Catalyzed by a rhodium complex of P-stereogenic diphosphine ligand (R)-2-tert-butylmethylphosphino-3-(di-tert-butylphosphino)quinoxaline ((R)-3H-QuinoxP*), five-membered cyclic α-dehydroamino ketones bearing endocyclic vinyl and endocyclic keto-carbonyl groups were sequentially hydrogenated to give chiral cyclic trans-β-amino alcohols with two contiguous stereocenters in quantitative conversions, excellent enantioselectivities and good diastereoselectivities.
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.
Enantioselective protonation by hydrophosphinylation of diarylphosphine oxides with 2-vinyl azaheterocycle Noxide derivatives was demonstrated using chiral bis(guanidino)iminophosphorane as the higher-order organosuperbase catalyst. It was confirmed by several control experiments that ac hiral weak conjugate acid of the chiral bis(guanidino)iminophosphorane,i nstead of achiral diarylphosphine oxides, directly functioned as the proton source to affordt he corresponding product in ahighly enantioselective manner in most cases.E nantioselective protonation by aw eak conjugate acid generated from the higher-order organosuperbase would broaden the scope of enantioselective reaction systems because of utilization of ar ange of less acidic pronucleophiles.T his method is highlighted by the valuable synthesis of as eries of chiral P, N-ligands for chiral metal complexes through the reduction of phosphine oxide and N-oxide units of the corresponding product without loss of enantiomeric purity. Figure 1. Chiral bis(guanidino)iminophosphoranes (M)-1 and corresponding conjugatea cid [(M)-1•H] + .
Catalyzed by a rhodium complex of P-stereogenic diphosphine trichickenfootphos, five-membered cyclic α-dehydroamino ketones bearing endocyclic acyl and endocyclic vinyl groups were hydrogenated to give chiral α-amino ketones with quantitative conversions and excellent enantioselectivities.
2-Benzylpyridine N-oxides possessing less acidic α-protons were utilized as pronucleophiles for the first time in enantioselective addition reactions under Brønsted base catalysis.
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