Ring synthesis cyclazine

Attempts to synthesize l,2-diazacycl[3.2.2]azines (l,2,4-triazolo)[3,4,5-ti/]indolizines, for example, 337, have met with very limited success. To date the ring system is known only when fused on its ef-faces to a cycloheptatriene ring (see Section 12.16.6.4). It may be that the 1,2-diazacyclazine system is more strained than that of the parent cyclazines, since the N-N bond of the triazole ring is expected to be shorter than a C-C or C-N bond. Similarly, all attempts to form the N-N bond as the final step in a synthesis of the 1,2,4-triazacyclazine ring system, 359, have been unsuccessful <1987J(P1)1159>. 

Synthetic routes to the benzocyclazines are analogues of those which lead to the cyclazines themselves. Representatives of the benzoh ]cycl[3.2.2]azine (indolizi no [3,4,5- ] isoindole, 365) ring system result from cycloaddition of, for example, DMAD to pyrido[2,l-tf]isoindole-6-carbonitrile 370 <1986H(24)3071> (Scheme 100). An alternative synthesis, which starts from the cyclazine 371 and involves construction of the additional benzenoid ring by a double Horner-Wadsworth-Emmons type of reaction, apparently gives the tetracyclic product 365 in only very low yields (Scheme 101) <1988H(27)2251>. 

A characteristic feature of a second type of [2.3.3]cyclazines is an odd number of peripheral heteroatoms contributing a pair of electrons to the 7r-system. The synthesis of cyclazines with a heteroatom in the five-membered ring (260) starting from 2,5-diaminoazoles (261) an ethyl 2-cyano-3-ethoxyacrylate has been described (Scheme 41) (76ACS(B)468). 

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