Rhodium-Catalyzed Regioselective and Chemoselective Deoxygenative Reduction of 1,3-Diketones

Abstract

The deoxygenative reduction of carbonyl compounds has been well established. However, most protocols developed typically require harsh reaction conditions or highly reactive/toxic reagents, and the deoxygenative reduction of 1,3-diketones is rarely explored despite their importance to synthetic chemistry and materials science. We describe here a rhodium-catalyzed regioselective and chemoselective deoxygenative reduction of 1,3-diketones under mild reaction conditions. This approach exhibited exceptionally high regioselectivity toward the aliphatic carbonyl reduction over aromatic carbonyl reduction. Moreover, the reaction showed good functional group tolerance and broad substrate scope as well as great potential in the late-stage modification and synthesis of natural products and pharmaceutical skeletons. Preliminary mechanistic studies and DFT calculations revealed that this reaction involved the deoxygenation of 1,3-diketone to α, β-unsaturated ketone and its subsequent 1,4-reduction. The noticeably lower energy barrier of the aliphatic C═O insertion into [Rh]-Bpin versus the aromatic C═O insertion was responsible for the high regioselectivity in this reduction.