杂环合成（英文版pdf参考资料）：Synthesis of aromatic heterocycles

REVIEW
J,Chem,Soc.,Perkin Trans,1,1999,2849–2866 2849
This journal is? The Royal Society of Chemistry 1999
Synthesis of aromatic heterocycles
Thomas L,Gilchrist
Chemistry Department,The University of Liverpool,Liverpool,UK L69 7ZD.
E-mail tlg57@liv.ac.uk
Received (in Cambridge,UK) 7th June 1999
Covering,March 1997 to February 1999
Previous review,J,Chem,Soc.,Perkin Trans,1,1998,615
1 Introduction
2 Furans and benzofurans
3 Thiophenes and benzothiophenes
4 Pyrroles
5 Indoles,indolizines and carbazoles
6 Oxazoles,thiazoles and benzothiazoles
7 Isoxazoles,isothiazoles and fused analogues
8 Imidazoles and benzimidazoles
9 Pyrazoles and indazoles
10 Oxadiazoles and thiadiazoles
11 Triazoles,benzotriazoles and tetrazoles
12 Pyrones,coumarins and chromones
13 Pyridines
14 Quinolines and isoquinolines
15 Pyrimidines and quinazolines
16 Other diazines,triazines and tetrazines
17 References
1 Introduction
This review,as with previous ones in the series,has the aim
of covering reports of new and improved methods of construc-
tion of aromatic heterocycles from acyclic precursors or by
ring interconversion,The coverage cannot be comprehensive
because of pressure of space,Many useful applications of exist-
ing methods are not included; in particular,several of those
that make use of solid phase and polymer bound reagents,since
the literature on these is now extensively covered elsewhere (for
example,in Perkin 1 Abstracts and in other reviews
1
),As with
the earlier literature surveys in this series the ring systems
covered are mainly restricted to the more common monocyclic
and bicyclic heterocycles.
New synthetic methods that make use of transition metals
as catalysts or metal complexes (e.g.,carbene complexes) as
reagents continue to appear; cyclisation reactions that are
catalysed by palladium(0) species have been extended to the
synthesis of many of the common ring systems,Some interest-
ing new cycloaddition reactions have also been reported in this
period,For example,Sauer’s group has made extensive use of
inverse electron demand Diels–Alder reactions of triazines and
tetrazines for the synthesis of new pyridines and pyridazines
and Wong and co-workers have made impressive use of
cycloaddition reactions of trialkylsilyl- and trialkylstannyl-
acetylenes to provide routes to 3,4-disubstituted furans,thio-
phenes and pyrroles,Rees and co-workers have continued to
nd new applications of trithiazyl chloride for the preparation
of?ve-membered heterocycles containing sulfur and nitrogen.
2 Furans and benzofurans
Methods for the synthesis of substituted furans,involving both
construction of the ring and substitution reactions,have been
reviewed.
2
The use of 3,4-bis(trialkylstannyl)furans and the
corresponding bis(trimethylsilyl)furan for the synthesis of other
3,4-disubstituted furans has also been reviewed.
3
An improved
version of Marshall’s synthesis of furans from β-alkynyl
allylic alcohols,making use of silver nitrate on silica gel as the
catalyst,has been described.
4
As in earlier reviews,several of the useful new routes to
furans involve cyclisation reactions in which oxygen nucleo-
philes undergo addition to alkynes,The intramolecular add-
ition of enolate anions to activated alkynes provides a simple
and versatile route to several furans,An example is shown
in Scheme 1; other terminal activating groups on the alkyne,
including benzenesulfonyl and vinyl groups,are also e?ective in
promoting the cyclisation.
5
Full details of the scope and limit-
ations of the similar base catalysed cyclisation of 1-aryl- and 1-
vinylpent-4-ynones to furans have also appeared.
6
Two other
related cyclisations of alkynes are shown in Scheme 2,Methyl
furan-2-acetates are formed by the palladium catalysed cyclis-
ation and carbonylation of 5-hydroxyenynes 1
7
and a related
cyclisation,using potassium tetraiodopalladate as a catalyst,
has been used in a new synthesis of rosefuran.
8
The base
induced cyclisation of acetylenic ketones such as 2 provides a
route to 2-alkenylfurans; the authors suggest that cumulenes
such as 3 are intermediates.
9
Two furan syntheses involving metal carbene complexes are
exempli?ed in Schemes 3 and 4,The aldehyde 4 reacts with the
carbene complex (CO)
5
CrC(Me)OMe to give the bicyclic furan
5 in which the carbon atoms from the carbene complex are
located in a side chain; an analogous cyclisation occurs with the
Scheme 1
Scheme 2
2850 J,Chem,Soc.,Perkin Trans,1,1999,2849–2866
methyl ketone corresponding to 4.
10
In an extension of a
method reported earlier
11
Iwasawa and co-workers have des-
cribed a synthesis of substituted methyl furan-3-carboxylates
such as 6 from tungsten carbene complexes,lithium acetylides
and aldehydes.
12
Tetrasubstituted furan-3-carboxylates have
also been synthesised in moderate yield from 3-hydroxy-
1,2-dioxane-4-carboxylates (cyclic peroxides) by reaction with
acids.
13
The palladium catalysed annelation of iodo compounds with
internal alkynes,previously used by Larock’s group to syn-
thesise a variety of heterocycles,has now been applied to furan
synthesis,For example,the tetrahydrobenzofuran 8 was pro-
duced (69%) from the vinyl iodide 7 and 4,4-dimethylpent-
2-yne.
14
The mercury() catalysed cyclisation of the allenic
alcohols 10,generated in situ from 3-methoxy-1-phenyl-
thioprop-1-yne 9 and aldehydes,leads to the 2,3-disubstituted
furans 11.
15
An unusual route to c-fused furans is illustrated in Scheme 5.
Intramolecular cycloaddition of conjugated ynones to triple
bonds leads to the formation of furans such as 12 which,the
authors suggest,are formed by way of strained bicyclic allenes
and carbenes.
16
Two existing routes to 3,4-disubstituted furans have been
improved,The Garst–Spencer furan annelation from 3-
(butylthio)enones was modi?ed by replacing the butyl group
with a 4-tolyl group and by using iodine as the aromatising
agent (Scheme 6).
17
The oxidation of 2-substituted and 2,3-
disubstituted but-2-ene-1,4-diols 13 in a two phase system led
to a variety of 3-substituted and 3,4-disubstituted furans in
good yield; for example,3,4-dibromofuran was prepared (83%)
in this way.
18
There are relatively few good methods for the synthesis of
furans with speci?c substituents at the 2 and 4 positions
and some useful new methods have been described,A simple
Scheme 3
Scheme 4
synthesis of 2-substituted furan-4-methanols involves the
intermediacy of enones 14,which are prepared by a Horner–
Wadsworth–Emmons reaction then cyclised by reaction with
HCl.
19
The dimerisation of terminal allenic ketones 15 leads to
2,4-disubstituted furans 16 in preparatively useful yields when
PdCl
2
(MeCN)
2
is used as the catalyst in acetonitrile.
20
A poten-
tially general route to 2,4-disubstituted furans has been used
by Fürstner and his co-workers in a synthesis of the terpene
ircinin-4,the structure of which incorporates a 2,4-dialkylfuran
subunit.
21
This makes use of essentially the same methodology
as was invented for 2,4-disubstituted pyrroles in Fürstner’s
route to roseophilin and which is outlined in Section 4 (see
Scheme 26).
Several furans have been prepared in moderate to good yield
by the reaction of α-bromomethyl ketones with enol ethers in
the presence of the catalyst [ReCl(N
2
)(PMe
2
Ph)
4
],It is pro-
posed that this generates acylmethyl radicals as the reactive
intermediates (Scheme 7).
22
Cyclisation reactions involving palladium catalysis are pre-
dominant among recently described methods for preparing
benzofurans,Details have been published of the sequential
palladium catalysed coupling of 2-iodophenols with alk-1-ynes
Scheme 5
Scheme 6
Scheme 7
J,Chem,Soc.,Perkin Trans,1,1999,2849–2866 2851
and endo cyclisation to 2-substituted benzofurans.
23
With silyl
protected alkynols the method provides a route to benzofuran-
3-methanol (Scheme 8) and to other alkan-3-ols.
24
A variant
which leads to 2,3-disubstituted benzofurans is to carry out
the reaction with allyl 2-alkynylphenyl ethers; for example,the
ether 17 gave 3-allyl-2-methylbenzofuran 18 (76%) on pal-
ladium(0) catalysed cyclisation,A π-allylpalladium complex is
suggested as an intermediate.
25
3-Allenylbenzofurans have also
been prepared by a similar method.
26
A di?erent approach to
3-allylbenzofurans has been described that is based on salicyl-
aldehyde derivatives; the aldehyde function is converted into an
allyl vinyl ether (such as 19) by Wittig ole?nation and this is
then subjected to Claisen rearrangement,The aldehydes (such
as 20) so formed are then converted into 3-allylbenzofurans by
acid catalysed cyclisation and dehydration.
27
Palladium catalysed cyclisation reactions involving allenes
have provided another route to 3-substituted benzofurans,The
allene 21 gave 3-azidomethylbenzofuran 22 (71%) with sodium
azide and a palladium(0) catalyst.
28
Other nucleophiles can be
used to capture the intermediate organopalladium species; thus,
with sodium benzenesul?nate,3-(phenylsulfonylmethyl)benzo-
furan was isolated,Phenyl allyl ethers such as 23 have been
cyclised to benzofurans by heating with caesium carbonate and
a palladium catalyst (Scheme 9).
29
It is suggested that the reac-
tion is promoted by the formation of phenolate anions,which
are more reactive than free phenols in the cyclisation step.
Intramolecular Heck reactions of allyl 2-iodophenyl ethers
have been applied to a solid phase synthesis of benzofuran-3-
ylacetamides.
30
A standard route to benzofurans is the acid catalysed
cyclodehydration of phenoxymethyl ketones 24,A versatile
route to these ketones,based on the reaction of anions of
1-phenoxymethylbenzotriazoles with aldehydes,has been des-
cribed; the complete sequence leading to the benzofurans can
be carried out in one pot.
31
Benzofuran has been isolated in
60% yield from the?ash pyrolysis of the cinnamyl ester 25; the
Scheme 8
Scheme 9
reaction probably involves the generation and cyclisation of a
phenoxy radical.
32
Two base-induced cyclisation reactions that lead to benzo-
furans are illustrated in Scheme 10
33
and in Scheme 11.
34
The
base induced fragmentation of 1,2,3-thiadiazoles is a prece-
dented reaction and results in the generation of the anions 26 as
intermediates in the route to 2-alkylthiobenzofurans.
3 Thiophenes and benzothiophenes
Several 2-alkylaminothiophenes have been prepared from
terminal alkynes and alkyl or aryl isothiocyanates by the route
shown in Scheme 12.
35
Similar syntheses of 2-alkylaminothio-
phenes bearing dialkylamino substituents at C-5
36
and hetero-
atom substituents at C-3
37
have also been described.
The tertiary amide 27 gave the 2-aminothiophene 28 (57%)
on reaction with Lawesson’s reagent.
38
When secondary amides
were used mixtures of aminothiophenes and pyrroles were
produced,3-Alkylaminothiophenes were obtained in high
yield from reactions of ketene N,S-acetals such as 29 with 1,3-
dicarbonyl compounds and mercury() acetate; an example is
shown in Scheme 13.
