Azirines from nitrenes

Photogenerated nitrenes can undergo cycloaddition with alkenes intermolecular reaction leads to aziridine products (5.38), and intramolecular reaction in vinyl azides gives azirines (5.39). The bicyclic azirine from phenyl azide has not been isolated, but it is the intermediate that best accounts for the formation of a substituted azepine when this azide is irradiated in the presence of a secondary amine (5.401. 

Although vinylnitrenes are not involved in the formation of 2ff-azirines from vinyl azides, such nitrenes must be invoked in order to explain the further reactions of the azirines (Scheme 2). Thermal or photochemical ring opening of the azirine to a nitrene, and subsequent 1,2-shifts explain the formation of ketenimines and benzyl cyanides. A competing electrocycliza-tion of the nitrene onto a phenyl substituent in the /(-position leads to the... 

With the assumption that the undetected precursors to triplet 1- and 2-naphthylnitrenes are the azirines seen in the low temperature experiments, we can reach useful conclusions about the photochemistry of polynuclear aromatic azides. First, unlike phenyl azide where the closed-shell singlet intermediate formed in room temperature irradiations is dehydroazepine [46, 49, 69], the intermediates formed from both 1- and 2-naphthyl azide are azirines. The difference in the chemistry of 1- and 2-naphthyl azides is traced to a difference in the lifetime of the respective azirines. The azirine from 2-naphthyl azide survives at least 200 times longer than does the azirine formed from 1-naphthyl azide. The increase in lifetime permits the bimolecular trapping reaction by diethylamine to compete with isomerization to the triplet nitrene in the case of the 2-naphthyl but not the 1-naphthyl azides. 

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]. 

Apart from the azirine pathway, a vinylnitrene 526 was postulated as a possible intermediate in the reaction (Scheme 14). The nitrene may be formed by a base-promoted elimination of the leaving group on the nitrogen and gives rise to the 277-azirine by electrocyclization (nitrene insertion) and, in view of current data, this pathway cannot be excluded. 

This hypothesis was supported by analysis of the transient spectrum obtained upon LFP of 2-fluorophenyl azide, which reveals the presence of triplet nitrene 20a despite the small ratio of kisc/koss- This is clearly evident in Fig. 16 (Insert Spectrum 1), which presents the spectrum of the products formed from the decay of singlet nitrene 16a at room temperature. This spectrum is the sum of the spectrum of triplet nitrene 20a (narrow band at 303 nm and weak absorption below 450 nm) and ketenimine 18a (broad band at 350 nm). This complicated spectrum can be eompared with the simpler spectrum of ketenimine 18b (Spectrum 2) and the spectrum of triplet nitrene 20a observed as a persistent species in a low-temperature matrix (Spectrum 3). It is clear that the yield of triplet nitrene 20a is significant at room temperature. However, if one postulates that azirine 17a does not inter-eonvert with singlet nitrene 16a (Scheme 6, -r). then the yield of... 

Most monoheterocycles with one cyclic double bond have been prepared by C-Z bond formation in which the Z atom acts as the nucleophile. However, for six-membered rings of this type, Diels-Alder reactions are especially important. Three-membered rings are also atypical azirines are often made by C-N bond formation from precursors in which N is electrophilic or has nitrene character, while oxirenes are but fleeting intermediates (CHEC 5.05.6.3). 

The question as to whether the thermal azirine formation proceeds through a vinyl nitrene intermediate or by a concerted mechanism is not as yet resolved. A nitrene intermediate seems most probable on the basis of its similarity with cyclopropene formation from alkenylcarbenesM>> and because either thermal or photochemical decomposition of vinyl azides yields die azirines (Table XI). 

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. 

The base-catalyzed condensation of a-azido esters and ketones with aromatic aldehydes has recently been developed as a new vinyl azide synthesis.42,43 The yields range from moderate to excellent in some cases. The thermal decomposition of ethyl a-azidocinnamate (87) in xylene gives only 2-ethoxycarbonylindole (88).44 The unstable 2-ethoxycarbonyl-3-phenyl-l-azirine could be detected if the thermolysis was carried out at a lower temperature. This fact indicates that the 1-azirine is probably an intermediate leading to the indole, although the intermediacy of the vinyl nitrene could not be established. This result is similar to that observed by Isomura et al. on the pyrolysis of terminal vinyl azides.27,28... 

A selective sampling of the photochemical cycloaddition and cyclization chemistry of 2H-azirines has been outlined in this chapter. Some photochemical sequences increase molecular complexity more than others, but each seems to provide complex heterocyclic structures in a very efficient manner. Indeed, many of these photoreactions rapidly construct hetero-polycyclic systems that are difficult to produce in other ways. In contrast to their photochemical behavior, the major thermal reaction of 2H-azirines generally involves C(2)-N bond cleavage to form vinyl nitrenes which further react by either insertion into an adjacent C-H bond or else undergo addition across a neighboring rc-bond. The 27i-electrons of the carbon-nitrogen double bond of 2H-azirines can also participate in thermal symmetry-allowed [4- -2]-cycloadditions with a variety of substrates. It is clear from the above discussion that the chemistry of 2H-azirines is both mechanistically complex and... 

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