Carbazole 1-methyl-, ring synthesis

The yellow colored, sparcely soluble 5-ethyl-2-methyl-l l/f-pyrido[3,4-u] carbazolium 347 isolated from Aspidosperma gilbertii exists as a hydroxide after filtration of the corresponding iodide over basic aluminum oxide. A short synthesis was described (80CB3245). The Pyrido[3,4-a]carbazole ring system is present in the alkaloid AG-1, whereas Cryptolepine (348) possesses the indolo[3,2-b]quinoline moiety (65MI1). 

A new benzannulation methodology was developed in order to overcome the limitations of electrocyclic ring closure of divinylindoles. The cyclization is achieved via an allene-mediated electrocyclic reaction of 2,3-difunctionalized indoles. This method is more efficient for the synthesis of highly substituted 2-methyl carbazole alkaloids (559). The 3-alkenyl-2-propargylindole 557, a precursor for the allene intermediate, was prepared from 2-formylindole over several steps using simple functional group transformations (536,537) (Scheme 5.20). 

An independent synthesis of ellipticine follows, in its initial stages, the first olivacine synthesis reported in Section VII, C. Instead of the mono-methylcyanophenylhydrazine (CCLXII), a corresponding dimethyl compound, 3-cyano-2,5-dimethylphenylhydrazine (CCXCI-A), was employed as starting material. As far as the ester, methyl 1,4-dimethyl-carbazole-2-carboxylate (CCXCI-B), the two syntheses are parallel. Ring D was then built up, however, by the series of reactions,... 

Scheme 37. Lescot et al. synthesis of the 5-methyl-1 l//-pyrido[3,4-a]carbazole ring system (226, 111) (700).

Scheme 38. Synthesis of the 5-methyl-7//-pyrido[4,3-c]carbazole ring system (e.g., 231, 233) by Roques and co-workers (102).

Archer and co-workers (103) have also employed the Snieckus oxidative pho-tocyclization in the key step of their synthesis of the 7//-pyrido[4,3-c]carbazole ring system (Scheme 40). Thus, a Wittig condensation between pyruvate 242 and pyridine 243 gave the unsaturated ester 244. Photocyclization gave the tetracyclic ester 245. Reduction and reaction with methyl isocyanate led to carbamate 247. Oxidation of alcohol 246 to aldehyde 248, followed by a standard one-carbon homologation, gave the desired ethyl derivative 249. These chemists also synthesized the 10-methoxyl derivative of each compound. 

Much research interest in the synthesis of carbazoles is directed at the preparation of natural products. The total syntheses of murrayafoline A 153 and murrayanine have been reported <04S2499>. The key step included a regioselective cycloaddition between oxazolidinone 150 and acrolein which led to benzoxazol-2-one 151 after DDQ oxidation. Ring opening of the oxazol-2-one ring of 151 followed by methylation provided A-phenylaniline 152. A palladium-catalyzed intramolecular cyclization of the latter then produced the natural product 153. Finally, venerable iron-mediated chemistry has been utilized in the total synthesis of furoclausine A 154 <04SL528> and 6-chlorohyellazole 155 <04SL2705>. 

Demetalation of 4 with trimethylamine N-oxide yields car-bazole 5. Methylation gives carbazomycin A (1) [12]. In addition to carbazoles, Kndiker and his students applied this iron-mediated chemistry to the preparation of dihydroindoles [13, 14], (anhydrolycotine), tetrahydroindoles [15], dihydrocarbazoles [16], perhydroacenaphihenes [17], and azaspiroannelated ring systans [18-21], Several shorter accounts of Kndlker s carbazole syntheses [22-25] and the overall utility of tricarbonyl(Tl -diene)iron complexes in organic synthesis are available [26-32],... 

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