Miscellaneous Nucleophilic Cyclizations that Form the Indole Ring

Miscellaneous Nucleophilic Cyclizations that Form the Indole Ring 

There exist a plethora of nucleophilic cyclizations leading to the indole ring that are not embraced by the name reactions presented hitherto. Although these indole syntheses are not (yet) graced by the name of their inventor, I will mention the senior author in each case. In many indole ring-forming reactions, the final step is an amino carbonyl cyclization, but the essence of the indolization may place this particular reaction in a separate chapter. 

The enormous reactivity of hexafluorobenzene is displayed in its reaction with enamines as discovered by Wakselman and Blazejewski (equation 4) [4]. Indoles 5 can be oxidized to their respective carbazoles with chlora-nil (refluxing toluene, 45%-79%). That one of the R groups is lost as RF from intermediate 7 is seen in the isolation of 

5 (R =(CH2)4F) when the pyrrolidine enamine is used. The intermediate C-arylation enamine 6 was observed by T-ISIMR. 

Ojima and colleagues found that enamine (imine) 9 from aldehyde 8 readily cycUzed to indoles 10 upon treatment with LDA (equation 5) [5, 6]. The A-allyl group in 10 was removed by rhodium trichloride isomerization followed by acidic hydrolysis of the A-enamine (97% yield). Along similar lines. Filler s team reported an improved synthesis of 4,5,6,7-tetrafluoroindole 13 (equation 6) [7] over the method they had reported earlier. The improvements are in the reduction of nitrile 11 to phenethylamine 12 and the final oxidation to 4,5,6,7-tetrafluoromdole (13). 

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Miscellaneous Nucleophilic Cyclizations that Form the Indole Ring 235 Ri 0... 

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