Electronically Activated Organoboron Catalysts for Enantioselective Propargyl Addition to Trifluoromethyl Ketones

• Published in: Angewandte Chemie Vol. 129; no. 30; pp. 8862 - 8867
• Main Authors: Mszar, Nicholas W., Mikus, Malte S., Torker, Sebastian, Haeffner, Fredrik, Hoveyda, Amir H.
• Format: Journal Article
• Language: English; German
• Published: Weinheim Wiley Subscription Services, Inc 17.07.2017
• Subjects: Alcohols; Ambient temperature; Aminophenol; Aromatic compounds; Arthritis; Catalysts; Chemistry; Enantiomers; Enantioselektive Synthesen; Homopropargylalkohole; Katalyse; Ketones; Propargylgruppen; Rheumatoid arthritis; Temperature effects; Trifluormethylgruppe
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201703844

A broadly applicable, practical, scalable, efficient and highly α‐ and enantioselective method for addition of a silyl‐protected propargyl moiety to trifluoromethyl ketones has been developed. Reactions, promoted by 2.0 mol % of a catalyst that is derived in situ from a readily accessible aminophenol compound at ambient temperature, were complete after only 15 minutes at room temperature. The desired tertiary alcohols were isolated in up to 97 % yield and 98.5:1.5 enantiomeric ratio. Alkyl‐, alkenyl‐, alkynyl‐, aryl‐ or heteroaryl‐substituted trifluoromethyl ketones can be used. Utility is highlighted by application to a transformation that is relevant to enantioselective synthesis of BI 653048, a compound active against rheumatoid arthritis. Schnell und selektiv: Ausgestattet mit einer Trifluormethylgruppe können chirale Organoborkatalysatoren die hoch enantioselektive Addition einer Silyl‐geschützten Propargylborverbindung an verschiedenste Trifluormethylketone vermitteln. Die Nützlichkeit der Methode wird in einem Prozess demonstriert, der zur enantioselektiven Synthese des Antirheumatikums BI 653048 genutzt werden könnte.