A general protocol for efficient construction of perfluoro-tert-butyl alkynes with (perfluoro-tert-butyl)propiolic acid

Abstract

The perfluoro-tert-butyl group (PFtB) stands out, in part, due to its unparalleled analytical capabilities, as an indispensable functional group for sensing and imaging within biological systems. Although previously we have accomplished the introduction of the perfluoro-tert-butyl group into sp³-and sp²-carbons, the perfluoro-tert-butylation of sp-carbon remains a challenging task. In this study, we develop a versatile method to construct structurally diverse PFtB-substituted alkynes, utilizing (perfluoro-tert-butyl)propiolic acid (PFtPA) as a new reagent. PFtPA is easy to synthesize and can undergo Pd/Cu-catalyzed decarboxylative coupling with a wide array of (aryl, alkyl, alkenyl, and alkynyl) halides and triflates. This synthetic protocol is not only high-yielding but also compatible with various functional groups. Furthermore, we demonstrate the potential of this new synthetic protocol by developing a ¹⁹F-labeled probe that is proficient in distinguishing analytes with distal chiral centers.