Stereodivergent Carbon-Carbon Bond Formation between Iminium and Enolate Intermediates by Synergistic Organocatalysis

• Published in: Journal of the American Chemical Society 2021-01, Vol.143 (1), p.73-79
• Main Authors: Kim, Byungjun, Kim, Yongjae, Lee, Sarah Yunmi
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.0c11077

We report here a stereodivergent method for the Michael addition of aryl acetic acid esters to α,β-unsaturated aldehydes catalyzed by a combination of a chiral pyrrolidine and a chiral Lewis base. This reaction proceeds through a synergistic catalytic cycle which consists of one cycle leading to a chiral iminium electrophile and a second cycle generating a nucleophilic chiral enolate for the construction of a carbon-carbon bond. By varying the combinations of catalyst enantiomers, all four stereoisomers of the products with two vicinal stereocenters are accessible with high enantio- and diastereoselectivity. The products of the Michael addition, 1,5-aldehyde esters, can be readily transformed into a variety of other valuable enantioenriched structures, including those bearing three contiguous stereocenters in an acyclic system, thus providing an efficient route to an array of structural and stereochemical diversity.