1.3.2- Dioxaphospholanes synthesis

A synthesis of alkenes from 1,2-diols depends upon the initial formation of the 1,3,2-dioxaphospholans (128), followed by rupture of the heterocyclic ring and removal of phosphorus with Li-NH3 or Na-Ci 0H 8. The reaction is reasonably stereo-... 

The reactivity and use in organic synthesis of l,3,2,>l5-dioxaphospholanes has been presented230. Further details on various topics can be found in the following reviews Gloede (1988)344 Markovskii et a/.342, work prior to 1987 on linear equilibria between phosphoranes and phosphonium salts and Polezhaeva and Cherkasov340, results obtained prior to 1982 with cyclic derivatives. 

Five-membered heterocycles with two vicinal chalcogen atoms in the ring system can be used as stable precursors for sulfur as well as for selenium-containing hetero-1,3-dienes in cycloaddition reactions. Consequently, 3//-1,2,4-thiaselenazoles have been used for the in situ formation of 4,4-bis(trifluoromethyl)-l-thia-3-azabuta-1,3-dienes, which exist at room temperature only as 4,4-bis(trifluoromethyl)-2//-l,3-thiazetes. This strategy was applied to the synthesis of the first stable selenophosphorane from bis(trifluoromethyl)-substituted 3//-diselenazol and 2-methoxy-1,3,2-dioxaphospholan [78AG(E)774] (Scheme 83). 

Stereoselective addition of a chiral cyclic phosphite to a cyclic imine was applied to the synthesis of phosphonic analogs of d- and L-penicillamine41. Enantiomerically pure dioxaphospholane oxide 6 underwent addition to 2,5-dihydro-2,2,5,5-tetramethylthiazole in the presence of boron trifluoride as a catalyst. The diastereomeric adducts 7, obtained in a 2 1 ratio, were easily separated on silica gel and their configuration assigned by X-ray analysis the (4/ )-isomer was shown to be the major diastereomer. Hydrolysis of each diastereomer gave pure enantiomers of phosphopenicillamine 841. 

A two step synthesis of 2-oxo-2-vinyl-l,3,2-dioxaphospholanes and dioxa-phosphorinane (392) involves transesterification of diethyl phosphite with selected diols followed by palladium catalysed coupling of the resultant cyclic phosphites (393) with vinyl bromide (Figure 67). ... 

The creation of diastereoisomeric molecules which are epimeric at phosphorus presents no fundamental difficulties. Such molecules are readily available by means of reactions between the dichlorides RP(=Z)Cl2 (Z = O, S or Se) and an appropriate chiral difunctional compound. Many reactions that lead to such products were indicated in the previous chapter in connection with the synthesis of enantiomers of, particularly, (l-aminoalkyl)phos-phonic acids and related compounds. With regard to the preparation of diastereoisomeric thio- or seleno-phosphoryl compounds epimeric at phosphorus, the chiral reactants first used were modified carbohydrates and, less successfully, simple mono- or di-substituted diols. The latter provided simple monocyclic 1,3,2-dioxaphospholanes and 1,3,2-dioxaphosphorinanes which could provide (a) chiral centre(s) on (a) ring carbon atom(s), but also generated compounds epimeric at phosphorus their inconvenience often lay in lack of availability of cheap starting materials. In the case of the carbohydrates, the substrates were readily available from cheap starting materials thus, methyl 2,3-di-(9-methyl-... 

A general method for the synthesis of cyclic H-phosphonates starting with phosphoms trichloride and aliphatic glycols has been described by Lucas (see Appendix) [25], 4-Methyl-2-oxo-2-hydro-l,3,2-dioxaphospholane was obtained in two stages ... 

Preparation 6-1 2-Methoxy-2-oxo-l,3,2-dioxaphospholane is synthesized by a modified Edmundson method (31,35-37). Phosphorus tinchloride is allowed to react with ethylene glycol dry 1,2-dichloroethane. The 2-chloro-l,3,2-dioxaphospholane is oxidized to give 2-chloro-2-oxo-l,3,2-dioxaphospholane. Finally this intermediate is reacted with methanol to give the desired 2-methoxy-2-oxo-l,3,2-dioxaphospholane. The synthesis is shown in Figure 6.11. 

Polyphosphoesters (PPE) is another important class of biomedical polymers [70] that can be prepared by stannous octoate catalyzed coordination-insertion polymerization method. A representative example is the synthesis of polyfethylene ethyl phosphate) (PEEP) as reported by Xiao et al. by the polymerization of the cyclic phosphoester 2-ethoxy-2-oxo-l,3,2-dioxaphospholane (EEP) using stannous octoate and dodecanol [71] (Fig. 2.20). 

The non-isothermal degradation kinetics of A, iV -di(diethoxythiopho-sphoryl)-l,4-phenylenediamine in N2 have been studied by TG-DTG techniques as mentioned earlier. The synthesis of dioxaphospholanes ligands... 

Cationic chelate (8) was prepared and reported to exhibit excellent catalytic properties in asymmetric hydrogenation reactions, The phosphitylation of methyl a-D-mannopyranoside with P(NEt2)3 has afforded the cyclic phosphite (9), and a similar reaction applied to D-xylose gave (16), whereas both the pyranose (11) and furanose (12) derivatives were obtained from 2-O-substituted D-glucoses. The synthesis of a carbohydrate derivative of a dibenzo-substituted phosphorus heterocycle is mentioned in Chapter 7, and the conversion of methyl a-D-glucopyranoside into epoxides via dioxaphospholanes is covered in Chapter S. 

As an example of phosphorus-containing heterocyclic monomers, Yan et al. recently presented the first synthesis of a water-soluble hyperbranched polyphosphate by SCROP, using the new inimer 2-[(2-hydroxyethoxy)ethoxy] 1,3,2-dioxaphospholan-2-one (HEEP). Polymerization was... 

Hydroxyl functionalized five-membered cyclic phosphoester monomers, namely 2-(2-hydroxyethoxy)ethoxy-2-oxo-1,3,2-dioxaphospholane (HEEP), have been prepared for the synthesis of a water-soluble hyperbranched polyphosphate (HPHEEP) (13). The polymer was synthesized through a so-called self-condensation ROP (SCROP) in bulk without the addition of any catalyst. The terminal hydroxyl groups potentially provide a unique opportunity for further modification and functionalization in biomedical applications. ... 

Studies on the synthesis of cage-like phosphoranes based on casade reactions of trivalent phosphorus derivatives with unsaturated activated compounds has continued. For example, reactions of phosphites bearing dioxaphosphorinane (1), dioxaphospholane (2) and catechol derivatives (3) with hexafluoroacetone, chloral, mesoxalic and trifluoropyruvic acid esters have been performed to produce a series of novel carcass -type pentacoordinated phosphoranes with high regio- and stereoselectivity. Hence, upon treatment of hexafluoroacetone (4) with phosphites (1) and (2), pen-taoxophosphoranes (5) and (6) were formed (Scheme 1). 

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