Asymmetric hydrogenation of γ-branched allylamines for the efficient synthesis of γ-chirogenic amines

Abstract

Abstract: The efficient construction of γ-chirogenic amines has been realized via asymmetric hydrogenation of γ-branched N-phthaloyl allylamines by using a bisphosphine-Rh catalyst bearing a large bite angle. The desired products possessing different γ-substituents were obtained in quantitative yields and with excellent enantioselectivities (up to >99% ee). This protocol provides a practical method for the preparation of γ-chirogenic amine derivatives such as the famous antidepressant drug Fluoxetine (up to 50000 S/C). The mechanistic calculations show an unusual P-Rh-P trans-chelating pattern and a weak interaction-promoted activation mode which are completely different from the traditional cis-chelating pattern and coordination-promoted activation mode in metal-catalyzed hydrogenations. Key points: Novel methodology of asymmetric hydrogenation was developed for efficient synthesis of γ-chirogenic amines. New synthetic route was developed for the well-known antidepressant drug Fluoxetine. Unusual mechanism information was found in the bidentate bisphosphine-Rh-catalyzed hydrogenation.