
a bis-Fischer indolization of the bisphenylhydrazone of 2,5-
dimethylcyclohexane-1,4-dione a?ords 5,11-dimethyl-6,12-
dihydroindolo[3,2-b]carbazole in 80% yield.
25
Scheme 2
Scheme 3
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1047
The synthesis of the marine alkaloid eudistomidin-A
featured a Fischer indolization (Scheme 4); this paper describes
the preparation of other 7-oxygenated indoles under conditions
that preclude formation of the,abnormal” indole product.
26
Along these lines,Szczepankiewicz and Heathcock employed
an oxygen bridge in a hydrazone to prevent the abnormal
cyclization.
27
Subsequent elimination and hydrolysis to remove
the oxyethylene bridge furnishes the desired 7-hydroxy-4-
nitrotryptophanol derivative (Scheme 5),The loss of an
ortho-oxygen substituent was encountered by White et al,in
a synthesis of 6,7-dimethoxytryptophanol,to a?ord the
abnormal product 4-methoxytryptophanol.
28
The indole diol 1 was easily crafted from a 2,3-dideoxy-
pentose as shown in Scheme 6.
29
The initial Fischer indole
product was a mixture of two isomeric hydroxybenzoates
resulting from benzoyl migration.
Numerous tryptamine derivatives have been synthesized via
the Fischer indole synthesis and some of these are listed below
(2,
30
3,
31
4
32
),Other tryptamines have been prepared via Fischer
indolization and studied as novel antagonists for the vascular
5-HT
1B
-like receptors,
33,34
5-HT
1D
receptor agonists,
35
and
melatonin analogs.
36
Several novel tetrazolylindoles 5 have also
been prepared in this fashion,
37
and improvements in the
Fischer indole step in the synthesis of the migraine treatment
drug sumatriptan
38
and analogs
39
have been described,Both
2- and 3-indolylquinazolinones (e.g.,6) are readily prepared,
40
and the thiocarbamates 7 are available in good yields by a
Fischer indolization.
41
An unexpected result in the Fischer
indole protocol gives rise to 3-aminoindole-2-carboxylates,
42
Scheme 4
Scheme 5
Scheme 6
and phenylhydrazones of bulky ketones can lead to rearranged
products.
43
Several indole alkaloid studies feature a Fischer indole syn-
thesis as a key step,including studies on uleine,
44
aspidosperm-
idine,
45
and ibophyllidine alkaloids.
46
The core of the leptosin
alkaloid family was nicely crafted by Crich et al,in this fashion
(Scheme 7).
47
The Fischer indole synthesis has been used to construct
numerous carbazoles including simple carbazole alkaloids,
48
rutaecarpine analogs,
49,50
biscarbazole alkaloids,
51
benzo-
indoloquinolines,
52
thiazolocarbazoles,
53
thienocarbazoles,
54
C-14 labelled benzocarbazole,
55
and other fused-indoles such
as indolo[3,2-d]benzoazepinones.
56
Novel 14-alkoxyindolo-
morphinans (e.g.,8),
57
4-hydroxy-3-methoxyindolomorph-
inans,
58
and indolinosteroids (e.g.,9)
59
are readily synthesized
via Fischer indolization,as are pyridoindolobenzodiazepines
(e.g.,10),
60
decal-1-one-derived indoles,
61
radiolabelled naltrin-
doles,
62
and 3-indolylcoumarins.
63
A series of novel fused indoles has been synthesized using a
Fischer indole strategy and one example is shown in Scheme
8.
64
Ketoindoles and ketobenzothiophenes were also employed
in this reaction.
Spiroindolines and spiroindolenines are readily synthesized
using the Fischer indolization and some examples include a
crown-linked spiroindolenine used to make new signal
transducers,
65
novel antipsychotics,
66
and MK-677,a growth
Scheme 7
1048 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
hormone secretagogue.
67
The Fischer indole sequence has been
used on an industrial scale in the manufacture of a pharm-
aceutical intermediate,
68
to prepare pyrrolo[2,3-d]pyrimidines
as potential new thymidylate synthase inhibitors,
69,70
and to
synthesize 7-bromo-2,3-bis(methoxycarbonyl)indole as a useful
substrate for Pd-catalyzed cross coupling reactions leading to
7-substituted indoles.
71
However,on rare occasions the Fischer indole synthesis
proceeds poorly or even fails altogether,For example,hydra-
zone 11 a?orded only 15% of the indole product,the major
product (41%) being an indazole,
72
and hydrazone 12 failed to
cyclize to an indole under all conditions tried
73
(Scheme 9),
presumably because of the deactivating e?ect of the (proton-
ated) pyridine ring.
2.1.3 Mechanism
An exhaustive study of the e?ects of acidity on the mechanism
of the Fischer indole synthesis reveals that four di?erent mech-
anistic variations can occur over the acidity range of H
0
= H110012
to H110028.
74
Thus,in strong acid the rate-determining step is
Scheme 8
Scheme 9
deprotonation to form the enehydrazine,whereas under weakly
acidic conditions tautomerization is su?ciently rapid that the
[3,3]-sigmatropic rearrangement is rate determining,MNDO
AM1 calculations have been performed on the conformations
and sigmatropic rearrangement of the phenylhydrazones of
ethyl pyruvate and acetaldehyde.
75,76
Murakami and co-workers continue their investigations of
the e?ects of ortho-substituents on the regiochemistry and rate
of Fischer indole cyclizations,
77–79
and,as shown in Scheme 10,
hydrazone 13 undergoes cyclization to the more electron-rich
benzene ring.
77
A novel abnormal rearrangement has been uncovered in the
Fischer indolization of the naltrexone N-methyl-N-(5,6,7,8-
tetrahydro-1-naphthyl)hydrazone.
80
Huisgen and co-workers
have found that under Fischer indole reaction conditions ene-
hydrazine 14 stops at the 2-aminoindoline stage 15,since indole
formation is precluded by ring strain in the product (Scheme
11).
81,82
2.2 Gassman indole synthesis
The beautiful Gassman indole-oxindole synthesis,
83–86
which
features a [2,3]-sigmatropic rearrangement,has been used to
prepare e?ciently 6,7-dihydroxyoxindole,a subunit of the
alkaloids paraherquamide A and marcfortine A.
87
Wright et al.
have developed a modi?cation of the Gassman synthesis that
a?ords improved yields in many cases.
88
The key feature of the
Wright modi?cation is the facile formation of the chlorosulf-
onium salt 16,which avoids elemental chlorine (Scheme 12).
Scheme 10
Scheme 11
Scheme 12
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1049
2.3 Bartoli indole synthesis
The fascinating Bartoli protocol,
89,90
which features a [3,3]-
sigmatropic rearrangement analogous to the Fischer indoliz-
ation step,has been used to prepare 7-bromo-4-ethylindole in a
synthesis of (±)-cis-trikentrin A,
91
and 7-bromoindole (Scheme
13) in a synthesis of hippadine.
92
2.4 Thyagarajan indole synthesis
Thyagarajan and co-workers discovered a novel indole ring-
forming reaction that involves sequential [2,3]- and [3,3]-
sigmatropic rearrangements from the N-oxide of the aryl
propynylamine 17 (Scheme 14).
93–95
In continuation of the original work,Majumdar et al,have
extended this reaction to the preparation of cyclic bisethers con-
taining two indole units (Scheme 15),
96,97
and to the synthesis
of dihydro-1H-pyrano[3,2-e]indol-7-ones.
98
The mechanism is
proposed to involve dimerization of 3-methyleneindoline 18.
A related tandem [2,3]- and [3,3]-sigmatropic rearrangement
sequence is suggested to explain the formation of N-alkyl-
2-vinylindoles from N-alkyl-N-allenylmethylanilines upon
exposure to MMPP (magnesium monoperoxyphthalate)
(Scheme 16).
99
2.5 Julia indole synthesis
Julia and co-workers have uncovered a novel indole ring syn-
thesis involving the [3,3]-sigmatropic rearrangement of the
readily available sul?namides 19 (Scheme 17).
100
More recently,
these workers have published a full account of their work
including many examples of this clever reaction.
101
Scheme 13
Scheme 14
Scheme 15
2.6 Miscellaneous sigmatropic rearrangements
A tandem Wittig–Cope reaction sequence converts a 2-
allylindoxyl to the corresponding indole in excellent yield
(Scheme 18).
102
3 Nucleophilic cyclization
3.1 Madelung indole synthesis
Although the classical Madelung synthesis is rarely employed
nowadays,the excellent Houlihan modi?cation,
103
which util-
izes BuLi or LDA as bases under milder conditions than the
original Madelung harsh conditions,has been extended in
several ways,For example,benzylphosphonium salts such as 20
undergo facile cyclization to indoles under thermal conditions
(Scheme 19).
104,105
The phosphonium salt can be generated
in situ from the corresponding benzyl methyl ether 21,The reac-
tion is especially valuable for the synthesis of 2-per?uoroalkyl-
indoles,although the yields are quite variable,The base-
catalyzed version of this reaction has been adapted to solid
phase synthesis.
106
A Madelung–Houlihan variation in which an intermediate
dianion derived from pyridine 22 is quenched with amides to
yield azaindoles has been described (Scheme 20).
107
This
reaction,which was?rst reported by Clark et al.,
108
has been
utilized in a synthesis of novel pyrano[2,3-e]indoles as potential
new dopaminergic agents.
109
An aza-Wittig reaction of iminophosphoranes 23 with acyl
cyanides leads to a novel indole synthesis (Scheme 21).
110
Moreover,quenching 23 with phenyl isocyanate yields carbo-
diimides which cyclize to 2-anilinoindoles with base.
110
These
methods are excellent for the preparation of 2-aryl-3-(aryl-
sulfonyl)indoles and 2-anilino-3-(arylsulfonyl)indoles.
Cyclization of phenylacetate imides such as 24 occurs readily
under the in?uence of base (Scheme 22).
111
An interesting attempt to cyclize the imines derived from
tri?uoromethylaryl ketones and o-toluidines with lithium
amides to indoles was not successful,yielding only amidines.
112
Scheme 16
Scheme 17
Scheme 18
1050 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
3.2 Schmid indole synthesis
No new examples were uncovered since the last review.
3.3 Wender indole synthesis
The Wender indole synthesis,
113
which involves the ortho-
lithiation of N-phenylamides followed by reaction of the
resulting dianion with α-haloketones and subsequent ring
closure and dehydration,has been extended to a convenient
synthesis of isatins by quenching with diethyl pyruvate
(Scheme 23).
114
A related isatin synthesis has been described by Smith and
co-workers
115
that involves the carbonylation of the dianion
derived from NH11032-(2-bromoaryl)-N,N-dimethylureas,The key
Scheme 19
Scheme 20
Scheme 21
Scheme 22
intermediate is an acyllithium species which cyclizes onto the
urea carbonyl group,This lithiation–carbonylation strategy was
adapted to the synthesis of 3-hydroxyoxindoles by the lithiation
of N-pivaloylanilines.
116
Smith and co-workers have also
employed the original Wender indole synthesis to the synthesis
of N-dimethylurea-protected indoles involving the dilithiation
of NH11032-phenyl-N,N-dimethylurea.
117
3.4 Couture indole synthesis
No new examples were reported since the last review.
3.5 Smith indole synthesis
The Smith indole synthesis,
118
which involves dilithiation of
N-trimethylsilyl-o-toluidine and subsequent reaction with a
non-enolizable ester to a?ord the 2-substituted indole,has been
used to synthesize 2-tri?uoromethylindole in 47% yield by
quenching the above mentioned dianion with ethyl tri?uoro-
acetate.
119
3.6 Kihara indole synthesis
Kihara et al,have described an indole ring formation that
involves an intramolecular Barbier reaction of phenyl and
alkyl N-(2-iodophenyl)-N-methylaminomethyl ketones as
summarized in Scheme 24.
120
The hydroxyindoline by-product,
if obtained,can be converted to the indole with aqueous
HCl.
3.7 Nenitzescu indole synthesis
The past?ve years have seen a resurrection of the Nenitzescu
indole synthesis and this classic sequence was used to construct
methyl 5-hydroxy-2-methoxymethylindole-3-carboxylate,the
key intermediate in a synthesis of the antitumor indolequinone
EO 9.
121
This reaction has also been used to prepare a series of
N-aryl-5-hydroxyindoles,
122
and it was utilized in the synthesis
of a key indole (Scheme 25) used to prepare potent and selective
s-PLA
2
inhibitors.
123
Scheme 23
Scheme 24
Scheme 25
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1051
3.8 Engler indole synthesis
In a series of papers rich in detail,Engler and co-workers have
described a new indole synthesis based on the Lewis acid-
promoted reactions of enol ethers and styrenes with benzo-
quinone imines.
124–127
An example is shown in Scheme 26 and
the reaction has obvious similarities to the Nenitzescu indole
ring synthesis,Engler can manipulate the reaction to a?ord
benzofurans instead of indoles by simply changing the Lewis
acid.
Kita and colleagues have reported a synthesis of indoles
closely related to the Engler synthesis.
128,129
Kita’s variation
involves the reaction of α-methylstyrene and phenyl vinyl
sul?de with p-methoxy-N-tosylaniline under the in?uence of
phenyliodonium bistri?uoroacetate,conditions that generate
benzoquinone intermediates similar to the Engler inter-
mediates.
3.9 Bailey–Liebeskind indole synthesis
Bailey and Liebeskind independently discovered the novel
indole ring-forming reaction shown in Scheme 27 and involving
anionic cyclization onto an N-allyl unit.
130,131
The resulting
indoline anion can be further treated with an electrophile and
then oxidized with chloranil? to the indole,The N-allylindole
can be deprotected with Pd.
132
This new synthesis has been used
to prepare a novel benzo[ f ]indole amino acid as a?uorescent
probe,
133
and Bailey has extended the reaction to include the
intermediacy of aryne intermediates in the sequence,the result
being that the alkyllithium used to generate the aryne is
incorporated into the cyclized indoline at the C-4 position.
134
3.10 Wright indoline synthesis
Wright and co-workers have developed an e?cient synthesis
of indoline-2,2-dicarboxylates by the tandem bis-alkylation of
o-bromomethyltri?uoroacetanilides 25 (Scheme 28).
135
The
Scheme 26
Scheme 27
Chloranil is 2,3,5,6-tetrachloro-p-benzoquinone.
indole nitrogen can be readily deprotected (Mg–MeOH) and
further functionalized as desired (acylation,alkylation),Pre-
sumably,these indolines can be converted to indole-2-carboxyl-
ates by decarboxylation and oxidation.
3.11 Saegusa indole synthesis
The cyclization of ortho-lithiated o-tolylisocyanides is a power-
ful indole synthesis discovered by Saegusa and co-workers in
1977 (Scheme 29).
136,137
The reaction is very general and has
been exploited by Makosza and co-workers in a synthesis of
5-allyloxy-3-(4-tolylsulfonyl)-1H-indole for use in 1,3,4,5-tetra-
hydrobenzo[cd]indole studies.
138
The requisite isocyanide pre-
cursor was synthesized by a vicarious nucleophilic substitution
(VNS) reaction as developed by Makosza.
139,140
The elegant free-radical cyclization version of the Saegusa
indole synthesis as developed by Fukuyama is presented in
Section 7.1.
3.12 Miscellaneous nucleophilic cyclizations
The known indoxyl dianion 26,which is used to synthesize
indigo,has now been successfully intercepted with carbon
disul?de to furnish indoxyls and indoles (Scheme 30).
141
The
trapped indoxyl ketene dithioacetals 27 and 28 can be used in
cycloaromatization reactions to make carbazoles,e.g.,29.
Scheme 28
Scheme 29
Scheme 30
1052 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
Filler et al,have improved the synthesis of 4,5,6,7-tetra-
uoroindole by the two-step reaction sequence of KF-induced
cyclization of 2,3,4,5,6-penta?uorophenethylamine and DDQ
oxidation of the resulting 4,5,6,7-tetra?uoroindoline.
142
Heat-
ing β,β-di?uorostyrenes bearing o-tosylamido groups with
NaH leads to the corresponding 2-?uoroindoles by a presumed
disfavored 5-endo-trig cyclization (Scheme 31).
143
Sutherland has uncovered a novel indole ring formation
involving DBU nucleophilic addition to an electron-de?cient
benzene ring and elimination of a nitro group from an inter-
mediate Meisenheimer complex 30 (Scheme 32).
144
In the case
of methyl 3,5-dinitrobenzoate,an isoquinolone also forms
depending on the initial site of attack by DBU.
A novel use of sulfonium ylides has led to 2-substituted
indoles (Scheme 33).
145
In the case of the non-stabilized ylide
(R = H),only N-tosylindoline was isolated (76%).
Arcadi and Rossi have published a very simple synthesis of
4,5,6,7-tetrahydroindoles by the nucleophilic addition of
benzylamine or ammonia to pent-4-ynones (Scheme 34).
146
This
addition–elimination–cycloamination sequence was used to
prepare a pyrrolosteroid from 17β-hydroxyandrost-4-en-3-one.
As will be seen in Section 10,these tetrahydroindoles can
usually be readily converted into indoles.
Kim and Fuchs have reported the reaction of cyclic epoxy
ketones with N,N-dimethylhydrazine to a?ord bicyclic per-
hydroindoles,Subsequent manipulation gives tetrahydroindoles
such as 31 (Scheme 35).
147
Scheme 31
Scheme 32
Scheme 33
A new indoline ring-forming reaction leads to the formation
of N-(cyanoformyl)indoline (Scheme 36),
148
and the reaction
between bislithiated substituted methylnitriles and methyl-
sulfones with oxalimidoyl chlorides provides 3-iminoindoles in
one step (Scheme 37).
149
4 Electrophilic cyclization
Several of the numerous electrophilic cyclization routes to
indoles have been available to synthetic organic chemists for 100
years or more,Nevertheless,new examples and applications
of this indole ring-forming strategy continue to appear in the
literature.
4.1 Bischler indole synthesis
Moody and Swann have described a modi?cation of the
Bischler synthesis wherein the intermediate α-(N-arylamino)-
ketones are prepared by a Rh-catalyzed insertion reaction.
150
Acid-catalyzed cyclization completes the synthesis (Scheme 38).
Further examples of rhodium-catalyzed indole ring forming
reactions are in Section 8.2.
