Phosphites bicyclic

A review on the application of the phosphoramidite method to the synthesis of phosphorylated biomolecules covered, inter alia, mononucleotides, glycosyl phosphates, inositol phosphates and inositol phospholipids. Dibenzyl iVA -diethyl phosphoramidite has been recommended as an efficient and convenient reagent for the preparation of dibenzyl glycosyl phosphites. Bicyclic phosphorylated carbohydrates have been reviewed (40 pp., 60 refs.) in Russian. The rearrangement of a sugar bicyclothiophosphate to a thiosugar bicyclophosphate is covered in Chapter 11. 

The bicyclic phosphite (11) with ozone gave a remarkably stable adduct (12) which decomposed to form singlet oxygen only above 0 °C. 

The bicyclic phosphites (44) and (46) did not react with benzil, even at 60 °C for 20 days. With diacetyl at 60 °C for 8 days the 1 2-adducts, e.g. (45) from (44), were obtained. The reluctance of these bicyclic phosphites to form stable phosphoranes is remarkable as their geometries appear to be ideal for this purpose. 

The preparation of the bicyclic phosphite (89) from tri(hydroxymethyl)-phosphine and trimethyl phosphite has been reinvestigated following reports that it could not be repeated. The reasons for the difficulties... 

The equilibrium interconversion between an ethylene phosphite and a bicyclic spirophosphorane is shown to proceed by the insertion of the phosphite into the labile O-H bond of the hydroxyethyl ester. The mechanism is similar to the insertion of carbenes or nitrenes. Energy relationships of reaction intermediates were studied by MO RHF, MP2(full), MP4SDTQ, and DFT calculations. In most cases, they predicted that hydroxyethyl ethylene phosphates were more stable than the strained spirophosphoranes, which is not supported by the experimental evidence. The best correspondence to experimental data was obtained by DFT calculations with Perdew-Wang correlation functions <2003JST35>. 

Since then, optically active a-aminophosphonates have been obtained by a variety of methods including resolution, asymmetric phosphite additions to imine double bonds and sugar-based nitrones, condensation of optically active ureas with phosphites and aldehydes, catalytic asymmetric hydrogenation, and 1,3-dipolar cycloadditions. These approaches have been discussed in a comprehensive review by Dhawan and Redmore.9 More recent protocols involve electrophilic amination of homochiral dioxane acetals,10 alkylation of homochiral imines derived from pinanone11 and ketopinic acid,12 and alkylation of homochiral, bicyclic phosphonamides.13... 

One notable advance in this chemistry since the publication of CHEC-II(1996) is the use of enantiomerically enriched 3,6-dihydro-l,2-thiazine 1-oxides in the rearrangement sequence. For instance, iV-Cbz-protected bicyclic 1,2-dihydrothiazine 44 undergoes ring opening upon treatment with phenylmagnesium bromide (Scheme 16). The synthesis of allylic amino alcohol 129 is completed in excellent yield upon exposure of the intermediate sulfoxide 130 to trimethyl phosphite and methanol at 80 °C <2002TA2407, 2000TL3743>. 

A rhodium-catalyzed hydroformylation was also carried out with the bicyclic terpenes [S-pinene and camphene [44, 45]. The influence of phosphine and phosphite ligands (L) on the formation of the different product isomers of the hydroformylation of [S-pinene was studied by adding different mono- and bidentate ligands. However, the basicity of the ligands proved to be relevant for favoring the c/.v-isomer. A steric influence of the ligands to favor one isomer was not found (Scheme 14). 

Incorporation of azo-links into polydienes markedly improves the stability of the polymer through a reversible cis-trans isomerization process. Apparently, the more mobile the polymer chains, the more effective the process. Other interesting systems include pyrene, lignin from sugar cane, acidic tar products,aromatic epoxypropylamines, 1,3,5-triphenylpyrazole, and hydroxyethylimides of bicyclic dicarboxylic acids in polyolefins. Studies on PVC stabilization include the effects of phosphites and absorbers. ... 

