Palladium‐Catalyzed Three‐Component Coupling Reaction via Benzylpalladium Intermediate

Abstract

Transition-metal catalyzed multi-component reactions have captured the attention of researchers in organic synthesis and drug synthesis due to their advantages of simple operation, easy availability of raw materials and without separation of intermediates. Among the multicomponent reactions, the three-component processes have been developed into effective organic procedures. This personal account reviews our and other group's studies on the development of three-component coupling reaction for the rapid construction of two new chemical bonds simultaneously via benzylpalladium intermediates. Catalyst-switched three-component reactions of benzyl halides, activated olefins, and allyltributylstannane were successfully conducted to produce the corresponding benzylallylation products. Activation and conversion of carbon monoxide and carbon dioxide via π-benzylpalladium intermediates provide access to a wide range of unsaturated ketones and esters with excellent functional group tolerance. Meanwhile, other methods to produce benzylpalladium intermediates, including Heck insertion of alkenes into arylpalladium complexes, the oxidative addition of benzyl carbonate to palladium complexes and palladiumÀ carbene migratory insertion, were also highlighted.

Regioselective coupling of benzyl chlorides with allyl and allenyl boronates catalysed by a bidentate phosphine ligand/palladium catalyst

“…Based on the above results and those of previous reports, 13 a plausible mechanism is proposed (Scheme 2). The oxidative addition of benzyl chloride 1a to a Pd(0) species would produce the benzylpalladium chloride intermediate A .…”

Palladium-catalyzed C–H dimethylamination of 1-chloromethyl naphthalenes with N,N-dimethylformamide as the dimethyl amino source

“…Based on the experimental results and previous reports, 12,13,17,18 a plausible mechanism for the palladium-catalyzed dimethylamination of 1-chloromethylnaphthalene derivatives with DMF is shown in Scheme 4. DMF is transformed into tert -butyl alcohol, sodium formate (confirmed by 1 H-NMR) and sodium dimethylamide in the presence of NaO t Bu and NaOH.…”

“…12 Therefore, it is a challenging task to realize regioselective dimethylamination at the aromatic ring. In the course of our continuous work on palladium-catalyzed C–H functionalization of chloromethyl aromatic rings, 13 we successfully achieved para -C–H bond dimethylamination of 1-chloromethylnaphthalene using DMF as the dimethylaminating reagent (Scheme 1b). The results are reported in the present work.…”

Synthesis of trans-stilbenes via phosphine-catalyzed coupling reactions of benzylic halides

“…Approaches to address the above challenges may include the development of new reaction pathways and the regulation of intermediate selectivity. Based on our interest in the conversion of benzylic halides, 17 herein, we report the first example of a phosphine-catalyzed coupling reaction of benzyl chlorides to generate trans -stilbenes (Scheme 1c). 18 31 P NMR tracking and HRMS analyses were used to detect the P-based key intermediates and understand the unexpected reaction processes.…”