Nickel-catalyzed intermolecular oxidative Heck arylation driven by transfer hydrogenation

Honggui Lv,Keary M Engle,Huiying Kang,Xiaosong Xue,Biying Zhou,Dongbing Zhao

doi:10.1038/s41467-019-12949-1

Honggui Lv, Keary M Engle + Show 4 more

Open Access

https://doi.org/10.1038/s41467-019-12949-1

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Abstract

The conventional oxidative Heck reaction between aryl boronic acids and alkenes typically involved the PdII/Pd0/PdII catalytic cycle incorporating an external oxidant and often suffered C=C bond isomerization for internal alkyl-substituted alkenes via chain-walking. Herein, we demonstrate that the regioselectivity (γ-selectivity vs. δ-selectivity) and pathway selectivity (hydroarylation vs. oxidative Heck coupling) of a directed Ni-catalyzed alkene arylation can be controlled by judicious tuning of the coordination environment around the nickel catalyst via optimization of an appropriate phosphine ligand and directing group. In this way, the Ni(0)-catalyzed oxidative Heck arylation that relies on transfer hydrogenation of an acceptor olefin is developed with excellent E/Z selectivity and regioselectivity. Mechanistic investigations suggest that the addition of the acceptor is crucial for lowering the energy for carbometalation and for enabling catalytic turnover.

Highlights

The conventional oxidative Heck reaction between aryl boronic acids and alkenes typically involved the PdII/Pd0/PdII catalytic cycle incorporating an external oxidant and often suffered C=C bond isomerization for internal alkyl-substituted alkenes via chain-walking
Despite significant advances during the past several decades[1,2,3,4,5,6,7,8,9,10], Heck-type reactions still suffer from significant limitations, including a difficulty controlling selectivity with internal alkyl-substituted alkenes due to the lack of steric and electronic differentiation in the key migratory insertion step and issues of C=C bond isomerization due to chain-walking[17]
We envisioned that selectivity for this pathway over other alternatives could be achieved by tuning the coordination environment around nickel with an appropriate phosphine ligand and directing group[45,46,47,48,49,50,51,52]

Summary

Introduction

The conventional oxidative Heck reaction between aryl boronic acids and alkenes typically involved the PdII/Pd0/PdII catalytic cycle incorporating an external oxidant and often suffered C=C bond isomerization for internal alkyl-substituted alkenes via chain-walking. We demonstrate that the regioselectivity (γ-selectivity vs δ-selectivity) and pathway selectivity (hydroarylation vs oxidative Heck coupling) of a directed Ni-catalyzed alkene arylation can be controlled by judicious tuning of the coordination environment around the nickel catalyst via optimization of an appropriate phosphine ligand and directing group. In this way, the Ni (0)-catalyzed oxidative Heck arylation that relies on transfer hydrogenation of an acceptor olefin is developed with excellent E/Z selectivity and regioselectivity. During the course of this study, we detected byproducts arising from hydrogenolysis of the Ar–B bond, indicating that transmetalation might precede migratory insertion In this case, a Ni(H)(Ar) intermediate would be the active form of the catalyst that engages the alkene (Fig. 1a, path B). These methods are efficient and scalable, providing a modular means of assembling δ-aryl olefinic acids, which are versatile building blocks for synthesizing drugs and other biologically active compounds (Fig. 1c)[53,54,55,56,57]

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Results

Conclusion