Catalytic Asymmetric Alkylations of Ketoimines. Enantioselective Synthesis of N-Substituted Quaternary Carbon Stereogenic Centers by Zr-Catalyzed Additions of Dialkylzinc Reagents to Aryl-, Alkyl-, and Trifluoroalkyl-Substituted Ketoimines
- 1 April 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 130 (16) , 5530-5541
- https://doi.org/10.1021/ja8001343
Abstract
Catalytic enantioselective alkylations of three classes of ketoimines are reported. Reactions are promoted in the presence 0.5–10 mol % of a Zr salt and a chiral ligand that contains two inexpensive amino acids (valine and phenylalanine) and involve Me2Zn or Et2Zn as alkylating agents. Requisite aryl- and alkyl-substituted α-ketoimine esters, accessed readily and in >80% yield on gram scale through a two-step sequence from the corresponding ketones, undergo alkylation to afford quaternary α-amino esters in 79–97% ee. Aryl-substituted trifluoroketoimines are converted to the corresponding amines by reactions with Me2Zn, catalyzed by a chiral complex that bears a modified N-terminus. The utility of the catalytic asymmetric protocols is illustrated through conversion of the enantiomerically enriched alkylation products to a range of cyclic and acyclic compounds bearing an N-substituted quaternary carbon stereogenic center.Keywords
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