Enantioselective reduction oxazaborolidine catalyst system

Addition of triethylamine to the oxazaborolidine reaction system can significantly increase the enantioselectivity, especially in dialkyl ketone reductions.79 In 1987, Corey et al.80 reported that the diphenyl derivatives of 79a afford excellent enantioselectivity (>95%) in the asymmetric catalytic reduction of various ketones. This oxazaborolidine-type catalyst was named the CBS system based on the authors names (Corey, Bakshi, and Shibata). Soon after, Corey s group81 reported that another fi-methyl oxazaborolidine 79b (Fig. 6-6) was easier to prepare and to handle. The enantioselectivity of the 79b-catalyzed reaction is comparable with that of the reaction mediated by 79a (Scheme 6-36).81 The -naphthyl derivative 82 also affords high enantioselectivity.78 As a general procedure, oxazaborolidine catalysts may be used in 5-10 mol%... 

The enantioselective reduction of ketones has become a key reaction not only for the production of chiral alcohols, but for the production of fimctionalized compounds in general, thanks to the versatility of the hydroxyl fimctionality. The oxazaborolidine-catalyzed borane reduction of ketones [2] has become an important reaction due to the fact that the stereochemistry of the alcohols can be predicted and because of the wide substrate acceptance of this catalytic system (it works with aromatic as well as with aliphatic ketones). Among all the known oxazaboroUdine catalysts, the proline-based one is very interesting not only because it is one of the most selective catalysts, but also because another related reagent, the 4-hydroproline, is commercially available and possesses a functional group which could be used for the linkage to a polymer. 

Borane is one of the most common agents for reducing C=0 and C=N bonds and its applications for the enantioselective reduction of ketones and imines have been extensively studied in past decades [77]. Among such agents, the Corey-Bakshi-Shibata (CBS) catalyst, a chiral oxazaborolidine complex, which was discovered by Itsuno in 1981 [78] and further developed by Corey in 1987 [79], was widely considered as the most successful catalytic system. Several excellent reviews are already available [77a, 80]. In this chapter, we only give limited coverage of the organocatalytic asymmetric reduction of ketones by catalytic systems other than chiral oxazaborolidines. 

This reduction method has a number of advantages that include wide scope, predictable absolute stereochemistry, ready availability of the chiral catalyst in both enantiomeric forms, high yields, experimental ease, recovery of the catalyst (as the amino alcohol), and low cost of goods. The most common form of the chiral oxazaborolidine is derived from prolinol and has a methyl substituent on the boron atom (B-Me-CBS) 1. When one conducts a reduction on a novel system for the first time, this catalyst provides a good compromise of cost, enantioselectivity, and experimental ease. If sufficient control is not observed with this reagent, one can then systematically evaluate the numerous variations of this framework. 

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