CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

36e
acid-derived boronate ester, with lithium borohydride (LiBH 4 ) or NaBH 4 are known to
reduce ketones and sometimes imines with high enantioselectivity. Amongst the LiAlH 4 –
based reagents those modified with BINAL-H, 37a ephedrine, 37b Darvon-alcohol
(CHIRALD ® ) 37c or TADDOL 37d are very popular and find widespread use in asymmetric
synthesis. Recently, chiral diols were also used as a chiral modifier in the LiAlH 4 reduction
of achiral ketones. For example, LiAlH 4 reduction of acetophenone (36) in presence of an
α-amino alcohol and 38 as the chiral modifier gave secondary alcohol 37 (Scheme II.1.4)
(>98% ee). 37e
O
CH 3
i
H
OH
CH 3
OH
H
36
37
H
OH
38
(i) LiAlH 4 , (Me) 2 NC 2 H 4 OH, 38, THF, -78 o C.
Scheme II.1.4
In addition a few B-based reagents, non-borohydrides such as Alpine Hydride ® ,
NB-Enantride, diisopinocampheyl boron chloride etc. also work efficiently especially
with conjugated or α-alkyne ketones. 37f The mechanism of reduction by these reagents is
postulated to involve the formation of a complex between the reagent (Lewis acid) and the
carbonyl compound, followed by transfer of a β-hydrogen. The hydrogen transfer is
usually depicted as proceeding through a six-membered cyclic 'boat-like' transition state.
The asymmetric induction is ascribed to an unfavourable steric interaction between the
larger of the two groups on the carbonyl and the alkyl groups in the reagents.
Finally, the importance of the ruthenium-based dihydrogenation or transfer
hydrogenation for asymmetric reduction of prochiral ketones needs special mention. 38
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