Nickel-catalyzed allylic carbonylative coupling of alkyl zinc reagents with tert-butyl isocyanide

Abstract

Transition metal-catalyzed carbonylation with carbon nucleophiles is one of the most prominent methods to construct ketones, which are highly versatile motifs prevalent in a variety of organic compounds. In comparison to the well-established palladium catalytic system, the nickel-catalyzed carbonylative coupling is much underdeveloped due to the strong binding affinity of CO to nickel. By leveraging easily accessible tert-butyl isocyanide as the CO surrogate, we present a nickel-catalyzed allylic carbonylative coupling with alkyl zinc reagent, allowing for the practical and straightforward preparation of synthetically important β,γ-unsaturated ketones in a linear-selective fashion with excellent trans-selectivity under mild conditions. Moreover, the undesired polycarbonylation process which is often encountered in palladium chemistry could be completely suppressed. This nickel-based method features excellent functional group tolerance, even including the active aryl iodide functionality to allow the orthogonal derivatization of β,γ-unsaturated ketones. Preliminary mechanistic studies suggest that the reaction proceeds via a π-allylnickel intermediate.

Abstract

In contrast to the well-established palladium-catalyzed version, the nickel-catalyzed carbonylative coupling is underdeveloped. Here the authors report a nickel-catalyzed allylic carbonylative coupling with alkyl zinc reagents, allowing for preparation of β,γ-unsaturated ketones in a linear-selective fashion.