Enantioselective remote meta-C-H arylation and alkylation via a chiral transient mediator.

Abstract

Enantioselective carbon-hydrogen (C-H) activation reactions by asymmetric metallation could provide new routes for the construction of chiral molecules^1,2. However, current methods are typically limited to the formation of five- or six-membered metallacycles, thereby preventing the asymmetric functionalization of C-H bonds at positions remote to existing functional groups. Here we report enantioselective remote C-H activation using a catalytic amount of a chiral norbornene as a transient mediator, which relays initial ortho-C-H activation to the meta position. This was used in the enantioselective meta-C-H arylation of benzylamines, as well as the arylation and alkylation of homobenzylamines. The enantioselectivities obtained using the chiral transient mediator are comparable across different classes of substrates containing either neutral σ-donor or anionic coordinating groups. This relay strategy could provide an alternative means to remote chiral induction, one of the most challenging problems in asymmetric catalysis^3,4.