2- aziridine derivatives

The application of 3-amino-2//-azirines as amino acid equivalents and their use in the synthesis of cyclic dipeptides presumably includes ring enlargement steps [14]. The formation of 12- or 15-membered cyclodepsipeptides from open chain precursors possibly includes ring enlargement steps [3] [15]. 

The few examples of ring enlargement reactions of 2H-azirines and aziridines discussed above demonstrate their vast application in the synthesis of hetero- 

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Other potential synthetic routes to these unsaturated aziridine derivatives which involve the addition of nitrenes to allenes <75JOC224), carbenes to imines with subsequent hydrolysis <67JA362), and of carbenoid species to ketenimines <76TL1317,79TL559) have been investigated but are collectively of little or no preparative value. 

A number of nonfused steroidal aziridines have been synthesized. The reduction of the azirine (118) over a platinum catalyst yields the spiro aziridine (119). Several aziridine derivatives of the type (120) have been... 

The present authors have found that the preparation of 7V-acetyl aziridine derivates provides the most secure method of differentiating aziridines from primary amines which are alternate reaction products in a number of cases. The infrared spectra of the former derivatives show only a peak at 1690 cm" for a tertiary amide peaks at ca. 3440 and 1530 cm" indicative of a secondary amide are absent. Acetylation also shifts the aziridine ring protons to a lower field in the NMR by ca. 1 ppm relative to the parent aziridine. The A"-acetyl aziridines are hydrolyzed with 3% methanolic potassium hydroxide. " Published NMR spectra of several 16j5,17j -aziridines reveal resonance patterns resembling those of the respective epoxides. " ... 

Enantioselective synthesis and transformations of oxirane and aziridine derivatives 99PAC423. 

By reaction of an imine 6 with a a-halo ester 2, an aziridine derivative 7 can be obtained " ... 

Thus, in contrast to benzothiepins, dibenzo compounds can be synthesized by direct acid-catalyzed elimination of water from hydroxy derivatives, or of amines from amino derivatives, at elevated temperatures due to their thermal stability. As in the case of benzothiepins, dibenzo derivatives can also be prepared by base-catalyzed elimination from the corresponding halo derivatives however, the yields are somewhat lower compared to the acid-catalyzed reactions. As a special case, an aziridine derivative was deaminated by palladium-catalyzed hydrogenation to afford the corresponding dibenzothiepin.69... 

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

In many instances, however, the intermediate triazoline can be isolated and separately converted into the aziridine, often with poor stereoselectivity. The first practical modification to the original reaction conditions generated the (presumed) nitrenes by in situ oxidation of hydrazine derivatives. Thus, Atkinson and Rees prepared a range of N-amino aziridine derivatives by treatment of N-aminophthali-mides (and other N-aminoheterocydes) with alkenes in the presence of lead tetraacetate (Scheme 4.10) [7]. 

The aminotin compounds are less readily prepared, and are more reactive both in substitution and addition processes, than the alkox-ides. The established routes to, and reactions of, these compounds are exemplified by recent work on the aziridine derivatives (217). 

Aziridines can be prepared directly from double-bond compounds by photolysis or thermolysis of a mixture of the substrate and an azide. The reaction has been carried out with R = aryl, cyano, EtOOC, and RSO2, as well as other groups. The reaction can take place by at least two pathways. In one, the azide is converted to a nitrene, which adds to the double bond in a manner analogous to that of carbene addition (15-62). Reaction of NsONHC02Et/ CuO [Ns = A(/7-toluenesulfonyl-inimo)] and a conjugated ketone, for example, leads to the A-carboethoxy aziridine derivative.Calcium oxide has also been used to generate the nitrene.Other specialized reagents have also been used." ... 

The elegant feature of this synthetic sequence is that an aziridine-derived chiral catalyst is used to achieve the desired diastereoselectivity. 

Photolysis of ferrocenylsulphonyl azide in cyclohexene gave the corresponding aziridine derivative (9%), but thermolysis did not 17>. This could be an addition of the triplet nitrene to the olefin and studies on the stereospecificity of this reaction are under way. 

Figure 15.7 The reaction of aziridine derivatives with fullerenes also can give pyrrolidine derivatives useful for...

