Synthesis of carbazoles

Previous reviews relating to the synthesis of carbazoles and newer methods of synthesis have been cited by Joule in an updated account (63). Methods related to recent syntheses of carbazole alkaloids are briefly enumerated here. 

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Synthesis of carbazoles from indoles by quinodlmethane intermediates... 

Vinylindoles have been studied extensively and used in the synthesis of carbazoles, alkaloids and other classes of pharmacologically active compounds. MMX force field calculations have shown that coplanar s-cis and. s-trans conformations of 3-vinylindole (84, Figure 2.11) are the most stable conformers they exhibit only slight differences in their thermodynamic stabilities [86]. 

Noland and coworkers have developed an interesting methodology for the in situ synthesis of carbazoles. This methodology combines the synthesis of 3-vinylindoles from indoles and acyclic ketones with the subsequent Diels-Alder cycloaddition in one flask to produce a variety of tetrahydrocarbazoles [88] (Scheme 2.36). 

Pindur U., Lemster T. Recent Advances in the Synthesis of Carbazoles and Anellated Indoles With Antitumor Activity DNA-Binding Ligands and Protein Kinase C Inhibitors Recent Res. Dev. Org. Bioorg. Chem. 1997 1 33-54 Keywords Diels-Alder reactions of a 4,7-dioxo-indole with carbodienophiles... 

Zhao and Larock have described the synthesis of carbazoles, indoles, and dibenzofurans 118 via a Ic type cyclization that follows a sequence of Pd-catalyzed cross-coupling of alkynes and aryl iodides 116, then nitrogen-directed palladium migration to an arylpalladium intermediate 117 that undergoes an intramolecular Mizoroki-Heck ring closure <06JOC5340>. 

Occurrence, Biological Activity, and Convergent Organometallic Synthesis of Carbazole Alkaloids... 

Convergent Synthesis of Carbazoles by Oxidative Coupling of Arylamines. .. 121... 

Scheme 8 Synthesis of carbazoles by oxidative coupling of arylamines...

The palladium(II)-mediated oxidative cyclization is also applied to the synthesis of carbazole-l,4-quinone alkaloids. The required arylamino-l,4-benzo-quinones are readily prepared by arylamine addition to the 1,4-benzoquinone and in situ reoxidation of the resulting hydroquinone [131]. 

Knoelker H-J (2005) Occurrence, Biological Activity, and Convergent OrganometaUic Synthesis of Carbazole Alkaloids. 244 115-148 Kolodziejski W (2005) Solid-State NMR Studies of Bone. 246 235-270 Koser GF (2003) C-Heteroatom-Bond Forming Reactions. 224 137-172 Koser GF (2003) Heteroatom-Heteroatom-Bond Forming Reactions. 224 173-183... 

A. Synthesis of Carbazoles by Deoxygenation of Nitrobiphenyls 1 Watermann and Vivian s Method... 

Among the two cyclization procedures that utilize 2,2 -diaminobiphenyls, the Tauber synthesis has been most widely used and proceeds in higher yields than the diazotization reaction. The application of this method to the synthesis of carbazoles is limited by the availability of 2,2 -diaminobiphenyls. 

The application of indolo-2,3-quinodimethanes and their cyclic analogs in the synthesis of carbazole alkaloids has attracted wide interest since they could undergo Diels-Alder reactions with a wide variety of dienophiles to afford functionalized carbazole derivatives. This represents the shortest and most elegant method for the preparation of selectively functionalized carbazole derivatives (514). 

Diels-Alder reaction of vinylindoles with dienophiles has been established as a versatile and flexible methodology for the synthesis of carbazole alkaloids. Among the two different vinylindoles, 3-vinylindoles were the first to be explored for the Diels-Alder cycloaddition methodology with a range of dienophiles to give polyfunctionalized carbazole derivatives. This reaction is catalyzed by tiifluoroacetic acid, and the yield in the absence of the acidic catalyst is very low. The reaction of substituted 3-vinylindoles 550 and 553 with ethylenic dienophiles 551 and acetylenic dienophiles 535 leads, via a tetrahydrocarbazole and a dihydrocarbazole, to the corresponding carbazoles (552 and 554), respectively (530,531) (Scheme 5.18). 

Despite many applications of the iron-mediated synthesis of carbazoles, this method offers limited access to 2-oxygenated tricyclic carbazoles due to the moderate yield... 

In this section, we cover the total synthesis of carbazole alkaloids that are not discussed in the previous sections because of their unique substitution pattern. 

Research Focus Synthesis of carbazole poly(terephthate ester-co-carbonate) and sulfone... 

The prototype reactions for synthesis of pyrrole, indole and carbazole by processes involving electrophilic nitrogen are outlined in Scheme 3 with a nitrene as the electrophilic form of nitrogen. This conceptual scheme must be generalized to include nitrenoids and nitrene equivalents to accomodate the range of cyclizations which can proceed by this mechanism. In practice, this mechanistic pattern is rare for pyrroles, known but only of moderate utility for indoles, and among the most efficient methods for the synthesis of carbazoles. 

Aromatizations play a particularly prominent role in the synthesis of carbazoles since both the Fischer cyclization (Borsche s method) of cyclohexanones (Section 3.06.3.4.2) and the cycloaddition of 2-vinylindole (Section 3.06.6.1) yield tetrahydrocarbazoles. Both catalytic dehydrogenation over palladium/carbon catalyst and dehydrogenation with chloranil have been employed to effect aromatization (80JA4772,79JOC4402). 

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