http://www.courses.fas.harvard.edu/~chem206/
Me2CH
Me
OH
Me
Ph
NHCONHPh
9-BBN OH
Me
Me2CH
OH
O
NHCONHPh
Ph
Me
Chem 206D. A. Evans
Matthew D. Shair Friday,October 4, 2002
a73 Reading Assignment for week
A. Carey & Sundberg: Part B; Chapter 4"Electrophilic Additions to C–C Multilple Bonds"
Olefin Addition Reactions: Part–1
Chemistry 206
Advanced Organic Chemistry
Lecture Number 8
Olefin Addition Reactions–1 a73 Problems of the Day: (To be discussed)
a73 Hydroboration
a73 Epoxidation & Directed Epoxidation
a73 Other Reading Material
Smith, K. and A. Pelter (1991). Hydroboration of C=C and Alkynes. Comprehensive Organic Synthesis. B. M. Trost and I. Fleming.
Oxford, Pergamon Press. 8: 703.
Beletskaya, I. and A. Pelter (1997). “Hydroborations catalysed by transition metal complexes.” Tetrahedron 53(14): 4957-5026.
Brown, H. C. and P. K. Jadhav (1983). Asymmetric Hydroboration. Asymmetric Synthesis. J. D. Morrison. New York, AP. 2: 1.
Hoveyda, A. H., D. A. Evans, et al. Chem. Rev. 1993,93: 1307-70 “Substrate-directable chemical reactions” (handout)
W. C. Still & J. C. Barrish, J. Am. Chem. Soc. 1983, 105, 2487.
diastereoselection 24:1H2O2
Rationalize the stereochemical outcome of this reaction
Roush, J. Org. Chem. 1987, 52, 5127.
m-CPBA
CH2Cl2, 0 °C
75 %
Diastereoselection = 95 : 5
Predict the stereochemical outcome of this reactionK. Houk, Tetrahedron. 1984, 40, 2257-2274Theoretical Studies of Stereoselective Hydroboration Reactions
(Handout)
C CHR HR
C CHR HR
M H
H H
C CHR HR –ROH
C CHR HR
–N2
C CHR HR
–N2
OsO4
C CHR HR
–N2
RO2H
R2C=N2
R2C=C=O
C C
H
R
H
R
M H
C C
H
R
H
R
O OOs
O O
C C
H
R
H
R
H H
C C
H
R
H
R
O
C C
H
R
H
R
OR
R
C C
H
R
H
R
R2C
C CHR HR
C CHR HR
C CHR HR
C CHR HR
H–X
Hg(OR)2
R–S–X
Br Br
C C
H
R H
RH
X
C C
H
R H
RRO
S–R
C C
H
R H
RBr
Br
C C
H
R H
RRO
Hg–OR
C C
H
R
H
R
X
C C
H
R
H
R
H
C C
R
H H
RH
X
D. A. Evans Chem 206Olefin Addition Reactions: Introduction
Representative Cis-Addition Processes
a73 Hydrometallation
+
M = B, Al, etc
+
a73 Hydrogenation
M-catalyst
+
a73 Group Transfer (epoxidation)
+
a73 Group Transfer (dihydroxylation)
+
a73 Group Transfer (cyclopropanation)
M-catalyst
Attributes:
Each process adds to the C=C via a stereospecific process
Intermediates may be involved in some of the indicated reactions
+
a73 Cycloadditions (one of many!)
Representative Trans-Addition Processes
a73 Halogenation
+
a73 Oxy–metallation (M = Hg(II), Tl(III)
+
a73 Oxy–sulfenation (M = S(II), Se(II)
+
Attributes:
Process may proceed via an bridged intermediate where H+ is the initiating electrophile
Olefin substitution, reaction conditions as well as halide type may disrupt bridging
a73 Addition of hydrogen halides
+ +
Attributes:
Each process may proceed via an bridged intermediate where X is the initiating electrophile
Olefin substitution may disrupt bridging
Me3C
H
CH2
A
B H
H
H
S
C CRR RR
RL OH
RM Me
B2H6
MCPBA
RL
RM H
CH C MeCH
2OR
HBH
H
H2O2
C RRCRR
B
S
H
H
H
RL
RM
MeRM
OHRL
OH
H
CH C MeCH
2OR
HBH
H
C
H
C
H2B
R
R
R
R
Me
OH
OMe
O
Me Me
OTrTrO
Me
OH
Me
O CH2OBn
Me Me
OH
Me
OH
Me
OH
Me
TrO OTr
Me
BnO OH
Me Me Me
B2H6
B2H6
B2H6
MeMe
CH2OBnO
OH
OH
TrO OTr
Me
OH
Me
OH
MeMe
O
OMe
Me
OH
OH
OH
MeMeMe
OHBnO
OH
Me
TrO
OH
Me
OH
Me
OH
Me
OH
OTr
Still, W.C.; Barrish, J. C. J. Am. Chem. Soc. 1983, 105, 2487.
