Phosphorochloridites reactions

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... 

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... 

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... 

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>. 

Diphenyl phosphorochloridite can be prepared from phenol and phosphorus (III) chloride, but a mixture of products is produced and the yield of the desired compound is low. Higher yields can be obtained from reaction of triphenyl phosphite with phosphorus(III) chloride, but this method is inconvenient because it involves a reaction which... 

Diphenyl phosphorochloridite hydrolyzes slowly in air and more rapidly in water, but it is less reactive toward nucleophilic reagents than most chlorine derivatives of phosphorus(III). The reaction with alcohols in the presence of a tertiary base is used to prepare diphenyl alkyl phosphites. Addition of sulfur occur.s on reaction with thiophosphoryl chloride. 

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. 

A different approach to the synthesis of aldosyl phosphates involves the intermediacy of aldosyl phosphites [470], The reaction of the anomeric hydroxyl group, with a trivalent phophitylating reagent, furnished an anomeric phosphorochloridite, which is able to react with a hydroxyl-containing compound, to generate a phosphorous triester which, upon oxidation gives the corresponding aldosyl phosphoric triester (O Scheme 83). 

Synthesis of olefins. In a new synthesis of olefins, a nonenolizable aldehyde or ketone, for example benzophenone, is treated with dimsyllithium in THF o-phenylene phosphorochloridite (2, 321-322) is added to the solution at -80°. The reaction is... 

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. 

Monodentate phosphites are another type of prominent monodentate phosphorus ligands applied in asymmetric hydrogenation of enamides for the synthesis of chiral amines. Chiral monodentate phosphites can be easily prepared from a chiral diol and an alcohol. Generally, the chiral diol was first reacted with a phosphorus trichloride to form a phosphorochloridite, followed by the reaction with an appropriate alcohol to yield a chiral monodentate phosphite [35[. The reaction of an alcohol with phos phorus trichoride to yield a phosphorodichloridite, which was then treated with a chiral diol, is also a good procedure for the synthesis of chiral monodentate phosphites [36]. 

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. 

Considerable research effort has been focused on the preparation of compounds of biochemical interest, using electrophilic reactions of phosphoramidites and phosphorochloridites to prepare modified phosphates of nucleosides or lipids. Intense interest has been shown in the synthesis of myoinositol phosphates, and also of aminoalkylphosphonic acids and their derivatives and analogues. Away from the biological emphasis, however, the first (recorded) syntheses of acetylenic phosphates have been described, and so have the first 1-alkoxyphosphole, the first cis amino-iminophosphine, and the first dithiaphospholium ions ex Phosphorus semper aliquid novi The use of silyl phosphites for synthetic purposes seems to be an increasing trend, while the number of papers on metaphosphate seems to be in decline. 

Alkoxy and/or aryloxy blocking groups are most effective only at low temperatures. Diphenyl phosphorochloridite (16) condensed with Grignard reagents in an exothermic process and the reaction mixture consequently required cooling (108). Yields of phosphonites were unstated in several examples. 

Other reactions between cyclic phosphorochloridites or cyclic esters and dienes are summarized in Scheme here, A and B are O, S or Se, and may be different or identical, and X = Cl, Br, NCS, or OR, and the conversion is brought about when mixtures of reactants are heated together in sealed tubes for extended time periods. As in the many examples known in which the reacting system, as a whole, is sulphur-free, the nature of the intermediate can be in doubt, and probably depends on the nature of the substituents, particularly those directly connected to phosphorus thus some reactants may interact through a covalent, pentacoordinate species 27, whereas others form a pseudoquatemary intermediate 28. It may also be that one intermediate structure is transformed into the second before the ultimate formation of the 3-phospholene (29). Also, in accord with these ideas, thiophosphorus(III) halides have been obseved to react with a,j5-unsaturated ketones to give, ultimately, l,2-oxa-4-phospholenes as their 2-sulphides (30) (Scheme 3)45 8. reactions carried out in acetic acid solution the products are said to be the esters... 

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