posted on 2023-06-21, 06:02authored byRaysa Khan, Sarote Boonseng, Paul Kemmitt, Robert Felix, Simon J Coles, Graham J Tizzard, Gareth Williams, Olivia Simmonds, Jessica-Lily Harvey, John Atack, Hazel CoxHazel Cox, John SpencerJohn Spencer
5-Phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-ones react under palladium- and visible light photoredox catalysis, in refluxing methanol, with aryldiazonium salts to afford the respective 5-(2- arylphenyl) analogues. With 2- or 4-fluorobenzenediazonium derivatives, both fluoroaryl- and methoxyaryl- products were obtained, the latter resulting from a SNAr on the fluorobenzenediazonium salt (“nuisance effect”). A computational DFT analysis of the palladium-catalysed and the palladium/ruthenium-photocalysed mechanism for the functionalization of benzodiazepines indicated that in the presence of the photocatalyst the reaction proceeds via a low-energy SET pathway avoiding the high-energy oxidative addition step in the palladium-only catalysed reaction pathway.
Funding
A Precompetitive Modular Peptidomimetic Toolkit for Targeting PPIs iCASE; G1436; EPSRC-ENGINEERING & PHYSICAL SCIENCES RESEARCH COUNCIL; EP/M507568/1