Stereoelectronic Effects in Ligand Design: Enantioselective Rhodium‐Catalyzed Hydrogenation of Aliphatic Cyclic Tetrasubstituted Enamides and Concise Synthesis of ( R )‐Tofacitinib
| Autor: | Feng Wan, Yuan Chen, Shu Yu, Chengxi Li, J. Christopher McWilliams, Henian Peng, Wenjun Tang, Lacey Samp, Jason Mustakis, Robert John Maguire |
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| Rok vydání: | 2019 |
| Předmět: |
Stereoelectronic effect
chemistry.chemical_element Ligands 010402 general chemistry 01 natural sciences Catalysis Rhodium Piperidines Pyrroles chemistry.chemical_classification 010405 organic chemistry Chemistry Ligand Asymmetric hydrogenation Enantioselective synthesis Stereoisomerism General Medicine General Chemistry Combinatorial chemistry 0104 chemical sciences Pyrimidines Heterocyclic amine Hydrogenation Enantiomer |
| Zdroj: | Angewandte Chemie International Edition. 58:13573-13583 |
| ISSN: | 1521-3773 1433-7851 |
| DOI: | 10.1002/anie.201908089 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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