Miro, Javier Gensch, Tobias Ellwart, Mario Han, Seo-Jung Lin, Hsin-Hui Sigman, Matthew S. Toste, F. Dean 2024-01-19T18:01:11Z 2024-01-19T18:01:11Z 2021-09-04 2020-04 0002-7863 https://pubs.kist.re.kr/handle/201004/118826 Herein we report the first highly enantioselective allenoate-Claisen rearrangement using doubly axially chiral phosphate sodium salts as catalysts. This synthetic method provides access to beta-amino acid derivatives with vicinal stereocenters in up to 95% ee. We also investigated the mechanism of enantioinduction by transition state (TS) computations with DFT as well as statistical modeling of the relationship between selectivity and the molecular features of both the catalyst and substrate. The mutual interactions of charge-separated regions in both the zwitterionic intermediate generated by reaction of an amine to the allenoate and the Na+-salt of the chiral phosphate leads to an orientation of the TS in the catalytic pocket that maximizes favorable noncovalent interactions. Crucial arene-arene interactions at the periphery of the catalyst lead to a differentiation of the TS diastereomers. These interactions were interrogated using DFT calculations and validated through statistical modeling of parameters describing noncovalent interactions. English American Chemical Society Enantioselective Allenoate-Claisen Rearrangement Using Chiral Phosphate Catalysts Article 10.1021/jacs.0c01637 1 Journal of the American Chemical Society, v.142, no.13, pp.6390 - 6399 Journal of the American Chemical Society 142 13 6390 6399 N scie scopus 000526393700059 2-s2.0-85083655039 Chemistry, Multidisciplinary Chemistry Article NONCOVALENT INTERACTIONS BASIS-SETS ACID SELECTIVITY ACTIVATION PROGRAM MODE