Aziridines from nitrenes

This nitrene-addition approach was used by Knight to synthesize vinyl aziridines from 1,3-dienes using PhI=NTs and a copper catalyst. The more electron-rich double bond is selectively transformed in most cases. When the electronic difference is negligible the regioselectivity is then determined by steric hindrance. A mixture of cis and tram isomers is usually obtained [95SL949],... 

The aziridination of olefins, which forms a three-membered nitrogen heterocycle, is one important nitrene transfer reaction. Aziridination shows an advantage over the more classic olefin hydroamination reaction in some syntheses because the three-membered ring that is formed can be further modified. More recently, intramolecular amidation and intermolecular amination of C-H bonds into new C-N bonds has been developed with various metal catalysts. When compared with conventional substitution or nucleophilic addition routes, the direct formation of C-N bonds from C-H bonds reduces the number of synthetic steps and improves overall efficiency.2 After early work on iron, manganese, and copper,6 Muller, Dauban, Dodd, Du Bois, and others developed different dirhodium carboxylate catalyst systems that catalyze C-N bond formation starting from nitrene precursors,7 while Che studied a ruthenium porphyrin catalyst system extensively.8 The rhodium and ruthenium systems are... 

For the aziridination of 1,3-dienes, copper catalysis gave better yields of A-tosyl-2-alkenyl aziridines with 1,3-cyclooctadiene, 1,4-addition occurred exclusively (50%) [46]. Good results were also obtained on rhodium catalysed decomposition of PhI=NNs (Ns = p-nitrophenylsulphonyl) with some alkenes the aziridination was stereospecific, whereas with chiral catalysts asymmetric induction (up to 73% ee) was achieved. However, cyclohexene gave predominantly (70%) a product derived from nitrene insertion into an allylic carbon-hydrogen bond [47]. 

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. 

This review is written to cover the needs of synthetic chemists with interests in oxidizing alkenes by addition of nitrogenous substituents. Whilst some aspects have been covered in previous reviews (noted in the text), most notably in the Tetrahedron Report No. 144, Amination of Alkenes and prior reviews on aziridines and nitrenes, the present review is the fust conq>ilation of references to the whole range of these particular bond-forming processes. A review by Whitham provides a useful general introduction to reaction mechanisms of additions to alkenes in greater detail than can be covered here. The oxidation requirement excludes from the scope the additions of N H and most additions of N + Metal or N + C. Hence, unmodified Michael and Ritter reactions are excluded. These topics are mostly covered in Volume 4 of the present series. 

The reaction of azides with 1,3-dienes affords vinyl aziridines (through nitrene or azide cycloaddition), which can be converted to dihydropyrroles. It is also possible that dihydropyrroles are directly produced from azidodienes. 

Aziridine-2-carboxylic acid, asymmetric derivatives of 87MI5. Aziridines, formation from nitrenes and unsaturated compounds 79ZVK485. 

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). ... 

Apart from cyclopropenation, catalytic aziridination with nitrene transfer to olefins is generally considered an analogue reaction of metal-catalyzed carbene-transferred cyclopropanation. Aziridination and cyclopropanation are proposed to share fundamental mechanistic features. Many of the catalysts that were successfully applied in aziridination are also efficient catalysts for cyclopropanation. For... 

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... 

With respect to the intermolecular nitrene addition to alkenes, the formation of aziridines is generally observed. Nevertheless, the use of sulfonimidamides has allowed the discovery of a highly chemoselective intermolecular aUylic C(sp )-H amination that can be applied to several classes of alkenes. Various terpenes and aUyl enol carbonates, particularly, undergo allylic amination in excellent yields of up to 98% (Scheme 28). The chemoselectivity was supposed to be controlled by the substrate. Hyperconjugation of the aUylic C—H bonds with the adjacent Jt-system would increase their reactivity, a result corroborated by the exclusive formation of the aziridine from P-caryophyUene whose structure does not display such a hyperconjugative effect for the aUylic C—H bonds. 

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]. 

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." ... 

Aziridines are important compounds due to their versatility as synthetic intermediates. In addition, aziridine rings are present in innumerable natural products and biologically active compounds. Nitrene addition to alkenes is one of the most well established methods for the synthesis of aziridines. Photolysis or thermolysis of azides are good ways to generate nitrenes. Nitrenes can also be prepared in situ from iodosobenzene diacetate and sulfonamides or the ethoxycarbonylnitrene from the A-sulfonyloxy precursor. 

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