Organic Chemistry

Merging Rh-catalyzed C-H Functionalization and Cascade Cyclization to Enable Propargylic Alcohols as Three-Carbon Synthons: Experimental and Computational Investigations

Authors

Abstract

Reported herein is an unprecedented reactivity of propargyl alcohols as “Three-Carbon Synthons” in a Rh(III)-catalyzed C-H functionalization of acetanilides, leading to the synthesis of core structures of isocryptolepine, gamma-carbolines, dihydrochromeno[2,3-b]indoles, and diindolylmethanes derivatives. The transformation involves a Rh(III)-catalyzed C-H functionalization and heteroannulation to yield indoles followed by a cascade cyclization with both external and internal nucleophiles to afford diverse products. The role of the hydroxy group, the key function of the silver additive, the origin of the unique reverse regioselectivity and the rate-determining step, are rationalized in conformity with the combination of experimental, noncovalent interaction analysis and DFT studies. This protocol is endowed with several salient features, including one-pot multistep cascade approach, exclusive regioselectivity, high bond-forming efficiency, and synthesis of a variety of molecular frameworks.

Version notes

DFT studies, along with non-covalent interaction analysis have been carried out to better understand the origin of the unique reverse regioselectivity and the rate-determining step.

Content

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Supplementary material

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ChemRxiv_Heteroannulation_Supp_Inf_Feb2022
Supporting Information File for: "Merging Rh-catalyzed C-H Functionalization and Cascade Cyclization to Enable Propargylic Alcohols as Three-Carbon Synthons: Experimental and Computational Investigations"