Organopalladium cross-coupling reactions

Direct lithiation of pyridine is a common method of generating the precursors required for the organopalladium cross-coupling reactions. However, if one is not carefiil, the pyridine ring is susceptible to direct addition of the alkyllithium reagent (Chichibabin reaction) as opposed to deprotonation of the ring. 

For Pd-catalyzed cross-coupling reactions the organopalladium complex is generated from an organic electrophile RX and a Pd(0) complex in the presence of a carbon nucleophile. Not only organic halides but also sulfonium salts [38], iodonium salts [39], diazonium salts [40], or thiol esters (to yield acylpalladium complexes) [41] can be used as electrophiles. With allylic electrophiles (allyl halides, esters, or carbonates, or strained allylic ethers and related compounds) Pd-i73-jt-allyl complexes are formed these react as soft, electrophilic allylating reagents. 

Oxidative addition [1, 38] of 1-alkenyl, i-alkynyl, allyl, benzyl, and aiyl halides to a palladium(O) complex affords a stable rra .s-<7-palladium(II) complex (11). The reaction proceeds with complete retention of configuration for alkenyl halides and with inversion for allylic and benzylic halides. Alkyl halides having /3-hydrogens are rarely useful because the oxidative addition step is very slow and may compete with /3-hydride elimination from the a-organopalladium(II) species. However, it has been recently shown that iodoalkanes undergo the cross-coupling reaction with organoboron compounds (Section 2.4.5). 

It is known that the halogen ligand on an organopalladium(II) halide is readily displaced by an alkoxy, hydroxy, or acetoxy anion to provide the reactive Pd-OR complexes 20 [58], which have been postulated as reaction intermediates [59] or isolated [55, 56] from the reaction of organopalladium(II) halides with sodium hydroxide or methoxide. It is not yet obvious, in many reactions, which process shown in Scheme 2-18 or 2-23 is predominant however, the formation of alkoxo-, hydroxo- or acetoxopalladium(II) intermediates should be considered to be one of the crucial transmetallation processes in base/palladium-induced cross-coupling reactions. 

Transmetallation of alkenylsilanes takes place with retention of the double bond configuration, as in other cross-coupling reactions [295]. Owing to the lower transmetallation rate, competing 1,2-insertion of the alkene in the intermediate organopalladium complex (as a Heck type reaction) may take place, which affects the regioselectivity of the Hiyama reaction in some cases (Scheme 1.38) [296]. This... 

Suzuki, A. (2002) in Handbook of Organopalladium Chemistry for Organic Synthesis (ed E. Negishi), Wiley-Interscience, New York, pp. 249-262 (b) Suzuki, A. (1998) in Metal-Catalyzed Cross-Coupling Reactions (eds F. Diederich and P.J. Stang) Chapter 2, Wiley-VCH Verlag GmbH, Weinheim (c) Miyaura, N. and Suzuki, A. (1995) Chem. Rev., 95, 2457-2483. 

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