The proline-catalyzed direct asymmetric three-component Mannich reaction: scope, optimization, and application to the highly enantioselective synthesis of 1,2-amino alcohols.
We have developed proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines. Several of the studied reactions provide beta-amino carbonyl compounds (Mannich products) in excellent enantio-, diastereo-, regio-, and chemoselectivities. The scope of each of the three components and the influence of the catalyst structure on the reaction are described. Reaction conditions have been optimized, and the mechanism and source of asymmetric induction are discussed. We further present application of our reaction to the highly enantioselective synthesis of 1,2-amino alcohols.
List
Benjamin
B
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. blist@scripps.edu
Pojarliev
Peter
P
Biller
William T
WT
Martin
Harry J
HJ
D000447:Aldehydes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000605:Amino Alcohols / Q000737:chemistry*; D002384:Catalysis; D007659:Ketones / Q000737:chemistry; D008352:Mannich Bases / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D000447:Aldehydes; D000588:Amines; D000605:Amino Alcohols; D007659:Ketones; D008352:Mannich Bases; D011392:Proline