Chemistry of O rganometallic Compounds and Applications Copper( I )-Promoted Aromatic Nucleophilic Substitution Reactions of o-Bromoaniline Derivatives with Active Methylene Carbanions'

Abstract

The reactions of copper ( I ) diethyl malonate [1] with sodium salts of N-acetyl- [2a], N-propionyl- [2b], and N-benzoyl-o-bromoaniline [2'c] afforded diethyl 2, 2 '-dioxo-3, indoline-3, 3-dicarboxylate [3] in 15∼22% yields. Activation of the aroma tic substitution observed for the sodium salts is attributed to the coordination of the anionic amide nitrogen to copper ( I ), leading to the formation of 3-ethoxycarbonyl-2-oxo-3-indolinyl-copper ( I )which subsequently undergoes thermal dimerization to give [3] J. Active methylene carbanions substituted with o-bromoanilino group cyclized in the presence of copper ( I ) salt to give indole derivatives.3-Acetyl-2-hydroxyindole [7a] and N-methyl-2-indolinone [7c] were obtained in 13 and 25% yield, respectively, when copper ( I ) complexes of N-acetoacetyl-obromoaniline [6a]and N-ethoxycarbonylacetyl-N-methyl-o-bromoaniline [6] cp were allowed to react.3-Acetyl-2-methylindole [9a] and 3-ethoxycarbony1-2-methylindole [9b] were isolated in 14 and 46% yield, respectively, from the reactions of copper ( I ) complexes of N(2-acety1-1-methylethylidene)-o-br omoaniline [8 a] and N-(2-ethoxycarbonyl-1-methylethylidene)o-bromoaniline [8b]. The relatively high yield of [9 b], the ease with which starting material [8b] is prepared, and the simple reaction procedu re make the aromatic nucleophilic cyclization reaction useful for the synthesis of 2-alkyl-3-(ethoxycarbonyl)indoles.