A Route to Carbasugar Analogues - Jonathan Clayden - The ...

Chapter 4 – Synthesis of carbasugars
plane of the olefin and the allylic C–O bond. Hydrogen-bonding reagents generally
proceed through a transition state with α ~120° whilst metal-alcoholate reagents prefer
α ~ 40°.
Adam applied this analysis to cyclohexenols, concluding that since α for equatorial
cyclohexenols is approximately 140°, hydrogen bonding reagents are more suited to
their epoxidation. This is somewhat borne out when such reagents are considered in a
rigid system such as allylic alcohols 290 (Table 4.4).
t-Bu
290a
pseudoaxial OH
OH
H
α
t-Bu
H
α
OH
α = +110° α = +140°
290b
pseudoequatorial OH
Me
R
Ox*
213
OH OH
α = +134°
syn : anti ratio
Entry oxidant solvent axial 290a equatorial 290b
a 168 mCPBA CH 2 Cl 2 90:10 98:2
b 189 CF 3 CO 3 H CH 2 Cl 2 99:1 99:1
c 168 DMDO CCl 4 58:42 82:18
d 168 DMDO acetone 30:70 60:40
Table 4.4 – epoxidation of allylic alcohols 290 by different reagents
However it should be noted that epoxidation of cyclohexen-3-ol (α = 110° or 140°)
with VO(acac) 2 proceeds with 98:2 syn-selectivity 190 despite the apparent unoptimal α-
values. This casts some doubt upon the validity of Adam’s argument, but with many
examples demonstrating their use, peracids are clearly the reagents of choice since they
are cheap, readily available and easily handled.
The crystal structure of 213 shows the allylic C6–C5=C4–O torsional angle to be 134°;
well-suited to the conditions suggested by Adam. To direct the mCPBA to the synface
the free alcohol 213 would be used for the epoxidation. The slightly more polar
epoxide is not expected to present any isolation problems since it has the same number
of hydrogen bonding sites as the diol which showed no hydrophilicity.
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