Secondary-sphere modification in proline catalysis: old friend, new connection. Issue 12 (19th January 2022)

• Record Type: Journal Article
• Authors: Domb, Ido; Lustosa, Danilo M.; Milo, Anat
• Is Part Of: Chemical communications. Volume 58:Issue 12(2022)
• Page Start: 1950
• Page End: 1953
• Publication Date: 2022-01-19
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d1cc05589e
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Proline catalysis sparked not only the golden age of organocatalysis, but also the design of elaborate proline derivatives; instead, we propose to modify organocatalysts in situ under reaction conditions. Abstract : In this work, we exploit our strategy of in situ secondary-sphere modification of organocatalysts to improve the reactivity and selectivity of amino catalysts. Herein, the carboxylic acid moiety of proline was targeted as a site for modification under catalytic reaction conditions with boronic acids. Intermolecular aldol reactions between aromatic aldehydes and cyclopentanone were selected as a proof-of-concept because cyclopentanone as an aldol donor was often associated with decreased selectivity compared to its 6-membered ring analog, hexanone. Our secondary-sphere modification strategy, using naturally occurring l -proline amino acid, enabled reactions at room temperature with high levels of diastereo- and enantio-selectivity and short reaction times. NMR and HR-MS studies shed light on the nature of the catalyst structure and on the role of water in our reactions.