Chiral auxiliary, organoboranes

Pyrrolidines are an important class of five-membered heterocycles with noteworthy biological properties [46]. In addition to pharmaceutical applications, the pyrrolidine moiety has also been widely used as a chiral auxiliary for asymmetric synthesis [47]. Although many elegant syntheses of chiral nonracemic pyrrolidines have been reported within the past decade or so [48-50], an alternative approach based on the intramolecular reaction of an azide and organoborane has been developed very recently [51-53], This approach utilizes the hydroboration-azide alkylation tandem reaction as a key sequence, taking advantage of the efficient stereocon-trolled steps. Scheme 20 shows an application of the synthesis of 3-substituted 5-(2-pyrrolidinyl)isoxazole which has been found to have nanomolar activity, comparable to (5)-nicotine, against whole rat brain [54]. 

A chiral, enantiomerically pure organoborane bound to an achiral phosphine could not only serve as a protecting group, but could also, in principle, deliver an asymmetric induction in stereoselective processes, thus playing the role of a chiral auxiliary. 

Secondly, the chiral auxiliary isopinocampheyl group is readily removed from the organoborane products by treatment with acetaldehyde84-105-106. The liberated a-pinene can be recovered and recycled. 

Brown HC, Bhat, KS, RandadRSJ (1989) Chiral Synthesis via Organoboranes. 21. Allyl- and Crotylboration of a-Chiral Aldehydes with Diisopinocampheylboron as the Chiral Auxiliary. 

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