Assembly of conjugated enynes and substituted indoles via CuI/amino acid-catalyzed coupling of 1-alkynes with vinyl iodides and 2-bromotrifluoroacetanilides.
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.
Liu
Feng
F
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China.
Ma
Dawei
D
D000083:Acetanilides / Q000737:chemistry*; D000114:Acetylene / Q000031:analogs & derivatives / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D001966:Bromine / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D007211:Indoles / Q000737:chemistry*; D007454:Iodides / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure
D000083:Acetanilides; D000480:Alkynes; D000596:Amino Acids; D007211:Indoles; D007454:Iodides; C044736:phenylacetylene; C009551:trifluoroacetanilide; D003300:Copper; C073870:cuprous iodide; D000114:Acetylene; D001966:Bromine