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Abstract Electrochemical approaches to form C(sp2)−C(sp3) bonds have focused on coupling C(sp3) electrophiles that form stabilized carbon‐centered radicals upon reduction or oxidation. Whereas alkyl bromides are desirable C(sp3) coupling partners owing to their availability and cost‐effectiveness, their tendency to undergo radical‐radical homocoupling makes them challenging substrates for electroreductive cross‐coupling. Herein, we disclose a metal‐free regioselective cross‐coupling of 1,4‐dicyanobenzene, a useful precursor to aromatic nitriles, and alkyl bromides. Alkyl bromide reduction is mediated directly by 1,4‐dicyanobenzene radical anions, leading to negligible homocoupling and high cross‐selectivity to form 1,4‐alkyl cyanobenzenes. The cross‐coupling scheme is compatible with oxidatively sensitive and acidic functional groups such as amines and alcohols, which have proven difficult to incorporate in alternative electrochemical approaches using carboxylic acids as C(sp3) precursors.
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Integrating Allyl Electrophiles into Nickel‐Catalyzed Conjunctive Cross‐Coupling
Abstract Allylation and conjunctive cross‐coupling represent two useful, yet largely distinct, reactivity paradigms in catalysis. The union of these two processes would offer exciting possibilities in organic synthesis but remains largely unknown. Herein, we report the use of allyl electrophiles in nickel‐catalyzed conjunctive cross‐coupling with a non‐conjugated alkene and dimethylzinc. The transformation is enabled by weakly coordinating, monodentate aza‐heterocycle directing groups that are useful building blocks in synthesis, including saccharin, pyridones, pyrazoles, and triazoles. The reaction occurs under mild conditions and is compatible with a wide range of allyl electrophiles. High chemoselectivity through substrate directivity is demonstrated by the facile reactivity of the β‐γ alkene of the starting material, whereas the ϵ‐ζ alkene of the product is preserved. The generality of this approach is further illustrated through the development of an analogous method with alkyne substrates. Mechanistic studies reveal the importance of the dissociation of the weakly coordinating directing group to allow the allyl moiety to bind and facilitate C(sp3)−C(sp3) reductive elimination.
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- Award ID(s):
- 1800280
- PAR ID:
- 10139430
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 59
- Issue:
- 18
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 7029-7034
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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