Asymmetric hydrogenation of all-carbon tetrasubstituted α-acylpyrazole-β-alkyl cycloalkenes

Abstract

Many bioactive molecules contain ring frameworks bearing 1,2-contiguous cis-stereocenters, but preparing such frameworks through asymmetric hydrogenation remains challenging. Here we report an Ir-catalyzed asymmetric hydrogenation of tetrasubstituted α-acylpyrazole-β-alkyl cycloalkenes to give 1,2-cis carbo- or heterocycles in yields up to 99% with enantioselectivities up to 99% ee. The acylpyrazole motif serves as a key directing group by coordinating the active Ir-complex with the alkene moiety. This work provides an efficient solution to the longstanding challenge of asymmetric hydrogenation of all-carbon tetrasubstituted β-alkyl cycloalkenes, which should be useful for the synthesis of bioactive molecules.