DFT Study on the Rhodium(II)-Catalyzed C–H Functionalization of Indoles: Enol versus Oxocarbenium Ylide

The
reaction of carbene insertion into the C–H bond of indole catalyzed
by the Rh2(HCO2)4 complex has been
investigated in detail through DFT calculations. Results indicate
that the indole can proceed via a nucleophilic attack at the carbene
first to generate a carbonium ylide intermediate followed by a [1,4]-proton
transfer to give a free enol. In this case, the final C–H insertion
product can be obtained through the self-catalyzed [1,3]-proton shift
of enol. Alternatively, the nucleophilic attack can also involve the
concerted formations of C–O and C–C bonds to produce
an oxocarbonium ylide intermediate. The subsequent [1,2]-proton shift
catalyzed by a molecule of enol is also energetically feasible to
give the C–H insertion product. It indicates the coexistence
of two distinct pathways for the C–H insertion reaction of
indole. However, the ratio between them can be regulated by the substituents
on both carbenoid and indole. For instance, the enol pathway is always
dominant for the phenyl-substituted carbenoid. However, the ratio
of the two pathways becomes comparable for the ethyl-substituted carbenoid.
The reason is mainly associated with the flexibility of the RhC
bond of the carbenoid, which plays an important role in determining
the approach of indole to the carbenoid. This finding is also useful
to understand the reaction mechanisms for the related [3 + 2] annulation
and the three-component reactions of indole.