Mechanistic study on the Rh(III)-catalyzed synthesis of indolines via selective O-atom transfer of arylnitrones: Origins of the regioselectivity and the improved yield with pivalic acid additive

Abstract

Recent development on Rh(III)-catalyzed synthesis of indolines from arylnitrones and alkynes provides an efficient redox-neutral method integrating C–H activation with O-atom transfer. Here density functional theory calculations were performed on the mechanism of a representative model system: [Cp*Rh]2+-catalyzed reaction of phenylnitrone with 1-phenylpropyne. The results suggest that the catalytic cycle involves a Rh(III)–Rh(I)–Rh(III) transformation and consists of C–H activation, alkyne insertion/O-atom transfer, and cyclization-protonation. The C–H activation, the rate-determining step, proceeds via a self-assisted deprotonation mechanism. The alkyne prefers the insertion into Rh–C(sp2) bond rather than Rh–O bond. The calculations locate an intermediate containing an enol unit, which plays a crucial role in facilitating the cyclization process. The theoretical results provide an explanation for the puzzling experimental observations. The regioselectivity of the reaction is stemmed from the electronic effect rather than steric effect and controlled by the alkyne insertion step. The improved yield with the addition of pivalic acid is attributed to the strong deprotonation capability of pivalate, which significantly facilitates the C–H activation via the concerted metalation–deprotonation (CMD) mechanism.