CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

IV.5: SSYNTHESSIISS OFF trraannss- t -OAK LACTONE
IV.5.1: Introduction
The 4,5-disubstituted γ-lactone units are often observed in many variety of
biologically relevant molecules. Two of them, the 4S,5R-(trans) and 4S,5S-(cis) isomers of
5-n-butyl-4-methyl-4,5-dihydro-2(3H)-furanone (VII and VIII) (Fig. IV.5.1), also known
as ‘oak lactone’ or ‘whisky lactone’, are natural oak components, extracted into wine and
spirits during oak barrel maturation. 171 The aroma of alcoholic beverages is believed to be
due to the presence of a pure enantiomer of these lactones. The cis- and transconfigurations
of the methyl and butyl groups have been determined by 1 H NMR
spectroscopy, and the absolute configurations were assigned on the basis of an empirical
correlation. 172 Hence, development of strategies to prepare VII and VIII can also be useful
towards the synthesis of other biomolecules possessing a similar γ-lactone moiety.
C 4 H 9
O
O
C 4 H 9
O
O
trans-Oak lactone (VII)
cis-Oak lactone (VIII)
Fig. IV.5.1. Structure of cis- and trans-Oak lactones.
IV.5.2: Previous syntheses
So far, several approaches for the synthesis of VII and VIII have been reported. 173
In one of the early synthesis, 173b trans-oak lactone (VII) was prepared using asymmetric
enzymatic reduction of ketones. Suzuki et al. 173d synthesized VII starting from the chiral
bicyclic lactone (+)-167, prepared from D-mannitol. Nucleophilic addition of n-BuLi to
177