Rh-Catalyzed One-Pot Sequential Asymmetric Hydrogenation of α‑Dehydroamino Ketones for the Synthesis of Chiral Cyclic <i>trans</i>-β-Amino Alcohols

Catalyzed by a rhodium complex of P-stereogenic diphosphine ligand (<i>R</i>)-2-<i>tert</i>-butylmethylphosphino-3-(di-<i>tert</i>-butylphosphino)­quinoxaline ((<i>R</i>)-<b>3H-QuinoxP</b>*), five-membered cyclic α-dehydroamino ketones bearing endocyclic vinyl and endocyclic keto-carbonyl groups were sequentially hydrogenated to give chiral cyclic <i>trans</i>-β-amino alcohols with two contiguous stereocenters in quantitative conversions, excellent enantioselectivities and good diastereoselectivities

Rh-Catalyzed Asymmetric Hydrogenation of Cyclic α‑Dehydroamino Ketones

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

Practical Asymmetric Hydrogenation-Based Synthesis of a Class-Selective Histone Deacetylase Inhibitor

Two syntheses of the class-selective histone deacetylase inhibitor <b>1</b> are reported. In the first, eight-step entailing synthesis, the key transformations were a highly efficient [3 + 2] dipolar cycloaddition affording <i>trans</i>-<i>rac</i>-<b>5</b> and its resolution. In the second, asymmetric approach, the key steps were a highly selective asymmetric hydrogenation to produce the <i>cis</i>-(<i>S,S</i>)-3,4-disubstituted pyrrolidine <b>18</b> followed by an amide formation with simultaneous chiral inversion of the carboxy stereocenter to generate the key intermediate <i>trans</i>-(<i>R,S</i>)-3,4-disubstituted pyrrolidine <b>19</b>. The overall yield increased from ∼6% for the resolution approach to ∼26% for the enantioselective approach