Mechanism of Lewis-acid-catalyzed intramolecular coupling of sp(3) C-H bond and alkene: A theoretical investigation

NSFC [21273177, 20973137]; MOE [20130121110004]; 973 project [2011CB808504]First-principle density functional calculations have been carried out to explore the mechanism of the BF3-catalyzed intramolecular coupling between a C(sp(3))-H bond in the alpha-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 Soc 131: 402, 2009]. The computations not only confirmed the previously proposed mechanism that coordination of BF3 (as Lewis acid catalyst) to the acetal oxygen atom triggers 1,5-hydride transfer from the alpha-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 -CO2Me 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