Enantioselective Dearomatization of Indoles via SmI2-Mediated Intermolecular Reductive Coupling with Ketones

Abstract

Samarium diiodide (SmI2) mediated reductive coupling reactions are powerful methods for the construction of carbon-carbon bond in organic synthesis. Despite the extensive development in recent decades, successful examples of the corresponding asymmetric reactions remained scarce, probably due to the involvement of highly reactive radical intermediates. In this Article, we report an enantioselective dearomatization of indoles via SmI2-mediated intermolecular reductive coupling with ketones. The utilization of samarium reductant supported by chiral tridentate aminodiol ligands allows the facile synthesis of indoline molecules bearing two contiguous stereogenic centers in high yields (up to 99%) and stereoselectivity (up to 99:1 er and >20:1 dr). Combined experimental and computational investigations suggested that parallel single-electron transfer to each substrate from the chiral samarium reductant allows the radical-radical recombination in an enantioselective manner, which is a unique mechanistic scenario in SmI2-mediated reductive coupling reactions.