Metal-mediated couplings

Pyridones can also be converted to 2-chloropyridines by exchanging the carbonyl functionality using phosphoroxychloride (POCI3) [72]. A combination of N-halosuccinimides and triphenylphosphine has also been applied to introduce halogens in this position [73]. The carbonyl functionality in 2-pyridones makes these systems reactive towards nucleophiles as well, which add in 1,4-reactions with displacement of halides [74]. The use of transition metal mediated couplings like Heck, and Suzuki have also been successfully applied on halogenated 2-pyridones (d. Scheme 10) [36,75]. 

Synthesis is typically by alkali metal-mediated coupling of dichlorosilanes or 1,2-dichlorodisilanes, although electrochemical coupling of chlorosilanes and dehydrocoupling of primary and secondary silanes also often lead to oligomeric (as opposed to high polymer) fractions. 

Many of the modern vinylallene syntheses involve metal-mediated coupling reactions, as shown by several typical examples summarized in Scheme 5.11. The treatment of the propargyl carbonate 83 with the alkenylborane 84 in the presence of a palladium catalyst furnished the substituted vinylallene 85 in excellent yield (Scheme 5.11) [28],... 

Replacement of a halogen by transition metal mediated coupling... 

To expand the diversity of their libraries Brill et al.16 also modified various heterocycles by alkylation, acylation, or metal-mediated coupling reaction prior to resin capture. A remaining chloro substituent was still available for nucleophilic displacement or a palladium-mediated coupling reaction with anilines, phenols, and boronic acids on solid phase [see Fig. 10 for the preparation of purine derivative (62)]. 

The use of hypervalent iodine reagents in carbon-carbon bond forming reactions is summarized with particular emphasis on applications in organic synthesis. The most important recent methods involve the radical decarboxylative alkylation of organic substrates with [bis(acyloxy)iodo]arenes, spirocyclization of para- and ortho-substituted phenols, the intramolecular oxidative coupling of phenol ethers, and the reactions of iodonium salts and ylides. A significant recent research activity is centered in the area of the transition metal-mediated coupling reactions of the alkenyl-, aryl-, and alkynyliodonium salts. 

Numerous reactions of alkenyl(phenyl)iodonium salts leading to the formation of new C-C bond have been reported in the literature. The most important and synthetically useful reactions include the generation and subsequent cyclization of alkylidenecarbenes, alkenylation of carbon substrates via nucleophilic vinylic substitution, and transition metal-mediated coupling reactions. 

It can be anticipated that these areas of synthetic application will continue to attract significant research activity in the future. The increasing use of the transition metal-mediated coupling reactions of iodonium salts may add a new dimension to the field of polyvalent iodine chemistry. 

Almost all alkylations at the carbocyclic rings of quinolines are effected by metal-mediated processes either by quenching of a quinolyl organometallic species with a suitable electrophile or by transition metal-mediated coupling of a haloquinoline or quinolyltriflate with an alkylmetal derivative. 

Hydrostannylation represents another class of important reaction that often gives rise to interesting polymeric materials as well as precursors for transition metal mediated coupling transformations such as the Stille coupling protocol15. 

Intermolecular free-radical additions of stannyl radicals to multiple bonds have emerged as important methods for the preparation of tetraorganostannanes which can be reacted further to afford new C—C bonds through transition metal mediated coupling processes (e.g. Stille coupling). There are numerous examples of this chemistry715-737, and this treatise will focus on a few selected examples. 

Kanomata N, Suzuki J, Kubota H, Nishimura K, Enomoto T (2009) Synthesis of planar-chiral bridged bipyridines and terpyridines by metal-mediated coupling reactions of pyridinophanes. Tetrahedron Lett 50 2740-2743... 

The precursor 46 (mixture of E/Z isomers), which is available from the reaction of thiophene-2-carboxaldehyde with tribromofluoromethane in the presence of triphenylphosphine, underwent metal mediated coupling giving the intermediate 47, which could in turn be annulated to the fluoro substituted bcnzo[/>]thiophcnc 48 <07JFC1052>. 

More elaborate coupling reactions see Organic Synthesis Using Metal-mediated Coupling Reactions) include the... 

Complexes of the type [Cp Rh(R)(/4-CH2)]2 have been studied to probe details of the coupling of alkyl and methylene groups that could be relevant to mechanisms for the Fischer-Tropsch process (see Organic Synthesis Using Metal-mediated Coupling Reactions) Reaction... 

Cp Rh(MeCN)(/r-CH2)]2 +, both methylene units couple with two alkyne molecules see Organic Synthesis Using Metal-mediated Coupling Reactions) to form (146). ... 

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