Deoxygenative Cross-Coupling of C(aryl)–O and C(amide)═O Electrophiles Enabled by Chromium Catalysis Using Bipyridine Ligand

Abstract

Deoxygenative cross-coupling between unactivated C–O and unsaturated C═O electrophiles remains an unsolved challenge in synthetic chemistry. Here, we report the deoxygenative cross-coupling of C–O/C═O electrophiles by reaction of unactivated aryl esters with unsaturated amides, enabled by chromium catalysis. Inexpensive and simple CrCl3 salt combined with bipyridine ligand, magnesium reductant, and chlorosilane, shows high reactivity in promoting the deoxygenative coupling between C–O and C═O bonds involving hydrogen transfer. This reaction provides a strategy to form pharmaceutically interesting diarylmethylated amines, by forging C(sp2)–C(sp3) bonds with impeding the competing ester homocoupling and carbonyl reduction that usually occur under reductive conditions. Mechanistic studies based on high-resolution mass spectrometry analysis and deuterium-labeling experiments indicate that cleavage of ester C–O bonds by Cr and subsequent silylation leads to the formation of arylated silachromate, which regioselectively adds to carbonyls of amides through reductive elimination and deoxygenative hydrogen transfer, resulting in the reductive cross-coupling of C(aryl)–O and C(amide)═O electrophiles.