Allenoates in Enantioselective [2+2] Cycloadditions: From a Mechanistic Curiosity to a Stereospecific Transformation

• Published in: Journal of the American Chemical Society 2018-11, Vol.140 (46), p.15943-15949
• Main Authors: Wahl, Johannes. M, Conner, Michael L, Brown, M. Kevin
• Format: Article
• Language: English
• Subjects: alkenes; catalysts; Cycloaddition Reaction; cycloaddition reactions; enantioselectivity; Molecular Structure; Naphthalenes - chemistry; Stereoisomerism; Styrenes - chemical synthesis; Styrenes - chemistry
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.8b10008

Identification of a novel catalyst–allenoate pair allows enantioselective [2+2] cycloaddition of α-methylstyrene. To understand the origin of selectivity, a detailed mechanistic investigation was conducted. Herein, two competing reaction pathways are proposed, which operate simultaneously and funnel the alkenes to the same axially chiral cyclobutanes. In agreement with the Woodward–Hoffmann rules, this mechanistic curiosity can be rationalized through a unique symmetry operation that was elucidated by deuteration experiments. In the case of 1,1-diarylalkenes, distal communication between the catalyst and alkene is achieved through subtle alteration of electronic properties and conformation. In this context, a Hammett study lends further credibility to a concerted mechanism. Thus, extended scope exploration, including β-substitution on the alkene to generate two adjacent stereocenters within the cyclobutane ring, is achieved in a highly stereospecific and enantioselective fashion (33 examples, up to >99:1 er).