Direct Carbon−Carbon Bond Formation via Soft Enolization: A Biomimetic Asymmetric Mannich Reaction of Phenylacetate Thioesters

• Published in: Organic letters Vol. 12; no. 15; pp. 3376 - 3379
• Main Authors: Kohler, Mark C, Yost, Julianne M, Garnsey, Michelle R, Coltart, Don M
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 06.08.2010; Amer Chemical Soc
• Subjects: Amines - chemistry; Carbon - chemistry; Catalysis; Chemistry; Chemistry, Organic; Cinchona Alkaloids - chemistry; Combinatorial Chemistry Techniques; Esters; Molecular Structure; Phenylacetates - chemistry; Physical Sciences; Science & Technology; Sulfur Compounds - chemistry; MICHAEL REACTION; HALF-THIOESTERS; TRIFLUOROETHYL THIOESTERS; DIRECT ALDOL ADDITION; BAYLIS-HILLMAN REACTION; CITRATE SYNTHASE; POLYKETIDE SYNTHASES; INTRAMOLECULAR REACTIONS; BIFUNCTIONAL ORGANOCATALYSTS; GROUP PARTICIPATION
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol101152b

An asymmetric Mannich reaction of phenylacetate thioesters and sulfonylimines using cinchona alkaloid-based amino (thio)urea catalysts is reported that employs proximity-assisted soft enolization. This approach to enolization is based on the cooperative action of a carbonyl-activating hydrogen bonding (thio)urea moiety and an amine base contained within a single catalytic entity to facilitate intracomplex deprotonation. Significantly, this allows thioesters over a range of acidity to react efficiently, thereby opening the door to the development of a general mode of enolization-based organocatalysis of monocarboxylic acid derivatives.