Gold(I)-Catalyzed Benzylic C(sp3)-H Functionalizations: Divergent Synthesis of Indole[a]- and [b]-Fused Polycycles

Phenyl azides substituted by an (alkylphenyl)ethynyl group facilitate benzylic sp(3)(C-H) functionalization in the presence of a JohnPhosAu catalyst, resulting in indole-fused tetra- and pentacycles via divergent N- or C-cyclization. The chemoselectivity is influenced depending on the counter-anion, the electron density of the alpha-imino gold(I) carbene, and the alkyl groups stabilizing the benzylic carbocation originating from a 1,5-hydride shift. An isotopic labeling experiment demonstrates the involvement of an indolylgold(I) species resulting from a tautomerization that is much faster than the deauration. The formation of a benzylic sp(3)(C-H) functionalization leading to an indole-fused seven-membered ring is also demonstrated.

Automated summary

In this study, phenyl azides substituted by an (alkylphenyl)ethynyl group were found to facilitate benzylic sp(3)(C-H) functionalization under the presence of a JohnPhosAu catalyst, resulting in the synthesis of indole-fused tetra- and pentacycles through divergent N- or C-cyclization. The chemoselectivity of the reaction was found to be influenced by the counter-anion, the electron density of the alpha-imino gold(I) carbene, and the alkyl groups stabilizing the benzylic carbocation.