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.
|Number of pages||7|
|Journal||Journal of the American Chemical Society|
|Publication status||Published - 2021 Jan 13|
Bibliographical noteFunding Information:
This work was supported by 1) the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2018R1C1B6005712), 2) the Yonsei University Future-leading Research Initiative of 2018 (22-0055), and 3) the POSCO Cheongam Foundation (Fellowship to S.Y.L.). We thank Yuna Song for assistance. S.Y.L. thanks Dr. Taegyo Lee (Pfizer) for helpful discussions.
© 2020 American Chemical Society.
All Science Journal Classification (ASJC) codes
- Colloid and Surface Chemistry