Sterically hindering the trajectory of nucleophilic attack towards p-benzynes by a properly oriented hydrogen atom: an approach to achieve regioselectivity

Abstract

Nucleophilic addition to p-benzynes derived via Bergman cyclization has become a topic of keen interest. Studying the regioselectivity in such addition can reveal important information regarding the parameters controlling such addition. Recently, high regioselectivity has been achieved in nucleophilic addition to a p-benzyne derived from an ortho substituted benzo fused cyclic azaenediyne. Rather than having a freely rotating substitution, a rigid hydrogen atom coming from a suitable naptho fused enediyne and residing in the plane of the p-benzyne ring can offer hindrance to the trajectory of the nucleophile. This can lead to regioselectivity provided the other side remains relatively free of such hindrance. Based on that approach, halide addition to p-benzynes derived from naphtho fused cyclic azaenediynes was studied and a high level of regioselectivity was observed. Steric hindrance to the trajectory of nucleophile by the bay hydrogen was found to be the main cause of such regioselectivity; however, differential electrostatic potential as well as distortions at reactive centres have a minor role in controlling the regioselectivity. The products of such high yielding addition are the halo naphtho tetrahydroisoquinolines.