Cyclic phosphite

Phosphites, such as triisopropyl and triphenyl phosphite, are weaker electron donors than the corresponding phosphines, but they are used in some reactions because of their greater rr-accepting ability. The cyclic phosphite trimethylol-propane phosphite (TMPP) or 4-ethyl-2,6,7-trioxa-l-phosphabicyclo[2.2.2]oc-tane (8), which has a small cone angle and small steric hindrance, shows high catalytic activity in some reactions It is not commercially available, but can be prepared easily[27]. 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

Examples of cyclic aliphatic or aryl phosphonate triesters, such as 36 or 37 have also been prepared by this HHT method from their cyclic phosphite precursors (2). 

Various cyclic phosphonate esters 36 and 37 have been described previously as products from the HHT reaction of 25 with the appropriate cyclic phosphite. A complementary method has also been developed from the V-protected phosphonyl chloride 84, which was readily prepared from the corresponding phosphonic acid 83. Subsequent reaction of 84 with the appropriate diol produced the cyclic phosphonate esters 85 (63). Higher homologs of 85 have also been prepared from the analogous propane or butane diols. 

Finally, new tricyclic hexacoordinated phosphoranes with internal P-N coordination were synthesized by Swamy and coworkers by oxidative addition of cyclic phosphite precursors with quinones or with a combination of diols and (z-Pr)2NCl [57, 58]. Various ring sizes from five to eight membered were obtained showing the generality of the approach. A selection of compounds (47a-47e) is presented in Fig. 8. 

A. Nucleophilic Reactions.—(/) Attack on Saturated Carbon. The Arbusov reaction has been used to prepare organosilicon-substituted phosphonates (1) and phosphorylated ethers (2a) and sulphides (2b). Bromo- and chloro-derivatives of the cyclic phosphite (3) do not react with ethyl halides... 

D. Cyclic Esters of Phosphorous Acid.—There has been some controversy about the stable stereochemistry at phosphorus in cyclic phosphites and phosphonites this now appears to be resolved by agreement in a series of papers. The stereochemistry of 2-alkoxy-4-methyl-l,3,2-dioxaphosphorins... 

Russian workers have studied secondary cyclic phosphites (113) and (114). Unfortunately, the situation is far from clear since m-(115) iso-nierizes to trans- 16) on standing, " but (117) is suggested to be thermodynamically more stable than (118). This apparent contradiction could be explained by either an incorrect assignment of isomers or a 1,3-interaction of the 4-methyl group in (114). 

An extensive paper by Burgada et l. reports the reactions of cyclic phosphites (75 ab) and cyclic phosphoramidites (76 ab) with trans-1,2-dibenzoylethene, methyl fumarate, benzalacetone (PhCH=CH COMe), methyl-4-keto-pent-2-enoate (MeCO.CH=CH.COgMe) and benzalacetophenone (PhCH=CHCOPh)95. These reactions lead to... 

A convenient synthesis of uridine 2, 3 -cyclic phosphite 15 (as a 3 4 mixture of diasteroisomers because of the chirality at phosphorus) was based on the reaction of the suitably protected uridine derivative 14 with ethyl dichlorophosphite carried out in the presence of triethylamine and anhydrous ethanol (Scheme 6) [21]. After adding ethanol into the reaction medium, an efficient chromatographic separation of the crude reaction product was achieved on silica gel with diethyl ether giving analytically pure phosphite 15 in 75% yield. It is interesting to note that without adding ethanol, 15 is very unstable. 

Nitrophenyl 2, 3 -0,0-cyclic phosphites 18a-d were formed rapidly and cleanly as two diasteroisomers in the reaction of 5 -0-protected ribonucleosides 16a-d with tris(4-nitrophenyl) phosphite (17) in the presence of pyridine [reaction time less than 3 min at room temperature in DMF/pyridine (9 1 v/v) solution (monitored by 31P-NMR )]. Their sulfhydrolysis, which is also very rapid using an excess of hydrogen sulfide at room temperature, gave cyclic //-phosphonothioatcs 19a-d (Scheme 7) [22], In this reaction, the corresponding 2, 3 -0,0-cyclic... 

Reaction of the sodium salt of a cyclic phosphite diester with a bis-benzylic halide... 

Hoppe, I., Schollkopf, U., Nieger, M., and Egert, E., Asymmetric addition of a chiral cyclic phosphite to a cyclic imine — synthesis of phosphonic acid analogues of d- and L-penicillamine, Angew. Chem., Int. Ed. Engl., 24, 1067, 1985. 

The phosphoranes, e.g. (69), which are intermediates in the Arbusov reactions of the cyclic phosphite (68) with chlorine, bromine, and benzenesulphenyl chloride have been detected at low temperatures by 31P n.m.r. spectroscopy.47 A similar technique revealed the intermediate (71) in the reaction of the thiophosphate (70) with chlorine.48... 

The stereochemistry of the seven-membered cyclic phosphites (94), (95), and (96), prepared from the base-catalysed reaction of triphenyl phosphite and the corresponding diol, has been investigated by 1H, 13C, and 31P n.m.r.73 The results suggest that each of the three heterocycles adopts a different conformation in solution. 

