Corey’s BLAs

Scheme 1.1 Generation of Corey s BLAs from the corresponding chiral oxazaborolidine (la) or (lb) and strong Bronsted acid.

The synthetic power of Corey s BLAs has been well demonstrated by their applications to the enantioselective syntheses of biologically important complex molecules through catalytic enantioselective Diels-Alder reactions as key steps (Scheme 1.2) [3g-i, 4]. The key Diels-Alder reactions proceed in excellent chemical yield with high enantioselectivity in all cases and the absolute configurations of the product are consistent with the proposed transition state assembly. 

Scheme 1.2 Enantioselective total syntheses of biologically important molecules using Corey s BLAs.

Among the many chiral Lewis acid catalysts described so far, not many practical catalysts meet these criteria. For a,/ -unsaturated aldehydes, Corey s tryptophan-derived borane catalyst 4, and Yamamoto s CBA and BLA catalysts 3, 7, and 8 are excellent. Narasaka s chiral titanium catalyst 31 and Evans s chiral copper catalyst 24 are outstanding chiral Lewis acid catalysts of the reaction of 3-alkenoyl-l,2-oxazolidin-2-one as dienophile. These chiral Lewis acid catalysts have wide scope and generality compared with the others, as shown in their application to natural product syntheses. They are, however, still not perfect catalysts. We need to continue the endeavor to seek better catalysts which are more reactive, more selective, and have wider applicability. 

The synthetic utility of Corey s chiral BLAs is quite obvious from many successful applications to other carbon-carbon bond-forming reactions described below. 

An enantioselective total synthesis of the apoptosis-inducing natural product, (-)-rasfoninhas been reported by Boeckman Jr. and coworkers in 2006 (Scheme 1.7) [9]. The crucial asymmetric vinylogous Mukaiyama aldol addition was achieved with high diastereoselectivity with chiral BLA (2b) through Corey s transition state model. 

The plausible generation of chiral LLA (9) is considered to be analogous to that of the CBS reduction system [18-20] and Corey s chiral BLAs [3-9]. Thus, the coordination of the achiral Lewis acid to the nitrogen atom of the chiral oxazaborolidine should serve to increase the Lewis acidity of boron atom. 

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