Nitrenes azirine cyclization

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). 

Althongh it is impossible to completely rnle ont the existence of the singlet VN, CASSCF(4,4)/6-31G prediction, that the nitrene can cyclize to the azirine withont any barrier snggests that, if a barrier does exist, it is probably very small. This conclnsion, based on the results of calculations, is wholly consistent with the fact, noted above, that the triplet and singlet vinyl nitrenes have escaped detection. However, further experimental stndies, using very fast laser flash photolysis techniques, along with higher level ab initio calculations, are certainly warranted. 

Curiously, the addition of a second orf/zo-fluorine substituent (i.e. in benzazirine 17d) raises the barrier to reversion to singlet nitrene 16d, relative to the mono orf/io-fluoro system (Fig. 14). This is partly due to steric hindrance by fluorine in the transition state for cyclization, but also to the stabilization of 17d by the fluorine attached directly to the azirine ring vide suprd)F The addition of the second fluorine substituent (benzazirine 17d) decreases the barrier to conversion of azirine 17d to ketenimine 18d slightly... 

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. 

Three plausible mechanisms20 have been postulated for the thermal decomposition of vinyl azides (41) to 1-azirines (47). The azide can either (1) lose nitrogen to give the vinyl nitrene which then cyclizes to the 1-azirine, (2) lose nitrogen with simultaneous ring closure (45), or (3) first cyclize to triazole (46) which then loses nitrogen. To date little experimental evidence exists to favor any of these alternatives. 

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... 

The mechanism of the photochemically induced conversion of vinylazides into 2H-azirines has been examined using ab initio MO calculations. A new approach to the elusive thionitrosobenzene system has been reported. Direct irradiation of the 3-azido-2,l-benzisothiazole (88) affords a transient 2-cyanothionitrosobenzene (89) which can be trapped as the cycloadduct (90) with cyclopentadiene. Nitrene cyclization is the preferred pathway on irradiation of the 5-formyl- or 5-benzoyl-6-azidouracils (91) and yields the isoxazolo[3,4-d]pyrimidines (92). In contrast, 5-phenyl- and 5-benzyl-6-azidouracils were converted into pyrimido[4,5-b]indoles and pyrimido[4,5-ti Jquinolines, respectively, by a pathway involving photochemically induced loss of nitrogen and intramolecular nitrene insertion. 

Vinyl nitrene intermediates may also be trapped intramolecularly by alkenes situated further from the azirine nucleus. A variety of products can result from these reactions, depending on the substituents present on the alkene. Scheme 16 illustrates the diverse processes that may operate <76JOC180, 78JOC2029). 2-Propargylic 2//-azirines also cyclize to provide pyridine derivatives (78JOC2029), while homoallylic substituents at C(2) allow cyclization to form pyridine and biphenyl derivatives (75CC789,77JA1871). 

Three plausible mechanisms were postulated to explain these observations the free nitrene route (pathway a), Ng extrusion in concert with three-membered ring formation (pathway b), and cyclization to a 4H-1,2,3-triazole followed by rearrangement to azirine (pathway c). ... 

Above 180 K, 70a decays by both intersystem crossing (kjsc) and cyclization (k[j), with the latter process gaining relative to the former as the temperature increases. The data in Figure 5.26 for temperatures above 180 K were explained by positing that singlet nitrene 70a and azirine 71a (Scheme... 

The usual photoreaction of a vinyl azide is intramolecular cyclization to yield a 2H-azirine. Although this process is a well-established path to these compounds, the details of the mechanism by which the reaction occurs is unresolved. In some instances the formation of the azirine is thought not to involve the nitrene intermediate. However, other studies have shown that azirines and vinyl nitrenes are in thermal equilibrium and thus it seems likely that a vinylnitrene is the key intermediate in such reactions. 

More recently, several reports on the utilization of a facile cyclization of analogous to 195 Rh-nitrenoids for the assembly of multisubstituted indole cores appeared in the literature. Along this line, Narasaka revealed that 2H-azirines 200 could serve as versatile surrogates of these highly reactive nitrene-metal complexes 201... 

Argon matrix photolysis of 1- and 2-naphthyl azides 79 and 80 at 313 nm initially produced the singlet naphthyl nitrenes, 81 and 82. Relaxation to the corresponding lower energy, persistent triplet nitrenes 81 and 82 competes with cyclization to the azirines 83 and 84 which can also be formed photochemically from the triplet nitrenes (Figures 11.20 and 11.21). On prolonged irradiation, the triplet nitrenes 81 and 82 can be converted to the 7-membered cyclic ketenimines 85 and 86, respectively, as described earlier by Dunkin and Thomson. ... 

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