39
Scheme 10
Scheme 11
Scheme 12
Scheme 13
2852 J,Chem,Soc.,Perkin Trans,1,1999,2849–2866
Details have been published of the remarkably e?cient syn-
thesis of 3,4-bis(trimethylsilyl)thiophene by the high temper-
ature Diels–Alder addition of bis(trimethylsilyl)acetylene to
4-phenylthiazole,The thiophene can be prepared in batches
of up to 8 g by this method,which has also been extended
to some other 3,4-disubstituted thiophenes.
40
A 1,3-dipolar
cycloaddition approach was also investigated (Scheme 14)
but was less e?cient,Experimental details have also been
provided for the preparation of 3,4-disubstituted thiophenes
from the diketones 30 by reductive cyclisation using titanium
reagents.
41
Thiophenes bearing bulky substituents (tert-butyl,
1-adamantyl,etc.) have been prepared by this route.
Two new thiophene syntheses have been described that make
use of the methodology previously developed for the prepar-
ation of other heterocycles,Marson and Campbell have applied
a synthesis of furans,based on the ring expansion of function-
alised epoxides,to analogous episul?des; for example,the
episul?de 31 gave the thiophene-2-methanol 32 (80%) when
treated with a catalytic amount of mercury() oxide in dilute
sulfuric acid at room temperature.
42
α-Fluoroalkylcarbonyl
compounds 33,which have previously been used in the syn-
thesis of?uoroalkyl substituted pyrazoles and pyrimidines,
gave 2-(α-?uoroalkyl)thiophenes on reaction with methyl
mercaptoacetate and sodium methoxide (Scheme 15).
43
Relatively few new routes to benzothiophenes have been
described in the period under review,The route to benzofurans
described by Katritzky and co-workers has also been used as a
one pot synthesis of benzothiophenes,the thioethers analogous
to 24 being intermediates.
31
6-Hydroxybenzothiophenes have
been synthesised by a procedure in which the benzene ring is
annelated to a 2-substituted thiophene by acid catalysed cyclis-
ation.
44
4-Chloro-1,2,3-dithiazole-5-thione,which is readily
prepared from 4,5-dichlorodithiazolium chloride (Appel’s salt)
and hydrogen sul?de,reacts with diphenyldiazomethane to give
the benzothiophene 35 by way of the isolable intermediate 34
(Scheme 16).
45
Scheme 14
Scheme 15
Scheme 16
In a continuation of their work on benzo[c]thiophenes,Cava
and his group have described a synthesis of the bis(2-thienyl)-
benzo[c]thiophene 36 from the phthalide 37.
46
They have also
described a much improved synthesis of naphtho[2,3-c]thio-
phene 38 which makes use of a base catalysed Pummerer
reaction.
47
4 Pyrroles
A review of routes to arylpyrroles covers both classical and
recent methods,with particular emphasis on the Tro?mov
synthesis from aryl ketoximes and acetylenes.
48
Several useful
variants of classical methods have been reported,The optimum
conditions for the preparation of 1-benzylpyrroles from
benzylamines and 2,5-dimethoxytetrahydrofuran require the
use of a mixture of pyridine and acetic acid as solvent.
49
This
synthetic method has also been adapted to provide a route to
3,4-dialkoxypyrroles.
50
5-Tri?uoromethylpyrroles have been
prepared by a modi?ed Hantzsch synthesis (Scheme 17) in
which the use of preformed enamines avoids the side reaction
that leads to furans.
51
The use of organotin enamines,which are
stable enough to be isolated and stored,also leads to pyrroles
in high yields.
52
The products of Knorr-type reductive con-
densation of 1,3-diketones with oximinocyanoacetate esters
depend on whether dry or aqueous acetic acid is used as the
solvent (Scheme 18).
53
Glyoxal monophenylhydrazone has been
used in Knorr-type condensations with β-keto esters to give
1,2,3,4-tetrasubstituted pyrroles.
54
Atmospheric nitrogen has
been used for the?rst time in place of the usual ammonia in
the synthesis of pyrroles from 1,4-dicarbonyl compounds,the
reaction involves the reduction of nitrogen by a mixture
of titanium() chloride,chlorotrimethylsilane and lithium
metal.
55
Some cyclisation reactions that were previously used to syn-
thesise furans have been successfully adapted to the preparation
of pyrroles,Thus,the imines 39,which are formed from the
corresponding ketones and primary amines,spontaneously
cyclise to pyrroles (Scheme 19).
6
Some related palladium
Scheme 17
Scheme 18
J,Chem,Soc.,Perkin Trans,1,1999,2849–2866 2853
catalysed cyclisations of ynone p-tolylsulfonylhydrazones to
1-(p-tolylsulfonylamino)aminopyrroles have been described.
56
Knight and co-workers have adapted their iodocyclisation
reactions to provide routes 2,5-disubstituted pyrroles with or
without an iodo substituent at C-3.
57,58
The methodology is
illustrated in Scheme 20.
58
The synthesis of methyl 2-aryl-
pyrrole-3-carboxylates from methyl buta-2,3-dienoate which
is exempli?ed in Scheme 21 is conceptually quite di?erent
but probably involves the same kind of endo-cyclisation and
aromatisation steps.
59
Other new cyclisation reactions in which the N–C2 bonds of
pyrroles are formed are illustrated in Scheme 22
60
and Scheme
23.
61
Trimethylsilyldiazomethyllithium is used to generate a
vinylidene carbene 40 from which the?ve-membered ring is
generated by intramolecular N–H insertion,The oxime tosylate
41 probably cyclises by N–O insertion of the palladium catalyst
followed by an intramolecular Heck reaction,2-Substituted-3-
nitropyrroles were isolated in good yield from the reaction of
aminoacetaldehyde dimethyl acetal with β-(methylthio)nitro-
alkenes.
62
The aza-Wittig reaction of azido ketones 42 has been previ-
ously reported as a route to pyrrolines 43,These pyrrolines have
now been e?ciently converted into 2-aryl-3-halopyrroles by
bis-halogenation at C-3 with NCS or NBS followed by base
Scheme 19
Scheme 20
Scheme 21
Scheme 22
induced dehydrohalogenation.
63
Other cyclisation reactions
that have been used for speci?cally substituted pyrroles include
the reaction of the diene 44 with arylamines to give 1-aryl-
2,3,4,5-tetrakis(tri?uoromethyl)pyrroles,
64
the cyclisation of
5-chloropent-3-en-2-one with homochiral amines to give chiral
1-substituted 2-methylpyrroles
65
and the reaction of the
dienones 45 with various amines to give 1,2,5-trisubstituted
pyrroles 46.
66
Two three-component pyrrole syntheses are illustrated in
Scheme 24
67
and in Scheme 25.
68
The samarium() iodide
catalysed condensation of alkylamines,aldehydes and nitro-
alkanes gave 1,2,3,4-tetrasubstituted pyrroles in moderate to
good yield,Katritzky and co-workers used benzotriazole
methodology to construct intermediates from which 1,2,3-
triarylpyrroles were obtained by acid catalysed cyclisation.
68
Fürstner’s remarkably short synthesis of the macrotricyclic
core of roseophilin,a pyrrolic antitumour agent,incorporates
a new and potentially more general method of synthesis of
2,4-disubstituted pyrroles; the key steps are outlined in
Scheme 26.
69,70
It includes the formation and reaction of two
π-allylpalladium intermediates.
A simple route to 2-(alkylthio)pyrroles is the base catalysed
cyclisation of allyl isothiocyanate followed by S-alkylation
(Scheme 27).
71,72
The use of isothiocyanate anions has been
extended to the synthesis of more highly substituted 2-(alkyl-
thio)pyrroles.
73
A similarly mild synthesis of 2-arylpyrroles
is the opening of cyclopropane-1,2-diammonium salts 47 with
aromatic aldehydes.
74
The reactions go in bu?ered methanol at
room temperature and bis(alkylammonium) salts can be used in
the same way.
β-Enaminocarbonyl compounds have been used to construct
Scheme 23
Scheme 24
Scheme 25
2854 J,Chem,Soc.,Perkin Trans,1,1999,2849–2866
a variety of new pyrroles,The little-used Zav’yalov pyrrole syn-
thesis,the cyclisation of enamino acids 48 to N-acetylpyrroles
49 with acetic anhydride and a base,has been reinvestigated
and applied to the synthesis of some novel [c]-fused pyrroles.
75
Several new tri?uoromethylpyrroles have been prepared by a
related base catalysed cyclisation of tri?uoroacetylenamines.
76
A synthesis of ethyl 3-arylpyrrole-2-carboxylates (Scheme 28)
involves the intermediacy of vinylogous amidinium salts.
77
3-Aminopyrrole-2,4-dicarboxylates 51 have been prepared by
the acid catalysed cyclisation of enaminones 50
78
and an e?-
cient solid phase pyrrole synthesis is based on the condensation
of resin bound enaminoamides with nitroalkenes.
79
An interesting new pyrrole synthesis was developed as part of
a route to the antibiotic streptorubin B.
80
An enyne metathesis
reaction (Scheme 29) was used as the key step in constructing
the pyrrolic core,Initially platinum() chloride was used as the
Scheme 26
Scheme 27
Scheme 28
catalyst but it was subsequently found that simple protic and
Lewis acids could also be used to bring about such cyclisations.
The dimerisation of propargylamines to pyrroles proceeds
under the in?uence of a lanthanide catalyst; an example is
shown in Scheme 30.
81
Isocyanides continue to be key intermediates in the synthesis
of novel pyrroles,The Barton–Zard reaction (the base catalysed
addition of alkyl isocyanoacetates to nitroalkenes) has been
used to prepare a variety of new pyrroles;
82
in particular,Lash’s
group has made extensive use of the reaction as a route to
pyrrolic intermediates for porphyrin synthesis starting from
polycyclic aromatic nitro compounds.
83–85
The fused pyrroles
52–54 are examples of compounds that have been obtained in
preparatively useful yields by this method,In an analogue of
the Barton–Zard reaction,addition of the anions of alkyl iso-
cyanoacetates to α,β-unsaturated sulfones led to the formation
of a variety of unusually substituted pyrroles,including the
bicyclic pyrrole 56 (60%) from the sulfone 55.
86
Tosylmethyl
isocyanide (TosMIC) has been used to make new [c]annelated
pyrroles
87
and 3-arylpyrroles.
88
By prior reaction with base and
chlorotrimethylstannane,its addition to enones provided a
direct route to 2-trimethylstannylpyrroles.
89
This provides the
basis for the preparation of other 2-substituted pyrroles,In a
similar way,3,4-bis(trimethylsilyl)pyrrole can be used as a pre-
cursor of other β-substituted pyrroles; this has been prepared
e?ciently by 1,3-dipolar cycloaddition of the azomethine ylide
derived from the aziridine 57 to bis(trimethylsilyl)acetylene.
90
Pyrroledicarboxylic esters have been prepared by similar 1,3-
dipolar addition of benzotriazolylaziridines 58 to acetylenic
esters.
91
5 Indoles,indolizines and carbazoles
Several useful new modi?cations of classical methods of indole
synthesis have been described,Two variants of the Fischer
indole cyclisation enable the method to be used for the prepar-
ation of indoles bearing oxygen substituents at C-7 and thus
avoid,abnormal” cyclisation on to the substituted carbon,A
temporary tether was used in the cyclisation of the hydrazone
59; the tether was subsequently removed by reaction with
sodium ethoxide to provide a route to the 7-hydroxy-4-nitro-
indole.
92
A sulfonyloxy group in hydrazones 60 also directs
cyclisation to give mainly 7-substituted indoles.
