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 variou s alcohols. The reactions of bis-PNP phosphonates in the presence of D BU, using both primary and secondary alcohols, phenols and amines, pro ceed rapidly and with high yield to afford the corresponding monoalkyl /aryl mono-PNP phosphonates as sole products (1, Scheme 2). The result ing monoalkyl/aryl mono-PNP phosphonates can be further reacted with a second alcohol to give the corresponding differently disubstituted ph osphonates 3, or selectively hydrolysed to yield the monoalkyl/aryl ph osphonic 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.