In search of simplicity and flexibility: a rational access to twelve fluoroindolecarboxylic acids

All twelve indolecarboxylic acids carrying both a fluorine substituent and a carboxy group at the benzo ring have been prepd. either directly from the corresponding fluoroindoles or from the chlorinated derivs. by hydrogen/metal permutation ("metalation"), or from the bromo- or iodofluoroindoles by halogen/metal permutation, the organometallic intermediate being each time trapped with carbon dioxide. In most, though not all cases, the nitrogen atom in the five-membered ring had to be protected by a trialkylsilyl group. Some of the bromo- or iodofluoroindoles were successfully subjected to a basicity gradient-driven selective migration of the heavy halogen. An unexpected finding on the way to the target compds. were the rigorously site-selective metalation of the 5-fluoro-N-(trialkylsilyl)indole (exclusive deprotonation of the 4-position). The fluoroindoles, although previously known, were accessed more conveniently from suitably substituted nitrobenzenes using the Bartoli or the Leimgruber-Batcho method. A new and very attractive indole synthesis was elaborated consisting of the ortho-lithiation of an N-acyl-protected aniline followed by ortho-formylation, Wittig chloromethylenation and base-catalyzed cyclization accompanied by dehydrochlorination. These five consecutive steps can be contracted to a convenient one-pot protocol. [on SciFinder (R)]


Published in:
European Journal of Organic Chemistry, 13, 2956-2969
Year:
2006
Keywords:
Note:
CAN 145:314758
27-11
Heterocyclic Compounds (One Hetero Atom)
Institute of Chemical Sciences and Engineering, BCh,Ecole Polytechnique Federale,Lausanne,Switz.
Journal
1434-193X
written in English.
348-54-9 (2-Fluoroaniline); 371-40-4 (4-Fluoroaniline); 446-10-6 (4-Fluoro-1-methyl-2-nitrobenzene); 460-00-4 (1-Bromo-4-fluorobenzene); 1073-06-9 (3-Fluorobromobenzene) Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of twelve indolecarboxylic acids carrying both a fluorine substituent and a carboxy group at the benzo ring); 321-23-3P (4-Bromo-2-fluoro-1-nitrobenzene); 364-73-8P (4-Bromo-1-fluoro-2-nitrobenzene); 367-24-8P (4-Bromo-2-fluoroaniline); 387-43-9P (4-Fluoroindole); 387-44-0P (7-Fluoroindole); 399-51-9P (6-Fluoroindole); 399-52-0P (5-Fluoroindole); 446-09-3P (1-Bromo-4-fluoro-2-nitrobenzene); 700-36-7P (2-Bromo-4-fluoro-1-nitrobenzene); 60144-53-8P; 98968-72-0P; 169674-02-6P (4-Chloro-5-fluoroindole); 169674-57-1P; 292636-09-0P (7-Bromo-4-fluoroindole); 344790-96-1P; 376646-56-9P; 408355-23-7P (7-Bromo-5-fluoroindole); 434960-42-6P; 844891-30-1P; 844891-31-2P; 883500-66-1P; 883500-73-0P; 885520-49-0P; 908600-76-0P; 908600-77-1P; 908600-78-2P; 908600-79-3P; 908600-80-6P; 908600-81-7P; 908600-82-8P; 908600-83-9P; 908600-84-0P; 908600-85-1P; 908600-86-2P; 908600-87-3P; 908600-88-4P; 908600-89-5P; 908600-90-8P; 908600-91-9P; 908600-92-0P; 908600-93-1P; 908600-94-2P; 908600-95-3P; 908600-96-4P; 908600-97-5P; 908600-98-6P; 908600-99-7P; 908601-00-3P; 908601-01-4P; 908601-02-5P; 908601-03-6P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of twelve indolecarboxylic acids carrying both a fluorine substituent and a carboxy group at the benzo ring); 256935-99-6P; 313337-34-7P (4-Fluoroindole-7-carboxylic Acid); 588688-52-2P; 875305-42-3P; 875305-87-6P; 885520-31-0P; 908600-70-4P; 908600-71-5P; 908600-72-6P; 908600-73-7P; 908600-74-8P; 908600-75-9P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of twelve indolecarboxylic acids carrying both a fluorine substituent and a carboxy group at the benzo ring)
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 Record created 2007-03-07, last modified 2018-01-27


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