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