Stereoelectronic Effects in Ligand Design: Enantioselective Rhodium‐Catalyzed Hydrogenation of Aliphatic Cyclic Tetrasubstituted Enamides and Concise Synthesis of ( R )‐Tofacitinib

We herein report the development of a conformationally defined, electron-rich, C2 -symmetric, P-chiral bisphosphorus ligand, ArcPhos, by taking advantage of stereoelectronic effects in ligand design. With the Rh-ArcPhos catalyst, excellent enantioselectivities and unprecedentedly high turnovers (TON up to 10 000) were achieved in the asymmetric hydrogenation of aliphatic carbocyclic and heterocyclic tetrasubstituted enamides, to generate a series of chiral cis-2-alkyl-substituted carbocyclic and heterocyclic amine derivatives in excellent enantiomeric ratios. This method also enabled an efficient and practical synthesis of the Janus kinase inhibitor (R)-tofacitinib.