Dataset Information

Cross-Electrophile Coupling of Unactivated Alkyl Chlorides.

ABSTRACT: Alkyl chlorides are bench-stable chemical feedstocks that remain among the most underutilized electrophile classes in transition metal catalysis. Overcoming intrinsic limitations of C(sp³)-Cl bond activation, we report the development of a novel organosilane reagent that can participate in chlorine atom abstraction under mild photocatalytic conditions. In particular, we describe the application of this mechanism to a dual nickel/photoredox catalytic protocol that enables the first cross-electrophile coupling of unactivated alkyl chlorides and aryl chlorides. Employing these low-toxicity, abundant, and commercially available organochloride building blocks, this methodology allows access to a broad array of highly functionalized C(sp²)-C(sp³) coupled adducts, including numerous drug analogues.

SUBMITTER: Sakai HA

PROVIDER: S-EPMC7750884 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cross-Electrophile Coupling of Unactivated Alkyl Chlorides.

Sakai Holt A HA Liu Wei W Le Chi Chip CC MacMillan David W C DWC

Journal of the American Chemical Society 20200626 27

Alkyl chlorides are bench-stable chemical feedstocks that remain among the most underutilized electrophile classes in transition metal catalysis. Overcoming intrinsic limitations of C(sp<sup>3</sup>)-Cl bond activation, we report the development of a novel organosilane reagent that can participate in chlorine atom abstraction under mild photocatalytic conditions. In particular, we describe the application of this mechanism to a dual nickel/photoredox catalytic protocol that enables the first cro ...[more]

PMID: 32564602

Similar Datasets

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

Cross-Electrophile Coupling of Unactivated Alkyl Chlorides.

Publications

Cross-Electrophile Coupling of Unactivated Alkyl Chlorides.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure