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Zirconium-Redox-Shuttled Cross-Electrophile Coupling of Aromatic and Heteroaromatic Halides.

ABSTRACT: Transition metal-catalyzed cross-electrophile coupling (XEC) is a powerful tool for forging C(sp²)-C(sp²) bonds in biaryl molecules from abundant aromatic halides. While syntheses of unsymmetrical biaryl compounds through multimetallic XEC is of high synthetic value, selective XEC of two heteroaromatic halides remains elusive and challenging. Herein we report a homogeneous XEC method which relies on a zirconaaziridine complex as a shuttle for dual palladium catalyzed processes. The zirconaaziridine-mediated palladium (ZAPd) catalyzed reaction shows excellent compatibility with various functional groups and diverse heteroaromatic scaffolds. In accord with density functional theory (DFT) calculations, a redox-transmetallation between the oxidative addition product and the zirconaaziridine is proposed as the crucial elementary step. Thus, cross-coupling selectivity using a single transition metal catalyst is controlled by the relative rate of oxidative addition of Pd(0) into the aromatic halide. Overall, the concept of a combined reducing and transmetallating agent offers opportunities for development of transition-metal reductive coupling catalysis.

SUBMITTER: Wu TF

PROVIDER: S-EPMC8492010 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Zirconium-Redox-Shuttled Cross-Electrophile Coupling of Aromatic and Heteroaromatic Halides.

Wu Ting-Feng TF Zhang Yue-Jiao YJ Fu Yue Y Liu Fang-Jie FJ Tang Jian-Tao JT Liu Peng P Toste F Dean FD Ye Baihua B

Chem 20210701 7

Transition metal-catalyzed cross-electrophile coupling (XEC) is a powerful tool for forging C(sp<sup>2</sup>)-C(sp<sup>2</sup>) bonds in biaryl molecules from abundant aromatic halides. While syntheses of unsymmetrical biaryl compounds through multimetallic XEC is of high synthetic value, selective XEC of two heteroaromatic halides remains elusive and challenging. Herein we report a homogeneous XEC method which relies on a zirconaaziridine complex as a shuttle for dual palladium catalyzed proces ...[more]

PMID: 34622088

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Project description:Cross-electrophile coupling, the cross-coupling of two different electrophiles, avoids the need for preformed carbon nucleophiles, but development of general methods has lagged behind cross-coupling and C-H functionalization. A central reason for this slow development is the challenge of selectively coupling two substrates that are alike in reactivity. This Account describes the discovery of generally cross-selective reactions of aryl halides and acyl halides with alkyl halides, the mechanistic studies that illuminated the underlying principles of these reactions, and the use of these fundamental principles in the rational design of new cross-electrophile coupling reactions. Although the coupling of two different electrophiles under reducing conditions often leads primarily to symmetric dimers, the subtle differences in reactivity of aryl halides and alkyl halides with nickel catalysts allowed for generally cross-selective coupling reactions. These conditions could also be extended to the coupling of acyl halides with alkyl halides. These reactions are exceptionally functional group tolerant and can be assembled on the benchtop. A combination of stoichiometric and catalytic studies on the mechanism of these reactions revealed an unusual radical-chain mechanism and suggests that selectivity arises from (1) the preference of nickel(0) for oxidative addition to aryl halides and acyl halides over alkyl halides and (2) the greater propensity of alkyl halides to form free radicals. Bipyridine-ligated arylnickel intermediates react with alkyl radicals to efficiently form, after reductive elimination, new C-C bonds. Finally, the resulting nickel(I) species is proposed to regenerate an alkyl radical to carry the chain. Examples of new reactions designed using these principles include carbonylative coupling of aryl halides with alkyl halides to form ketones, arylation of epoxides to form β-aryl alcohols, and coupling of benzyl sulfonate esters with aryl halides to form diarylmethanes. Arylnickel(II) intermediates can insert carbon monoxide to form acylnickel(II) intermediates that react with alkyl halides to form ketones, demonstrating the connection between the mechanisms of reactions of aryl halides and acid chlorides with alkyl halides. The low reactivity of epoxides with nickel can be overcome by the use of either titanium or iodide cocatalysis to facilitate radical generation and this can also be extended to enantioselective arylation of meso-epoxides. The high reactivity of benzyl bromide with nickel, which leads to the formation of bibenzyl in attempted reactions with bromobenzene, can be overcome by using a benzyl mesylate along with cobalt phthalocyanine cocatalysis to convert the mesylate into an alkyl radical.

Dataset Information

Zirconium-Redox-Shuttled Cross-Electrophile Coupling of Aromatic and Heteroaromatic Halides.

Publications

Zirconium-Redox-Shuttled Cross-Electrophile Coupling of Aromatic and Heteroaromatic Halides.

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