93
The N–H
insertion reaction of rhodium carbenoids has been used by
Moody and Swann to construct α-arylamino ketone inter-
Scheme 29
Scheme 30
J,Chem,Soc.,Perkin Trans,1,1999,2849–2866 2855
mediates similar to those in the Bischler indole synthesis;
these were then cyclised under acidic conditions to produce
a variety of indole-2-carboxylic acid esters.
94
A route to 2-
substituted 5-hydroxyindoles that provides an alternative to the
Nenitzescu synthesis makes use of cyclohexane-1,4-dione as the
6-membered ring component; an example is shown in Scheme
31.
95
The Sundberg indole synthesis has been used to provide
the?rst preparation of 2-nitroindole,2-azido-β-nitrostyrene
was heated in xylene to give the indole in 54% yield.
96
The cyclisation of 2-alkynylaniline derivatives provides a
versatile synthesis of indoles and several new variants of the
reaction have been reported,3-Arylindoles are obtained by
the palladium catalysed endo cyclisation of 2-ethynyltri?uoro-
acetanilide and trapping of the intermediate palladium species
with aryl iodides (Scheme 32).
97
2-Substituted 3-allylindoles
have also been prepared by a palladium catalysed cyclisation
and capture of the intermediates by allylic esters.
98
Similar syn-
theses of 2,3,6-trisubstituted indoles have been carried out in
the solid phase.
99
Such cyclisations can also be brought about
by bases and this methodology has been applied to the synthesis
of 4,5,7-trimethoxyindole and other oxygen substituted
indoles.
100
Molybdenum catalysed cyclisations of this type have
also been reported; indole itself has been prepared in good yield
from 2-ethynylaniline with the aid of a molybdenum catalyst.
101
Cyclisations of 2-alkynylanilines to 2-substituted indoles can
also be catalysed by TBAF,and in this mild procedure other
reactive functional groups are una?ected.
102
Scheme 31
Scheme 32
The reductive palladium catalysed endo cyclisation of 2-nitro-
styrenes has previously been shown to provide a route to
indoles; new,milder conditions for the reaction,involving
heating the precursor and catalyst at 70 H11034C under 4 atm carbon
monoxide,have now been described,The indoles are isolated
in moderate to excellent yield; for example,4-methoxy-2-nitro-
styrene 61 gave 6-methoxyindole 62 in 89% yield.
103
A base
induced endo cyclisation of the di?uoroalkene 63 led to the
formation of 3-butyl-2-?uoro-1-(p-tolylsulfonyl)indole in high
yield; a similar methodology was used to produce the corre-
sponding benzofuran and benzothiophene.
33
Although limited in scope,the radical cyclisation process
shown in Scheme 33 represents an unusual method for the con-
struction of the N–C2 bond of indoles.
104
Another reaction
which is represented as a new method of constructing this bond
(intramolecular nucleophilic addition to an allyl cation) is the
cyclisation of the enaminone 64 to the benzindole 65 with
methanesulfonyl chloride.
105
A route to substituted tryptamines from iodoanilines makes
use of a Heck vinylation reaction followed by a hydroformyl-
ation to construct an intermediate aldehyde from which the
N–C2 bond is formed,For example,the intermediate aniline 66,
formed from the iodoaniline by a Heck reaction,was converted
into the substituted tryptamine 67 (Scheme 34).
106
A new route to indoles,outlined in Scheme 35,makes use
of the reaction of the air stable complex Cp
2
TiCl
2
with aryl
Grignard reagents to generate a titanocene–benzyne complex,
which undergoes insertion reactions with alkenes,The indole
ring is constructed by bromination followed by palladium
catalysed amination of the resulting aryl bromide.
107
Scheme 33
Scheme 34
2856 J,Chem,Soc.,Perkin Trans,1,1999,2849–2866
An electrochemical method,involving the use of a redox?ow
cell,has provided an e?cient synthesis of 1-alkylaminoindoles
from the nitroamines 68.
108
3-Cyano-1-hydroxyindoles have
been prepared in good yield by base catalysed cyclisation of the
aromatic nitro compounds 69.
109
In concentrated hydrochloric
acid 4-amino-2-methylbenzofurans 70 are converted in high
yield into the isomeric 4-hydroxy-2-methylindoles 71,The reac-
tion requires the 2-methyl substituent and occurs only in the
presence of concentrated acids,indicating that a tertiary carbo-
cation intermediate is involved.
110
The known,lateral lithi-
ation” of the methyl group of Boc-protected o-toluidines has
been applied to the synthesis of ethyl indole-2-carboxylates by
quenching the anion with diethyl oxalate; the reaction allows
the preparation of indole esters bearing a range of substituents
in the six-membered ring.
111
New examples of base catalysed reactions which lead to
formation of the indole C2–C3 bond include the cyclisation of
the succinimide 72 to the indole 73
112
and the intramolecular
addition of benzyl sulfones to imines and carbodiimides.
113
Palladium catalysed cyclisation reactions are increasingly
important methods for the formation of the C3–C3a bond of
indoles,The methodology illustrated in Scheme 9 for the con-
struction of hydroxybenzofurans has also been applied to
indole synthesis
29
as has the solid phase intramolecular Heck
reaction.
30
A simple condensation–cyclisation procedure,
shown in Scheme 36,is the palladium catalysed reaction of
2-iodoanilines with ketones.
114
Related cyclisations of pre-
formed enamines to 2-tri?uoromethylindole-3-carboxylic acid
esters have been described.
115
A new indole synthesis makes use of radical cyclisation for
the construction of the C3–C3a bond,The radical intermedi-
Scheme 35
Scheme 36
ates 74 were generated from the corresponding diazonium
tetra?uoroborates with sodium iodide in acetone and cyclised
to the indoles 75.
116
The cyclisation onto a vinyl bromide allows
a wider variety of indoles to be constructed than the analogous
radical cyclisation onto a triple bond,Vinyl bromides are also
used as precursors in the synthesis of 3,4-disubstituted indoles
shown in Scheme 37.
117
This reaction is rationalised as involving
an aryne intermediate; after cyclisation the aryllithium species
is intercepted by electrophiles such as benzaldehyde and ethyl
chloroformate,Kuehm-Caubère and co-workers have also
described an e?cient synthesis of 2-substituted indoles by
arynic cyclisation,The aryl imines 76 derived from methyl
ketones gave the indoles 77 in the presence of the complex base
derived from sodamide and sodium tert-butoxide.
118
3-Methylindoles can be prepared from propargylanilines
(prop-2-ynylanilines) by the new and conceptually simple
method illustrated in Scheme 38.
119
There are several con-
straints on the method which were established experimentally:
the trialkylsilyl group and the nitrogen protecting group were
chosen in order to be stable to methanesulfonic acid,the cyclis-
ing agent,and the position at which the cation cyclises must
be su?ciently activated by ring substituents,Another acid
catalysed cyclisation procedure which leads to indoles unsubsti-
tuted in the?ve-membered ring,is the reaction of anilines with
triethanolamine in the presence of tin() chloride and a
ruthenium catalyst.
120
The indoloquinone 79 has been synthesised by a route in
which the key step is intramolecular 1,3-dipolar addition of the
azomethine ylide 78.
121
The 1,3-dipole was generated from an
N-methyloxazolium salt by ring opening with cyanide,A novel
Scheme 37
Scheme 38
J,Chem,Soc.,Perkin Trans,1,1999,2849–2866 2857
synthesis of 3-nitroindoles is based on the construction of the
six-membered ring from a 3-nitropyrrole intermediate.
122
One of the standard synthetic methods for indolizines is the
reaction of activated alkenes or alkynes with pyridinium ylides.
This method has been used to prepare some new 1-tri?uoro-
methylindolizines from 2-bromo-3,3,3-tri?uoropropene.
123
Methods of synthesis that start from pyrroles are much less
common,A method involving (stepwise) cycloaddition of rad-
ical cations such as 80 to β-acceptor substituted enamines has
been described,The cations were generated by electrochemical
oxidation of the corresponding pyrroles and the?nal products
were indolizines such as 81 (X = CN,CO
2
Me,etc.).
124
The thermal ring closure of N-arylketenimines 82 to benzo-
[b]carbazoles 83 is proposed to involve a diradical intermedi-
ate.
125,126
Cyclisations of this type can also lead to the formation
of quinolines,depending on the nature of the substituents
(Section 14),Examples of the formation of carbazoles by oxid-
ative cyclisation of diphenylamines
127
and from pentacarbonyl-
chromium carbene complexes
128
have also been reported.
6 Oxazoles,thiazoles and benzothiazoles
A synthesis of 5-amino-4-cyanooxazoles with a functionalised
side chain at C-2 has been described; the procedure is simple
and uses aminomalononitrile toluene-p-sulfonate,a carboxylic
acid and DCC in pyridine (Scheme 39).
129
2-Substituted 5-aryl-
oxazoles are produced in good yield by the oxidation of
aryl methyl ketones and tri?uoromethanesulfonic acid in an
aliphatic nitrile (Scheme 40),Both thallium() acetate
130
and
iodosylbenzene diacetate
131
have been used as oxidants,The
mechanism probably involves formation and cyclisation of a
nitrilium salt,In a simple synthesis of 2-substituted 4-phenyl-
oxazoles,phenacyl carboxylates were heated with acetamide
and boron tri?uoride–diethyl ether at about 140 H11034C,The
N-acetylimines 84 are formed as intermediates.
132
N-Acyl-
isoxazolones 85 lose carbon dioxide on?ash pyrolysis or on
photolysis to give trisubstituted oxazoles 86.
133,134
When N-thio-
acylisoxazoles are used instead,they give thiazoles in an analo-
gous manner.
135
5-Arylisoxazole-4-carbaldehydes have been
isolated in moderate yield from the reaction of aryl 2-azido-
methyl ketones with the Vilsmeier reagent at 80–90 H11034C.
136
A full paper has appeared on the insertion of rhodium
carbenoids derived from diazocarbonyl compounds into the
N–H bonds of amides.
137
This leads to dihydrooxazoles,which
were oxidised by the use of triphenylphosphine,iodine and tri-
ethylamine,a method?rst described by Wipf,A comparative
study of methods for the oxidation of 4,5-dihydrooxazoles to
oxazoles has also been published.
138
A solid phase adaptation of the Hantzsch synthesis of
2-aminothiazoles has been achieved.
139
The solution synthesis
of N-substituted 2-aminothiazoles from α-haloketones,potas-
sium thiocyanate and a primary amine has been simpli?ed to an
e?cient one pot procedure.
140
Several N-substituted 2-amino-
thiazoles have also been prepared from N-thiocarbamoyl-
imidates and activated haloalkanes.
141
2-Cyanobenzothiazoles are formed by the sequence shown in
Scheme 41,The second reaction step can be carried out by
conventional heating,or,more e?ciently,by microwave irradi-
ation.
142
7 Isoxazoles,isothiazoles and fused analogues
3-Substituted 5-aminoisoxazoles have been produced from
oximes of α-haloketones and isocyanides (Scheme 42); trans-
ient vinylnitroso compounds are probably intermediates.
143
A
synthesis of trisubstituted isoxazoles from aromatic aldehydes
and nitroethane or nitropropane (Scheme 43) requires the
incorporation of two moles of the nitroalkane in the product.
144
A simple route to 3,5-disubstituted isoxazole-4-carb-
aldehydes,and also to the corresponding pyrazoles,depends
upon the clean reduction of ketene dithioacetals with zinc and
acetic acid,For example,the dithioacetal 87 was reduced to the
diketone 88,from which 3,5-dimethylisoxazole-4-carbaldehyde
Scheme 39
Scheme 40
Scheme 41
Scheme 42
Scheme 43
2858 J,Chem,Soc.,Perkin Trans,1,1999,2849–2866
was formed by conventional reaction with hydroxylamine
and deprotection.
