Aziridines nitrene intermediates

The Nagata group also developed a new approach to the construction of bridged aziridines via nitrene intermediates that led to the total synthesis of the indole alkaloids, ibogamine, velbanamine, and coronaridine (1968-1971). 

Thus far, enantioselective intramolecular aziridination via metal nitrene intermediates has not been successful. Bromamine-T has recently been shown to be a viable source of nitrene for addition to alkenes in copper halide catalyzed reactions, " and so has iodosylbenzene (Phl=0) that forms 44 in situ. Conceptually, aziridination does not necessarily fall between cyclopropanation and epoxidation, as some have suggested. Instead, metal nitrene chemistry has unique problems and potential advantages associated with the electron pair at nitrogen that are yet to be fully overcome. 

Kwart and Kahn have found that benzenesulfonyl azide forms a complex with freshly reduced copper powder.189 190 This copper azide complex decomposes at a lower temperature than the pure sulfonyl azide. In refluxing methanol, benzene-sulfonamide (27) is isolated as the major product. In the presence of dimethyl sulfoxide, N-benzenesulfonyldimethyl-sulfoximine (28) is obtained in almost quantitative yield. In cyclohexene solution benzenesulfonamide (29), N-benzenesul-fonyl-7-azabicyclo[4.1.0]heptane (30), and 1-cyclohexenylben-zenesulfonamide (31) are isolated as the main reaction products. According to the authors, Schemes VII and VIII represent an acceptable interpretation of the experimental data.189 190 In pure alcohol, the decomposition should occur by two competitive reactions (Scheme VII) producing benzenesulfonamide together with a ketone and oxidized copper. These last two products have indeed been observed in the reaction mixture. In the presence of DMSO, it seems that a copper-nitrene intermediate is formed which is trapped by DMSO. In cyclohexene solution, the authors have observed that the aziridine (30) disappears from the product composition when DMSO is added. The yield of enamine 31, however, is... 

There have been a number of reports where alicyclic-bridged precursors underwent an IAAC reaction. Thus, the dioxolane (203b), formed from triflate (203a), cyclized in situ to a tricyclic triazoline (Scheme 63).113 Treatment of this triazoline with sodium ethoxide converted it to a diazopyrrolidine in 86% yield, which underwent smooth catalytic hydrogenation in 89% yield. The (Z)-azidoalkene (204), bridged by a (3-lactam, cyclized at 20 °C to triazoline (205).114 The triazoline (205) extruded nitrogen at 80 C providing a tricyclic aziridine. The ( )-isomer of (204) did not cyclize to a triazoline but instead produced an azirine, presumably via a nitrene intermediate. 

More recently, the effect of substituents in the arenesulfonyl moiety on Cu(I)-catalyzed aziridinations of cyclohexene with a series of [(arenesulfonyl-imino)iodo]benzenes was evaluated (Scheme 65) [177]. Iminoiodanes possessing p-OMe,p-CF3, andp-N02 substituents gave higher yields of aziridines than the tosylimino analog. Product yields in these reactions are not simply related to relative rates of aziridination (p-MeO >p-Me >p-N02), and appear to reflect partitioning of the copper(III)-nitrene intermediates between aziridination of the C,C-double bond and reduction to the corresponding sulfonamides. 

For example, Jacobsen has studied the asymmetric aziridination of alkenes using (diimine)-copper(I)-catalysts 85. The results support the intermediacy of a discrete Cu(III)-nitrene intermediate and thus suggests mechanistic similarity (particularly regarding transition state geometry) to asymmetric cyclopropanation [95JA5889]. 

The aziridination works for both aromatic and aliphatic olefins, including less active linear terminal olefins. Most reactions proceed in good yield at room temperature. The use of ci.v-stilbene at 0°C gives predominately cis aziridine product in about 90 10 cis trails ratio (Table 6.1). The conservation of cis structure suggests that a discrete silver nitrene intermediate is involved in the reaction path. Because of the unique disilver structure and unlikely formation of a silver(III) species, the authors suspect that a bridged nitrene intermediate between the two silver atoms may be responsible for this transformation in which each silver atom donates one electron to the nitrenoid. However, further research is necessary to prove this hypothesis and a fast radical reaction mechanism cannot be eliminated on the basis of current evidence. 

After successful application of the silver catalyst shown in olefin aziridination (Section 6.1.1), He and coworkers showed that intramolecular amidation was possible with both hydrocarbon-tethered carbamates and sulfamate esters.24 They found that only the Bu3tpy silver complex could catalyze efficient intramolecular amidation, while other pyridine ligands gave either dramatically lower yields or complicated product mixtures. In an interesting control study, both copper and gold were also tested in this reaction. Both the copper and gold Bu tpy complexes can mediate olefin aziridination, but only silver can catalyze intramolecular C-H amidation, indicating that the silver catalyst forms a more reactive metal nitrene intermediate. 

The reaction of A -[A -(benzoylimino)-A -phenylsulfonyl]amide 429 with iodosylbenzene 426 leads efficiently to nitrene intermediates that convert olefins 411 into aziridines 430 in good yields, through a copper(ll)-mediated (Cu(OTf)2) reaction. Owing to the stereogenic sulfur atom present in the molecules, the reactions proceed with some degree of diastereoselectivity (Scheme 111) <2004OL3573>. 

Sulfur stabilized nitrenes have been implicated in aziridination reactions example using oxidative conditions is shown in Equation (60) <94CPB27>. The authors favor an (arenesulfenyl)nitrene intermediate. 

Photocrosslinking of glycidyl azide polymers, supposedly via nitrene intermediates, has been studied. Addition of an unsaturated hydrocarbon polymer accelerates the crosslinking process, and this is thought to be due to the formation of aziridine rings by nitrene addition to the carbon-carbon double bonds. 

Carbenoid ring-expansion of thiophen to a 2/f-thiopyran has been observed in the rhodium-catalysed reaction with (132), which gave (133) and (134). Evidence has been presented that the nitrene intermediate (135), obtained from the corresponding nitro- or azido-derivatives in the usual way, first gives the aziridine intermediate (136), which then leads to interesting heteropolycyclic systems such as 3-(2-thienyl)indole derivatives. ... 

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... 

Whilst there are several examples of late transition-metal stabilised nitrenes in the literature (see below), very few experimental studies are available for copper-nitrene intermediates. These are proposed as important intermediates in copper-catal3 ed alkane amination and alkene aziridination reactions, therefore identification and characterisation is critical for providing new mechanistic insights. Ray et recently... 

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]. 

Iron-nitrene/imido complexes are proposed to be the reaction intermediates in nitrogen group transfer reactions. The nitrene group can be transferred to organic substrates. Aziridination and amination are the well-known nitrogen atom/group... 

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