S(N)2 ring opening of beta-lactones: an alternative to catalytic asymmetric conjugate additions

Scott G Nelson; Zhonghui Wan; Magdalena A Stan

doi:10.1021/jo025519n

S(N)2 ring opening of beta-lactones: an alternative to catalytic asymmetric conjugate additions

J Org Chem. 2002 Jul 12;67(14):4680-3. doi: 10.1021/jo025519n.

Authors

Scott G Nelson¹, Zhonghui Wan, Magdalena A Stan

Affiliation

¹ Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. sgnelson@pitt.edu

PMID: 12098275
DOI: 10.1021/jo025519n

Abstract

Merging catalytic asymmetric acyl halide-aldehyde cyclocondensation (AAC) reactions with ensuing Grignard-mediated ring opening of the derived enantiomerically enriched beta-lactones is presented as a generally useful asymmetric synthesis of beta-disubstituted carboxylic acids. Enantiomerically enriched beta-lactones are subject to efficient S(N)2 ring opening with a variety of copper-modified alkyl Grignard reagents, including highly branched nucleophiles. Considerable structural variation in the lactone electrophile is also tolerated. Phenyl- and vinyl-derived organometallics are not efficient nucleophiles for the ring-opening reactions.