Tetrazolides

Tetrazolides of phosphorous acid esters or amides have been developed for the phos-phitilation of nucleosides. For instance, the tetrazolide of the diester of phosphorous acid (Af-tetrazolyldiethoxyphosphine) can be prepared either from diethylchlorophosphite and sodium tetrazolide (Method A) or from diethoxydiisopropylaminophosphine and two equivalents of tetrazole. The latter reaction (Method B) was undertaken to verify formation of a tetrazolide in the activation of phosphoramidites by tetrazole.[27]... 

Even tetrazolides, which are among the most reactive azolides, have been applied in esterifications. 

Methyl and other alkyl esters were prepared in THF, also in high yields.[130] b) Arachidonic acid was converted via its tetrazolide with the aid of oxalyldi(l,2,3,4-tetrazole), prepared in situ, into the methyl ester.[1113... 

A wide array of aliphatic and aromatic amines has been converted to amides in very high yields by the particularly reactive tetrazolides. The reaction temperature was 10 °C to 20 °C. Higher temperatures (refluxing THF) should be avoided because of instability of the tetrazolide, which in this case was prepared from benzoyl chloride and phenyltetrazole in 68% yield.[99],[100]... 

Tetrazolides are excellent starting materials for the synthesis of 1,3,4-oxadiazoles, as the following examples demonstrate. 

A more versatile approach is the thermolysis of tetrazolides, which leads to oxadiazoles in excellent yield [142],[143]... 

Reaction of the tetrazolide of phosphorous acid diester with a S -protected thymidine and subsequent oxidation with iodine yields the corresponding thymidine phosphortriester [961... 

The phosphitylation agent A-tetrazolyldiethoxyphosphine (phosphorous diester tetrazolide) can be made in situ from diethoxydiisopropylaminophosphine and two moles of tetrazole (tetrazole activation of phosphoramidites). 961... 

Tetrazolide-activated nucleotide phosphites have been employed in the synthesis of polynucleotides on a polymer support using methoxybistetrazolylphosphine as phosphi-tylating agent [104]... 

Tetrazolides can also be formed from phosphoramidites (phosphorous amides) by reaction of tetrazoles in the presence of p-dimethylaminopyridine [ 105]... 

Unreacted support-bound nucleoside hydroxy groups can be blocked with diethoxy-triazolylphosphine. Oxidation of the phosphite triester to phosphate triester was achieved by I2. Yields in the condensation exceeded 95%. Tetrazolide as phosphitylating reagent is superior to a 4-nitroimidazolide, a triazolide, or even a chloride.11061... 

Imidazolides, 1,2,4-triazolides, or tetrazolides of arylsulfonic acids have been used as condensing agents in expedient syntheses of oligodeoxynucleotides. 

In ref. [123], 1-triisopropylbenzenesulfonyl- or mesitylenesulfonyl-5-(pyridine-2-yl)-tetrazole (VIII) was successfully used as a coupling agent for the synthesis of protected di- and trinucleotides. In comparison with the sulfonic acid tetrazolides these are able to achieve a stereoselective synthesis of dinucleoside monophosphate aryl esters. 311 1241... 

A phosphitylation instead of an azole transfer occurred in the reaction of a guanosine derivative with phosphorous diester tetrazolide (diethoxytetrazolylphosphine) [2003,[2013... 

Silver l-benzeneazothiocarbonyl-2-phenylhydrazide, 3605 Sodium 5(5/-hydroxytetrazol-3/-ylazo)tetrazolide, 0682... 

Silver 5-aminotetrazolide, 0392 Silver hexanitrodiphenylamide, 3429 Silver imide, 0030 Silver nitride, 0038 Silver iV-nitrosulfuric diamidate, 0016 Silver /V-pcrchlorylbcnzylamidc. 2734 Silver tetrazolide, 0366... 

Sodium dinitromethanide, 0384 Sodium 5-(dinitromethyl)tetrazolide, 0681 Sodium 1,1,2,2-tetranitroethanediide, 1007 Sodium 2,2,2-trinitroethanide, 0713 Tetrakis(2,2,2-trinitroethyl) orthocarbonate, 3132... 

The tetrazole-catalysed alcoholysis of simple dialkylphosphoramidates (267) in THE to yield trialkylphosphites (268) occurs via nucleophilic catalysis (Scheme 29). The proposed mechanism sees tetrazole acting first as an acid catalyst to give the protonated intermediate (269), which then reacts with tetrazolide anion to yield the tetrazolylphosphite (270) alcoholysis of the latter (270) then yields the final product, the trialkylphosphite (268). ... 

The scope of the rearrangement reaction whereby azido-l,2,3-triazolide ion (66) is converted to the (diazomethyl)tetrazolide ion (68) has been studied. Where R = H, substituted phenyl, Me, and C02Me the reaction proceeds at a rate which is largely independent of substituent extensive decomposition is observed where R = COMe, COAr, and CN. PM3 calculations used to explore the energy profile of the reaction pathway indicate that the order of anion stability is (67) < (66) < (68) and that the rearrangement is of the type (66) (67) (68) for which 2 and k i ki. 

Stereochemical studies on the formation of chiral internucleotide linkages using the phosphoroamidite approach which are relevant to the mechanism of the activation process have been initiated by Stec and Zon [15]. When tetra-zole was used as the activator, however, complete epimerization at the phosphorus centre was observed and this was explained by the rapid and multiple ligand exchange at the intermediate tetrazolide. In spite of these early discouraging observations highly promising results have been recently disclosed. 

First phosphitylation was performed by 0-benzyl-bis(iV,iV,-diisopropyl)-phosphoroamidite in the presence of diisopropyl-ammonium tetrazolide at room temperature in dichloromethane solution (step a). The intermediate phosphoroamidite was coupled with a glycerol moiety in the presence of tetrazole in boiling CH2CI2 to give the benzyl phosphite (step b), which was oxidized by CPBA in CH2CI2 into the corresponding phosphate (step c). In the final step d total debenzylation was achieved by Pd/C transfer hydrogenol-ysis in the presence of formic acid and methanol at room temperature. 

Methyl 3-methoxycarbonylazocrotonate, 2830 a-Phenylazobenzyl hydroperoxide, 3609 a -Phenylazo-4-bromobenzyl hydroperoxide, 3607 a -Phenylazo-4-iluorobenzyl hydroperoxide, 3608 Potassiiun azodisulfonate, 4663 Potassiiun 4-nitrobenzeneazosulfonate, 2175 Silver l-benzeneazothiocarbonyl-2-phenylhydrazide, 3605 Sodiiun 5(5 -hydroxytetrazol-3 -ylazo)tetrazolide, 0682... 

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