Borane Exchange Enables Photocatalytic Alkylation of Pyridylic C(sp³)−H Bonds with Olefins

Abstract

Direct C(sp³)−H alkylation of alkylpyridines provides an efficient route to C(sp³)-rich pyridine motifs, which are highly prevalent in pharmaceuticals and agrochemicals. While numerous ionic methods have been developed, they typically require strong bases, elevated temperatures, or pre-functionalized substrates. To circumvent these limitations, photocatalytic methods relying on radical reactions have emerged, however, pre-activation of the substrates is required or the olefin scope is limited. Here, we report a visible light photocatalytic strategy for pyridylic C(sp³)−H alkylation via in situ borane exchange between pyridine substrates and triphenylphosphine-borane. This method operates under mild conditions, avoids the need for strong bases or metal catalysts, and accommodates both styrenes and unactivated olefins as coupling partners. Mechanistic studies revealed that borane exchange enhances the acidity of the C(sp³)−H bonds, thereby enabling rapid deprotonation to form a pyridylic carbanion intermediate. Subsequent single-electron oxidation by the oxidized form of the photocatalyst (PC) then generates the key pyridylic radical intermediate, which adds to olefins to generate another carbon-centered radical. Final hydrogen atom transfer from an arylthiol affords the desired product in good yields.

Keywords

Photocatalysis / Borane exchange / C−H alkylation / Alkylpyridines / Olefins / Visible light / Single-electron transfer / Hydrogen atom transfer

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