Scheme 34
Scheme 35
Scheme 36
Scheme 37
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1053
4.2 Nordlander indole synthesis
Although no new examples of this modi?cation of the Bischler
indole synthesis were found per se,Zard and co-workers have
e?ected the Lewis acid induced cyclization of 2,2-dimethoxy-
arylacetanilides to 3-aryloxindoles.
151
4.3 Nitrene cyclization
4.3.1 Cadogan–Sundberg indole synthesis
This powerful indole ring formation method involves the
deoxygenation of o-nitrostyrenes or o-nitrostilbenes with tri-
ethyl phosphite and cyclization of the resulting nitrene to
form an indole,Holzapfel and Dwyer have used this method
to synthesize several carbazoles and norharman from the
appropriate 2-nitrobiphenyls,and also several 2-methoxy-
carbonylindoles from methyl o-nitrocinnamates.
152
Another
group has synthesized several 2,2H11032-biindolyls by the deoxygen-
ation–cyclization of the appropriate 2-(o-nitrostyryl)indoles.
153
The presumed novel generation of nitrenes from o-nitro-
stilbenes using CO and Se leads to an e?cient synthesis of
2-arylindoles (Scheme 39).
154
The authors propose the form-
ation of carbonyl selenide (COSe) which is the deoxygenation
agent,Both 2- and 3-methylindole can be synthesized in good
yields (70%,69%) from the corresponding o-nitrostyrenes,and
indole is obtained in 55% yield.
4.3.2 Sundberg indole synthesis
Molina et al,have employed the Sundberg indole synthesis,
which involves the thermolysis of o-azidostyrenes and cycliz-
ation of the resulting nitrene to form indoles,to prepare
2-(2-azidoethyl)indole (Scheme 40).
155,156
The lack of reactivity
of the aliphatic azido group is noteworthy.
Scheme 38
Scheme 39
Scheme 40
This research group has also used this methodology to
synthesize the indole alkaloids cryptosanguinolentine (33)
and cryptotackieine (34) from the common starting azide
32 (Scheme 41).
157
A very similar strategy to synthesize the
alkaloids 33 and 34 was reported earlier by Timári et al.
158
Depending on the solvent,the photolysis of 2-amino-2H11032-
azidobiphenyl yields small amounts of 4-aminocarbazole and
4,10-dihydroazepino[2,3-b]indole,amongst two non-indolic
products.
159
Thermolysis of 1-benzylpyrazole a?ords α-carbol-
ine as the major product.
160
The reaction is proposed to involve
a pyridylnitrene,We have used the Sundberg indole synthesis
to synthesize the previously unknown 2-nitroindole from
2-(2-azidophenyl)nitroethylene in 54% yield.
161
4.3.3 Hemetsberger indole synthesis
The Hemetsberger indole synthesis is related to the Sundberg
indole synthesis except that the azido group is on the side
chain (i.e.,α-azidocinnamate) rather than on the benzene ring.
This indole synthesis has been used to prepare 2-methoxy-
carbonyl-6-cyanoindole
162
and 2-ethoxycarbonyl-3-methyl-
indole.
163
The latter study includes a new preparation of
the precursor α-azidocinnamates by azide ring opening of
epoxides,The Hemetsberger protocol has been used to syn-
thesize the ABC rings of nodulisporic acid,
164
the thieno-
[3,2-g]indole and thieno[3,2-e]indole ring systems,
165
and a
precursor (35) to CC-1065 and related antitumor alkaloids
(Scheme 42).
166
Molina et al,have described a variation of the Hemetsberger
synthesis involving the thermolysis of 2-alkyl- and 2-aryl-
amino-3-(2-azidoethyl)quinolines to give the corresponding
pyrrolo[2,3-b]quinolines in 39–70% yield.
167
4.4 Quéguiner azacarbazole synthesis
Quéguiner and co-workers have extended their short and
e?cient synthesis of azacarbazoles to the construction of
α-substituted δ-carbolines (Scheme 43).
168
Scheme 41
Scheme 42
1054 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
4.5 Iwao indole synthesis
Iwao has published a new indole synthesis in which the ring-
forming step is a thermal sila-Pummerer rearrangement
(Scheme 44).
169
Oxidation of the 2-thioindolines with MCPBA
furnishes the corresponding indoles (R
1
= R
2
= H,100%),A
related Pummerer rearrangement leading to an indole inter-
mediate was used by Fukuyama and Chen in an elegant
synthesis of (H11002)-hapalindole G.
170
4.6 Magnus indole synthesis
Magnus and Mitchell have discovered that terminal tri-
isopropylsilylprop-2-ynylanilines a?ord 3-methylindoles upon
treatment with methanesulfonic acid (Scheme 45).
171
4.7 Feldman indole synthesis
Feldman and co-workers have found that phenyl(propynyl)-
iodonium tri?ate reacts with lithiated N-phenyl-p-toluene-
sulfonamide to a?ord indoles in one operation (Scheme
46).
172,173
The reaction is believed to involve a vinyl carbene
which undergoes electrophilic cyclization to form an indole.
Scheme 43
Scheme 44
Scheme 45
Scheme 46
4.8 Miscellaneous electrophilic cyclizations
Several new routes to o-aminophenylacetaldehyde derivatives
have provided new indole ring syntheses,Oxidative cleavage of
the allyl side chain in aniline 36 a?ords indole 37,used in a
synthesis of (H11001)-desmethoxymitomycin A (Scheme 47),
174
and
a similar osmium tetroxide oxidative cyclization yields 1-acetyl-
5-methoxycarbonyl-7-chloro-4-methoxyindole (77%) from the
corresponding o-allylacetanilide.
175
The use of 2-(2-amino-
phenyl)acetaldehyde dimethyl acetal to synthesize a series
of N-acylindoles by acid-catalyzed cyclization has been
described.
176
The N-acylindoles can be converted into esters,
amides,and aldehydes,but not ketones,by treatment with
suitable nucleophiles.
A synthesis of psilocin revealed the interesting indole syn-
thesis shown in Scheme 48 wherein 2,3-dihydro-2,5-dimethoxy-
furan 38,prepared by Pd-catalyzed cross-coupling,is cyclized
to indole 39.
177
An unexpected rearrangement of 4-amino-
2-methylbenzofurans to 4-hydroxy-2-methylindoles under
strongly acidic conditions was recently reported.
178
The authors
propose the generation of a vinyl carbocation by opening of the
furan ring and then cyclization to the more stable indole ring
system.
Ishikawa and co-workers have uncovered a remarkable two-
step rearrangement while studying the Bischler–Napieralski
reaction of 40,a double transformation that leads to 41
(Scheme 49),
179,180
and a,cume” question par excellence!
The mechanism of the previously known aromatization of
cyclic p-quinomethanes to indoles has been investigated and
extended to the synthesis of benzo[e]indoles.
181,182
Thus,the
reaction of vinylmagnesium bromide with 2-benzylamino-
naphtho-1,4-quinone followed by treatment with MsCl–Et
3
N
gives 5-mesyl-3-benzylbenzo[e]indole in 58% yield,The
cyclization of diazoanilides to oxindoles,which is normally
performed with rhodium (cf,Section 8.2),can also be accom-
plished with Na?on-H.
183
The authors propose an electrophilic
mechanism by protonation of the diazo group and loss of N
2
,
presumably to a carbene intermediate,An example is shown in
Scheme 50,Noteworthy is that the methoxycarbonyl group is
invariably lost under these conditions,and the azetidin-2-ones
Scheme 47
Scheme 48
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1055
are minor products,Smith et al,have studied this cyclization to
oxindoles as in?uenced by zeolite catalysts and they speculate
that di?erent carbenes are involved in the formation of oxin-
doles and azetidin-2-ones.
184
The ancient Sandmeyer isatin synthesis,which involves the
electrophilic cyclization of an α-isonitrosoacetanilide,has
been employed in a synthesis of the marine natural product
convolutamydine A via 4,6-dibromoisatin.
185
A new entry to
1,4,5,6-tetrahydro-2H-indol-2-ones involves 5-endo-trig cycliz-
ation of a sulfoxide amide 42 in a Pummerer rearrangement
(Scheme 51).
186
Padwa et al,have developed elegant,domino
Pummerer” cycloaddition
187
or cyclization
188
protocols to con-
struct complex oxindoles.
189,190
5 Reductive cyclization
Like the Fischer indole synthesis,and the Madelung cycliz-
ation and its modi?cations,and the numerous variations of
electrophilic cyclization to indoles,reductive cyclization
of nitro aromatics is a powerful means of forming indoles,
and several new developments have been described in recent
years.
Scheme 49
Scheme 50
Scheme 51
5.1 o,afii9826-Dinitrostyrene reductive cyclization
Corey and co-workers
191
have used the Borchardt modi?cation
(Fe–HOAc–silica gel–tol–re?ux)
192
of the reductive cyclization
of o,β-dinitrostyrenes to prepare 6,7-dimethoxyindole in a total
synthesis of aspidophytine,This modi?cation was employed in
the preparation of 7-acetoxy-6-methoxyindole and 4-acetoxy-
5-methoxyindole,which were used in syntheses of gastropod
indolequinones.
193
Fukuyama and Chen have used this reduc-
tive cyclization to prepare a potential indole precursor to a
synthesis of hapalindole G.
170
The synthesis of 5,6-methylene-
dioxyindole by the catalytic reduction of the corresponding
o,β-dinitrostyrene proceeds in 94% yield.
194
The very labile 5,6-
dihydroxyindole can be synthesized using the Zn-controlled
conditions shown in Scheme 52.
195
All other conditions tried
were unsatisfactory.
5.2 Reissert indole synthesis
The classic Reissert indole synthesis,involving the reductive
cyclization of o-nitrophenylpyruvic acid to indole-2-carboxylic
acid,was used by Shin and co-workers to prepare a series
of 2-ethoxycarbonyl-4-alkoxymethylindoles in a synthesis of
fragment E of nosiheptide,
196
and by Sato en route to a series
of tricyclic indole derivatives.
197
The modi?ed Reissert reaction,
involving the reductive cyclization of an o-nitrophenyl-
acetaldehyde or o-nitrophenyl methyl ketone,has been adapted
to solid-phase synthesis.
198
Kraus and Selvakumar have
employed the reductive cyclization of a nitro aldehyde to syn-
thesize a tricyclic indole related to the pyrroloiminoquinone
marine natural products.
199
Related synthetic targets have been
attacked by Joule and co-workers and a reductive cyclization
step (Scheme 53) was used in a synthesis of several of
these alkaloids.
200–202
Zard and co-workers have used form-
amidinesul?nic acid as a reducing agent in the reductive cycliz-
ation of nitroketones to pyrroles and a tetrahydroindole.
203
Rawal and Kozmin have utilized a Reissert reaction in a
synthesis of tabersonine that features an elegant construc-
tion of the requisite nitro ketone 44 using the new reagent
o-nitrophenylphenyliodonium?uoride (NPIF) to join the
o-nitrophenyl unit to silyl enol ether 43 (Scheme 54).
204,205
The reductive cyclization of o-nitrophenylacetic acids or
esters leading to oxindoles has been employed by Williams and
co-workers to prepare 6-hydroxy-7-methoxyoxindole in a syn-
thesis of (H11001)-paraherquamide B,
206
and a similar reduction
sequence yielded several chlorinated oxindoles and isatins.
207
5.3 Leimgruber–Batcho indole synthesis
The Leimgruber–Batcho indole synthesis involves the conver-
sion of an o-nitrotoluene to a β-dialkylamino-o-nitrostyrene
with dimethylformamide acetal,followed by reductive cycliz-
ation to an indole,Ochi and co-workers have used this protocol
to prepare 6-bromo-5-methoxyindole for use in the synthesis of
Scheme 52
Scheme 53
1056 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
marine bromoindoles,
208
and Showalter et al,synthesized
6-amino-5-ethoxycarbonylindole and 6-amino-7-ethoxycarbon-
ylindole from the appropriate o-nitrotoluenes.
209
The
Leimgruber–Batcho method has been used to make C-4 substi-
tuted indoles for elaboration to conformationally-restricted
analogs of indolmycin,
210
and in a synthesis of arcyriacyanin
A.
211
It has been used in a large-scale synthesis of 6-
bromoindole.
212
An important extension of this indole ring
synthesis is the functionalization of the intermediate β-
dialkylamino-o-styrene,Thus,Clark and co-workers have
acylated this intermediate enamine to yield 45 which was con-
verted to indole 46 after reductive cyclization (Scheme 55).
213
Prashad and co-workers have also used this tactic to construct
3-methoxycarbonylindoles by exposing the Leimgruber–
Batcho enamine to phosgene and then methanol,prior to
reductive cyclization.
214
An enamine dimer was also identi?ed
in this study.
Coe and co-workers have interrupted the Leimgruber–
Batcho sequence by converting the intermediate enamine to
an o-nitrophenylacetaldehyde acetal,which was reductively
N-alkylated,and then cyclized with acid to give a series of
1-alkyl-6-methoxycarbonylindoles.
215
5.4 Makosza indole synthesis
The essence of the Makosza indole synthesis is the vicarious
nucleophilic substitution (VNS)
139,140
of hydrogen to install the
requisite side chain (usually acetonitrile) for reductive cycliz-
ation onto a nitro group,Makosza has used this method to
Scheme 54
Scheme 55
synthesize a series of N-hydroxyindoles and indoles,
216
and to
prepare several pyrrolo[4,3,2-de]quinolines for use in the syn-
thesis of the marine pyrroloiminoquinone alkaloids (Scheme
56).
217,218
The selectivity observed in the nitro group reduction
is noteworthy; shorter reduction periods lead to the cyano-
quinolone,indicating that the less hindered nitro group is
reduced?rst.
Makosza has also described the condensation of m-nitro-
aniline with ketones under strongly basic conditions to form
4- and 6-nitroindoles.
219
Remarkably,imines are not involved in
this reaction,but,rather,oxidative nucleophilic substitution
of hydrogen by the ketone enolate occurs,Subsequent amine
carbonyl condensation yields the indole,The similarity of this
oxidative substitution of hydrogen to the VNS reaction is clear.
6 Oxidative cyclization
6.1 Watanabe indole synthesis
The Watanabe indole synthesis is the metal-catalyzed indole
synthesis from anilines and glycols,or ethanolamines,and the
related intramolecular cyclization of o-aminophenethyl alco-
hols to indoles,Watanabe,Shim,and co-workers have now
extended this reaction to the synthesis of N-alkylindoles in
yields up to 78% (N-methylindole) from the reaction of N-alkyl-
anilines with triethanolamine and the catalyst RuCl
2
-
(PPh
3
)
3
.
220,221
This oxidative cyclization has also been used to
prepare a wide range of substituted indoles from ring-
substituted (methyl,methoxy,chloro,isopropyl,dimethyl,
dimethoxy) anilines.
222
Other catalysts have been studied in
this reaction and CdBr
2
H115543KBr is particularly e?ective.
223,224
The intramolecular version of this reaction occurs with an
aluminium orthophosphate–Pd system
225
and also with
tetrakis(triphenylphosphine)palladium (Scheme 57).
226
This
method also furnishes 4,5,6,7-tetrahydroindoles and pyrroles,A
related electrolytic cyclization of o-nitrophenethylamines gives
N-aminoalkylindoles.
227
6.2 Kn?lker indole-carbazole synthesis
Over the past several years Kn?lker and co-workers have
parlayed the oxidative cyclization of tricarbonyliron–cyclo-
hexadiene complexes into a remarkably versatile synthesis of
Scheme 56
Scheme 57
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1057
indoles and,especially,carbazoles,Recent synthetic successes
in this arena include carazostatin,
228
carquinostatin A,
229
carbazomycins C and D,
230
G and H,
231
A and B,
232
carb-
azoquinocin C,
233
neocarazostatin B,
234
lavanduquinocin,
235
hyellazole,
236,237
4a,9a-dihydro-9H-carbazoles,
238
indolo[2,3-b]-
carbazole (Scheme 58),
239
and furostifolin.
240
The key oxidation
cyclization step can usually also be accomplished with active
manganese dioxide or ferricenium hexa?uorophosphate–
sodium carbonate,but in the case shown in Scheme 58 these
reagents led to decomposition.
This oxidative cyclization sequence has been applied to the
synthesis of the 2,3,3a,7a-tetrahydroindole nucleus by two
groups,apparently independently.
241,242
7 Radical cyclization
As was true in the earlier review,
1
radical cyclization routes to
indoles and indolines are very popular amongst synthetic
chemists,and several new such methodologies have been
invented in recent years for the construction of indoles.
7.1 Tin-mediated cyclization
Boger has been one of the pioneers in the development of tin-
mediated radical cyclization,notably in the area of CC-1065
and duocarmycin synthetic studies.
243–247
An example is
depicted in Scheme 59.
245
Patel and co-workers have improved upon this method by
e?ecting a similar 5-exo-trig cyclization onto a tethered vinyl
chloride (Scheme 60).
248
Jones and co-workers have reported a similar tin-mediated
cyclization of o-bromoacryloylanilides leading to oxindoles,a
method which employs in situ N-silylation to bias the requisite
conformation for cyclization.
249
This group has also described
the radical cyclization onto a pyrrole ring leading either to
spirooxindoles or to the martinelline core (pyrrolo[3,2-c]-
quinolone) (Scheme 61).
250,251
The tin-mediated cyclization
Scheme 58
Scheme 59
onto a linked dihydropyrrole ring leads also to a spirooxindole
and a pyrrolidinoquinolone in a 7:3 ratio.
252
Curran and co-workers who also were pioneers in
the development of tin-mediated 5-exo-trig cyclization to
indolines,
253
have described the?uorous and the microwave-
promoted?uorous versions of this reaction.
254,255
Other 5-exo-
trig variations include the cyclization of 2-allyl thiocarbazones
to hexahydroindoles,featuring a new source of nitrogen cen-
tered radicals,
256
the cyclization of o-bromo α-cyanoanilines to
spiroindoxyls,
257
cyclization of o-haloaryl allenylmethyl amines
to a?ord 3-ethenyl-2,3-dihydroindoles,
258
and cyclization of
the o-bromo benzimidate of phenethylamine to N-benzoyl-
indoline.
259
The Boger cyclization,which uses a TEMPO radical
trap,has been used in concert with the Hemetsberger indole
synthesis to prepare a duocarmycin model.
166
Murphy and co-
workers have reported the tin-induced cyclization of an ortho-
iodo tethered vinyl bromide leading,after loss of HBr,to a
tetrahydrocarbazole.
