SN2 Ring Opening of β-Lactones:  An Alternative to Catalytic Asymmetric Conjugate Additions

• Published in: Journal of organic chemistry Vol. 67; no. 14; pp. 4680 - 4683
• Main Authors: Nelson, Scott G, Wan, Zhonghui, Stan, Magdalena A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 12.07.2002
• Subjects: Aliphatic compounds; Chemistry; Exact sciences and technology; Organic chemistry; Preparations and properties; Catalytic reaction; Lactone; SN2 mechanism; Aluminium complex; Aldehyde; Oxygen heterocycle; Ring cleavage; Acyl bromide; Grignard reagent; Cyclization; Asymmetric synthesis; Carboxylic acid; Copper Organic compounds; Chemical synthesis
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo025519n

Merging catalytic asymmetric acyl halide-aldehyde cyclocondensation (AAC) reactions with ensuing Grignard-mediated ring opening of the derived enantiomerically enriched β-lactones is presented as a generally useful asymmetric synthesis of β-disubstituted carboxylic acids. Enantiomerically enriched β-lactones are subject to efficient SN2 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.