Diels-Alder reactions of enantiomerically enriched 2H-azirine 3-phosphon-ates (281), a new class of chiral iminodienophiles, and dienes stereoselectively furnish optically pure, bicyclic aziridine adducts (282). Hydrogenation of (282) results in a ring opening that affords the first examples of optically pure quaternary piperidine phosphonates. Two step synthesis of an enantiomeric pure cyclic phosphite (283) and its application as a chiral phosphorus nucleophile in the asymmetric Michael addition to nitroalkenes (284) provides an efficient... 

The deuterium labelling established that the y, 5-unsaturated, nitrile 241 equilibrates at room temperature with the iV-allylketene imine 242 through an intramolecular rearrangement mechanism. Deuterium has been applied in the study of the novel palladium(0)-catalysed cyclization of 2,7-octadienyl carbonate containing an allylsilane moiety, 243, to product 244 (in 89%) and some 245 in the presence of phosphite 246 (equation 99). Intramolecular KlEs (Ah/Ad =3.0 and 3.5) have been observed in a bicyclic olefin formation (monoterpinene biosynthesis from [1- H,4- H2]- and [10- H2]-geranyl pyrophosphates) catalysed by pinene synthases from sage (Salvia officinalis). ... 

Even in the early days of homogeneous hydrocyanation the reaction of norbor-nene with hydrogen cyanide in the presence of tetrakisftriphenyl phosphite)palla-dium(O) 12 indicated the influence of steric factors, since exo-5-cyanobicy-clo[2.2.1]heptane (Structure 10) is obtained stereospecifically. This result was confirmed in similar reactions showing that the entering cyano group is directed into the exo-position of the norbomene system [28]. This is due to the complexa-tion of the palladium(O) center to the exo-face of norbomene. Recent experiments have also utilized the bicyclic system to demonstrate asymmetric hydrocyanation induced by chiral palladium diphosphine complexes. Depending on the applied ligand system 11-17, an enantiomeric excess (ee) up to 40% is obtained [25]. 

Lei, G., Xu, H., Xu, X. Staudinger reaction between bicyclic phosphites and azides. Phosphorus, Sulfur Silicon Relat. Elem. 1992, 66,101-106. 

Bicyclic phosphites. Trimethylolethane when heated with triethyl phosphite and a trace of triethylamine affords a crystalline phosphite, m.p. 94°. ... 

Reaction of the benzoxazaphospholine 47 with the hydroxymethyl bicyclic phosphite 48 gave the polycyclic compound 51 by dimerisation of the intermediate 50. A similar reaction of 47 with pentamethylene diol (52) gave an unsymmetrical spirophosphorane (54) with a P-C bond via 53. ... 

The success of cycloisomerization reactions of this type is critically dependent on factors that influence the conformational mobility of the side chain bearing the alkene moiety. Additionally, functional groups which are able to serve as ligands at palladium may also be of importance. As an example, neither the (E)- nor the (Z)-crotonate derivative ( -IS or (Z)-13 gives rise to the formation of bicyclic products on treatment with bis(dibenzylideneacetone)palladium/tri-isopropyl phosphite. Instead, the corresponding isomeric substituted butadienes, methyl (2E or 2Z,6 )-7,8-dimethylnona-2,6,8-trienoate (14) and methyl (2E or 2Z)-8-methyl-7-methyl-enenona-2,8-dienoate (15), are formed. 

The five-co-ordinate species (80) and (81) formed by the oxidative addition of pseudohalogens to (79) have been detected by n.m.r. spectroscopy at low temperatures. The compound (80 R=OPh) was stable at room temperature. Phosphoranes have been obtained from the bicyclic phosphites (70) with perfluorobi-acetyl and 3,4-bistrifluoromethyldithieten, and their variable-temperature n.m.r. 

Bicyclic phosphites (107) and related compounds have recently been shown to possess very high toxicity, and so their X-ray structural analysis is of interest (see Chapter 11). 

A study of the shifts produced by europium and praseodymium reagents on a series of ethoxy and ethyl phosphinous and phosphoryl compounds showed that the phosphorus shifts of the phosphines and phosphoryl compounds differed from the proton and carbon shifts in that they were dominated by contact interactions. Large pseudocontact phosphorus shifts for triethyl phosphite indicate that there is little direct P - La interaction. Shift reagents have been used in the stereochemical assignments of some bicyclic oxides such as (57) and the conformational analysis of dioxaphosphorinans (58) and dithiaphosphorinans (59). The conformational... 

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