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. 2022 Aug 19;24(32):6093-6098.
doi: 10.1021/acs.orglett.2c02481. Epub 2022 Aug 4.

Synthesis of Vicinal Carbocycles by Intramolecular Nickel-Catalyzed Conjunctive Cross-Electrophile Coupling Reaction

Kirsten A Hewitt  1 , Claire A Herbert  1 , Elizabeth R Jarvo  1
Affiliations

Synthesis of Vicinal Carbocycles by Intramolecular Nickel-Catalyzed Conjunctive Cross-Electrophile Coupling Reaction

Kirsten A Hewitt et al. Org Lett. .

Abstract

A nickel-catalyzed intramolecular conjunctive cross-electrophile coupling reaction has been established. This method enables the synthesis of 3,5-vicinal carbocyclic rings found in numerous biologically active compounds and natural products. We provide mechanistic experiments that indicate this reaction proceeds through alkyl iodides formed in situ, initiates at the secondary electrophilic center, and proceeds through radical intermediates.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Previous Work in Conjunctive XEC Reactions and Medicinally Relevant Vicinal Carbocycles
Scheme 2
Scheme 2. Conjunctive XEC Reaction Scope
Reaction performed on 0.1 mmol scale unless otherwise noted. Reaction performed on 0.5 mmol scale. Yield in parentheses is 1H NMR yield compared to PhTMS as an internal standard.
Scheme 3
Scheme 3. Control Reaction with Single Alkene Diastereomer
Scheme 4
Scheme 4. Competition Experiments and Proposed Reaction Mechanism (R1 = 4-MeO-C6H4, R2 = 4-BnO-C6H4)
See this image and copyright information in PMC

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