Palladium-Catalyzed Dehydrogenative Fluoroalkoxylation of Benzaldehydes

Abstract

A direct and efficient palladium-catalyzed oxidative dehydrogenative fluoroalkoxylation of benzaldehydes is reported here for the first time. The method features mild reaction conditions, good tolerance of functional groups, and a broad substrate scope. The protocol employs the transient directing group strategy, thereby avoiding the additional installation and removal of directing groups, endowing the method with great advantages of atom and step economy. The approach should find broad applications in drug synthesis and discovery processes.

Palladium-Catalyzed Weakly Coordinating Lactone-Directed C–H Bond Functionalization of 3-Arylcoumarins: Synthesis of Bioactive Coumestan Derivatives

“…On the basis of the experimental results and related literature, ,,, it is proposed that the possible mechanism for the palladium-catalyzed weakly coordinating lactone-directed C–H bond functionalization of 3-arylcoumarins might involve a Pd­(II)–Pd­(IV) redox cycle. A proposed mechanism for hydroxylation of 3-arylcoumarins is shown in Scheme .…”

“…Similarly, the reaction of 3-arylcoumarins ( 1b – e ) bearing substituents on both C3-phenyl ring as well as on the benzene ring of the coumarin scaffold reacted with TFE to afford the corresponding ortho -trifluoroethoxylated products ( 7b – i ) in moderate to good yields (54–63%) as shown in Table . The mechanism of the reaction is believed to involve a Pd­(II)/Pd­(IV) cycle …”

Transient directing group enabled Pd-catalyzed C–H oxygenation of benzaldehydes and benzylic amines

“…Based on our experiments and related literature, 3 d , k ,6–8 a putative mechanism was proposed for the palladium-catalyzed ortho -C(sp 2 )–H oxidation of benzaldehydes (Scheme 4). Benzyl amines get converted into imine intermediate by the [F + ] bystanding oxidant, which in turn could be hydrolyzed to the aldehydes.…”

“…2 While most of the achievements for TDG-mediated and Pd-catalyzed C(sp 2 )–H functionalization are restricted in C(sp 2 )–H arylation, 3 alkylation, 4 and alkenylation, 5 efforts to develop Pd-catalyzed C(sp 2 )–O and C(sp 2 )–N bond forming reactions have recently afforded new advances. 6 Recently, the seminal examples of these rare reactions, which were reported by Erik J. Sorensen and co-workers, featured the utilization of 4-chloroanthranilic acid as the bidentate transient directing group (BiTDG), and 1-fluoro-2,4,6-trimethylpyridnium triflate as the bystanding oxidant. 7 Soon after, ortho -C–H methoxylation and fluoroalkoxylation of benzaldehydes were also realized by employing monodentate directing groups 8 a and BiTDG respectively which form N , O -bis-coordinated complexes with Pd( ii ) catalyst and promote the C–H activation process.…”

Transient Directing Groups in Metal−Organic Cooperative Catalysis

“…As a note, the group of Wang further extended this process to the perfluoroalkoxylation of these substrates under similar conditions, however using L-valine as the transient directing mediator. [91] Scheme 51. Pd-catalyzed ortho-hydroxylation of benzaldehydes with p-TsOH through transient imine directing strategy with 4-chloroanthranilic acid as the transient directing mediator.…”