Heterocyclic Chemistry Other Cyclizations

Useful reviews on redox transformations of thiophen derivatives (179 references), on the stereochemistry of carbonyl derivatives of five-membered heterocycles (257 references), on synthetic approaches to dihydrothiophens (135 references), and on biosteric thiophens" have been published. Aspects of thiophen chemistry have been treated in reviews on the synthesis of heterocycles by thermal [2 + 2] cycloaddition reactions of acetylenes and on aspects and perspectives of organic heterocyclic chemistry. A review comparing the chemistry of thieno[2,3-h]- and thieno [3,2-i ]-thiophen with that of benzo[ft] thiophen and quinoline has been published. In Advances in Heterocyclic Chemistry, the development of benzo[6] thiophen from 1968 to 1980 and of selenophen from 1970 to 1980 was presented. Other aspects of thiophen chemistry are treated in chapters on Dewar Heterocycles," on Cyclizations under Vilsmeier Conditions, on Polyfluoroheteroaromatic Compounds, and on Reactions of Benzyne with Heterocyclic Compounds. " Several dissertations treating various aspects of thiophen chemistry have appeared. " ... 

Some other examples of radical cyclizations in heterocyclic chemistry have been collected by Gilchrist. ... 

Intramolecular versions and domino reactions involving appropriately functionalized aryl halides and alkynes offer useful synthetic methods for a variety of heterocycles and carbocycles. Few other methods can compete with these Pd-catalyzed cyclizations in versatility. Numerous reports and a number of excellent reviews covering the carbo- and heteroannulations have been pubhshed [10]. In order to aid understanding of this somewhat complex chemistry, the cyclizations are classified in to three types (Scheme 3.8). 

Pyrrolo[2,1,5-cd]indolizines and porphyrins It has recently been found that McMurry coupling opens an efficient route for the preparation of pyrrolo[2,l,5-cdjindolizines 101 and other substituted derivatives, by intramolecular reductive condensation of 3,5-diacylindolizines [139] (Figure 6.18). Another application of the McMurry reaction in nitrogen heterocyclic chemistry is in the synthesis of porphyrinoids octaethylisocorrole 102 and corphycene 103 have been synthesized by intramolecular cyclization of the corresponding tetrapyrrolic a,porphyrin derivatives have been obtained by tandem reactions (Section 6.2.3). 

The primary synthesis of 1,5-naphthyridines may be accomplished by double cyclization of appropriate aliphatic substrates by cyclization of appropriately substituted pyridines by cyclocondensation of pyridine substrates with one or more aliphatic synthons or from other heterocyclic substrates by degradation, rearrangement, or the like. Partially or fully reduced 1,5-naphthyridines are often made by somewhat similar procedures such cases are usually illustrated toward the end of each subsection. Some reviews of naphthyridine chemistry contain material on the primary synthesis of 1,5-naphthyridines49 52 61 231 265 670 1260 1273 1430 1432... 

Historically, the use of pyridine derivatives as cyclization substrates in the synthesis of fused heterocyclic systems has had great impact in pharmaceuticals, metal-chelation chemistry and other applications. Fused heterocycles incorporating different regioisomers... 

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... 

Synthesis of diaryl heteroarotinoids (11) and (12) [27,30,31] began with a Lewis acid-catalyzed cyclization of tertiary alcohol (34) to give dihydroben-zothiophene (36) as the sole isolated product. The chemistry of the ensuing steps was similar to that used to prepare (9) and (10) and other diaryl heteroarotinoids and involved (a) Friedel-Crafts acylation of a fused aromatic-heterocyclic system, (b) reduction of the resulting ketone to a benzylic carbinol, (c) phosponium salt formation, and finally (d), Wittig coupling to methyl 4-formylbenzoate. The free acids (13) and (14) were obtained by saponification. 

Other potentially useful reactions, similarly unexplored, involve the lateral met-allation cyclization to oxindoles, 86 —> 88, the N-to-ortho-C carbamoyl migration to anthranilamides, 86 —> 89, and the thereby facilitated further DoM chemistry to produce 90, substances that may further be used in cross-coupling reactions, for example, E = hal, B(OR)2 [133], This anionic arene chemistry has complementarity to the Friedel-Crafts reactions (for 85 and 87) and synthetic consequences for a variety of heterocyclic frameworks represented in the structures in Scheme 14.21. 

Other Systems.—Interest continues in the chemistry of boron-nitrogen heterocycles, and several new syntheses have been noted this year. Direct cyclization of arylsulphonylhydrazones ArCH=NNHS02Ar with hot (60 °C) boron tribromide affords a novel route to the aromatic 2,3,1-diazaborines (373). Similar treatment of the jS -naphthyl hydrazone yields only the linear isomer (373a). Syntheses of borazarofuro- (374) and borazarothieno-[3,2-c]- (375) and borazaro-... 

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