Integrating Allyl Electrophiles into Nickel‐Catalyzed Conjunctive Cross‐Coupling. Issue 18 (13th March 2020)

• Record Type: Journal Article
• Authors: Tran, Van T.; Li, Zi‐Qi; Gallagher, Timothy J.; Derosa, Joseph; Liu, Peng; Engle, Keary M.
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 18(2020)
• Page Start: 7029
• Page End: 7034
• Publication Date: 2020-03-13
• Subjects: allylation -- conjunctive cross-coupling -- dicarbofunctionalization -- heterocycles -- nickel catalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201915454
• Languages: English
• ISSNs: 1433-7851

Abstract

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(sp 3 )−C(sp 3 ) reductive elimination. Abstract : Nickel catalysis enables regioselective 1, 2‐allylmethylation of unactivated alkenes in a variety of N ‐allyl heterocycles. The resulting alkene product remains untouched and can be easily diversified.