Copper catalyzed reactions with metal-halide

The opening step of the Buchwald-Hartwig reaction, similarly to the previous cases, is the oxidative addition of an aryl halide or sulfonate onto a low oxidation state metal. Although the term Buchwald-Hartwig reaction is usually reserved for palladium catalyzed processes, carbon-heteroatom bond formation also proceeds readily with nickel and copper. The nickel catalyzed processes follow a similar mechanism, while the distinctly different copper catalyzed reactions will be discussed in Chapter 2.5. 

There are many other transition-metal catalyzed coupling reactions that are based on organic halides in aqueous media. One example is the coupling of terminal alkyne with aryl halides, the Sonogashira coupling, which has been discussed in detail in the chapter on alkynes (Chapter 4). An example is the condensation of 2-propynyl or allyl halides with simple acetylenes in the presence of copper salts. 

Hashmi et al. investigated a number of different transition metals for their ability to catalyze reactions of terminal allenyl ketones of type 96. Whereas with Cu(I) [57, 58] the cycloisomerization known from Rh(I) and Ag(I) was observed (in fact the first observation that copper is also active for cycloisomerizations of allenes), with different sources of Pd(II) the dimer 97 was observed (Scheme 15.25). Under optimized conditions, 97 was the major product. Numerous substituents are tolerated, among them even groups that are known to react also in palladium-catalyzed reactions. Examples of these groups are aryl halides (including iodides ), terminal alkynes, 1,6-diynes, 1,6-enynes and other allenes such as allenylcarbinols. This che-moselectivity might be explained by the mild reaction conditions. 

Thus far, enantioselective intramolecular aziridination via metal nitrene intermediates has not been successful. Bromamine-T has recently been shown to be a viable source of nitrene for addition to alkenes in copper halide catalyzed reactions, " and so has iodosylbenzene (Phl=0) that forms 44 in situ. Conceptually, aziridination does not necessarily fall between cyclopropanation and epoxidation, as some have suggested. Instead, metal nitrene chemistry has unique problems and potential advantages associated with the electron pair at nitrogen that are yet to be fully overcome. 

The reaction of heterocyclic lithium derivatives with organic halides to form a C-C bond has been discussed in Section 3.3.3.8.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp2 carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable heterocyclic metal derivative. The metal is usually zinc, magnesium, boron or tin occasionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated heterocycles with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. 

Heavy-metal salts, particularly those of silver, mercury, and copper, catalyze SX1 reactions of alkyl halides in much the same way that acids catalyze the SN reactions of alcohols. A heavy-metal ion functions by com-plexing with the unshared electrons of the halide, thereby making the leaving group a metal halide rather than a halide ion. This acceleration of the rates of halide reactions is the basis for a qualitative test for alkyl halides with silver nitrate in ethanol solution ... 

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. 

Copper(I) derivatives of metal diynyl complexes have proven to be useful synthetic intermediates in Cadiot-Chodkiewicz coupling reactions,290 292 and similar species are implicated in coupling of metal diynyls with aryl halides under Pd/Cu catalyzed (Sonogashira) conditions241,242 and in the Cul-catalyzed coupling reactions of metal diynyl species with other metal halides.293... 

A radical species may also be generated by reduction of an electron-deficient compound and a classical entry to 4,4 -bipyridines is the reduction of a pyridine by sodium and subsequent rearomatization. Figure 8a illustrates the use of such a reduction in order to prepare the precursor of a sodium-ion molecular switch [30], A more general route, derived from the ancient copper-catalyzed Ullmann coupling, is the metal-induced dimerization of an aryl halide. The key step is a reductive elimination within the coordination sphere of the metal. A nickel(O) complex, in stoichiometric quantities, is usually selected for this purpose. Constable and Ward have used such a reaction to prepare a bis-terpyridine from an interesting synthon, which would have otherwise required a more specialized strategy with dedicated intermediates (Figure 8b) [31]. 

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