A C=O⋅⋅⋅Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols. Issue 12 (19th February 2018)

• Record Type: Journal Article
• Authors: 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 Ha‐Yeon; Smith, Andrew D.
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 12(2018)
• Page Start: 3200
• Page End: 3206
• Publication Date: 2018-02-19
• Subjects: acylation -- kinetic resolution -- Lewis bases -- organocatalysis -- tertiary alcohols; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201712456
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : Test your resolve : Experimental and computational studies have identified a C=O⋅⋅⋅isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols with up to three potential recognition motifs at the stereogenic tertiary carbinol center. The kinetic resolution of a range of such alcohols was achieved with an isothiourea catalyst and either isobutyric or acetic anhydride.