145
A route to unsymmetrically 3,5-disubsti-
tuted isoxazoles,outlined in Scheme 44,avoids the problems
of regiocontrol inherent in reactions of 1,3-diketones with
hydroxylamine.
146
Anthranils can be prepared by dehydration of 2-nitrobenzyl
derivatives and this method has been used as a route to the
sulfones 90 from the readily available nitro compounds 89.
147
3-Alkylaminoanthranils have been obtained by cyclisation of
the nitrobenzylphosphonates 91.
148
Further experimental and mechanistic details have appeared
of the unusual conversion of 2,5-diarylfurans into 3,5-disubsti-
tuted isothiazoles which was described in the previous
report.
149,150
The dithiazole 92,which is easily prepared from
Appel’s salt and malononitrile,has been converted in high
yield into the isothiazole 93 by heating with benzyltriethyl-
ammonium chloride.
45
3-Dialkylamino-1,2-benzisothiazoles 95
are formed in excellent yields from the disul?de 94 by nucleo-
philic addition of the amide R
2
NMgBr to the nitrile followed
by oxidative cyclisation with copper() chloride.
151
8 Imidazoles and benzimidazoles
A compilation of methods of synthesis of imidazoles and benz-
imidazoles is available.
152
Several new routes to tri- and tetrasubstituted imidazoles are
based on the cyclisation of amino(thiocarbonyl)amidines 96
and related species,Two of these routes are outlined in Scheme
45.
153
Oxidative cyclisation followed by treatment with base
(Route 1) resulted in the extrusion of sulfur,probably by way
of the thiadiazine shown,Alternatively the imidazole could
be formed by S-methylation followed by the elimination of
methanethiol (Route 2),This second route is related mech-
anistically to a di?erent synthesis of imidazoles of this type
which is shown in Scheme 46.
154
In this synthesis the carbenoid
attacks the nitrogen and the reaction then follows the same
course as in Route 2 above.
In a new application of their isocyanide methodology,van
Leusen and his co-workers have prepared a series of 4(5)-
monosubstituted imidazoles by the addition of tosylmethyl
Scheme 44
isocyanide (TosMIC) to N-tosyl- or N-(dimethylsulfamoyl)-
aldimines 97.
155
The N-substituent is easily removed from the
imidazoles,either spontaneously or by reaction with aqueous
HBr,Tetrasubstituted imidazoles 99 have been prepared by
heating the amides 98 with ammonium tri?uoroacetate.
156
The
reaction of methyl isothiocyanate with LDA can take di?erent
courses that are dependent on the reaction conditions (Scheme
47),The thiazole 100 is isolated after methylation of the reac-
tion mixture with dimethyl sulfate,but the imidazole 101 is
obtained if the reaction mixture is quenched with water before
methylation.
157
A new synthesis of 2-acylaminobenzimidazoles has been
described that is a re?nement of a method?rst published 80
years ago by Pellizzari,Arylhydrazines were converted by suc-
cessive cyanation and acylation into the hydrazides 102,These
rearranged cleanly to benzimidazoles when heated in diphenyl
ether at 190 H11034C.
158
This method was earlier shown to go by way
Scheme 45
Scheme 46
Scheme 47
J,Chem,Soc.,Perkin Trans,1,1999,2849–2866 2859
of a [3,3] sigmatropic shift (Scheme 48),A new procedure for
preparing 2-alkylaminobenzimidazoles from o-phenylene-
diamine and primary amines has also been described.
159
2-Methylbenzimidazole has been prepared by irradiating
o-dinitrobenzene with titanium dioxide in ethanol,The reaction
goes by way of 2-nitroaniline which condenses with acetalde-
hyde (formed by oxidation of ethanol) and is then further
reduced.
160
9 Pyrazoles and indazoles
A new synthesis of 3-aryl- and 3-vinylpyrazoles is based on the
palladium catalysed endo cyclisation previously used for
pyrroles (Scheme 19) and for other?ve-membered heterocycles.
N-Propargyl-N-tosylhydrazine 103 was successively arylated by
reaction with iodoarenes and cyclised under the in?uence of
palladium catalysts to give the 3-arylpyrazoles 104,The steps
could be carried out as a one pot procedure,giving the
pyrazoles in 28–69% yield,Vinyl tri?ates were also used in place
of aryl iodides in the?rst step.
161
Another simple synthesis
of 3-substituted pyrazoles is based on the cyclisation of
tosylhydrazone salts of α,β-unsaturated aldehydes which
were produced from readily available starting materials by
a Wadsworth–Emmons reaction (Scheme 49).
162
4-Alkynyl-
pyrazoles were prepared by regioselective addition of diazo-
methane to the double bond of the sulfones 105 followed by
base catalysed elimination of benzenesul?nic acid.
163
5-Tri?uoromethylpyrazoles 107 have been isolated in good
yield from reaction of the imidoyl iodides 106 with the dianions
of methyl ketone phenylhydrazones; the methyl group of
the phenylhydrazone becomes C-4 of the new pyrazole.
164,165
A
di?erent route to 5-tri?uoromethylpyrazoles 109 is provided
by the reaction of the ketene dithioacetal 108 with methyl-
hydrazine.
166
Several syntheses of new pyrazoles make use of the reaction
of β-enaminocarbonyl compounds and related species with
hydrazines,For example,4-amino-3-phenylpyrazole 111 was
isolated in 78% yield from the reaction of the enaminone 110
with an excess of hydrazine
167
and enaminonitriles such as 112
were similarly used for the synthesis of a variety of 5-amino-
pyrazoles.
168–170
The hydrazones 113 cyclised to the indazoles 114 when
heated to 250 H11034C;
171
an oxidative cyclisation of the hydrazone
115 to an indazoloquinone (a type of,aza-Nenitzescu
reaction”) has also been reported.
172
An example of indazole
synthesis from pyrazoles by benzo annelation has been
described.
173
Scheme 48
Scheme 49
10 Oxadiazoles and thiadiazoles
Ketenylidene triphenylphosphorane 116 is easy to prepare
and is storable,It has been found to react with acylhydrazides
to give a series of 2-methyl-5-substituted 1,3,4-oxadiazoles in
moderate to good yields.
174
An intriguing problem is to explain
how the methyl substituent is produced,The authors favour
a mechanism (Scheme 50) in which methylenetriphenyl-
phosphorane is eliminated and then reincorporated into the
product,Hydrogen chloride is eliminated in the base catalysed
cyclisation of aldehyde trichloroacetylhydrazones,which leads
to 5-substituted-2-dichloromethyl-1,3,4-oxadiazoles.
175
A more
standard synthesis of 1,3,4-oxadiazoles is the cyclodehydration
of 1,2-diacylhydrazines and this reaction has been carried out
under palladium catalysis.
176
Palladium catalysis is also integral
to another 1,3,4-oxadiazole synthesis,palladium catalysed
carbonylation of aryl iodides followed by reaction with
5-phenyltetrazole gives 2-aroyl-5-phenyltetrazoles,from which
1,3-oxadiazoles are formed by thermal elimination of nitro-
gen.
177
A similar carbonylation procedure is involved in a one
pot synthesis of 1,2,4-oxadiazoles (Scheme 51).
178
Trithiazyl chloride,(NSCl)
3
,has proved to be a rich source of
new 1,2,5-thiadiazoles,Alkenes and alkynes react readily with it
to give mono- or disubstituted 1,2,5-thiadiazoles in one step;
for example,DMAD gave the 3,4-dicarboxylic acid dimethyl
ester 117 (84%).
179
Activated methylene compounds similarly
give disubstituted 1,2,5-thiadiazoles; thus,the thiadiazole 118
was isolated (41%) from a reaction with dibenzoylmethane.
180
More exotic structures are obtained from reactions of trithiazyl
Scheme 50
Scheme 51
2860 J,Chem,Soc.,Perkin Trans,1,1999,2849–2866
chloride with pyrroles; an example is the bis(thiadiazole)
119 formed (45%) with 1-methyl-2,5-diphenylpyrrole.
181
1,2,5-
Thiadiazoles have also been isolated in moderate yield from the
reaction of tetrasulfur tetranitride or its antimony(?) chloride
complex with oximes
182,183
and with isoxazoles.
184
Ethyl diazoacetate and other diazo compounds react with
thiocarbonylbis(imidazole) to give 1,3,4-thiadiazoles by 1,3-
dipolar addition to the CH5008
H5008
S bond,and not 1,2,3-thiadiazoles as
was reported earlier.
185
11 Triazoles,benzotriazoles and tetrazoles
1,2,3-Triazole has been isolated in up to 75% yield from
the reaction of dichloroacetaldehyde tosylhydrazone with
ammonia (Scheme 52),When primary amines are used in
place of ammonia,1-substituted triazoles are formed in good
yield.
186
Another synthesis of 1,2,3-triazole starts from glyoxal
187
and a third new route is based on the 1,3-dipolar cycloaddition
of 4-methoxybenzyl azide to acetylenedicarboxylic acid,The
resulting triazole-4,5-dicarboxylic acid is decarboxylated and
the nitrogen protecting group is subsequently removed by
treatment with HBr.
188
These authors also describe a synthesis
of 1-benzyloxy-1,2,3-triazole from glyoxal monobenzyloxime.
Diazo transfer from methanesulfonyl azide to β-enamino-
carbonyl compounds 120 led to the formation of the 1,2,3-
triazoles 121 in moderate to high yields.
189
Ethyl 1-hydroxy-
triazole-4-carboxylate 123 was designed as a new coupling
reagent for peptide synthesis; it was prepared from ethyl
diazoacetate and the Vilsmeier reagent,followed by reaction of
the iminium salt 122 with hydroxylamine.
190
The previously unknown 1,4-dialkyl-1,2,4-triazolium salts
124 have been prepared from imidoyl chlorides and 1-alkyl-
1-formylhydrazines.
191
Samarium diiodide was used as the
reducing agent in the cyclisation of the 2-nitroazobenzene 125
to the corresponding 2-aryl-1,2,3-benzotriazole.
192
5-Substituted tetrazoles have been prepared in good yield
from aliphatic and aromatic nitriles with sodium azide in tolu-
ene,Triethylamine hydrochloride acts as a catalyst and this
allows a small amount of triethylammonium azide to be present
Scheme 52
in the organic solvent.
193
A micelle medium (hexadecyltrimethyl-
ammonium bromide) has also been used for the reaction.
194
12 Pyrones,coumarins and chromones
A palladium catalysed synthesis of tri- and tetrasubstituted
2-pyrones has been described and is illustrated in Scheme 53.
As shown in this example,when unsymmetrical alkynes are
used in the reaction the bulkier group tends to be located at C-6
in the pyrone.
195
A simple route to 3,4-disubstituted 2-pyrones,
based on a Wittig reaction and cyclisation,is illustrated in
Scheme 54.
196
A useful method for the conversion of 4-pyrones into
pyrylium hydrobromides is to heat the pyrones in chloroform
under re?ux with tert-butyl bromide.
197
3-Formyl-4-pyrones
126 have been prepared from 3-arylpropan-2-ones and four
equivalents of the Vilsmeier reagent
198
and a synthesis of 2-
tri?uoromethyl-4-pyrones 128 is based on the base catalysed
condensation of epoxyketones 127 with ethyl tri?uoro-
acetate.
199
Coumarin and some derivatives can be synthesised by?ash
vacuum pyrolysis of methyl 2-hydroxycinnamates.
