LAUSR

Abstract We report our complete mechanistic study on the highly diastereo- and enantioselective reductive coupling of isoquinoline templated by a chiral diboron. An uncommon activation mode, activation of the B-B bond via double N-B coordination followed by [3,3]-sigmatropic migration was computed to be more preferable over the radical pathway involving the B-B bond homolysis. On the basis of this mechanism, origins of the excellent enantio- and chemoselectivity were found to be driven by less steric repulsion and more secondary orbital interactions in the most favorable reductive coupling transition state. The reductive coupling of dihydroisoquinoline was also investigated and found to have a lower barrier and a larger thermodynamic driving force for the rate-determining second N-B coordination concerted with sigmatropic migration step, compared to isoquinoline. Higher chemoselectivity for the reductive coupling was computed to be achieved by using a strong Lewis-acidic diboron (B2F4). These computational results should be helpful for future development of this unusual reductive coupling by diborons.