Heteroatomic coupling halides

Cross-coupling to form carbon heteroatom bonds occurs by oxidative addition of an organic halide, generation of an aryl- or vinylpalladium amido, alkoxo, tholato, phosphido, silyl, stannyl, germyl, or boryl complex, and reductive elimination (Scheme 2). The relative rates and thermodynamics of the individual steps and the precise structure of the intermediates depend on the substrate and catalyst. A full discussion of the mechanism for each type of substrate and each catalyst is beyond the scope of this review. However, a series of reviews and primary literature has begun to provide information on the overall catalytic process.18,19,22,23,77,186... 

During the cross-couplings to form C—N, C—O, C—S, and C—P bonds, the arylpalladium halide complexes are converted to arylpalladium amide, alkoxide, thiolate, and phosphide complexes. Examples of each type of complex have now been isolated, and the reductive elimination of the organic products has been studied. Although the reductive elimination to form carbon-hydrogen and carbon-carbon bonds is common, reductive elimination to form carbon-heteroatom bonds has been studied only recently. This reductive elimination chemistry has been reviewed.23... 

Very few transition-metal catalyzed electroreductive carbon-heteroatom bond formations have been described. The electrochemical silylation of allylic acetates was carried out in the presence of Pd-PPha [131]. The electrosynthesis of arylthioethers from thiophenol and aryl halides [132] and the coupling of bromobenzene with dichlorophenylphosphine [133] were performed with Ni-bpy as catalyst. 

The palladium catalyzed coupling of haloazines and olefins is a robust process, which is usually run at an elevated temperatures in the presence of a simple catalyst and at least an equimolar amount of base to neutralise the formed hydrogen halide. The presence of a ring heteroatom might in certain cases lead to complex formation, which deactivates the catalyst and kills the process.63 The regioselectivity of the coupling is predominantly governed by... 

C—H bond alkenylations, 10, 222—223 in cross-coupling polymerization, 11, 687 N-Heteroaromatic compounds, hydrogenation, 1, 792 Heteroaromatic stannanes, preparation, 3, 828 Heteroaryl halides, aminocarbonylatioon, 11, 527 Heteroarylstannanes, preparation, 3, 826 Heteroatoms... 

As described in Section III.1.4.1.1, the catalytic direct arylation reactions of aromatic compounds occurs effectively via C-H bond cleavage when the substrates are appropriately functionalized. On the other hand, various five-membered heteroaromatic compounds involving one or two heteroatoms, even without a functional group, are known to undergo arylation, usually at their 2- and/or 5-posi-tion(s), on treatment with aryl halides under the action of palladium catalysis. The coupling has recently been developed significantly [1, 2]. Representative examples with some mechanistic discussion are summarized in this section. 

The heteroatom cross-coupling reaction of N-H, 0-H, S-H and P-H compounds is a topic of current interest. Alkenyl halides were converted into the... 

Murahashi, S.-l. Palladium-catalyzed cross-coupling reaction of organic halides with Grignard reagents, organolithium compounds and heteroatom nucleophiles. J. Organomet. Chem. 2002, 653, 27-33. 

Glycosyl halides are popular electrophilic coupling partners for C-glycoside synthesis. The area of a-monohalo ethers in synthesis has been reviewed [118]. Heteroatoms at the 2-position have been well tolerated, as can be seen from the examples shown in Scheme 71. Alkylation of 407 with the potassium salt of diethylmalonate... 

Because of the radical mechanism for SET reactions, introduction of both a perfluoroalkyl group and a heteroatom moiety to the carbon-carbon double [17-20] and even triple [21] bonds is possible. The initially generated perfluoroalkyl radicals add first to olefins to form a new radical intermediate (23), which then couples with anions (22) to form new anion radicals (24). The formation of the product (25) and the chain propagation via electron transfer from anion radicals (24) to perfluoroalkyl halides constitutes a chain reaction as shown in Scheme 2.38. Sulfur [19], selenium [20], tellurium [21], and phosphorus [22] anions (22) have been employed for these reactions [23]. 

The Ullmann coupling [30] involves treatment of aryl halides with stoichiometric copper at high temperatures to yield biaryl compounds. Considerable effort has been made to lower the temperature necessary for initiation of the reaction, as well as decrease the required amount of copper salts. These advances served as the basis for extending this method for the synthesis of aryl heteroatom bonds, known as the Ullmann Condensation Reaction [22, 31, 32]. After several reports for C-O and C-N bond formation, methods for C-S bond formation began to emerge. 

Cross-coupling reactions leading to the formation of C-X (X = heteroatom) bonds catalyzed by Pd(dba)2 have been reported. Aniline derivatives have been prepared via reaction of amine nucleophiles with aryl halides in the presence of Pd(dba)2 and phosphines, especially P( Bu)3. Likewise, diaryl and aryl alkyl ethers are produced from aryl halides (Cl, Br, I) and sodium aryloxides and alkoxides under similar conditions. Conditions effective for the coupling of aryl chlorides with amines, boronic acids, and ketone enolates using an easily prepared phosphine chloride as a ligand have recently been uncovered (eq 22). The preparation of aryl siloxanes and allyl boronates via Pd(dba)2-catalyzed C-Si and C-B coupling have been reported as well. 

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