Synthesis of 4-functionalized indoles via benzyne cyclization of N-(2-lithioallyl)-2-fluoroanilines
4-Substituted 3-methylindole derivatives are easily prepared by treatment of N-(2-bromoallyl)-2-fluoroanilines with tert-butyllithium and further reaction with electrophiles, via intramolecular addition to a benzyne intermediate
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Nucleophilic Coupling with Arynes
2014, Comprehensive Organic Synthesis: Second EditionSynthesis of heterocyles by cyclization of unsaturated organolithiums: A review
2002, Journal of Organometalic ChemistryChapter 5.2 Five membered ring systems: Pyrroles and benzo derivatives
2000, Progress in Heterocyclic ChemistryCitation Excerpt :This author now reports that tetrabutylammonium fluoride (TBAF) is capable of inducing cyclization to the indoles 68 without affecting functionalities such as bromo, cyano, ethoxycarbonyl, and ethynyl <99JCS(P1)529>. Barluenga has extended the intramolecular carbolithiation reaction of N-allyl-N-r-(2-lithioallyI)amines to the synthesis of 4-substituted indoles using a benzyne-cyclization methodology <99TL1049>. Thus, treatment of N-(2-bromoallyl)-N-methyl-2-fluoroaniline (69) with 3.3 equiv of t-butyllithium effects halogen-metal exchange followed by abstraction of the proton adjacent to the fluorine to yield intermediate 70.
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