Ag-Catalyzed Asymmetric Mannich Reactions of Enol Ethers with Aryl, Alkyl, Alkenyl, and Alkynyl Imines
Nathan S. Josephsohn, Marc L. Snapper and Amir H. Hoveyda*
*Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut
Hill, Massachusetts 02467, Email: amir.hoveyda
bc.edu
N. S. Josephsohn, M. L. Snapper, A. H. Hoveyda, J. Am. Chem. Soc., 2004, 126, 3734-3735.
DOI: 10.1021/ja049388e
Abstract
An efficient catalytic and enantioselective method for Mannich reactions between trimethylsilyl enol ethers derived from acetone and acetophenone and aryl, alkenyl, alkynyl, and alkyl imines allows the synthesis of a various β-amino ketones in the presence of 1-5 mol % AgOAc and an inexpensive amino acid-derived phosphine.
see article for more examples
Details
The document discusses the development of a general Ag-catalyzed asymmetric method for the addition of silyl enol ethers to various imines, resulting in the efficient production of β-amino ketones with high optical purity (up to >98% ee). The method utilizes 1-5 mol % of AgOAc and iso-Leu-derived phosphine 1, and can be performed with undistilled solvents and in air. The reactions are effective with aryl, alkyl, alkenyl, and alkynyl imines, and the resulting β-amino ketones can be converted to amides or amines. The utility of this method is demonstrated through the enantioselective synthesis of the alkaloid sedamine. The study highlights the efficiency and versatility of the Ag-catalyzed protocol, which can be applied to a wide range of imines and silyl enol ethers, making it valuable for the synthesis of biologically active molecules. The document also includes detailed experimental results, showing high yields and enantioselectivities for various substrates, and outlines the potential for further development and application of this catalytic asymmetric Mannich reaction.
Key Words
Mannich reaction, β-amino ketones, multicomponent reactions
ID: J48-Y2004-1450
