Transition metal-catalyzed C(sp2/sp3)–H α-fluoroalkenylation from gem-(bromo/di)fluoroalkenes to monofluoroalkenes: scope, mechanisms, and synthetic applications

Abstract

Organofluorines have a broad range of industrial applications, such as pharmaceuticals, liquid crystal displays (LCDs), solar cells, textiles, and construction coatings, and are used in peptidomimetics, surfactants, refrigerants, anesthetics, and agrochemicals. Among them are versatile monofluoroalkenes that play a crucial role in medicinal and synthetic chemistry. The synthetic strategies for this class of molecules are limited, and prior efforts frequently suffered from poor atom- and step-economies. As a surrogate pathway for traditional cross-coupling transformations, transition metal (TM)-catalyzed C–H direct α-fluoroalkenylation overcomes these obstacles and provides straightforward techniques to access monofluoroalkenes. Nevertheless, substrate scope is still a challenge for catalysis, where gem-bromofluoroalkene synthons are applicable with electronically biased substrates such as azoles, while gem-difluoroalkene-based strategies are limited to substrates containing N-based directing groups. Herein, we review the cutting-edge fluoroalkenylation research for direct synthesis of monofluoroalkenes achieved during the last decade (2013–2023). This review is divided into two main parts: the first part discusses TM-catalyzed direct α-fluoroalkenylation via the merging of C–H activation and C(sp²)–Br cleavage strategies using gem-bromofluoroalkenes, and the second part describes the same reaction, albeit with C(sp²)–F cleavage of highly explored gem-difluoroolefins. Our review surveys all previously reported monofluoroalkenes in this research area, including their preparation techniques, stereoselectivity, and yield percentages. Furthermore, optimal conditions, reactant scope, mechanistic investigations, synthetic applications, benefits, and drawbacks of each presented methodology are critically discussed.