http://www.courses.fas.harvard.edu/~chem206/
Me Me
HOOC
Me
I2, NaHCO3
NMe
O OH
NMe HM–H
LiAlH4
R2AlH
O
O
Me
Me
Me I
NMe
H
OH
Chem 206D. A. Evans
Matthew D. Shair
Monday,October 7, 2002
a73 Reading Assignment for week
A. Carey & Sundberg: Part B; Chapter 4"Electrophilic Additions to C–C Multilple Bonds"
Olefin Addition Reactions: Part–2
Chemistry 206
Advanced Organic Chemistry
Lecture Number 9
Olefin Addition Reactions–2
K. Houk, Science. 1986, 231, 1108-1117Theory & Modeling of Stereoselective Organic Reactions (Handout)
a73 Epoxidation & Directed Epoxidation
a73 Hydrogenation
a73 Hydride Reduction
K. Houk, Tetrahedron. 1984, 40, 2257-2274Theoretical Studies of Stereoselective Hydroboration Reactions
(Handout)
Hoveyda, Evans, & Fu (1993). Substrate-directable chemical reactions. Chem. Rev. 93: 1307-70 (Handout)
a73 Problems of the Day: (To be discussed)
a73 Other Reading Material
Takaya, H., T. Ohta, et al. (1993). Asymmetric Hydrogenation. Catalytic Asymmetric Synthesis. I. Ojima. New York, VCH: 1-39.
Bolm, C. (1993). “Enantioselective transition metal-catalyzed hydrogenation for the asymmetric synthesis of amines.” Angew.
Chem., Int. Ed. Engl. 32: 232.
diastereoselection: 20:1
Predict the stereochemical outcome of the indicated reaction.
Bartlett, P. A.; Richardson, D.; Myerson, J. Tetrahedron 1984, 12, 2317
Kinetic Control: 3 eq. I2, MeCN, NaHCO3, 0°C
R. NoyoriBull. Chem. Soc. Japan 47, 2617, (1974) 28 : 7297 : 3
Rationalize the stereochemical outcome of the indicated reaction.
For a recent general review of the Simmons-Smith reaction see:Charette & Beauchemin, Organic Reactions, 58, 1-415 (2001)
X
R
A B
A B
X A B
R
B
A
X
B
A
A B
C C
H HH
C C
H HH
A B
A B
A B
OH
OH
R
R
OH
MCPBA
Et2Zn
Cl CO3H
t-BuOOH
Et2Zn
CH2I2
OH
Me
CH2I2
R
O CH2
R
O Zn CH2I
R
H
OH
O
Me
OH
CH2
OH
R
R
O
CH2
OH
R
(Ir+) Stork
JACS 105, 1072 (1983)
(Rh+) Evans
JACS 106, 3866 (1984)
M(I) + H2
Mechanism-based: (HO & C=C must be allylic)
Simmons-Smith Reaction
Claisen Rearrangement
[3,3]
via Reagent Ligation
Heteroatom-directed Reactions
ratio 90 : 10
Winstein JACS 91, 6892, (1969)
Henbest J. Chem. Soc. 1958, (1957)
SharplessJACS 95, 6136, (1973)
VO(acac)2 ratio 98 : 2
ratio 92 : 8
Hydroxyl-directed Reactions
Directed C–C Bond Constructions
Directed Reductions
HydrogenationHydride reduction
EpoxidationHydroboration
Directed Oxidations
Agenda
Directed Reactions
favored
disfavoredfavored product
a73 Associative Substrate-Reagent Interactions
Noncovalent Interaction favors the syn diastereoface
Review: Hoveyda, Evans, Fu Chem. Reviews 1993, 93, 1307
a73 Steric control:
Stereochemical Control Elements for all reactions
a73 Steric & Electronic Factors
a73 Stereoelectronic Considerations
a73 Associative Substrate-Reagent Interactions
favored product favored
disfavored
Nonbonding Interactions disfavor the syn diastereoface
Chem 206D. A. Evans Directed Reactions: An Introduction
OHR O
O
O
R
R
R
R
a71
a71
O
O
H
O
R
O
O
H
O
R
????
