Download Epoxide Use - Dr. May Group

CHEM 6352 Organic Reactions & Synthesis
Epoxides: Synthetic Applications
Introduction: (Review in Tet. 1983, 39, 2323; Synth. 1984, 629)
Epoxides can be transformed into a variety of products with predictable regio- and
stereocontrol.
O
OH
H
OH
OH
O
OH
OH
OR
OH
OH
NR1R2
R
Epoxide opening can be effected under either basic or acidic conditions.
Base: Nucleophile is under Steric Approach control
R
R
Nu
O
Nu
OH
Acid: Nucleophile (X) is delivered to the site best able to stabilize a carbocation
R
HX
O
R !+
X
R
O
X
H
OH
Opening of Epoxides by External Nucleophiles:
(General Review: Asymmetric Synthesis Vol. 5; J.D. Morrison, Academic Press: 1985, pp 216-246)
A. Hydride: Reagents Include: H2/Cat., LAH, ALH3, LiEt3BH, Li/NH3
--Different Reagents have different selectivity
--Different Reagents have varied interactions with other functional groups
H
[H]
O
OH
H OH
LiAlH4 98:2
AlH3
5:95
O
OH
LiEt3BH
THF, 25 °C
5 min
JACS 1973, 95, 8486
OH
O
OH
BnO
OH
BnO
OH
REDAL 150:1
DIBAL 1:13
OH OH
TL 1982, 23, 2719
O
BnO
REDAL
O
BnO
(76% yield)
OH
OH
BnO
OH
>100:1 dr
Note selectivity difference between protected and unprotected ends
TL 1982, 23, 2719; TL 1982, 23, 4541; JACS 1982, 104, 1378
DIBAL
O
BnO
CO2Me
BnO
CO2Me
OH
JCS CC 1982, 1292
B. Heteroatom (O, N, S):
Opening can be acid or base catalyzed (best aqueous acid is HClO4)
H2O
O
OH
H3O+ OR OHOH
OMe
MeOH
O
Al2O3, Et2O
good catalyst for
epoxide openings
O
C7H15
JACS 1977, 99, 8208
Nu
Nu-
CO2H
OH
OH
CO2H
C7H15
CO2H
C7H15
OH
JOC 1985, 50, 1560
O
R
CO2H
HN3•i-Pr2NEt
Nu
Et2NH-Ti(i-PrO)4
PhSH-Ti(i-PrO)4
Et2NH
PhSNa
N3
R
>20:1
10:1
1:6
1:13
OH
CO2H
CO2H
R
OH
TL 1991, 32, 667
R=
C3H7
OH
Nu-
n-C3H7
n-C5H11
c-C6H11
t-Bu
Ph
1:12
1:10
1:29
1:43
1:1.5
Nu
Ti(i-OPr)4
O
N3
OH
C3H7
OH
C3H7
OH
JOC 1985, 50, 1557
R2NH
ROH
PhSH, PhSNa, or PhSeH
TNS-N3
NH4OBz
PhCO2H or t-BuCO2H
OH
Nu
20-100:1
100:1
6.4-9:1
14:1
100:1
100:1
O
N3
Ti(i-PrO)2(N3)2
R
OH
OH
R
OH
R
OH
OH
JOC 1988, 53, 5185
N3
n-C3H7
Bn
c-C6H11
t-Bu
Ph
R=
36:1
27:1
20:1
2:1
100:1
C. Carbon
OH
O
OH
BnO
OH
BnO
OH TL 1983, 24, 1377
BnO
OH
6:1
1:5
Me2CuLi
Al(Me)3
C7H15
O
OH
Me2CuLi
OH
C7H15
OH
C7H15
OH
TL 1985, 26, 4683
OH
8:1
CO2H
C7H15
OH
AlMe3
C7H15
CO2H
O
C7H15
CO2H
OH
17:1
MgBr
OH
O
OH
In the presence of CuI
In the absence of CuI
AlMe2
O
O
S
TL 1985, 26, 4683
TL 1978, 4069
91:9
1:99
OH
JACS 1981, 103, 7520
OH
S
S Li
JOC 1974, 3645
S
D. Opening of 2,3-Epoxy Alcohols
Payne Rearrangement: Nu=HO-, RS-, RR’NH, N3OH
O
R
OH
O
R
OH
O
BnO
JOC 1962, 27, 3819
Nu Review:
Aldrich. Acta 1983, 16, 67
R
O
OH
OH
OH
NaCN, aq. ETOH, !
aq. Dioxane
CO2H
JOC 1983, 48, 3761
OH
PhSH, NaOH
OH
OH
Nu-
SPh
BnO
OH
JOC 1982, 47, 1373
E. Internal Nucleophilic Opening
O
R
O
OH
BnN
1) PhCH2NCO, i-Pr2NEt
O
R
JACS 1982, 104, 1109
2) t-BuOK, THF
OH
R
O
O
1) PhCH2OCOCl, pyr
2) AlCl3, Et2O
O
OH
O
R
or
1) PhNCO, Et3N
2) 5% aq. HClO4
JOC 1982, 47, 1373
OH
F. Epoxide Transposition
(±) R O
OH
1) MsCl, pyr
OH
2) cat. HClO4, H2O
R
OMs
OH
Aldrich. Acta 1983, 16, 67
NaH
O
R
OH