Diethyl phosphorochloridite

Indole-3-thiol (93) reacts with diethyl phosphorochloridite or... 

Diethyl phosphorochloridite (0.714 ml, 5 mmol) was added dropwise to a stirred solution of 2,5-dimethoxytetrahydrofuran (0.65 ml, 5 mmol) in methylene chloride at 0°C under an argon atmosphere. The solution was then stirred at room temperature for 12 h, after which the solution was concentrated under reduced pressure and the residue subjected to Kugelrohr distillation (120°C/0.03 torr). There was in this manner isolated the pure diethyl 5-methoxytetrahydrofuran-2-ylphosphonate (0.475 g, 48%) as a colorless oil. 

The myotic, toxic and other physiological properties of the dialkyl phosphorofluoridates, POF(O.R)2, have been fully described on pp. 42, 68 et seq. In 19444 we described an analogous compound of the phosphorofluoridite series, namely, diethyl phosphorofluoridite, PF(OEt)2. This could not be prepared by the action of sodium fluoride on the corresponding diethyl phosphorochloridite (the preparation of which is considered below). We obtained it, however, by the action of ethyl alcohol on phosphorus dichlorofluoride,... 

Although diethyl phosphorochloridite is hydrolysed by water it did not react readily with sodium fluoride (referred to above) or potassium cyanide, but it gave derivatives with aniline and / -naphthylamine, viz. diethyl phenylphosphoramidite, (EtO)2P NHC6H5, and diethyl / -naphthylphosphoramidite, (EtO)2P NHC10H7. 

On the basis of earlier studies on reactions between trialkyl phosphites and oxo-phosphoranesulphenyl chlorides, Gusar et al. predicted that the latter should react with diethyl phosphorochloridite (112 X = OR1 = OEt) and ethyl phosphorodi-chloridite (112 X = Cl R1 = Et) according to pathway (a). The unexpected... 

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... 

The reaction of a phosphonamidite (79) with a trifluoracetyl ester (80), to give a phosphonite (81), has been shown to be catalysed by 4-dimethylaminopyridine. In contrast to an earlier report where a similar reaction proceeded with retention of configuration at phosphorus, the present system gave an equal amount of the two diastereomers (81). A mechanism is proposed which involves attack of an alkoxide, formed by de-trifluoracetylation of (80), on an equilibrating DMAP-intermediate (82). Another unusual substitution reaction is one between an alkoxyborane (83) and a phosphite (84). The phosphite was prepared in situ from acetylacetone and diethyl phosphorochloridite, and the substitution occurred under very mild conditions and gave high yields of phosphates after oxidation. 

Lee, K., and Wiemer, D.E, Reaction of diethyl phosphorochloridite with enolates. A general method for synthesis of P-keto phosphonates and a-phosphono esters through C-P bond formation, J. Org. Chem., 56, 5556, 1991. 

Attack on saturated carbon.- a-Hydroxyketones with diethyl-phosphorochloridite and ferric chloride gave 2-oxoalkylphospho-nates (1), probably via 2-oxoalkyl phosphites (2) which rearrange to (1) in the presence of the Lewis acid catalyst. No rearranged product was observed in the absence of the oxo group, and a-hydroxy esters gave the H-phosphonates (3). The 1,3,2-oxaza-... 

Mechanistic Studies. - The mechanism of the reaction of tetra-zole-activated phosphoramidites with alcohols has been studied. A series of diethyl azolyl phosphoramidites (85) was prepared from diethyl phosphorochloridite and fully characterized, and the same compounds shown to be formed from the phosphoramidite (86) and azole. The degree of formation of (85) from (86) increases with the acidity of the azole, and the proposed mechanism is a fast protonation of (86), followed by a slow, reversible formation of (85) and a fast reaction of (85) with alcohols. Another study was concerned with the influence of amine hydrochlorides on the rate of methanolysis of the phosphoramidites (87) or (88), or tris(diethylamino)phosphine.The chloride content was measured to be 10-20 mM in doubly distilled samples which explains that "uncatalysed alcoholysis is possible. Intensive purification, including treatment with butyllithium and distillation from sodium, brought the chloride content down to 0.1-1 mM. The methanolysis reaction, in methanol as the solvent, was found to be first-order in catalyst concentration. An aJb initio calculation on N- and P-protonated aminophosphine (89) gave similar proton affinities for N and P this contrasts with earlier MNDO calculations which had ff-protonated species as the most stable. The M-protonated compound had an electronic structure reminiscent of a phosphenium ion-ammonia complex. 

Phosphitylation of 8-bromo-2, 3 -0-isopropylideneadenosine with diethyl phosphorochloridite and triethylamine followed by irradiation of the resultant phosphite triester in acetonitrile affords (111) as a mixture of diastereoisomers which on deprotection gives P/ 5 -anhydroadenosine-8-phosphonic acid. The mechanism proposed involves homolytic fission of the carbon-bromine bond followed by attack on the phosphite by the C-8 radical. 

We prepared diethyl phosphorochloridite, PCl(OEt)2, (a) by the action of phosphorus trichloride on triethyl phosphite, 2P(OEt)2-l-PCl3 ---> 3PCl(OEt)2, or (b) by the action of phos-... 

An alternative to the Arbuzov route to P-keto phosphonates (40), alkylation of diethyl phosphorochloridite (41) with enolates followed by air-oxidation of the phosphonite, has been evaluated. Although some enolphosphate was formed, the ratios of P-C to P-O products were better than 12.5 1 under optimized conditions, and the products were easy to purify. The reaction is also useful for preparation of a-phosphono esters (42). A full paper has appeared on a new reagent (43) for the determination of optical purities of chiral alcohols or thiols. It is superior to previous reagents because of the large chemical shift difference between the diastereomeric products (44). 

The reaction between cyclic ketone enolates and diethyl phosphorochloridite followed by aerial oxidation of the intermediate P(III) esters, yields mixtures of C - and (7-phosphorylated products. The formation of the (1 -oxoalkyl)phosphonic diesters was optimized using diethyl ether as solvent (although better yields were sometimes obtained for reactions in Et20/THF when hexamethylphosphoric triamide was added) when the... 

Two reports dealing with the Ferrier rearrangement of 3-OH glycals have appeared. In the first protocol, 4,6-di-0-benzyl-3-hydro g -D-glycal 64 was reacted with diethyl phosphorochloridite in the presence of EtsN (3.0 equiv.) to produce a transient 3-0-dietho3grphosphanyl-D-glycal... 

Diethyl phosphorochloridite in benzene added dropwise at 20° to a stirred soln. of diethyl hydrogen thiophosphite (prepn. s. 632) in the same solvent, and stirring continued for 45 min. -> tetraethyl thiopyrophosphite. Y 71%. C. Kra-wiecki and J. Michalski, Soc. 1960, 881. 

HgS passed slowly for 3 hrs. at 5° into a stirred mixture of diethyl phosphorochloridite and pyridine or other tert. amine in benzene diethyl hydrogen thiophosphite (startg. m. f. 631). Y 83%. F. e. and isolation of intermediate thiopyrophosphites s. C. Krawiecki and J. Michalski, Soc. 1960, 881. 

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