SpinPhox/Iridium(I)-Catalyzed Asymmetric Hydrogenation of Cyclic α-Alkylidene Carbonyl Compounds

Optically active medium-sized cyclic carbonyl compounds bearing an α-chiral carbon center are of interest in pharmaceutical sciences and asymmetric synthesis. Herein, SpinPhox/Ir(I) catalysts have been demonstrated to be highly enantioselective in the asymmetric hydrogenation of the CC bonds in the exocyclic α,β-unsaturated cyclic carbonyls, including a broad range of α-alkylidene lactams, unsaturated cyclic ketones, and lactones. It is noteworthy that the procedure can be successfully used in the asymmetric hydrogenation of the challenging α-alkylidenelactam substrates with six- or seven-membered rings, thus affording the corresponding optically active carbonyl compounds with an α-chiral carbon center in generally excellent enantiomeric excesses (up to 98 % ee). Synthetic utility of the protocol has also been demonstrated in the asymmetric synthesis of the anti-inflammatory drug loxoprofen and its analogue, as well as biologically important ε-aminocaproic acid derivatives.