3-Pyrrolidinecarboxylic Acid for Direct Catalytic Asymmetric anti-Mannich-Type Reactions of Unmodified Ketones

Haile Zhang, Maria Mifsud, Fujie Tanaka,* and Carlos F. Barbas, III*;
The Skaggs Institute for Chemical Biology and the Departments of Chemistry and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037
J. Am. Chem. Soc., 2006, 128 (30), pp 9630–9631
DOI: 10.1021/ja062950b
Publication Date (Web): July 11, 2006
Copyright © 2006 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, ftanaka@scripps.edu, ; , carlos@scripps.edu

Abstract

Abstract Image

We report the development of direct catalytic, enantioselective, anti-selective Mannich-type reactions between unmodified ketones and α-imino esters under mild conditions. The reactions were performed using 5−10 mol % of (R)-3-pyrrolidinecarboxylic or (R)-β-proline as catalyst in an environmentally benign solvent, 2-PrOH, at room temperature. The anti-Mannich products were obtained in good yields with high diastereo- and enantioselectivities (up to anti/syn >99:1, 99% ee). While (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid is an excellent catalyst for the anti-Mannich-type reactions of aldehydes, it did not efficiently catalyze the corresponding Mannich-type reactions of ketones; (R)-3-pyrrolidinecarboxylic acid did efficiently catalyze the Mannich-type reactions of ketones. (S)-Proline or (S)-2-pyrrolidinecarboxylic acid has been reported to catalyze the Mannich-type reactions of ketones to afford the syn-products. Thus, the position of the carboxylic acid group on the pyrrolidine ring directs the stereoselection of the catalyzed reaction, providing either syn- or anti-Mannich products.

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History

  • Published In Issue August 02, 2006
  • Received April 27, 2006

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