Azides to nitrenes

Metal nitrene complexes were used in a number of C-H amination reactions (recent reviews [358, 359]). Copper ketiminate complexes react with azides to nitrene complexes, which were isolated [360]. (p-Ketiminate)copper(I) complex 262 (2.5 mol%) serves therefore as an efficient catalyst for the intermolecular C-H amination of alkylarenes, cycloalkanes, or benzaldehydes 260 using adamantyl azide 261 as the nitrogen source ig. 68) [361]. The corresponding adamantyl amines or amides 263 were isolated in 80-93% yield. Copper complex 262 forms initially a dinuclear bridged complex with 261. From this a copper nitrene complex is generated by elimination of nitrogen, which mediates the hydrogen abstraction from 260. 

The main example of a category I indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from ot-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3]. 

Important synthetic paths to azirines and aziridines involve bond reorganization, or internal addition, of vinylnitrenes. Indeed, the vinylnitrene-azirine equilibrium has been demonstrated in the case of trans-2-methyl-3-phenyl-l-azirine, which at 110 °C racemizes 2000 times faster than it rearranges to 2-methylindole (80CC1252). Created in the Neber rearrangement or by decomposition of vinyl azides, the nitrene can cyclize to the p -carbon to give azirines (Scheme 4 Section 5.04.4.1). 

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]. 

N-benzylaniline with phosgene, and then with sodium azide to produce carbonyl azide 52. On heating, nitrogen is evolved and a separable mixture of nitrene insertion product 53 and the desired ketoindazole 54 results. The latter reaction appears to be a Curtius-type rearrangement to produce an N-isocyanate (54a), which then cyclizes. Alkylation of the enol of 54... 

The rate of decomposition of benzenesulphonyl azide to benzene-sulphonamide is said to be accelerated appreciably by thiophenol 18> in a radical-catalyzed process probably not involving a free nitrene intermediate. 

Despite the volume of work concerned with metal-catalyzed decomposition of diazo compounds and carbenoid reactions 28>, relatively little work has been reported on the metal-catalyzed decomposition of sulphonyl azides. Some metal-aryl nitrene complexes have recently been isolated 29 31>. Nitro compounds have also been reduced to nitrene metal complexes with transition metal oxalates 32K... 

Addition of carbethoxynitrenes to olefinic double bonds occurs readily. Addition of both the singlet and the triplet species can take place, the former stereospecifically, the latter not 49>. Additions of sulphonyl nitrenes to double bonds have not been demonstrated except in two instances in which metals were present. The reason is that either addition of the starting sulphonyl azide to the double bond occurs to give a triazoline that loses nitrogen and yields the same aziridine as would have been obtained by the direct addition of the nitrene to the olefin, or the double bond participates in the nitrogen elimination and a free nitrene is never involved 68>. The copper-catalyzed decomposition of benzenesulphonyl azide in cyclohexene did give the aziridine 56 (15%), which was formulated as an attack by the sulphonyl nitrene-copper complex on the double bond 24>. 

The intramolecular insertion of a sulphonyl nitrene into a side-chain methyl group to give 36 and 37 has already been mentioned, as has the intramolecular cyclization of ferrocenylsulphonyl azide to give the bridged ferrocene derivative (17). 

Figure 5.35 ABH reacts with aldehyde-containing compounds through its hydrazide end to form hydrazone linkages. Glycoconjugates may be labeled by this reaction after oxidation with sodium periodate to form aldehyde groups. Subsequent photoactivation with UV light causes transformation of the phenyl azide to a nitrene. The nitrene undergoes rapid ring expansion to a dehydroazepine that can couple to nucleophiles, such as amines.

Aryl sulfinyl azides, ArS(0)N3, can be prepared at low temperature by reaction of sulfinyl chloride ArS(0)Cl with sodium azide (Maricich and Hoffman, 1974). On warming to 0° they decompose with evolution of nitrogen, their decomposition exhibiting clean first-order kinetics ( = 3 x 10-4 s-1 for PhS(0)N3 in acetonitrile at 0°). The rate-determining step of the decomposition is loss of nitrogen from the sulfinyl azide to form the sulfinyl nitrene ArS(0)N (143). The subsequent behavior of this nitrene suggests (Maricich and... 

This property is relatively rare in the very large number of reactions for which substituent effects were evaluated quantitatively106. It seems to be common, however, for all dediazoniations of arenediazonium ions and of related compounds, e.g. of substituted phenyl azides forming nitrenes, as well as for additions of carbenes to alkenes. 

FeCl2 has been used to catalyse nitrene transfer from l-butyloxycarbonyl azide to sulfoxides (to form sulfoximides), sulfides (to give sulfimides), and a ketene acetal (to form an a-amino ester). ... 

