CBS reduction
| Corey–Itsuno reduction | |
|---|---|
| Named after |
Elias James Corey Shinichi Itsuno |
| Reaction type | Organic redox reaction |
| Identifiers | |
| Organic Chemistry Portal | corey-bakshi-shibata-reduction |
The Corey–Itsuno reduction, also known as the Corey–Bakshi–Shibata (CBS) reduction, is a chemical reaction in which an achiral ketone is enantioselectively reduced to produce the corresponding chiral, non-racemic alcohol. The oxazaborolidine reagent which mediates the enantioselective reduction of ketones was previously developed by the laboratory of Itsuno and thus this transformation may more properly be called the Itsuno-Corey oxazaborolidine reduction.
In 1981, Itsuno and coworkers first reported the use of chiral alkoxy-amine-borane complexes in reducing achiral ketones to chiral alcohols enantioselectively and in high yield. Several years later in 1987, E. J. Corey and coworkers developed the reaction between chiral amino alcohols and borane (BH3), generating oxazaborolidine products which were shown to rapidly catalyze the enantioselective reduction of achiral ketones in the presence of BH3•THF.
The CBS Reduction has since been utilized by organic chemists as a reliable method for the asymmetric reduction of achiral ketones. Notably, it has found prominent use not only in a number of natural product syntheses, but has been utilized on large scale in industry (See Scope Below). Several reviews have been published.
Corey and coworkers originally proposed the following reaction mechanism to explain the selectivity obtained in the catalytic reduction.
The first step of the mechanism involves the coordination of BH3 to the nitrogen atom of the oxazaborolidine CBS catalyst 1. This coordination serves to activate the BH3 as a hydride donor and to enhance the Lewis acidity of the catalyst’s endocyclic boron. X-ray crystal structures and 11B NMR spectroscopic analyses of the coordinated catalyst-borane complex 2 have provided support for this initial step. Subsequently, the endocyclic boron of the catalyst coordinates to the ketone at the sterically more accessible electron lone pair (i.e. the lone pair closer to the smaller substituent, Rs). This preferential binding in 3 acts to minimize the steric interactions between the ketone (the large RL substituent directed away) and the R’ group of the catalyst, and aligns the carbonyl and the coordinated borane for a favorable, face-selective hydride transfer through a six-membered transition state 4. Hydride transfer yields the chiral alkoxyborane 5, which upon acidic workup yields the chiral alcohol 6. The last step to regenerate the catalyst may take place by two different pathways (Path 1 or 2).
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