Efficient Access to Multifunctional Trifluoromethyl Alcohols through Base‐Free Catalytic Asymmetric C−C Bond Formation with Terminal Ynamides

Abstract

The asymmetric addition of terminal ynamides to trifluoromethyl ketones with a readily available chiral zinc catalyst gives CF3‐substituted tertiary propargylic alcohols in up to 99 % yield and 96 % ee. The exclusion of organozinc additives and base as well as the general synthetic utility of the products are key features of this reaction. The value of the β‐hydroxy‐β‐trifluoromethyl ynamides is exemplified by selective transformations to chiral Z‐ and E‐enamides, an amide, and N,O‐ketene acetals. The highly regioselective hydration, stereoselective reduction, and hydroacyloxylation reactions proceed with high yields and without erosion of the ee value of the parent β‐hydroxy ynamides.

Dinuclear Metal‐ProPhenol Catalysts: Development and Synthetic Applications

“…In 2016, Wolf and co‐workers reported the asymmetric addition of terminal ynamides 118 to an array of trifluoromethyl aryl ketones 117 catalyzed by Zn‐ProPhenol (Scheme ) . In contrast to previous publications, Zn(OTf) 2 was utilized to generate the active catalyst, suggesting that the Zn‐ProPhenol system was only acting as a Lewis acid in this transformation.…”

Organocatalytic Decarboxylative Cyanomethylation of Difluoromethyl and Trifluoromethyl Ketones

“…In recent years, we have developed an interest in catalytic nucleophilic addition reactions with trifluoromethyl ketone substrates. [14] We now report the first organocatalytic decarboxylative cyanomethylation of trifluoromethyl and difluoromethyl ketones. This method is applicable to aromatic and aliphatic substrates, operationally simple and it avoids the previously prevailing problem with concurrent water elimination (Scheme 1).…”

Zweikernige Metall‐ProPhenol‐Katalysatoren: Entwicklung und Anwendungen in der Synthese

“…Im Jahr 2016 berichteten Wolf und Mitarbeiter über die Zn‐ProPhenol‐katalysierte asymmetrische Addition terminaler Inamide 118 an eine Anzahl von Aryltrifluormethylketonen 117 (Schema ) . Anders als bei früheren Veröffentlichungen hat man den aktiven Katalysator aus Zn(OTf) 2 hergestellt, was den Schluss zulässt, dass das Zn‐ProPhenol‐System bei dieser Umwandlung lediglich als Lewis‐Säure agiert.…”