Assembly of Conjugated Enynes and Substituted Indoles via CuI/Amino Acid-Catalyzed Coupling of 1-Alkynes with Vinyl Iodides and 2-Bromotrifluoroacetanilides

Abstract

Cross-coupling of 1-alkynes with vinyl iodides occurs at 80 degrees C in dioxane catalyzed by CuI/N,N-dimethylglycine to afford conjugated enynes in good to excellent yields. Heating a mixture of 2-bromotrifluoroacetanilide, 1-alkyne, 2 mol % of CuI, 6 mol % of L-proline, and K(2)CO(3) in DMF at 80 degrees C leads to the formation of the corresponding indole. This conversion involves a CuI/L-proline-catalyzed coupling between aryl bromide and the 1-alkyne followed by a CuI-mediated cyclization process. An ortho-substituent effect directed by NHCOCF3 enables the reaction to proceed under these mild conditions. Both aryl acetylenes and O-protected propargyl alcohol can be applied, leading to 5-, 6-, or 7-substituted 2-aryl and protected 2-hydroxymethyl indoles in good yields. With simple aliphatic alkynes, however, lower yields were observed.

One-Pot Synthesis of Benzo[f]indole-4,9-diones from 1,4-Naphthoquinones and Terminal Acetylenes

“…According to the optimal reaction conditions reported by our group, 24) all experiments were performed with 2.0 eq of acetylene, 0.8 eq of an additive, 20 mol% of copper salt, and 200 eq of pyridine in N,NЈ-dimethylformamide (DMF) at 80°C. 32) However, bidentate ligands such as trans-N,NЈ-dimethylcyclohexane-1,2-diamine, 2,2Ј-bipyridine, L-proline, and 1,10-phenanthroline, which are typically used in copper-mediated coupling reactions, 25,26) were ineffective in promoting the reaction (Table 1, entries 3-6). In contrast, most inorganic bases proved applicable and furnished the cyclized product 4aa in 13-63% yields with K 2 CO 3 being suitable ( To determine the optimal copper salts, reactions with various copper(I) (CuI, CuBr, and CuOTf) and copper(II) salts (CuO, CuBr 2 , and CuCl 2 ) 33) were examined.…”

“…According to the reported methods typically used for indole syntheses, we tested the reactions using a catalytic amount of copper(I) salts with bidentate ligands such as bipyridine, 1,10-phenanthroline, and trans-N,NЈ-dimethylcyclohexane-1,2-diamine. [25][26][27] However, no coupling reactions were observed, and degradation of the starting naphthoquinone to a dehalogenated compound gradually occurred during the reaction.…”

Cross‐coupling reactions using porous multipod Cu2O microcrystals as recoverable catalyst in aqueous media

“…Since Miura and co-workers reported that CuI/PPh 3 catalyzed cross-couplings of aryl iodides and terminal alkynes, [13] much attention has been focused on the use of copper complexes as the catalysts for the Sonogashira cross-coupling for copper is less toxic and far more economic than palladium. [14][15][16][17][18][19][20][21] Although copper-based catalysts have been proposed as an alternative to palladium-based catalysts for Sonogashira couplings, these catalyst systems generally require high copper loadings to maintain a catalytic cycle. Therefore, the development of an efficient reaction system with recyclable copper catalysts is highly desirable.…”

A practical Cu(I)-catalyzed domino approach to 1,2-disubstituted indoles and its application for the assembly of indolophenanthridines

“…3,4 Popular approaches to these heterocycles include N-modification of 2-substituted NH indoles, 5-7 2-arylation of N-substituted indoles, [8][9][10] coupling/annulation of o-haloanilines with alkynes, [11][12][13] and intramolecular cyclization of o-(gem-dihalovinyl)anilines. [14][15][16] Several one-pot synthetic protocols have also been developed recently.…”