Regio- and Enantioselective Iridium-Catalyzed Amination of Alkyl-Substituted Allylic Acetates with Secondary Amines

Woo-Ok Jung, Minjin Yoo, Madyson M. Migliozzi, Jason R. Zbieg*, Craig E. Stivala* and Michael J. Krische*

*Genentech, South San Francisco, California 94080; University of Texas, Austin, Texas 78712, United States, Email: zbieg.jasongene.com, stivala.craiggene.com, mkrischemail.utexas.edu

W.-O. Jung, M. Yoo, M. M. Migliozzy, J. R. Zbieg, C. E. Stivala, M. J. Krische, Org. Lett., 2022, 24, 441-445.

DOI: 10.1021/acs.orglett.1c04135

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Abstract

Robust air-stable cyclometalated π-allyliridium C,O-benzoates modified by (S)-tol-BINAP catalyze an enantioselective allylic amination of racemic alkyl-substituted allylic acetates with secondary aliphatic amines with high levels of enantioselectivity and complete branched regioselectivity.

see article for more examples

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General procedure

A pressure tube equipped with a magnetic stir bar was charged with Cs₂CO₃ (130.3 mg, 0.4 mmol, 200 mol%) and (S)-Ir-tol-BINAP (4.4 mg, 0.004 mmol, 2 mol%). The tube was purged with argon for 2 minutes. DME (0.2 mL, 1.0 M) or DMF (0.2 mL, 1.0 M) was added followed by the allylic acetate (0.2 mmol, 100 mol%) and the amine (0.2 mmol, 100 mol%). The tube was sealed with a PTFE lined cap and was placed in an oil bath at 30°C and stirred for 24 hours. After reaching ambient temperature, the crude reaction mixture was directly subjected to flash column chromatography.

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Regio- and Enantioselective Iridium-Catalyzed Amination of Racemic Branched Alkyl-Substituted Allylic Acetates with Primary and Secondary Aromatic and Heteroaromatic Amines

S. W. Kim, L. A. Schwartz, J. R. Zbieg, C. E. Stivala, M. J. Krische, J. Am. Chem. Soc., 2019, 141, 671-676.

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Key Words

allylic amination

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ID: J54-Y2022