Halide exchange, with aryl halides

Zincio-I,3-dithianes are valuable reagents. Based on reactions of organozincs 4-acetoxy-l,3-dioxanes serve as precursors of anti-l,3-diols." A synthesis of 1,1-diarylallenes involves Pd-catalyzed coupling of the organozinc species which are derived from 1-arylpropynes by lithiation and Li/Zn exchange with aryl halides. By an sp -sp bond formation process to introduce a dienyl substituent to C-2 of 2-cyclopentenones a facile synthesis of nakienone-A was developed. - ... 

By Metal-Halogen Exchange with Aryl Halides... 

Halogen exchange with aryl and vinyl halidesv This nickel complex is a particularly active catalyst lor exchange between haloarcnes or vinylic halides and inorganic halide salts. In the case of ihe vinylic halides the exchange is particularly... 

Aromatic substitution, The reagent (1) reacts with aryl halides by halogen-metal exchange as the initial step to give (CH3)3SnAr. ArH is formed when proton donors are present. 

At equilibrium, therefore, the Li becomes attached preferentially to the organic group best able to stabilize the negative charge. Hence, extensive exchanges and useful preparations are available from reaction of alkyl Li with aryl halides, cyclopropyl halides, alkenyl halides, alkynyl halides and a-heterosubstituted alkyl halides (including per- and polyhaloalkanes), but not with simple alkyl halides e.g., interaction of EtLi and Mel provides a mixture of EtLi and MeLi. 

Exchanges between aryl halides and aryllithiums are second order with four-center transition states . A free-radical component, i.e., some homolytic fission, is detected in some reactions , e.g., of alkyl halides and alkyllithium. However, the complete retention of configuration, e.g., of cycloalkyL and alkenyF" halides, and the partial retention in others, e.g., of chiral alkyl halides , suggest that the radical component is small. 

An important extension to the Fischer route is the ability to prepare arylhydrazones in ways other than from ketones/aldehydes. A generally applicable process is the palladium(0)-catalysed coupling of benzo-phenone hydrazone with aryl halides, which allows the convenient preparation of a wide range of arylhydrazones of benzophenone, then the benzophenone arylhydrazone can be either hydrolysed to the arylhydrazine, or even more conveniently, used directly in the Fischer cyclisation, where exchange occurs with the ketone. ... 

Imamoto reported that Pd-catalyzed coupling of phosphine-borane with aryl halides is useful for preparation of asymmetric phosphines. Phosphines can be easily isolated from phosphine-boranes by exchange reaction with amines such as pyrrolidine and DABCO [10]. Lipshutz found that aryl nonaflates ( Nf = nonafluorobutanesulfonate) and triflates are good substrates for coupling with BHs-stabilized diaryIphosphines. Selective coupling with nonaflate without... 

Simple 2-halopyrroles are very unstable compounds whereas 3-halopyrroles are stable, as indeed are 2-halopyrryl ketones and esters. Pyrryl halides have typical aryl halide reactivity, being inert to nucleophilic displacement but undergoing exchange with -butyllithium and palladium-catalysed couplings. Pyrryl halides... 

Fig. 22 Seiected examples of the use of lithium alkyl magnesiates in metal-halogen exchange reactions with aryl halides...

In general, exchange between aryl halide and zincate is an efficient and broad-spectrum method for synthesis of aryl zincates, with wide applications. Research in this area is continuing, aimed at development of new exchange methods and synthetic applications. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

The mechanism of action of the cyanation reaction is considered to progress as follows an oxidative addition reaction occurs between the aryl halide and a palladium(O) species to form an arylpalladium halide complex which then undergoes a ligand exchange reaction with CuCN thus transforming to an arylpalladium cyanide. Reductive elimination of the arylpalladium cyanide then gives the aryl cyanide. 

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