Cross-coupling products

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]... 

The postulated steps that constitute the Suzuki coupling process are shown in Scheme 25. After oxidative addition of the organic halide to the palladium(o) catalyst, it is presumed that a metathetical displacement of the halide substituent in the palladium(ii) complex A by ethoxide ion (or hydroxide ion) takes place to give an alkoxo-palladium(ff) complex B. The latter complex then reacts with the alkenylborane, generating the diorganopalladium complex C. Finally, reductive elimination of C furnishes the cross-coupling product (D) and regenerates the palladium(o) catalyst. 

Silyi enol ethers can be dimerized to symmetrical 1,4-diketones by treatment with Ag20 in DMSO or certain other polar aprotic solvents." The reaction has been performed with R , R = hydrogen or alkyl, though best yields are obtained when r = r = H. In certain cases, unsymmetrical 1,4-diketones have been prepared by using a mixture of two silyi enol ethers. Other reagents that have been used to achieve either symmetrical or cross-coupled products are iodosobenzene-Bp3-Et20," ceric ammonium nitrate," and lead tetraacetate." If R =0R (in which case the substrate is a ketene silyi acetal), dimerization with TiCU leads to a dialkyl succinate (34, r =0R)." ... 

Lu, F. Ralph, J. Morreel, K. Messens, E. Boerjan, W. Preparation and relevance of a cross-coupling product between sinapyl alcohol and sinapyl p-hydroxybenzoate. Org. Biomol. Chem. 2004, 2, 2888-2890. 

Through the use of arenediazonium salts, the straightforward transformation of amines into cross-coupling products can be realized. Whenever the diazonium salts do not tolerate bases and strong nucleophiles (e.g., phosphines), base- and phosphine-free protocols have to be used. Heterocyclic carbene ligands serve well in cross-coupling of Aryl- and vinylboronic acids, or alkylboronates with arenediazonium salts.369,370 Several convenient phosphine-free protocols have been developed for the same purpose.371-373... 

These ligands afford high yields of cross-coupling products in the highly sterically burdened reactions of aryl bromides with arylboronic acids when both contain substituents in the ortho- (or equivalent) positions, although drastic reaction conditions are required (110). 

Recently, interest in copper-catalyzed carbon-heteroatom bond-forming reactions has shifted to the use of boronic acids as reactive coupling partners [133], One example of carbon-sulfur bond formation is displayed in Scheme 6.65. Lengar and Kappe have reported that, in contrast to the palladium(0)/copper(l)-mediated process described in Scheme 6.55, which leads to carbon-carbon bond formation, reaction of the same starting materials in the presence of 1 equivalent of copper(II) acetate and 2 equivalents of phenanthroline ligand furnishes the corresponding carbon-sulfur cross-coupled product [113]. Whereas the reaction at room temperature needed 4 days to reach completion, microwave irradiation at 85 °C for 45 min in 1,2-dichloroethane provided a 72% isolated yield of the product. 

The tandem use of asymmetric allylboration to give enantiomerically pure ho-moallyHc alcohols followed by cross-metathesis of homoallylic silyl ethers with p-substituted styrenes has been reported [120] (Eq. 19). Exclusively trans cross-coupled products were formed in 50-75% yields. 

Particularly noteworthy was the rhenium catalysed cross-metathesis of trans-hex-3-ene with vinyl acetate or a,p-unsaturated esters [4]. For example, crossmetathesis of methyl frans-crotonate with frans-hex-3-ene gave the desired cross-coupled product without any self-metathesis of the crotonate (Eq. 2). 

Since one of the substrates is a cyclic alkene there is now the possibility of ring-opening metathesis polymerisation (ROMP) occurring which would result in the formation of polymeric products 34 (n >1). Since polymer synthesis is outside the scope of this review, only alkene cross-metathesis reactions resulting in the formation of monomeric cross-coupled products (for example 30) will be discussed here. 

Palmisano and Santagostino first reported Stille reactions of indole-ring stannylindoles with their detailed studies of 1V-SEM stannane 159 [170], Thus 159, which is readily prepared by C-2 lithiation of A-SEM indole and quenching with Bu3SnCl (88%), couples under optimized Pd(0)-catalyzed conditions to give an array of cross-coupled products 160. Some other examples and... 

The Hiyama coupling offers a practical alternative when selectivity and/or availability of other reagents are problematic. Hiyama et al. coupled alkyltrifluorosilane 74 with 2-bromofuran 73 to give the corresponding cross-coupled product 75 in moderate yield in the presence of catalytic Pd(Ph3P)4 and 3 equivalents of TBAF [65]. In this case, more than one equivalent of fluoride ion was needed to form a pentacoordinated silicate. On the other hand, alkyltrifluorosilane 74 was prepared by hydrosilylation of the corresponding terminal olefin with trichlorosilane followed by fluorination with C11F2. This method provides a facile protocol for the synthesis of alkyl-substituted aromatic compounds. 

Cyclopentadienylstannanes can be used in the Migita-Kosugi-Stille reaction with organic iodides, RI, to give the cross-coupled product Cp-R, for example, Equation (117).310... 

Substituted propargylic carbonates react with terminal acetylenes in the presence of a catalytic amount of Pd(PPh3)4 and Cul to produce Sonogashira-type cross-coupling products (Eq. 9.114) [84]. Presumably, the reaction proceeds through an allenylpalladium complex. Addition of a salt, such as KBr, increased the yield of the coupling product. Only tetrasubstituted allenes could be obtained by this procedure. 

A theoretical study of the 5 n2 reaction of MeBr with MeaCuLi.LiCl has addressed two mechanistic possibilities a simple S 2 reaction with the carbon nucleophile (eq. 4) and the S 2 reaction with the copper atom (followed by rapid reductive elimination of a triallylcopper(III) intermediate in a manner which forms only the cross-coupling product RR ) (eq. 5). ... 

Vinylic tellurides react with Grignard reagents under Ni(II) or Co(II) complex catalysis giving cross-coupling products, with results that depend on the nature of the substrate or the Grignard reagent." ... 

However, solvent viscosity, rather than polarity, has been a useful tool for mechanistic purposes. Although the quantum yield of the ortho-rearranged product of 4-methylphenyl acetate (20) does not change with viscosity of the medium, the formation of 4-methylphenol (22) is highly sensitive to this factor. Thus, its quantum yield is 0.45 in ethanol (1.00 cP) but only 0.02 in Carbowax 600 (109 cP) (Scheme 8 Table 3) [13], This clearly supports the mechanism involving caged radical pairs. A related aspect is the intramolecular nature of the process confirmed by the lack of cross-coupling products in crossover experiments with mixtures of different esters [10]. 

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