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A C=O⋅⋅⋅Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols
Author(s) -
Greenhalgh Mark D.,
Smith Samuel M.,
Walden Daniel M.,
Taylor James E.,
Brice Zamira,
Robinson Emily R. T.,
Fallan Charlene,
Cordes David B.,
Slawin Alexandra M. Z.,
Richardson H. Camille,
Grove Markas A.,
Cheong Paul HaYeon,
Smith Andrew D.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201712456
Subject(s) - stereocenter , kinetic resolution , chemistry , acetic anhydride , catalysis , combinatorial chemistry , organic chemistry , enantioselective synthesis
A combination of experimental and computational studies have identified a C=O⋅⋅⋅isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea‐catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200). The reaction proceeds at low catalyst loadings (generally 1 mol %) with either isobutyric or acetic anhydride as the acylating agent under mild conditions.