Copper-catalyzed cross-couplings

In recent years, cross-coupling methodology has emerged as a viable tool for enamide synthesis, and, indeed, there are a number of published protocols which employ palladium- or copper-catalyzed stereospecific amidations of vinyl halides [17]. For example, Buchwald and coworkers had recently shown that a copper-catalyzed cross-coupling of vinyl bromides or iodides proceeded with retention of stereochemistry (Scheme 9.16), though the only example using a tetrasubstituted vinyl halide, 23, lacked the need for any stereochemical control in the halide portion [18]. Based on this it seemed feasible that the desired enamide 22 could potentially be assembled via a comparable coupling between amide 24 and a stere-odefined vinyl halide such as 25. 

Tributylstannyl)-3-cyclobutene-1,2-diones and 4-methyl-3-(tributylstan-nyl)-3-cyclobutene-l,2-dione 2-ethylene acetals undergo the palladium/copper-catalyzed cross coupling with acyl halides, and palladium-catalyzed carbon-ylative cross coupling with aryl/heteroaryl iodides [45]. The coupling reaction of alkenyl (phenyl )iodonium triflates is also performed by a palladium/copper catalyst [46],... 

Figure 2 Recently developed ligands and bases for copper-catalyzed cross-coupling reactions. 

Subsequently, a copper-catalyzed cross-coupling [with substoichiometric amounts of copper(l) iodide and N,N -dimethylethylenediamine (DMEDA)] between aryl halides and sulfoximines was developed [52]. In this case, both aryl bromides and aryl iodides reacted well. For the conversion of the former substrates an in-situ copper-catalyzed aryl Finkelstein reaction [53] had to be performed first, as shown in Scheme 2.1.1.22 for the preparation of 64 starting from bromobenzene (62). 

Introduction of the silylmethyl group into organic halides, tosylates, and epoxides is achieved by nickel, palladium-, or copper-catalyzed cross-coupling reactions. 

Waterlot, C., D. Couturier, and B. Rigo. 2000. Montmorillonite-palladium-copper catalyzed cross-coupling of methyl acrylate with aryl amines. Tetrahedron Lett. 41 317-319. 

The copper-catalyzed cross coupling reaction of thiophenol and aryl halide was also studied by ESl-MS. In this study, reported in 2011, three anionic complexes were assigned as key intermediates, Analysis of the same mixture by positive ion mode ESI revealed only the potassium adducts of thiophenol. An anionic... 

Scheme 7. Suggested catalytic cycle for copper-catalyzed cross coupling reaction ofthiophenol and aryl halide based on detected species by ESI-MS 54. ...

Although copper-catalyzed homocoupling of alkynes and Ni(0)-catalyzed homocoupling of aryl halides were well known, Cadiot and Chodkiewicz gave first-time synthetically more useful copper-catalyzed cross-coupling of alkynes. 

Copper-catalyzed cross-couplings between unactivated alkyl halides and organomagne-sium compounds have been known since the late 1960s and probably are the most studied alkyl-alkyl coupling reactions. The main drawback of this protocol was the need of stoichiometric amounts of copper salts for the formation of the organocuprate, and consequently this led to loss of 1 equiv. of the non-transferred alkyl group. 

Kang, S. K., Kim, W. Y., Jiao, X. G. Copper-catalyzed cross-coupling of 1-iodoalkynes with organostannanes. Synthesis-Stuttgart 1998, 1252-1254. 

The synthesis of sodium channel inhibitor 1 [82] illustrates the utility of the /V-oxide strategy by using it not only to form the biaryl carbon-carbon bond, but also to form the C4 carbon-nitrogen bond. Diaryl ether 3, prepared by a copper catalyzed cross-coupling of 4-fluorophenol and l-bromo-4-iodobenzene [83], was coupled... 

Scheme 68 Copper-catalyzed cross-coupling of an H-phosphonate and an isoquinoline...

Selective Nl-arylation via copper-catalyzed cross-coupling reaction may be achieved tmder ligand-free conditions or Hgand-promoted conditions. 

The palladium-copper-catalyzed cross-coupling of acetylenic systems with aryl halide has been used successfully to homopolymerize p-bromoethynylbenzene (eq 4) [8]. The poly-p-ethynylbenzene was isolated as a white pol3nmer of relatively low molecular weight. The coupling of acetylenic reagents with aryl halides has been noted to lead to explosions and therefore due care should be exercised. 

A newly introduced method for a one-pot unsymmetrical biaryl construction takes advantage of an initial selective iodination of one of the coupling partners, followed by copper-catalyzed cross-coupling. Since the mechanism by which an arene undergoes iodination varies by the nature of the arene, the iodination step needed to be worked out for each type of arene (i.e., electron-rich, electron-poor, both 5- and 6-membered aromatics and heteroaromatics, etc.). Common to each set of conditions is the use of molecular iodine as the oxidant. Moreover, Cul complexed by phenanthroline could be used in all cases. The base and solvent, therefore, were two key parameters that need to be varied. Reaction temperatures in all cases are between 100 °C and 135 and reaction times can vary from hours to, often, days. Yields in most cases tend to be moderate. The method does not apply to two electron-rich arenes. Also, arenes with protons that are of pKa greater than that of DMSO i.e., 37) are not amenable as they fail to form the intermediate copper species required for the... 

I 5 Metal-Catalyzed Aiylations of Nonactivated Alkyl (Pseudo) Halides via Cross-Coupling Reactions Table 5.4 Copper-catalyzed cross-coupling reactions between unactivated alkyl halides and aryl metal reagents. copper catalyst... 

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