Heterocycles synthesis from azides

In the alkaloid domain, several hydroxylated alkaloids were chosen to demonstrate that arene cw-dihydrodiols can serve as synthons in heterocyclic synthesis. The first venture into this area was the enantiodivergent synthesis of pyrolizidine triols from erythruronolactone 30, as shown in Figure 8 (30-32). The same principles of enantiodivergent design of the pinitols were applied here to yield the two enantiomeric azido dienes 40 and 41, which were then transformed to the alkaloids by previously documented azide-diene cycloaddition followed by vinylaziridine- yrroline rearrangement (33). 

In 1961, Smolinsky reported on vapor phase pyrolysis of a-azidostyrene (52, Scheme 5.8), which furnished 3-phenyl-2//-azirine as the main product and provided the first example of the synthesis of such strained heterocycles from vinyl azides. By analyzing the IR data of the pyrolysates produced from 52, it was shown one year later that N-phenylketenimine is formed as a side product. By utilizing IR and NMR spectroscopy at low temperature, Wentrup and coworkers have smdied recently the detailed structures of another azirine-ketenimine pair, generated by thermal or photochanical decomposition of an enazide. The transformation of vinyl azides into 2//-azirines is currently the most frequently used access to these heterocycles. The manifold chemistry of azirines was reviewed several times," " and most of the aspects of their synthesis from alkenyl azides are summarized in Chapter 6 (Gilchrist Alwes). Therefore, only some additional certain points are included here. 

Ferndndez-Bolanos JG, Lopez 6 (2007) Synthesis of Heterocycles from Glycosylamines and Glycosyl Azides. 7 31-66... 

Aryl and heteroaryl nitrene insertion processes have also been employed in the synthesis of heterocycles. The azide 459, for example, is converted on irradiation into the imidazole 460,383 and dihydro-10-thiaisoalloxazines are obtained in good yield on photoelimination of nitrogen from 6-(2-azido-phenylthio)uracils.384... 

Boyer and Gunasekaren reported the synthesis of the furazan-based heterocycle NOTO (44), which contains 50 % by mass of nitrogen and is a liquid at room temperature. The flve-step synthesis of NOTO (44) starts from the diazotization of 4,4 -diamino-3,3 -azoxyfurazan (DAAF) (27), followed by reaction with sodium azide to form the diazide (42). Heating the diazide (42) as a solution in acetonitrile induces cyclization to the triazole (43) and this is followed by reduction and oxidation of the remaining azide group to complete the synthesis of NOTO (44). 

Since the discovery of triazole formation from phenyl azide and dimethyl acetylenedicarboxylate in 1893, synthetic applications of azides as 1,3-dipoles for the construction of heterocychc frameworks and core structures of natural products have progressed steadily. As the 1,3-dipolar cycloaddition of azides was comprehensively reviewed in the 1984 edition of this book (2), in this chapter we recount developments of 1,3-dipolar cycloaddition reactions of azides from 1984 to 2000, with an emphasis on the synthesis of not only heterocycles but also complex natural products, intermediates, and analogues. 

D. Lloyd and H. McNab, Angew. Chem., Int. Ed. Engl. 15,459-468 (1976). Synthesis of heterocycles, from vinyl azides ... 

The heterocyclic hemi-aminal 44 was formed as a model for the synthesis of the marine alkaloids zoanthamine and zoanthenol and is derived from the cyclic imine formed by the reduction of an appropriated substituted azide <07H(72)213>. A pyrrolidine-fused azepine has been isolated from the venom of the ant Myrmicaria melanogaster and assigned as 45 based upon GC and FT-IR comparison with synthetic material <07JNP160>. The axially chiral doubly bridged biphenyl azepine 46 has been synthesised and used with oxone as an epoxidation catalyst in a biphasic system <070BC501>. 

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