An Efficient and Mild CuI/l-Proline-Catalyzed Arylation of Acetylacetone or Ethyl Cyanoacetate

Abstract

The coupling reaction of aryl iodides with acetylacetone or ethyl cyanoacetate under catalysis of CuI/L-proline works at relatively mild conditions to provide 3-aryl-2, 4-pentanediones and a-aryl cyanoacetates in moderate to good yields.Reaction of aryl halides with carbon nucleophiles, such as anions of active methylene compounds, is a useful tool for the preparation of substituted aromatic compounds, 1 such as 3-aryl-2,4-pentanediones and a-aryl cyanoacetates, which are very important building blocks for synthesizing various heterocycles, amino alcohols and amino acids. 2,3Among the many methods available for the a-aryl carbonyl compounds, a great deal of recent attention has focused on the development of palladium-catalyzed arylation methodology. 4 Some exciting achievements have already appeared in this field. For instance, the coupling of diethyl malonate or ethyl cyanoacetate with aryl chloride could be carried out at 70°C using certain phosphines as the ligands. 4c However, high costs and toxicity of Pd reagents and the relative ligands limit their application in industrial employment.The arylation of activated methylene compounds mediated by copper salts is a well-established process, 5 but the reaction usually requires a stoichiometric amount of copper salt unless the halides are activated by an o-carboxylate group. 6 In 1993, Miura et al. reported a coppercatalyzed arylation of malononitrile, ethyl cyanoacetate and acetylacetone using aryl iodides. 7 However, their system required harsh condition (120°C) and the substrate scope was limited. In recent years, research efforts in several laboratories have delivered a series of mild Ullmanntype methodologies based on employing some specific ligands. For examples, Buchwald and co-workers reported copper-catalyzed methods for arylation of amides, amines, N-heterocycles, hydrazides, phenols and a-aryl malonates using suitable additives such as glycol and diethylsalicyamide. 8 Ma's group discovered that L-proline and other amino acids were another type of effective ligands for copper-catalyzed coupling reactions of aryl halides with amines, N-heterocycles, sodium azide, sulfinic acid salts, phenols, and 1-alkynes. 9 Cristau and co-workers have also developed mild copper-catalyzed Narylation and C-arylation by employing chelating Schiff base Chxn-Py-Al as the ligand. 10 Stimulated by their results, we recently found that L-proline could serve as a promoter for CuI-catalyzed coupling reaction of aryl iodides with acetylacetone or ethyl cyanoacetate, giving cross-coupling products in relatively mild conditions. Herein we wish to detail our results.Initially, we used the reaction of iodobenzene with acetylacetone as a model to explore the suitable reaction conditions. It was found that under the conditions of 10 mol% CuI, 20 mol% L-proline, and 4 equivalents K 2 CO 3 in DMSO the reaction gave 3-phenyl-2,4-pentanedione in 76% yield at 90°C (Equation 1, entry 1 in Table 1). In the absence of L-proline, the reaction gave only 35% yield at 90°C (entry 2), which indicat...

Supramolecular Columnar Liquid Crystals with Tapered‐Shape Simple Pyrazoles Obtained by Efficient Henry/Michael Reactions

“…[12] More recently,i th as been reportedt hat acetylacetone can be arylated with iodoarenes under milder conditions by treatment with ac atalytic amount of copper(I) iodide and l-proline as ap romoter. [13] In this way, and after optimizing the reaction temperature and time in order to avoid the deacylations ider eaction that leads to benzylm ethyl ketones, [14] the synthesis of 3-aryl-2,4-pentanodiones with one electron-withdrawing group (NO 2 ), or with one electron-donating group (OH or OCH 3 )inthe para-position was achieved with yields of 74 %a nd 44 %, respectively in our previouswork. [5] This route could be applied to the required 1,3-diketones by using the commerciallya vailable 4-iodo-1,2-dimethoxybenzene and 5-iodo-1,2,3-trimethoxybenzene.…”

Light-driven water oxidation for solar fuels

“…Synthesis of aryl-acetylacetonate from aryl halides via 3,5-dimethyl-isoxazole adduct (route A) [28, 29] or via CuI/L-proline-catalyzed substitution with 2,4-pentanedione (route B) [30]. …”

Copper(I) Enolate Complexes in α‐Arylation Reactions: Synthesis, Reactivity, and Mechanism

“…(1)]. [1–2] Recently, significant improvements in the scope and reaction conditions of these copper-catalyzed Hurtley-type reactions have been achieved using a combination of copper complexes with ancillary ligands, such as 2-phenylphenol, [3] chelating Schiff bases, [4] l -prolines, [5] and 2-picolinic acid. [6] …”