Page 438 - Advanced Organic Chemistry Part B - Reactions & Synthesis

component because the stereoselectivity corresponds to placing the unsaturated groups 411
in the perpendicular position.
SECTION 5.3
Group III
O OH OH Hydride-Donor Reagents
R NaBH 4 R R
Ph Ph + Ph
CH 3 CH 3 CH 3
R anti:syn
C H 57:43
2 5
CH 2 CH 70:30
HC C 89:11

Steric factors arising from groups that are more remote from the center undergoing
reduction can also influence the stereochemical course of reduction. Such steric factors
are magnified by use of bulky reducing agents. For example, a 4.5:1 preference for
stereoisomer 14 over 15 is achieved by using the trialkylborohydride 13 as the reducing
agent in the reduction of a prostaglandin intermediate. 126

O CH 3 O
O CH CH 3 O
3
B – CH(CH )
3 2
+ H
O
C H C H
5 11
5 11
ArCO CH 3 ArCO
X Y
O O
13
14 X = H, Y = OH 82%
15 X = OH, Y = H 18%
5.3.2.3. Chelation Control. The stereoselectivity of reduction of carbonyl groups can
be controlled by chelation when there is a nearby donor substituent. In the presence
of such a group, specific complexation among the substituent, the carbonyl oxygen,
and the Lewis acid can establish a preferred conformation for the reactant. Usually
hydride is then delivered from the less sterically hindered face of the chelate so the
hydroxy group is anti to the chelating substituent.

O O – OH
R′ M H HO H R′
R R O R O R″ R
OR″ R″ OR″
R' R′

-Hydroxy 127 and -alkoxyketones 128 are reduced to anti 1,2-diols by Zn BH
4 2
through a chelated TS. This stereoselectivity is consistent with the preference for TS F

126
E. J. Corey, S. M. Albonico, U. Koelliker, T. K. Schaaf, and R. K. Varma, J. Am. Chem. Soc., 93, 1491
(1971).
127 T. Nakata, T. Tanaka, and T. Oishi, Tetrahedron Lett., 24, 2653 (1983).
128
G. J. McGarvey and M. Kimura, J. Org. Chem., 47, 5420 (1982).