Cyclic phosphoramidate

Applications of oxazaphospholidine-borane complexes, cyclic phosphoramides, compounds with N—P=0 function, and other P-heterocycles in enantio-selective catalysis 99SL377. 

Cyclic phosphoramidates (phosphoric amides) were obtained by the reaction of amino alcohols with a phosphoric diimidazolide.tl933,[2]... 

The arylsulfonyl carbanion accelerated Claisen rearrangement is completely regioselective and has also been found to be highly diastereoselective (Scheme 2). The stereochemical course of the reaction conforms to the familiar chair-like transition state model usually invoked for the classic thermal process. Recently, high degrees of asymmetric induction have been observed in tlie rearrangements of chiral cyclic phosphoramidate stabilized carbanion derivatives. ... 

Reactions of Phosphoric Acids and Their Derivatives. - Numerous investigations of phosphate ester hydrolysis continue to be reported. The hydrolysis between 1.5 < pH < 4 of five- and six-membered cyclic phosphoramides (71) has been followed by UV and NMR spectroscopy. Small differences in hydrolysis reactivity for n = 5 and n = 6 constitutes evidence for syn lone pair catalysis. The product ratios from the hydrolysis shows that in the five-membered rings the main product is the one produced by endocyclic cleavage meanwhile, in the six- membered cyclic phosphoramide the kinetic product is the one produced by exocyclic cleavage. The syn orientation of two electron pairs on nitrogen stabilizes the transition state of water approach to the phosphoramides by ca. 3 kcal/moN when compared to the orthogonal attack. (Scheme 12). ... 

Metabolism of the important cancer chemotherapeutic agent cyclophosphamide (Cytoxan) follows a hydroxylation pathway similar to that Just described for cyclic amides. This drug is a cyclic phosphoramide derivative and, for the motit part, is the phosphorous counterpart of a cyclic amide. Because cyclophosphamide itself is pharmacologically inac-... 

Chiral phosphoramides, particularly C2-symmetric examples, are widely used in asymmetric synthesis (see section 3.2). One example is the asymmetric catalysis of Aldol reactions, where the phosphoramide catalyst is used in combination with a Lewis base. A solid state and solution study of the structure of chiral phosphoramide-tin complexes used in such reactions has now been reported. A number of chiral, non-racemic cyclic phosphoramide receptors (387) have been synthesised and their interactions with homochiral amines studied using electrospray ionisation MS. Although (387) bind the amines strongly, no evidence of chiral selectivity was found. Evidence from a combination of its X-ray structure, NMR, and ab initio calculations suggests that the cyclen phosphorus oxide (388) has an N-P transannular interaction in the solid state. A series of isomers of l,3,2-oxazaphosphorino[4,3-a]isoquinolines(389), containing a novel ring-system, have been prepared and their stereochemistry and conformation studied by H, C, and P NMR spectroscopy and X-ray crystallography... 

Details have appeared of the formation of six-co-ordinate species from o-phenylene phosphonites and catechol in the presence of triethylamine and of the remarkable properties of these salts. The formation of the phosphorane (68) in small yield from the reaction of the cyclic phosphoramidate (67) and... 

The influence of an external stereogenic center P to position 2 has been intensively studied in the rearrangement of cyclic phosphoramidates 2 and 6105-517-634 (see also p 3304). 

The preparation of (Rp) and (Sp)-N, N, O -tribenzoyladenosine 3, 5 -phosphoranilidates (96) has been greatly improved by treating the cyclic phosphate (97) with oxalyl chloride and a catalytic amount of DMF, rather than the triphenylphosphine-carbon tetrachloride mixture (Appel reaction) used previously, followed by addition of aniline. 5 near-quantitative yield of (97) obtained as a mixture of diastereoisomers is easily separated. The cyclic phosphoramidates (98-100) have also been obtained in improved yield by treating cAMP with a mixture of phosphoryl chloride and trimethyl phosphate (which had previously been pretreated with one-half a molar equivalent of water) at 0°, followed by ammonium carbonate or the appropriate amine. x e (Sp)-diastereoisomers are formed in excess, e.g. for (100) yields of 13 % of the Rp-isomer and 54 % of the Sp-isomer are obtained, and the proportion of Rp-product decreases further if pre-treatment with... 

Preparative studies have been reported on the phosphorylation of a series of hydrazines and hydrazones and on the phosphorylation of vicinal diamines with diphenyl phosphorochloridate. The cyclic phosphoramidate esters (12) and (13) may be obtained by treatment of the appropriate acyclic... 

An early study on the hydrolysis of the cyclic phosphoramidate [65] in base demonstrated exclusive endocyclic P—O bond cleavage, in contrast with the P—N bond cleavage observed for the corresponding phosphonamidate [66] (Brown et al., 1976) (Scheme 24). This observation is consistent with the similar apical potentialities of oxy and azo ligands derived by Hall and Inch in their elegant stereochemical studies of similar cyclic compounds (p. 144). 

Finally, a bidentate ligand has also been employed to prepare cyclic phosphoramidate esters such as the cyclic compounds 67 [145]. The (N-3-hydroxypropyl)-amino esters could be prepared from commercially available amino acids, ultimately allowing preparation of both the Sp and Rp isomers, and the phosphoms stereochemistry was assigned based on NMR data. Small differences in activity were found between the phosphorus stereoisomers, and the most... 

Basic hydrolysis of the products from the reaction of 3-P-D-ribofuranosyl-adenine with phosphorus oxychloride in trimethyl phosphite gave the cyclic phosphoramidate (620) as well as the expected 5 -phosphate. Phosphoramid-ates e.g. (621)] have been obtained from the reaction between nucleoside 5 -azides and 3 -silylphosphites the silylation reaction and azide condensation were conducted simultaneously (Scheme 95). ... 

Nagarkar et al. recently showed an efficient method to synthesize amine-end-functional ROMP polymers using the sacrificial block copolymer method (Figure 3.8) [53]. A cyclic phosphoramide was used to form the second sacrificial block, which could be hydrolyzed under acidic conditions. As the propagation rate of the cyclic phosphoramide was found to be very small, only a slight excess of the sacrificial monomer was necessary to achieve full end-functionalization. 

Figure 3.8 Sacrificial synthesis of amine-terminated ROMP polymers using a cyclic phosphoramide.

Reaction of a nucleoside with thiophosphoryl chloride, followed by base-promoted cyclization, provides a direct synthesis of nucleoside-3, 5 -cycllc phosphorothioates (both epimers at phosphorus). 125 Treatment of cyclic AMP with dlphenylphosphoiyl chloride produces the mixed anhydride, predominantly of Rp configuration (62), due to the greater basicity of the axial oxygen in the cAMP. The anhydride reacted with dimethylamine with inversion to give the cyclic phosphoramidate.i26 Activation of cAMP with POCI3 in (MeOlaPO, followed by treatment with an amine, also gave predominantly the Sp-phosphoramidate (63),127 and in the case of a protected cAMP, oxalyl chloride activation achieved a similar result. 128 The hydrolysis of... 

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