Willis indole synthesis

Ackermann employed a different reaction order to meld 1,2-dihaloaryls together with anilines to access a series of carbazoles, including murrayafoline A (Scheme 2, equations 1 and 2) [23]. Jean and colleagues reported a tandem Suzuki/aryl-Heck protocol to prepare functionalized carbazoles and glycosinine (equation 3) [24]. Larock and Liu synthesized a series of carbazoles and the alkaloid muko-nine via an aryl-Heck reaction, which featured an aryne mediated preparation of the requisite diaryl amines [25]. Willis and coworkers reported an indole synthesis involving Heck arylation followed by double bond isomerization (equation 4) [26]. Urabe and colleagues described a similar aryl-Heck indolization from p-bromo-Al-aryl enamines giving 2-alkylindoles [27]. 

Scheme 12.55. An early synthesis of indole from o-nitrotolnene (after U.S. Patents 3,732,245 and 3,976,639 to Willy Leimbgruber and Hoffmann-La Roche Ltd.).

The utility of this route was demonstrated with a synthesis of the natural product demethylasterriquinone A [44], -(Reverse prenyl)indole 15 was utilized as a key intermediate in this synthesis, which also demonstrates that sterically demanding N-nucleophiles can be incorporated. Willis and co-workers have also reported a copper-catalyzed version. In general, this variant was more limited however, greater... 

Banwell MG, Lupton DW, Willis AC. Application of the palladium(0)-catalyzed Ullmann cross-coupling reaction in a total synthesis ( )-aspidospermidine and thus representing an approach to the lower hemisphere of the binary indole-indoline alkaloid vinblastine. Aus. J. Chem. 2005 58 722-737. 

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