Reactions phosphitylation

The Mitsunobu conditions also can be used to effect a variety of other important and useful nucleophilic substitution reactions, such as conversion of alcohols to mixed phosphite esters.56 The active phosphitylating agent is believed to be a mixed phospho-ramidite. 

Reaction of a 5 -0-protected nucleoside with moipholinophosphorous ditetrazolide (phosphitylation),... 

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

Dabkowski et al [28] have found that 2,4-dinitrophenol (DNP), whose pKa=4.1 is close to that of tetrazole pKa 4.9, acts as an efficient activator of phosphate synthesis via the phosphoroamidite procedure. The reaction of amidites with an equivalent amount of nucleoside in the presence of 2,4-dinitrophenol proceeds in very high yield and at rates comparable or higher than those when tetrazole is used. Phosphitylations activated by 2,4-dinitrophenol (DNP) take place at room temperature in aprotic solvents like THE,... 

Example 7 the bis(2,4-dinitrophenyl)phosphoroamidite which can be prepared by a standard procedure reacts with alcohols in a non-selective way which leads to a mixture of products [28]. From a mechanistic point of view this result is consistent with spontaneous displacement of a 2,4-dinitro-phenoxy group in the reaction with alcohol which liberates free DNP. The latter activates the amino group allowing further ligand exchange. However if phosphitylation by the bis(2,4-dinitrophenyl)phosphoroamidite is performed in the presence of one equivalent of triethylamine, high chemoselec-tivity is observed, and the nucleoside (2,4-dinitrophenyl)phosphoramidite is formed in over 92% yield. 

A phosphitylation procedure was carried out in THF using tetrazole as the activator subsequent oxidation was performed by TBHP in THF (steps a and b). Simultaneous cleavage of 2-cyanoethyl and Fmoc groups was achieved by DBU in dichloromethane solution (step c). Finally the tert-butyl group was removed under acidic conditions by trifluoroacetic acid (TFA). In phosphitylation reactions leading to the phosphopeptides, symmetrically protected phosphoroamidites have formerly been used [53]. 

The phosphitylation reaction (step a) and sulfurization leading to the corresponding thiophosphate (step b) proceeded under standard conditions. After deprotection (step c) and selective introduction of the DMTr group (step d) no transphosphorylation 2 3 was noted. This fact can be explained by the steric factor combined with the lower activity of thiophos-phates in comparison with normal phosphates. This enabled further phosphitylation (step e) by the customary phosphoroamidites. A difficulty in Se-kine s procedure is that the phosphitylating reagent must be prepared in situ and has relatively low purity. Luckily the by-products formed are inert tetra-coordinate species. 

No phosphitylation of biotin nitrogen N2 was observed under these reaction conditions. The phosphoroamidite formed was designed for direct use in automated DNA synthesized using standard phosphoroamidite chemistry to introduce a photocleavable biotin label on the 5 -terminal phosphate of synthetic oligonucleosides. 

The phosphitylation described in the step b leads to the dinucleoside phosphoroamidite that gave the dinucleoside phosphoroamidite which was turned into the dinucleoside arylphosphite by the reaction with 4-nitrophe-... 

Phosphitylation of inositol 3,4,5,6-tetra-O-benzyl myo-inositol by diben-zyl-iV,Ar-diisopropylphosphoroamidite gave the corresponding bis-diben-zylphosphite (step a). After 12 h at 80 °C the Arbuzov-Michaelis reaction with the excess of benzyl bromoacetate at 80 °C gave after 12 h the fully protected bis-l,2-diphosphonate (step b), which was totally deprotected by catalytic hydrogenolysis to give the desired product (step c). 

A synthetic approach to /3-sultams containing a direct bond between a tri- or tetracoordinated phosphorus atom and the nitrogen atom of the 1,2-thiazetidine 1,1-dioxide ring has been realized by direct phosphitylation or phosphorylation at nitrogen. Unfortunately, attempts to synthesize N-phosphorylated /3-sultams by reaction with diethyl phosphorochloridate and diethyl phosphorobromidate, generated in situ from diethyl phosphate and carbon tetrachloride or carbon tetrabromide, failed. However, when the /3-sultam is treated with freshly distilled diethyl phosphorochloridite or tetramethylphosphorodiamidous chloride in the presence of triethylamine, the expected AHliethy I phosphite and iV-phosphorodiamidous /3-sultams 150 are obtained (Equation 10). /3-Sultams unsubstituted... 

Oxidation of A-diethylphosphito to A-diethylphosphono derivatives 151 has been performed using 2-picoline A-oxide, MCPBA, diphenyl selenoxide, or 7-butyl hydroperoxide (TBHP). The latter was selected as the most efficient reagent. Similarly, the N-phosphitylated /3-sultams undergo reactions of oxidative addition of elemental sulfur and selenium giving 2-thio- and 2-selenophosphono /3-sultams 152 and 153, respectively, in satisfactory yields (Scheme 46) <1999HAC61>. 

X = Cl, R = 2-tetrahydropyranyl). Phosphitylation of the product from the latter reaction with the cyclic phosphorochloridlte (36) and subsequent hydrolysis afforded the phosphinlc acid (33c). Further... 

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