Theoretical investigation of a chiral Brønsted acid (CBA)-catalyzed isomerization reaction of BCB: mechanism and origin of stereoselectivity

Abstract

The highly strained bicyclo[1.1.0]butanes (BCBs) have exhibited excellent synthetic value and have attracted increasing attention in the field of organic synthesis. However, the mechanism of the activation of such materials under organocatalysis has been studied little. In the present study, the mechanism and origin of stereoselectivity for a chiral Brønsted acid (CBA)-catalyzed isomerization reaction of BCB were systematically investigated using the DFT method. Based on computational results, the β-H elimination step is the stereoselectivity-determining step, through which the S-configured product is generated preferentially. Furthermore, non-covalent interaction (NCI) and atom-in-molecule (AIM) analyses were performed to disclose the origin of the stereoselectivity and show the relatively many and strong noncovalent interactions to be the key for stabilizing the S-configured transition state and thus inducing the stereoselectivity.