??
a71
a71 a71
??
a71
Me
Me OH
H
H
C
OH
H Me
HC
Me
H
RCO3H
Me
Me OH
X
CH
Me
C
OH
HMe
H
C H
C H
R
R
R
R
R
R
Me
Me
Me
O
R
OO
H
C
CR
R
H
H
OH
Me
Me
O
R
OO
H
C
CR
H
H
OAc
OH
H
MeMe
Me
Me
C
CR
H
H
O
OHR
Chem 206D. A. Evans Directed Reactions: An Introduction
Orientation of the Directing Group
?
~ 120 °
~ 50 °
> 99 : 1
95 : 5
71 : 29
CH2I2, Zn–Cu
Φ EstimateSelectivityReagent
reagent
t-BuO2H, V +5
X = O, CH2
Reag Reag
?maj
?min
? ?
TSmajor TSminor
The transition state bite angles for the above reactions are either not known or have been only crudely estimated.
The "best guesses" are provided.
Orientation of directing group is not the same for all reactons
Peracid Epoxidation
note labeled oxygen is transferfedLUMO
σ*O–O
a73 General Reaction:
+ +
HOMO
piC–C
a73 Reaction rates are governed by olefin nucleophilicity. The rates of epoxidation of the indicated olefin relative to cyclohexene are provided
below:
a73 The indicated olefin in each of the diolefinic substrates may be oxidized selectively.
1.0 0.6 0.05 0.4
a73 Transition state: What about lone pairs. [Consider a71 to be Sp2 hybridized].
O-O bond energy: ~35 kcal/mol
A. Rao in Comprehensive Organic Synthesis, Trost, Ed., 1992, Vol 7, Chapter 3.1
HOMO piC–C
LUMO: σ?O–O
HOMO: O lone pair
LUMO:pi? C–C
O
R
OO
H O
C H
CH
2
O
C
HR
R
O
H
O
R
O
C
CC
H2
H R
H
OR
CF3
OO
H
O
CH
CH
2
OR
C H
R
O
O
H
O
CF3
CH
2
OR
C H
C RH
????
R
OO
HO
O
O
H O HCR
CR
H
CH
2
O
C
CR
R H
CH
2
O
H
O
H
O
CF3
OH OTBS
OH
Me3C Me3C
OTBS
O
H
OO
Me3C
OH OTBS
Me3C
a71
a71
1 : 7 5 : 1
12 : 11 : 8
1 : 4 1 : 6100 : 1
24 : 1 100 : 1
5 : 1
50 : 124 : 1
Syn : Anti
(CF3CO3H)Syn : Anti(m-CPBA) Syn : Anti(m-CPBA)
Syn : Anti
(CF3CO3H)
Ganem Tet. Let. 1985, 26, 4895
require more acidic peracid both allylic alcohols and ethers OK
require allylic or homoallylic alcohol
a73 Transition State Hydrogen Bonding: Peracid as H-bond donor (Ganem)
?
?
a73 Transition State Hydrogen Bonding: Substrate as H-bond donor (Henbest)
The Directed Peracid Epoxidation
Chem 206D. A. Evans Diastereoselective Peracid Epoxidation
a73 Per-arachidonic acid Epoxidation: Corey, JACS 101, 1586 (1979)
Stereoelectronic Implications of intramolecular Peracid Epoxidation
a71 a71
a71 a71
Conditions: Perbenzoic acid, or meta-chloroperbenzoic acidin benzene or cyclopentane.
O
PhHN
O
HN Ph
O
HO
HO
HN Me
O
O
HN
HO
HO
Me
O
O R
O O
RO
O
Me
R R
Me
O
AcO
RO
AcO O
RO
OH OHO
Me
Et Me
HO
OH OH
HO O
Et
Me
Me
HO
Me
OHO
Me
O
Me
HO
O
Me
HO
Me
HO
Me
HO
AcO
HOH2C
OAcO
HOH2C
(Table 14, p1318, from the Evans, Hoveyda, Fu review article)
SelectivityMajor ProductSubstrate
9 : 1
"highlyselective"
16 : 1
1 : 1
5 : 1
21 : 1
Epoxidation of Cyclic Homoallylic Alcohols
(Table 11, p1316, from the Evans, Hoveyda, Fu review article)
Conditions: Perbenzoic acid, or meta-chlorobenzoic acid in benzene.
