Polyheterocyclic ring systems

Lautens and coworkers [9] ultimately used this approach to prepare a multitude of different polyheterocyclic ring systems 4-29, using 4-20 and 4-28 as substrates (Table 4.1). Unsymmetrical tethered bisfurans and acetylene dicarboxyclic acid derivatives have also been used in this domino process to allow the formation of three new rings with up to six stereogenic centers. 

These 107i-systems are isoelectronic with the pentalene dianion and have been of some theoretical interest. 1,5-Diheteropentalene systems are very popular substrates for the investigation of inter- and intramolecular cycloaddition reactions due to their diene character. Such cycloaddition processes allow for a rapid entry into complex polyheterocyclic rings and makes these compounds potentially useful for natural product synthesis. 

Recently, Buchwald and Hartwig have developed the palladium-catalyzed coupling reaction of aryl halides with amines (Scheme 165), and they have extended this reaction to the intramolecular version to give a variety of the aza-heterocyclic compounds 547 (Scheme 166).231 This methodology has provided a wide variety of alkaloids, such as indoles,232 inda-zoles,233 benzimidazoles,234 benazepines,235 phena-zines,236 carbapenems,237 the mitomycin ring system,238 a-carbolines,239 and polyheterocycles.240 Pharmacologically active natural products, such as (—)-asperlicin (550) (Scheme 167),241 dehydrobufotenine (553) (Scheme 168),242 and makaluvamine C... 

MSubstituted-2-pyridones can be used as substrates for ring closure to a number of polyheterocyclic systems, as an alternate to the Pschorr cycliza-tion Of to the cyclizations of the corresponding At-alkyl-2-halopyridinium halides. 2-Substituted pyridines (MI-625 X =C1, Br, OC Hj) and 3-(2-bromo-ethyl)indole give -[2-(3-indolyl)ethyl]-2-substituted pyridinium bromide... 

By integrating the polyacetylene moiety into a polyheterocyclic system, the electron donating function of N or S ring atoms stabilizes the conjugated system, especially in the doped, positively charged highly conductive state (bipolaron state). 

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