260
Parsons and co-workers have presented
a full account of his elegant tandem radical cyclization lead-
ing to lysergic acid derivatives
261
and to a pseudocopsinine
model.
262
An exciting development in the area of radical cyclization
is Fukuyama’s tin-mediated indole synthesis featuring the
cyclization of o-isocyanostyrenes via an α-stannoimidoyl
radical (Scheme 62).
263–265
This powerful methodology leads
to 2-substituted indoles by a Stille palladium-cross coupling
reaction of the intermediate 2-stannylindole,
263,264
and has been
featured in syntheses of indolocarbazoles,
264
biindolyls,
264
and
total syntheses of (±)-vincadi?ormine and (H11002)-tabersonine.
265
Others have used the Fukuyama synthesis to prepare 6-
hydroxyindole-3-acetic acid
266
and 3-(trimethylsilyl)methyl-
indoles.
267
The latter paper describes both the tin-mediated and
a thiol-mediated cyclization of an o-isocyanophenyl trimethyl-
silyl alkyne to indoles.
Fukuyama and co-workers have extended their indole radical
cyclization chemistry to the use of o-alkenylthioanilides,These
substrates furnish 2,3-disubstituted indoles in good to excellent
yields (Scheme 63).
268
Fukuyama has also developed a
phosphorus-initiated radical cyclization of thioanilides in the
context of a synthesis of (±)-catharanthine.
269
Scheme 60
Scheme 61
Scheme 62
1058 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
7.2 Samarium-mediated cyclization
Samarium iodide has been used with o-iodoaniline derivatives
to synthesize spirooxindoles,
270
and,with a TEMPO trap,
indolines (Scheme 64).
271
7.3 Murphy indole-indoline synthesis
Murphy and co-workers have engineered an elegant new radical
cyclization methodology involving,radical-polar crossover
chemistry”,which uses tetrathiafulvalene (TTF) or sodium
iodide to mediate the 5-exo-trig cyclization to indolines or
indoles.
260,272–275
A simple indole example is shown in Scheme
65,
260
but the method is particularly useful for the construction
of the tetracyclic-indoline core of Aspidosperma alkaloids.
273,275
This methodology has been extended to the use of polymer-
supported TTF reagents.
276
7.4 Miscellaneous radical cyclizations
Several newer means to e?ect a radical cyclization leading to
indoles or indolines have recently appeared in the literature.
These include Mn() cyclization of α-thioamides,
277
the electro-
chemical-induced cyclization of N-allyl-2-chloroacetanilides,
278
the Grignard-induced cyclization of N,N-diprenyl-2-iodo-
aniline (Scheme 66),
279
the thermal radical cyclization of
α,α,α-trichloroanilides to oxindoles,
280
the cyclization of
α-xanthylanilides to oxindoles (Scheme 67),
281
the tris-
(trimethylsilyl)silane-induced cyclization onto the nitrogen of
an imidate ester,
259
the tris(trimethylsilyl)silane-induced cycliz-
ation onto an alkene and the radical so-formed onto an azide,
282
the NBS-triggered cyclization of lactam m-cyclophanes to yield
tricyclic indoles (Scheme 68),
283
the Mn()-induced coupling of
ethyl α-nitroacetate with 2-aminonaphthoquinones to furnish
benzoindoloquinones,
284
and the thiol-triggered cyclization of
o-alkynylanilines
285
and o-alkynylphenyl azides
286,287
to indoles.
These novel reactions would seem to o?er enormous promise
for future development and applications in synthesis.
8 Metal-catalyzed indole synthesis
8.1 Palladium
The use of palladium in indole and indoline ring synthesis has
Scheme 63
Scheme 64
Scheme 65
received such extraordinary attention that this section has been
further subdivided from those divisions in the earlier review.
1
More importantly,proper credit (I hope!) has been given to the
several discoverers of this chemistry.
8.1.1 Hegedus–Mori–Heck indole synthesis
The application of the intramolecular Heck reaction to the syn-
thesis of indoles,oxindoles and indolines,depending on the
cyclization substrate,was apparently discovered independently
by Hegedus,
288–293
Mori
294,295
and Heck,
296
although Hegedus
was the?rst in print,These workers found that Pd e?ects the
cyclization of either o-allylanilines or N-allyl-o-haloanilines to
indoles under standard Heck conditions.
297–300
Two of the
original examples are shown in Scheme 69
288,289
and Scheme
70.
291
Hegedus was also the?rst to report the CO insertion
version of this Pd-catalyzed cyclization reaction leading to
indoline-2-acetic acid derivatives.
290
Larock and Babu have greatly improved upon the original
Hegedus conditions for the cyclization of N-allyl-o-haloanilines
and N-acryloyl-o-haloanilides,
301
such that,for example,the
Scheme 66
Scheme 67
Scheme 68
Scheme 69
Scheme 70
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1059
reaction shown in Scheme 70 can be performed at lower
temperature,with shorter reaction time and less catalyst to
give 3-methylindole in 97% yield,Larock and co-workers have
extended this Pd-mediated cyclization in other ways,
302–305
notably involving the cross-coupling of o-allylic and o-vinylic
anilides with vinyl halides and tri?ates to produce 2-vinyl-
indolines
303–305
(Scheme 71).
305
The related,Larock indole
synthesis” is presented in Section 8.1.3.
Numerous examples of the Hegedus–Mori–Heck indole
synthesis have been described,including applications to the
synthesis of CC-1065 precursors,
306–308
5-methyl- and 7-methyl-
indole featuring a new ortho-vinylation of anilines with SnCl
4
–
Bu
3
N,
309
indole-3-acetic acids,
310
indole-3-pyruvic acid oxime
ethers,
311
3-siloxyindoles,
312
δ-carbolines from the cyclization
onto a cyano group (Scheme 72),
313
7-bromoindoles related
to sumatriptan (Scheme 73),
314
and a total synthesis of the
alkaloid gelsemine.
315
The Pd-catalyzed synthesis of indoles
316,317
and oxindoles
318
has been adapted to the solid phase,and new?uorinated phos-
phine palladium complexes in supercritical carbon dioxide have
been invented for these reactions.
319
Overman and co-workers
have utilized the oxindole version of this reaction in the course
of total syntheses of the Calabar bean alkaloids physostigmine
and physovenine,
320
and,via a spectacular bis-Pd-catalyzed
cyclization (Scheme 74),for total syntheses of chimonanthine
and calycanthine.
321
Scheme 71
Scheme 72
Scheme 73
Grigg and co-workers have described a series of Pd-catalyzed
cyclizations leading to indoles,indolines,and oxindoles,includ-
ing the reaction of o-haloanilines with vinyl halides or tri?ates
and CO to produce 3-spiro-2-oxindoles,
322
cyclization protocols
to yield 3-spiroindolines,
323,324
and cyclization–anion capture
sequences to construct various indoles (Scheme 75).
325,326
Rawal and co-workers have reported that the Pd-catalyzed
cyclization of N-(2-bromoallyl)anilines a?ords indoles,and
they have used this to synthesize 4- and 6-hydroxyindoles.
327
Likewise,it has long been known that 2-(o-bromoanilino)
enones undergo the intramolecular Heck reaction to form
3-acylindoles.
328
A recent example of this version of the
Hegedus–Mori–Heck indole synthesis is shown in Scheme
76.
329
This cyclization has been applied to the synthesis of
3-ethoxycarbonyl-2-tri?uoromethylindoles from the appro-
priate o-haloanilino vinylogous carbamates
330,331
and to
2-benzyloxycarbonyl-4-hydroxymethyl-3-methylindoles from a
2-(o-iodoanilino) unsaturated ester.
332
A nice variation on this
theme utilizes the in situ preparation of o-iodoanilino enamines
(Scheme 77).
333
Scheme 74
Scheme 75
Scheme 76
Scheme 77
1060 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
More than 20 years ago?kermark and co-workers?rst
reported that 2-anilino-p-benzoquinones are cyclized to carb-
azolequinones with Pd(OAc)
2
.
334
Recently,this research group
has extended this reaction to additional examples (Scheme
78).
335
This cyclization has been used in the synthesis of bis-
carbazoles,
51
kinamycin analogs,
336,337
carbazomycins G and
H,
338
carbazoquinocin C,
339
(±)-carquinostatin A,
340
and 8,10-
dimethoxyellipticine.
341
The?nal cyclization involves a diaryl
amine precursor.
8.1.2 Yamanaka–Sakamoto indole synthesis
Although the Yamanaka–Sakamoto indole synthesis does not
necessarily involve Pd in the indole ring-forming step,it is
included in this section in view of its close similarity to both the
Hegedus–Mori–Heck and the Larock indole syntheses,This
reaction is also related to the copper-promoted Castro indole
synthesis (Section 8.5.1).
The Yamanaka–Sakamoto indole synthesis
298
features a Pd-
catalyzed coupling of a terminal alkyne with an o-haloaniline
to a?ord an o-alkynylaniline derivative which then readily
cyclizes with base to yield an indole,The prototypical reaction
is shown in Scheme 79.
342
The cyclization is either spontaneous
or involves Pd mediation,This cyclization can also be e?ected
with?uoride.
343
In subsequent papers,these workers reported that copper
is bene?cial to the overall reaction (Scheme 80),
344
and this
combination of catalysts has been used to e?ect a synthesis
of 7-substituted indoles,
345
oxygenated indoles,
346
3-methoxy-
carbonylindoles by CO carbonylation,
347
and 3-alkenylindoles
by an in situ Heck reaction.
348
The power of this indole ring synthesis has not gone
unnoticed,and Cacchi and co-workers have made outstanding
Scheme 78
Scheme 79
Scheme 80
contributions in this general area of indole ring construction.
For example,vinyl tri?ates react with o-aminophenylacetylene
to a?ord 2-substituted indoles in excellent yield (Scheme 81).
349
A carbonylation variation provides 3-acylindoles,
350
and 3-aryl-
2-unsubstituted indoles
351
and 3-allylindoles
352
are readily
crafted using Pd-catalyzed coupling,followed by cyclization.
The Yamanaka–Sakamoto indole synthesis has been used in
a synthesis of carazostatin,
353
the solid-phase syntheses of 2-
354
and 3-substituted indoles
355
and 2,3-disubstituted indole-
6-carboxylic acids,
356
2-dienylindoles,
357
and biindolyls
358,359
(Scheme 82),
359
the latter of which utilizes the Cacchi variation.
Grigg and co-workers have extended this methodology to
cyclization reactions of o-iodo-N-alkynylanilines leading to
polycyclic indoles,Two examples of this cascade process are
shown in Schemes 83
360
and 84.
361
Scheme 81
Scheme 82
Scheme 83
Scheme 84
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1061
8.1.3 Larock indole synthesis
The Larock indole synthesis
362,363
refers to the intermolecular
Pd-catalyzed reaction of o-haloanilines and alkynes (usually
internal) to give indoles in one operation,Examples of allenes
and alkenes functioning in this manner are also cited in this
section,An example is shown in Scheme 85.
363
The Larock indole synthesis with internal alkynes has been
used to synthesize 5-azaindoles,
364
5-,6-,and 7-azaindoles,
365
7-azaindoles (Scheme 86),
366
pyrrolo[3,2-c]quinolines,
367
pyrrolo[3,2,1-ij]quinolines,
368a
isoindolo[2,1-a]indoles,
368b
5-
(triazolylmethyl)tryptamine analogs,
369
tetrahydroindoles,
370
and N-(2-pyridyl)indoles.
371
The Larock method has been applied to solid-phase
synthesis,
372–374
terminal alkynes,
375,376
including chiral examples
(Scheme 87),
376
and some alkenes.
377–379
For example,this
last combination was used to synthesize indole-3-acetic acid
(Scheme 88).
378
Larock has also utilized allenes to craft 3-methylene-
indolines,including asymmetric synthesis (Scheme 89).
380,381
Allenes in this Pd-catalyzed indole synthesis variation lead to
Scheme 85
Scheme 86
Scheme 87
Scheme 88
7-azaindolinones following ozonolysis of the initially formed
exo-methyleneindoline,
382
and 1-sulfonyl-1,3-dienes in the
Larock methodology lead to 2-vinylindolines.
383
1-Oxygenated
dienes also work well.
384
8.1.4 Buchwald indoline synthesis
Buchwald has parlayed a powerful aryl amination tech-
nology
385
into a simple and versatile indoline synthesis.
386
Indole 48,which has been used in the total syntheses of the
marine alkaloids makaluvamine C and damirones A and B,
was readily synthesized using a Pd-mediated cyclization of 47
(Scheme 90).
387
This intramolecular Pd-catalyzed amination is applicable to
the synthesis of N-substituted optically active indolines,
388
and
o-bromobenzylic bromides can be employed in this indole
ring synthesis (Scheme 91).
389
Recently,Yang and Buchwald
have described improvements in this methodology.
390
8.1.5 Miscellaneous
Several examples of Pd-mediated cyclization leading to indoles
or indolines do not?t into the previous categories and are
presented here.
The indole ring can be easily fashioned by the Pd-catalyzed
cyclization of o-nitrostyrenes.
391,392
S?derberg and co-workers
have developed this,reductive N-heteroannulation” reaction
into a very attractive and general indole ring synthesis,
393,394
both for simple indoles (Scheme 92)
393
and fused indoles
(Scheme 93).
394
A related cyclization of o-aminophenethyl
alcohol was cited earlier.
226
Scheme 89
Scheme 90
Scheme 91
1062 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
Yang has reported the Pd-induced cyclization of an aryl-
bromide to a pendant cyano group leading to γ-carbolines and
related compounds.
395
8.2 Rhodium and ruthenium
The rhodium()-catalyzed decomposition of α-diazocarbonyl
compounds to yield oxindoles is an important synthetic oper-
ation,and Moody,Padwa,and co-workers have made several
important contributions in this area.
396–399
Notably,the use of a
per?uorinated carboxamide ligand on the rhodium catalyst
decidedly promotes attack on the aromatic ring rather than
leading to a β-lactam or other products,This reaction is a key
step (Scheme 94) in a synthesis of the marine alkaloid convo-
lutamydine C by Moody and co-workers.
398
The use of chiral α-diazocarbonyl compounds in this process
preserves the optical activity in furnishing N-substituted
oxindoles,
400
and Rh() also catalyzes the carbenoid insertion
into a C–H bond of a pyrrolidine leading to 1,2-disubstituted
mitosene 49 (Scheme 95).
401–403
This cyclization is also e?ected
by chiral bis(oxazoline)copper(?) catalysts to give some
enantioselectivity.
The Rh-catalyzed hydroformylation of functionalized anil-
ines leads to tryptophanols and tryptamines (Scheme 96).
404
The Rh-catalyzed carbonylation of o-alkynylanilines yields
oxindoles,
405
and a Rh-catalyzed process,using Wilkinson’s
catalyst,has been discovered that converts azobenzenes into
N-anilinoindoles.
406,407
For example,under these conditions
Scheme 92
Scheme 93
Scheme 94
Scheme 95
azobenzene reacts with diphenylacetylene to give N-anilino-2,3-
diphenylindole in 90% yield.
Witulski has reported a very general Rh-catalyzed arom-
atic ring-forming reaction with alkynes leading to indolines
(Scheme 97).
408
This [2H110012H110012] cycloaddition provides 4,5,6,7-
tetrasubstituted indolines in good to excellent yields.
A ruthenium catalyst converts o-alkylbenzonitriles to
indoles,
409
and a 3-enylalkynylindole to a carbazole in low
yield.
410
8.3 Titanium
8.3.1 Fürstner indole synthesis
The Fürstner indole synthesis is the Ti-induced reductive cycliz-
ation of oxo amides leading to an indole ring.
411
Fürstner et al.
have revealed the enormous power and versatility of this coup-
ling reaction,illustrated by total syntheses of the indole alkal-
oids (H11001)-aristoteline,
412
camalexin,
413
avopereirine and other
indolo[2,3-a]quinolizine alkaloids,
413,414
and secofascaplysin.
414
The reaction is general for simple indoles (Scheme 98),
415
including highly strained examples (2,3-di-tert-butyl-1-methyl-
indole
412
),It is also particularly useful for the preparation of
2-arylindoles.
416
An improvement over the original procedure is the so-called
“instant” method utilizing TiCl
3
–Zn,and these newer condi-
tions have been employed to synthesize a variety of bi-,ter-,
and quaterindoles (Scheme 99).
417
For example,indoles 50 and
51 can be easily assembled using this Ti-induced,zipper
reaction”.
8.3.2 Miscellaneous
Mori and co-workers have continued their use of Ti–nitrogen
Scheme 96
Scheme 97
Scheme 98
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1063
complexes (nitrogen?xation) in pyrrole ring formation leading
to tetrahydroindoles (Scheme 100).
418,419
The low-valent titanium reductive cyclization of aryl iso-
thiocyanates to a?ord indole-2-carbothioamides has been
described,
420
and Cha and co-workers have utilized an intra-
molecular Ti-coupling procedure to construct mitomycin
indole analogs from o-imidostyrenes.
421
8.4 Zirconium
The Buchwald indole-indoline ring synthesis,involving intra-
molecular alkene insertion into a zirconium-stabilized aryne
complex and subsequent oxidation,has been used by Buchwald
and co-workers to prepare 3,4-disubstituted indoles,
422
trypto-
phans and serotonin analogs (Scheme 101),
423
and dehydro-
bufotenine.
387
Scheme 99
Scheme 100
Scheme 101
Tietze and Grote have employed this intramolecular
insertion reaction of zirconocene-stabilized aryne complexes to
synthesize the indoline portion of the CC-1065 pharmaco-
phore.
306,307
8.5 Copper
Although copper has played a role in earlier indole ring
synthesis (vide supra),other indole ring-forming reactions
prompted this separate section.
8.5.1 Castro indole synthesis
Castro et al,were the?rst to discover the metal-catalyzed
cyclization of o-alkynylanilines to indoles using copper.
424–427
Their early contributions to this?eld are often overlooked,but
Castro’s discoveries include the copper acetylide coupling with
o-iodoanilines and the CuI-induced cyclization of o-alkynyl-
anilines to yield indoles,both of which are illustrated in
Scheme 102.