200
The (E)-
con?guration of the double bond normally precludes cyclis-
ation but the barrier to isomerisation is overcome by the high
temperature method,A simple synthesis of some coumarin-4-
carboxylic esters,illustrated in Scheme 55,involves the reaction
of phenols with the betaine formed by the addition of tri-
phenylphosphine to DMAD.
201
3-Arylcoumarins have been
produced from the protected alkynylphenol 129 by palladium
catalysed arylation followed by oxidative cyclisation.
202
A syn-
thesis of isomeric 3-arylisocoumarins 131 also involves pal-
ladium catalysis,the styryl bromides 130 were coupled with
aryltrimethylstannanes and the intermediate esters were then
cyclised.
203
A new route to 3-styrylchromones 133 from the hydroxy-
ketones 132 and trimethyl orthoformate in methanol is based
Scheme 53
Scheme 54
Scheme 55
J,Chem,Soc.,Perkin Trans,1,1999,2849–2866 2861
on the oxidative rearrangement of an intermediate ketone with
thallium() nitrate.
204
13 Pyridines
In a series of recent papers Sauer and his co-workers have
greatly increased the scope of the known synthesis of pyridines
by cycloaddition of electrophilic 1,2,4-triazines to alkynes.
They have shown that stannylated acetylenes are particularly
good partners in these reactions,with the added advantage of
giving pyridines in which the trialkylstannyl group is available
for coupling.
205,206
An example is shown in Scheme 56,By mak-
ing use of reactions of this type,Sauer’s group has been able to
build up a series of oligopyridines and related oligomers.
207–210
Norbornadiene was also shown to be an e?ective synthetic
equivalent of acetylene in these cycloadditions; it adds to the
1,2,4-triazines in boiling 1,2-dichlorobenzene and cyclopenta-
diene is spontaneously eliminated from the cycloadduct.
211
A
di?erent approach to bipyridines,illustrated in Scheme 57,is
the cobalt catalysed [2 H11001 2 H11001 2] addition of alkynyl nitriles with
mono- and diacetylenes.
212,213
A further application of the
cobalt catalysed [2 H11001 2 H11001 2] addition of ynamines to chloro-
pyridazines,described in the last report,has also been pub-
lished.
214
A rare example of a [4 H11001 2] cycloaddition to an
unactivated nitrile provides a synthesis of furopyridines; a
tungsten substituted 1,3-diene is the reaction partner,as shown
in Scheme 58.
215
Pentasubstituted pyridines have been obtained
by the addition of ynamines to styryl carbodiimides and related
cumulenes.
216
The classical methods of pyridine synthesis continue to be
extended,A simple,regioselective synthesis of 4-tri?uoromethyl-
pyridines from β-diketones is shown in Scheme 59.
217
2-
Tri?uoromethylpyridines and other trihalomethylpyridines
have been synthesised in a similar way from α-trihalomethyl-
enones and enamines.
218,219
Surprisingly,reaction of the
Scheme 56
Scheme 57
Scheme 58
enaminoketones 134 with β-dicarbonyl compounds and TFA
led to the formation of 2-tri?uoromethylpyridines 135 instead
of the expected 4-tri?uoromethyl isomers.
220
The pyrimidinone
136 has been shown to act as a synthetic equivalent of 2-
nitropropane-1,3-dione in pyridine synthesis; in reactions with
aliphatic ketones and ammonia,3-nitropyridines 137 are
formed.
221
1,1,1-Ethanetriacetonitrile 138 reacts with Grignard reagents
to give 2-aminopyridines; for example the aminopyridine 139
was formed (40%) with phenylmagnesium bromide.
222
2-Alkyl-
aminopyridines 141 have been prepared by the reaction of
benzotriazolylacetonitrile 140 with enones and alkylamines.
223
When aqueous sodium hydroxide is used in place of the alkyl-
amine,2-pyridones are formed.
A simple route to 2-pyridones which,surprisingly,has not
been carried out before in satisfactory yield is the dimerisation
of substituted acetoacetamides,This has now been achieved
by heating the compounds with toluene-p-sulfonic acid in the
absence of a solvent; yields of the pyridones 142 are high.
224
2-Pyridones 144 have been isolated in moderate yield from the
acid catalysed dehydration of the spiro compounds 143,which
are derived from β-oxonitriles and cyclohexanone.
225
The pyrid-
2-one esters 146 have been synthesised from methyl propiolate
and magnesium salts 145 of β-aminoacrylates.
226
A new route
to pyridine-2-thiones,illustrated in Scheme 60,makes use of an
electrocyclic ring closure to construct the ring system.
227
Scheme 59
Scheme 60
2862 J,Chem,Soc.,Perkin Trans,1,1999,2849–2866
14 Quinolines and isoquinolines
Several 4-per?uoroalkylquinolines have been prepared by Fried-
l?nder-type syntheses from 2-per?uoroalkylanilines; one such
route is illustrated in Scheme 61.
228,229
A modi?ed Friedl?nder
synthesis is also used to prepare a series of 5-methoxy-
quinolines 148,The amide 147 is formylated at C-2 by directed
lithiation and reaction with DMF; the aldehyde is then con-
densed with ketones to give the quinolines.
230
Several examples
of the synthesis of 2-aminoquinolines by reductive cyclisation
of o-nitrocinnamonitriles have also been reported.
231,232
Quino-
line and a few substituted quinolines have been isolated from
the Baker’s yeast reductive cyclisation of o-nitrocinnamyl
ketones.
233
As indicated in Section 5,alkynyl ketenimines of structure 82
can cyclise to fused indoles by way of biradical intermediates;
they can also give quinolines when R = H,Similarly,the carbo-
diimide 149 cyclised to the aminoquinoline 150 (49%) when
heated with a hydrogen donor.
234
Several syntheses of new quinolines are based on the N-alkyl-
ation of anilines followed by acid catalysed cyclisation,Thus,
reaction of the allenylphosphine oxides 151 with anilines,fol-
lowed by reaction with an isocyanate and cyclodehydration,
gives the quinolylphosphine oxides 152.
235,236
The ruthenium
catalysed reaction of triallylamine with anilines results in the
formation of 2-ethyl-3-methylquinolines.
237
3-Cyanoquinolines
have been formed from the condensation of the sodium salt
153 of 3,3-dimethoxy-2-formylpropanenitrile with activated
anilines followed by acid catalysed cyclisation.
238
Other cyclis-
ation processes involving formation of the C4–C4a bond have
been reported.
239–241
Methods of forming the quinoline ring by cycloaddition are
not common,an exception being the reaction of activated
acetylenes and alkenes with N-aryliminium cations,These
cations have been generated by benzotriazole methodology
and N-alkylquinolinium salts were formed by cycloaddition
to acetylenes.
242
A cycloaddition process that is mainly of
mechanistic interest is the Diels–Alder reaction of 1,2,3-
benzotriazine with enamines,from which 2- and 3-substituted
quinolines were isolated in low yields.
243
Cyclisation reactions
Scheme 61
in which the N–C8a bond is formed are also fairly uncommon,
but a series of such reactions involving cyclisation of oximes
has been reported.
244,245
The example in Scheme 62 has been
shown to go by way of an isolable spiro intermediate.
245
The Baylis–Hillman reaction of 2-nitrobenzaldehyde with
but-3-en-2-one and other enones leads to the allylic alcohols
154,which can be reduced and cyclised to 2-substituted quino-
line 1-oxides,When methyl acrylate is used in the Baylis–
Hillman reaction the product is 3-methyl-2-quinolone.
246
2-
Quinolones have also been formed by reductive cyclisation of
the nitrocinnamate esters 155
247
and by base catalysed cyclis-
ation of the amides 156.
248
Both these precursors were obtained
by palladium catalysed coupling reactions.
The Jackson variation of the Pomeranz–Fritsch isoquinoline
synthesis results in the formation of 2-tosyl-1,2-dihydroiso-
quinolines,but the tosyl group can be di?cult to remove,By
replacing the tosyl group with the isomeric benzylsulfonyl
group the method has been improved,the protecting group
can be removed by brief heating with Raney nickel without
reducing the ring system.
249
Palladium coupling methods have been applied to isoquino-
line synthesis,An example of the coupling of 2-iodobenz-
aldehyde N-tert-butylimine with an acetylene is shown in
Scheme 63
250
and Grigg’s group has used intramolecular
palladium catalysed addition to allenes (analogous to the
conversion of 21 into 22) in a synthesis of isoquinolones.
28
15 Pyrimidines and quinazolines
In a recent solid phase synthesis of pyrimidines,referred to in
the last report,the ring system is constructed from alkynyl
ketones and amidines,This methodology has now been adapted
to the synthesis of pyrimidin-4-yl substituted α-amino acids
(Scheme 64).
251
2-Substituted pyrimidines have been isolated in
good yield from the reaction of amidine hydrochlorides with
malonodialdehyde tetramethyl acetal when the reactions are
carried out in a sealed tube.
252
A new synthesis of 2-trichloro-
methylpyrimidines,illustrated in Scheme 65,involves alkynyl
Fischer carbene complexes {[M] = Cr(CO)
5
,W(CO)
5
} as dieno-
philes.
253
Reactions of azadienes of this type with β-keto esters
and with isocyanates have also been used in the synthesis of
pyrimidinones and quinazolinones.
254
New routes to 4-arylaminoquinazolines from 2-amino-N-
Scheme 62
Scheme 63
J,Chem,Soc.,Perkin Trans,1,1999,2849–2866 2863
arylbenzamidines
255
and from the amidines 157 with anilines
256
have been described,These amidines are formed by thermal
decomposition of intermediate triazolines; by analogy,the
decomposition of the triazolines 158 in the presence of ammo-
nium acetate leads to the formation of the quinazolines 159.
257
A cyclisation route to 2-diethylaminoquinazolines from imidoyl
chlorides has also been reported.
258
16 Other diazines,triazines and tetrazines
An optimised procedure for the formation of the parent 1,2,4,5-
tetrazine from formamidine acetate and hydrazine has been
described.
259
The tetrazine undergoes Diels–Alder cycloaddi-
tion to a variety of acetylenes and cyclic alkenes,The reaction is
of the inverse electron demand type and bis(trimethylstannyl)-
acetylene is amongst the most reactive with this tetrazine,This
study provides data on the relative reactivities of electron rich
dienophiles which should have more general applicability.
Related routes to 3-aryltetrazines
260
and 3,6-dichlorotetra-
zine
261
are also reported,The bis(tri?uoromethyl)pyridazines
161 have been isolated in moderate yield after heating the
hydrazones 160 in TFA
262
and the pyridazine ester 162
was formed in high yield from methyl 9,12-dioxostearate and
aqueous hydrazine under ultrasound irradiation.
263
A new route to unsymmetrically 2,6-disubstituted 1,3,5-
triazines is shown in Scheme 66.
264
This synthesis probably
involves the condensation of two moles of the isothioureas with
the Vilsmeier reagent,The alkylthio substituent can be oxidised
to the sulfoxide and displaced by amines,making the method
suitable for combinatorial synthesis,The 1,3,5-triazines 163 are
formed from cyanamides and formamides by heating them
together under high pressure (Scheme 67).
265
An unusual synthesis of cinnolines is illustrated in Scheme
68,The reaction is limited to TCNE and the choice of
Scheme 64
Scheme 65
acetonitrile as a solvent is important; the mechanism has not
been established.
