Synthesis of Annulated Indolines by Reductive Fischer Indolization

Cyclic β-oxoesters and arylhydrazine derivatives were converted at ambient temperature under modified Fischer indolization conditions to furnish annulated indolines with quaternary bridgehead carbon center. Reaction conditions were Brønsted acidic (with CF₃ CO₂ H), but also reductive (with Et₃ SiH). The latter reduced intermediate iminium ions under formation of the 2,3-dihydroindole product constitutions. Racemic products (13 examples) were obtained as single diastereoisomers with relative cis-configuration, which was proved in two cases by single-crystal X-ray structure analysis. Conversion of 4-bromo-1-indanone-2-carboxylate and 4-bromophenylhydrazine gave indeno[1,2-b]indolines with either 1-bromo, 8-bromo, or 1,8-dibromo substitution, which were further diversified by Suzuki coupling reactions with several arylboronic acids (nine examples).