摘要：Zhi-MingSu, Jieru Zhu, Darren L. Poole, Mohammad Rafiee, Robert S. Paton, Daniel J.Weix, and Shannon S. Stahl*

转自：康龙化成

Selective Ni-Catalyzed Cross-Electrophile Coupling of Heteroaryl Chlorides and Aryl Bromides at 1:1 Substrate Ratio

Zhi-MingSu, Jieru Zhu, Darren L. Poole, Mohammad Rafiee, Robert S. Paton, Daniel J.Weix, and Shannon S. Stahl*

Department of Chemistry, University ofWisconsin-Madison, Madison, Wisconsin 53706, United States;

Molecular Modalities Capabilities, GSKMedicines Research Centre, Stevenage SG1 2NY, U.K.;

Department of Chemistry, University ofMissouri-Kansas City, Kansas City, Missouri 64110, United States;

Department of Chemistry, Colorado StateUniversity, Fort Collins, Colorado 80523, United States.

—J.Am. Chem. Soc., 2024, DOI：https://doi.org/10.1021/jacs.4c10776

Recommended by Yuting Gao_MC3

KEYWORDS: cross-electrophilecoupling (反应类型),C(sp2)-C(sp2) (成键类型),heteroaryl chloride, aryl bromide (原料), nitrogen-containing biaryls (产物),NiBr2(dme) (催化剂)

ABSTRACT: Inthis study, an informer library of heteroaryl chloride and aryl bromidecoupling partners is used to identify Ni-catalyzed XEC conditions that accesshigh selectivity for the cross-product when using equimolar quantities of thetwo substrates. Two different catalyst systems are identified that showcomplementary scope and broad functional-group tolerance, and time-course datasuggest that the two methods follow different mechanisms. A NiBr2 /terpyridine catalyst system with Zn asthe reductant converts the aryl bromide into an arylzinc intermediate that undergoes in situcoupling with 2-chloropyridines, while a NiBr2 /bipyridinecatalyst system with tetrakis(dimethylamino)ethyleneas the reductant uses FeBr2 and NaI as additives to achieve selectivecross-coupling.

Background

Optimization Studies

Substrates Scope

Proposed Mechanism for Condition A

Summary and Comments

TheGroup of Prof. Shannon S. Stahl introducedtwo highly effective Ni-only catalyst systems to support XEC that accessesheteroaryl−aryl structures. Both reaction conditions (A and B) enable XEC witha 1:1 ratio of heteroaryl chloride and aryl bromide substrates, and theyexhibit high cross-selectivity, good functional-group tolerance, andcompatibility with multiple different aromatic heterocycles. The reactions showcomplementary reactivity, and mechanistic studies provide evidence for differentXEC pathways for the reactions under conditions A and B.

来源：新浪财经