266
Cyclisation reactions that lead to 2,3-diphenylquinoxaline 1-
oxides,
267
1,2,4-benzotriazine 1-oxides
268
and phthalazinones
269
have been reported,Two syntheses of 1,2,4-benzotriazines
make use of 1-substituted benzotriazoles as precursors,Flash
pyrolysis of the ylide 164 gave 3-acetyl-1,2,4-benzotriazine
in moderate yield
270
and reaction of the tosylhydrazones 165
with butyllithium in excess led to the isolation of 3-aryl-1,2,4-
benzotriazines.
271
In both procedures the triazine ring is formed
by cleavage and recyclisation of the benzotriazole.
17 References
1 J,W,Corbett,Org,Prep,Proced,Int.,1998,30,489.
2 X,L,Hou,H,Y,Cheung,T,Y,Hon,P,L,Kwan,T,H,Lo,
S,Y,Tong and H,N,C,Wong,Tetrahedron,1998,54,1955.
3 X.-S,Ye,P,Yu and H,N,C,Wong,Liebigs Ann./Recl.,1997,
459.
4 J,A,Marshall and C,A,Sehon,Org,Synth.,1998,76,263.
5 D,I,Ma Gee and J,D,Leach,Tetrahedron Lett.,1997,38,8129.
6 A,Arcadi and E,Rossi,Tetrahedron,1998,54,15253.
7 B,Gabriele,G,Salerno,F,DePascali,G,T,Sciano,M,Costa and
G,P,Chiusoli,Tetrahedron Lett.,1997,38,6877.
8 B,Gabriele and G,Salerno,Chem,Commun.,1997,1083.
9 P,Wipf,L,T,Rahman and S,R,Rector,J,Org,Chem.,1998,63,
7132.
10 J,W,Herndon and H,X,Wang,J,Org,Chem.,1998,63,4564.
11 N,Iwasawa,K,Maeyama and M,Saitou,J,Am,Chem,Soc.,1997,
119,1486.
12 N,Iwasawa,T,Ochiai and K,Maeyama,J,Org,Chem.,1998,63,
3164.
13 S,Kajikawa,Y,Noiri,H,Shudo,H,Nishino and K,Kurosawa,
Synthesis,1998,1457.
14 R,C,Larock,M,J,Doty and X,J,Han,Tetrahedron Lett.,1998,39,
5143.
15 H.-H,Tso and H,Tsay,Tetrahedron Lett.,1997,38,6869.
16 M,S,B,Wills and R,L,Danheiser,J,Am,Chem,Soc.,1998,120,
9378.
17 M,Kurosu,L,R,Marcin and Y,Kishi,Tetrahedron Lett.,1998,39,
8929.
18 G,A,Kraus and X,M,Wang,Synth,Commun.,1998,28,1093.
19 R,Díaz-Cortés,A,L,Silva and L,A,Maldonado,Tetrahedron
Lett.,1997,38,2207.
20 A,S,K,Hashmi,T,L,Ruppert,T,Knofel and J,W,Bats,J,Org.
Chem.,1997,62,7295.
Scheme 66
Scheme 67
Scheme 68
2864 J,Chem,Soc.,Perkin Trans,1,1999,2849–2866
21 A,Fürstner,T,Gastner and J,Rust,Synlett,1999,29.
22 Y,Koga,H,Kusama and K,Narasaka,Bull,Chem,Soc,Jpn.,1998,
71,475.
23 N,G,Kundu,M,Pal,J,S,Mahanty and M,De,J,Chem,Soc.,
Perkin Trans,1,1997,2815.
24 B,C,Bishop,I,F,Cottrell and D,Hands,Synthesis,1997,1315.
25 N,Monteiro and G,Balme,Synlett,1998,746.
26 N,Monteiro,A,Arnold and G,Balme,Synlett,1998,1111.
27 M,G,Kulkarni and R,M,Rasne,Synthesis,1997,1420.
28 M,Gardiner,R,Grigg,V,Sridharan and N,Vicker,Tetrahedron
Lett.,1998,39,435.
29 D,D,Hennings,S,Iwasa and V,H,Rawal,Tetrahedron Lett.,1997,
38,6379.
30 H.-C,Zhang and B,E,Maryano?,J,Org,Chem.,1997,62,1804.
31 A,R,Katritzky,L,Serdyuk and L,H,Xie,J,Chem,Soc.,Perkin
Trans,1,1998,1059.
32 M,Black,J,I,G,Cadogan,H,McNab,A,D,MacPherson,
V,P,Roddam,C,Smith and H,R,Swenson,J,Chem,Soc.,Perkin
Trans,1,1997,2483.
33 J,Ichikawa,Y,Wada,T,Okauchi and T,Minami,Chem,Commun.,
1997,1537.
34 B,D’hooge,S,Smeets,S,Toppet and W,Dehaen,Chem,Commun.,
1997,1753.
35 O,A,Tarasova,L,V,Klyba,V,Y,Vvedensky,N,A,Nedolya,
B,A,Tro?mov,A,Brandsma and H,D,Verkruijsse,Eur,J,Org.
Chem.,1998,253.
36 O,A,Tarasova,N,A,Nedolya,V,Y,Vvedensky,L,Brandsma and
B,A,Tro?mov,Tetrahedron Lett.,1997,38,7241.
37 L,Brandsma,V,Y,Vvedensky,N,A,Nedolya,O,A,Tarasova and
B,A,Tro?mov,Tetrahedron Lett.,1998,39,2433.
38 T,Nishio,Helv,Chim,Acta,1998,81,1207.
39 B,S,Kim,K,S,Choi and K,Kim,J,Org,Chem.,1998,63,6086.
40 X.-S,Ye and H,N,C,Wong,J,Org,Chem.,1997,62,1940.
41 J,Nakayama,R,Hasemi,K,Yoshimura,Y,Sugihara,S,Yamaoka
and N,Nakamura,J,Org,Chem.,1998,63,4912.
42 C,M,Marson and J,Campbell,Tetrahedron Lett.,1997,38,
7785.
43 H.-P,Guan,B.-H,Luo and C.-M,Hu,Synthesis,1997,461.
44 A,V,Kelin and Y,Y,Kozyrkov,Synthesis,1998,729.
45 K,Emayan,R,F,English,P,A,Koutentis and C,W,Rees,J,Chem.
Soc.,Perkin Trans,1,1997,3345.
46 A,K,Mohanakrishnan,M,V,Lakshmikantham,C,McDougal,
M,P,Cava,J,W,Baldwin and R,M,Metzger,J,Org,Chem.,1998,
63,3105.
47 A,K,Mohanakrishnan,M,V,Lakshmikantham,M,P,Cava,
R,D,Rogers and L,M,Rogers,Tetrahedron,1998,54,7075.
48 S,E,Korostova,A,I,Mikhaleva,A,M,Vasiltsov and B,A.
Tro?mov,Russ,J,Org,Chem,(Engl,Transl.),1998,34,967.
49 C,D’Silva and D,A,Walker,J,Org,Chem.,1998,63,6715.
50 A,Merz and T,Meyer,Synthesis,1999,94.
51 V,Kameswaran and B,Jiang,Synthesis,1997,530.
52 M,Yasuda,J,Morimoto,I,Shibata and A,Baba,Tetrahedron Lett.,
1997,38,3265.
53 L,J,Cheng and D,A,Lightner,Synthesis,1999,46.
54 S,Jolivet-Fouchet,J,Hamelin,F,Texier-Boullet,L,Toupet and
P,Jacquault,Tetrahedron,1998,54,4561.
55 M,Mori,K,Hori,M,Akashi,M,Hori,Y,Sato and M,Nishida,
Angew,Chem.,Int,Ed.,1998,37,636.
56 A,Arcadi,R,Anacardio,G,Danniballe and M,Gentile,Synlett,
1997,1315.
57 D,W,Knight,A,L,Redfern and J,Gilmore,Synlett,1998,731.
58 D,W,Knight,A,L,Redfern and J,Gilmore,Chem,Commun.,1998,
2207.
59 Z,R,Xu and X,Y,Lu,J,Org,Chem.,1998,63,5031.
60 T,Yagi,T,Aoyama and T,Shioiri,Synlett,1997,1063.
61 H,Tsutsui and K,Narasaka,Chem,Lett.,1999,45.
62 N,Terang,B,K,Mehta,H,Ila and H,Junjappa,Tetrahedron,1998,
54,12973.
63 N,De Kimpe,K,A,Tehrani,C,Stevens and P,De Cooman,
Tetrahedron,1997,53,3693.
64 R,D,Chambers,W,K,Gray,S,J,Mullins and S,R,Korn,J,Chem.
Soc.,Perkin Trans,1,1997,1457.
65 A,S,Demir,I,M,Akhmedov,C,Tanyeli,Z,Gercek and R,A.
Gadzhili,Tetrahedron,Asymmetry,1997,8,753.
66 C,W,Ong,C,M,Chen,L,H,Wang,J,J,Jan and P,C,Shieh,J,Org.
Chem.,1998,63,9131.
67 H,Shiraishi,T,Nishitani,S,Sakaguchi and Y,Ishii,J,Org,Chem.,
1998,63,6234.
68 A,R,Katritzky,Z,Q,Wang,J,Q,Li and J,R,Levell,J,Heterocycl.
Chem.,1997,34,1379.
69 A,Fürstner and H,Weintritt,J,Am,Chem,Soc.,1997,119,2944.
70 A,Fürstner and H,Weintritt,J,Am,Chem,Soc.,1998,120,2817.
71 N,A,Nedolya,L,Brandsma,H,D,Verkruijsse and B,A.
Tro?mov,Tetrahedron Lett.,1997,38,7247.
72 N,A,Nedolya,L,Brandsma and B,A,Tro?mov,Russ,J,Org.
Chem,(Engl,Transl.),1998,34,950.
73 N,A,Nedolya,L,Brandsma,O,A,Tarasova,H,D,Verkruijsse
and B,A,Tro?mov,Tetrahedron Lett.,1998,39,2409.
74 W,von der Saal,R,Reinhardt,J,Stawitz and H,Quast,Eur,J,Org.
Chem.,1998,1645.
75 C,D,Gabbutt,J,D,Hepworth,B,M,Heron,M,R,J,Elsegood
and W,Clegg,Chem,Commun.,1999,289.
76 R,Bartnik,A,Bensadat,D,Cal,R,Faure,N,Khatimi,
A,Laurent,E,Laurent and C,Rizzon,Bull,Soc,Chim,Fr.,1997,
134,725.
77 J,T,Gupton,K,E,Krumpe,B,S,Burnham,K,A,Dwornik,
S,A,Petrich,K,X,Du,M,A,Bruce,P,Vu,M,Vargas,K,M.
Keertikar,K,N,Hosein,C,R,Jones and J,A,Sikorski,
Tetrahedron,1998,54,5075.
78 L,Selicˇ and B,Stanovnik,Helv,Chim,Acta,1998,81,1634.
79 A,W,Trautwein and G,Jung,Tetrahedron Lett.,1998,39,8263.
80 A,Fürstner,H,Szillat,B,Gabor and R,Mynott,J,Am,Chem.
Soc.,1998,120,8305.
81 Y,W,Li and T,J,Marks,J,Am,Chem,Soc.,1998,120,1757.
82 J,Bo?lle,R,Schneider,P,Gérardin and B,Loubinoux,Synthesis,
1997,1451.
83 T,D,Lash,C,Wijesinghe,A,T,Osuma and J,R,Patel,
Tetrahedron Lett.,1997,38,2031.
84 T,D,Lash,P,Chandrasekar,A,T,Osuma,S,T,Chaney and
J,D,Spence,J,Org,Chem.,1998,63,8455.
