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

Yangyang Weng,Jingping Qu,Zaiquan Tang,Mohini Shrestha,Chenhuan Zhang,Wenyi Huang,Yifeng Chen

doi:10.1038/s41467-020-14320-1

Yangyang Weng, Jingping Qu + Show 5 more

Open Access

https://doi.org/10.1038/s41467-020-14320-1

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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.

Highlights

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
Pioneering work developed by Heck in the 1970s catapulted palladium (Pd)-catalyzed three component reactions with carbon monoxide (CO) as a powerful strategy for introduction of carbonyl group[1,2,3,4,5,6,7,8]
Isocyanide is an important array of organic reagent widely used in transition metal catalyzed carbonylations as C-1 source and in heterocycle synthesis[27,28,29,30,31,32,33,34,35,36,37,38]

Summary

Introduction

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. Pioneering work developed by Heck in the 1970s catapulted palladium (Pd)-catalyzed three component reactions with carbon monoxide (CO) as a powerful strategy for introduction of carbonyl group[1,2,3,4,5,6,7,8] Among these processes, the use of carbon-based nucleophiles allows for the convenient synthesis of ketones with broad applications[9]. Zhu and co-workers[58] illustrate that the allyl imidoylpalladium intermediate is extremely prone to undergo β-H elimination to provide the ketenimine intermediate, which could further hydrolyze to β,γ-unsaturated amide[59] To overcome these challenges, we envisioned that the use of functional group compatible organozinc reagents that are highly effective for transmetallation might disfavor the overcarbonylation process. We report the highly regio- and chemoselective nickel-catalyzed allylic carbonylative Negishi reaction with tert-butyl isocyanide[63], which allows the expedient synthesis of β,γ-unsaturated ketones with broad substrate scope under mild conditions (Fig. 1c)

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Results

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