CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

IIII. .11 IINTRODUCTIION TO CHIIRAL CARBIINOLSS
Majority of the natural and non-natural chiral organic molecules owe their chirality
to the presence of an alkyl (primarily methyl) branching and/or oxygenated functionality.
Hence, in the context of asymmetric synthesis, development of synthetic protocols for (i)
the formation of carbon-carbon bond, and (ii) the reduction of prochiral ketones remain
two most fundamental and important goals. The most commonly adopted method for the
former is by addition of a nucleophile, usually an organometallic species, to a carbonyl
function (aldehyde/ketone). Enveloped within this class of reactions is the conjugate
addition of various organometallic reagents to the enals/enones, that leads to specific
introduction of a hydrocarbon unit to the position β to a carbonyl function. 27 On the other
hand, with a simple carbonyl compound, a secondary or tertiary alcohol is obtained.
Alternatively, addition of a hydride as the nucleophile to the ubiquitous ketones provides
chiral alcohols that are often useful target bioactive compounds or their precursors. 28
Notably, the secondary carbinols are often functionalized further to the required target
compounds like lactones, deoxysugars, sugar modified nucleosides, macrolides,
spiroketals, allenes, amines and even heterocycles. 3,29 Yet another alternative for the
synthesis of the carbinols is the asymmetric dihydroxylation (ADH) of alkenes, for which
the inventor, Prof. K. B. Sharpless got the Nobel Prize in chemistry. In a nutshell, the
important reagent- and/or substrate-controlled asymmetric strategies for the formation of
chiral carbinols have been (a) ketone reduction, (b) ADH route, and (c) addition of
organometallic species to carbonyls. These strategies have been briefly presented in this
section.
20