Aziridine synthesis

The authors report reaction times similar to those achieved with a preheated oil bath at 130 °C on a small scale on a larger scale, however, microwave-assisted reactions seem to proceed more rapidly. 

Solvent Time (min) Power (W) Final temp. (°C) Yield of 18 (%) 

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The photolytic and thermolytic decomposition of azides in the presence of olefins has been applied to aziridine synthesis. However, only a limited number of steroid aziridines have been prepared in this manner. The patent literature reports the use of cyanogen azide at ca. 50° for 24 hours in ethyl acetate for the preparation of an A-nor- and a B-norsteroidal aziridine. The addition is believed to proceed via a triazoline. The reaction of cholest-2-ene with ethyl azidoformate takes place in a nonselective manner to produce a mixture of substances, including C—H insertion products. 

The Hoch-Campbell aziridine synthesis entails treatment of ketoximes with excess Grignard reagents and subsequent hydrolysis of the organometallic complex. ... 

An intramolecular trapping variant of the Hoch-Campbell aziridine synthesis was reported by Taguchi et When 2-(l-p-chlorophenylcyclohexyl)cyclohexanone (16)... 

The Wenker aziridine synthesis entails the treatment of a P-amino alcohol 1 with sulfuric acid to give P-aminoethyl sulfate ester 2 which is subsequently treated with base to afford aziridine 3. Before the discovery of the Mitsunobu reaction, wbicb transforms an amino alcohol into an aziridine in one step under very mild conditions, the Wenker reaction was one of the most convenient methods for aziridine synthesis. However, due to the involvement of strong acid and then strong base, its utility has been limited to substrates without labile functionalities. 

A related aziridine synthesis is the Gabriel reaction (a.k.a. Gabriel-Cromwell reaction), which involves an intramolecular Sn2 reaction of a P-amino halide. However, the reaction has become so common that the name Gabriel is not tightly related to the transformation. 

The mechanism for the Wenker aziridine synthesis is very straightforward. As depicted by conversion 2—>3, the transformation is a simple case of intramolecular Sn2 displacement process, in which the sulfate ester is the leaving group. 

As described in Section 1.7.1, the utility of the Wenker reaction is limited to substrates without labile functionalities because of the involvement of strong acid and then strong base. The Fanta group prepared a variety of aziridines by taking advantage of the Wenker reaction.For example, 6-aza-bicyclo[3.1.0]hexane (14) was produced from the ring-closure of ( )-rra s-2-aminocyclopentanol hydrochloride (13). In a similar fashion, sulfate ester 16 was prepared from A-methyl dl-trans- >-ssmnoA-hydroxytetrahydrofuran (15). Subsequent treatment of sulfate ester 16 with NaOH then delivered aziridine I . " Additional examples of Wenker aziridine synthesis may also be found in references 15-17. 

Table 1.16 Chiral tert-butylsulfinylimines in asymmetric aziridine synthesis.

Saito has recently reported high yields and enantioselectivities in aziridine synthesis through reactions between aryl- or vinyl-substituted N-sulfonyl imines and aryl bromides in the presence of base and mediated by a chiral sulfide 122 (Scheme 1.41) [66]. Aryl substituents with electron-withdrawing and -donating groups gave modest transxis selectivities (around 3 1) with high enantioselectiv-... 

Unsaturated oximes are attractive substrates for aziridine synthesis. Treatment of oxime 77 with Red-Al yielded vinylaziridines 78, 79, and 80, in various ratios depending on the E/Z ratio of the starting oxime 77 (Scheme 2.22) [38]. This reaction should proceed through abstraction of HA, Hb, or He in the intermediate 81, followed by hydride reduction of the resulting 2H-azirines 82-84. 

In 1999, Bob Atkinson wrote [1] that aziridination reactions were epoxida-tion s poor relation , and this was undoubtedly true at that time the scope of the synthetic methods available for preparation of aziridines was rather narrow when compared to the diversity of the procedures used for the preparation of the analogous oxygenated heterocycles. The preparation of aziridines has formed the basis of several reviews [2] and the reader is directed towards those works for a comprehensive analysis of the area this chapter presents a concise overview of classical methods and focuses on modern advances in the area of aziridine synthesis, with particular attention to stereoselective reactions between nitrenes and al-kenes on the one hand, and carbenes and imines on the other. 

The Gabriel-Cromwell aziridine synthesis involves nucleophilic addition of a formal nitrene equivalent to a 2-haloacrylate or similar reagent [29]. Thus, there is an initial Michael addition, followed by protonation and 3-exo-tet ring-closure. Asymmetric variants of the reaction have been reported. N-(2-Bromo)acryloyl camphor-sultam, for example, reacts with a range of amines to give N-substituted (azir-idinyl)acylsultams (Scheme 4.23) [30]. 

Aziridines were amongst the first heterocycles to be prepared by synthesis, and they occupy a special place in organic synthesis. This chapter has, we hope, indicated the rich chemistry associated with this area of synthetic endeavor in both the distant and the recent past it is clear that the recent exciting developments in asymmetric aziridine synthesis indicate a most promising future for the practitioners in the field and the greater synthetic community at large. 

A convenient aziridine synthesis using 2-iodoalkyl azides and triphenyl-phosphine has been reported. The reaction is stereospecific and is thought to proceed by attack of the phosphine on azide ... 

Aziridine synthesis can be achieved via nitrene addition to alkenes making use of a sulfonoxycarbamate [112]. Treatment of this reagent vith potassium carbonate in the presence of an alkene together with a PTC leads to the aziridine (Eq. 3.20). The reaction time is reduced from 2-3 h to 15 min when sonication is applied. 

Another aziridine synthesis based on intermediary nitrenes derived from the oxidation of aminotriazole 22 with IBD in the presence of alkenes is outlined in Scheme 11 (74TL2945). 

Scheme 17.27 Bicyclic aziridine synthesis from homoallyl sulfamates.

Oxidative amination of carbamates, sulfamates, and sulfonamides has broad utility for the preparation of value-added heterocyclic structures. Both dimeric rhodium complexes and ruthenium porphyrins are effective catalysts for saturated C-H bond functionalization, affording products in high yields and with excellent chemo-, regio-, and diastereocontrol. Initial efforts to develop these methods into practical asymmetric processes give promise that such achievements will someday be realized. Alkene aziridina-tion using sulfamates and sulfonamides has witnessed dramatic improvement with the advent of protocols that obviate use of capricious iminoiodinanes. Complexes of rhodium, ruthenium, and copper all enjoy application in this context and will continue to evolve as both achiral and chiral catalysts for aziridine synthesis. The invention of new methods for the selective and efficient intermolecular amination of saturated C-H bonds still stands, however, as one of the great challenges. 

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