The Castro indole synthesis has been used to prepare 5-
azaindoles,
364
a 2-(benzotriazolylmethyl)indole,
428
an indolo-
[7,6-g]indole,
429
a series of 5,7-disubstituted indoles and
pyrroloindoles,
430
5,7-di?uoro- and 5,6,7-tri?uoroindole,
431
1,2-
dialkyl-5-nitroindoles,
432
and α-C-mannosylindole 52 (Scheme
103).
433
In some cases the Castro cyclization of o-alkynyl-
anilines succeeds where the Larock method of Pd-catalyzed
coupling of o-iodoaniline with an alkyne fails.
428b
The reaction
of o-ethynyltri?uoroacetanilide with Cu(OAc)
2
yields both
indole and 2-alkynylindoles resulting from alkyne coupling and
mono-cyclization.
359
8.5.2 Miscellaneous
Early uses of copper(?) in combination with NaH to e?ect the
cyclization of o-halogenated β-cyano- and β-oxoenamines to
indoles were discovered by Kametani
434
and Suzuki.
435,436
More
recently,this method has been used to make carbazoles
(Scheme 104)
45
and carbazole quinone alkaloids.
437
Copper(?) has been used in a modi?ed intramolecular Gold-
berg amide arylation to forge several β-carbolines,
438
and we
have already cited the use of CuOTf to promote the decom-
position of α-diazo carbonyl compounds and C–H bond
Scheme 102
Scheme 103
1064 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
insertion leading ultimately to tricyclic indoles.
401–403
A nice
variation of this latter reaction leads to the indole ring directly
from acylenamines and methyl diazoacetate (Scheme 105).
439
Barluenga et al,have reported a novel copper-promoted
carbometalation of o-bromo-N-(2-bromoallyl)anilines leading
to 2-substituted or 2,3-disubstituted indoles (Scheme 106).
440
8.6 Chromium
Chromium is a new entrée to the indole ring synthesis arena.
S?derberg et al,have found that substituted indoles are formed
from anilino-substituted Fischer chromium carbenes having
o-alkenyl substituents on the benzene ring (Scheme 107).
441
The
related cyclization of o-alkynylanilino chromium carbene com-
plexes leads to indol-3-ylketene complexes by a tandem alkyne
insertion–carbonylation sequence,Chromium removal and
hydrolysis furnishes indole-3-acetic acids.
442
Benzocarbazoles
and other fused indoles were prepared using this method-
ology.
442
Rahm and Wul? have described the Cr-induced cycliz-
ation of amine-tethered bisalkyne carbene complexes leading
to 5-hydroxyindolines (Scheme 108).
443
8.7 Molybdenum
McDonald and Chatterjee have discovered the molybdenum-
promoted cyclization of 2-ethynylanilines to indoles (Scheme
109).
444
Scheme 104
Scheme 105
Scheme 106
9 Cycloaddition and electrocyclization
9.1 Diels–Alder cycloaddition
Padwa and co-workers have used inter- and intramolecular
Diels–Alder reactions of 2-substituted aminofurans to e?ect
the syntheses of indolines and indoles.
190,445–449
For example,
indoline 53 was crafted in this fashion and then used to syn-
thesize the alkaloid oxoassoanine (Scheme 110).
448
Intramolecular Diels–Alder reactions of pyrazin-2(1H)-
ones,with an o-alkynylanilino side chain,have been employed
to access α- and β-carbolinones.
450
9.2 Photocyclization
9.2.1 Chapman photocyclization
The well-established Chapman photocyclization of N-aryl-
enamines to indolines
451
has been used in the synthesis
of 8,10-dimethoxyellipticine,
341
uorocarbazoles,
452
aza-
tetrahydrocarbazolones,
329
and hexahydrocarbazolones.
453
Photocyclization routes to indoline spirolactones,
454
spiro-
imides,
455,456
and spirolactams
456
have also been developed,An
example of the latter transformation is 54 to 55.
456
Scheme 107
Scheme 108
Scheme 109
Scheme 110
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1065
9.2.2 Miscellaneous photochemical reactions
The photolysis of o-alkynyltelluroimidates yields 3-acyl-
indoles,
457
and the photolysis of the benzotriazolyladamantane
56 leads to oxindole 57 after hydrolysis (Scheme 111).
458,459
This
reaction,which was?rst discovered by Wender and Cooper,
460
has been employed in a total synthesis of gelsemine.
461
Photolysis of α-diazo ketone 58 a?ords indolylketene 59
which is only stable below 58 K,Above this temperature tetra-
meric indole 60 forms in high yield (Scheme 112).
462,463
Giese has observed that o-acylaniline derivatives undergo
photocyclization to 3-hydroxyindolines.
464
9.3 Dipolar cycloaddition
Vedejs and Monahan have reported the intramolecular 1,3-
dipolar cycloaddition of an N-methyloxazolium species to an
alkyne giving rise to indoloquinones.
465
A münchnone gener-
ation and intramolecular cycloaddition protocol by Martinelli
and co-workers leads to 4-oxo-4,5,6,7-tetrahydroindoles
(Scheme 113).
466,467
Ishar and Kumar have described 1,3-dipolar cycloadditions
between allenic esters and nitrones to yield benzo[b]indolizines,
the result of a novel sequence of molecular reorganizations
(Scheme 114).
468
Scheme 111
Scheme 112
Scheme 113
9.4 Miscellaneous
The biradical cyclization of enyne-ketenimines and enyne-
carbodiimides is a powerful route to nitrogen heterocycles,
469–471
including fused indoles such as benzocarbazoles (Scheme
115)
470
and indolo[2,3-b]quinolines.
471
These reactions appear
to involve a stepwise biradical alternative mechanism to the
concerted Myers–Saito cycloaromatization pathway.
Cava and co-workers discovered the surprising cyclization
shown in Scheme 116 en route to the preparation of a wakayin
model system.
472
The N-methyl group was necessary for a
successful reaction,as the NH compound failed to undergo
formation of the pyrrole ring.
10 Indoles from pyrroles
10.1 Electrophilic cyclization
10.1.1 Natsume indole synthesis
Natsume and co-workers have adapted their indole synthesis
to the preparation of herbindole and trikentrin model com-
pounds,
473
as well as to the syntheses of several of these marine
alkaloids.
474
This latter study established the absolute con?gur-
ation of these indole alkaloids,This synthetic strategy,which
involves electrophilic cyclization to C-2 or C-3 of a suitably
tethered pyrrole substrate,has been used to construct the indole
Scheme 114
Scheme 115
Scheme 116
1066 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
ring in hapalindole O
475
and in mitosene analogs related to FR
900482 and FR 66979.
476
The method is particularly e?ective
for the preparation of 4-hydroxyindoles (Scheme 117).
476
The Natsume protocol has been used to synthesize (S)-(H11002)-
pindolol and chuangxinmycin,
477
and Katritzky et al,have
developed an alternative route to the Natsume cyclization sub-
strates using the lithiation of 2-benzotriazolylmethylpyrroles
followed by reaction with α,β-unsaturated aldehydes and
ketones.
478–480
Recently,Natsume and co-workers have syn-
thesized (H11001)-duocarmycin SA using his indole ring synthesis.
481
10.1.2 Miscellaneous
Murakami and co-workers have described an electrophilic
cyclization route to 7-oxo-4,5,6,7-tetrahydroindole,initiated
by the reaction of ethyl pyrrole-2-carboxylate and succinic
anhydride (Scheme 118).
482
Another route to oxotetrahydro-
indoles involves the Friedel–Crafts acylation of N-methyl-
pyrrole with lactones.
483
For example,the reaction of
γ-valerolactone and N-methylpyrrole with AlCl
3
a?ords 1,4-
dimethyl-7-oxo-4,5,6,7-tetrahydroindole in 65% yield.
483
4-Oxotetrahydroindoles are important indole precursors
and Edstrom and Yu have employed these intermediates in
concise syntheses of 5-azaindole analogs
484
and 3-substituted
4-hydroxyindoles,
485,486
which were used to prepare indole-
quinones,Other routes to 4-oxo-4,5,6,7-tetrahydroindoles
have been described,including the synthesis of 6-amino-
methyl derivatives
487
and the enol tri?ate of N-tosyl-4-oxo-
4,5,6,7-tetrahydroindole which was employed in Pd-catalyzed
cross-coupling reactions.
488
Other electrophilic cyclization
methodologies for converting pyrroles to indoles have been
reported for the synthesis of 6-azaindoles,
489
novel fused indoles
as potential dopamine receptor agonists,
490
7-chloroindoles,
491
4,5,6,7-tetrasubstituted and related indoles (Scheme 119),
492
and 1-benzyl-3-phenylindole and related indoles.
493
Wasserman and Blum have reported a general synthesis of
Scheme 117
Scheme 118
2-alkoxycarbonyl-3-hydroxyindoles that involves a Diels–Alder
cycloaddition,pyrrole ring formation from the tricarbonyl
cycloadduct 61,and DDQ oxidation (Scheme 120).
494
The interesting rearrangement of nicotine pyrrole 62 to
1-methylindole-7-carbaldehyde has been uncovered (Scheme
121),
495
and 7-azaindoles are fashioned in one-pot by the
annulation of 2-aminopyrroles with the enolates of 3,3-
dimethoxy-2-formylpropanenitrile and ethyl 3,3-diethoxy-2-
formylpropanoate.
496
10.2 Palladium-catalyzed cyclization
Palladium has been employed in a synthesis of duocarmycin
SA as illustrated in Scheme 122.
497,498
10.3 Cycloaddition routes
10.3.1 From vinylpyrroles
The Diels–Alder cycloaddition of 2- and 3-vinylpyrroles is an
attractive route to indoles,and several new examples of this
Scheme 119
Scheme 120
Scheme 121
Scheme 122
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1067
strategy have been reported in recent years,Ketcha and Xiao
have synthesized 2- and 3-vinyl-1-(phenylsulfonyl)pyrroles and
examined their Diels–Alder chemistry.
499
Domingo et al,have
presented theoretical studies of the reactions of 1-methyl-
2-vinylpyrroles with dimethyl acetylenedicarboxylate,
500,501
studies that suggest the existence of two competitive mechan-
isms depending on the solvent,an asynchronous concerted
mechanism and a stepwise mechanism (Michael addition
reaction),Harman and co-workers have developed an indole
synthesis from Diels–Alder reactions of pentaammineosmium-
pyrrole complexes (Scheme 123).
502,503
An approach to the alkaloid martinelline utilizes an indium-
catalyzed Diels–Alder reaction between aryl imines and N-acyl-
2,3-dihydropyrroles.
504
Photolysis of 2-styrylpyrroles a?ords
indoles,
505
and photolysis of thiobenzamide and 3-furyl-
propenal,which may involve a pyrrole intermediate,a?ords
benzo[g]indoles.
506
10.3.2 From pyrrole-2,3-quinodimethanes
The synthesis of 3-nitroindoles via the electrocyclization of
nitropyrrole-2,3-quinodimethanes,reported in the last review,
has been extended to a general synthesis of these compounds
(Scheme 124).
507
10.3.3 Miscellaneous
The sealed-tube reaction of 4,5-dicyanopyridazine with indole
or N-methylindole a?ords the corresponding 2,3-dicyano-
carbazoles in 59% and 53% yields,respectively.
508
However,
a similar cycloaddition reaction with N-methylpyrrole gives
5,6-dicyano-1-methylindole in only 15–17% yield,Per?uoro-
3,4-dimethylhexa-2,4-diene reacts with anilines in the presence
of?uoride to yield pyrroloquinoline derivatives (Scheme
125).
509
The thermolysis of N-alkyl-N-vinylprop-2-ynylamines pro-
vides 7-oxo-4,5,6,7-tetrahydroindoles in good yield (Scheme
126).
510
Scheme 123
Scheme 124
10.4 Radical cyclization
New routes to 4,5,6,7-tetrahydroindoles involving the radical
cyclization of an iodoalkyl-tethered pyrrole (Scheme 127)
511
and a 2-alkenyl-tethered 3-iodopyrrole have been elaborated.
512
11 Aryne intermediates
11.1 Aryne Diels–Alder cycloaddition
The ergot model 63 was obtained in essentially quantitative
yield via the intramolecular aryne cycloaddition reaction shown
in Scheme 128.
513
11.2 Nucleophilic cyclization of arynes
Caubère and co-workers have described in full their synthesis
of tetrahydrocarbazoles and other indoles using the complex
base NaNH
2
–t-BuONa to generate the requisite arynes for
cyclization.
514
More recently,this group has extended this
methodology to an e?cient synthesis of 2-substituted indoles
by the arynic cyclization of halogenated aryl imines (Scheme
129).
515
Beller et al,have discovered a novel,domino hydroamination
aryne cyclization reaction” to give N-aryl indolines from
o-chlorostyrenes in good yields (Scheme 130).
516
This method is
superior to previous cyclizations of 2-(2-chlorophenyl)ethyl-
amines.
Scheme 125
Scheme 126
Scheme 127
Scheme 128
1068 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
In chemistry similar to the Bailey–Liebeskind indole syn-
thesis (Section 3.9),Barluenga and co-workers have found
that the treatment of N-(2-bromoallyl)-N-methyl-2-?uoro-
aniline with tert-butyllithium gives 1,3-dimethyl-4-lithioindole
by intramolecular aryne cyclization,Quenching this intermedi-
ate with suitable electrophiles a?ords the 4-functionalized
indoles.
517
12 Miscellaneous indole syntheses
12.1 Oxidation of indolines
Although indolines (2,3-dihydroindoles) are an obvious vehicle
for the synthesis of indoles,there has never been an e?cient,
general method for this oxidation reaction,However,a few new
methods to address this problem have been described in recent
years.
The use of catalytic tetra-n-propylammonium perruthenate
in the presence of N-methylmorpholine N-oxide is reported by
Goti and Romani to oxidize indoline to indole in 73% yield.
518
The generality of this conversion remains to be seen,Carter
and Van Vranken have observed the photooxidation of 2-indol-
2-ylindolines to 2,2H11032-biindolyls,
519
and Giethlen and Schaus
have investigated the mechanism of the oxidation of indolines
with potassium nitrosodisulfonate (Frémy’s salt) to furnish
either indoles or 5-hydroxyindoles.
520
It was determined by isol-
ation that an intermediate iminoquinone forms in this reaction.
Ketcha et al,have utilized Mn() in the oxidation of 2-methyl-
1-(phenylsulfonyl)indolines to the corresponding 2-acetoxy-
methylindoles (Scheme 131).
521
12.2 From oxindoles,isatins and indoxyls
Since we have included in this review the synthesis of oxindoles,
isatins,and indoxyls,it seems appropriate to cite newer methods
and applications for the conversion of these compounds to
indoles.
Williams and co-workers have employed the combination of
NaBH
4
and BF
3
H11554OEt
2
to reduce an oxindole to an indole in
their synthesis of (H11001)-paraherquamide B.
206
Other reduction
methods were unsuccessful,Black and Rezaie have coupled
oxindoles with benzofurans using tri?ic anhydride to give 2-
indolylbenzofurans,
522
and Beccalli and Marchesini have syn-
thesized 3-acyl-2-vinylindoles from chloroalkylidene oxindoles
Scheme 129
Scheme 130
Scheme 131
using a Stille reaction on the corresponding indolyl-2-
tri?ates.
523
The chloroalkylidene oxindoles can also be easily
transformed into 3-alkynylindoles.
524
The reduction of N-acyl-
isatins to N-alkylindoles proceeds excellently with diborane,
525
and isatins are converted into oxindoles with hydrazine.
526
Merlic and co-workers have e?ected a Friedlander quinol-
ine synthesis on an N-acylindoxyl to a?ord a quindoline,
which was used to prepare the RNA-binding?uorochrome
Fluoro Nissl Green.
527
As mentioned earlier (Section 2.6),
Sakamoto and co-workers have used a tandem Wittig–Cope
reaction sequence on 2-allylindoxyls to prepare 3-substituted
indoles (Scheme 18).
102
Earlier work showed that Wittig reac-
tions of indoxyls that cannot undergo a Cope reaction a?ord 3-
substituted indoles.
528
12.3 Miscellaneous
The thermolysis (900 H11034C) of N-(2-acetoxyethyl)acetanilide
yields many products including some indole,
529
and?ash
vacuum pyrolysis of 1-phenyl-4-methoxycarbonyl-1,2,3-
triazole a?ords a small amount of 3-methoxycarbonylindole
via an imino carbene intermediate.
530
Treatment of N-(methyl)-
anthranilic acids with the Vilsmeier reagent (POCl
3
–DMF)
leads to 3-chloroindole-2-carbaldehydes.
531
Meth-Cohn has
uncovered interesting chemistry when Vilsmeier reagents are
generated under basic conditions.
532–534
Thus,exposure of
formanilides sequentially to oxalyl chloride,Hünig’s base,
and bromine a?ords,after hydrolysis,the corresponding isatin
(Scheme 132).
532–534
Under slightly di?erent conditions,
N-alkylformanilides and POCl
3
yield the indolo[3,2-b]quinol-
ines (Scheme 133).
534
An unusual cyanide-induced skeletal rearrangement of 3-
acyl- and 3-ethoxycarbonyl-1,2-dihydrocinnoline-1,2-dicarbox-
imides leads to 2-acyl- and 2-ethoxycarbonyl-3-cyanoindoles
(Scheme 134),
535
a reaction based on similar rearrangements
discovered earlier.
536–538
Ciufolini et al,have used the cyclization of 2-amino-2,3-
dihydrobenzoquinone monoketals to obtain fused indolines
after appropriate manipulation.
539
Studies by Paz and Hopkins
Scheme 132
Scheme 133
Scheme 134
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1069
on the antitumor antibiotic agents FR66979,FR900482,and
FK973,which are DNA crosslinkers similar to mitomycin C,
indicate that cyclization to an indole is likely involved in the
mode of action of these compounds.
540
Rigby and co-workers
have developed several variations of the reaction between vinyl
isocyanates and isocyanides or nucleophilic carbenes to a?ord
functionalized oxindoles or isatins,Thus,these workers have
prepared simple hydrooxindoles,
541–543
oxindoles (Scheme
135),
544
hydroisatins,
545–546
and the alkaloid degradation product
(±)-α-lycorane.
547
An unusually facile cyclization of tetrahydroisoquinoline 64
leads to the indolo[2,1-a]isoquinoline ring system (Scheme
136).
548
Several examples of this reaction were reported.
