Aziridines phosphorylation

Epoxide Aziridine Phosphoryl/phosphonyl/ phosphinyl halide Azo... 

A convenient route to steroidal aziridines from the diaxial IN3-olefin adducts, e.g., (99), which undergo elimination with lithium aluminum hydride, was developed by Galle and Hassner. Upon treatment with trialkyl phosphite, these adducts are converted to A-phosphorylated aziridines which are reduced by lithium aluminum hydride to the free steroidal aziridine. 

The TV-phosphorylated aziridines (127) are conveniently obtained by intramolecular cyclization of iV-2-chloroethylphosphoramidate anions. The latter can be obtained by addition of AW-dichlorophosphoramidates to alkenes and hydrolytic removal of the chlorine on nitrogen.96... 

Aroylphosphonates undergo conversion, in high yield, into aroylmethylphos-phonates [(133)- (134)] when they react with diazomethane at 0 °C,108 and they also react photochemically with 3-phenyl-2//-aziridines to give C-phosphorylated oxazolines (135).109... 

Exploiting the Lewis basic phosphoryl oxygen of Im, Terada reported the direct alkylation of a-diazoesters with N-acyl imines to afford P-amino-a-diazoesters in high yields and ee s (Scheme 5.12) [23]. Earlier, Johnston had observed that catalytic TfOH promoted aziridine formation (Aza-Darzens reaction) between diazoacetates and N-benzyl imines [24]. The authors propose that aziridine formation is circumvented through C—H bond cleavage by the phosphoryl oxygen of 1 (Intermediate A). However, as noted by the authors, the low nucleophilicity of N-acyl imines might also be considered as the cause of this selective transformation. 

Despite this tendency, examples of alkylation, acylation, sulfonylation, halogenation, silylation, and phosphorylation of aziridines at nitrogen abound. Aziridinium salts can be prepared by further alkylation of the aziridine nitrogen. Aziridines can also be alkylated on nitrogen with epoxides producing -hydroxyamines. 

Diethylphosphoryl azide gives an Mo-triazoline with noibomene subsequent photolysis gives the phosphorylated aziridine, but pyrolysis gives the imine isomer. Maikovnikov addition of diethyl dibro-mophosphoramidate to alkenes (BF3 catalysis) occurs in high yield the initial adducts were converted to IV-unsubstituted products but would be readily convertible to phosphorylated aziridines ty the Gabriel method.In any case, IV-unsubstituted aziridines are readily phosphoiylated. > ... 

A synthesis of -phosphorylated aziridines commenced with the interaction of lithiated (chloromethyl)phosphonic diesters and aldimines in a highly stereoselective process yielding mainly (95%) the cis stereoisomer (171). Incorporation of CCl into the reaction system afforded a -chloro derivatives of the aziridines, a... 

Osowska-Pacewicka, K., Zwierzak, A. Reactions of N-phosphorylated aziridines with dianions derived from ethyl acetoacetate and 1,3-diketones new route to substituted pyrrolines and pyrrolidines. Synth. Commun. 1998, 28,1127-1137. 

The phosphoric acid is expected to promote the substitution reaction as a result of its dual function (Figure 3.3a). Intracomplex deprotonation from B by the basic phosphoryl oxygen would allow the direct substitution of diazoacetate, giving a Mannich type product without the formation of aziridine products. 

Amino-2, 5 -dideoxythymidine has been treated with bis(ethyleneimine) phosphinic chloride to afford the diaziridinylphosphinic amide (16), and its isomer (17) has reportedly been prepared by treating 3 -amino-2, 3 -dideoxythymidine with phosphoryl chloride and triethylamine in THF-DMSO, followed by aziridine. The latter showed higher activity in inhibiting replication of LI 210 cells. 

The conditions required for the Michaelis-Becker reaction are generally mild, from the point of view of temperature, in contrast to the higher temperatures normally required in the Michaelis-Arbuzov procedure, and this important feature allows its use in the formation of peptides containing terminal (aminoalkyl)phosphonic ester groups. Even so, the alkalinity of the media in which the former reactions take place may result in secondary reactions when A-protection in a substrate is afforded by a phosphoryl substituent, as in a dialkyl A-(2-bromoethyl)phosphoramidate, loss of HBr may occur with the formation of dialkyl A-ethenylphosphoramidate and l-(dialkoxyphosphinyl)aziridine ... 

The displacement of halide ions from N-(2-halogenoethyl) phosphoramidates under conditions of electrophilic or basic catalysis occurs with the preferential formation of aziridine derivatives a 1,5-intramolecular reaction involving the phosphoryl oxygen atom was not observed. By contrast, however, 30—50% conversions into 2-(alkylamino)-3-(2-chloroethyl)-2-oxo-l,3,2-oxazaphospho-lidines by intramolecular O-alkylation have been reported in an extensive and detailed study of the chemistry of AW-bis(2-chloroethyl) phosphoramidic acid amides [114 = H, R = Me, Bu, or cycloHex or R -R = (CH2)6]. At... 

When treated with four molar equivalents of a primary amine RNH2. the phosphoramidic dichloride (184) yields the triamide (185). When these (R = Me or Bn) are further treated with NaH, the sole products are the A/-phosphorylated aziridines (186), but for (185 R = aryl), a mixture of (186) and the cyclic triamide (187) results. 

Palacios, R Ochoa de Retana, A.M. Alonso, J.M. Regioselective synthesis of fluoroalkylated 3-aminophosphorus derivatives and aziridines from phosphorylated oximes and nucleophilic reagents. J. Org. Chem. 2006, 71, 6141. 

Atherton-Todd phosphorylation, 353 Azetidinecarboxylic acids, 260 Azidoalkanes, 153 Aziridine, 52 Aziridines, 106 Azirines, 322, 323 Azobenzene, 331, 332, 392 Azobisisobutyionitrile, 224 Azoxybenzene, 331, 332 Azoxybenzenes, 12... 

Aziridine-2-phosphonates spiro-fused with 2-oxindole (790) have been prepared by a straightforward Horner-Wadsworth-Emmons reaction of ethyl 7V- [(4-nitrophenyl)sulfonyl]oxy -carbamate (791) and 3-(phosphoryl-methylene)oxindoles (792) in the presence of calcium oxide. Oxindoles (792) were also transformed into novel oxirane-2-phosphonates (793), as oxygen analogues of (790), by reaction with H202/Na0H (Scheme 201). " Cinchonine-based thiourea (797) catalysed asymmetric Michael addition of simple p-oxo-alkyl phosphonates (794) to nitro olefins (795), which afforded valuable a-substituted p-oxo phosphonates (796) in satisfactory yields with good to excellent enantioselectivities (up to 98% ee) (Scheme 202). ... 

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