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

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