Pd(0)-Catalyzed Asymmetric Carbohalogenation: H-Bonding-Driven C(sp³)–Halogen Reductive Elimination under Mild Conditions

Abstract

Carbon−halogen reductive elimination is a conceptually novel elementary reaction. Its emergence broadens the horizons of transition-metal catalysis and provides new access to organohalides of versatile synthetic value. However, as the reverse process of facile oxidative addition of Pd(0) to organohalide, carbon−halogen reductive elimination remains elusive and practically difficult. Overcoming the thermodynamic disfavor inherent to such an elementary reaction is frustrated by the high reaction temperature and requirement of distinctive ligands. Here, we report a general strategy that employs [Et 3 NH] + [BF 4 ] − as an H-bond donor under a toluene/water/(CH 2 OH) 2 biphasic system to efficiently promote C(sp 3 )−halogen reductive elimination at low temperature. This enables a series of Pd(0)-catalyzed carbohalogenation reactions, including more challenging and unprecedented asymmetric carbobromination with a high level of efficiency and enantioselectivity by using readily available ligands. Mechanistic studies suggest that [Et 3 NH] + [BF 4 ] − can facilitate the heterolytic dissociation of halogen−Pd II C(sp 3 ) bonds via a potential H-bonding interaction to reduce the energy barrier of C(sp 3 )−halogen reductive elimination, thereby rendering it feasible in an S N 2 manner.

Recent Strategies for Carbon−Halogen Bond Formation Using Nickel

“…[58][59][60] Recently, the Tong group reported a novel strategy to induce asymmetric carboiodination and carbobromination reactions enabled by the addition of ammonium salts. [61] Typically, the palladium carbohalogenation reactions are believed to proceed via initial oxidative addition of the carbon À halogen bond, followed by a 1,2-migratory insertion across a p-system. The resulting organopalladium species are unable to undergo b-hydride elimination due to lack of b-hydrogen atoms or the C(sp 2 ) hybridization of the organometallic species, and thus with the correct choice of the ligand system, reductive elimination of the carbon À halogen bond occurs.…”

Recent Strategies for Carbon−Halogen Bond Formation Using Nickel

“…[58][59][60] Recently,t he Tong group reported an ovel strategy to induce asymmetric carboiodination and carbobromination reactions enabled by the addition of ammonium salts. [61] Ty pically,t he palladium carbohalogenation reactions are believed to proceed via initial oxidative addition of the carbon À halogen bond, followed by a1,2-migratory insertion across a p-system. Theresulting organopalladium species are unable to undergo b-hydride elimination due to lack of b-hydrogen atoms or the C(sp 2 )h ybridization of the organometallic species,a nd thus with the correct choice of the ligand system, reductive elimination of the carbon À halogen bond occurs.…”

“…A catalytic method was reported by Lautens and Newman in 2011 using a palladium precatalyst in the presence of bulky phosphine ligands such as QPhos and P( t Bu) 3 , followed by a related method reported by Tong using bidentate ligands employing vinyl halides [58–60] . Recently, the Tong group reported a novel strategy to induce asymmetric carboiodination and carbobromination reactions enabled by the addition of ammonium salts [61] . Typically, the palladium carbohalogenation reactions are believed to proceed via initial oxidative addition of the carbon−halogen bond, followed by a 1,2‐migratory insertion across a π‐system.…”

DFT Study on Dinuclear Palladium Complex Catalyzed Pyrrole Formation From tert‐Butyl Isocyanide and Alkynes

“…A series of catalytic processes have been successfully implemented with palladium catalysis, which have greatly promoted the development of organic synthesis technology during the recent decades. [1][2][3][4][5][6][7][8] As the field moves forward, the rich organometallic chemistry of palladium is not based entirely on monopalladium complexes. Numbers of examples have been reported for dinuclear palladium catalysts showing distinct advantages over mononuclear ones.…”

“…Palladium is a versatile element and common transition metal for catalysis. A series of catalytic processes have been successfully implemented with palladium catalysis, which have greatly promoted the development of organic synthesis technology during the recent decades [1–8] …”