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Chiral γ-Amino Amide Synthesis by Heterobimetallic Lanthanum/Lithium/Pybox-Catalyzed Direct Asymmetric Mannich-Type Reactions of α-Keto Anilides


  • This work was supported by Grant-in-Aid for Specially Promoted Research, the Sumitomo Foundation, and partially by Grant-in-Aid for Scientific Research on Priority Areas (No. 20037010, Chemistry of Concerto Catalysis). H.M. thanks JSPS Fellowship for Young Scientists. We thank Prof. J. C. Carretero and Dr. R. Gómez Arrayás for their helpful advice on imine synthesis.pybox=pyridine bisoxazoline


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Not so Mannich now: A heterobimetallic La/Li/pybox complex was key in direct catalytic asymmetric Mannich-type reactions, using α-keto anilides as synthetic homoenolate equivalents to afford γ-amino amide products in up to >99 % yield, 95 % ee, and >97:3 syn-selectivity. Stereoselective reduction of the α-keto moiety afforded the β-alkyl-γ-amino-α-hydroxy amide with three contiguous stereocenters (PG=protecting group).