The reaction of diarylnitrones with trimethylsilylketene
a?ords oxindoles,
549
and 1,4-naphthoquinone reacts with aza-
ortho-xylylenes,which were generated from benzosultams,to give
naphthoquinone spiroindolines.
550
Base-induced dimerization
of 4H-3,1-benzothiazines gives 2-substituted indoles after reduc-
tion of the intermediate diindolyl disul?des (Scheme 137).
551
13 Acknowledgements
The author wishes to thank Professor Phil Crews and his
colleagues and students at the University of California,Santa
Cruz,for their hospitality during a sabbatical leave in 1999–2000
when this article was written,This paper is dedicated to the
memory of Dr Pierre D,Lord,1936–1999,fellow graduate
student,indole chemist and friend.
Scheme 135
Scheme 136
Scheme 137
14 References
1 G,W,Gribble,Contemp,Org,Synth.,1994,145.
2 The reader is also referred to these other reviews (a) U,Pindur and
R,Adam,J,Heterocycl,Chem.,1988,25,1; (b) C,J,Moody,Synlett,
1994,681; (c) R,J,Sundberg,Indoles,Academic Press,San Diego,
CA,1996; (d) T,L,Gilchrist,J,Chem,Soc.,Perkin Trans,1,1999,
2848.
3 B,Robinson,The Fischer Indole Synthesis,Wiley-Interscience,
New York,1982.
4 D,L,Hughes,Org,Prep,Proced,Int.,1993,25,607.
5 V,Sridar,Indian J,Chem.,Sect,B,1996,35,737.
6 V,Sridar,Indian J,Chem.,Sect,B,1997,36,86.
7 J,An,L,Bagnell,T,Cablewski,C,R,Strauss and R,W,Trainor,
J,Org,Chem.,1997,62,2505.
8 T,Lipinska,E,Guibé-Jampel,A,Petit and A,Loupy,Synth.
Commun.,1999,29,1349.
9 G,Penieres,R,Miranda,J,García,J,Aceves and F,Delgado,
Heterocycl,Commun.,1996,2,401.
10 M,S,Rigutto,H,J,A,de Vries,S,R,Magill,A,J,Hoefnagel and
H,van Bekkum,Stud,Surf,Sci,Catal.,1993,78,661.
11 P,J,Kunkeler,M,S,Rigutto,R,S,Downing,H,J,A,de Vries and
H,van Bekkum,Stud,Surf,Sci,Catal.,1997,105B,1269.
12 Y,Cheng and K,T,Chapman,Tetrahedron Lett.,1997,38,1497.
13 S,M,Hutchins and K,T,Chapman,Tetrahedron Lett.,1996,37,
4869.
14 R,M,Kim,M,Manna,S,M,Hutchins,P,R,Gri?n,N,A,Yates,
A,M,Bernick and K,T,Chapman,Proc,Natl,Acad,Sci,USA,
1996,93,10012.
15 O,Miyata,Y,Kimura,K,Muroya,H,Hiramatsu and T,Naito,
Tetrahedron Lett.,1999,40,3601.
16 K,Maruoka,M,Oishi and H,Yamamoto,J,Org,Chem.,1993,58,
7638.
17 (a) S,Wagaw,B,H,Yang and S,L,Buchwald,J,Am,Chem,Soc.,
1998,120,6621; (b) S,Wagaw,B,H,Yang and S,L,Buchwald,
J,Am,Chem,Soc.,1999,121,10251.
18 K,Yamada and M,Somei,Heterocycles,1998,48,2481.
19 R,Liu,P,W,Zhang,T,Gan and J,M,Cook,J,Org,Chem.,1997,
62,7447.
20 T,Gan,R,Liu,P,Yu,S,Zhao and J,M,Cook,J,Org,Chem.,1997,
62,9298.
21 Z,P,Zhang,L,M,V,Tillekeratne and R,A,Hudson,Synthesis,
1996,377.
22 Z,P,Zhang,L,M,V,Tillekeratne and R,A,Hudson,Tetrahedron
Lett.,1998,39,5133.
23 Y,Bessard,Org,Process Res,Dev.,1998,2,214.
24 M,Jukic,M,Cetina,G,Pavlovic and V,Rapic,Struct,Chem.,1999,
10,85.
25 J,Tholander and J,Bergman,Tetrahedron,1999,55,12577.
26 Y,Murakami,T,Watanabe,H,Takahashi,H,Yokoo,Y,Nakazawa,
M,Koshimizu,N,Adachi,M,Kurita,T,Yoshino,T,Inagaki,
M,Ohishi,M,Watanabe,M,Tani and Y,Yokoyama,Tetrahedron,
1998,54,45.
27 B,G,Szczepankiewicz and C,H,Heathcock,Tetrahedron,1997,53,
8853.
28 J,D,White,K,M,Yager and T,Yakura,J,Am,Chem,Soc.,1994,
116,1831.
29 S,Lajsic,G,Cetkovic,M,Popsavin,V,Popsavin and D,Miljkovic,
Collect,Czech,Chem,Commun.,1996,61,298.
30 L,Novák,M,Hanania,P,Kovács,J,Rohály,P,Kolonits and
C,Szántay,Heterocycles,1997,45,2331.
31 C,Chen,C,H,Senanoyake,T,J,Bill,R,D,Larsen,T,R,Verhoeven
and P,J,Reider,J,Org,Chem.,1994,59,3738.
32 L,J,Street,R,Baker,W,B,Davey,A,R,Guiblin,R,A,Jelley,A,J.
Reeve,H,Routledge,F,Sternfeld,A,P,Watt,M,S,Beer,D,N.
Middlemiss,A,J,Noble,J,A,Stanton,K,Scholey,R,J,Hargreaves,
B,Sohal,M,I,Graham and V,G,Matassa,J,Med,Chem.,1995,38,
1799.
33 G,P,Moloney,G,R,Martin,N,Mathews,H,Hobbs,
S,Dodsworth,P,Y,Sang,C,Knight,M,Maxwell and R,C,Glen,
J,Chem,Soc.,Perkin Trans,1,1999,2699.
34 G,P,Moloney,G,R,Martin,N,Mathews,H,Hobbs,
S,Dodsworth,P,Y,Sang,C,Knight,M,Maxwell and R,C,Glen,
J,Chem,Soc.,Perkin Trans,1,1999,2713.
35 Y.-C,Xu,J,M,Schaus,C,Walker,J,Krushinski,N,Adham,
J,M,Zgombick,S,X,Liang,D,T,Kohlman and J,E,Audia,
J,Med,Chem.,1999,42,526.
36 W,Marias and C,W,Holzapfel,Synth,Commun.,1998,28,
3681.
37 G,W,Fischer,J,Heterocycl,Chem.,1995,32,1557.
38 B,Pete,I,Bitter,C,Szántay,Jr.,I,Sch?n and L,T?ke,Heterocycles,
1998,48,1139.
1070 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
39 P,Remuzon,C,Dussy,J,P,Jacquet,M,Soumeillant and D.
Bouzard,Tetrahedron Lett.,1995,36,6227.
40 I,Hermecz,J,K?k?si,B,Podányi and G,Szász,Heterocycles,1994,
37,903.
41 N,M,Przheval’skii,I,V,Magedov and V,N,Drozd,Chem.
Heterocycl,Compd,NY,1997,33,1475.
42 K,Cucek and B,Vercek,Synlett,1999,120.
43 C,C,Boido,V,Boido,F,Novelli and F,Sparatore,J,Heterocycl.
Chem.,1998,35,853.
44 J,Gràcia,N,Casamitjana,J,Bonjoch and J,Bosch,J,Org,Chem.,
1994,59,3939.
45 D,Desma?le and J,d’Angelo,J,Org,Chem.,1994,59,2292.
46 J,Bonjoch,J,Catena and N,Valls,J,Org,Chem.,1996,61,7106.
47 D,Crich,E,Fredette and W,J,Flosi,Heterocycles,1998,48,
545.
48 Y,Murakami,H,Yokoo and T,Watanabe,Heterocycles,1998,49,
127.
49 I,Hermecz,P,Forgó,Z,B?cskei,M,Fehér,J,K?k?si and G,Szász,
J,Heterocycl,Chem.,1996,33,799.
50 I,Hermecz,J,K?k?si,B,Podányi and Z,Liko,Tetrahedron,1996,
52,7789.
51 G,Lin and A,Zhang,Tetrahedron Lett.,1999,40,341.
52 C,H,Nguyen,C,Marchand,S,Delage,J.-S,Sun,T,Garestier,
C,Hélène and E,Bisagni,J,Am,Chem,Soc.,1998,120,2501.
53 L,Martarello,D,Joseph and G,Kirsch,J,Chem,Soc.,Perkin
Trans,1,1995,2941.
54 L,Martarello,D,Joseph and G,Kirsch,Heterocycles,1996,43,367.
55 J,A,Hill and J,F,Eaddy,J,Labelled Compd,Radiopharm.,1994,34,
697.
56 C,Schultz,A,Link,M,Leost,D,W,Zaharevitz,R,Gussio,
E,A,Sausville,L,Meijer and C,Kunick,J,Med,Chem.,1999,42,
2909.
57 H,Schmidhammer,R,Krassnig,E,Greiner,J,Schütz,A,White
and I,P,Berzetei-Gurske,Helv,Chim,Acta,1998,81,1064.
58 A,Coop,R,B,Rothman,C,Dersch,J,Partilla,F,Porreca,P,Davis,
A,E,Jackson and K,C,Rice,J,Med,Chem.,1999,42,1673.
59 D,W,Brown,M,F,Mahon,A,Ninan and M,Sainsbury,J,Chem.
Soc.,Perkin Trans,1,1997,2329.
60 L.-H,Zhang,W,Meier,E,Wats,T,D,Costello,P,Ma,C,L.
Ensinger,J,M,Rodgers,I,C,Jacobson and P,Rajagopalan,
Tetrahedron Lett.,1995,36,8387.
61 D,W,Brown,M,F,Mahon,A,Ninan and M,Sainsbury,J,Chem.
Soc.,Perkin Trans,1,1997,1699.
62 J,R,Lever and S,M,Johnson,J,Labelled Compd,Radiopharm.,
1997,39,115.
63 L,Rao and A,K,Mukerjee,Indian J,Chem.,Sect,B,1994,33,166.
64 H,Royer,D,Joseph,D,Prim and G,Kirsch,Synth,Commun.,1998,
28,1239.
65 M,Inouye,K,Akamatsu and H,Nakazumi,J,Am,Chem,Soc.,
1997,119,9160.
66 F,Fernández,X,García-Mera,G,Rodríguez and A,Urrutia,Chem.
Pharm,Bull.,1999,47,1006.
67 P,E,Maligres,I,Houpis,K,Rossen,A,Molina,J,Sager,
V,Upadhyay,K,M,Wells,R,A,Reamer,J,E,Lynch,D,Askin,
R,P,Volante and P,J,Reider,Tetrahedron,1997,53,10983.
68 N,G,Anderson,T,D,Ary,J,L,Berg,P,J,Bernot,Y,Y,Chan,C.-K.
Chen,M,L,Davies,J,D,DiMarco,R,D,Dennis,R,P,Deshpande,
H,D,Do,R,Droghini,W,A,Early,J,Z,Gougoutas,J,A,Grosso,
J,C,Harris,O,W,Haas,P,A,Jass,D,H,Kim,G,A,Kodersha,
A,S,Kotnis,J,LaJeunesse,D,A,Lust,G,D,Madding,S,P,Modi,
J,L,Moniot,A,Nguyen,V,Palaniswamy,D,W,Phillipson,J,H.
Simpson,D,Thoraval,D,A,Thurston,K,Tse and R,E,Polomski,
Org,Process Res,Dev.,1997,1,300.
69 E,C,Taylor and B,Hu,Heterocycles,1996,43,323.
70 A,Gangjee and L,Chen,J,Heterocycl,Chem.,1999,36,441.
71 Y,Miki,K,Matsushita,H,Hibino and H,Shirokoshi,Heterocycles,
1999,51,1585.
72 S,Caron and E,Vazquez,Synthesis,1999,588.
73 A,Molina,J,J,Vaquero,J,L,Garcia-Navio,J,Alvarez-Builla,
B,de Pascual-Teresa,F,Gago,M,M,Rodrigo and M,Ballesteros,
J,Org,Chem.,1996,61,5587.
74 D,L,Hughes,J,Phys,Org,Chem.,1994,7,625.
75 J,Kereselidze and N,Raevski,Soobshch,Akad,Nauk,Gruz.,1996,
153,380; Chem,Abstr.,1998,128,243632.
76 J,Kereselidze and K,Raevski,Izv,Akad,Nauk Gruz.,Ser,Khim.,
1996,22,170; Chem,Abstr.,1999,130,281694.
77 Y,Murakami,T,Watanabe,T,Hagiwara,Y,Akiyama and H,Ishii,
Chem,Pharm,Bull.,1995,43,1281.
78 Y,Murakami,T,Watanabe,T,Otsuka,T,Iwata,Y,Yamada and
Y,Yokoyama,Chem,Pharm,Bull.,1995,43,1287.
79 Y,Murakami,H,Yokoo,Y,Yokoyama and T,Watanabe,Chem.
Pharm,Bull.,1999,47,791.
80 H,Fujii,A,Mizusuna,R,Tanimura and H,Nagase,Heterocycles,
1997,45,2109.
81 K,Bast,T,Durst,R,Huisgen,K,Lindner and R,Temme,
Tetrahedron,1998,54,3745.
82 K,Bast,T,Durst,H,Huber,R,Huisgen,K,Lindner,D,S.
Stephenson and R,Temme,Tetrahedron,1998,54,8451.
83 P,G,Gassman,T,J,van Bergen,D,P,Gilbert and B,W,Cue,Jr.,
J,Am,Chem,Soc.,1974,96,5495.
84 P,G,Gassman and T,J,van Bergen,J,Am,Chem,Soc.,1974,96,
5508.
85 P,G,Gassman,G,Gruetzmacher and T,J,van Bergen,J,Am.
Chem,Soc.,1974,96,5512.
86 P,G,Gassman,G,Gruetzmacher and T,J,van Bergen,J,Am.
Chem,Soc.,1973,95,6508.
87 B,M,Savall and W,W,McWhorter,J,Org,Chem.,1996,61,8696.
88 S,W,Wright,L,D,McClure and D,L,Hageman,Tetrahedron
Lett.,1996,37,4631.
89 G,Bartoli,M,Bosco,R,Dalpozzo,G,Palmieri and E.
Marcantoni,J,Chem,Soc.,Perkin Trans,1,1991,2757.
90 M,Bosco,R,Dalpozzo,G,Bartoli,G,Palmieri and M,Petrini,
J,Chem,Soc.,Perkin Trans,2,1991,657.
91 P,Wiedenau,B,Monse and S,Blechert,Tetrahedron,1995,51,
1167.
92 D,C,Harrowven,D,Lai and M,C,Lucas,Synthesis,1999,1300.
93 B,S,Thyagarajan,J,B,Hillard,K,V,Reddy and K,C,Majumdar,
Tetrahedron Lett.,1974,1999.
94 J,Hillard,K,V,Reddy,K,C,Majumdar and B,S,Thyagarajan,
J,Heterocycl,Chem.,1974,11,369.
95 B,S,Thyagarajan and K,C,Majumdar,J,Heterocycl,Chem.,
1975,12,43.
96 K,C,Majumdar,G,H,Jana and U,Das,Chem,Commun.,1996,
517.
97 K,C,Majumdar,G,H,Jana and U,Das,J,Chem,Soc.,Perkin
Trans,1,1997,1229.
98 K,C,Majumdar and S,K,Ghosh,J,Chem,Soc.,Perkin Trans,1,
1994,2889.
99 T,Balasubramanian and K,K,Balasubramanian,J,Chem,Soc.,
Chem,Commun.,1994,1237.
100 J.-B,Baudin and S,A,Julia,Tetrahedron Lett.,1986,27,837.
101 J.-B,Baudin,M.-G,Comménil,S,A,Julia,R,Lorne and
L,Mauclaire,Bull,Soc,Chim,Fr.,1996,133,329.
102 T,Kawasaki,K,Watanabe,K,Masuda and M,Sakamoto,
J,Chem,Soc.,Chem,Commun.,1995,381.
103 W,J,Houlihan,V,A,Parrino and Y,Uike,J,Org,Chem.,1981,46,
4511.
104 K,Miyashita,K,Tsuchiya,K,Kondoh,H,Miyabe and T.
Imanishi,Heterocycles,1996,42,513.
105 K,Miyashita,K,Kondoh,K,Tsuchiya,H,Miyabe and T.
Imanishi,J,Chem,Soc.,Perkin Trans,1,1996,1261.
106 I,Hughes,Tetrahedron Lett.,1996,37,7595.
107 D,Hands,B,Bishop,M,Cameron,J,S,Edwards,I,F,Cottrell and
S,H,B,Wright,Synthesis,1996,877.
108 R,D,Clark,J,M,Muchowski,M,Souchet and D,B,Repke,
Synlett,1990,207.
109 R,E,Mewshaw,K,L,Marquis,X,Shi,G,McGaughey,G,Stack,
M,B,Webb,M,Abou-Gharbia,T,Wasik,R,Scerni,T,Spangler,
J,A,Brennan,H,Mazandarani,J,Coupet and T,H,Andree,
Tetrahedron,1998,54,7081.
110 M,Takahashi and D,Suga,Synthesis,1998,986.
111 G,Kim and G,Keum,Heterocycles,1997,45,1979.
112 A,S,Kiselyov,Tetrahedron Lett.,1999,40,4119.
113 P,A,Wender and A,W,White,Tetrahedron,1983,39,3767.
114 P,Hewawasam and N,A,Meanwell,Tetrahedron Lett.,1994,35,
7303.
115 K,Smith,G,A,El-Hiti and A,C,Hawes,Synlett,1999,945.
116 K,Smith,G,A,El-Hiti,G,J,Pritchard and A,Hamilton,J,Chem.
Soc.,Perkin Trans,1,1999,2299.
117 K,Smith,G,A,El-Hiti and A,P,Shukla,J,Chem,Soc.,Perkin
Trans,1,1999,2305.
118 A,B,Smith,III,M,Visnick,J,N,Haseltine and P,A,Sprengeler,
Tetrahedron,1986,42,2957.