"highlyselective"
"highlyselective"
Substrate Major Product Selectivity
10 : 1
3 : 1
5 : 1
a. R = NH2
b. R = NHBn
c. R = NMe2
>20 : 1
>20 : 1
a. R = OCONHBn
b. R = OCONMe2
6 : 1a. R = CONH2
b. R = CONHBn
c. R = CONMe2
>10 : 1
2 : 1
Epoxidation of Cyclic Olefins with Amide &Urethane Directing Groups
Diastereoselective Peracid EpoxidationD. A. Evans Chem 206
43
2
1
Relative Rates (Diastereoselectivities) for the Epoxidation of Cyclohexene Derivatives
JACS 1973, 95, 6136
OH O
O
MeOH
Me
Me
OHO
Mo(CO)6
TBHP
OH
ROOH
O
V
OR
O
O
RO
O
O V
OR
O-OtBu
OHO
V
O
O
OORO
tBu
OHO
OHMe
Me
Me
OH
OAc
OH
OH OH
O
Mo(CO)6
Mo(CO)6
t-BuOH
RDS
HO
O
tBu
V
RO
O OO
O
OR
V
RO
O
OR
O
O
V
RO
O
HO
R
–ROH
HO
O
OVORO
OR
a,b The relative rate data apply only to a given column.
Values in parenthesis refer to the ratio of syn:anti epoxide.
krela,b (diastereoselectivityc )
10.0 (98 : 2)11.0 (98 : 2)
--0.07 (40 : 60)
>200 (98 : 2)4.5 (98 : 2)
1.001.00
0.42 (60 : 40)
0.046 (37 : 63)
0.55 (92 : 8)
1.00
Substrate VO(acac)
2peracid
80 °C
Stereoselection 98:2 (90 % yield)TBHP
a73 Next step: Sharpless, Michaelson JACS 1973, 95, 6136
Regioselection 20:1
80 °C
TBHP
VO(acac)2
a73 The literature precedent: Sheng, Zajecek, J. Org. Chem. 1970, 35, 1839
4 : 1VO(acac)2
80 oC
1 : 1Catalyst
t-BuOOH
slowChem 3D Transition State
Aldrichimica Acta, 12, 63 (1979)
O–C2–C3–C4 = 41°The Sharpless estimate: ~50°
The Sharpless Epoxidation
+
Sharpless Epoxidation (V+5)D. A. Evans Chem 206
a71
a71
a71
a71a71 a71
a71
a71 a71
OHMe
MeMe
Me
Me OH
C
Me
H
CH
Me C
Me
H
OH
C
HO
H
MeH
H
O Me
Me OH
Me
OHMe
MeO
CH
Me
C
Me
H C
Me
H
OH
C
HO
H
Me
OHMe
MeOMe
O Me
Me OH
H
H
Me Me
OH
R1 R2
SiMe3
OH
OEt
OH
O
O
EtO Me Me
Me
Me
O
EtO O
OH
OEt
OH
Me
HO
t-BuOOH
t-BuOOH
t-BuOOH
H
OH
MeMe O
C5H11
OH
SiMe3
R2R1 O
O
NHCONHPh
Ph
MeMe
Ph
NHCONHPh
O
OEt
OH
O
O
EtO Me Me
Me
Me
O
EtO O
OH
OEt
O
Bu
Me
HO
Me
OH
O
OMe Me
OH
OR1 R2SiMe
3
OH
Ph
NHCONHPh
O
Me
Reagent
+
64 : 36t-BuOOH / (t-BuO)3Al
29 : 71
64 : 36
t-BuOOH / VO(acac)2
m-CPBA
RatioReagent
t-BuOOH / Mo(CO)6 62 : 38
a73 Allylic Alcohols:
Epoxidation of Acyclic AlcoholsD. A. Evans Chem 206
~ 120 °
40-50 °
Φ Estimate
71 : 29
95 : 5
t-BuOOH / VO(acac)2
m-CPBA
RatioReagent
t-BuOOH / Mo(CO)6 84 : 16
erythrothreo
Reagent +
a73 RCO3H Transition States: Φ ~ 120 °
TSminorTSmajor
a73 V(+) Transition States: Φ ~ 45 °
TSminorTSmajor
K. B. Sharpless & CoworkersTetrahedron Lett. 1979, 20, 4733.
K. Oshima & CoworkersTetrahedron Lett. 1980, 21, 1657, 4843.
100 : 0t-BuOOH / (t-BuO)3Al
86 : 14
95 : 5
t-BuOOH / VO(acac)2
m-CPBA
RatioReagent
t-BuOOH / Mo(CO)6 95 : 5
+Reagent
threo erythro
70 %
84 %
YieldR1
99 : 1
99 : 1
RatioR2
+VO(acac)
2
Oshima, Tetrahedron Lett. 1982, 23, 3387.