Acyl azides 268, derived from furan, thiophene and selenophene, add slowly at room temperature to the strained double bond of 5-methylenebicyclo[2.2.1]hept-2-ene. Two regioisomeric triazolines, 269 and 270, which form in the first step, are unstable and decompose with elimination of nitrogen to provide aziridine derivatives 271. Products 271 are isolated in good yield (73-85%). It is worthy to note that not only the terminal, unstrained double bond in the starting material, 5-methylenebicyclo[2.2.1]hept-2-ene, is unaffected, but also the typical dipolarophiles like esters of crotonic, propiolic and byt-2-ynoic acids do not react with azides 268 under these conditions (Scheme 39) <2002J(P1)1420>. 

Some fragmentation reactions from cyclopropyl carbenes and aziridine derivatives are as follows ... 

An interesting contrast is shown in the stabilities of the aziridines derived from the isomeric A-/erf-butyl 2-methylpropylideneimine and A-iso-propyl 2,2-dimethyl-propylidineimine. Solvolysis of the A-terr-butyl derivative occurs readily under the basic conditions, whereas the aziridine derived from the A-wo-propyl compound is more stable and can be isolated in 75% yield. 

Further band-shape work (35) has been performed on malonic ester derivatives 9 (R = H R, R2 = —(CH2) —, with n increasing from 2 to 5). The C=C barriers showed a steady decrease from AG > 23.2 kcal/mol for n = 2 to 14.6 kcal/mol for n — 5, whereas the C—N barriers were less dependent on the ring size. An exception was the aziridine derivative, for which the C—N barrier was <7.3 kcal/mol. 

However, it is worth noting that anodic oxidations of aziridine derivatives can give a mixture of opened compounds [242]. 

The aza-Payne rearrangement and its use as a synthetically valuable equilibration process has been reviewed. Unusual diazadioxabicyclo[2.2.2]octanes (352) have been obtained by the acid-catalysed rearrangement of A -quinazolinonyl- and A -phthalimido-aziridines derived from 3-phenylcyclohex-2-enol. ° A probable mechanism is outlined in Scheme 108. A-Acyl-2,2-dimethylaziridines have been isomerized by sodium iodide into three isomers whose yields appear to depend... 

In addition, the three-component coupling reaction of aliphahc aldehydes 45, aliphahc amines 46 and ethyl diazoacetate (EDA) 47 was achieved under the influence of an [IrCl(cod)]2 catalyst to afford the aziridine derivatives 48, under mild condihons (Equation 10.9) [25]. 

In cyclic amines rigidity of the ring and a small angle between the C-N bonds characteristically result in a relatively high energy barrier to inversion of configuration at the nitrogen atom. The effect is most marked for aziridine derivatives, for which the kinetics of inversion processes are conveniently studied by variable-temperature NMR... 

Stance, although Mn(TPP)Cl-catalyzed reaction of 19 with styrene affords aziridine derivative in 80% yield (Eq. 13), significantly lower yields are obtained with other olefins. Allylic insertion by the metal nitrenoid is frequently the major side reaction encountered during olefin aziridination (88TL1927) (Eq. 14). 

At about the same time, Wenkert and c-workers (75) reported a similar smdy into the intramolecular 1,3-dipolar cycloaddition of 2-alkenoyl-aziridine derived azomethine ylides. Thermolysis of 231 at moderate temperature (85 °C) produced 232 as a single isomer in 58% yield. Similarly, 233 furnished 234 in 67% yield. In each case, the same stereoisomers were produced regardless of the initial stereochemistry of the initial aziridine precursors. However, the reaction proved to be sensitive to both the substituents of the aziridine and tether length, as aziridines 235 and 236 furnished no cycloadducts, even at 200 °C (Scheme 3.79). 

Bei der Hydrogenolyse [a]-anellierter Aziridin-Derivate kann Ringerweiterungunter Spal-tung einer C —N-Bindung eintreten, z.B. bei der katalytischen Hydrierung des Aziridins II zu 7,8-Dimethoxy-2-phenyl-2,3,4,5-tetrahydro-IH-3-benzazepin (82%)4 ... 

Isodrin (56) gives with f-butyl azidoformate an isolable triazoline (addition in position QQ) which decomposes into aziridine by chromatography over neutral alumina. 55 With tosyl azide, on the other hand, only the aziridine derivative could be isolated. Both aziridines undergo a series of transformations leading to a so-called bird-cage hydrocarbon 57. ... 

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