Phosphorochloridites

Cyclic phosphorochloridites are reported to undergo rapid inversion at phosphorus. This has now been shown to depend on the purity of the sample, and pure samples, which show high barriers to inversion, have been obtained. ... 

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

A successful synthesis (Scheme 19) of the phosphonic acid analogues of D-and L-penicillamine commences with the cyclic phosphorochloridite (132). Other attempts using (132 ... 

Preparation of diethyl 5-methoxytetrahydrofuran-2-ylphosphonate — Reaction of an acetal with a phosphorochloridite... 

The reaction is performed most simply by the addition of the propargylic alcohol to a solution of the phosphorus halide. Rearrangement of the phosphorus ester proceeds at ambient temperature or with mild heating. When phosphorus trihalides are used, the product can be isolated as the phosphonic dichloride.168169 Aqueous workup provides the phosphonic acid.162 In most instances, however, a dialkyl phosphorochloridite with only a single halogen on phosphorus available for reaction with alcohol has been used.165 170 174... 

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... 

The very high accuracy which may be obtained by the pulsed Fourier transform method has been demonstrated using o-phenylene phosphorochloridite.1... 

The mono- to tetraethylene glycol modified phosphites 14a-d have been synthesized according to the first-described method starting from commercially available (o-phenylene) phosphorochloridite 13 in > 90% yield (Scheme 2). 

The aminosugar was allowed to react with phosphorus trichloride to give the intermediate cyclic phosphorochloridite (step a). The latter was trans-... 

QUINAPHOS ligands are usually synthesized in a one-pot-procedure from readily available 8-substituted quinolines [8] via nucleophilic addition of a lithium reagent [9] to the azomethinic double bond and direct quenching of the resulting 1,2-dihydroquinoline amide 1 with a phosphorochloridite derived from enantio-merically pure binaphthol (1) or from 3,3 -di-t-butyl-5,5 -dimethoxybiphenyl-2,2 -diol (m) [10] (Scheme 2.1.5.1, Method A). Alternatively, the anion 1 can be reacted with an excess (in order to avoid multiple substitution) of phosphorous trichloride to obtain the corresponding phosphorous dichloridite 2, which can be isolated (Scheme 2.1.5.1, Method B). In a second step, 2 is converted into 4 by reaction with the desired diol in the presence of triethylamine. 

The chemical basis for the phosphite triester approach is the observation, that dialkyl phos-phorochloridites such as (CjHjOJjPCI react very rapidly at the 3 -OH of nucleosides in pyridine even at low temperatures. In contrast, the reactions of analogous chloridates, e.g. (C2HjO)2POCIi require several hours at room temperature. It was later found that phosphite esters can be oxidized quantitatively to the phosphates by using iodine in water and that clean condensation of phosphorochloridites with nucleosides can be achieved in THF at -78 °C. To develop this chemistry into a useful synthetic procedure it was necessary to establish which... 

As we had hoped, the phosphorochloridite procedure, which goes at low temperature under very mild conditions, was indeed usable with the oxazoline The treatment of 4 with trichloro-... 

Reaction of an alcohol with the reagent o-phenylene phosphorochloridite followed by treatment of the alkyl o-phenylene phosphite so obtained with iodine in dichloromethane at room temperature results in a good yield of alkyl iodide. This method, exemplified by the preparation of 1-iodoheptane (Expt 5.60), is the preferred procedure when acid-sensitive functional groups are present. 

Heptyl o-phenylene phosphite. Place 87.0 g (0.5 mol) of o-phenylene phosphorochloridite, 39.5 g (0.05 mol) of dry redistilled pyridine and 500 ml of dry ether, in a 2-litre conical flask and cool to 0 °C. Add 58.1 g (0.5 mol) of heptan-l-ol dissolved in 400 ml of dry ether during about 5 minutes with occasional shaking. Stopper the flask and allow the reaction to proceed at room temperature overnight. Filter off the precipitated pyridinium chloride under suction, wash well with dry ether and remove the ether from the combined filtrate and washings on a rotary evaporator to obtain 127.0 g (100%) of heptyl o-phenylene phosphite as a colourless oil of sufficient purity for use in the next stage. 

The chloridodithioite does not react with neutral thiol, whereas the corresponding dialkyl phosphorochloridite reacts rapidly with ethanol. Consequently the latter reaction proceeds to completion even when the alkoxide has been neutralised. 

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 reactions of 7-aldiminoalcohol 296 with diethyl and diisopropyl phosphorochloridites in CHCI3 at 0°C afforded diastereomeric mixtures of substituted benzylphosphonates 299 and 300, respectively, which are believed to be formed from a common intermediate, 298 <2005RCB1496>. 

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