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

Abstract

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.

Synthesis of Highly Functionalized Allylic Alcohols from Vinyl Oxiranes and N-Tosylhydrazones via a Tsuji–Trost-Like “Palladium–Iodide” Catalyzed Coupling

“…The only regioisomer derived from the conjugated addition of the nucleophile to the C4 of the vinyloxirane is observed. In our opinion, this control of the regioselectivity is due to steric reasons, which facilitate the formation of the linear product rather than the eventual hard/soft character of the nucleophile. , Also, the presence of iodide salts can influence the regiocontrol, which afforded the linear product exclusively, as already reported . Therefore, I – ions could both sustain the catalytic cycle and increase the coupling regioselectivity.…”