Review on Modern Advances of Chemical Methods for the Introduction of a Phosphonic Acid Group

An overview of the physical-organic chemistry properties of the phosphonic acid group in connection to medicinal chemistry aspects is presented. A review on advances and modern synthetic methods for its introduction with respect to substrate-carbon hybridization is also presented. An alternative approach for the introduction of a dialkyl phosphonate group on to a benzyl halide is by a palladium(0)-catalyzed crosscoupling reaction, originally developed by Laven et al. In the presence of the Pd(O) catalyst Pd 2(dba) 3(CHCl 3) and Xantphos, a reactive Pd(O) Xantphos complex is formed, which undergoes oxidative addition to the benzyl halide substrate. Gelman et al. reported a method for the synthesis of aryl- and vinyl-phosphonic acids using copper(I) iodide and Cs 2CO 3 as base in toluene. Ishii et al. have developed a method for the addition H-phosphonate to nucleophilic alkenes, which relies on the use of MnOAc) 2 as catalyst.