The reaction of Tetrazole with Phosphoramidites as a Model for the Nucleotide Coupling Step

Amides of Trivalent Phosphorus Acids as Phosphorylating Reagents for Proton-Donating Nucleophiles

“…Thus, these reactions can hardly be classified as catalyzed reactions. In this connection, note that 31 P NMR spectra of the reaction mixtures containing excess tetrazole exhibit a signal due to the transamidation product, namely, P(III)-tetrazolide, which is considered to be an intermediate product. − The possible formation of P(III)-tetrazolides has served as the subject of special studies emphasizing the role of the acidity of activators, which are able, in the opinion of the authors cited, to protonate the initial ATPA. ,,, The researchers were able to perform kinetic measurements in the ATPA−tetrazole system and proposed a scheme for the phosphorylation of alcohols (Scheme ) 10 …”

“…[88][89][90][91][92] The possible formation of P(III)-tetrazolides has served as the subject of special studies emphasizing the role of the acidity of activators, which are able, in the opinion of the authors cited, to protonate the initial ATPA. 74,89,91,92 The researchers were able to perform kinetic measurements in the ATPA-tetrazole system and proposed a scheme for the phosphorylation of alcohols (Scheme 10). 92 Unfortunately, no thorough analysis of this scheme was carried out.…”

Novel Organophosphate Ligand O-(2-Fluoroethyl)-O-(p-Nitrophenyl)Methylphosphonate: Synthesis, Hydrolytic Stability and Analysis of the Inhibition and Reactivation of Cholinesterases

“…For preparation of [ 18 F] 1 , beta -fluoroethyl tosylate was reacted with MeP­(O) (OPNP)­O – Cs + using microwave-assisted accleration . Since neither approach was found to be amenable to a larger scale, a new experimental protocol was examined − (Scheme ). Commercially available dichloromethylphosphine 2 ( 31 P NMR 191.0 ppm) was reacted sequentially with diisopropylamine and p -nitrophenol to afford phosphonamidite 4 ( 31 P NMR 128.0 ppm; 185.71 ppm in protonated form).…”

“…The synthetic sequence relies upon in situ protonation of the phosphonamidite nitrogen to convert the diisopropylamine to a better leaving group and permit reaction with the weakly nucleophilic fluoroethanol. Reaction of alcohols with N , N -dialkylphosphonamidites is typically conducted in sequence with tetrazole and oxidizing agents. − ,− However, in this reaction sequence triethylamine hydrochloride or p -nitrophenol serves as the proton donor, and the use of oxidizing agents such as m -CPBA and t -BuOOH to produce 1 from 6 was less effective than air exposure. Product 1 may also be accessed via purification of 4 by column chromatography followed by the addition of tetrazole and fluoroethanol, and oxidation with t -BuOOH (∼25% from 4 ).…”