85 B,H,Novak and T,D,Lash,J,Org,Chem.,1998,63,3998.
86 Y,Abel,E,Haake,G,Haake,W,Schmidt,D,Struve,A,Walter
and F.-P,Montforts,Helv,Chim,Acta,1998,81,1978.
87 H,Spreitzer,W,Holzer,C,Puschmann,A,Pichler,A,Kogard,
K,Tschetschkowitsch,T,Heinze,S,Bauer and N,Shabaz,Hetero-
cycles,1997,45,1989.
88 N,P,Pavri and M,L,Trudell,J,Org,Chem.,1997,62,2649.
89 H,P,Dijkstra,R,ten Have and A,M,van Leusen,J,Org,Chem.,
1998,63,5332.
90 H.-W,Chan,P.-C,Chan,J.-H,Liu and H,N,C,Wong,Chem.
Commun.,1997,1515.
91 A,R,Katritzky,J,C,Yao,W,L,Bao,M,Qi and P,J,Steel,J,Org.
Chem.,1999,64,346.
92 B,G,Szczepankiewicz and C,H,Heathcock,Tetrahedron,1997,
53,8853.
93 Y,Murakami,T,Watanabe,H,Takahashi,H,Yokoo,Y.
Nakazawa,M,Koshimizu,N,Adachi,M,Kurita,Y,Yoshino,
T,Inagaki,M,Ohishi,M,Watanabe and M,Tani,Tetrahedron,
1998,54,45.
94 C,J,Moody and E,Swann,Synlett,1998,135.
95 Y,Ozaki,K,Okamura,A,Hosoya and S,W,Kim,Chem,Lett.,
1997,679.
96 E,T,Pelkey and G,W,Gribble,Tetrahedron Lett.,1997,38,5603.
97 S,Cacchi,G,Fabrizi,F,Marinelli,L,Moro and P,Pace,Synlett,
1997,1363.
98 S,Cacchi,G,Fabrizi and P,Pace,J,Org,Chem.,1998,63,1001.
99 M,D,Collini and J,W,Ellingboe,Tetrahedron Lett.,1997,38,
7963.
100 Y,Kondo,S,Kojima and T,Sakamoto,J,Org,Chem.,1997,62,
6507.
101 F,E,McDonald and A,K,Chatterjee,Tetrahedron Lett.,1997,38,
7687.
102 A,Yasuhara,Y,Kanamori,M,Kaneko,A,Numata,Y,Kondo and
T,Sakamoto,J,Chem,Soc.,Perkin Trans,1,1999,529.
103 B,C,S?derberg and J,A,Shriver,J,Org,Chem.,1997,62,5838.
104 P,C,Montevecchi,M,L,Navacchia and P,Spagnolo,Eur,J,Org.
Chem.,1998,1219.
105 T,A,Kshirsagar and L,H,Hurley,J,Org,Chem.,1998,63,5722.
106 Y,Dong and C,A,Busacca,J,Org,Chem.,1997,62,6464.
107 K,Aoki,A,J,Peat and S,L,Buchwald,J,Am,Chem,Soc.,1998,
120,3068.
108 B,A,Frontana-Uribe,C,Moinet and L,Toupet,Eur,J,Org.
Chem.,1999,419.
109 Z,Wróbel and M,Makosza,Tetrahedron,1997,53,5501.
110 A,Chilin,P,Rodighiero and A,Guiotto,Synthesis,1998,309.
111 D,A,Allen,Synth,Commun.,1999,29,447.
112 G,Kim and G,Keum,Heterocycles,1997,45,1979.
113 M,Takahashi and D,Suga,Synthesis,1998,986.
114 C,Y,Chen,D,R,Lieberman,R,D,Larsen,T,R,Verhoeven and
P,J,Reider,J,Org,Chem.,1997,62,2676.
115 E,J,Latham and S,P,Stanforth,J,Chem,Soc.,Perkin Trans,1,
1997,2059.
116 J,A,Murphy,K,A,Scott,R,S,Sinclair and N,Lewis,Tetrahedron
Lett.,1997,38,7295.
J,Chem,Soc.,Perkin Trans,1,1999,2849–2866 2865
117 J,Barluenga,F,J,Fananas,R,Sanz and Y,Fernandez,Tetrahedron
Lett.,1999,40,1049.
118 C,Kuehm-Caubère,I,Rodriguez,B,Pfei?er,P,Renard and
P,Caubère,J,Chem,Soc.,Perkin Trans,1,1997,2857.
119 P,Magnus and I,S,Mitchell,Tetrahedron Lett.,1998,39,4595.
120 C,S,Cho,H,K,Lim,S,C,Shim,T,J,Kim and H.-J,Choi,Chem.
Commun.,1998,995.
121 E,Vedejs and S,D,Monahan,J,Org,Chem.,1997,62,4763.
122 R,ten Have and A,M,van Leusen,Tetrahedron,1998,54,1913.
123 X,C,Zhang and W,Y,Huang,Synthesis,1999,51.
124 T,Peglow,S,Blechert and E,Steckhan,Chem,Eur,J.,1998,4,107.
125 M,Schmittel,J,P,Ste?en,M,A,W,ángel,B,Engels,C,Lennartz
and M,Hanrath,Angew,Chem.,Int,Ed.,1998,37,1562.
126 C,S,Shi and K,K,Wang,J,Org,Chem.,1998,63,3517.
127 A,B,Mandal,F,Delgado and J,Tamariz,Synlett,1998,87.
128 K,H,Dotz and T,Leese,Bull,Soc,Chim,Fr.,1997,134,503.
129 F,Freeman,T,Chen and J,B,van der Linden,Synthesis,1997,861.
130 J,C,Lee and T,Y,Hong,Tetrahedron Lett.,1997,38,8959.
131 R,S,Varma and D,Kumar,J,Heterocycl,Chem.,1998,35,1533.
132 W,W,Pei,S,H,Li,X,P,Nie,Y,W,Li,J,Pei,B,Z,Chen,J,Wu
and X,L,Ye,Synthesis,1998,1298.
133 R,H,Prager,J,A,Smith,B,Weber and C,M,Williams,J,Chem.
Soc.,Perkin Trans,1,1997,2665.
134 J,Khalafy,C,E,Svensson,R,H,Prager and C,M,Williams,
Tetrahedron Lett.,1998,39,5405.
135 R,H,Prager,M,R,Taylor and C,M,Williams,J,Chem,Soc.,
Perkin Trans,1,1997,2673.
136 V,J,Majo and P,T,Perumal,J,Org,Chem.,1998,63,7136.
137 M,C,Bagley,R,T,Buck,S,L,Hind and C,J,Moody,J,Chem.
Soc.,Perkin Trans,1,1998,591.
138 P,M,Pihko and A,M,P,Koskinen,J,Org,Chem.,1998,63,92.
139 P,C,Kearney,M,Fernandez and J,A,Flygare,J,Org,Chem.,
1998,63,196.
140 J,G,Schantl and I,M,Lagoja,Synth,Commun.,1998,28,1451.
141 K,Dridi,M,L,El Efrit,B,Baccar and H,Zantour,Synth.
Commun.,1998,28,167.
142 T,Besson,M.-J,Dozias,J,Guillard and C,W,Rees,J,Chem,Soc.,
Perkin Trans,1,1998,3925.
143 C,Buron,L,El Ka?m and A,Uslu,Tetrahedron Lett.,1997,38,
8027.
144 W,M,Best,E,L,Ghisalberti and M,Powell,J,Chem,Res,(S),
1998,388.
145 J,M,Mellor,S,R,Scho?eld and S,R,Korn,Tetrahedron,1997,53,
17151.
146 W,H,Bunnelle,P,R,Singam,B,A,Narayanan,C,W,Bradshaw
and J,S,Liou,Synthesis,1997,439.
147 Z,Wróbel,Synthesis,1997,753.
148 B,Boduszek,A,Halama and J,Zon,Tetrahedron,1997,53,11399.
149 X.-L,Duan,R,Perrins and C,W,Rees,J,Chem,Soc.,Perkin
Trans,1,1997,1617.
150 C,W,Rees and T,Y,Yue,J,Chem,Soc.,Perkin Trans,1,1997,
2247.
151 T,Nakamura,H,Nagata,M,Muto and I,Saji,Synthesis,1997,
871.
152 M,R,Grimmett,Imidazole and Benzimidazole Synthesis,
Academic Press,London,1997.
153 A,Rolfs and J,Liebscher,J,Org,Chem.,1997,62,3480.
154 S,Jayakumar,M,P,S,Ishar and M,P,Mahajan,Tetrahedron Lett.,
1998,39,6557.
155 R,ten Have,M,Huisman,A,Meetsma and A,M,van Leusen,
Tetrahedron,1997,53,11355.
156 C,F,Claiborne,N,J,Liverton and K,T,Nguyen,Tetrahedron
Lett.,1998,39,8939.
157 N,A,Nedolya,L,Brandsma and B,A,Tro?mov,Tetrahedron
Lett.,1997,38,6279.
158 M,Carvalho,A,M,Lobo,P,S,Branco and S,Prabhakar,
Tetrahedron Lett.,1997,38,3115.
159 J,J,Perkins,A,E,Zartman and R,S,Meissner,Tetrahedron Lett.,
1999,40,1103.
160 H,Y,Wang,R,E,Partch and Y,Z,Li,J,Org,Chem.,1997,62,
5222.
161 S,Cacchi,G,Fabrizi and A,Carangio,Synlett,1997,959.
162 N,Almirante,A,Cerri,G,Fedrizzi,G,Marazzi and M.
Santagostino,Tetrahedron Lett.,1998,39,3287.
163 M,Yoshimatsu,M,Kawahigashi,E,Honda and T,Kataoka,
J,Chem,Soc.,Perkin Trans,1,1997,695.
164 H.-B,Yu and W.-Y,Huang,Synlett,1997,679.
165 H.-B,Yu and W.-Y,Huang,J,Fluorine Chem.,1997,84,65.
166 J,M,Mellor,S,R,Scho?eld and S,R,Korn,Tetrahedron,1997,53,
17163.
167 C,Chen,K,Wilcoxen and J,R,McCarthy,Tetrahedron Lett.,1998,
39,8229.
168 R,D,Wilson,S,P,Watson and S,A,Richards,Tetrahedron Lett.,
1998,39,2827.
169 C,Reidlinger,R,Dworczak and H,Junek,Monatsh,Chem.,1998,
129,1207.
170 C,Reidlinger,R,Dworczak,H,Junek and H,Graubaum,
Monatsh,Chem.,1998,129,1313.
171 F,Halley and X,Sava,Synth,Commun.,1997,27,1199.
172 V,M,Lyubchanskaya,L,M,Alekseeva and V,G,Granik,
Tetrahedron,1997,53,15005.
173 P,G,Baraldi,B,Cacciari,G,Spalluto,R,Romagnoli,G,Braccioli,
A,N,Zaid and M,J,P,de las Infantas,Synthesis,1997,1140.
174 J,Ler and R,Schobert,Synlett,1997,283.
175 L,El Ka?m,I,Le Menestrel and R,Morgentin,Tetrahedron Lett.,
1998,39,6885.
176 S,Lutun,B,Hasiak and D,Couturier,Synth,Commun.,1999,29,
111.
177 A,Kraft,Liebigs Ann./Recl.,1997,1463.
178 J,R,Young and R,J,DeVita,Tetrahedron Lett.,1998,39,3931.
179 X.-G,Duan,X.-L,Duan,C,W,Rees and T.-Y,Yue,J,Chem,Soc.,
Perkin Trans,1,1997,2597.
