title: N-heterocyclic carbene-catalyzed enantioselective Mannich reactions with alpha-aryloxyacetaldehydes.
abstract: N-Heterocyclic carbenes (NHCs) catalyze a new Mannich-type reaction to form beta-amino acid derivatives in high yield and enantioselectivity. The reaction is initiated by the addition of an NHC to an alpha-aryloxyaldehyde followed by elimination of a phenoxide anion which generates an enol/enolate. A Mannich addition to a tosylimine proceeds with excellent control over enantioselectivity. In a new carbene catalysis concept, catalyst regeneration is promoted by return, or rebound, and acylation of the phenoxide group which served as the activating component in the first step of the catalytic cycle. The activated ester products formed in situ are manipulated to form a variety of useful compounds including beta-amino acids, beta-amino amides, and peptides.
authors.affiliation: Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Chemistry of Life Processes Institute, Silverman Hall, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kawanaka
authors.forename: Eric M
authors.initials: EM
authors.lastname: Phillips
authors.forename: Karl A
authors.initials: KA
authors.lastname: Scheidt
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry*; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008352:Mannich Bases; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000588:Amines; D004952:Esters; D006571:Heterocyclic Compounds; D008352:Mannich Bases; C030011:carbene; D000079:Acetaldehyde; D008697:Methane