119 K,E,Henegar and D,A,Hunt,Heterocycles,1996,43,1471.
120 M,Kihara,Y,Iwai and Y,Nagao,Heterocycles,1995,41,2279.
121 M,Kinugawa,H,Arai,H,Nishikawa,A,Sakaguchi,T,Ogasa,
S,Tomioka and M,Kasai,J,Chem,Soc.,Perkin Trans,1,1995,
2677.
122 M,S,Mayadeo and S,A,Gandhi,J,Indian Chem,Soc.,1994,71,
281.
123 J,M,Pawlak,V,V,Khau,D,R,Hutchison and M,J,Martinelli,
J,Org,Chem.,1996,61,9055.
124 T,A,Engler,K,O,Lynch,Jr.,W,Chai and S,P,Meduna,
Tetrahedron Lett.,1995,36,2713.
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1071
125 T,A,Engler,W,Chai and K,O,Lynch,Jr.,Tetrahedron Lett.,1995,
36,7003.
126 T,A,Engler,S,P,Meduna,K,O,LaTessa and W,Chai,J,Org.
Chem.,1996,61,8598.
127 T,A,Engler,W,Chai and K,O,LaTessa,J,Org,Chem.,1996,61,
9297.
128 T,A,Engler and J,Wanner,Tetrahedron Lett.,1997,38,6135.
129 H,Tohma,H,Watanabe,S,Takizawa,T,Maegawa and Y,Kita,
Heterocycles,1999,51,1785.
130 W,F,Bailey and X.-L,Jiang,J,Org,Chem.,1996,61,2596.
131 D,Zhang and L,S,Liebeskind,J,Org,Chem.,1996,61,2594.
132 S,Lemaire-Audoire,M,Savignac,J,P,Genet and J.-M,Bernard,
Tetrahedron Lett.,1995,36,1267.
133 T,S,Yokum,P,K,Tungaturthi and M,L,McLaughlin,
Tetrahedron Lett.,1997,38,5111.
134 W,F,Bailey and M,W,Carson,Tetrahedron Lett.,1997,38,1329.
135 S,W,Wright,R,L,Dow,L,D,McClure and D,L,Hageman,
Tetrahedron Lett.,1996,37,6965.
136 Y,Ito,K,Kobayashi and T,Saegusa,J,Am,Chem,Soc.,1977,99,
3532.
137 Y,Ito,K,Kobayashi,N,Seko and T,Saegusa,Bull,Chem,Soc.
Jpn.,1984,57,73.
138 M,Makosza,J,Stalewski,K,Wojciechowski and W,Danikiewicz,
Tetrahedron,1997,53,193.
139 M,Makosza,Synthesis,1991,103.
140 M,Makosza and K,Wojciechowski,Liebigs Ann./Recl.,1997,
1805.
141 M,V,Basaveswara Rao,U,K,Syam Kumar,H,Ila and H.
Junjappa,Tetrahedron,1999,55,11563.
142 R,Filler,W,Chen and S,M,Woods,J,Fluorine Chem.,1995,73,
95.
143 J,Ichikawa,Y,Wada,T,Okauchi and T,Minami,Chem,Commun.,
1997,1537.
144 J,K,Sutherland,Chem,Commun.,1997,325.
145 P,Dalla Croce,R,Ferraccioli and C,La Rosa,Heterocycles,1996,
43,2397.
146 A,Arcadi and E,Rossi,Synlett,1997,667,
147 S,H,Kim and P,L,Fuchs,Tetrahedron Lett.,1996,37,2545.
148 T,Besson,G,Guillaumet,C,Lamazzi,C,W,Rees and V,Thiéry,
J,Chem,Soc.,Perkin Trans,1,1998,4057.
149 P,Langer and M,D?ring,Synlett,1998,396.
150 C,J,Moody and E,Swann,Synlett,1998,135.
151 T.-M,Ly,N,M,Laso and S,Z,Zard,Tetrahedron,1998,54,
4889.
152 C,W,Holzapfel and C,Dwyer,Heterocycles,1998,48,1513.
153 K,Jesudoss and P,C,Srinivasan,Synth,Commun.,1994,24,
1701.
154 Y,Nishiyama,R,Maema,K,Ohno,M,Hirose and N,Sonoda,
Tetrahedron Lett.,1999,40,5717.
155 P,Molina,J,Alcántara and C,López-Leonardo,Tetrahedron Lett.,
1995,36,953.
156 P,Molina,J,Alcántara and C,López-Leonardo,Tetrahedron,
1996,52,5833.
157 P,M,Fresneda,P,Molina and S,Delgado,Tetrahedron Lett.,1999,
40,7275.
158 G,Timári,T,Soós and G,Hajós,Synlett,1997,1067.
159 S,Murata,H,Tsuji and H,Tomioka,Bull,Chem,Soc,Jpn.,1994,
67,895.
160 I,A,Bhatti,R,E,Busby,M,bin Mohamed,J,Parrick and
C,J,G,Shaw,J,Chem,Soc.,Perkin Trans,1,1997,3581.
161 E,T,Pelkey and G,W,Gribble,Tetrahedron Lett.,1997,38,5603.
162 A,S,Kiselyov,K,Van Aken,Y,Gulevich and L,Strekowski,
J,Heterocycl,Chem.,1994,31,1299.
163 Y,Murakami,T,Watanabe,H,Suzuki,N,Kotake,T,Takahashi,
K,Toyonari,M,Ohno,K,Takase,T,Suzuki and K,Kondo,
Chem,Pharm,Bull.,1997,45,1739.
164 P,Magnus and T,E,Mansley,Tetrahedron Lett.,1999,40,6909.
165 S,S,Samanta,S,C,Ghosh and A,De,J,Chem,Soc.,Perkin Trans.
1,1997,3673.
166 M,Tercel,M,A,Gieseg,W,A,Denny and W,R,Wilson,J,Org.
Chem.,1999,64,5946.
167 P,Molina and J,Alcántara and C,López-Leonardo,Tetrahedron,
1997,53,3281.
168 E,Arzel,P,Rocca,F,Marsais,A,Godard and G,Quéguiner,
J,Heterocycl,Chem.,1997,34,1205.
169 M,Iwao,Heterocycles,1994,38,45.
170 T,Fukuyama and X,Chen,J,Am,Chem,Soc.,1994,116,3125.
171 P,Magnus and I,S,Mitchell,Tetrahedron Lett.,1998,39,4595.
172 K,S,Feldman,M,M,Bruendl and K,Schildknegt,J,Org,Chem.,
1995,60,7722.
173 K,S,Feldman,M,M,Bruendl,K,Schildknegt and A,C.
Bohnstedt,J,Org,Chem.,1996,61,5440.
174 F,E,Ziegler and M,Y,Berlin,Tetrahedron Lett.,1998,39,2455.
175 T,Kakigami,T,Usui,K,Tsukamoto and T,Kataoka,Chem.
Pharm,Bull.,1998,46,42.
176 E,Arai,H,Tokuyama,M,S,Linsell and T,Fukuyama,Tetra-
hedron Lett.,1998,39,71.
177 H,Sakagami and K,Ogasawara,Heterocycles,1999,51,1131.
178 A,Chilin,P,Rodighiero and A,Guiotto,Synthesis,1998,309.
179 T,Ishikawa,T,Saito,S,Noguchi,H,Ishii,S,Ito and T,Hata,
Tetrahedron Lett.,1995,36,2795.
180 T,Ishikawa,T,Saito and H,Ishii,Tetrahedron,1995,51,8447.
181 T,A,Kshirsagar and L,H,Hurley,J,Org,Chem.,1998,63,5722.
182 T,A,Kshirsagar and L,H,Hurley,Heterocycles,1999,51,185.
183 A,G,Wee and B,Liu,Tetrahedron,1994,50,609.
184 K,Smith and D,Bahzad,J,Chem,Soc.,Perkin Trans,1,1996,
2793.
185 S,J,Garden,J,C,Torres,A,A,Ferreira,R,B,Silva and A,C.
Pinto,Tetrahedron Lett.,1997,38,1501.
186 H,Ishibashi,M,Higuchi,H,Masuko,K,Kodama and M,Ikeda,
Heterocycles,1997,46,37.
187 A,Padwa,R,Hennig,C,O,Kappe and T,S,Reger,J,Org,Chem.,
1998,63,1144.
188 A,Padwa and J,T,Kuethe,J,Org,Chem.,1998,63,4256.
189 For a review of the Pummerer reaction to construct complex
carbocycles and heterocycles,see A,Padwa and D,E,Gunn,Jr.,
Synthesis,1997,1353.
190 For a review of his work in this area,see A,Padwa,Chem.
Commun.,1998,1417.
191 F,He,Y,Bo,J,D,Altom and E,J,Corey,J,Am,Chem,Soc.,1999,
121,6771.
192 A,K,Sinhababu and R,T,Borchardt,J,Org,Chem.,1983,48,
3347.
193 Y,Fukuyama,C,Iwatsuki,M,Kodama,M,Ochi,K,Kataoka and
K,Shibata,Tetrahedron,1998,54,10007.
194 L.-M,Yang,C.-F,Chen and K.-H,Lee,Bioorg,Med,Chem,Lett.,
1995,5,465.
195 L,Novellino,M,d’Ischia and G,Prota,Synthesis,1999,793.
196 C,Shin,Y,Yamada,K,Hayashi,Y,Yonezawa,K,Umemura,
T,Tanji and J,Yoshimura,Heterocycles,1996,43,891.
197 M,Taga,H,Ohtsuka,I,Inoue,T,Kawaguchi,S,Nomura,
K,Yamada,T,Date,H,Hiramatsu and Y,Sato,Heterocycles,
1996,42,251.
198 H,Stephensen and F,Zaragoza,Tetrahedron Lett.,1999,40,5799.
199 G,A,Kraus and N,Selvakumar,Synlett,1998,845.
200 D,Roberts,M,Alvarez and J,A,Joule,Tetrahedron Lett.,1996,37,
1509.
201 M,Alvarez,M,A,Bros and J,A,Joule,Tetrahedron Lett.,1998,
39,679.
202 M,Alvarez,M,A,Bros,G,Gras,W,Ajana and J,A,Joule,Eur,J.
Org,Chem.,1999,1173.
203 B,Quiclet-Sire,I,Thévenot and S,Z,Zard,Tetrahedron Lett.,
1995,36,9469.
204 S,A,Kozmin and V,H,Rawal,J,Am,Chem,Soc.,1998,120,
13523.
205 T,Iwama,V,B,Birman,S,A,Kozmin and V,H,Rawal,Org,Lett.,
1999,1,673.
206 T,D,Cushing,J,F,Sanz-Cervera and R,M,Williams,J,Am.
Chem,Soc.,1996,118,557.
207 E,A,Kraynack,J,E,Dalgard and F,C,A,Gaeta,Tetrahedron
Lett.,1998,39,7679.
208 M,Ochi,K,Kataoka,S,Ariki,C,Iwatsuki,M,Kodama and Y.
Fukuyama,J,Nat,Prod.,1998,61,1043.
209 H,D,H,Showalter,L,Sun,A,D,Sercel,R,T,Winters,W,A.
Denny and B,D,Palmer,J,Org,Chem.,1996,61,1155.
210 D,R,Witty,G,Walker,J,H,Bateson,P,J,O’Hanlon,D,S.
Eggleston and R,C,Haltiwanger,Tetrahedron Lett.,1996,37,
3067.
211 M,Brenner,G,Mayer,A,Terpin and W,Steglich,Chem,Eur,J.,
1997,3,70.
212 G,M,Carrera,Jr,and G,S,Sheppard,Synlett,1994,93.
213 C,I,Clark,J,M,White,D,P,Kelly,R,F,Martin and P.
Lobachevsky,Aust,J,Chem.,1998,51,243.
214 M,Prashad,L,L,Vecchia,K,Prasad and O,Repic,Synth.
Commun.,1995,25,95.
215 J,W,Coe,M,G,Vetelino and M,J,Bradlee,Tetrahedron Lett.,
1996,37,6045.
216 Z,Wróbel and M,Makosza,Tetrahedron,1997,53,5501.
217 M,Makosza and J,Stalewski,Tetrahedron,1995,51,7263.
218 M,Makosza,J,Stalewski and O,S,Maslennikova,Synthesis,1997,
1131.
219 N,Moskalev and M,Makosza,Tetrahedron Lett.,1999,40,5395.
220 S,C,Shim,Y,Z,Youn,D,Y,Lee,T,J,Kim,C,S,Cho,S,Uemura
and Y,Watanabe,Synth,Commun.,1996,26,1349.
1072 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
221 D,Y,Lee,C,S,Cho,J,H,Kim,Y,Z,Youn,S,C,Shim and
H,Song,Bull,Korean Chem,Soc.,1996,17,1132.
222 C,S,Cho,H,K,Lim,S,C,Shim,T,J,Kim and H.-J,Choi,Chem.
Commun.,1998,995.
223 T,Seto and M,Imanari,Bull,Chem,Soc,Jpn.,1994,67,3139.
224 T,Seto,K,Kujira,H,Iwane and M,Imanari,Bull,Chem,Soc.
Jpn.,1995,68,3665.
225 J,Afxantidis,N,Bouchry and J.-P,Aune,J,Mol,Catal,A,Chem.,
1995,102,49.
226 Y,Aoyagi,T,Mizusaki and A,Ohta,Tetrahedron Lett.,1996,37,
9203.
227 B,A,Frontana-Uribe,C,Moinet and L,Toupet,Eur,J,Org.
Chem.,1999,419.
228 H.-J,Kn?lker and T,Hopfmann,Synlett,1995,981.
229 H.-J,Kn?lker and W,Fr?hner,Synlett,1997,1108.
230 H.-J,Kn?lker and G,Schlechtingen,J,Chem,Soc.,Perkin Trans,1,
1997,349.
231 H.-J,Kn?lker and W,Fr?hner,Tetrahedron Lett.,1997,38,4051.
232 H.-J,Kn?lker and W,Fr?hner,Tetrahedron Lett.,1999,40,6915.
233 H.-J,Kn?lker and W,Fr?hner,Tetrahedron Lett.,1997,38,1535.
234 H.-J,Kn?lker,W,Fr?hner and A,Wagner,Tetrahedron Lett.,1998,
39,2947.
235 H.-J,Kn?lker and W,Fr?hner,Tetrahedron Lett.,1998,39,2537.
236 H.-J,Kn?lker,E,Baum and T,Hopfmann,Tetrahedron Lett.,
1995,36,5339.
237 H.-J,Kn?lker,E,Baum and T,Hopfmann,Tetrahedron,1999,55,
10391.
238 H.-J,Kn?lker,G,Baum and J.-B,Pannek,Tetrahedron,1996,52,
7345.
239 H.-J,Kn?lker and K,R,Reddy,Tetrahedron Lett.,1998,39,
4007.
240 H.-J,Kn?lker and W,Fr?hner,Tetrahedron Lett.,1996,37,9183.
241 H.-J,Kn?lker,A.-A,El-Ahl and G,Weing?rtner,Synlett,1994,
194.
242 A,McKillop,G,R,Stephenson and M,Tinkl,Synlett,1995,669.
243 D,L,Boger,Isr,J,Chem.,1997,37,119.
244 D,L,Boger,C,W,Boyce,R,M,Garbaccio and J,A,Goldberg,
Chem,Rev.,1997,97,787.
245 D,L,Boger and J,A,McKie,J,Org,Chem.,1995,60,1271.
246 D,L,Boger,R,M,Garbaccio and Q,Jin,J,Org,Chem.,1997,62,
8875.
247 D,L,Boger,C,W,Boyce,R,M,Garbaccio and M,Searcey,
Tetrahedron Lett.,1998,39,2227.
248 V,F,Patel,S,L,Andis,J,K,Enkema,D,A,Johnson,J,H.
Kennedy,F,Mohamadi,R,M,Schultz,D,J,Soose and M,M.
Spees,J,Org,Chem.,1997,62,8868.
249 K,Jones,J,Wilkinson and R,Ewin,Tetrahedron Lett.,1994,35,
7673.
250 K,Jones,T,C,T,Ho and J,Wilkinson,Tetrahedron Lett.,1995,36,
6743.
251 T,C,T,Ho and K,Jones,Tetrahedron,1997,53,8287.
252 J,Cossy,M,Cases and D,Gomez Pardo,Tetrahedron Lett.,1998,
39,2331.
253 D,P,Curran,H,Yu and H,Liu,Tetrahedron,1994,50,7343.
254 D,P,Curran,S,Hadida,S.-Y,Kim and Z,Luo,J,Am,Chem,Soc.,
1999,121,6607.
255 K,Olofsson,S.-Y,Kim,M,Larhed,D,P,Curran and A,Hallberg,
J,Org,Chem.,1999,64,4539.
256 A.-C,Callier-Dublanchet,B,Quiclet-Sire and S,Z,Zard,Tetra-
hedron Lett.,1995,36,8791.
257 R,Sulsky,J,Z,Gougoutas,J,Di Marco and S,A,Biller,J,Org.
Chem.,1999,64,5504.
258 T,Balasubramanian and K,K,Balasubramanian,Synlett,1994,
946.
259 C,K,McClure,A,J,Kiessling and J,S,Link,Tetrahedron,1998,
54,7121.
260 J,A,Murphy,K,A,Scott,R,S,Sinclair and N,Lewis,Tetrahedron
Lett.,1997,38,7295.
261 Y,Ozlu,D,E,Cladingboel and P,J,Parsons,Tetrahedron,1994,50,
2183.
262 P,J,Parsons,C,S,Penkett,M,C,Cramp,R,I,West and E,S.
Warren,Tetrahedron,1996,52,647.
263 T,Fukuyama,X,Chen and G,Peng,J,Am,Chem,Soc.,1994,116,
3127.
264 Y,Kobayashi and T,Fukuyama,J,Heterocycl,Chem.,1998,35,
1043.
265 S,Kobayashi,G,Peng and T,Fukuyama,Tetrahedron Lett.,1999,
40,1519.
266 T,Shinada,M,Miyachi,Y,Itagaki,H,Naoki,K,Yoshihara and
T,Nakajima,Tetrahedron Lett.,1996,37,7099.
267 J,D,Rainier,A,R,Kennedy and E,Chase,Tetrahedron Lett.,
1999,40,6325.
268 H,Tokuyama,T,Yamashita,M,T,Reding,Y,Kaburagi and
T,Fukuyama,J,Am,Chem,Soc.,1999,121,3791.
