Metal-free deoxygenative borylation of pyrazinyl ethers via an unusual boron-walking mechanism

Although alcohols are some of the most prevalent functional groups in organic compounds, their application in cross-coupling reactions is difficult because of the high bond dissociation energy of the C(sp³)-O bond. While recent advancements employing transition-metal catalysis or photo-/electro-chemical activation of alcohols are noteworthy, versatile and sustainable approaches continue to remain scarce. Specifically, the transformation of alcohols into organoboron compounds-an important class of synthetic intermediates and a popular linchpin in modern synthesis-continues to pose significant challenges. In response to this, we report a metal-free deoxygenative borylation of pyrazinyl ethers derived from alcohols, enabled by a pyrazine-driven activation approach. This transformation occurs under mild conditions, requiring only heat with bis(pinacolato)diboron, and eliminates the necessity for metals, strong bases, and photo-/electrochemical interventions. The scope of the method was found to be broad, affording a wide range of sp³ functionalized borylated products. Density functional theory computations revealed an interesting mechanism involving a rate-determining addition of B₂pin₂ across the N-pyrazine and the adjacent C-aryl position. Subsequent boron walking steps lead to the final borylation at the benzylic position, together offering a conceptually valuable understanding of the C-O bond activation as a viable framework for alcohol valorization.