Aziridine formate reactions

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)... 

The synthesis of aziridines through reactions between nitrenes or nitrenoids and alkenes involves the simultaneous (though often asynchronous vide supra) formation of two new C-N bonds. The most obvious other alternative synthetic analysis would be simultaneous formation of one C-N bond and one C-C bond (Scheme 4.26). Thus, reactions between carbenes or carbene equivalents and imines comprise an increasingly useful method for aziridination. In addition to carbenes and carbenoids, ylides have also been used to effect aziridinations of imines in all classes of this reaction type the mechanism frequently involves a stepwise, addition-elimination process, rather than a synchronous bond-forming event. 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

Photoelimination of nitrogen from 1,2,3-triazolines has been widely used as a synthetic route to aziridines the reaction has been reviewed.355 Recent applications include the formation of a new valence isomer (425) of azepine from the triazoline 426,356 and conversion of the triazoline 427 into the aziridine 428, a process with potential as a synthetic route to mitomycins.357... 

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. 

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... 

The synthesis of chiral w-amino phosphonic acids (analogues of natural amino acids) may be accomplished from imines. The key step in this synthesis is the formation of an aziridine by reaction of a phosphonamide with an imine (equation 153)555. The reaction occurs in very good yield in THF, at —78 °C with BuLi. 

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). 

Compound 46 and benzaldehyde are considered to be most likely formed by the ring-opening reaction of aziridine 44, giving an azomethine ylide, followed by hydrolysis. Thermolysis of 32 also affords 44-46, and benzaldehyde in 79%, 100%, 15%, and 16% NMR yield, respectively. This is the first example of aziridine formation from heterocyclobutanes with high coordinate main-group elements. 

Diazoacetates are commonly used for the formation of aziridines from imines under Lewis or Bronsted acidic conditions - a process known as the aza-Darzens reaction. A useful twist on the reaction is achieved if the 1,2-addition intermediate undergoes deprotonation of the a proton prior to intramolecular aziridine formation with N2 extrusion. Such an interrupted aza-Darzens reaction accomplishes a... 

To explain the enantioselectivity obtained with semi-stabilized ylides (e.g., benzyl-substituted ylides), the same factors as for the epoxidation reactions discussed earlier should be considered (see Section 10.2.1.10). The enantioselectivity is controlled in the initial, non-reversible, betaine formation step. As before, controlling which lone pair reacts with the metallocarbene and which conformer of the ylide forms are the first two requirements. The transition state for antibetaine formation arises via a head-on or cisoid approach and, as in epoxidation, face selectivity is well controlled. The syn-betaine is predicted to be formed via a head-to-tail or transoid approach in which Coulombic interactions play no part. Enantioselectivity in cis-aziridine formation was more varied. Formation of the minor enantiomer in both cases is attributed to a lack of complete control of the conformation of the ylide rather than to poor facial control for imine approach. For stabilized ylides (e.g., ester-stabilized ylides), the enantioselectivity is controlled in the ring-closure step and moderate enantioselectivities have been achieved thus far. Due to differences in the stereocontrolling step for different types of ylides, it is likely that different sulfides will need to be designed to achieve high stereocontrol for the different types of ylides. 

Aziridine formation can therefore never be a proof for the involvement of a nitrene. Addition of carbethoxy nitrenes to carbon-carbon double bonds is observed in solution 35,79-83) as weu as in the gas phase 84,85), in these reactions the singlet and the triplet species are involved, the former add stereospecific-ally 80,81,83) an(j the latter nonstereospecifically. The addition of singlet and triplet carbethoxynitrene 29 to cis- and trans-4-methylpentene-2 37 has been studied very carefully 80,83,86) Both adducts 38 and 39 were formed — showing that the reaction was not stereospecific. 

Aziridine formation fix>m arylnitrenes, rather than via triazolines, is known for highly fluorinated arenes. Phenyl azide with trifluoroacetic acid generates a nitrenium ion which adds stereospecifically to alkenes to give aziridines. Yields are rather low, partly due to concurrent ring opening of the aziridine by addition of trifluoroacetic acid. Similar reactions can be achieved with Lewis acids such as AlCb Enamines with aryl azides can yield either 2-aminoaziridines or amidines. ... 

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