269 M,T,Reding and T,Fukuyama,Org,Lett.,1999,973.
270 W,Cabri,I,Candiani,M,Colombo,L,Franzoi and A,Bedeschi,
Tetrahedron Lett.,1995,36,949.
271 T,Nagashima and D,P,Curran,Synlett,1996,330.
272 C,Lampard,J,A,Murphy,F,Rasheed,N,Lewis,M,B.
Hursthouse and D,E,Hibbs,Tetrahedron Lett.,1994,35,8675.
273 M,Kizil,C,Lampard and J,A,Murphy,Tetrahedron Lett.,1996,
37,2511.
274 J,A,Murphy,F,Rasheed,S,Gastaldi,T,Ravishanker and
N,Lewis,J,Chem,Soc.,Perkin Trans,1,1997,1549.
275 R,Fletcher,M,Kizil,C,Lampard,J,A,Murphy and S,J,Roome,
J,Chem,Soc.,Perkin Trans,1,1998,2341.
276 B,Patro,M,Merrett,J,A,Murphy,D,C,Sherrington and
M,G,J,T,Morrison,Tetrahedron Lett.,1999,40,7857.
277 H,Ishibashi,A,Toyao and Y,Takeda,Synlett,1999,1468.
278 M,Dias,M,Gibson,J,Grimshaw,I,Hill,J,Trocha-Grimshaw and
O,Hammerich,Acta Chem,Scand.,1998,52,549.
279 (a) Y,Hayashi,H,Shinokubo and K,Oshima,Tetrahedron Lett.,
1998,39,63; (b) for related radical cyclizations using Bu
3
MnLi
or Bu
3
MnMgBr see,R,Inoue,J,Nakao,H,Shinokubo and K.
Oshima,Bull,Chem,Soc,Jpn.,1997,70,2039.
280 J,Boivin,M,Yous? and S,Z,Zard,Tetrahedron Lett.,1994,35,
9553.
281 J,Axon,L,Boiteau,J,Boivin,J,E,Forbes and S,Z,Zard,
Tetrahedron Lett.,1994,35,1719.
282 M,Kizil and J,A,Murphy,Chem,Commun.,1995,1409.
283 R,Rezaie and J,B,Bremner,Synlett,1996,1061.
284 C.-P,Chuang,Y.-L,Wu and M.-C,Jiang,Tetrahedron,1999,55,
11229.
285 P,C,Montevecchi and M,L,Navacchia,Tetrahedron Lett.,1998,
39,9077.
286 P,C,Montevecchi,M,L,Navacchia and P,Spagnolo,Tetrahedron
Lett.,1997,38,7913.
287 P,C,Montevecchi,M,L,Navacchia and P,Spagnolo,Eur,J,Org.
Chem.,1998,1219.
288 L,S,Hegedus,G,F,Allen and E,L,Waterman,J,Am,Chem,Soc.,
1976,98,2674.
289 L,S,Hegedus,G,F,Allen,J,J,Bozell and E,L,Waterman,J,Am.
Chem,Soc.,1978,100,5800.
290 L,S,Hegedus,G,F,Allen and D,J,Olsen,J,Am,Chem,Soc.,1980,
102,3583.
291 R,Odle,B,Blevins,M,Ratcli? and L,S,Hegedus,J,Org,Chem.,
1980,45,2709.
292 (a) P,J,Harrington and L,S,Hegedus,J,Org,Chem.,1984,49,
2657; (b) P,J,Harrington,L,S,Hegedus and K,F,McDaniel,
J,Am,Chem,Soc.,1987,109,4335.
293 L,S,Hegedus,P,R,Weider,T,A,Mulhern,H,Asada and
S,D’Andrea,Gazz,Chim,Ital.,1986,116,213.
294 M,Mori,K,Chiba and Y,Ban,Tetrahedron Lett.,1977,1037.
295 M,Mori and Y,Ban,Tetrahedron Lett.,1979,1133.
296 M,O,Terpko and R,F,Heck,J,Am,Chem,Soc.,1979,101,5281.
297 L,S,Hegedus,Angew,Chem.,Int,Ed,Engl.,1988,27,1113.
298 T,Sakamoto,Y,Kondo and H,Yamanaka,Heterocycles,1988,27,
2225.
299 A,de Meijere and F,E,Meyer,Angew,Chem.,Int,Ed,Engl.,1994,
33,2379.
300 M,Ikeda,S,A,A,El Bialy and T,Yakura,Heterocycles,1999,51,
1957.
301 R,C,Larock and S,Babu,Tetrahedron Lett.,1987,28,5291.
302 R,C,Larock,T,R,Hightower,L,A,Hasvold and K,P,Peterson,
J,Org,Chem.,1996,61,3584.
303 R,C,Larock,H,Yang,P,Pace,S,Cacchi and G,Fabrizi,
Tetrahedron Lett.,1998,39,1885.
304 R,C,Larock,P,Pace and H,Yang,Tetrahedron Lett.,1998,39,2515.
305 R,C,Larock,P,Pace,H,Yang,C,E,Russell,S,Cacchi and
G,Fabrizi,Tetrahedron,1998,54,9961.
306 L,F,Tietze and T,Grote,J,Org,Chem.,1994,59,192.
307 L,F,Tietze and W,Buhr,Angew,Chem.,Int,Ed,Engl.,1995,34,
1366.
308 L,F,Tietze,R,Hannemann,W,Buhr,M,L?gers,P,Menningen,
M,Lieb,D,Starck,T,Grote,A,D?ring and I,Schuberth,Angew.
Chem.,Int,Ed,Engl.,1996,35,2674.
309 M,Yamaguchi,M,Arisawa and M,Hirama,Chem,Commun.,
1998,1399.
310 D,Wensbo,U,Annby and S,Gronowitz,Tetrahedron,1995,51,
10323.
311 D,Wensbo and S,Gronowitz,Tetrahedron,1996,52,14975.
312 M,Gowan,A,S,Caillé and C,K,Lau,Synlett,1997,1312.
313 C.-C,Yang,P.-J,Sun and J.-M,Fang,J,Chem,Soc.,Chem.
Commun.,1994,2629.
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1073
314 J,E,Macor,R,J,Ogilvie and M,J,Wythes,Tetrahedron Lett.,
1996,37,4289.
315 N,J,Newcombe,F,Ya,R,J,Vijn,H,Hiemstra and W,N.
Speckamp,J,Chem,Soc.,Chem,Commun.,1994,767.
316 W,Yun and R,Mohan,Tetrahedron Lett.,1996,37,7189.
317 H.-C,Zhang and B,E,Maryano?,J,Org,Chem.,1997,62,1804.
318 V,Arumugam,A,Routledge,C,Abell and S,Balasubramanian,
Tetrahedron Lett.,1997,38,6473.
319 M,A,Carroll and A,B,Holmes,Chem,Commun.,1998,1395.
320 T,Matsuura,L,E,Overman and D,J,Poon,J,Am,Chem,Soc.,
1998,120,6500.
321 L,E,Overman,D,V,Paone and B,A,Stearns,J,Am,Chem,Soc.,
1999,121,7702.
322 R,Grigg,B,Putnikovic and C,J,Urch,Tetrahedron Lett.,1996,37,
695.
323 R,Grigg and J,M,Sansano,Tetrahedron,1996,52,13441.
324 P,Evans,R,Grigg,M,I,Ramzan,V,Sridharan and M,York,
Tetrahedron Lett.,1999,40,3021.
325 (a) R,Grigg,J,M,Sansano,V,Santhakumar,V,Sridharan,
R,Thangavelanthum,M,Thornton-Pett and D,Wilson,Tetra-
hedron,1997,53,11803; (b) R,Grigg,S,Brown,V,Sridharan and
M,D,Uttley,Tetrahedron Lett.,1998,39,3247.
326 R,Grigg,J,P,Major,F,M,Martin and M,Whittaker,Tetrahedron
Lett.,1999,40,7709.
327 D,D,Hennings,S,Iwasa and V,H,Rawal,Tetrahedron Lett.,1997,
38,6379.
328 H,Iida,Y,Yuasa and C,Kibayashi,J,Org,Chem.,1980,45,2938.
329 Y,Blache,M.-E,Sinibaldi-Troin,A,Voldoire,O,Chavignon,
J.-C,Gramain,J.-C,Teulade and J.-P,Chapat,J,Org,Chem.,1997,
62,8553.
330 E,J,Latham and S,P,Stanforth,Chem,Commun.,1996,2253.
331 E,J,Latham and S,P,Stanforth,J,Chem,Soc.,Perkin Trans,1,
1997,2059.
332 K,Koerber-Plé and G,Massiot,Synlett,1994,759.
333 C,Chen,D,R,Lieberman,R,D,Larsen,T,R,Verhoeven and
P,J,Reider,J,Org,Chem.,1997,62,2676.
334 B,?kermark,L,Eberson,E,Jonsson and E,Pettersson,J,Org.
Chem.,1975,40,1365.
335 B,?kermark,J,D,Oslob and U,Heuschert,Tetrahedron Lett.,
1995,36,1325.
336 H.-J,Kn?lker and N,O’Sullivan,Tetrahedron Lett.,1994,35,1695.
337 H.-J,Kn?lker and N,O’Sullivan,Tetrahedron,1994,50,10893.
338 H.-J,Kn?lker and W,Fr?hner,J,Chem,Soc.,Perkin Trans,1,1998,
173.
339 H.-J,Kn?lker,K,R,Reddy and A,Wagner,Tetrahedron Lett.,
1998,39,8267.
340 H.-J,Kn?lker and K,R,Reddy,Synlett,1999,596.
341 A,M,F,Oliveira-Campos,M.-J,R,P,Queiroz,M,M,M,Raposo
and P,V,R,Shannon,Tetrahedron Lett.,1995,36,133.
342 (a) T,Sakamoto,Y,Kondo and H,Yamanaka,Heterocycles,1986,
24,31; (b) T,Sakamoto,Y,Kondo,S,Iwashita and H,Yamanaka,
Chem,Pharm,Bull.,1987,35,1823.
343 A,Yasuhara,Y,Kanamori,M,Kaneko,A,Numata,Y,Kondo and
T,Sakamoto,J,Chem,Soc.,Perkin Trans,1,1999,529.
344 T,Sakamoto,Y,Kondo,S,Iwashita,T,Nagano and H,Yamanaka,
Chem,Pharm,Bull.,1988,36,1305.
345 Y,Kondo,S,Kojima and T,Sakamoto,Heterocycles,1996,43,
2741.
346 Y,Kondo,S,Kojima and T,Sakamoto,J,Org,Chem.,1997,62,
6507.
347 Y,Kondo,F,Shiga,N,Murata,T,Sakamoto and H,Yamanaka,
Tetrahedron,1994,50,11803.
348 A,Yasuhara,M,Kaneko and T,Sakamoto,Heterocycles,1998,48,
1793.
349 S,Cacchi,V,Carnicelli and F,Marinelli,J,Organomet,Chem.,
1994,475,289.
350 A,Arcadi,S,Cacchi,V,Carnicelli and F,Marinelli,Tetrahedron,
1994,50,437.
351 S,Cacchi,G,Fabrizi,F,Marinelli,L,Moro and P,Pace,Synlett,
1997,1363.
352 S,Cacchi,G,Fabrizi and P,Pace,J,Org,Chem.,1998,63,1001.
353 K,Shin and K,Ogasawara,Chem,Lett.,1995,289.
354 M,C,Fagnola,I,Candiani,G,Visentin,W,Cabri,F,Zarini,
N,Mongelli and A,Bedeschi,Tetrahedron Lett.,1997,38,2307.
355 H.-C,Zhang,K,K,Brum?eld,L,Jaroskova and B,E,Maryano?,
Tetrahedron Lett.,1998,39,4449.
356 M,D,Collini and J,W,Ellingboe,Tetrahedron Lett.,1997,38,7963.
357 M,S,Yu,L,Lopez de Leon,M,A,McGuire and G,Botha,
Tetrahedron Lett.,1998,39,9347.
358 K,Shin and K,Ogasawara,Synlett,1995,859.
359 M,G,Saulnier,D,B,Frennesson,M,S,Deshpande and D,M.
Vyas,Tetrahedron Lett.,1995,36,7841.
360 R,Grigg,V,Loganathan and V,Sridharan,Tetrahedron Lett.,
1996,37,3399.
361 D,Brown,R,Grigg,V,Sridharan,V,Tambyrajah and M.
Thornton-Pett,Tetrahedron,1998,54,2595.
362 R,C,Larock and E,K,Yum,J,Am,Chem,Soc.,1991,113,6689.
363 R,C,Larock,E,K,Yum and M,D,Refvik,J,Org,Chem.,1998,
63,7652.
364 L,Xu,I,R,Lewis,S,K,Davidsen and J,B,Summers,Tetrahedron
Lett.,1998,39,5159.
365 F,Ujjainwalla and D,Warner,Tetrahedron Lett.,1998,39,5355.
366 S,S,Park,J.-K,Choi,E,K,Yum and D.-C,Ha,Tetrahedron Lett.,
1998,39,627.
367 S,K,Kang,S,S,Park,S,S,Kim,J.-K,Choi and E,K,Yum,
Tetrahedron Lett.,1999,40,4379.
368 (a) P,Blurton,A,Brickwood and D,Dhanak,Heterocycles,1997,
45,2395; (b) K,R,Roesch and R,C,Larock,Org,Lett.,1999,1,
1551.
369 (a) C,Chen,D,R,Lieberman,R,D,Larsen,R,A,Reamer,T,R.
Verhoeven,P,J,Reider,I,F,Cottrell and P,G,Houghton,
Tetrahedron Lett.,1994,35,6981; (b) C,Chen,D,R,Lieberman,
L,J,Street,A,R,Guiblin,R,D,Larsen and T,R,Verhoeven,
Synth,Commun.,1996,26,1977.
370 R,C,Larock,M,J,Doty and X,Han,Tetrahedron Lett.,1998,39,
5143.
371 F,Maassarani,M,Pfe?er,J,Spencer and E,Wehman,
J,Organomet,Chem.,1994,466,265.
372 H.-C,Zhang,K,K,Brum?eld and B,E,Maryano?,Tetrahedron
Lett.,1997,38,2439.
373 A,L,Smith,G,I,Stevenson,C,J,Swain and J,L,Castro,
Tetrahedron Lett.,1998,39,8317.
374 Y,Wang and T.-N,Huang,Tetrahedron Lett.,1998,39,9605.
375 C,Amatore,E,Blart,J,P,Genet,A,Jutand,S,Lemaire-Audoire
and M,Savignac,J,Org,Chem.,1995,60,6829.
376 M,Botta,V,Summa,F,Corelli,G,Di Pietro and P,Lombardi,
Tetrahedron,Asymmetry,1996,7,1263.
377 R,C,Larock,C.-L,Liu,H,H,Lau and S,Varaprath,Tetrahedron
Lett.,1984,25,4459,who reported the?rst example of this
reaction.
378 K,Samizu and K,Ogasawara,Synlett,1994,499.
379 K,Samizu and K,Ogasawara,Heterocycles,1995,41,1627.
380 R,C,Larock and J,M,Zenner,J,Org,Chem.,1995,60,482.
381 J,M,Zenner and R,C,Larock,J,Org,Chem.,1999,64,7312.
382 E,Desarbre and J.-Y,Mérour,Tetrahedron Lett.,1996,37,43.
383 T,G,Back and R,J,Bethell,Tetrahedron Lett.,1998,39,5463.
384 R,C,Larock and L,Guo,Synlett,1995,465.
385 J,P,Wolfe,S,Wagaw,J.-F,Marcoux and S,L,Buchwald,Acc.
Chem,Res.,1998,31,805.
386 J,P,Wolfe,R,A,Rennels and S,L,Buchwald,Tetrahedron,1996,
52,7525.
387 A,J,Peat and S,L,Buchwald,J,Am,Chem,Soc.,1996,118,1028.
388 S,Wagaw,R,A,Rennels and S,L,Buchwald,J,Am,Chem,Soc.,
1997,119,8451.
389 K,Aoki,A,J,Peat and S,L,Buchwald,J,Am,Chem,Soc.,1998,
120,3068.
390 B,H,Yang and S,L,Buchwald,Org,Lett.,1999,1,35.
391 S,Tollari,S,Cenini,C,Crotti and E,Gianella,J,Mol,Catal.,1994,
87,203.
392 M,Akazome,T,Kondo and Y,Watanabe,J,Org,Chem.,1994,59,
3375.
393 B,C,S?derberg and J,A,Shriver,J,Org,Chem.,1997,62,5838.
394 B,C,S?derberg,S,R,Rector and S,N,O’Neil,Tetrahedron Lett.,
1999,40,3657.
395 C.-C,Yang,H.-M,Tai and P.-J,Sun,J,Chem,Soc.,Perkin Trans,1,
1997,2843.
396 D,S,Brown,M,C,Elliott,C,J,Moody,T,J,Mowlem,J,P.
Marino,Jr,and A,Padwa,J,Org,Chem.,1994,59,2447.
397 S,Miah,A,M,Z,Slawin,C,J,Moody,S,M,Sheehan,J,P.
Marino,Jr.,M,A,Semones,A,Padwa and I,C,Richards,
Tetrahedron,1996,52,2489.
398 S,Miah,C,J,Moody,I,C,Richards and A,M,Z,Slawin,J,Chem.
Soc.,Perkin Trans,1,1997,2405.
399 C,J,Moody,S,Miah,A,M,Z,Slawin,D,J,Mans?eld and I,C.
Richards,Tetrahedron,1998,54,9689.
400 F,Zaragoza,Tetrahedron,1995,51,8829.
401 (a) H.-J,Lim and G,A,Sulikowski,J,Org,Chem.,1995,60,2326;
(b) S,Lee,H.-J,Lim,K,L,Cha and G,A,Sulikowski,Tetrahedron,
1997,53,16521.
402 K,Burgess,H.-J,Lim,A,M,Porte and G,A,Sulikowski,Angew.
Chem.,Int,Ed,Engl.,1996,35,220.
403 S,Lee,W.-M,Lee and G,A,Sulikowski,J,Org,Chem.,1999,64,
4224.
404 Y,Dong and C,A,Busacca,J,Org,Chem.,1997,62,6464.
1074 J,Chem,Soc.,Perkin Trans,1,2000,1045–1075
405 K,Hirao,N,Morii,T,Joh and S,Takahashi,Tetrahedron Lett.,
1995,36,6243.
