Iron-catalysed reductive coupling for the synthesis of polyfluorinated compounds

Abstract

Iron-catalysed reductive cross-coupling of difluorobromo acetic acid derivatives with trifluoromethyl olefins to afford polyfluorinated molecules, containing a difluorenyl and difluoroalkyl group, with a broad substrate scope.

Transition-Metal-Free Hydrodefluoroamination of Trifluoromethyl Enones for the Synthesis of α-Fluoroenamides

“…Based on mechanistic verification experiments and literature reports, − a plausible reaction mechanism is depicted in Scheme . Initially, the selective defluorinative multihydrogenation of β-CF 3 -enones with PhSiH 3 occurs through a sequence of carbonyl reduction (via OH-containing trifluoromethyl alkene A ) and downstream hydrodefluorination (via intermediate B ), leading to hydroxyl-containing gem -difluoroalkene C (pathway a).…”

“…Readily available α-trifluoromethyl alkenes have been demonstrated as robust and ideal substrates for the construction of oligofluorinated or nonfluorinated skeletons with structural diversity and complexity . Consequently, diverse gem -difluoroalkenes, allyl fluorides, and monofluorinated heterocycles become easily accessible through γ- or ipso -selective cleavage of a single C–F bond and a sequential two-fold C–F bond activation procedure (Scheme A). However, intermolecular three-component approaches for multifunctionalization of CF 3 -alkenes by activating the CF 3 group, concomitant with the attached π-system have not been thoroughly established, despite that such a strategy facilitates the straightforward synthesis of privileged fluorine-containing derivatives, which is highly attractive (Scheme B).…”

Nickel-catalysed highly regioselective synthesis of β-acyl naphthalenes under reductive conditions

“…Based on the above experiments and literature reports, 9–12 a plausible reaction mechanism is proposed (Scheme 6). Initially, the active Ni(0) A was generated under Zn reductive conditions, followed by oxidative addition with benzoyl chloride to form nickel( ii ) species B .…”

“…9 Inspired by these elegant examples, we envisioned that the regioselective synthesis of β-acyl naphthalenes could be achieved through cross ring-opening reaction of 7-oxabenzonorbornadienes with acyl chlorides and subsequent aromatization processes, via semi preparation of the naphthalene pathway. With our continuous interest 10 in transition metal promoted cross-electrophile coupling under reductive conditions, 11,12 herein we disclose a nickel-catalysed reductive coupling of 7-oxabenzonorbornadienes with acyl chlorides for the synthesis of β-acyl naphthalenes (Scheme 1c). Salient features of our findings include (a) highly regioselective formation of β-acyl naphthalenes without any α isomers; (b) an interesting semi synthesis of naphthalene protocol was employed; (c) simple and mild reaction conditions.…”

Cobalt‐Catalyzed Allylic Defluorinative Cross‐Electrophile Coupling between 1,1‐Difluoroalkyl Halides and α‐Trifluoromethyl Styrenes

“…Because gem ‐difluoroalkane moiety also plays important roles in medicinal chemistry and agrochemistry, [13] our attention was attracted to develop a reaction, which can incorporate gem ‐difluoroalkane and gem ‐difluoroalkene in one molecular motif. In this context, we addressed the challenge of the application of 1,1‐difluoroalkyl halides in the defluorinative XEC reaction with α‐trifluoromethyl styrenes through engaging cobalt‐catalysis in the assistance of zinc as a stoichiometric reductant, allowing for the efficient synthesis of diverse gem ‐difluoroalkenes bearing a difluorinated homoallylic position (Scheme 1B) [14] …”