Mechanism of Lewis-acid-catalyzed intramolecular coupling of sp3C–H bond and alkene: A theoretical investigation

Abstract

First-principle density functional calculations have been carried out to explore the mechanism of the BF 3-catalyzed intramolecular coupling between a C ( sp 3)- H bond in the α-position of such heteroatom as O and an electron-deficient alkene that has an electron-withdrawing substitute, e.g. acetal or carbonyl [McQuaid KM, Sames D, J Am Chem Soc131:402, 2009]. The computations not only confirmed the previously proposed mechanism that coordination of BF 3 (as Lewis acid catalyst) to the acetal oxygen atom triggers 1,5-hydride transfer from the α- C ( sp 3)- H bond to the alkenic carbon, followed by 1,6-cyclization ( C – C bond formation) between the carbon atom of the as-formed oxacarbenium and another alkenic carbon atom, but also disclosed that the 1,5-hydride transfer step is rate-limiting and the cyclization step accounts for the stereoselectivity. In addition, the following substituent effects were disclosed, i.e. the efficacy of intramolecular coupling can be significantly improved by introducing a more electron-donative amino group as the closest neighbor of the hydride donor, but retarded by introducing a less electron-withdrawing – CO 2 Me group as the closest neighbor of the hydride acceptor or by introducing an aromatic phenyl linkage, instead of the saturated linkages exploited in experiments, between the two reacting groups.