Corey-Bakshi-Shibata reduction CBS

The Corey-Bakshi-Shibata reduction (CBS reduction) is a highly enantioselective method for arylketones, diaryl ketones, and dialkylketones. In addition, cyclic a,p-unsaturated ketones, acyclic a,p-unsaturated ketones, and a,p-ynones are reduced enantioselectively in a 1,2-fashion. The high enantioselective nature of this reduction relies on the chiral oxazaborolidine catalyst, shown in the reaction scheme, in the presence of borane or a dialkylborane. Reviews (a) Singh, V. K. Synthesis 1992, 605-617. (b) Deloux, L. Srebnik M. Chem. Rev. 1993,93,163-1. (c) Corey, E. J. Helal, C. J. Angew. Chem. Int. Ed. 1998, 37. 1986-2012. 

The reduction of ketones by borane catalyzed by chiral oxazaborolidines such as (136), derived from the enantiomeric amino alcohols, has been applied to the synthesis of several drug candidates (127). This system is known as the CBS (Corey, Bakshi, Shibata) reduction (153), and Corey himself has applied it to the synthesis of pharmaceutical compounds (154). A further example is provided by the synthesis of MK-499 (137), a... 

The pioneering studies by Itsuno [1] and Corey [2] on the development of the asymmetric hydroboration of ketones using oxazaborolidines have made it possible to easily obtain chiral secondary alcohols with excellent optical purity [3]. Scheme 1 shows examples of Corey s (Corey-Bakshi-Shibata) CBS reduction. When oxazaborolidines 1 were used as catalysts (usually 0.01-0.1 equiv), a wide variety of ketones were reduced by borane reagents with consistently high enan-tioselectivity [2]. The sense of enantioselection was predictable. Many important biologically active compounds and functional materials have been synthesized using this versatile reaction [2-4]. 

Numerous theoretical treatments have been carried out to understand the mode of asymmetric induction of the Corey-Bakshi-Shibata (CBS) reduction, more thoroughly.12 Liotta et al. carried out computational studies to identify the transition states for CBS reductions of various ketones13 (Scheme 4.3k).In the asymmetric reduction of acetophenone with the catalyst (R)-28a, four transition states were found. Of the lowest energy is chairlike transition state A, which would lead to formation of the major enantiomer. In transition state A, the phenyl group of acetophenone occupies an equatorial position that is free from any steric interaction, as it is 5.5 A away from one of the two phenyl groups of the diphenylprolinol ring. On the other hand, transition state B, leading to the... 

For aryl ketones the Corey-Bakshi-Shibata (CBS) reduction using oxazaborolidines as catalysts for the boron hydride mediated hydrogenation is particularly useful, with maximum selectivities up to 99 % ee (see Scheme 4) [34]. The excellent review by Corey et al. [35] also shows clearly the power for chemo- and enantioselective reduction of purely aliphatic a,//-enones and -ynones only on the carbonyl group. In the re-... 

Related reactions Corey-Bakshi-Shibata (CBS) reduction, Noyori asymmetric hydrogenation ... 

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