title: ZnCl2 -promoted asymmetric hydrogenation of β-secondary-amino ketones catalyzed by a P-chiral Rh-bisphosphine complex.
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.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (P. R. China) http://wanbin.sjtu.edu.cn.
authors.forename: Qiupeng
authors.initials: Q
authors.lastname: Hu
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yangang
authors.initials: Y
authors.lastname: Liu
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Imamoto
authors.forename: Wanbin
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000586:Amination; D000605:Amino Alcohols / Q000138:chemical synthesis*; D000069445:Atomoxetine Hydrochloride; D002384:Catalysis; D002712:Chlorides / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry; D000068736:Duloxetine Hydrochloride; D005473:Fluoxetine / Q000138:chemical synthesis; D006865:Hydrogenation; D007659:Ketones / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry; D011437:Propylamines / Q000138:chemical synthesis; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism; D013876:Thiophenes / Q000138:chemical synthesis; D017967:Zinc Compounds / Q000737:chemistry*
chemical_list: D000605:Amino Alcohols; D002712:Chlorides; D056831:Coordination Complexes; D007659:Ketones; D010720:Phosphines; D011437:Propylamines; D013876:Thiophenes; D017967:Zinc Compounds; D005473:Fluoxetine; D000069445:Atomoxetine Hydrochloride; C016837:zinc chloride; D000068736:Duloxetine Hydrochloride; D012238:Rhodium; C044646:phosphine
keywords: P ligands; amino alcohols; asymmetric catalysis; hydrogen; rhodium