The reaction of l,3-bis(trimethylsilyl)-l,3-diaza-2-germa(II)-indane (365) with trimethylsilyl azide to give (366) may seem to be reminiscent of several preceding transformations but, as was shown with open-chain germylenes, the process is not a cycloaddition and probably involves nitrene intermediates <89CB245>. 

The loss of nitrogen from an azide to form a nitrene can b /isuatlzed as shown, atthougi. vhether the fragmentation involves two electrons (doubte-headedi arrows) or a single electron (fish-hooks) is not important to this discussion ... 

Another quinoxaline-yielding rearrangement, reported by Hanaineh-Abdelnour and coworkers, entailed treating imides 182 with sodium azide to produce quinoxalines 183 in moderate to good yields <99H2931, 99T11859>. The reaction presumably proceeds by a nitrene insertion to close the pyrazine ring. 

However, product smdies indicate that the chemistry of sulfonyl azides and nitrenes is complicated by rearrangement to form intermediates, such as 21. ... 

To add to the confusion, various groups reported that gas-phase photolysis of phenyl azide produced the absorption and emission spectra of triplet phenylni-trene. " These observations were reconciled by the work of Leyva et al. who discovered that the photochemistry of phenyl azide in the presence of diethylamine was very sensitive to temperature. Above 200 K, azepine 30 is formed, but <160 K, azobenzene, the product of triplet nitrene dimerization, is produced. The ketenimine can react with itself or with phenyl azide to produce a polymer, which can be converted into an electrically conducting material. Gritsan and Pritchina pointed out that at high-dilution ketenimine 30 can interconvert with singlet phenylnitrene which eventually relaxes to the lower energy triplet that subsequently dimerizes to form azobenzene. 

Oxidative addition of organic azides to low valent species, mainly in oxidation state +III, was found to be a general method for obtaining pentavalent mono- or di-nuclear nitrene derivatives.294 Applied to Nb1 compounds, it led to the first dinitrene compound. 

Azido-l-methylbenzimidazole with diphenylketene gave the imidazobenzimidazole (232 R = Ph), but decomposition of the azide to give a nitrene, followed by cycloaddition to the ketene, was ruled out as a mechanism. Instead, the authors propose that 232 is formed by attack of the endocyclic ring nitrogen on the C=C bond of the ketene followed by nucleophilic displacement of N2 from the azide.168 Preparation of an analog (232, R = H) would constitute a possible route to an aromatic azapentalene 233. 

Pyrazole react with HCC13 at 550°C (with CC12 formation) to give 2-chloropyrimidines in good yields. 1-Alkyl-1,2,4-triazoles react with nitrenes formed by the irradiation of azides to give /V-imines (Scheme 46) <74AHC(17)213>. 

The addition reactions of organic azides to unsaturated systems can occur by two mechanisms.1 If the reaction temperature is lower than the decomposition temperature of the azide, a 1,3-dipolar addition is observed. When, however, the reaction is carried out at the wavelength or at the decomposition temperature of the azide, the addition proceeds through an intermediate nitrene. 

Photolysis or thermolysis of azides leads to nitrenes. Such nitrenes, attached to the thiophene ring, have been extensively investigated. 

The photochemistry of aryl azides is quite complex, suggesting that the nitrene 14 may not be the only reactive intermediate and that insertion reactions may not be the only route to form photoconjugates.Although aryl nitrenes are much less susceptible to rearrangements than acyl nitrenes, they may still occur and lead to the formation of reactive intermediates such as azepines, which may go on to react with nucleophiles.[911 141 Addition of nitrenes to double bonds will generate azirines, while dimerization will produce azobenzenesJ11 Aryl azides are stable to most of the procedures used in the course of peptide synthesis except for reduction reactions. Non-photochemical reduction of aryl azides to the primary amines by thiols has been reported by Staros et al.[15]... 

Thermal decomposition of aryl azides under a nitrogen atmosphere leads to nitrenes which are able to substitute fluorine in polyfluorinated naphthalenes, albeit with a poor yield (4%). Since no substitution product was isolated when oxygen was present during this reaction, the intermediacy of a triplet nitrene was proposed, which is completely trapped by oxygen.207... 

In this laboratory a number of experiments have been conducted to trap or obtain evidence for the hitherto unknown thioacyl azides, thioacyl nitrenes, and thiazirines during thermally19 or photochemically... 

The formation of anils 129 occurs in accordance with the generally accepted mechanism for thermal rearrangements of aliphatic azides to imines which involves nitrenes 127 as the intermediate (74JA480). Ni-trenes may undergo cyclization to aziridines 105 [cf. Section I1I,C,1 (Scheme 6) and Section lII,C,4,b(ii)] which are converted into ben-... 

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