ZnCl2‐Promoted Asymmetric Hydrogenation of β‐Secondary‐Amino Ketones Catalyzed by a P‐Chiral Rh–Bisphosphine Complex |
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| Authors: | Qiupeng Hu Dr Zhenfeng Zhang Prof Yangang Liu Prof Tsuneo Imamoto Prof Wanbin Zhang |
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| Affiliation: | 1. School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (P. R. China) http://wanbin.sjtu.edu.cn;2. Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263‐8522 (Japan);3. School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (P. R. China) |
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| Abstract: | 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, (S)‐duloxetine, (R)‐fluoxetine, and (R)‐atomoxetine, in high yields and with excellent enantioselectivities. |
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| Keywords: | amino alcohols asymmetric catalysis hydrogen P ligands rhodium |
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