Buchwald coupling reaction

The Ullmann and Buchwald coupling reaction has also been employed for the synthesis of HCP networks by coupling polyanilines and... 

Scheme 3.13. Arylamine substituted HBCs prepared by Buchwald coupling reactions.

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

The coupling between an aryl halide or triflate and an amine is known as the Buchwald-Hartwig amination [138]. Originally it was described using a tributyltin amine [139,140] and was thus considered to be a coupling reaction. Subsequently, tributyltin amine was replaced by a standard amine and a strong base. It is a reaction of great academic and industrial interest [11]. 

However, the Buchwald-Hartwig reaction with NHCs as hgands is not limited to palladium. Nickel has also been successfully employed in this catalytic amination. In situ procedures have been described for the coupling of aryl chlorides [163] and tosylates [164] and, more interestingly, anisoles [165]. The use of well-defined Ni(0) catalysts has also been studied [166] (Scheme 6.49). 

Jiang L, Buchwald SL (2004) Palladium-catalyzed aromatic carbon-nitrogen bond formation. In de Meijere A, Diedeiich F (eds) Metal-catalyzed cross-coupling reactions, 2nd edn. Wiley-VCH, Weinheim... 

The Harmata group also found that certain ort/w-bromocinnamates underwent a Michael addition during the course of the Buchwald-Hartwig reaction. This one-pot process produced the same products as the two step process and with the same, complete stereoselectivity. For example, this was first observed with bromocinnamate 107, where the reaction with (7 )-77b afforded a 53% yield of sulfoximine 108 as well as a 36% yield of benzothiazine 95 under standard coupling conditions (Scheme 27). The cyclization was attributed to a buttressing effect of the ortho-methoxy in bromocinnamate 107. This presumably favored a conformation that placed the methyl group of its sulfoximine functionality near the p-carbon of the a,P-unsaturated ester, thus favoring cyclization. 

Dihydrobenzo[b]furans can be synthesized by using Pd(dba)2/PhsFcP(r-Bu)2 as an efficient catalyst at room temperature, and some interesting discussions related to this catalyst discovery are also addressed <00JA10718>. Buchwald also shows that bulky, electron-rich o-biarylphosphines are effective in PdfOAcfe-catalyzed cross-coupling reactions for the generation of 2,3-dihydrobenzo[6]furans <00JA12907>. 

Scheme 4.29 Pd(O)-mediated Buchwald-Hartwig and Suzuki cross-coupling reactions.

Other successful examples of catalysts containing NHC ligands are found in palladium- and nickel-catalyzed carbon-carbon bond formations. The catalyst development with these metals has focused in particular on Heck-type reactions, especially the Mizoroki-Heck reaction itself [Eq. (42)] and various cross coupling reactions [Eq. (43)], e.g., the Suzuki-Miyaura reaction ([M] = and the Kumada-Corriu reaction ([M] = MgBr). " Related reactions like the Sonogashira coupling [Eq. (44)]326-329 Buchwald-... 

Very efficient cross coupling reactions of tin derivatives with [4- F]fluorobro-mo and [4- F]fluoroiodobenzenes have been carried out [162, 163] (Scheme 42). Reaction of the appropriate piperazine with [4- F]fluorobro-mobenzene under Hartwig-Buchwald conditions [187] yields [ F]RP 62203 in high specific activity and biologically usable amounts. This method appears superior to the one described previously starting from [ F]fluoronitrobenzene (Scheme 18). 

The synthetic potential of palladium-mediated cross-coupling reactions (Heck, Suzuki, Stille, Sonogashira, Buchwald-Hartwig) led to the search for a practical synthesis of p-[ F]fluoroiodo- and p-[ F]fluorobromobenzene. p-[ F]Fluoroio-dobenzene (G, X = iodine) can be obtained in poor yield from p F]fluoride and a trimethylammonium precursor (P7). p-p F]Fluorobromobenzene can be prepared in a more reproducible way from 5-bromo-2-nitrobenzaldehyde (radiochemical yields > 70%). The synthesis involves a two-step procedure radiofluorination (F for NO2 substitution), then a catalysed decarbonylation [190,191]. Also very efficient is the one-step reaction of p F]fluoride with a suitable diaryliodonium salt (P6) giving >70% radiochemical yield [192-194]. 

B-2004MI699 L. Jiang and S. L. Buchwald in Metal-Catalyzed Cross-Coupling Reactions , 2nd Edn., A. De Meijere and F. Diederich,... 

Hartwig-Buchwald, Suzuki, and Stille type cross-coupling reactions with key intermediate 46 led to a wide range of substituted sulfoximines such as 47-49 [37]. In order to demonstrate the synthetic utility of the resulting products, pseudo tripeptide 50 was prepared from a related intermediate. 

The final step of the process is the detachment of the product from the metal in reductive elimination. Unlike in most cross-coupling reactions, this step was the limiting factor in the early reports on the Buchwald-Hartwig reaction. The use of sterically demanding mono and bidentate ligands, however helped to overcome this difficulty by facilitating the closing step. 

Transition-metal-catalyzed synthesis of poly(arylene)s via carbon-carbon coupling reactions was started by Yamamoto et al. three decades ago [52,53] since then various carbon-carbon bond formation processes with transition-metal catalysts have been applied to polycondensation [54-57]. In recent years, Buchwald et al. and Hartwig et al. developed Pd-catalyzed amination and etherification of aromatic halides by using bulky, electron-rich phosphine ligands [58-60], and this chemistry has been applied to polycondensation for... 

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