Cross-coupling reactions synthetic applications

The preparation of perfluoroalkylzinc compounds has been achieved earlier 111 ethereal solvents [26] However, solvent effects play a significant role in the course of this reaction When a mixture of acetic anhydride and methylene chloride is used, coupled and cross-coupled products can be formed [27, 28] (equations 19 and 20) However, the cross-coupling reaction often gives mixtures, a fact that seriously restricts the synthetic applicability of this reaction [27, 28, 29]... 

Major advancements in the chemistry of pyrazoles, imidazoles, triazoles, tetrazoles, and related fused heterocyclic derivatives continued in 2000. Solid-phase combinatorial chemistry of pyrazoles and benzimidazoles has been particularly active. Synthetic routes to all areas continue to be pursued vigorously with improvements and applications. Notably, metal-promoted and cross-coupling reactions of all classes seemed to be a dominant theme in 2000. Applications of pyrazole-, imidazole-, and 1,2,3-benzotriazole-containing reagents to a wide array of synthetic applications remained active. 

Besides the above electrophiles, the acetylene—titanium complexes react regioselectively with other acetylenes providing the corresponding titanacyclopentadienes. An example of a homo-coupling reaction is shown in Eq. 9.11 [30], which also displays some synthetic applications [30,31]. Especially noteworthy is the highly regioselective cross-coupling reaction of unsymmetrical internal and terminal acetylenes, which is illustrated in Eq. 9.12... 

The cross-coupling reactions of allenes with components containing sp-carbon atoms are useful synthetic transformations since they provide yne-allenes and enyne-allenes, respectively. Due to the synthetic potential of these classes of carbon-rich unsaturated compounds, the scope and limitations were systematically investigated [1, 16-18]. The first synthetic application was reported in 1981, describing the preparation of alkynyl-substituted allenes by coupling of alkynylzinc chlorides with allenyl halides (Scheme 14.8) [11]. 

The transition metal cross-couplings of allenes described here offer practical solutions for the modification of 1,2-dienes and access to the preparation of highly functionalized 1,3-dienes, alkynes and alkenes, which are often not easily accessible in a regio- and stereoselective manner by classical methods. Some of the prepared alkynes or functionalized allenes serve as important intermediates in syntheses of natural products, biologically active compounds, e.g. enynes and enyne-allenes, and new materials. It can be predicted that further synthetic efforts will surely be focused on new applications of allenes in transition metal-catalyzed cross-coupling reactions. 

Disubstituted 4-chloro-2-cyclobutenones 75 undergo the palladium-catalyzed cross-coupling reaction with vinyl- and arylstannanes 76 or vinylzir-conium reagents to give the 4-R sa,-2-cyclobutenones 77. Without isolation, these cyclobutenones 77 are rearranged to the substituted phenols 78 on thermolysis [38], Application of this method to the stannylated heteroaromatics 79 provides a synthetic route to the aromatic benzoheterocycles 80 [39]. (Scheme 27 and 28)... 

Suzuki cross-coupling has found applications in the preparation of specialty polymers, too. Rigid rod polymers may have very useful properties (the well-known Kevlar, poly(p-phenyleneterephtalamide) belongs to this family, too) but they are typically difficult to synthetize, characterize and process. Such materials with good solubility in organic solvents [38] or in water [39] were obtained in the reactions of bifunctional starting compounds under conventional Suzuki conditions with [Pd(PPh3)4] and [Pd(TPPMS)3] catalysts, respectively (Scheme 6.15). 

From the synthetic point of view, choice of the starting halide or sulfonate is usually based on availability. Reactivity and economy usually work antiparallel with bromides being the most frequently used substrates. The recent invention of highly active catalyst systems, on the other hand, broadened the applicability of aryl chlorides considerably in cross-coupling reactions.3... 

As a further synthetic application, 3-lithioindole 1 was converted to 1 -(tert-butyldimethylsilyl)-3-indolylzlnc chloride, which has been successfully employed in the heteroarylation of the indole 3-position by a palladium(0)-catalyzed cross-coupling reaction.8... 

Scheme 2-30 Synthetic applications of the cross-coupling reaction.

A major part of this chapter will show the synthetic applications of these transmetallation reactions for the perfonnancc of cross-coupling reactions. After a short description of the methods of preparation of organozinc halides (RZnX) and diorganozincs (R2Zn), the utility of these reagents for forming new carbon-carbon bonds will be presented. Emphasis will be... 

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