Synthetic Applications of Dialkyl (Chloromethyl)phosphonates and N,N,N‘,N‘-Tetraalkyl(chloromethyl)phosphonic Diamides

Synthesis and enzymatic evaluation of ketose phosphonates: the interplay between mutarotation, monofluorination and acidity

“…This property has made these compounds attractive as phosphate analogues in numerous applications. [4][5][6][7][8][9][10][11] However, phosphonates are not universal replacements for phosphates. A case-by-case analysis is often required to determine the efficacy of phosphonates as phosphate analogues due to differences in bond lengths, geometry, acidity, sterics, and electronegativity, and the relative importance of each property.…”

“…The challenges associated with the chemical synthesis of a-monofluoromethylene phosphonates has limited their study, 14 however, experimental [15][16][17] and theoretical reports have suggested rationales to explain why they may mimic a phosphate better than either methylene or difluoromethylene derivatives. [6][7][8][9][10][11][12][13][14][15][16][17][18] Several monofluoromethylene phosphonates have been studied as potential enzyme inhibitors and as probes for the elucidation of biochemical processes. 18,19 In a recent study, McKenna and co-workers 20 showed that b,g-fluoromethylene analogues of dGTP are useful substrate mimics for DNA polymerase b (pol b).…”

Synthesis of (poly)alkoxymethylphosphine oxides by classical and phase transfer catalyzed Williamson reactions

“…Moreover, in order to benefit from chelating effects, our goal was the synthesis of PCOC compounds by the use of chloromethylphosphine oxide precursors. Although the Williamson reaction appears to be a good process in this case, some problems may occur, particularly due to the formation of the undesired phosphine oxide carbanion [4]. Furthermore, chloromethylphosphine oxides undergo the Williamson reaction with alkoxides, but the poor leaving character of chlorine requires the use of high boiling solvents like toluene or xylene [5]: under these conditions, some alkyl [6], aryl [7], and pyridinoethers [8] have been synthesized in moderate yields.…”

Synthesis and Reactivity of Azidoalkylphosphonates, -Phosphinates and -Phosphine Oxides

“…However, similarly to the azidation ofsulfonyloxyphosphonates mentioned earlier, the substitution of 1-halogenoalkylphosphonates requires heating for several hours at high temperatures. It competes with the attack of the azide on the carbon atom of the ester group of phosphyl moiety, resulting in the mono-dealkylation of the substrate and/or product [42]. The formation of such by-products can be avoided by the application of phosphonamidates as starting materials or by using the phosphonates esters bearing sterically hindered or electron-withdrawing groups.…”

“…The nucleophilic azidation of chloromethylphosphonic diesters [42] was studied by Savignac et al [46]. They obtained an almost quantitative yield of bis-(2,2,2-trifluoroethyl) azidomethylphosphonate 44a in the reaction of bis-(2,2,2-trifluoroethyl) chloromethylphosphonate 43a with sodium azide in DMSO at 90 o C. Analogously, bis-(2,2,2-trifluoroethyl) dideuterioazidomethylphosphonate (not shown) was obtained from bis-(2,2,2-trifluoroethyl) dideuteriochloromethylphosphonate.…”