Total Synthesis of Hetero-annulated Carbazoles and Development of Radical Precursors Enabled by Visible-light Photoredox Catalysis

Abstract

Furo[3,2-a]carbazole is a hetero-annulated carbazole with furan ring attached on carbazole core ring and remarkably diverse family of natural products. Furo[3,2-a]carbazole mostly isolated from plants of the genus Murraya, Glycosmis, and Clausena from the family Rutaceae. Herein, an early stages synthesis of 7-methylbenzofuran moiety from commercially available o-cresol following by a short, efficient, and divergent synthetic approach to three furo[3,2-a]carbazole alkaloids, namely furostifoline, furoclausine A, and un-named furo[3,2-a]carbazole alkaloid has been developed with the integration of tandem cross-coupling and reductive amination as a key step.

The formation of C-C bond is fundamental to constructing versatile organic compounds. The development of photochemistry and photocatalyst has encouraged chemists to explore various radical precursors for generating reactive intermediates in C-C bond formation. Many radical precursors have been thoroughly investigated. However, the generation of radical precursors still has limitations, such as being restricted to primary alkyl radicals or yielding useless byproducts. In this study, we present a novel radical precursor derived from readily available feedstock chemicals, enabling the generation of primary, secondary, and tertiary alkyl radicals through visible-light photoredox catalysis. The method involves intermolecular PCET, wherein the generation of O-centered radicals mediated β-scission of adjacent C−C bonds, followed by subsequent fragmentation to generate alkyl radical species, which undergo C–C bond formation with non- or activated alkenes. This strategy has been successfully applied to conjugate addition reactions, featuring mild reaction conditions and a broad substrate scope, by using metal-free photocatalyst.

Neutral Silicon is one of promising radical precursors that is still underdeveloped compared with another radical precursor such as carboxylate and borate. Herein, we report a new strategy for photoinduced C-C bond forming reaction using neutral silicon as a radical precursor. We are using α-silyl ethers/thioethers and coupled with trifluoromethyl alkenes or Michael acceptors to generate several products via single electron oxidation. Various functional groups were tolerated and provided good to excellent yields in mild conditions. A preliminary mechanistic investigation provides evidence for reaction mechanism involving a photoinduced electron transfer.