1,8-Diazabicyclo[5.4.0]undecene mediated transesterification of p-nitrophenyl phosphonates: A novel route to phosphono esters

DBU (1,8-diazabicyclo[5.4.0]undecene) was found to efficiently mediate the transesterification of p-nitrophenyl (PNP) phosphonates by various alcohols. The reactions of bis-PNP phosphonates in the presence of DBU, using both primary and secondary alcohols, phenols and amines, proceed rapidly and with high yield to afford the corresponding monoalkyl/aryl mono-PNP phosphonates as sole products (1, Scheme 2). The resulting monoalkyl/aryl mono-PNP phosphonates can be further reacted with a second alcohol to give the corresponding differently disubstituted phosphonates 3, or selectively hydrolysed to yield the monoalkyl/aryl phosphonic acids 2. We have applied this chemistry to the preparation of a series of phosphono ester transition state analogues 11a-e (Scheme 3) that were used as haptens for raising catalytic antibodies.