Deciphering the Origin of Enantioselectivity on the Cis-Cyclopropanation of Styrene with Enantiopure Di-chloro,Di-gold(I)-SEGPHOS Carbenoids Generated from Propargylic Esters

• Published in: Journal of organic chemistry 2019-06, Vol.84 (12), p.7664-7673
• Main Authors: Villar, Pedro, González-Pérez, Adán B, de Lera, Angel R
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b00250

The stereoselective synthesis of cis-disubstituted cyclopropanes by the Au­(I)/PPh3-catalyzed cycloaddition of propargylic esters and styrene has been studied using density functional theory calculations. The computed mechanistic scheme involves the rate-limiting 1,2-rearrangement of the propargylic ester with the π-coordinated gold complex, followed by the (2 + 1)-cheletropic reaction of styrene with the alkenyl–Au­(I) carbene intermediate to afford the cis-disubstituted cyclopropane derivative in a high cis/trans diastereomeric ratio. With a (R)-di-chloro,di-gold-DTBM-SEGPHOS complex as the catalyst, computations are consistent with a rate-determining (2 + 1)-cheletropic reaction, in which facial discrimination is proposed to result from a combination of subtle steric and electronic effects in the SiRe facial approach transition structure, which favor the formation of the cis-cyclopropane diastereomer of 1R,2S absolute configuration, as experimentally observed.