Copper-catalyzed reaction

2 Copper-Catalyzed Reactions 20.2.2.1 Regular Cross-CoupUng 

TRANSITION METAL-MEDIATED CARBON-HETEROATOM CROSS-COUPLING 

FIGURE 20.3 Ligands of the Cu-catalyzed cross-coupling of alkyl amines with aryl hahdes. 

SCHEME 20.19 Cu-catalyzed room temperature arylation of aliphatic amines. 

SCHEME 20.20 Ligand-assisted Cu-catalyzed C—N cross-coupling. 

It is now well known that the use of cocatalytic Cu salts dramatically enhances the reaction rate of sluggish Stille couplings by transmetaUating the organostan-nane (see Section 6.2.1.1.2). Several studies established that the resulting organo- 

It was also demonstrated that a-heteroatom-substituted alkyltributyltins cross-coupled in the presence of catalytic amounts of Cu [157]. This catalytic use of copper salts was extended to various aryl-aryl, aryl-heteroaryl and aryl-vinyl crosscouplings [158]. 

In addition to the use of Cu [159], Cu salts such as CuCh [160] and Cu(N03)2 [161] efficiently mediated and catalyzed the homocoupling of aryl, alkenyl and alkynyl stannanes. 

Finally, a catalytic enantioselective approach for the formation of allyl a-amino acid derivatives by reaction of N-tosyl-a-imino esters with alkylstannanes catalyzed by chiral Cu complex was developed [162]. 

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Furan and thiophene undergo addition reactions with carbenes. Thus cyclopropane derivatives are obtained from these heterocycles on copper(I) bromide-catalyzed reaction with diazomethane and light-promoted reaction with diazoacetic acid ester (Scheme 41). The copper-catalyzed reaction of pyrrole with diazoacetic acid ester, however, gives a 2-substituted product (Scheme 42). 

Another rather peculiar asymmetric copper-catalyzed reaction was published some years earlier by Miura et al. [75]. The reaction is outlined in Scheme 6.31... 

Copper complexes of sparteine have also been used for the catalysis of asymmetric carbon-carbon bond formation. The copper-catalyzed reaction... 

Copper-catalyzed reactions are particularly effective with a-diazo-P-dicarbonyl compounds such as diethyl diazomalonate. 

Scheme 8.4. Copper-Catalyzed Reactions of Grignard Reagents...

Introduction of Other Nucleophiles Using Diazonium Ion Intermediates. Cyano and azido groups are also readily introduced via diazonium intermediates. The former involves a copper-catalyzed reaction analogous to the Sandmeyer reaction. Reaction of diazonium salts with azide ion gives adducts that smoothly decompose to nitrogen and the aryl azide.56... 

Meerwein Arylation Reactions. Aryl diazonium ions can also be used to form certain types of carbon-carbon bonds. The copper-catalyzed reaction of diazonium ions with conjugated alkenes results in arylation of the alkene, known as the Meerwein arylation reaction.114 The reaction sequence is initiated by reduction of the diazonium ion by Cu(I). The aryl radical adds to the alkene to give a new (3-aryl radical. The final step is a ligand transfer that takes place in the copper coordination sphere. An alternative course is oxidation-deprotonation, which gives a styrene derivative. 

Reduction of aryl diazonium ions by Ti(III) in the presence of a,(3-unsaturated ketones and aldehydes leads to (3-arylation and formation of the saturated ketone or aldehyde. The early steps in this reaction parallel the copper-catalyzed reaction. However, rather than being oxidized, the radical formed by the addition step is reduced by Ti(III).116... 

These copper-catalyzed reactions are generally applicable to aryl halides with either EWG or ERG substituents. The order of reactivity is I > Br> Cl > 0S02R, which is consistent with an oxidative addition mechanism. 

Some other examples of metal-catalyzed substitutions are given in Scheme 11.10. Entries 1 to 3 are copper-catalyzed reactions. Entry 1 is an example of arylation of imidazole. Both dibenzylideneacetone and 1,10-phenanthroline were included as ligands and Cs2C03 was used as the base. Entry 2 is an example of amination by a primary amine. The ligand used in this case was (V,(V-diethyl sal icyl amide. These conditions proved effective for a variety of primary amines and aryl bromides with both ERG and EWG substituents. Entry 3 is an example of more classical conditions. The target structure is a phosphodiesterase inhibitor of a type used in treatment of asthma. Copper powder was used as the catalyst. 

