Etherification reactions initiated by BiBr 3: Total synthesis of (+)-(S,S)-(cis-6-methyltetrahydropyran-2-yl)acetic acid and its trans-diastereomer

ORGN 115

Yajing Lian, yxlian@wm.edu and Robert J. Hinkle, rjhink@wm.edu. Department of Chemistry, College of William and Mary, P.O. Box 8795, Williamsburg, VA 23187-8795

            The increasing use of relatively non-toxic Bi(III) compounds in organic synthesis has led to a number of transformations under mild conditions. Cyclization of delta-silyloxy aldehydes and ketones followed by in-situ addition of π-nucleophiles provides 2,6-disubstituted tetrahydropyran systems in which the trans-diastereomer predominates by 5-6:1. The diastereoselectivities of reductive etherification reactions between beta-keto esters containing a pendant triethylsilyl ether group and triethylsilane are greater than 30:1 and the cis-isomers are preferred. Stereochemical preference is rationalized in terms of a rapidly formed cyclic oxocarbenium ion followed by intermolecular axial addition of a π-nucleophile. Several different π-nucleophiles as well as triethylsilane were utilized in several approaches to the target molecule. The effects of catalyst and substrate on the chemical yields and diastereoselectivities of these tandem reactions will be presented.