180 X.-G,Duan,X.-L,Duan and C,W,Rees,J,Chem,Soc.,Perkin
Trans,1,1997,2831.
181 X.-G,Duan and C,W,Rees,Chem,Commun.,1997,1493.
182 S,C,Yoon,J,Cho and K,Kim,J,Chem,Soc.,Perkin Trans,1,
1998,109.
183 K.-J,Kim and K,Kim,Heterocycles,1999,50,147.
184 K.-J,Kim and K,T,Kim,J,Chem,Soc.,Perkin Trans,1,1998,
2175.
185 G,Mloston,T,Gendek,A,Linden and H,Heimgartner,Helv.
Chim,Acta,1998,81,66.
186 K,Harada,M,Oda,A,Matsushita and M,Shirai,Heterocycles,
1998,48,695.
187 K,Harada,M,Oda,A,Matsushita and M,Shirai,Synlett,1998,
431.
188 P,Uhlmann,J,Felding,P,Veds? and M,Begtrup,J,Org,Chem.,
1997,62,9177.
189 G,A,Romeiro,L,O,R,Pereira,M,C,B,V,de Souza,V,F.
Ferreira and A,C,Cunha,Tetrahedron Lett.,1997,38,5103.
190 L,Jiang,A,Davison,G,Tennant and R,Ramage,Tetrahedron,
1998,54,14233.
191 J,H,Teles,K,Breuer,D,Enders and H,Gielen,Synth,Commun.,
1999,29,1.
192 B,H,Kim,S,K,Kim,Y,S,Lee,Y,M,Jun,W,Baik and B,M,Lee,
Tetrahedron Lett.,1997,38,8303.
193 K,Koguro,T,Oga,S,Mitsui and R,Orita,Synthesis,1998,910.
194 B,S,Jursic and B,W,LeBlanc,J,Heterocycl,Chem.,1998,35,
405.
195 R,C,Larock,X,J,Han and M,J,Doty,Tetrahedron Lett.,1998,
39,5713.
196 T,Dubu?et,B,Cimetiere and G,Lavielle,Synth,Commun.,1997,
27,1123.
197 E,A,Cio? and W,F,Bailey,Tetrahedron Lett.,1998,39,2679.
198 Josemin,K,N,Nirmala and C,V,Asokan,Tetrahedron Lett.,1997,
38,8391.
199 V,I,Tyvorskii,D,N,Bobrov,O,G,Kulinkovich,N,De Kimpe and
K,A,Tehrani,Tetrahedron,1998,54,2819.
200 G,A,Cartwright and H,McNab,J,Chem,Res,(S),1997,296.
201 I,Yavari,R,Hekmat-Shoar and A,Zonouzi,Tetrahedron Lett.,
1998,39,2391.
202 S,Cacchi,G,Fabrizi,L,Moro and P,Pace,Synlett,1997,1367.
203 L,Wang and W,Shen,Tetrahedron Lett.,1998,39,7625.
204 A,M,S,Silva,J,A,S,Cavaleiro and J,Elguero,Liebigs Ann./Recl.,
1997,2065.
205 J,Sauer and D,K,Heldmann,Tetrahedron Lett.,1998,39,2549.
206 J,Sauer,D,K,Heldmann and G,R,Pabst,Eur,J,Org,Chem.,
1999,313.
207 G,R,Pabst,K,Schmid and J,Sauer,Tetrahedron Lett.,1998,39,
6691.
208 G,R,Pabst and J,Sauer,Tetrahedron Lett.,1998,39,8817.
209 O,C,Pfüller and J,Sauer,Tetrahedron Lett.,1998,39,8821.
210 G,R,Pabst,O,C,Pfüller and J,Sauer,Tetrahedron Lett.,1998,39,
8825.
211 G,R,Pabst and J,Sauer,Tetrahedron Lett.,1998,39,6687.
212 J,A,Varela,L,Castedo and C,Saá,J,Org,Chem.,1997,62,4189.
213 J,A,Varela,L,Castedo and C,Saá,J,Am,Chem,Soc.,1998,120,
12147.
214 K,Iwamoto,E,Oishi,T,Sano,A,Tsuchiya,Y,Suzuki,T.
Higashino and A,Miyashita,Heterocycles,1997,45,1551.
215 W.-T,Li,F.-C,Lai,G.-H,Lee,S.-M,Peng and R.-S,Liu,J,Am.
Chem,Soc.,1998,120,4520.
216 J,Barluenga,M,Ferrero and F,Palacios,Tetrahedron,1997,53,
4521.
2866 J,Chem,Soc.,Perkin Trans,1,1999,2849–2866
217 I,Katsuyama,S,Ogawa,Y,Yamaguchi,K,Funabiki,M,Matsui,
H,Muramatsu and K,Shibata,Synthesis,1997,1321.
218 J,W,B,Cooke,M,J,Coleman,D,M,Caine and K,P,Jenkins,
Tetrahedron Lett.,1998,39,7965.
219 I,Katsuyama,S,Ogawa,H,Nakamura,Y,Yamaguchi,K.
Funabiki,M,Matsui,H,Muramatsu and K,Shibata,Hetero-
cycles,1998,48,779.
220 E,Okada,T,Kinomura,Y,Higashiyama,H,Takeuchi and
M,Hojo,Heterocycles,1997,46,129.
221 N,Nishiwaki,Y,Tohda and M,Ariga,Synthesis,1997,1277.
222 S,Mathé and A,Rassat,Tetrahedron Lett.,1998,39,383.
223 A,R,Katritzky,S,A,Belyakov,A,E,Sorochinsky,S,A.
Henderson and J,Chen,J,Org,Chem.,1997,62,6210.
224 I,Furukawa,H,Fujisawa,M,Kawazome,Y,Nakai and T,Ohta,
Synthesis,1998,1715.
225 J,F,Stambach,L,Jung and R,Hug,Synthesis,1998,265.
226 T,Koike,N,Takeuchi and S,Tobinaga,Chem,Pharm,Bull.,1999,
47,128.
227 N,A,Nedolya,L,Brandsma,A,van der Kerk,V,Yu,Vvedensky
and B,A,Tro?mov,Tetrahedron Lett.,1998,39,1995.
228 A,Czarny,H,Lee,M,Say and L,Strekowski,Heterocycles,1997,
45,2089.
229 L,Strekowski,S.-Y,Lin,H,Lee,Z.-Q,Zhang and J,C,Mason,
Tetrahedron,1998,54,7947.
230 J,I,úbeda,M,Villacampa and C,Avenda?o,Synthesis,1998,
1176.
231 R,S,Compagnone,A,I,Suárez,J,L,Zambrano,I,C,Pi?a and
J,N,Domínguez,Synth,Commun.,1997,27,1631.
232 L,H,Zhou and Y,M,Zhang,J,Chem,Soc.,Perkin Trans,1,1998,
2899.
233 W,Baik,D,I,Kim,H,J,Lee,W.-J,Chung,B,H,Kim and
S,W,Lee,Tetrahedron Lett.,1997,38,4579.
234 C,S,Shi,Q,Zhang and K,K,Wang,J,Org,Chem.,1999,64,925.
235 F,Palacios,D,Aparicio and J,Garciá,Tetrahedron,1997,53,
2931.
236 F,Palacios,D,Aparicio and J,Garciá,Tetrahedron,1998,54,
1647.
237 C,S,Cho,B,H,Oh and S,C,Shim,Tetrahedron Lett.,1999,40,
1499.
238 P,Charpentier,V,Lobrégat,V,Levacher,G,Dupas,G,Quéguiner
and J,Bourguignon,Tetrahedron Lett.,1998,39,4013.
239 M,Schlosser,H,Keller,S,Sumida and J,Yang,Tetrahedron Lett.,
1997,38,8523.
240 L,Brandsma,N,A,Nedolya,H,D,Verkruijsse,N,L,Owen,D,Li
and B,A,Tro?mov,Tetrahedron Lett.,1997,38,6905.
241 H.-J,Ha,Y.-S,Lee and Y.-G,Ahn,Heterocycles,1997,45,2357.
242 A,R,Katritzky,D,Semenzin,B,Z,Yang and D,P,M,Pleynet,
J,Heterocycl,Chem.,1998,35,467.
243 J,Koyama,I,Toyokuni and K,Tagahara,Chem,Pharm,Bull.,
1998,46,332.
244 K,Uchiyama,Y,Hayashi and K,Narasaka,Synlett,1997,445.
245 H,Kusama,Y,Yamashita,K,Uchiyama and K,Narasaka,Bull.
Chem,Soc,Jpn.,1997,70,965.
246 O,B,Familoni,P,T,Kaye and P,J,Klaas,Chem,Commun.,1998,
2563.
247 C,W,Holzapfel and C,Dwyer,Heterocycles,1998,48,215.
248 A,Arcadi,S,Cacchi,G,Fabrizi,F,Manna and P,Pace,Synlett,
1998,446.
249 E,L,Larghi and T,S,Kaufman,Tetrahedron Lett.,1997,38,3159.
250 K,R,Roesch and R,C,Larock,J,Org,Chem.,1998,63,5306.
251 R,M,Adlington,J,E,Baldwin,D,Catterick and G,J,Pritchard,
Chem,Commun.,1997,1757.
252 T,S,Wang and I,S,Cloudsdale,Synth,Commun.,1997,27,2521.
253 J,Barluenga,L,A,López,S,Martínez and M,Tomás,Synlett,
1999,219.
254 P,Dalla Croce,R,Ferraccioli and C,La Rosa,Heterocycles,1997,
45,1309.
255 W,Szczepankiewicz and J,Suwinski,Tetrahedron Lett.,1998,39,
1785
256 E,Erba and D,Sporchia,J,Chem,Soc.,Perkin Trans,1,1997,
3021.
257 E,Erba,D,Pocar and M,Valle,J,Chem,Soc.,Perkin Trans,1,
1999,421.
258 W,K,Zielinski,A,Kudelko and E,M,Holt,Heterocycles,1998,
48,319.
259 J,Sauer,D,K,Heldmann,J,Hetzenegger,J,Krauthan,H,Sichert
and J,Schuster,Eur,J,Org,Chem.,1998,2885.
260 J,Sauer and D,K,Heldmann,Tetrahedron,1998,54,4297.
261 T,J,Sparey and T,Harrison,Tetrahedron Lett.,1998,39,5873.
262 Y,Kamitori,M,Hojo and T,Yoshioka,Heterocycles,1998,48,
2221.
263 M,S,F,Lie Ken Jie and P,Kalluri,J,Chem,Soc.,Perkin Trans,1,
1997,3485.
264 T,Masquelin,Y,Delgado and V,Baumlé,Tetrahedron Lett.,1998,
39,5725.
265 I,Shibuya,A,Oishi and M,Yasumoto,Heterocycles,1998,48,
1659.
266 Y,Matsubara,A,Horikawa and Z,Yoshida,Tetrahedron Lett.,
1997,38,8199.
267 A,J,Maroulis,K,C,Domzaridou and C,P,Hadjiantoniou-
Maroulis,Synthesis,1998,1769.
268 H,Suzuki and T,Kawakami,Synthesis,1997,855.
269 A,M,Bernard,M,T,Cocco,C,Congiu,V,Onnis and P,P,Piras,
Synthesis,1998,317.
270 R,A,Aitken,I,M,Fairhurst,A,Ford,P,E,Y,Milne,D,W.
Russell and M,Whittaker,J,Chem,Soc.,Perkin Trans,1,1997,
3107.
271 A,R,Katritzky,J,Wang,N,Karodia and J,Q,Li,Synth.
Commun.,1997,27,3963.
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