Copper halides amides

Scheme 9.16 Copper-catalyzed amidation of vinyl halides.

Parco et al. described a copper-catalyzed amidation of vinyl iodide 115 to give 116 (Scheme 20).28e Enhanced conversions were attained using copper(i) thiophenecarboxylate (GuTG) in a polar aprotic solvent such as NMP. The total synthesis of the antitumor natural product, lobatamide G, has been accomplished by using this reaction.28f Buchwald et al. developed a general and efficient copper-catalyzed method using N,N -dimethyl ethylenediamine L8. The double-bond geometry of the alkenyl halides was retained under the reaction conditions. 

Sandimyar raaction A reaction of dlazo-nium salts used to prepare chloro- or bromo-substituted aromatic compounds. The method is to diazotize an aromatic amide at low temperature and add an equimolar solution of the halogen acid and copper I) halide. A complex of the dlazo-nium salt and copper halide forms, which decomposes when the temperature is raised. The copper halide acts as acatalyst in the reaction of the halide ions from the acid, for example... 

Network of various proposed mechanisms for the reaction of copper alkoxides, amides, and amides with aryl halides. 

More detailed mechanistic studies have been conducted with isolated ligated copper complexes, along with kinetic studies on reactions catalyzed by complexes of diamine ligands. These studies have shown that copper(I) amidate and imidate complexes are competent to be intermediates in the catalytic coupling of aryl halide with amides and imi-des. These studies also implied that two-coordinate anionic cuprate complexes undergo oxidative addition of the aryl halide more slowly than do related three-coordinate, neutral copper complexes containing a bidentate dative ligand. This conclusion is shown clearly by the formation of coupled product from iodotoluene and the species that equilibrates between the ionic and three-coordinate neutral species (Equation 19.119) and the lack of... 

Scheme 32 Copper-catalyzed amidations of allenyl halides...

It has been found that a number of bidentate ligands greatly expand the scope of copper catalysis. Copper(I) iodide used in conjunction with a chelating diamine is a good catalyst for amidation of aryl bromides. Of several diamines that were examined, rra s-yV,yV -dimethylcyclohexane-l,2-diamine was among the best. These conditions are applicable to aryl bromides and iodides with either ERG or EWG substituents, as well as to relatively hindered halides. The nucleophiles that are reactive under these conditions include acyclic and cyclic amides.149... 

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. 

Elimination-addition reactions of aryl halides with alkali-metal amides are discussed in Section 14-6C high-temperature copper-catalyzed amination, also effective, usually does not lead to rearrangement. 

Allylic amination of allyl halides can also be achieved using lithium and potassium bis(trimethylsilyl)amides [34] and potassium 1,1,3,3-tetramethyldisilazide [35] as the nucleophiles. It has been found that for the reaction of alkyl-substituted allyl chlorides using lithium bis(trimethylsilyl)amides as the nucleophile the allylic amination proceeds smoothly in a SN2 fashion to give /V,Af-disilylamines in high yields when silver(I) iodide was used as an additive. Other metal complexes such as copper ) iodide and other silver(I) salts can also be used as additives for the reaction. 

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