Chromium-Catalyzed Allylic Defluorinative Ketyl Olefin Coupling

Abstract

Herein we report a chromium-catalyzed allylic defluorinative ketyl olefin coupling between aldehydes and α-trifluoromethyl alkenes, which provides novel and efficient access to diverse gem-difluorohomoallylic alcohols. Remarkably, the high chemoselectivity of this reaction enables the conversion of the formyl moiety in the presence of various easily reducible functionalities including ketone, organohalides, aziridine, sulfone, alkyne, and unactivated alkene. The utility of this method is demonstrated by various simple derivatizations of the attached hydroxyl group of the coupling products. The preliminary mechanistic investigations suggest a reaction pathway with a rate-limiting C–C forming step followed by facile β-fluoro elimination.

Recent Advances in the Synthesis of Difluorinated Architectures from Trifluoromethyl Groups

“…[50] Recently, Wang's group envisaged a method of allylic monodefluorinative ketyl olefin coupling between aldehydes 143 and αtrifluoromethylalkenes 142 to provide a convenient path to a variety of gem-difluorohomoallylic alcohols 144 with high efficiency and chemoselectivity in the presence of Zn and TMSCl (Scheme 32). [51] Under optimal reaction conditions, various easily reducible functional units, including ketones, alkynes, alkenes, aziridines, sulfones, and halides, remain intact. Compared with the aforementioned Ni-catalyzed reports, this unique allylic defluorinative coupling reaction proceeded by harnessing Cr as the sole catalyst.…”

Enantioselective nickel-catalyzed dicarbofunctionalization of 3,3,3-trifluoropropene

“…Because such a strategy can simultaneously form two new carbon-carbon bonds and generate one new α-CF 3 stereogenic center without tedious synthetic procedure, thereby providing an attractive opportunity to diversely construct complex chiral trifluoromethylated structures. However, this process is plagued by the high tendency of β-H 38 – 40 and β-F 39 – 43 eliminations from the resulting α-CF 3 alkyl-metal intermediate (Fig. 1b ).…”

Synthesis of Five-Membered Ring Systems Bearing gem-Difluoroalkenyl and Monofluoroalkenyl Substituents via Radical β-Bromo Fragmentation

“…Recently, S N 2′-type, − transition-metal-catalyzed, − and photocatalytic − defluorofunctionalizations of α-trifluoromethyl alkenes or gem -difluoroalkenes have been extensively explored to construct fluoroalkenes (Figure a); these methods consist of β-fluoride anion fragmentation as a key step. In the cases of photocatalyzed defluorofunctionalizations of α-trifluoromethyl alkenes, α-CF 3 alkyl radicals generated via the addition of alkyl, − acyl, or boryl radicals to α-CF 3 alkenes are further SET reduced by the photocatalyst to afford carbanion intermediates, which then engage in ionic β-fluoride fragmentation to eventually afford the targeted gem -difluoroalkene moieties (Figure b).…”