Y = OEt) have been detected in the reactions of halogen with a cyclic phosphite 40 the reaction with chlorine gave a resonance at dp +35 and bromine gave a resonance at dp +195 p.p.m. The latter is at higher field than the tribromo-compound (21 X = Y = Br dp +189 p.p.m.) and the chlorodibromo-compound (21 X = Br,... 

Shift reagents have been used for the configurational and conformational analysis of cyclic phosphites (34).65 The reagent Eu(fod)3 moved Ha of the vinylphosphine oxide (35) twice as far downfield as the corresponding proton in the spectrum of the... 

The molecular ion appears to retain its cyclic structure, but several ions with two or three phosphorus atoms can be detected.192 The fragmentation patterns of a number of dialkylphosphines (157) show initial loss of an alkyl group as a neutral particle formed by the transposition of hydrogen.193 Some six-membered cyclic phosphites (158 X = OEt, OPh, or Cl) have been studied.194 The mass spectra of a wide variety of phosphine sulphides (159 Z = Ph, Me, CH2Ph, COPh, NH2, N=CHPh, or... 

Although the presence of BINOL in the ligands so far discussed has shown itself to be particular effective, modification of the diol moiety provides new classes of ligands for this addition reaction. Alexakis, screening a number of chiral phosphites in the Cu(OTf)2-catalyzed 1,4-addition, showed that an ee of 40% could be obtained for the addition of Et2Zn to 2-cyclohexenone and of 65% for addition to chalcone, by using cyclic phosphites derived from diethyl tartrate [51]. 

The phosphite formed was efficiently oxidized by MPBA (step b). Use of trimethylamine N-oxide as an oxidant was investigated in the hope that this reagent would oxidize the cyclic phosphite and that trimethylamine formed would be employed in the ring opening reaction (step c) to produce the phosphorylcholine in a one-flask procedure. In this case to avoid the residual oxidant in the product less than one equivalent of the oxidant was used and it was necessary to add an additional amount of trimethylamine to form the desired 2-(methacryloxy)ethylphosphorocholine in good yield. 

Among the nucleophilic monomers studied are 5,6-dihydro-4T/-l,3-oxazines, cyclic phosphites and phosphonites, iminodioxolanes, and imines electrophilic monomers include... 

Cyclic chlorophosphite 69 was obtained in the reaction of 68 with PC13 under conditions elaborated by Lucas et al.57). Hydrolysis of 69 with less than stoichiometric amounts of water produced the required five-membered cyclic phosphite 70, being stable at least for a few days. The monosubstituted five-membered cyclic phosphites are known to undergo spontaneous polymerization when prepared by hydrolysis with a stoichiometric amount of water in the presence of tertiary amines used for HC1 traping S8,59). 

Carbonylation of propargyl carbonates bearing an amino group yields lactams. The a-vinylidene /1-lactams 82 are prepared by the carbonylation of 4-benzylamino-2-alkynyl methyl carbonates 81 [20], The best results are obtained by using the cyclic phosphite (4-ethyl-2,6,7-trioxa-l-phosphabicyclo[2,2,2]octane) (83). The lactam formation is carried out in THF or MeCN as solvents at 50 °C under 1-10 atm of CO. 

The reactivity of cyclic phosphites also depends strongly on the mutual orientation of nP and Wq lone pairs. Triethyl phosphite (1) (Scheme2.12), for instance,... 

With cyclic phosphite 3, when the trapping reagent used in reaction is phenol, we obtain a quantitative yield of ylid. Between 0° and 20° this ylid undergoes a complete rearrangement leading to a phosphorane (J ) ... 

The nature of alkyl halide and the environment of the phosphorus atom make a substantial contribution to the direction of the reaction. Thus, cyclic phosphites [108], like trialkyl phosphites [110], react with preservation of the coordination of the P(III) phosphorus atom (126-132 ppm). If the alkoxyl group is substituted by amide, alkyl, or aryl, the nucleophilicity of the phosphorus atom in the corresponding amidophosphite (phosphonite) increases in comparison with the trialkyl phosphite. This probably promotes attack by 1 -haloalkyl-2-pyrrolidone at the phosphorus atom and not the oxygen, and this was confirmed experimentally. As a result of the investigated reactions amidophosphonates or ethyl phenyl phosphinates llOa-c were isolated compounds with P(III) were not detected in these cases. 

In addition to the copolymerizations involving 34 and ME monomers (Table 2), several new copolymerizations of P(III) compounds have been discovered. One prototype is seen in the combination of a cyclic phosphite 38 and an a-keto acid 39 (Eq. (25))34l35). 

According to Eq. (25), a cyclic phosphite monomer (MN) 38 is oxidized to a phosphate unit yielding copolymer 40 whereas the a-keto acid monomer (ME) 39 is reduced to the corresponding a-hydroxy acid ester. Thus, the term redox copolymerization has been proposed to designate this type of copolymerization in which one monomer is reduced and the other monomer oxidized. The redox copolymerization clearly differs from the so-called redox polymerization in classical polymer chemistry where the redox reaction between the two catalyst components (oxidant and reductant) is responsible for the production of free radicals. 

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