Phosphitylating agents

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. 

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... 

In the phosphite triester approach to the synthesis of nucleotides, morpholinophos-phorous ditetrazolide is used as the phosphitylating agent. The procedure generally consists of three steps ... 

Polynucleotides. These compounds are now generally prepared by use of a bifunctional phosphitylating agent such as o-chlorophenylphosphorodichloridite (6, 114-115) or methoxydichlorophosphine, CHjOPCl,. The intermediate nucleoside phosphites from these reagents tend to be unstable. This difficulty can be alleviated by use of I, which reacts with suitably protected nucleosides to form stable phosphoramidales 2 in good yield. These products can be activated for formation of a dinucleotide phosphite (4) by treatment with a weak acid such as N,N-dimethylaniline hydrochloride or l/Z-tetrazole (5). 

Perich, J.W. and Johns, R.B. (1988) Di-ferf-butyl WA-diethylphosphoramidite. A new phosphitylating agent for the efficient phosphorylation of alcohols. Synthesis 142-144. 

Polystyrene loaded with cyanoethoxy N,N-diisopropylamine phosphine 35 has turned out to be a versatile and mild phosphitylating agent (Scheme 15) [41]. The intermediate phosphite triester 36 was oxidized and the cyanoethoxy group was removed using DBU followed... 

The synthesis of the phosphitylating agents is exemplified by the preparation of dker/-butyl /V.TV-diethylphosphoramidite [Scheme 7.12].6 The hindered phos-phoramidites are convenient reagents being exceptionally resistant to hydrolysis or oxidation ... 

The single reported synthesis of D-(l-IPj ) started from L-quebrachitol. The main problems were the stereospecific inversion of one OH group and the demethylation from oxygen. Phosphorylation of a benzylated intermediate was achieved using the cyclic phosphoramidite (7) as phosphitylating agent with subsequent... 

Phosphorylation of alcohols can also be achieved through the phosphitylation with some kinds of tri-valent phosphorus reagents followed by oxidation. The phosphitylating agents are generally more reactive than the corresponding pentavalent analogs. Thus this approach has been used very frequently for the preparation of phosphoryl derivatives of less reactive alcdiols, such as nucleosides. ... 

Sinha N, Biernat J, Koster H. Cyanoethyl iV,iV-dialkylamino N-morpholino-monochloro phosphoamidites. New phosphitylating agents facilitating ease of deprotection and work-up of synthesized oligonucleotides. Tetrahedron Lett 24 5843-5846, 1983. 

The preparation of myo-inositol 1,4,5-triphosphate by a process involving selective formation of diastereomeric menthyl esters in a similar way to that described in Vol. 25, p. 209, ref. 59 or by resolution of racemic derivatives with R-mandelic acid or l-/-menthoxyacetyl chloride (which involves the use of a new phosphitylating agent, o-xylene AT,lV-diethylphosphoramidite) have been reported. 

The use of A -morpholino-0,0-bis[(6-trifluoromethyl)benzotriazolyl] phosphate and 2-chloro-4iV-l,3,2-benzodioxaphosphorin-4-one as phosphoiylating and phosphitylating agents, respectively, and the activation of nucleoside 3 -phosphonates by tris(2,4,6-tribromophenoxy)dichlorophosphorane are covered in Chapter 20, as is the synthesis of cytidine diphosphate 3,6-dideoxyhexoses (synthetic nucleosides). 

Trimethylsilyl)ethanol has been used as a protecting group in phosphate monoester synthesis and involves the use of 2-(lrimethylsilyl)ethyl dichlorophosphite (eq 14). Bis[2-(trimethylsilyl)ethyl] (V,(V-diisopropylphosphoramidite has been prepared from dichloro(diisopropylamino)phosphine and 2-(trimethylsilyl) ethanol and used as a phosphitylating agent in the synthesis of phosphotyrosine containing peptides (eq 15). ... 

The preparation of L-cAirt -inositol 2,3,S-trijdiosphate from L-quebrachitol has been reported/ The synthesis uses the conunercially available phosphitylating agent diethylchlorophosphine for the first time in inositol chemistry. 

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