Alcoholysis of Phosphaisocoumarins and Synthesis of 2-(2-Oxoalkyl)phenylphosphonates

Phosphaisocoumarins do not undergo aminolysis, but instead they were found to be susceptible to alcoholysis in the presence of alcohols and primary amines. This paper examined this unexpected alcoholysis reaction and found that in the presence of Et3N or K2CO3, 4-unsubstituted- and 4-chlorophosphaisocoumarins underwent the alcoholysis reaction smoothly to give a series of 2-(2-oxoalkyl)phenylphosphonates in good yields, whereas 4-iodo- and 4-bromophosphaisocoumarins underwent a dehalogenation–alcoholysis tandem reaction. The possible mechanism for the alcoholysis reaction was discussed. In addition, direct access to 2-(2-oxoalkyl)phenylphosphonates was developed by the mercury(II)-catalyzed hydration of 2-(1-alkynly)phenylphosphonates with high regioselectivity. In a preliminary study, the obtained novel keto phosphonates showed medium inhibitory activity towards α-chymotrypsin. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)