Palladium‐Catalyzed Defluorinative Coupling of Difluoroalkenes and Aryl Boronic Acids for Ketone Synthesis

Abstract

The transition‐metal‐catalyzed carbonylation reaction is a useful approach for ketone synthesis. However, it is often problematic to use exogenous carbonyl reagents, such as gaseous carbon monoxide. In this manuscript, we report a novel palladium‐catalyzed coupling reaction of gem‐difluoroalkenes and aryl boronic acids that yields bioactive indane‐type ketones with an all‐carbon α‐quaternary center. Characterization and stoichiometric reactions of the key intermediates RCF2PdII support a water‐induced defluorination and cross‐coupling cascade mechanism. The vinyl difluoromethylene motif serves as an in situ carbonyl precursor which is unprecedented in transition‐metal‐catalyzed coupling reactions. It is expected to raise broad research interest from the perspectives of ketone synthesis, fluoroalkene functionalization, and rational design of new synthetic protocols based on the unique reactivity of difluoroalkyl palladium(II) species.

Rhodium‐Catalyzed Enantioselective 1,4‐Oxyamination of Conjugated gem‐Difluorodienes via Coupling with Carboxylic Acids and Dioxazolones

“…This product is likely generated from an oxyamination‐hydrolysis pathway. Thus, ( E )‐4‐aminobut‐2‐enoates were isolated in good yields under these modified reaction conditions ( 63 – 65 , Scheme 3), which offered a new strategy to yield a range of racemic γ‐amino α, β‐unsaturated carboxylic acid esters [22] . The asymmetric version of this reaction, however, failed after extensive attempts.…”

Synthesis of Dihydropyrazoles via Palladium‐Catalyzed Cascade Heterocyclization/Carbonylation/Arylation of β,γ‐Unsaturated N‐Tosyl Hydrazones

“…Further screening demonstrated that employing DMF as solvent further increased the efficiency of the reaction resulting in a 78% yield of 3 a (Table 1, entries 13-21). [14] Aiming to reduce the degradation of boronic acid species, we tested the slow release of the boronic acid precursor using protected groups such as the pinacol ester, [11][12] but no reaction was observed (Table 1, entry 22). Additional assessment of the reaction conditions including the use of H 2 O as an additive, or variation of the oxidant source did not lead to improved yields (Table S2, ESI).…”

“…At this stage, a variety of bases were evaluated (Table 1, entry 9–13) revealing that carbonates – p K a around 10 [13] – were most effective with the use of a Zn‐counterion leading to the highest observed yield. Further screening demonstrated that employing DMF as solvent further increased the efficiency of the reaction resulting in a 78% yield of 3 a (Table 1, entries 13–21) [14] . Aiming to reduce the degradation of boronic acid species, we tested the slow release of the boronic acid precursor using protected groups such as the pinacol ester, [11–12] but no reaction was observed (Table 1, entry 22).…”

Palladium-Catalyzed [3 + 2] Annulation of ortho-Substituted Iodoarenes with Maleimides via a Consecutive Double Heck-type Strategy

“…. 54 An oven-dried 100 mL round-bottom flask equipped with a stir bar was charged with 2-iodobenzaldehyde (462 mg, 2.0 mmol) and acetophenone (240 mg, 1.0 mmol) in ethanol (10 mL). To the solution was added NaOH (60 mg, 1.5 mmol) at 0 °C.…”