Alkyl cross coupling with copper

Although there have been few new developments in the period since 1993, halogenopyrazines 42 have been convenient precursors for a variety of pyrazine derivatives. For example, the halogenopyrazines 42 are cyanated by palladium-catalyzed cross-coupling with alkali cyanide or by treatment with copper cyanide in refluxing picoline, to yield cyanopyrazines 48. Alkoxypyrazines 49 are produced by treatment with alkoxide-alcohol, and aminopyrazines 50 are prepared by amination with ammonia or appropriate amines. The nucleophilic substitution of chloropyrazine with sodium alkoxide, phenoxide, alkyl- or arylthiolate is efficiently effected under focused microwave irradiation <2002T887>. 

Mercury, Zinc, and Copper. The thermal decomposition of 2-thienylmercury thiocyanate, azide, acetate, and trifluoromethylsulphonate has been investigated. Thienylmercury derivatives have been cross-coupled with primary and secondary alkyl- and alkenyl-cuprate reagents. 2-Thienylzinc chloride has been coupled with iodobenzene and vinyl bromide, using Pd catalysis. ... 

Copper complexes have been used as reagents and as catalysts for the formation of carbon-carbon bonds. The most utilized reactions mediated by copper have been couplings of alkyl halides and sulfonates because copper complexes were unique for many years as reagents that would mediate the nucleophilic substitution of alkyl and aryl nucleophiles with alkyl halides. In recent years, work has been conducted to develop copper-catalyzed versions of cross couplings with aryl halides to address the issues of the cost of palladium catalysts. Although few examples of these processes currently rival those catalyzed by palladium complexes, they do illustrate the potential of copper complexes to catalyst these types of cross-coupling processes. 

Lithium dialkylcuprates and diarylcuprates (R2CuLi and Ar2CuLi) are prepared by the reaction of a copper(I) salt with two equivalents of the corresponding organolithium reagent and undergo cross-coupling with primary alkyl halides and aryl and vinylic halides. 

A(-Iminopyridinium yhdes (62) undergo direct C-H bond alkylation by cross-coupling with A(-tosylhydrazones, using unhganded copper(I) iodide and hthium t-butoxide. DFT calculations suggest a Cu carbene migratory insertion. Direct Cu carbene C-H insertion was ruled out by a diphenyldiazomethane control reaction which only gave (63) if the requisite base was present (the direct carbene process does not need base). 

It is also possible to perform copper-catalyzed alkylation of arylmagnesium compounds. Thus, the copper reagent 48 undergoes a selective cross-coupling [28] with ethyl 4-iodobutyrate to furnish the desired product 49 in 69% yield (Scheme 2.12) [29]. 

As well as alkenylstannanes [106-108], other classes such as a-heteroatom-substituted alkyltributylstannanes [109] and, more importantly, allylic stannanes [110, 111] also undergo these Sn-Cu transmetalations. Otherwise difficult to prepare, allylic copper reagents may, however, be obtained by treatment of allylic stannanes (produced in turn from organolithium, magnesium, or zinc organometallics) with Me2CuLi LiCN. They enter into cross-coupling reactions with alkyl bromides [110] or vinyl triflates (Scheme 2.52) [111]. 

Chiral butenolides are valuable synthons towards y-butyrolactone natural products [37] and have also been successfully applied to the synthesis of paraconic acids. The lactone 91, readily available from the hydroxyamide (rac)-90 by enzymatic resolution [38] followed by iodolactonization, proved to be an especially versatile key intermediate. Copper(I)-catalyzed cross coupling reactions with Grignard reagents allowed the direct introduction of alkyl side chains, as depicted in 92a and 92b (Scheme 13) [39, 40]. Further... 

C. Cross Coupling of Grignard Reagents and Alkyl Halides with Copper(I) CatalystiT Copper(I) specifically catalyzes the cross coupling (Equation 35) between Grignard reagents and alkyl bromides when carried out in THF solutions at 0°C or lower.(39)... 

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