ZnCl2‐Promoted Asymmetric Hydrogenation of β‐Secondary‐Amino Ketones Catalyzed by a P‐Chiral Rh–Bisphosphine Complex1. (29th December 2014)

• Record Type: Journal Article
• Authors: Hu, Qiupeng; Zhang, Zhenfeng; Liu, Yangang; Imamoto, Tsuneo; Zhang, Wanbin
• Is Part Of: Angewandte Chemie. Volume 127:Number 7(2015)
• Page Start: 2288
• Page End: 2292
• Publication Date: 2014-12-29
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201411384
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A new catalytic system has been developed for the asymmetric hydrogenation of β‐secondary‐amino ketones using a highly efficient P‐chiral bisphosphine–rhodium complex in combination with ZnCl₂ as the activator of the catalyst. The chiral γ‐secondary‐amino alcohols were obtained in 90–94 % yields, 90–99 % enantioselectivities, and with high turnover numbers (up to 2000 S/C; S/C=substrate/catalyst ratio). A mechanism for the promoting effect of ZnCl₂ on the catalytic system has been proposed on the basis of NMR spectroscopy and HRMS studies. This method was successfully applied to the asymmetric syntheses of three important drugs, (<italic>S</italic>)‐duloxetine, (<italic>R</italic>)‐fluoxetine, and (<italic>R</italic>)‐atomoxetine, in high yields and with excellent enantioselectivities.</p> </abstract>