Diastereoselection; 4: 1
ThexylBH2,
then BH3
ThexylBH2,
then BH3
Diastereoselection; 5 : 1
H2O2
Diastereoselection = 3:1
C. H. Heathcock et. al. Tetrahedron Lett 1984 25 243.
H2O2
diastereoselection 12:1
Y. Kishi & Co-workers, J. Am. Chem. Soc. 1979, 101, 259.
diastereoselection 8:1
H2O2
Hydroborations dominated by A(1,3) Strain
Staggered transition states
Steric effects; RL vs RM
A(1,3) allylic straincontrol elements
Houk, "Theoretical Studies of Stereoselective Hydroboration Reactions" Tetrahedron 1984, 40, 2257 (Handout)
major diastereomer
a73 Acyclic hydroboration can be controlled by A(1,3) interactions:
BH3, H2O2 34:66 JOC, 1970, 35, 2654
JOC, 1967, 32, 136369:31
ReferenceRatio, A:EOxidant
E
a73 Response to steric effects: Here is a good calibration system:
?
a73 The basic process
Allylic Strain & Olefin HydroborationD. A. Evans Chem 206
δ+
δ–
major minor
H
H
HH
H
H
H H
H
H
RL
RL
HMe C MeC
HCH C Me
H Me
HC
H C Me
Me
CH C MeMe
H
B
HH
H
C C
H
HMe
B
H
H
C MeCHH
H
RM H
R B
C
H
CHH Me
R
H
CMe C H
H
BH R
R
OH
Me
R
OH
R
Me
OH
9-BBN
R2BH
RL
H2O2 H
Me
H
H
CH2OHMe
H
Me CH
2
H
H
Me
RM
Me
RL OH 9-BBNTS1 RM BH3A
RL
H2O2 OHRL
Me
RM
TS2 BH3RMB
H2O2
RM
Me
RL OHTS2 R2BH
H2O2 OHRL
Me
RM
R2BH
RL
Me
RM
H2O2 OHRL
Me
RM
H2O2
RM
Me
RL OH TS1 RM R2BHR2BH
R2BH structure is a potential variable
Allylic Strain & Olefin HydroborationD. A. Evans Chem 206
What about the following substitution pattern?
Houk's rules: Orient RL anti-periplanar to incoming reagents to avoid TS eclipsing:
favored for BH3
from Lecture 4:
a73 Case I: Borane
+2.68kcal
+1.39 kcal
+0.06 kcal
Φ = 180
Φ = 110
Φ = 50
Φ = 0
Φ = 180Φ = 0
The Torsional Energy Profile
Midland finds that TS1 favored for R2BH reagents, but TS1 ~ TS2 for BH3
Others have found that TS1 favored over TS2 for BH3
favored for R2BH
a73 Case II: Dialkylboranes
Representative Examples
1 : 1 4 : 1
14 : 126 : 1
diastereoselection
borane methylsulfidethexylborane
9-BBNdicyclohexylborane
M. M. Midland & Co-workers,J. Am. Chem. Soc. 1983, 105, 3725..
H2O2
W. C. Still & J. C. Barrish, J. Am. Chem. Soc. 1983, 105, 2487.
R = CHMe2: diastereoselection 24:1
R = n-Bu: diastereoselection 11:1H
2O2
Model is consistent if you presume HO = RM: R = RL
major
minor
major
minor
RM
RO
RO
RM RM
RM
RO
RO
O
Me
Me
OMe
Me
OMeMe
O
H
OH
Me
O N
O
Bn
A
Lonomycin A
RL
CMe C H
H
BH R
R
R B
C
H
CHH Me
R
B
H
RL
H
CHOHO2C O
Me
OMeMe
Me
OMe
Me
OHMe
O
O
Me
Me O O
OMeMe Me
OMe
Me
Me OH
H H
D
F
C
B
C
H
MeHH
H
H
C
B
C
H
MeHH
R
R
RL
RL
H
H
RL
B
H H
H
C C
H
HMe
B
H
H
C MeCHH
H
H
RL
H
RL
RL
C
H
C
B
HMe
H
HH
C
H
C
B
HMe
H
R
R
H
H
E
9
TS2
TS1
H2O2
R2BH
H2O2
R2BH
BH3?SMe2
9-BBN
RM
Me
RL OH
OHRL
Me
RM
OXP
Me
Me
OMe
Me
OMeMe
O
H
OH
Me
OH
OH
OXP
Me
Me
OMe
Me
OMeMe
O
H
OH
Me
TS2
TS1 A
B BH3
BH3
H2O2
H2O2 OHRL
Me
RM
RM
Me
RL OH
Allylic Strain & Olefin HydroborationD. A. Evans Chem 206
favored for BH3
favored for R2BH
a73 Case I: Dialkylboranes a73 Case II: Borane
TS1 favored TS2 disfavored
1
5
9
9
5
1
1
5
10
diastereoselection> 95 : 5
diastereoselection92 : 8
85%
60%
TA1 disfavored TA2 favored
Evans, Ratz, Huff, Sheppard, JACS 1995, 117, 3448-3467.
