Aziridines from azides

Synthesis of triazolines or aziridines from azides by photodecomposition or flash vacuum pyrolysis of 1,2,3-triazolines. 

Scheme 6.23) (see also Chapter 7). Under these conditions the intermediate triazoline is not isolable the Lewis acid appears to have the dual role of activating the enone and facilitating the decomposition of the triazoline. Triflic acid is a very efficient catalyst for promoting the formation of aziridines from azides and electron deficient alkenes such as but-3-en-2-one (Scheme 6.23). ° The acid appears to activate the alkene to nucleophilic attack by the azide it is not necessary to invoke triazolines as intermediates although they may be involved. 

A straightforward synthesis of aziridines from electron-rich azide R-N3 (R = alkyl or aryl), electron-deficient alkene, and triflic acid in cold acetonitrile has been reported. The only byproduct was dinitrogen (N2).143... 

In addition to epoxides, three-membered nitrogen heterocycles, aziridines, can be obtained by means of catalytic asymmetric aziridinations (Eq. 30). To this aim, chiral ruthenium(salen) complexes 67 [56] and 68 [57] were useful (Fig. 1). The former phosphine complexes 67 gave the aziridine from two cy-cloalkenes with 19-83% ee [56]. On the other hand, terminal alkenes selectively underwent aziridination in the presence of the latter carbonyl complex 68 with 87-95% ee [57]. In these examples, N-tosyliminophenyliodinane or N-tosyl azide were used as nitrene sources. Quite recently, catalytic intramolecular ami-dation of saturated C-H bonds was achieved by the use of a ruthenium(por-phyrin) complex (Eq. 31) [58]. In the presence of the ruthenium catalyst and 2 equiv iodosobenzene diacetate, sulfamate esters 69 were converted into cyclic sulfamidates 70 in moderate-to-good yields. 

The addition of alkoxycarbonyl nitrenes, generated photochemically from azides, to substituted dihydropyrans and tri-O-acetyl-D-glycal57"59 in alcoholic solution gave the products of alcoholysis 30 and 31-33 of the intermediate aziridines by a one-pot procedure59. The attack of the nitrene takes place mainly on the less hindered face of the double bond, but complete control of the diastereoselectivity was not accomplished even the ring opening of the aziridine can follow both anti and syn stereochemistry. 

Functionalized aziridines, especially optically active ones, are important intermediates in organic synthesis. The reaction of cyclic sulfates prepared from homochiral diols with amines or azide ion provides an efficient route to homochiral aziridines (equation 56). Formation of aziridines from cyclic sufates occurs with inversion at the stereogenic center. The reaction of the cyclic sulfates with an excess of a primary amine gives /2-... 

Direct preparation of an aziridine from an alkene is possible by reaction of the alkene with a nitrene or metal nitrenoid species. Nitrenes can be generated thermally or photochemically from azides, although their reaction with alkenes to give aziridines is often low yielding and is complicated by side reactions. Oxidation of iV-amino-phthalimide or related hydrazine compounds (e.g. with Pb(OAc>4 or by electrolysis) and reaction with an alkene has found some generality. The metal-catalysed reaction of nitrenes with alkenes has received considerable study. A variety of metal catalysts can be used, with copper(II) salts being the most popular. For example, styrene was converted to its A-tosyl aziridine 72 by reaction with [A-(tosyl)imino]phenyliodinane (PhI=NTs) and copper(II) triflate (5.75). ... 

Although the formation of aziridines from olefins and azides may not in all cases involve a nitrene intermediate, some recent literature reports of reactions of this type have for convenience been included in this section (see also the section on ring contraction). Alkoxycarbonyl nitrenes (R = Me or Et),... 

Many of the methods used for the synthesis of aziridines rely directly or indirectly upon the use of azides. The formation of aziridines from organic azides and aUcenes can proceed by either one of two well-established mechanisms (1) the initial loss of nitrogen from the azide to generate a nitrene intermediate that then adds to the double bond or (2) the [3h-2] cycloaddition of the azide to the alkene to form a triazoUne that then loses nitrogen (Scheme 6.10). In practical terms the distinction is not always clear-cnt becanse... 

Scheme 6.10 Alternative mechanisms for the formation of aziridines from alkenes and organic azides ...

Some applications of the triazoline route to aziridines from alkenes and azides are described below. 

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 properties of chlorine azide resemble those of bromine azide. Pon-sold has taken advantage of the stronger carbon-chlorine bond, i.e., the resistance to elimination, in the chloro azide adducts and thus synthesized several steroidal aziridines. 5a-Chloro-6 -azidocholestan-3 -ol (101) can be converted into 5, 6 -iminocholestan-3l -ol (102) in almost quantitative yield with lithium aluminum hydride. It is noteworthy that this aziridine cannot be synthesized by the more general mesyloxyazide route. Addition of chlorine azide to testosterone followed by acetylation gives both a cis- and a trans-2iddMct from which 4/S-chloro-17/S-hydroxy-5a-azidoandrostan-3-one acetate (104) is obtained by fractional crystallization. In this case, sodium borohydride is used for the stereoselective reduction of the 3-ketone... 

A solution of hydrazoic acid (prepared from about 30 g sodium azide) in ca. 200 ml chloroform is prepared in a well-ventilated hood. Cholesterol (15 g) is dissolved in the hydrazoic acid solution and 3.5 ml of triethylamine is added. The reaction mixture is then stirred at room temperature while 7 g of A-chlorosuccinimide is added. The reaction mixture is allowed to stand overnight and then the chloroform solution is washed successively with dilute sodium bisulfite, dilute soldium bicarbonate solutions and finally with water. The chloroform extract is then dried (Na2S04) and the solvent removed in vacuo. The residue is crystallized from ethanol to yield ca. 8.5 g of (101) in colorless needles mp 138-139°. The chloro azide is reduced to the aziridine by lithium aluminum hydride according to the foregoing procedure. 

Another conceptually unique approach in alkene aziridination has come from Johnston s labs. These workers shrewdly identified organic azides as nitrene equivalents when these compounds are in the amide anion/diazonium resonance form. Thus, when a range of azides were treated with triflic acid and methyl vinyl ketone at 0 °C, the corresponding aziridines were obtained, in synthetically useful yields. In the absence of the Bronsted acid catalyst, cycloaddition is observed, producing triazolines. The method may also be adapted, through the use of unsaturated imi-des as substrates, to give anti-aminooxazolidinones (Scheme 4.25) [32]. 

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