Depezay, Tetrahedron Lett. 1978, 19, 2869.
only isomerVO(acac)260 %
60 %
t BuOOH
VO(acac)2 only isomer
Boeckman, JACS 1977, 99, 2805. Diastereoselection = 7 : 1
60 %
VO(acac)2
Roush, J. Org. Chem. 1987, 52, 5127.
m-CPBA
CH2Cl2, 0 °C
75 %
+
Diastereoselection = 95 : 5
a71 a71
a71 a71
a71 a71
a71 a71
a71
a71
a71
a71 a71
H ROMe
H
H
VO
Me
O
L
H
H
H
VO
L
O
O
Et
H
H
RMe
V OR
2
R
H
O
Me
O
L
H
HR1
H R1
H H
VO
L
O
O
Me
H
H
RR
2
L'
L'
L' L'
OH
Me Me
t-BuOOH
MeMe
OH
O
O
HO
MeMe
O
OH
Me Me
Me
R2
R1
OH
OH
R1
R2
Me
t-BuOOH
t-BuOOH
OH
Me
Me
Hex R
OH
OH
Me
Me
C5H11
OH
Et
Me
O
OH
Et
Me
OO
Me
Et
OHOH
Et
Me
Me
OH
t-BuOOH
t-BuOOH
R1
Me
Me
R1
Me
C6H13
C6H13
Me
OH
R1
R2
O
O
R2
R1
OH
Me
O
Me
Me
OH
C5H11
Me
Me
OH O
OH
Me
O
OH
RHex O
Me
Me
i-Pr
Me
C5H11
Me
O
R2
R1
OH
OH
R1
R2
O
Me
OH
Me
Me
O
C5H11
Epoxidation of Homoallylic Alcohols with TBHP, VO(acac)2
1.4 : 1
R = (CH2)7CO2Me
4.6 : 1
Substrate Product Selectivity
2 : 1
Syn diastereomer
Anti diastereomer
Syn diastereomerAnti diastereomer
Anti should be more diastereoselective
than syn
Homoallylic Alcohols (Mihelich, JACS 1981, 103, 7690)
Prediction
Control Elements
Directed Rxn
Diastereoselection 12 : 1
VO(acac)2 +
Directed Rxn
A(1,3) Strain
Control Elements
+VO(acac)
290 %
Diastereoselection > 400 : 1 R2 Ratio
104 : 1
> 400 : 1
Yield
92 %
97 %
VO(acac)2 +
+VO(acac)
2
70 %
73 %
Yield
85 : 1
70 : 1
RatioR2
81 % 16 :1
VO(acac)2 +
Diastereoselection = 211 : 1E. D. Mihelich & CoworkersJ. Am. Chem. Soc. 1981, 103, 7690.
Epoxidation of Acyclic Homoallylic AlcoholsD. A. Evans Chem 206
a71
a71 a71
a71
a71
a71 a71
a71
a71
a71 a71
a71 a71
a71 a71
a71
a71
a71
a71
HO O
CO2H
Me
Me Me
OH O
Et O
Me
Et
Me Et
H
H OH
A
Epoxidation & Cyclization of Bishomoallylic Alcohols
A
H
Et
Me
Et
Me
OH
OAr
B
Me CHMe2
Et
OH
OH
Et
CHMe2Me
Me
Me
Me CHMe2
Et
OH
Me
MeH
O V
H R
Et
O
O R
H
MeH
O V
H R
Et
O
O R
O R
V O
Et
O
RMe H Me
H
OH
Et
CHMe2Me
O
O
MeR
Et
OH
Me
O
Me CHMe2
Et
OH
Me
Me
OH
Et
CHMe2Me
O
Me
OH
Et
R Me
O
OH
Et
R Me
O
iPr
R Et
MeOH
A
EtAr
Me
OH
Et
Me
N Et
O
OBn
OH
MeO
Me
Ph
O
B
TBHP
AcOH
O O O O
OHMe
Me
Me
OH
Me Me
O
Me
OH
OHOH O O
Et OH
Me
H
MeOH
Me
MeH
O
OH Me
EtR
iPr
C
TBHP
D
AcOH
HOAc
OXN Et
O
OBn OHMe
Me
OH
OBn
O
EtXN
O
D
F
Et OH
MeOiPr
R
Bishomoallylic Alcohols (Kishi, Tet. Lett. 1978, 19, 2741)
Epoxidation of Acyclic Homoallylic AlcoholsD. A. Evans Chem 206
C6H6, RT
t-BuOOH, VO(acac)2
diastereoselection ~ 9 : 1
C6H6, RT
t-BuOOH, VO(acac)2
diastereoselection ~ 20 : 1
C6H6, RT
t-BuOOH, VO(acac)2
diastereoselection ~ 6 : 1
2nd stereocenter is reinforcing
Diastereoselection 8:1
VO(acac)2
Ar = p-MeOPh
VO(acac)2
The Kishi Lasalocid Synthesis (JACS 1978, 100, 2933)
E
Evans X-206 Synthesis JACS 1988, 110, 2506.
