Highly Diastereoselective [3 + 2] Cycloaddition of Aziridines with Difluorinated Silyl Enol Ethers: Divergent Synthesis of 4,4-Difluoropyrrolidines and 4-Fluoropyrroles

Abstract

A highly diastereoselective [3 + 2] cycloaddition of aziridines with difluorinated silyl enol ethers has been developed. This approach provides a facile methodology for highly functionalized gem-difluorinated pyrrolidines in good to excellent yields with good functional group tolerance. A one-pot, two-step approach for synthesis of structurally interesting fluorinated pyrroles has also been developed through a cycloaddition/ aromatization/desulfonation sequence. Moreover, readily available substrates, mild reaction conditions, and easy scale-up synthesis show practical advantages.

gem-Difluoroalkylation of Cyclic Ethers Enabled by Cobalt-Catalyzed C(sp3)–H Oxidation under Mild Conditions

“…Difluoro enol silyl ethers are readily available and environmentally benign difluoroalkylation reagents, which have been widely employed in different types of chemical transformations, such as ionic condensation reactions, cross-coupling reactions, and radical-promoted reactions, allowing for the synthesis of diverse fluorinated compounds. As an extension of our work on the synthesis of pharmaceutically significant difluoro-containing compounds utilizing difluoroenoxysilanes, we herein reported an efficient and direct C–H oxidation/ gem -difluorination reaction of readily available cyclic ethers with difluoroenoxysilanes using a cobalt complex as the catalyst and molecular oxygen as the oxidant (Scheme c).…”