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Electronically Activated Organoboron Catalysts for Enantioselective Propargyl Addition to Trifluoromethyl Ketones.

ABSTRACT: A broadly applicable, practical, scalable, efficient and highly ?- 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.

SUBMITTER: Mszar NW

PROVIDER: S-EPMC5535737 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Electronically Activated Organoboron Catalysts for Enantioselective Propargyl Addition to Trifluoromethyl Ketones.

Mszar Nicholas W NW Mikus Malte S MS Torker Sebastian S Haeffner Fredrik F Hoveyda Amir H AH

Angewandte Chemie (International ed. in English) 20170621 30

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-, alk ...[more]

PMID: 28560721

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