C-9 → C10
10
10
9
major
major
minor
minor
CO2H
CH2
Me
Me
Me
CH2OH
Me
Me
Me
CH2
CO2H
Me
OH CH2
Me
Me
CH2OH
Me
Me
OH CH2
Me
O O MeEt
OHHEt
Me
Et
Et Et
Et
Me
Et
OH
RO
O
O Me
Me
Me Me
Me
MeO
O
HO
O
OBn
O
O CH3
CH3
R
H
CH3
CH3
O
O
OBn
OHO
R
H
OHR R
OH
OH
H
B2H6
BH3.THF
BH3.THF
BH3.THF
O
OMe
MeH
H
H Me
Me O
O
Me
OH
MeH
OH
OH
H Me
OH
Me
Me
OH
MeH
OH
OH
H Me
OH
Me
Chem 206D. A. Evans Represetative Hydroboration Examples: Acyclic Control
Y. Kishi & Co-workers, J. Am. Chem. Soc. 1978, 100, 2933. "one isomer"
H2O2
diastereoselection 12:1Mori, K. Tetrahedron 1976, 32, 1979
R=H; Diastereoselection = 6.8:1R=OBn Diastereoselection = 6.6:1Oikawa et. al.
Tetrahedron Lett. 1983, 19, 1987.
R = CH3; Diastereoselction = 6.7:1
R = isopropyl "One Compound" Birtwistle et. al. Tetrahedron Lett. 1986, 25, 243.
B2H6/[O]
B2H6/[O]
B2H6/[O]
Schulte-Ette, K.H.; Ohloff, G.Helv. Chim. Acta 1967, 50, 153.
Diastereoselection = 4.6:1
Diastereoselection = 10:1
Diastereoselection = 32:1
Diastereoselection = 19:1
B2H6/[O]
1. 9-BBN
2. H2O2, NaOH
Diastereoselection = 10:1Wolinsky, J.; Nelson, D. Tetrahedron. 1968, 25, 3767.
Wolinsky, J.; Eustace, E. J. J. Org. Chem. 1972, 37, 3376. Diastereoselection = 7:1
1. 9-BBN
2. H2O2, NaOH
For each of the examples shown below, attempt to rationalize the stereochemical outcome of the reaction in terms of one of the models
presented in the discussion.
Me3C
CH2 BH3.THF
CH2
Me3C MeMe
CH2
Me3C Me
Me3C
CH2
Me
Me
CH2
BH3.THF
BH3.THF
BH3.THF
BH3.THF OH
Me
MeMe
3C
OH
MeMe3C
Me3C
OH
OH
MeMe3C
OH
Me
Me
OH
BnOHO O H
H
O
N–NHAr
Me
Me
Me
H
HNO
O O
CH2
HH
CH3
O CH2Me
CO2Me
H
Me
BH3.THF
BH3.THF
BH3.THF
BH3.THF
H
Me
Me
Me
N–NHAr
OH
O
O HH
HOBnO
OH
Me
OH
Me
H
CO2Me
Me O OH
H
CH3
H H
OO
O HN
OH
Chem 206D. A. Evans Representative Hydroboration Examples: Cyclic Systems
Diastereoselection = 2.1:1
Diastereoselection = 3.3:1
Diastereoselection = 2.4:1
Diastereoselection = 4.9:1(Compare with H.C. Brown's
case, with 9-BBN; 1.5:1)Y. Senda et. al. Tetrahedron 1977, 33, 2933.
Diastereoselection = 1.2:1
Minor diastereomer not detectedMcMurry, J. E.J. Am. Chem. Soc. 1968, 90, 6321.
Ley, S. et.al. J. Chem. Soc. Chem. Commun. 1983 630.
Major isomer; no ratio given.B. Fraser-Reid et. al. J. Am. Chem. Soc. 1984, 106, 731.
90% yield, no diastereoselection givenSallay, S. I. J. Am. Chem. Soc. 1967, 89, 6762.
55% yield with the diastereomeric alcohol produced in an unspecified
amount. Recycling of the minor isomer furtherprovided 15% of the
desired material
X
R
A B
A B
X A B
R
B
A
X
B
A
A B
C C
H HH
A B
C C
H HH
A B
A B
OH
OH
R
R
OH
Et2Zn
MCPBA
Cl CO3H
t-BuOOH
Et2Zn
CH2I2
OH
Me
CH2I2
R
O CH2
R
O Zn CH2I
R
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
O
O
H
O
R
????
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
OAc
OH
H
MeMe
Me
Me
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 The transition state:
View from below olefin
O-O bond energy: ~35 kcal/mol
A. Rao in Comprehensive Organic Synthesis, Trost, Ed., 1992, Vol 7, Chapter 3.1
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