Aziridine formation

Iodine azide, on the other hand, forms pure adducts with A -, A - and A -steroids by a mechanism analogous to that proposed for iodine isocyanate additions. Reduction of such adducts can lead to aziridines. However, most reducing agents effect elimination of the elements of iodine azide from the /mwj -diaxial adducts of the A - and A -olefins rather than reduction of the azide function to the iodo amine. Thus, this sequence appears to be of little value for the synthesis of A-, B- or C-ring aziridines. It is worthy to note that based on experience with nonsteroidal systems the application of electrophilic reducing agents such as diborane or lithium aluminum hydride-aluminum chloride may yet prove effective for the desired reduction. Lithium aluminum hydride accomplishes aziridine formation from the A -adducts, Le., 16 -azido-17a-iodoandrostanes (97) in a one-step reaction. The scope of this addition has been considerably enhanced by the recent... 

The azidohydrins obtained by azide ion opening of epoxides, except for those possessing a tertiary hydroxy group, can be readily converted to azido mesylates on treatment with pyridine/methanesulfonyl chloride. Reduction and subsequent aziridine formation results upon reaction with hydrazine/ Raney nickel, lithium aluminum hydride, or sodium borohydride/cobalt(II)... 

Due to the convenience of the Wenker aziridine formation from P-aminoethyl sulfate ester (4) and base, many improvements ensued. Leighton et al. improved the yield of the first step for the formation of sulfate ester 4. First of all, both ethanolamine and 95% sulfuric acid were diluted with half of their weight of water and then slowly mixed together at 0 C. Finally, by keeping the temperature below 145 C, sulfate ester 4 was obtained in 90-95% yield. 

A novel guanidinium ylide-mediated procedure has recently been reported by Ishi-kawa [62]. Though not an imine transformation, it does employ an imine precursor in the fonn of an aldehyde. Guanidinium ylides react with aldehydes to form aziridines (Scheme 1.35). The mechanism for the formation of the aziridine is believed to involve [3+2] cycloaddition between the guanidinium ylide 112 and the aldehyde, followed by stereospecific extrusion of the urea with concomitant aziridine formation. 

Figure 11.8 Hypothetical mechanism for aziridine formation in mitomycin C X = leaving group.

It is likely that the madurastatins are biosynthesized on a nonribosomal peptide synthetase, from salicylic acid as the starter acid. L-Serine is probably the precursor to the aziridine moiety, with epimerization occurring on the enzyme-bound amino acid as found for other nonribosomal peptides, with aziridine formation occurring at a late stage. Compounds 120 and 123 could therefore be biosynthetic precursors to 119 and 122, respectively. 

Table D.3) for aziridine formation from dialkyl 2-chloroalkylamines. The EM for the cyclization of Me2N(CH2)2Cl (D.3.4) for example is 1.3 M, significantly smaller than that for the reaction of the parent compound (D.3.1). The corresponding figure for the diethylamine derivative (D.3.6) is much greater (200 M), however clearly, much larger effects come into play here. The influence of alkyl substitution on the efficiency of cyclization is a complex subject and is discussed in the next section. 

The effect of N,N-dialkyl substitution on the efficiency of aziridine formation... 

Scheme 27 I -mediated regioselective conversion of a diamide to an enamide with subsequent aziridine formation and methanolysis.

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. 

Another similar, but less frequently used method for incorporation of dihydrothiazole units into cyclic peptide precursors is the Mitsunobu reaction.15135641 This reaction, however, is not suitable for the simultaneous production of dihydrooxazole rings, because of predominant aziridine formation. 571 ... 

Doyle and co-workers have recently reported Rh(ii) or copper complex-catalyzed reaction of aryldiazoacetate or vinyldiazoacetate with imines. " Diastereoselective aziridine formation is observed in the Rh2(OAc)4-catalyzed diazo decomposition of diazo phenylacetate in the presence of arylimine (Equation (28)). " When the reaction was carried out with aldehyde, epoxide 187 was obtained. 

Substituent effects on aziridine formation from N-(2-halogenoethy 1) arylsulphonamides by cyclization in basic media have been studied,425 and Hammett equation studies have also been of utility in determination of mechanisms of thermal decomposition of 3-chloro-3-aryldiazirines,426 427 the acid-catalyzed methanolysis of arylepoxides,428 and the ring expansion reactions of 2-aryl-l,l-dimethylaziridinium salts with benzaldehyde to form 5-aryl-3,3-dimethyl-2-phenyloxazolidinium salts.429... 

Epoxidation of cyclohexene by MovO(TPP)X-Bu 02H has been reported.131 Demethylation of JV,A -dimethylaniKne by Fem(TPP)Cl-PhIO offers a model for P-450-catalyzed JV-dealkylation reactions.132 The aziridine formation from acylimino Mn(Por) and alkene may be taken for the nitrogen analogue of the oxygen transfer reaction (Scheme 32).133... 

Enamine-aziridine formation is also influenced by reaction conditions. Whereas phenyl azide addition to cinnamonitrile at 90°C results exclusively in the enamine,284 thermolysis of the independently synthesized l,5-diaryl-4-cyanotriazoline (Scheme 90) yields a mixture of the aziridine and enamine from phenyl migration.332... 

Triazolines bearing three electron-withdrawing groups (Scheme 85) undergo complex thermolysis reactions. Aziridine formation is observed but sometimes the azide cycloreversion operates pyrrolidines are thus formed by reaction of the olefins with the azomethine ylides from the aziridines. The aziridines also dimerize to piperazines under the conditions of thermolysis.446... 

Interestingly, the catalytic reaction yielded predominantly the threo-4-(chloro-methyl)oxazolidinones, whereas under thermal conditions in 1,1,2,2-tetrachlo-roethane (TCE) the eryth.ro isomer was formed exclusively. If the reaction proceeded via aziridine formation followed by nucleophilic ring opening, the product stereochemistry would be erythro. As this was not the case, the involvement of an N-centered radical species was suggested (Figure 3.8). 

A computational study has probed the origin of the diastereoselectivity in aziridine formation from sulfur ylides, Me2S+-CH -R, and imines.62 For semi-stabilized cases (R = Ph), betaine formation is non-reversible, so that selectivity is determined in the (g) initial addition step. In contrast, for stabilized ylides (R = C02Me), betaine formation is endothermic, and the elimination step becomes rate and selectivity determining. 

Silylmethylamines and Their Derivatives Chemistry and Biological Activities 281 a. Aziridine formation... 

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