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Stereoelectronic Effects in Ligand Design: Enantioselective Rhodium‐Catalyzed Hydrogenation of Aliphatic Cyclic Tetrasubstituted Enamides and Concise Synthesis of ( R )‐Tofacitinib
Author(s) -
Li Chengxi,
Wan Feng,
Chen Yuan,
Peng Henian,
Tang Wenjun,
Yu Shu,
McWilliams J. Christopher,
Mustakis Jason,
Samp Lacey,
Maguire Robert J.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201908089
Subject(s) - enantioselective synthesis , chemistry , ligand (biochemistry) , catalysis , enantiomer , stereochemistry , rhodium , tofacitinib , asymmetric hydrogenation , amine gas treating , imine , combinatorial chemistry , organic chemistry , receptor , rheumatoid arthritis , medicine , biochemistry
We herein report the development of a conformationally defined, electron‐rich, C 2 ‐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.
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