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Integrating Allyl Electrophiles into Nickel-Catalyzed Conjunctive Cross-Coupling

preprint
submitted on 26.08.2019 and posted on 27.08.2019 by Van Tran, Zi-Qi Li, Timothy Gallagher, Joseph Derosa, Peng Liu, Keary Engle
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 azaheterocycle directing groups, that 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 in the facile reactivity of the β-γ alkene of the starting material, while the ε-ζ alkene of the product is preserved. The generality of this approach is further illustrated through the development of analogous method with alkyne substrates. Mechanistic studies reveal the importance of the weakly coordinating directing group in dissociating to allow binding of the allyl moiety to facilitate C(sp3)–C(sp3) reductive elimination.

Funding

NSF/CHE-1800280

NIH/R35GM128779

Bristol-Myers Squibb (Unrestricted Grant)

Skaggs Graduate School (Frank J. Dixon Fellowship)

Claremont McKenna College (CMC Sponsored Internships & Experiences Program)

NSF/DGE-1346837

History

Email Address of Submitting Author

keary@scripps.edu

Institution

The Scripps Research Institute

Country

USA

ORCID For Submitting Author

0000-0003-2767-6556

Declaration of Conflict of Interest

No conflict of interest to declare.

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