Hidden Brønsted acid catalysis in the Kabachnik–Fields reaction: the key role of in situ generated phosphorous acid

The Kabachnik–Fields (KF) reaction is a key multicomponent route to α-aminophosphonates, yet its mechanism remains debated. Here, a combined experimental and DFT study reveals that phosphorous acid (H3PO3), formed in situ via partial phosphite hydrolysis, acts as a key Brønsted acid catalyst under these conditions. Strong solvent effects and limited impact of added acids are rationalized by pH measurements and 31P NMR evidence. Computations show that H3PO3 lowers the activation barriers of the key steps, while the pathway involving the Abramov adduct is kinetically inaccessible. The reaction proceeds via imine formation followed by phosphite addition, involving either the phosphite or its tautomer depending on the solvent. Notably, diphenyl phosphite readily undergoes the reaction under mild conditions, whereas dimethyl phosphite is significantly less reactive due to unfavorable hydrolysis and reduced availability of H3PO3.