C6H6, RT
diastereoselection 20 : 1(89 %)
VO(acac)2
a71
a71 a71
a71
a71 a71
a71
a71 a71
a71
a71
a71
a71
a71
OMe
O
O
CO2Et
CH2OH
O
O
OMe
LiAlH4
C CHR HR
C C
H
R
H
R
H H
EtOH
H2 Pd-C
EtOH
H2 Pd-C
C C
H
R
H
R
M
C C
H
R
H
R
M HH
CO2Et
O
O
OMe
H
H
OMe
O
O
CH2OH
C CHR HR
C CHR HR
M
M
H
H
H H
N
O
HO
H
H
H
OH
CH3
CHMe2
CHMe2
O
CH3
H2
H2
H
H N
OH
HO
H
H
H
H
HO
N
OH
H
H
CHMe2
H
OH
CH3
O
CH3
CHMe2
Historically, primary stereochemical control designed around analysis ofsteric environment in vicinity of C=C.
However, the influence of polar effects was documented
only isomerH2, Pd-C
however
trans:cis = 55:45H2, Pd-C
J. E. McMurry & Co-workers, Tetrahedron Lett.. 3731 (1970)
Chem 206D. A. Evans Diastereoselective Hydrogenation: Introduction
The Hydrogenation Reaction
Relevant Review articles: J. M. Brown, Angew. Chem. Int. Edit. 26, 190-203 (1987).
trans : cis5 : 95Thompson, J.Org. Chem. 36, 2577 (1971)
trans : cis85 : 15
Y. Kishi & Co-workers, J. Am. Chem. Soc. 102, 7156 (1980)
10% Pd-C
5% Pd-Al2O3
sole product
12 : 1
Steric Control
Directed ?
Polar functional groups may play a role in controlling the diastereoselectivityof the hydrogenation process;
however, the control elements were not well-defined.
+
a73 General Mechanism
M(0)
+M(0)
Pd(0) Pd(II)
Rh
S S
Ph2P
PPh2RhS
S
Ph2P
PPh2
RhH S
Ph2P
PPh2
H
RhH S
Ph2P
PPh2H
2C
H
CH2OK
MeO
O
O
RCH3O
(Ph3P)3RhCl
R
CH2OH
CHO
CNCOONa
COOH
COOMe
COMeCONH
2
MeO
CH2O–Rh(PPh3)3
MeO
CH2OH
H
CH3O R
O
O
H
H2
RhPh
2P PPh2
Rh PPh
2Ph2P
SS
(+S)
CH3–CH3
CH2=CH2
H2
H2
(–S)
Ir
Py PCy3
RhH
H
SS
Ph2P
PPh2
Oxidative Addition
Mechanism of Hydrogenation Cationic Rhodium-(I) Catalysts.
