Abstract
The Mizoroki-Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Here we report an atom-economical cross-coupling of halopyridines and unactivated alkenes under photoredox catalysis to afford a series of alkene halopyridylation products. This protocol with mild and redox neutral conditions contributes broad substrate scope. As a complement to conventional Heck-type reaction, this radical process avoids the involvement of β-H elimination and thus useful pyridyl and halide groups could be simultaneously and regioselectively incorporated onto alkenes. The success depends on TFA-promoted domino photocatalytic oxidative quenching activation and radical-polar crossover pathway. Plausible mechanism is proposed based on mechanistic investigations. Moreover, the reserved C − X bonds of these products are beneficial for performing further synthetic elaborations.
Highlights
The Mizoroki-Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation
Intrigued by these precedents and our continued interest on alkenes functionalizations[64,65,66,67], we questioned whether it is possible to simultaneously install both pyridyl and halide groups onto alkenes which possess a potential syn β-H atom. This goal has been achieved by coupling of unactivated alkenes and halopyridines under visible light condition (Fig. 1d). This halopyridylation transformation is enabled by domino photocatalytic oxidative quenching activation and radical-polar crossover pathway
According to general principle for the construction of C–X bond, we envisioned that oxidative quenching activation of halopyridine would divert the reactivity from hydropyridylation towards halopyridylation of alkenes
Summary
The Mizoroki-Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Owing to the ubiquitous role of pyridyl motifs as aromatic heterocycle in ligand scaffolds, natural products, and medically relevant molecules[49,50,51,52,53], significant efforts have been devoted to visible lightdriven pyridylation of alkenes[54,55,56,57,58,59,60,61,62,63] Intrigued by these precedents and our continued interest on alkenes functionalizations[64,65,66,67], we questioned whether it is possible to simultaneously install both pyridyl and halide groups onto alkenes which possess a potential syn β-H atom. It provides an important complement for known precedents about Heck reactions with respect to product diversity and atom economy
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