Periodic Reporting for period 1 - B_ELECTRO (Large-Scale Electrosynthesis of Borylated Azines)
Período documentado: 2024-01-01 hasta 2025-06-30
Azines are among the most frequently used heteroaromatics in drugs and agrochemicals, and modern discovery relies on modular cross-coupling—especially Suzuki–Miyaura—to introduce these motifs efficiently. Two entrenched bottlenecks block this route: (1) direct C–H borylation next to the ring nitrogen is largely inaccessible with transition-metal methods; and (2) even when prepared, many borylated azines—especially 2-pyridyl derivatives—are unstable and fail under standard coupling conditions (the “2-pyridyl problem”). The consequence is longer, costlier, and less sustainable syntheses.
Our group’s ERC-funded work provided a lab-scale solution: radical borylation from inexpensive amine–boranes, delivering stable azine–borane building blocks that do couple reliably. However, the photochemical activation that enabled this breakthrough is hard to scale (heterogeneous media; light-penetration limits; precious photocatalysts), preventing commercialization despite strong vendor and end-user interest. B-ELECTRO is the response: replace light with electrochemistry to unlock scale and market uptake.
Expected impact:
• Supply-chain innovation. Make previously inaccessible, stable borylated azines commercially available, filling a large area of currently empty chemical space and giving the community a reliable answer to the 2-pyridyl problem.
• Process and design impact. Provide end-users with building blocks that actually survive and perform in Suzuki–Miyaura couplings, increasing the success rate of fragment-coupling campaigns on complex scaffolds.
• Knowledge creation. Establish the first electrochemical generation of boryl radicals, defining principles and parameters others can generalize, and anchoring future advances in radical borylation science.
• Economic and environmental significance. Shorter, modular routes mean fewer steps, lower energy input, and less waste; combined with a clear path to market (vendor listings, MTAs, trade-fair outreach), the project is positioned to accelerate industry uptake and strengthen European competitiveness in small-molecule manufacturing.
Our group’s ERC-funded work provided a lab-scale solution: radical borylation from inexpensive amine–boranes, delivering stable azine–borane building blocks that do couple reliably. However, the photochemical activation that enabled this breakthrough is hard to scale (heterogeneous media; light-penetration limits; precious photocatalysts), preventing commercialization despite strong vendor and end-user interest. B-ELECTRO is the response: replace light with electrochemistry to unlock scale and market uptake.
Expected impact:
• Supply-chain innovation. Make previously inaccessible, stable borylated azines commercially available, filling a large area of currently empty chemical space and giving the community a reliable answer to the 2-pyridyl problem.
• Process and design impact. Provide end-users with building blocks that actually survive and perform in Suzuki–Miyaura couplings, increasing the success rate of fragment-coupling campaigns on complex scaffolds.
• Knowledge creation. Establish the first electrochemical generation of boryl radicals, defining principles and parameters others can generalize, and anchoring future advances in radical borylation science.
• Economic and environmental significance. Shorter, modular routes mean fewer steps, lower energy input, and less waste; combined with a clear path to market (vendor listings, MTAs, trade-fair outreach), the project is positioned to accelerate industry uptake and strengthen European competitiveness in small-molecule manufacturing.
We executed a challenging optimisation campaign to scale the radical borylation of azines into a broadly applicable process. Generalisation proved non-trivial: substrate/class effects meant a single “global” recipe was unreliable, so we devoted significant effort to targeted, per-family re-optimisations to ensure translatability. With the refined conditions, we prepared several derivatives on ≥5 g scale with purity suitable for downstream use. Multiple samples were supplied to industrial collaborators, who have begun cross-coupling evaluations.
Outcome: gram-scale feasibility across representative azine classes and an actionable re-optimisation playbook for further scale-up.
Outcome: gram-scale feasibility across representative azine classes and an actionable re-optimisation playbook for further scale-up.
We developed novel methods to access unique azine–organoboron building blocks in gram-scale quantities and with suitable purity to support future commercialization. In parallel, we are establishing directly compatible cross-coupling conditions (e.g. Suzuki–Miyaura) so these building blocks can be used as-made in synthetic chemistry, enabling faster fragment assembly and streamlined workflows.