Alkyl copper-catalyzed arylations

Feringa and coworkers reported a copper-catalyzed O-arylation of dialkyl phosphonates and phosphoramidates with diaryliodonium triflates and 2,6-di-ferf-butylpyridine (DTBP), giving easy access to mixed alkyl aryl phosphonates via elimination of one of the alkyl groups as the alkyl triflate prior to arylation (Scheme 10a) [133]. Aryl(mesityl)iodonium salts reacted in a chemoselective way. Copper-catalyzed arylations of hydroxamic acids [134] and carboxylic acids [135] have also been reported, the latter utilizing thiophosphoramides as cooperative catalysts to allow arylation at room temperature. Onomura s group discovered a Cu-catalyzed monoarylation of vicinal diols in toluene at 100 °C. Only traces of product were obtained with alcohols lacking the vicinal hydroxyl group [136]. 

The first series of soluble oligo(/ ara-phenylene)s OPVs 24 were generated by Kern and Wirth [48] and shortly after by Heitz and Ulrich [49]. They introduced alkyl substituents (methyls) in each repeat unit and synthesized oligomers 24 up to the hexamer. Various synthetic methods, like the copper-catalyzed Ullmann coupling, the copper-catalyzed condensation of lithium aryls, and the twofold addition of organomelallic species to cyclohexane-1,4-dione, have been thereby investigated. 

A palladium-catalyzed one-step synthesis of dihydrobenzo[fc]furan-based fused aromatic heterocycles from bifunctional bromoenoates or bromoalkyl indoles and iodoarenes was reported, and an example is provided in the scheme below <060L3601>. 2-Alkyl- or 2-aryl-substituted benzo[ >]furans were synthesized by a copper-TMEDA catalyzed intramolecular annulation from the corresponding ketones <06OL1467>. 

Allylic substitutions with nonstabilized C-nucleophiles are an important domain of organocopper chemistry [51]. However, on close inspection of the literature, it becomes apparent that regioselectivity in favor of the branched allylic alkylation products is only obtained with alkyl copper compounds, while aryl copper compounds mainly give the linear alkylation products. This observation was an incentive for Alexakis et al. [52] to probe the reactions of aryl zinc hahdes in the Ir-catalyzed allylic substitution (Scheme 9.18). 

However, very few catalyst systems reported to date are highly effective for both p- aryl and p-alkyl acyclic enone substrates in the copper-catalyzed asymmetric 1,4-addition. Ligand 27, developed by Hoveyda, shows high enantioselectivity in the 1,4-addition of dialkylzinc reagents to various acyclic enones (Figure 3.6). " ... 

A copper(ii) oxide-catalyzed regioselective synthesis of 1-alkyl- and l-aryl-l//-indazoles from ortho-hzXogcnztcA alkanoylphenones, benzophenones, and arylcarboxylic acids with hydrazines in the presence of potassium carbonate has been developed <20070L525>. A palladium-catalyzed C-H activation/intramolecular amination reaction sequence provided a new route to 3-aryl/alkylindazoles <20070L2931>. 

Savarin, C., SrogI, J., Liebeskind, L. S. A Mild, Nonbasic Synthesis of Thioethers. The Copper-Catalyzed Coupling of Boronic Acids with N-Thio(alkyl, aryl, heteroaryl)imides. Org. Lett. 2002,4, 4309-4312. 

Palladium(ll)-catalyzed intramolecular stereoselective Irons alkoxycarbonylation of 4-alkyl- and 4-aryl-3-butyn-l-ols 7 gives /f-tetrasubstituted a-methylene-y-butyrolactones 8 if conducted in the presence of copper(II) chloride, methyloxirane and triethyl orthoacetate. In the absence of the copper salt, intramolecular dicarbonylation occurs (e.g., giving 9, see Section 1.5.8.3.3.). The latter reaction type is also observed if the alkyne moiety is substituted by a trimethylsilyl instead of an alkyl or aryl group60,61. 

Scheme 15.64. Copper-catalyzed generation of alkyl aryl ethers.

Regiospecific synthesis of 2-substituted-l,2,3-triazoles are rare. 5-Carbomethoxy-2-carbomethoxymethyl-4-trinitromethyl-l,2,3-triazole (84a) was prepared by 1,3-dipolar cycloaddition/ alkylation of NCC(N02)3 with Me02CCHN2. X-ray crystallographic data shows the trinitromethyl substituent of 83a is a strained sp center which infers chemical reactivity comparable to that observed for polynitrometnanes thus, 84a with ethanolic KOH afforded potassium 4-dinitromethyl-l,2,3-triazole salt (84b) [93ZOR(29)1231]. Copper-catalyzed oxidative cyclizations of arylhydrazones, while sensitive to substituent effects, provides 2-aryl-l,2,3-triazoles (85) [94H(38)739]. 

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