Regioselectivity and stereoselectivity of nucleophilic addition to glycal and imino‐glycal vinyl epoxides and their carba analogs: a rationalization based on HSAB theory and MEP

Besides the usual parameters for softness (Fukui indexes) and hardness (atomic charges), novel parameters, obtained from the molecular electrostatic potential on the van der Waals surface (ESP-indexes), were considered as stereochemical and possible hardness descriptors. The effect of oxirane ring activation by electrophiles was modeled by scanning the aforementioned parameters over the epoxide ring opening in the neutral substrates and in two corresponding protonated derivatives. C(1) is a softer center than C(3), but oxirane activation rapidly levels softness and shifts hardness from C(3) to C(1); with carbocycles, C(1) and C(3) hardness are leveled, and with heterocycles, C(1) becomes harder than C(3). ESP-indexes are suitable parameters to account for stereoselectivity and more reliable hardness descriptors than the atomic charges. An explanation for the prevailing syn-C(1)-selectivity observed with glycals and iminoglycals epoxides versus the anti-C(3)-selectivity observed with carba analogs is given. A rationalization of Ferrier rearrangement is also provided. Copyright © 2015 John Wiley & Sons, Ltd.