Mechanism and Stereochemistry of Rhodium-Catalyzed [5 + 2 + 1] Cycloaddition of Ene-Vinylcyclopropanes and Carbon Monoxide Revealed by Visual Kinetic Analysis and Quantum Chemical Calculations.

Abstract

Previously, we developed a rhodium-catalyzed [5 + 2 + 1] cycloaddition of ene-vinylcyclopropanes (ene-VCPs) and carbon monoxide to synthesize eight-membered carbocycles. The efficiency of this reaction can be appreciated from its application in the synthesis of several natural products. Herein we report the results of a 15-year investigation into the mechanism of the [5 + 2 + 1] cycloaddition by applying visual kinetic analysis and high-level quantum chemical calculations at the DLPNO-CCSD(T)//BMK level. According to the kinetic measurements, the resting state of the catalyst possesses a dimeric structure (with two rhodium centers) whereas the active catalytic species is monomeric (with one rhodium center). The catalytic cycle consists of cyclopropane cleavage (the turnover-limiting step), alkene insertion, CO insertion, reductive elimination, and catalyst transfer steps. Other reaction pathways have also been considered but then have been ruled out. The steric origin of the diastereoselectivity (cis versus trans) was revealed by comparing the alkene insertion transition states. In addition, how the double-bond configuration of the VCPs (Z versus E) affects the substrate reactivity and the origins of chemoselectivity ([5 + 2 + 1] versus [5 + 2]) were also investigated. The present study will provide assistance in understanding other carbonylative annulations catalyzed by transition metals.