406 U,R,Aulwurm,J,U,Melchinger and H,Kisch,Organometallics,
1995,14,3385.
407 P,Reisser,Y,Wakatsuki and H,Kisch,Monatsh,Chem.,1995,
126,1.
408 B,Witulski and T,Stengel,Angew,Chem.,Int,Ed.,1999,38,
2426.
409 G,C,Hsu,W,P,Kosar and W,D,Jones,Organometallics,1994,13,
385.
410 C,A,Merlic and M,E,Pauly,J,Am,Chem,Soc.,1996,118,11319.
411 A,Fürstner and B,Bogdanovic,Angew,Chem.,Int,Ed,Engl.,
1996,35,2442.
412 A,Fürstner,A,Hupperts,A,Ptock and E,Janssen,J,Org,Chem.,
1994,59,5215.
413 A,Fürstner and A,Ernst,Tetrahedron,1995,51,773.
414 A,Fürstner,A,Ernst,H,Krause and A,Ptock,Tetrahedron,1996,
52,7329.
415 A,Fürstner and A,Hupperts,J,Am,Chem,Soc.,1995,117,4468.
416 A,Fürstner,D,N,Jumbam and G,Seidel,Chem,Ber.,1994,127,
1125.
417 A,Fürstner,A,Ptock,H,Weintritt,R,Goddard and C,Krüger,
Angew,Chem.,Int,Ed,Engl.,1995,34,678.
418 M,Mori,K,Hori,M,Akashi,M,Hori,Y,Sato and M,Nishida,
Angew,Chem.,Int,Ed.,1998,37,636.
419 M,Akashi,M,Nishida and M,Mori,Chem,Lett.,1999,465.
420 J,Li,D,Shi and W,Chen,Heterocycles,1997,45,2381.
421 J,Lee,J,D,Ha and J,K,Cha,J,Am,Chem,Soc.,1997,119,8127.
422 J,H,Tidwell,A,J,Peat and S,L,Buchwald,J,Org,Chem.,1994,
59,7164.
423 J,H,Tidwell and S,L,Buchwald,J,Am,Chem,Soc.,1994,116,
11797.
424 C,E,Castro and R,D,Stephens,J,Org,Chem.,1963,28,2163.
425 R,D,Stephens and C,E,Castro,J,Org,Chem.,1963,28,3313.
426 C,E,Castro,E,J,Gaughan and D,C,Owsley,J,Org,Chem.,1966,
31,4071.
427 C,E,Castro,R,Havlin,V,K,Honwad,A,Malte and K,Mojé,
J,Am,Chem,Soc.,1969,91,6464.
428 (a) A,R,Katritzky,J,Li and C,V,Stevens,J,Org,Chem.,1995,60,
3401; (b) A,R,Katritzky,C,N,Fali and J,Li,J,Org,Chem.,1997,
62,4148.
429 J,Soloducho,Tetrahedron Lett.,1999,40,2429.
430 J,Ezquerra,C,Pedregal,C,Lamas,J,Barluenga,M,Perez,
M,A,García-Martín and J,M,González,J,Org,Chem.,1996,61,
5804.
431 W,Zhong,J,P,Gallivan,Y,Zhang,L,Li,H,A,Lester and
D,A,Dougherty,Proc,Natl,Acad,Sci,USA,1998,95,12088.
432 L,F,Kuyper,D,P,Baccanari,M,L,Jones,R,N,Hunter,R,L.
Tansik,S,S,Joyner,S,K,Rudolph,V,Knick,H,R,Wilson,J,M.
Caddell,H,S,Friedman,J,C,W,Comley and J,N,Stables,J,Med.
Chem.,1996,39,892.
433 T,Nishikawa,M,Ishikawa and M,Isobe,Synlett,1999,123.
434 T,Kametani,K,Takahashi,M,Ihara and K,Fukumoto,
Heterocycles,1975,3,691.
435 A,Osuka,Y,Mori and H,Suzuki,Chem,Lett.,1982,2031.
436 H,Suzuki,S,V,Thiruvikraman and A,Osuka,Synthesis,1984,
616.
437 W,S,Murphy and M,Bertrand,J,Chem,Soc.,Perkin Trans,1,
1998,4115.
438 W,Schlecker,A,Huth,E,Ottow and J,Mulzer,Tetrahedron,1995,
51,9531.
439 A,Müller,A,Maier,R,Neumann and G,Maas,Eur,J,Org.
Chem.,1998,1177.
440 J,Barluenga,R,Sanz,A,Granados and F,J,Fa?anás,J,Am.
Chem,Soc.,1998,120,4865.
441 B,C,S?derberg,E,S,Helton,L,R,Austin and H,H,Odens,
J,Org,Chem.,1993,58,5589.
442 T,Leese and K,H,D?tz,Chem,Ber.,1996,129,623.
443 A,Rahm and W,D,Wul?,J,Am,Chem,Soc.,1996,118,1807.
444 F,E,McDonald and A,K,Chatterjee,Tetrahedron Lett.,1997,38,
7687.
445 C,O,Kappe,J,E,Cochran and A,Padwa,Tetrahedron Lett.,1995,
36,9285.
446 W,S,Kissel and A,Padwa,Tetrahedron Lett.,1999,40,4003.
447 A,Padwa,M,A,Brodney and M,Dimitro?,J,Org,Chem.,1998,
63,5304.
448 A,Padwa,M,Dimitro?,A,G,Waterson and T,Wu,J,Org,Chem.,
1998,63,3986.
449 A,Padwa,M,A,Brodney,B,Liu,K,Satake and T,Wu,J,Org.
Chem.,1999,64,3595.
450 A,Tahri,K,J,Buysens,E,V,Van der Eycken,D,M.
Vandenberghe and G,J,Hoornaert,Tetrahedron,1998,54,13211.
451 O,L,Chapman,G,L,Eian,A,Bloom and J,Clardy,J,Am,Chem.
Soc.,1971,93,2918.
452 P,W,Groundwater,D,Hughes,M,B,Hursthouse and R,Lewis,
J,Chem,Soc.,Perkin Trans,1,1996,669.
453 D,Dugat,N,Benchekroun-Mounir,G,Dauphin and J.-C.
Gramain,J,Chem,Soc.,Perkin Trans,1,1998,2145.
454 M,Ibrahim-Ouali,M.-E,Sinibaldi,Y,Troin,A,Cuer,G,Dauphin
and J.-C,Gramain,Heterocycles,1995,41,1939.
455 M,Ibrahim-Ouali,M.-E,Sinibaldi,Y,Troin and J.-C,Gramain,
Tetrahedron Lett.,1996,37,37.
456 M,Ibrahim-Ouali,M.-E,Sinibaldi,Y,Troin,D,Guillaume and
J.-C,Gramain,Tetrahedron,1997,53,16083.
457 Y,Ueda,H,Watanabe,J,Uemura and K,Uneyama,Tetrahedron
Lett.,1993,34,7933.
458 D,P,M,Pleynet,J,K,Dutton,M,Thornton-Pett and A,P.
Johnson,Tetrahedron Lett.,1995,36,6321.
459 J,K,Dutton,D,P,M,Pleynet and A,P,Johnson,Tetrahedron,
1999,55,11927.
460 P,A,Wender and C,B,Cooper,Tetrahedron,1986,42,2985.
461 J,K,Dutton,R,W,Steel,A,S,Tasker,V,Popsavin and A,P.
Johnson,J,Chem,Soc.,Chem,Commun.,1994,765.
462 G,G,Qiao and C,Wentrup,Tetrahedron Lett.,1995,36,3913.
463 G,G,Qiao,M,W,Wong and C,Wentrup,J,Org,Chem.,1996,61,
8125.
464 M,Seiler,A,Schumacher,U,Lindermann,F,Barbosa and
B,Giese,Synlett,1999,1588.
465 E,Vedejs and S,D,Monahan,J,Org,Chem.,1997,62,4763.
466 D,R,Hutchison,N,K,Nayyar and M,J,Martinelli,Tetrahedron
Lett.,1996,37,2887.
467 N,K,Nayyar,D,R,Hutchison and M,J,Martinelli,J,Org,Chem.,
1997,62,982.
468 M,P,S,Ishar and K,Kumar,Tetrahedron Lett.,1999,40,175.
469 M,Schmittel,M,Strittmatter and S,Kiau,Angew,Chem.,Int,Ed.
Engl.,1996,35,1843.
470 M,Schmittel,J.-P,Ste?en,M,á Wencesla ángel,B,Engels,
C,Lennartz and M,Hanrath,Angew,Chem.,Int,Ed.,1998,37,
1562.
471 M,Schmittel,J.-P,Ste?en,B,Engels,C,Lennartz and M,Hanrath,
Angew,Chem.,Int,Ed.,1998,37,2371.
472 L,Zhang,M,P,Cava,R,D,Rogers and L,M,Rogers,Tetrahedron
Lett.,1998,39,7677.
473 H,Muratake,A,Mikawa,T,Seino and M,Natsume,Chem.
Pharm,Bull.,1994,42,846.
474 H,Muratake,A,Mikawa,T,Seino and M,Natsume,Chem.
Pharm,Bull.,1994,42,854.
475 M,Sakagami,H,Muratake and M,Natsume,Chem,Pharm,Bull.,
1994,42,1393.
476 I,Utsunomiya,H,Muratake and M,Natsume,Chem,Pharm.
Bull.,1995,43,37.
477 H,Ishibashi,S,Akamatsu,H,Iriyama,K,Hanaoka,T,Tabata and
M,Ikeda,Chem,Pharm,Bull.,1994,42,271.
478 A,R,Katritzky,J,R,Levell and J,Li,Tetrahedron Lett.,1996,37,
5641.
479 A,R,Katritzky,S,A,Henderson and B,Yang,J,Heterocycl.
Chem.,1998,35,1123.
480 A,R,Katritzky,J,Li and L,Xie,Tetrahedron,1999,55,8263.
481 H,Muratake,N,Matsumura and M,Natsume,Chem,Pharm.
Bull.,1998,46,559.
482 M,Tani,T,Ariyasu,M,Ohtsuka,T,Koga,Y,Ogawa,Y.
Yokoyama and Y,Murakami,Chem,Pharm,Bull.,1996,44,55.
483 D,C,Harrowven and R,F,Dainty,Tetrahedron Lett.,1995,36,
6739.
484 E,D,Edstrom and T,Yu,Tetrahedron Lett.,1994,35,6985.
485 E,D,Edstrom,Synlett,1995,49.
486 E,D,Edstrom,T,Yu and Z,Jones,Tetrahedron Lett.,1995,36,
7035.
487 C,F,Masaguer and E,Ravi?a,Tetrahedron Lett.,1996,37,5171.
488 K,Doi and M,Mori,Heterocycles,1996,42,113.
489 M,Dekhane,P,Potier and R,H,Dodd,Tetrahedron,1993,49,8139.
490 V,J,Demopoulos,A,Gavalas,G,Rekatas and E,Tani,
J,Heterocycl,Chem.,1995,32,1145.
491 N,De Kimpe and M,Keppens,Tetrahedron,1996,52,3705.
492 J,R,Suresh,P,K,Patra,H,Ila and H,Junjappa,Tetrahedron,
1997,53,14737.
493 S,Lim,I,Jabin and G,Revial,Tetrahedron Lett.,1999,40,4177.
494 H,H,Wasserman and C,A,Blum,Tetrahedron Lett.,1994,35,
9787.
495 H,A,Etman,Indian J,Chem.,Sect,B,1995,34,285.
496 V,Levacher,C,Leroy,G,Dupas,J,Bourguignon and G.
Quéguiner,Synth,Commun.,1994,24,2697.
497 H,Muratake,M,Tonegawa and M,Natsume,Chem,Pharm,Bull.,
1996,44,1631.
J,Chem,Soc.,Perkin Trans,1,2000,1045–1075 1075
498 H,Muratake,M,Tonegawa and M,Natsume,Chem,Pharm,Bull.,
1998,46,400.
499 D,Xiao and D,M,Ketcha,J,Heterocycl,Chem.,1995,32,499.
500 L,R,Domingo,R,A,Jones,M,T,Picher and J,Sepúlveda-
Arques,Tetrahedron,1995,51,8739.
501 L,R,Domingo,M,T,Picher,J,Andrés,V,Moliner and V,S.
Safont,Tetrahedron,1996,52,10693.
502 L,M,Hodges,M,W,Moody and W,D,Harman,J,Am,Chem.
Soc.,1994,116,7931.
503 L,M,Hodges,M,L,Spera,M,W,Moody and W,D,Harman,
J,Am,Chem,Soc.,1996,118,7117.
504 M,Hadden and P,J,Stevenson,Tetrahedron Lett.,1999,40,1215.
505 J.-Y,Wu,J.-H,Ho,S.-M,Shih,T.-L,Hsieh and T.-I,Ho,Org,Lett.,
1999,1,1039.
506 K,Oda,H,Tsujita,M,Sakai and M,Machida,Chem,Pharm.
Bull.,1998,46,1522.
507 R,ten Have and A,M,van Leusen,Tetrahedron,1998,54,1913.
508 R,Nesi,D,Giomi,S,Turchi and A,Falai,J,Chem,Soc.,Chem.
Commun.,1995,2201.
509 R,D,Chambers,W,K,Gray,S,J,Mullins and S,R,Korn,
J,Chem,Soc.,Perkin Trans,1,1997,1457.
510 J,Cossy,C,Poitevin,L,Sallé and D,Gomez Pardo,Tetrahedron
Lett.,1996,37,6709.
511 D,R,Artis,I,Cho,S,Jaime-Figueroa and J,M,Muchowski,
J,Org,Chem.,1994,59,2456.
512 M,A,Fagan and D,W,Knight,Tetrahedron Lett.,1999,40,6117.
513 I,R,Hardcastle,R,F,Hunter,P,Quayle and P,N,Edwards,
Tetrahedron Lett.,1994,35,3805.
514 C,Caubère,P,Caubère,S,Ianelli,M,Nardelli and B,Jamart-
Grégoire,Tetrahedron,1994,50,11903.
515 C,Kuehm-Caubère,I,Rodriguez,B,Pfei?er,P,Renard and
P,Caubère,J,Chem,Soc.,Perkin Trans,1,1997,2857.
516 M,Beller,C,Breindl,T,H,Riermeier,M,Eichberger and
H,Trauthwein,Angew,Chem.,Int,Ed.,1998,37,3389.
517 J,Barluenga,F,J,Fa?anás,R,Sanz and Y,Fernández,Tetrahedron
Lett.,1999,40,1049.
518 A,Goti and M,Romani,Tetrahedron Lett.,1994,35,6567.
519 D,S,Carter and D,L,Van Vranken,Tetrahedron Lett.,1996,37,
5629.
520 B,Giethlen and J,M,Schaus,Tetrahedron Lett.,1997,38,8483.
521 D,M,Ketcha,Q,Zhou and D,Grossie,Synth,Commun.,1994,24,
565.
522 D,St,C,Black and R,Rezaie,Tetrahedron Lett.,1999,40,4251.
523 E,M,Beccalli and A,Marchesini,Tetrahedron,1995,51,2353.
524 E,M,Beccalli,A,Marchesini and T,Pilati,Tetrahedron,1994,50,
12697.
525 A,C,Pinto,F,S,Q,da Silva and R,B,da Silva,Tetrahedron Lett.,
1994,35,8923.
526 C,Crestini and R,Saladino,Synth,Commun.,1994,24,2835.
527 C,A,Merlic,S,Motamed and B,Quinn,J,Org,Chem.,1995,60,
3365.
528 T,Kawasaki,Y,Nonaka,M,Uemura and M,Sakamoto,
Synthesis,1991,701.
529 J,Afxantidis and J.-P,Aune,Bull,Soc,Chim,Fr.,1996,133,395.
530 B,E,Fulloon and C,Wentrup,J,Org,Chem.,1996,61,1363.
531 V,J,Majo and P,T,Perumal,J,Org,Chem.,1996,61,6523.
532 Y,Cheng,S,Goon and O,Meth-Cohn,Chem,Commun.,1996,
1395.
533 O,Meth-Cohn and S,Goon,Tetrahedron Lett.,1996,37,9381.
534 Y,Cheng,S,Goon and O,Meth-Cohn,J,Chem,Soc.,Perkin
Trans,1,1998,1619.
535 S,Tanaka,K,Seguchi and A,Sera,J,Chem,Soc.,Perkin Trans,1,
1995,519.
536 S,Tanaka,K,Seguchi and A,Sera,Heterocycles,1994,38,2581.
537 S,Tanaka,K,Seguchi,K,Itoh and A,Sera,Chem,Lett.,1994,
771.
538 S,Tanaka,K,Seguchi,K,Itoh and A,Sera,J,Chem,Soc.,Perkin
Trans,1,1994,2335.
539 M,A,Ciufolini,Q,Dong,M,H,Yates and S,Schunk,Tetrahedron
Lett.,1996,37,2881.
540 M,M,Paz and P,B,Hopkins,J,Am,Chem,Soc.,1997,119,5999.
541 J,H,Rigby,A,Cavezza and G,Ahmed,J,Am,Chem,Soc.,1996,
118,12848.
542 J,H,Rigby,R,C,Hughes and M,J,Heeg,J,Am,Chem,Soc.,1995,
117,7834.
543 J,H,Rigby and S,Laurent,J,Org,Chem.,1999,64,1766.
544 J,H,Rigby and M,D,Danca,Tetrahedron Lett.,1999,40,6891.
545 J,H,Rigby,S,Laurent,A,Cavezza and M,J,Heeg,J,Org,Chem.,
1998,63,5587.
546 J,H,Rigby,A,Cavezza and M,J,Heeg,Tetrahedron Lett.,1999,
40,2473.
547 J,H,Rigby and M,E,Mateo,Tetrahedron,1996,52,10569.
548 K,Orito,M,Miyazawa,R,Kanbayashi,M,Tokuda and H.
Suginome,J,Org,Chem.,1999,64,6583.
549 K,Takaoka,T,Aoyama and T,Shioiri,Tetrahedron Lett.,1999,40,
3017.
550 S,Kosinski and K,Wojciechowski,Pol,J,Chem.,1998,72,2546.
551 S,I,El-Desoky,E,M,Kandeel,A,H,Abd-el-Rahman and
R,R,Schmidt,J,Heterocycl,Chem.,1999,36,153.
Review a909834h