CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

Scheme II.1.2
However, availability of ketoreductases with anti-Prelog enantioselectivity, broader
substrate specificity, larger active site for bulky substrates, higher thermostability and
tolerance of organic solvents remains a challenge in the biocatalytic reductive protocols.
Regarding chemocatalysis, a variety of reagents, prepared using various aluminum
or boron hydrides and enantiomers of diols or amino alcohols have been formulated. 34a
Due to the empirical character and the often uncertain nature of the reducing species and
their mode of action, the results with most of these proved disappointing. 34b Among the
borohydride reagents, those obtained through modification of mild and inexpensive sodium
borohydride (NaBH 4 ) are of particular interest. 35a,b Particularly, lithium and potassium tris-butylborohydrides
(L and K-Selectride ® ), and lithium triethyl borohydride were found
useful. A good example can be the substrate-controlled reduction of (R) -2,3-
cyclohexylideneglyceraldehyde-derived ketone 34 by K-Selectride ®
developed by our
group that provided the syn-alcohol 35a with >99% ee (Scheme II.1.3). 35c
O
i
O
O
+ O
O
O
O
OH
34 35a 35b
OH
(i) K-Selectride ® , dry THF, -78 o C.
Scheme II.1.3
Several researchers found that both reaction rate and chiral induction improved
when Lewis acids, such as salts of zinc or zirconium, were included in the reaction
mixture. 36a,b In this category, the Corey-Bakshi-Shibata (CBS) catalyst, 36c Mukaiyama’s
alcohol-modified NaBH 4 with catalytic amount of a chiral Co(II) complex 36d and a tartaric
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