Buchwald cross-coupling

Scheme 7.8 Buchwald cross-coupling in the final route.

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. 

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... 

In recent years, cross-coupling methodology has emerged as a viable tool for enamide synthesis, and, indeed, there are a number of published protocols which employ palladium- or copper-catalyzed stereospecific amidations of vinyl halides [17]. For example, Buchwald and coworkers had recently shown that a copper-catalyzed cross-coupling of vinyl bromides or iodides proceeded with retention of stereochemistry (Scheme 9.16), though the only example using a tetrasubstituted vinyl halide, 23, lacked the need for any stereochemical control in the halide portion [18]. Based on this it seemed feasible that the desired enamide 22 could potentially be assembled via a comparable coupling between amide 24 and a stere-odefined vinyl halide such as 25. 

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>. 

Commensurately with the development of various catalyst systems, the Pd-catalyzed G-O cross-coupling has found a number of synthetic applications. Examples include the syntheses of the protein kinase G (PKC) activator (+)-decursin,104 the natural product heliannuol E,105 a chiral 2-methyl chroman,106 and a series of aryloxy and alkoxy porphyrins.107 The Buchwald-Hartwig coupling has also been utilized in the preparation of a heterocycle library.108 Intramolecular O-arylation has also been achieved in the reactions of enolates with aryl halides leading to benzofur-ans.109,110 Finally, a double cross-coupling between an 0-dibromobenzene and a glycol has also been applied for the preparation of benzodioxanes (Equation (16)).1... 

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. 

To our delight we found that palladium-catalyzed cross-couplings between sulfoximines and aryl halides (or aryl nonaflates) work very well, affording N-arylated products in high yield [45]. Generally, Buchwald s Pd(OAc)2/BlNAP catalyst system (with CS2CO3 and toluene at 100 °C) was applied, and thereby a variety of N-aryl sulfoximines 58 - including enantiopure ones - were prepared (Scheme 2.1.1.17). 

Pioneering studies with trialkylphosphines by Fu and coworkers88 and with dialkylarylphosphines by Buchwald and coworkers89 have provided solutions to many pending problems of the Pd-catalyzed cross-coupling, such as those shown in Scheme 26. Applications of bulky alkyl-containing phosphines are further discussed also in later sections. 

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. 

The Chan-Lam Coupling may be conducted at room temperature in air, which gives it a certain advantage over the Buchwald-Hartwig Cross Coupling. 

Keywords Homogeneous catalysis Cross-coupling Microwave Heck Sonogashira Buchwald-Hartwig... 

The cyclization of a-chloroacetanilides reported by Buchwald may also involve C-H activation (also Scheme 5). As mentioned above, acetanilides are among the most reactive substrates in this reaction. The presence of a base (Et3N), and 2-PhC6H4PBu2 as the ligand, are conditions more typical of cross-coupling of halides and therefore the sequence may start this way, followed by intramolecular... 

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