SpmPhox/Iridiuni(I)-Catalvzed Asymmetric Hydrogenation of Cyclic a-Alkylidene Carbonyl Compounds

摘要

Optically active medium-sized cyclic carbonyl compounds bearing an a-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 a-alkylidene lactams, unsaturated cyclic ketones, and lactones. It is noteworthy that the procedure can be successfully used in the asymmetric hydrogenation of the challenging a-alkylidenelactam substrates with six-or seven-membered rings, thus affording the corresponding optically active carbonyl compounds with an a-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 e-aminocaproic acid derivatives.