Carbazole synthesis Subject

The antitumor alkaloid ellipticine (5,1 l-dimethyl-6//-pyrido[4,3-b]carbazole) has been isolated from many species of Ochrosia and Aspidosperma. Ellipticine and its derivatives are highly active versus several experimental neoplasms, and the compound has been widely subjected to studies devoted to its total synthesis, the preparation of derivatives, and metabolism. Metabolic transformation studies with ellipticines have been conducted, using microorganisms, in vivo and in vitro... 

The radical cation Diels-Alder reaction has been the subject of many mechanistic and theoretical investigations and has been shown to have much synthetic potential. With regard to heteroaromatics, the reaction has been exploited by Steckhan in the cycloaddition of indoles and 1,3-dienes. This reaction occurs smoothly upon photosensitization by triarylpyrrilium tetrafluoroborates. The reaction is satisfactory rationalized as involving addition of the indole radical cation to electron-rich dienes (Scheme 35), and the regioselectivity is in accord with theoretical predictions [104]. The reaction with exocyclic dienes has been developed for the synthesis of carbazole derivatives such as 52 and 53 [105]. 

Construction of the Dolby model system began with epoxidation of cyclohexene 209 employing mCPBA in chloroform. The epoxide product was then subjected to a base-promoted cyclization via amide deprotonation and oxirane opening to provide benzamide 210 (Scheme 23). Hydroxyl oxidation using the Jones conditions next furnished cyclohexanone 211. A Fischer indole synthesis on this scaffold, followed by amine deprotection using sodium hydroxide, led to the desired l,3-(iminoethano)carbazole 83. While the yield of this route was low, it was the first example of a method to fashion the 2-azabicyclo[3.3.1]nonan-8-one system 211, and importantly demonstrated that indoHzation on such a scaffold was possible. 

In 2006, Lu and coworkers [53] described a method for the synthesis of carbazoles using the palladium(ll)-catalysed oxidative Heck reaction (Scheme 9.25). Indole 177 was subjected to catalytic Pd(OAc)2 and 2.1equiv of benzoquinone to afford carbazole 178 in 88% yield. Because the alkene is 1,1-disubstituted, a 5-exo cyclization mode (as seen in Ferreira and Stoltz s [48] indole annulation) is unproductive, and a 6-endo cyclization ultimately occurs. The putative intermediate is then believed to be oxidized to the aromatic carbazole by the excess benzoquinone. When indole 179, featuring a terminal alkene, was treated with these oxidative conditions, a mixture of products from 6-endo cyclization (180) and 5-exo cyclization (and subsequent isomerization and [3+2] cycloaddition, 181) was observed. A variety of substituted carbazoles were obtained by this palladium(n)-catalysed oxidative cyclization. 

Although their work is of marginal preparative value, Klemm, Horaguchi, and colleagues effected the synthesis of carbazole and related fused indoles by subjecting primary arylamines to calcium oxide at high temperatures... 

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