フェニルビスオキサゾリンロジウム（III）錯体を用いたα-ケトエステルおよびα-ケチミノエステルに対する直接的触媒的不斉アルキニル化反応の開発

<p>Direct catalytic enantioselective alkynylation of carbonyl compounds and imines is one of the most efficient approaches for the synthesis of propargylic alcohols and propargylamines, which are potent building blocks for synthesizing functionalized molecules. While a variety of methods for the reactions with aldehydes and aldimines have been established, the reactions with ketones and ketimines remain underdeveloped due to their reduced reactivity and difficulty in stereocontrol. In this account, we summarized our studies on direct enantioselective alkynylation reaction of α-ketoester and α-ketiminoesters catalyzed by phenylbis(oxazoline)(phebox)-rhodium(III) complexes, affording enantioenriched propargyl alcohols and propargylamines with a tetrasubstituted carbon stereocenter under proton-transfer conditions. The catalytic system was compatible to a wide range of functional groups, including electrophilic formyl groups, and allowed for the development of an efficient method to access enantioenriched α-CF₃-substituted thalidomide analogs. Mechanistic studies revealed that generation of the (alkynyl)(phebox)Rh(III) complex from the (diacetato)(phebox)Rh(III) complex determined the overall reaction rate in the initial stages of the reaction. These results, along with the observed facile exchange of the alkynyl ligand on the (alkynyl)(phebox)Rh(III) complexes, led us to use (trimethylsilylethynyl)(phebox)Rh(III) complexes as a new pre-catalyst. The new catalytic system with (trimethylsilylethynyl)(phebox)Rh(III) precatalysts exhibited enhanced catalytic performance, reduced catalyst loading to as low as 0.5 mol%, and expanded the substrate scope of the reaction with less reactive α-ketiminophosphonate and cyclic <i>N</i>-sulfonyl α-ketiminoesters.</p>