Addition of in situ-generated enol silanes and zinc acetylides to nitrones mediated by trimethylsilyl trifluoromethanesulfonate

Highly electrophilic nitrone substrates show affinity for Mukaiyama-Mannich style onepot additions by ketones, amides, and thioesters in the presence of TMSOTf and a mild amine base. Aryl ketones, thioesters, and amides are readily converted to their enol silane intermediates in situ for nucleophilic addition to the nitrone acceptor. This reaction yields silylated products in high yield and purity. Zinc acetylide compounds also show promise for addition reactions to nitrones, forming new carbon-carbon bonds. Deprotection of these addition products by acid affords a cyclized 1,3-isoxazolidine product after chromatography. This simple and safe synthetic method for nitrone additions leads to the generation of a variety of biologically active organic compounds that have significance in the pharmaceutical industry