Copper -promoted oxidative coupling

SCHEME 41. Copper-promoted oxidative phenol-couplings of 2,6-dimethylphenol... 

Enol Ether Synthesis. A 2-(trimethylsilyl)ethyl-based dithioorthoformate was prepared via copper(II) bromide-promoted oxidative coupling of bis(phenylthio)-methyltributylstannane. The dithioorthoformate thus prepared is treated with a titanocene(II) reagent followed by the addition of ketones or esters to promote alkoxymethylidenation as exemplified in eq 32. ... 

Since then, experiments have been reported which indicate that (1) organocopper compounds will couple with aryl halides (2) arylcopper compounds can be oxidatively and thermally dimerized (3) arylcopper compounds are intermediates in the Ullmann reaction (4) organocopper compounds are intermediates in copper-catalyzed decarboxylations and (5) copper-promoted coupling reactions are not restricted to aromatic halides. The copper(I) oxide-promoted coupling reactions, however, have still to yield firm evidence of a copper intermediate. 

It has been known for some time that ligands 27, 35, and 36 can be used for direct synthesis of oxidized Cu(I) chloride solutions which are useful catalysts for oxidative coupling processes (26,27). Amide and lactam ligands contain the nitrogen atoms of amines (which generally promote Cu(I) oxidation, see above) and also serve as crude models for the peptide link of proteins, which is the general environment of copper found in oxidases (28). 

Diketones. Lithium enolates of ketones are coupled to 1,4-diketones in the presence of copper(Il) triflate (1 equiv.). Unlike the related oxidative coupling promoted by CuCU (6, 139),- the present reaction is not limited to enolates of methyl ketones. Isobutyronitrile is used as cosolvent. 

Disubstituted isocoumarins arise from the copper(II)-catalyzed addition of o-halobenzoic acids to active internal alkynes (13JOC1660), rhodium(III)-mediated oxidative coupling ofbenzoic acids with disubsti-tuted alkynes (13T4454), palladium(II)-catalyzed tandem annulation reaction of o-alkynylbenzoates with methyl vinyl ketone (13T8626), and nickel(II)-promoted t-butyl isocyanide insertion in 2-(o-bromophenyl)-1-ethanones followed by hydrolysis (Scheme 69) (13SC3262). 

The oxidative coupling of benzothiazoles with azine JV-oxides is promoted by catalytic Pd(OAc)2 and CuBr and stoichiometric Cu(OPiv)2 (eq 142). The copper pivalate salt plays a dual role oxidant and concerted metalation-deprotonation (CMD) promoter, while the role of copper bromide is less obvious. 

The copper-promoted coupling of vinylboronic acids with amines and amides bearing reactive N-H groups has been achieved (Scheme 3.118) [125]. Using the combination of copper acetate and pyridine along with air as an oxidant, a number of enamines and enamides were prepared in moderate to excellent yield. One practical advantage to this chemistry was the observation that it could be carried out in air. 

Copper(I) complexed with 1,10-phenanthroline has been used in the arylation of imidazo[l,2-a]pyridines by aryl bromides, iodides, and triflates to give products, (139), substituted at the 3-position. The mechanism is likely to involve initial deprotonation at the 3-position followed by cupration and oxidative addition of the aryl halide. The copper-mediated cross-coupling of indoles with 1,3-azoles is assisted by chelation of a, readily removed, 2-pyrimidyl group and leads to products such as (140). In this reaction, two carbon-hydrogen substitutions are required and it is likely that initial cupration of the 1,3-azole is followed by chelation-assisted formation of a bis(heteroaryl) copper species before oxygen-promoted reductive elimination... 

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