18-e-16-e–(CH2)n
– BF4
Schrock & Osborne,
J. Am. Chem. Soc. 91, 2816 (1969)
(CH2)n
R. Crabtree J. Organomet. Chem. 168, 183 (1979)
– PF6
– BF4
Cationic Hydrogenation CatalystsThe first rational attempt to identify those FGs which will direct the reaction
H. Thompson & Co-workers, J. Am. Chem. Soc. 95, 838 (1973)
10
H2, 5% Pd-C
cis : trans
95 : 593 : 7
75 : 2555 : 45
18 : 8215 : 85
14 : 8610 : 90
The first rational attempt to associate catalyst with substrate:
cis : trans>98 : 2
Thompson & Coworkers, J. Am. Chem. Soc. 97, 6232 (1974)
H2 100 psi
Rxn Catalytic in Rh (4 mol%)
50 °C, C6H6
Diastereoselective Hydrogenation: Introduction-2D. A. Evans Chem 206
S = solvent
S = solvent
Reductive Elimination
Rh(+I): d8
Rh
PPh2Ph2P
SS
+
– BF4
CH2OH
CH3 H2
CH3
OH
CH3
CH2OH
H2
CH2Cl2
CH3
OH
OH
CH3
H2
OH
CH3
RhH
H
SS
Ph2P
PPh2
R2
H
H2
C
H
RhP
P
OH
H
C
OH
H H
Rh
P P
HBHA
CH3
CHH
RhP
P
H2
2H2
RhHA
HB
PP
OH
C
HH
R2
R2
O
Rh
P P
HB
R2HA
H
H
H
MeMe
Me
H
MeH
CO2H
H
Me
H
Me
OH
Me Me MeMe
OH
Me
Me
OH
Me Me MeMe
OH
Me
H
HA
H2
CHH
OH
CH2
R2
R2
CH3
OH
Rh
Ph2P PPh2
THF is important to success of rxn to buffer the Lewis acidity of the catalyst which causes elimination of ROH under normal conditions
Chem 206D. A. Evans Diastereoaselective Hydrogenation: Cationic Catalysts
– BF4
16-e- 18-e-
Mechanism of Hydrogenation Cationic Rhodium-(I) Catalysts.
+
+
+
Which hydrogen migrates ??
A potential stereoelectronic effect
+
That H atom lying parallel to the pi-system (HA) should migrate preferentially
if the dihydride is an intermediate.
Rh(DIPHOS-4)+ 200 : 1 (89%) 300 : 1 (95%)
50 : 1 (82%)
150 : 1 (85%)
Catalyst H2 Pressure trans:cis (Yield)
15 psi H2
375 psi H2
15 psi H2
15 psi H2
Mol% Catalyst
17.5
3.5
20.0
2.5
Ir(pyr)PCy3
19 : 1
Rh +
65 : 1
}
Rh(DIPHOS-4)+ H2 1000 psi CH2Cl2
D. A. Evans & M. M. Morrissey JACS 106, 3866 (1984)
Retigeranic Acid
Excessive Steric Hindrance
Rh +
75 : 1 (95%)
Rh(DIPHOS-4)+ H2 800 psi THF
Rh +
+2 S
O N
Me
CO2Me
CH3
CO2Me
H2C
CO2Me
CH3
CO2Me
CH3
Me
NO
H
CH3
O
XCH
3
Me
O
X
OCH3
CH3
N
N
MeH
H
O
H
OH NH O
H
O
H
HMe N
CH2OMe
N
CH3 O
CH3CH3
O
N
CH3
CH2OMe
CH3
CONC4H8
CH3X
O
CH3
X
O
Me
CH3
OCH3
CONC4H8
CH3
X
X
OMe
NC4H8
OMe
NC4H8
Chem 206D. A. Evans Diastereoaselective Hydrogenation: Cyclic Substrates
Polar functional groups other than OH may also direct the process
A.G. Schultz and P.J. McCloskey, J. Org. Chem., 1985, 50, 5907.
J.M. Brown and S.A. Hall, J. Organomet. Chem., 1985, 285, 333.
Ir(pyr)Pcy3+
H2
diastereoselection 91 : 9
H2
Ir(pyr)Pcy3+
Rh(DIPHOS-4)+
H2
diastereoselection 89:11
diastereoselection >99:1
Ir(pyr)Pcy3+
H2
diastereoselection >99:1
H2
Ir(pyr)Pcy3+ Diastereoselection
55:45
99:1
Ir(pyr)Pcy3+
H2
99:1
>99:1
Diastereoselection
H2
Ir(pyr)Pcy3+
diastereoselection >99:1
A.G. Schultz and P.J. McCloskey, J. Org. Chem., 1985, 50, 5907.
15 psi H2
Ir(pyr)Pcy3+
R.H. Crabtree and M.W. Davis, J. Org. Chem., 1986, 51, 2655.
