CuI/L-proline

The direct alkenylation of arylamines at the ortho position has been reported in reactions of o -chloroalkenylmagnesium chloride with N-lithioarylamines.22 Use of the CuI-L-proline catalyst system in DMSO has been found to be successful in promoting reactions of aryl iodides and bromides with activated methylene compounds, such as ethyl acetoacetate and diethyl malonate.23 The same catalyst in dioxane has been used in intramolecular cyclization of ene-carbamates leading to indoles or pyrrolo[2,3-cjpyridines.24... 

The arylation of ethyl acetoacetate, ethyl benzoylacetate, and diethyl malonate under the catalysis of CuI/L-proline in DMSO has been performed at 40-50 °C in the presence of CS2CO3 to provide the 2-aryl-1,3-dicarbonyl compounds in good yields.38 Both aryl iodides and aryl bromides are compatible with these reaction conditions. 

Although the CuI/L-proline (LI) catalytic system showed no obvious acceleration effect for the coupling of aryl halide and amides, the Ma group found that N,N-dimethylglycine (L2) was a suitable promoter for the coupling reaction of vinyl halides with amides, and, in many cases, the reaction worked at room temperature (entry 3) [39], Another combination (Cu(CH3CN)4PF,s/L15/Rb2C03) was recently found effective for this transformation (entry 4) [40],... 

Scheme 2.95 CuI/L-proline-catal) ed s aithesis of indoles from propiolic acids.

Copper-Catalyzed Reactions The use of Cul was explored in combination with several ligands for the coupling of aryl halides with hydroxide nucleophiles. In 2006, Leadbeater reported the coupling aryl halides with NaOH using CuI/L-proline in water under... 

Lu and Ma [116c] applied the same catalytic system (CuI/L-proline) in the intramolecular couphng of p-keto-2-iodoanilides in DMSO, at room temperature, affording substituted 3-acyloxindoles in good yields (Scheme 8.65). 

A CuI/L-proline mediated synthesis of 3-exomethylene P-lactams via Kinugasa reaction has been reported by Basak and Ghosh [106]. Coupling of propargylic alcohol (341) with nitrone (313) in the presence of Cul/r-proline resulted in good yield of the desired 3-exomethylene P-lactam (342), but enantioselectivity was... 

X. Diao, Y. Wang, Y. Jiang, D. Ma, Assembly of substituted IH-benzimidazoles and l,3-dihydrobenzimidazol-2-ones via CuI/L-proline catalyzed coupling of aqueous ammonia with 2-iodoacetanilides and 2-iodophenylcarbamates, J. Org. Chem. 74 (2009) 7974-7977. 

CuI/L-proline was found by Abbott chemists to be able to catalyze the intramolecular C-N bond formation of ene-carbamates 32, affording 2-substituted indoles 33 [39] (Scheme 11). Using Pd2(dba)3/fBu3P as the catalyst gave similar results. 

Scheme 11 Assembly of 2-substituted indoles via CuI/L-proline-catalyzed intramolecular C-N bond formation...

Scheme 16 CuI/L-proline-catalyzed synthesis of substituted benzimidazoles from 2-haloanilides...

Two other Cu-catalyzed reactions have been reported for preparing 2-aryl-2//-indazoles 114 (Scheme 40) [76] and 1-substituted indazolones 116 (Scheme 41) [77]. The first one started from protected hydrazines 112, which underwent intramolecular amidation and subsequent deacylation and oxidation to afford 114 with moderate yields. In this case, if base was switched from K2CO3 to CS2CO3, no ligand was required. The secondary one using amides 115 as substrates, which were catalyzed by CuI/L-proline to provide 116 with good yields. 

Scheme 66 Pyrrolo[l,2-a]quinoxaline formation via CuI/L-proline catalyzed coupling of 2-halotrifluoroacetanilides and pyrrole-2-carboxylate esters...

CuI/L-proline-catalyzed coupling of 2-halotrifluoroacetanilides 187 with pyrrole-2-carboxylate esters 188 in dimethyl sulfoxide (DMSO) at 80-90°C followed by in situ hydrolysis and condensative cyclization at60°C affordedpyrrolo[l,2-a]quinoxalines 189 with good yields (Scheme 66) [111]. Indole-2-carboxylate esters underwent the same process smoothly to provide the corresponding tetracychc products. 

CuI/L-Proline/[Bniim][BF4] Ionic Liquids with Aryl/Heteroaryl Bromides. 122... 

CuI/L-Proline/[Bmim]BF4 Ionic Liquids with Vinyl Halides. 124... 

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