Quinones Methyllithium

Addition of the arylamines 117 to 2-methoxy-3-methyl-l,4-benzoquinone 118 affords regioselectively the 5-arylamino-2-methoxy-3-methyl-l,4-benzo-quinones 119 (Scheme 37). Palladium(II)-catalyzed oxidative cyclization leads to the carbazole-l,4-quinones 28 [135,136],previously obtained by the iron-mediated approach (cf. Scheme 14). Regioselective addition of methyllithium to the quinones 28 provides carbazomycin G 29a and carbazomycin H 29b [96,135]. Reduction of 29a with lithium aluminum hydride followed by elimination of water on workup generates carbazomycin B 23a [135]. Addition of heptylmag-... 

Hibino et al. reported the total synthesis of carbazomycin G (269) by the regioselective addition of methyllithium onto 3-methoxy-2-methylcarbazole-l,4-quinone (941) (653). The required immediate precursor of carbazomycin G, carbazole-l,4-quinone 941, was obtained from 3-(2-methoxyethenyl)-N-(phenylsul-fonyDindole (986). The benzannulation involves an allene-mediated electrocyclic reaction of a 67t-electron system generated from the 2-propargylindole 989, which was derived from the 3-vinylindole 986 in three steps. 

Two years later, the same group reported a formal synthesis of ellipticine (228) using 6-benzyl-6H-pyrido[4,3-f>]carbazole-5,ll-quinone (6-benzylellipticine quinone) (1241) as intermediate (716). The optimized conditions, reaction of 1.2 equivalents of 3-bromo-4-lithiopyridine (1238) with M-benzylindole-2,3-dicarboxylic anhydride (852) at —96°C, led regioselectively to the 2-acylindole-3-carboxylic acid 1233 in 42% yield. Compound 1233 was converted to the corresponding amide 1239 by treatment with oxalyl chloride, followed by diethylamine. The ketone 1239 was reduced to the corresponding alcohol 1240 by reaction with sodium borohydride. Reaction of the alcohol 1240 with f-butyllithium led to the desired 6-benzylellipticine quinone (1241), along with a debrominated alcohol 1242, in 40% and 19% yield, respectively. 6-Benzylellipticine quinone (1241) was transformed to 6-benzylellipticine (1243) in 38% yield by treatment with methyllithium, then hydroiodic acid, followed... 

Reductive metky/atum of quinones.2 Dimethylarenes can be obtained in high yield by reaction of quinones with methyllithium (excess) in benzene to form a dimethyl dihydrodiol, which is reduced without purification with HI in refluxing acetic acid. 

Electrophilic aromatic substitution of 5-hydroxy-2,4-dimethoxy-3-methylaniline by reaction with the iron complex salts affords the corresponding aryl-substituted tricarbonyliron-cyclohexadiene complexes. O-Acetylation followed by iron-mediated arylamine cydization with concomitant aromatization provides the substituted carbazole derivatives. Oxidation using cerium(IV) ammonium nitrate (CAN) leads to the carbazole-l,4-quinones. Addition of methyllithium at low temperature occurs preferentially at C-1, representing the more reactive carbonyl group, and thus provides in only five steps carbazomycin G (46 % overall yield) and carbazomycin H (7 % overall yield). 

---