15 psi H2
Ir(pyr)Pcy3+ diastereoselection
>99:1
diastereoselection >99:1
A.G. Schultz and P.J. McCloskey, J. Org. Chem., 1985, 50, 5907.
R1R2
CH2
OH
Rh
P
P
RhP
P
Rh
P
P
OH
CH3
R2 R1
RhP
P
C
H
R2
C
H
H
CH
H
CR2
H
Rh
P
P
C
OH
R1 H
Rh
P
P
RhP
P
OH
C
HR1
P Rh
P
OH
C
H R1
C
OH
R1H
CH3
CH2R2
CH3
CH2R2
H2
H2
H2
H2 R
1R2
CH3
OH
R1R2
CH3
OH
OH
CH3
R2 R1
OH
CH3
R2 R1
R1R2
CH2
OH
OH
CH3
R2 R1
T
D
T
D
O
Ph
CH3
N
O
O
CH3
OH
CH3
R
R N
CH2
OH
CH3
O
O
CH3
Ph
O
Rh
P
P
RhP
P
C
H
H
CR2H
C
OH
R1 H
Rh
P
P
RhP
P
OH
C
HR1
CH3
CH2R2
H2
H2
R COXn
CH3
OH
CH3
COXn
CH3 CH3
OH
R
R1R2
CH3
OH
OH
CH3
R2 R1
640 psi H2
H2
Rh(DIPHOS-4)+
25 : 75 (23%)
52 : 48 (35%)
71 : 29 (-)
13 : 87 (6%)
12 : 88 (8%)
21 : 79 (-)
93 : 7
94 : 6
93 : 7
9 : 91
8 : 92
6 : 94
Anti : Syn Ratio
Hydroxy-Olefin
R = CH3
R = (CH3)2CH
R = Ph
R = CH3
R = (CH3)2CH
R = Ph
15 psi H2
+
+
low pressure
syn
anti
H2
Rh(DIPHOS-4)+
+
+
anti > 93 : 7
syn > 91 : 9
D. A. Evans & M. M. Morrissey JACS 106, 3866 (1984)
syn
anti
Acyclic Allylic Alcohols
+
+
+
+
favored
+
disfavored
disfavored
favored
+
+
+
syn
anti
Diastereoaselective Hydrogenation: Acyclic SubstratesD. A. Evans Chem 206
OH
CH3
R
CH3
RhP
P
Rh
P
P
B
A
HO
CH3
CH3
OTBS
HO OTBS
CH3CH3
CCH
3
R
CR
CH3
O
H
RhP
P
CH2
C
HCH3
C
CH2
CH3
O
H
Rh
H
P
P
H
H
H2
H2
CH3 CH3
OTBSHO
HO OTBS
CH3CH3
CH3
R
CH3
OH
OH
CH3
R
CH3
Me
HO
Me
Me
EtO2C
OHCH3O2C
CH3 CH3
CH3
CH3
H2
Me
EtO2C
Me
HO
Me
CHO
Me
HO
Me
O
OH
Me
O
Me
O
Me
Me
Me
Et
MeOH
HOOC
O O Me
OH
OHOH
CH3CH3CH3
CH3CH3
CH3 CH3 CH3 CH3HHO
O
H2
A
A
B
CH3
CH3
CH3CH3
CH3O2C OH
Evans, DiMare, JACS, 1986, 108, 2476)
}
a54
a54
a54
with Dow, Shih, Zahler, Takacs, JACS 1990, 112, 5290
Rh(DIPHOS-4)+
Diastereoselection: 94 : 6 (93%)
The Ionomycin Synthesis
The Premonensin Synthesis
Rh +
RatioCatalyst
98 : 2 (90%)
65 : 35
85 : 15
Rh(+)(BINAP) +
Rh(–)(BINAP) +
Rh(DIPHOS-4) +
anti
syn
Catalyst (H2 Pressure) syn : anti
Rh(DIPHOS-4)+ (1000 psi)
Ir(pyr)PCy3+ (15 psi, 2.5 mol%)
Rh(DIPHOS-4)+ (1000 psi)
95 : 5
73 : 27
9 : 91
Olefin
A(1,3) destabilization
+
+
+
+
Homoallylic Alcohols Evans, Morrissey Tetrahedron Lett. 26 6005 (1985)
syn
anti
Diastereoaselective Hydrogenation: Acyclic SubstratesD. A. Evans Chem 206
favored
disfavored