Enantioselective remote meta C H arylation and alkylation via a chiral transient mediator
Enantioselective carbon hydrogen (C H) activation reactions by asymmetric metallation could provide new routes for the construction of chiral molecules1,2. 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 s 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 catalysis3,4.Remote, enantioselective C H activation reactions can be achieved by relaying ortho C H activation to the meta position, using a chiral norbornene as the mediator.
Nature