Polysilmethylene chains also are formed in the thermal, copper-catalyzed reactions of methylene chloride and chloroform with elemental... 

From the copper-catalyzed reaction of methyl 2-diazo-3-oxobutyrate 57 a with Z-3-methoxystyrene, dihydrofuran 59 (formed with retention of olefin configuration) and butadienol 60 result130). Such an acyclic by-product also occurs when benzofuran is the cycloaddition partner. In that case, however, regioisomers 61 and 62, arising from the connection of the former diazo carbon with either the 2- or 3-position of the heterocycle, are obtained similarly, two isomeric dihydrofurans 63 and 64 are formed under Cu(hfacac)2 catalysis130). 

Whereas metal-catalyzed decomposition of simple diazoketones in the presence of ketene acetals yields dihydrofurans 121,124,134), cyclopropanes usually result from reaction with enol ethers, enol acetates and silyl enol ethers, just as with unactivated alkenes 13). l-Acyl-2-alkoxycyclopropanes were thus obtained by copper-catalyzed reactions between diazoacetone and enol ethers 79 105,135), enol acetates 79,135 and... 

C/H-insertions have been reported to occur in copper-catalyzed reactions between diazomalonates and cyclohexene as well as some alkylated derivatives 9,57. Some acyclic alkenes behave similarly9, but not so 1,1-dicyclopropylethylene150), An abstraction/recombination mechanism via intermediates of type 103 has been proposed53 which would account not only for the three insertion products 104-106... 

Contrary to P-lactams, N/H insertion is only a minor process in the copper-catalyzed reaction between 2-pyrrolidinone and methyl diazoacetate. With pyrro-lidine-2-thione, this process does not take place at all. For 2-piperidinone, N/H insertion seems to be easier, but once again, the corresponding thione fails to produce such an insertion product (Scheme 35) 322),... 

Palladium/copper catalyzed reactions of 3-iodothiophene-2-carboxylic acid 48 with two equivalents of a terminal alkyne gives selective access to 5-substituted 4-alkynylthieno[2,3-c]pyran-7-ones, for example the system 49 <06TL83, 06T9554>. 

Hoveyda and co-workers also tested optically active A-heterocyclic carbenes and their silver complexes in copper-catalyzed reactions of allylic phosphates with dialkylzincs.402 The ratios of Sn2 SN2 products were higher than 98 2 and the ee varied from 34% to 98%. 

Recently, a new method for synthesis of tertiary amines 326 from iV,iV-dialkyl O-benzoyl hydroxylamines 325 was proposed.425 The protocol is based on the copper-catalyzed reaction of hydroxylamines 325 with dialkyl- and diarylzinc reagents (Scheme 166). It is noteworthy that alkyl- and phenylzinc halides also reacted with compounds 325, however, yields were significantly lower than those for ZnR2 (18-29% vs. 69-98%). 

Rouhi, M. (2004) High-yield path to dendrimers. Copper-catalyzed reaction offers easy, efficient route to globular molecules. Chem. Eng. News 82(28), 5. 

Most of the work on the C-N bond-forming crosscoupling reactions has concentrated on the formation of aromatic C-N bonds. Recent studies show that the application of cross-coupling reactions to alkenyl halides or triflates furnished enamines (Scheme 19) (for palladium-catalyzed reaction, see 28,28a-28d, and for copper-catalyzed reaction, see 28e-28g). Brookhart et al. studied the palladium-catalyzed amination of 2-triflatotropone 109 for the synthesis of 2-anilinotropone 110.28 It was found that the reaction of 109 proceeded effectively in the presence of racemic BINAP and a base. As a simple method for the synthesis of enamines, the palladium-catalyzed reactions of alkenyl bromide 111 with secondary amine were achieved under similar conditions.2841 The water-sensitive enamine 112 was isolated as pure compound after dilution with hexane and filtration through Celite. The intramolecular cyclization of /3-lactam 113, having a vinyl bromide moiety, was investigated by Mori s... 

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