PtI4-catalyzed oxidative and hydrogenative dearomative [3+2] cycloaddition of 1H-indole N-tethered o-alkynylbenzaldehydes

A synthetic method for the chemodivergent assembly of a diverse range of highly functionalized and architecturally challenging cyclohepta[b]indolines which relies on PtI4-catalyzed oxidative and hydrogenative dearomative [3 + 2] cycloaddition of 1H-indole N-tethered o-alkynylbenzaldehydes in a single operation is described. For the synthesis of a key structural feature that is found in a myriad of bioactive natural products and pharmaceutical compounds, the proposed cascade chemodivergent process delineates the first example of an in situ formed Pt-bound benzopyrylium intermediate that participates in [3 + 2] cycloaddition with the C(2) 00000000 00000000 00000000 00000000 11111111 00000000 11111111 00000000 00000000 00000000 C(3) bond of an aromatic N-heterocycle as the 2 pi cycloaddition partner with exclusive exo-selectivity in a highly efficient manner. It also offers a unique instance of the resulting metallocarbene species generated in this manner undergoing either oxidation by phenylmethylsulfoxide or reduction by THF, with the solvent as both the hydride and alkyl reagent source. The chemodivergent protocol exhibits exceptional functional group tolerance and is amenable to the late-stage modification of a series of structurally complex bioactive natural products and drug molecules.

Automated summary

This article describes a synthetic method for the assembly of highly functionalized and structurally challenging cyclohepta[b]indolines. The method involves PtI4-catalyzed oxidative and hydrogenative dearomative [3 + 2] cycloaddition in a single operation. The method exhibits excellent functional group tolerance and is suitable for late-stage modification of complex bioactive natural products and drug molecules.