This review summarizes the main synthetic routes towards α-hydroxyphosphonates that are known as enzyme inhibitors, herbicides and antioxidants, moreover, a number of representatives express antibacterial or antifungal effect. Special attention is devoted to green chemical aspects. α-Hydroxyphosphonates are also versatile intermediates for other valuable derivatives. O-Alkylation and O-acylation are typical reactions to afford α-alkoxy-, or α-acyloxyphosphonates, respectively. The oxidation of hydroxyphosphonates leads to ketophosphonates. The hydroxy function at the α carbon atom of hydroxyphosphonates may be replaced by a halogen atom. α-Aminophosphonates formed in the nucleophilic substitution reaction of α-hydroxyphosphonates with primary or secondary amines are also potentially bioactive compounds. Another typical reaction is the base-catalyzed rearrangement of α-hydroxy-phosphonates to phosphates. Hydrolysis of the ester function of hydroxyphosphonates leads to the corresponding phosphonic acids.

α-Hydroxyphosphonates constitute a class of organophosphorus compounds famous for their bioactive properties. α-Hydroxyphosphonates may easily be functionalized due to their free hydroxy function in the α position resulting in new families of compounds of synthetical and biological interest. This review paper summarizes the main reaction types of α-hydroxyphosphonates. First, the syntheses of α-aminophosphonates and α-hydroxyphosphonic acids are discussed, as from a biological point of view, these are the most important classes of compounds derived from α-hydroxyphosphonates. After that, the O-acylation and O-alkylation of α-hydroxyphosphonates to afford O-acyloxy and O-alkoxyphosphonates are presented. The discussion continues with the synthesis of α-halophosphonates and α-ketophosphonates that are valuable synthetic intermediates. After that, a few examples for the reduction of α-hydroxyphosphonates are presented, followed by the rearrangement of α-hydroxyphosphonates to the corresponding benzyl phosphates. Beside the interesting examples from the literature, the main synthetic results of our research group in this field are also discussed.

The two-step acidic hydrolysis of α-hydroxybenzylphosphonates and a few related derivatives was monitored in order to determine the kinetics and to map the reactivity of the differently substituted phosphonates in hydrolysis. Electron-withdrawing substituents increased the rate, while electron-releasing ones slowed down the reaction. Both hydrolysis steps were characterized by pseudo-first-order rate constants. The fission of the second P-O-C bond was found to be the rate-determining step.

The Pudovik reaction between substituted benzaldehydes and dialkyl phosphites has been accomplished in a new, environmentally friendly way to afford the corresponding α-hydroxyphosphonates. During the substitution of α-hydroxyphosphonates by primary amines an unexpected neighboring group effect was found that promoted the formation of α-aminophosphonates. The phenomenon was justified by high-level quantum chemical calculations.

Direct derivatizations, such as esterification and amidation of 1-hydroxy-3-methyl-3-phospholene oxide and subsequent transformations including ring enlargement of the phosphinates, and phosphorylation of the phosphinic amides so obtained are described.