P—N bond, cleavage

The reaction of 3 -amino-3 -desoxyadenosine 133 with thiophosphoryl chloride alTorded3, 5 -cyclothionophosphonate derivative 134 asamixture of P-diastereomcrs, which were separated by chromatography (Scheme 39) [70], The P-N bond cleavage,... 

The thionation of 2-substituted-4-aryl-5,5-dimethyl-l,3,2-dioxaphosphorinanones with Lawessen s reagent proceeded predominantly with retention of configuration and a cyclic pentacoordinated intermediate was proposed.248 Both P—N bond cleavage in acidic solution and P—C and P—O bond cleavage in basic solution occur in the hydrolysis of A-(methoxycarbonyl)carbamoylmcthoxyphosphonyl)-a-amino acid ester. Only P—O bond cleavage occurs with the ATisopropy Icarbamoy I) compound.249... 

As a consequence of the different electronic interactions within the phosphoramidate group, P-N bond cleavage in phosphoric amides, contrary to the behavior of analogous carboxylic compounds, is accelerated by the electron - donation at the nitrogen atom. 

In contrast, an analogous cyclic compound is reduced without P—N bond cleavage ... 

Since both amino and bulky substituents are known to stabilize cycloprope-nium salts [20], we chose to investigate the Lewis-acid induced P-N bond cleavage of the phosphaalkene 9, which is readily synthesized from the corresponding bis(phosphino)diazomethane 8 [21]. Indeed, treatment of 9 with two equivalents of BF3.Et2NH complex at room temperature afforded diphosphirenium salt 2 Pa as non-air sensitive pale-yellow crystals (mp 118°C) in 60% yield [22a] (Scheme 6). Subsequently, we found that using BF3.Et20 in the place of... 

Since obtaining a stable free diphosphirenylium salt 2P was quite unlikely, we chose to prepare this type of compound in the coordination sphere of a transition metal via the Lewis-acid induced P-N bond cleavage of the 1,3-diamino-diphosphirene complex l Pd. Treatment of l Pd at -78 °C with two equivalents... 

Nucleophilic substitution reactions at tervalent phosphorus centres continue to be an area of active research. Pudovik et al. have studied substitution reactions on several 1,3,2-oxazaphospholans (Scheme 5). For compounds with an exocyclic P-N bond e.g., 77) the major reaction pathway is substitution of the exocyclic substituent. The reactions however may not be simple substitutions since (78) is found to give first (79) derived from endocyclic P-N bond cleavage (79) then... 

H and n.m.r.) when (82 X = O) was treated with alcohols at room temperature the subsequent intermediate (85), which is the result of P-0 and not the expected P-N bond cleavage, was inferred from the results of model reactions. In contrast to (86), the analogue (87) does not show any evidence for a hydroxyphosphorane during hydrolysis, although with alcohols (88) is the stable product. ... 

Large rate enhancements (> 10 -10 ) are observed for hydrolysis of [24a,b,c] relative to acyclic analogues [25a,b], consistent with breakdown of the initial TBP [27] via endocyclic P—N bond cleavage (Scheme 11). However, the cyclic phenyl ester also undergoes hydrolysis by exocyclic P—O... 

These results allow formulation of mechanistic pathways for hydrolysis of the cyclic phenyl ester (Scheme 11). Whereas [24a] is postulated to hydrolyse via mixed reaction pathways, the cyclic alkyl esters [24b,c] hydrolyse exclusively via initial P—N bond cleavage. 

Mulliez and Wolf (1986) have studied the aminolysis and alcoholysis of similar five-membered species [29] to those studied by Kluger et al. (1987). Initial exocyclic cleavage is observed in solvolysis of the phosphoramidate diester [29a], whereas the phosphonamidate [29b] undergoes alcoholysis and hydrolysis with endocyclic P—N bond cleavage. These reactivity patterns are most easily accommodated by a mechanistic scheme in which initial attack is apical to nitrogen. 

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). 

N-Solvation may be important in base-catalysed P—N bond cleavage. The steric bulk of the A-aryl substituent of [67] will hinder N-solvation and hence P—N cleavage. 

P-N bond cleavage) or alkaline hydrolysis (P-O bond cleavage), and both reactions yield... 

Aspartame (Enichem/Anic). L-Phenylalanine is an intermediate for the aspartame sweetener. For a few years, it has been produced by Enichem/Anic on a scale of ca. 15 t, using a variant of the L-dopa procedure (36). The Rh/eniphos catalyst was considerably less selective than Rh/dipamp but easier to prepare and much cheaper. Crystallization of the methyl ester gave a product of 97% ee. Owing to the low stability of the ligand (P-N bond cleavage), reaction conditions had to be carefully controlled. 

The sodium salt of fV benzyltriflamide has been found useful in an approach to fV sulfonyl-phosphoramidates (eq 13). The neutral conditions during the final deprotection step avoid the P-N bond cleavage associated with a final hydrolysis under acidic conditions. Adducts formed between copper(I) cyanide and... 

The vast majority of the stereochemical studies that have been performed to date are those of enzymes that utilize a nucleotide as a substrate. However, Bruzik and Tsai reported the synthesis of the diastereomers of phosphatidylethanolamine that are chiral by virtue of substitution with 0 and 0 (Bruzik and Tsai, 1982). Their route to the desired product involves the acid-catalyzed hydrolysis of a five-membered ring cyclic phosphoiami-date, which directly yields the ethanolamine moiety on P—N bond cleavage the steps in the synthesis are shown in Fig. 5. dearly, this synthetic strategy is relatively inflexible as to the types of phospholipids that are directly accessible, but the known abihty of phospholipase D to catalyze a facile transphosphorylation reaction (with retention of configuration) does increase the number of chiral phospholipids that can be synthesized. 

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