Using indole: oxidative coupling

Copper salts and complexes are used either as oxidant or as catalysts in the presence of a ligand/additive. Cu(acac)2 in THF has been used for oxidative coupling between an indole and a chiral nickel(II) complex (4) in the presence of lithium diisopropylamide (base). The resulting adduct, formed in 63% yield with >99% de, disproportionates readily to 3-indolylglycine derivatives in high yields. 

Most of the early applications of palladium to indole chemistry involved oxidative coupling or cyclization using stoichiometric Pd(II). Akermark first reported the efficient oxidative coupling of diphenyl amines to carbazoles 37 with Pd(OAc)2 in refluxing acetic acid [45]. The reaction is applicable to several ring-substituted carbazoles (Br, Cl, OMe, Me, NO2), and 20 years later Akermark and colleagues made this reaction catalytic in the conversion of arylaminoquinones 38 to carbazole-l,4-quinones 39 [46]. This oxidative cyclization is particularly useful for the synthesis of benzocarbazole-6,11-quinones (e.g., 40). 

Oxidative homocoupling of aromatic and heteroaromatic rings proceeds with Pd(OAc)2 in AcOH. Biphenyl (165) is prepared by the oxidative coupling of benzene [104,105], The reaction is accelerated by the addition of perchloric acid. Biphenyl-tetracarboxylic acid (169), used for polyimide synthesis, is produced from dimethyl phthalate (168) commercially [106], Intramolecular coupling of the indole rings 170 is useful for the synthesis of staurosporine aglycone 171 [107]. 

Although beyond the scope of this section, some related approaches to these compounds are worth mentioning. 2-Substituted pyridines and quinolines can be obtained in two steps from the parent compounds following nucleophilic attack by an aryllithium (e.g. 2-thienyllithium) and then oxidiation. Intramolecular oxidative coupling reactions between the 2-positions of two indole nuclei can be achieved using DDQ, in the presence of a trace of tosic acid. A very efficient route to a variety of unsymmetri-... 

The oxidative coupling reactions of benzofuran and N-substituted indoles with benzene and derivatives have also been achieved using oxygen as an oxidant (Equation 11.37) [76]. This methodology for synthesizing heterocoupled biaryls... 

In the enantioselective total synthesis of okaramine N, Corey carried out intramolecular oxidative coupling of congested trisubstituted alkene at C-2 of indole in a complex molecule to give 172 in 44% yield using Pd(OAc)2 (1 equiv.) at room... 

It was also reported that the use of quinoxaline A-oxide gives rise to coupling in even a higher yield than the parent indole-pyridine coupling reaction (Scheme 8) [26], The coupling reactions with isoquinoline, phthalazine, and pyrimidine A-oxides proved to proceed smoothly, and their regioselective outcomes were found to be consistent with the parent coupling reaction. 

Attempts to use any other carbonyl compounds in this process led to either trace amounts of indole or no reaction at aU. That is why an alternative two-step, one-pot procedure utilizing p-ketoesters was explored. Similarly to the method originally discovered by Glorious and coworkers (08AGE7230), SFs-anilines 11 and 39 were first condensed with P-ketoesters in the presence of InBr3 under solvent free conditions, and the in situ formed enamine carboxylates then underwent subsequent cyclization by Pd-catalyzed, intramolecular oxidative coupling to give 2-methyl-3-carbalkoxy-5(6)-SF5-indoles (42a—h) in 40—46% yields (Scheme 10). 

Fujiwara and coworkers [23] recently described a single example of a catalytic inter-molecular oxidative coupling using the free NH indole nucleus. Under Pd(OAc)2 and a... 

Gu and coworkers reported an 2-iodoxybenzoic acid (IBX) induced oxidative coupling of in situ formed Baylis-Hillman adducts 114 with a nucleophile in water (Scheme 12.44) [68]. As nucleophiles, styrenes, P-dicarbonyl compounds, benzamides, and less reactive indoles can be used. This strategy offers an alternative path to the methylenylation of fS-dicarbonyl compounds with formaldehyde for the formation of a methylene intermediate. In the reaction of 112 and the styrenes 113 (R = Ph), a 5,6-dihydropyran 114 is formed. 

Oxidative coupling between pyridine A-oxides (and analogues) and A-substituted indoles via twofold C-H bond activation was achieved in up to 88% yield with high selectivity using Ag2C03 as the oxidant and Pd(OAc)2 as the catalyst in the presence of DMF and pyridine as base and tetrbutylammonium bromide as additive. ... 

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