Carbazole derivatives synthesis from indoles

Pyrroles, H.M.L. Davies. Synthesis of Porphyrins with Exocy-clic Rings from Cycloalkenopyrroles, T.D. Lash. Palladium-Catalyzed Coupling Reactions of Indoles, A.R. Martin and Q. Zheng. Cycloaddition Reactions of Indole Derivatives, U. Pindur. Transition-Metal Mediated Synthesis of Carbazole Derivatives, H. J. Knoiker. Synthesis of [b]-Annelated Indoles by Thermal Electrocyclic Reactions, S. Hibino and E. Sugi-no. Total Synthesis of (-) and ent (-) Duocarmycin SA, D.L. Boger. Index. I... 

Blechert and coworkers have developed a very efficient one-pot synthesis of 2-vinylindole derivatives, starting from an aldehyde, phenyUiydroxylamine, and cyanoallene [64], These 2-vinyl indole species have demonstrated good synthetic utility in constructing linear carbazole skeletons that could be useful as key intermediates in the assembly of indole alkaloids [65]. Early on, it was discovered that the Diels-Alder reactions of the 2-vinylindole species 150 did not proceed under thermal conditions, and the use of Lewis acids did not offer any advantages. However, cycloadditions with electron-deficient dienophiles 151 (at room temperature in chloroform/dichloromethane and in the presence of trifluoroacetic acid), followed by aromatization, led to the formation of the tetrahydrocarbazole structures 152 (Scheme 38). These reactions were found to proceed with high selectivity for the endo products. The tetrahydrocarbazoles 152 could then be oxidized with DDQ to form the corresponding carbazoles in good yields. 

This reaction was first reported by Hantzsch in 1890. It is the preparation of 2,5-dialkyl or 2,4,5-trialkylpyrrole derivatives from the condensation of of-halo-ketones, )0-ketoesters and ammonia or amines. Therefore, it is often known as the Hantzsch pyrrole synthesis or simply the Hantzsch synthesis. During this synthesis, ammonia or amine reacts quickly with y0-keto esters to form enamine esters or 3-amino crotonates that cyclize with of-halo-ketones to form pyrrole derivatives upon heating, and the regioselectivity strongly depends on the substituents on the starting materials. Thus, this reaction can directly start from 3-amino crotonates or enamines of 0-keto esters. Further extension of this reaction from aromatic amines results in the formation of indole derivatives, or carbazole derivatives if cyclized with a-halo-cyclohexanones. The synthesized pyrroles have wide application in medicinal chemistry, conducting polymers, molecular optics, sensors,etc. 

Bereman and Nalewajek (72) described the synthesis of dithiocarbamates derived from indole, indoline, carbazole, and imidazole (Fig. 7). Again, the amides are initially generated in dry THF upon addition of potassium metal, and later addition of excess carbon disulfide at —78°C leads to generation of the potassium salts of the dithiocarbamates (Eq. 4). While the indoline and imidazole derivatives are relatively air stable, the others are extremely air sensitive decomposing in a matter of minutes. The potassium salt of the dithiocarbamate derived from 2,2 -dipyridylamine (Fig. 7) has been prepared in a similar fashion, and while air stable, it is extremely hygroscopic (73). 

The hydrolysis and alcoholysis reactions have been extended to the heterocyclic series. A systematic study has been published of the hydrolysis of unsaturated oxazolones derived from a selection of heterocyclic aldehydes. A detailed study of the synthesis and stereospecific hydrolysis and methanolysis of the (Z) and ( ) isomers of 2-methyl (or phenyl)-4-(thienylmethylene)-5(4F/)-oxazo-lones 435 and 437 has also been described (Scheme 7.144). The synthesis of 2-acylamino-3-(indol-3-yl or carbazol-3-yl)acryhc acid derivatives as potential antifertility agents via oxazolone hydrolysis has also been published. ... 

A further extension of this strategy has been employed as a route to carbazoles, as illustrated by the synthesis of the system 116 from the 2-nitrobiphenyl derivative 117 (Equation 30) <20040L533>. A substituted 2-nitrobiphenyl derivative has been cyclized to a carbazole using P(OEt)3 en route to the pyridocarbazole alkaloid ellipticine <2006HCA111>. It should also be mentioned that annulation of o-(alkynyl)nitrobenzene precursors with TBAF or pyridine gave access to indol-3-one-l-oxides (isatogens) <2003T2497>. 

From a retrosynfhetic viewpoint, N-aryl-l,2-diimine Ni precatalysts are synthesized by (i) reaction of 1,2 diimines with nickel halides from (ii) 1,2-diimine ligands which in turn are obtained by (iii) condensing 1,2-dicarbonyl substrates with two equivalents of primary aromatic amines, usually under acidic conditions [11]. In analogy, the synthesis of N-hetaryl 1,2 diimine catalysts starts from the corresponding substituted N-heterocyclic primary amines as the amine building blocks. The synthesis of three types of such heterocycles, N-amino-pyrroles, -indoles and -carbazoles, and their corresponding diimine derivatives is presented in the following sections. 

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