Catalyst-Controlled Selective Functionalization of Unactivated C–H Bonds in the Presence of Electronically Activated C–H Bonds

A new
chiral dirhodium tetracarboxylate catalyst, Rh2(S-2-Cl-5-BrTPCP)4, has been developed for C–H
functionalization reactions by means of donor/acceptor carbene intermediates.
The dirhodium catalyst contains four (S)-1-(2-chloro-5-bromophenyl)-2,2-diphenyl­cyclopropane-1-carboxylate
ligands, in which all four 2-chloro-5-bromophenyl groups are on the
same face of the catalyst, leading to a structure, which is close
to C4 symmetric. The catalyst induces
highly site selective functionalization of remote, unactivated methylene
C–H bonds even in the presence of electronically activated
benzylic C–H bonds, which are typically favored using earlier
established dirhodium catalysts, and the reactions proceed with high
levels of diastereo- and enantioselectivity. This C–H functionalization
method is applicable to a variety of aryl and heteroaryl derivatives.
Furthermore, the potential of this methodology was illustrated by
sequential C–H functionalization reactions to access the macrocyclic
core of the cylindrocyclophane class of natural products.