（来源：康龙化成）

转自：康龙化成

Hydrogen-Mediated Reductive Cross-Coupling of Aryl Iodides with Activated Aryl and Heteroaryl Bromides

Weijia Shen, Yu-Hsiang Chang, Brandon I. Gonzalez, Aidan P. Looby, Jordan J. Dotson,* Nicholas A. White,* Brad P. Carrow,* and Michael J. Krische*

Genentech, Inc, South San Francisco, California 94080, United States; Department of Chemistry, University of Houston, Houston, Texas 77204, United States; Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States;

—J. Am. Chem. Soc. 2025. https://doi.org/10.1021/jacs.5c15725

Recommended by Xuemei Yao_MC3

KEY WORDS: Pd catalysis, Reductive Cross-Coupling(反应类型), aryl iodides, aryl bromides (原料), biaryl (产物), Csp2-Csp2 (成键类型), cine-substitution (其他)

ABSTRACT:Hydrogen-mediated reductive cross-couplings of aryl iodides with activated aryl and heteroaryl bromides are described, along with related homocouplings (Ullmann reactions) and vinylic reductive couplings that occur with cine-substitution. To corroborate key events in the catalytic cycle, Pd-to-Pd transmetalation and cross-selective reductive elimination, dianionicdiarylpalladate complexes [Pd(Aryl)(μ-Br)Br]2[NPr4]2 bearing p-fluorophenyl, p-methoxyphenyl and p-nitrophenyl moieties were prepared. Stoichiometric reactions of these complexes in the presence of iodide demonstrate that Pd-to-Pd transmetalation by way of monomeric arylpalladates occurs at a greater rate than reductive elimination and that cross-selective C–C reductive elimination is favored for electronically distinct aryl partners. Hydrogen-mediated reductive cross-coupling of aryl iodides with α-bromostyrene occurs with cine-substitution (as observed in related formate-mediated processes), consistent with carbopalladation of α-bromostyrene by monomeric arylpalladates Pd(Aryl)I2[NBu4] that arise upon dissociation of [Pd(Aryl)(μ-I)I]2[NBu4]2. 

Substrate Scope

cine vs ipsosubstitution

Prof. Michael J. Krische and his co-workers systematically explored the use of catalytic hydrogenation and transfer hydrogenation in catalytic C−C couplings beyond carbonylative processes. In prior work, reductive cross-couplings of aryl halides via formate-mediated transfer hydrogenation catalyzed by the dianionicPd(I) dimer [Pd2(μ-I)2I2][NBu4]2 was demonstrated, along with related reductive cross-couplings of vinyl triflates or vinyl halides with aryl iodides. Here, they demonstrate that the same Pd(I) catalyst promotes biaryl and vinyl cross-couplings via catalytic hydrogenation. Furthermore, they show that the diarylpalladates [Pd(Aryl)(μ-Br)Br]2[NPr4]2 bearing p-fluorophenyl (Pd-1m), p-methoxyphenyl (Pd-2b) and p-nitrophenyl (Pd-2t) moieties react in the presence of iodide to form products of cross-coupling, corroborating Pd-to-Pd transmetalation from a bimetallic precursor. This work and other data demonstrate that reactions associated with premetalated reagents can be conducted in the absence of stoichiometric carbanions or metallic reductants via catalytic hydrogenation.