Fused indolizines

Compounds in this section comprise indolizines and their hetero-substituted analogues which are fused through the /-edge to a six-membered heterocycle. Where the fused six-membered ring is pyridine, however, these compounds are named not as fused indolizines but as pyrrolonaphthyridines. 

Finally, Fiirstner provided a single example of the Pt(II)-catalyzed [307] annulation of the same substrate 365 into the fused indolizine derivative 372, proceeding through a facile cyclization of Pt-vinylidene 371 (Scheme 9.130) [308, 309). 

The major internal comparisons to be made within this chapter are between (13) pyrrole (1), furan (2), thiophene (3), selenophene (4) and tellurophene (5) b) pyrrole (1) and indole (6) (c) indole (6), benzo[6 Jfuran (7) and benzo[6]thiophene (8) d) indole (6), isoindole (9) and indolizine (10) and (e) benzo[6] and benzo[c] fused systems. The names of relevant heterocyclic radicals are given with the structures of the parent heterocycle. 

It is of interest to compare the stability of the protonated forms of benzo[u], benzo[Z>] and benzo[c] fused pyrroles, i.e. the cations derived from indolizines, indoles and isoindoles. Indolizine gives a stable pyridinium ion and does not polymerize in the presence of acid. 

The acid catalyzed condensation of benzaldehydes with 2-acetyIpyridine provides access to hydroxy- or amino-indolizines (Scheme 58a) (71CB1629,71CB1645). A remarkable synthesis of fused pyrrolidines in which aldehydes also provide C-2 is exemplified in Scheme 58b... 

Indolizines a- or b-Fused to a Five-Membered Ring Containing Two or Three... 

All compounds reported within the review period are indolizines or their hetero-substituted derivatives, fused through the a- or -edge to a five-membered heterocyclic ring. 

Whereas reaction of the cyano-substituted indolizine 251 with a base results in the tf-fused product (Equation 34), the diester 255 reacts to give only the Afused product 256 <1987CL2043> (Equation 37). Similarly, when the acylindolizines 257 are prepared (Equation 38), very small amounts of the thienoindolizines are found in the product mixture. When such indolizines are substituted with both cyano and keto groups, treatment with a base gives a mixture of products resulting from reaction of the ester enolate with either of these electrophiles <1989BCJ119> (Equation 39). 

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>. 

Indolizines and their hetero-analogues fused to a six-membered heterocycle... 

Compounds within the scope of this section comprise indolizines, and indolizine analogues containing additional heteroatoms, fused through the e-, g-, or -edge to a six-membered heterocycle. 

Pyrimidine as the outer ring. Indolizines and their aza analogues fused to a uracil ring are produced in several ways (1) by thermal cyclization of 5-(2,2-dicyanoethenyl)-6-pyrrolidinouracil (Equation 66) <1998JCM502,... 

The condensation of DMDP with carbon disulfide/dicyclohexylcarbodiimide (DCC) afforded the indolizine derivative—potentially biological active thionocarbamate on carbohydrate scaffold, fused from the nitrogen side. 

Thus, the main products from quinaldine in aprotic solvent acetonitrile are quinolizine 280 and indolizine 281a (rather than pyridoazepine 282) in protic solvent methanol only indolizine 281a forms, but in both cases higher-fused products (1 3 and 1 4 adducts) are accompanying. Also the long-lasting discussion about the products obtained from 6-bromoquinaldine has been settled in favor of the two isomers 283 (76J(P1)692). 

By contrast to the bases, the cationic species have long been known. In addition to Fozard and Jones bicyclic salts already described (307, 308), benzo-fused derivatives were synthesized in the context of the aromatic cyclodehydration series by Bradsher s group (Scheme 71). Different from the 2-propenylpyridinium salts 316 just mentioned, the cycHzation of 2-benzylpyridinium 318 salts does not give indolizines unless under basic conditions in the acidic medium morphanthridizinium salts, such as 319a and b, are formed (59JA2547). This cyclization (after iodo-chloro metathesis) takes place in several days but in the case of the... 

The benzo[a] (19), benzo[/t (15) and benzo[c] (16) fused heterocycles are heterocyclic analogues of naphthalene, with the dibenzo heterocycles (17) bearing a similar electronic relationship to phenanthrene. Some of these compounds are still known by their trivial names indole (15 Z = NH), isoindole (16 Z = NH), carbazole (18) and indolizine (19). The names thianaphthene and pyrrocoline for (15 Z = S) and (19) respectively are now little used. Particular confusion can arise in consulting... 

Stelzner Fusion System. Stelzner fusion principles can be applied to heterocyclic components. However, strict application of the system is not always possible, and problems associated with deciding upon the degree of hydrogenation of the parent fused molecule often arise. For example, 34 and 35 are named thieno[3,2-a]indolizine and thieno-[2,3- >]indole by the IUPAC system. The Stelzner name for 35 would be thieno(2, 3 2,3)indole, but 34 cannot be similarly named, since in no... 

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