Heterocycles indolizine

A rigorous theoretical treatment of the non-alternant and heterocyclic indolizine is extremely difficult and, even for the related isoconjugate hydrocarbon, far from conclusive. Many questions, however, in which experimentalists are interested may be answered in a satisfactory way on the basis of a perturbational treatment. This approach has been used for a discussion of the electronic spectra of indolizine and some azaindolizines (63JCS3999). Following first-order PMO theory the 7r-stabilization which follows from aza substitution at the different positions of the model molecule depends on the ir-electron density qt as well as the change in electronegativity Sat (B-75MI30801). The perturbations caused by aza substitution of the indenyl anion are depicted in Scheme 1. 

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. 

Very few reactions of carbenes with heterocyclic systems containing more than one hetero atom have been studied. They are confined to variants of the Reimer-Tiemann formylation of thiazoles, pyra-zoles, iminazoles, and indolizines/ and ring expansion does not appear to have been observed. 

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. 

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

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. 

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. 

Electron-rich heterocyclic systems such as indolizines react readily with DEAZD (and PTAD) to give substitution products (Eq. 16).141 None of the formal [8 + 2] cycloaddition products (e.g., 89) are observed. This is in direct contrast to the reaction of indolizines with electrophilic acetylenes which gives high yields of cycloaddition products, presumably via a stepwise mechanism, in the presence of palladium on charcoal.142 This example of... 

The utilization of solid-support pyridinium salts in the synthesis of bicyclic pyridines has been reported. Yue et al. synthesized 1,2,3,7-tetrasubstituted indolizines using poly(ethyleneglycol)bound pyridinium salts <06JHC781>. The PEG-bound pyridinium salts 53 were reacted with alkenes or alkynes in the presence of Et3N, via 1,3-dipolar cycloaddition, to give polymer-bound indolizines 54 and 55, respectively. Liberation of the heterocycle with KCN/MeOH afforded 1,2,3,7-tetrasubstituted indolizines 56 and 57 in good to excellent yield. 

Indolizines, aromatic heterocycles with 12-jr-elec-tron system salts, isomeric with indole and isoindole, are prepared in good yields from pyrylium salts with active a-methylene groups.215 216 Aromatics derived from pyrylium salts by substitution of one or two fi-CW group(s) with a heteroatom are also possible. 

The 1,3-dipolar cydoaddition reactions ([3-1-2]) are often used to synthesize five member aza- or azoxaheterocycles. Depending on the nature of the 1,3-dipoles employed in the transformation, different types of heterocycles such as isoxaza-zoles [270], isoxazolines (Scheme 3.22) [110], hydantoins [271], pyrrolidines [272], indolizines [273] or pyrazoles [274] are obtained. 

Similar studies have also been carried out on condensed heterocyclic systems with a bridgehead nitrogen. Indolizine [175] and its 2-methyl-, 1,2-, 2,6- and 2,8-dimethyl- and 1,2,3-trimethyl derivatives protonate preferentially on C-3 in trifluoroacetic acid, giving cations [176] (Fraser et al., 1962). In general, when position 3 is... 

W. L. Mosby, Chem. Heterocycl. Comp. 15, 878 (1961). (In table s-Triazolo[2,3-a]pyrimidines, pages 884-888, he used -contrary to his explanations in page 878 - erroneously the ring atom numbering of the simple indolizine system, as in lc.)... 

Just as there is a family of heterocycles isoelectronic with the indene monoanion (13)27 (indole, isoindole, indolizine, pseudoazulenes, etc.), there are several hundred possible systems derived from the pentalene dianion (14).2 Scheme 3 shows some examples (15-20) derived (formally) from each canonical form of 14. 

Further substitution of the peripheral carbon atoms of the cyclazines by heteroatoms (N, S, etc.) is indicated in this chapter according to the replacement nomenclature system (aza, thia, etc.). Although, strictly, this runs contrary to the rules,lc since it is a heterocyclic, not a hydrocarbon, system which is replaced, the connection between closely related compounds can more clearly be seen. It should be noted that Chemical Abstracts employs the systematic fusion nomenclature I, for instance, is pyrrolo[2,l,5-cd]indolizine. 

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... 

Indolizines rank among the class of 7r-excessive heterocycles, i.e. they readily undergo electrophilic substitution and are inert to nucleophilic attack. Many of them are easily oxidized and therefore unstable in the presence of air. 

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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