Alkenes oxidative cross-coupling

Oxidative cross-coupling with alkenes is possible with Pd(OAc)2 [109], The reaction proceeds by the palladation of benzene to form phenylpalladium acetate (164), followed by alkene insertion and elimination of /1-hydrogen. Heteroaromatics such as furan and thiophene react more easily than benzene [109]. Stilbene (177) is formed by the reaction of benzene and styrene. The complex skeleton of paraberquamide 179 was obtained in 80% yield by the Pd(II)-promoted coupling of the indole ring with the double bond in 178, followed by reduction of the intermediate with NaBELt [110]. 

Miura, M. Tsuda, T. Satoh, T. Pivsa-Art, S. Nomura, M. Oxidative cross-coupling of N-(2 -phenylphenyljbenzenesulfonamides or benzoic or naphthoic acids with alkenes using a Pd-Cu catalyst system under air. J. Org. Chem. 1998, 63, 5211-5215. 

Coupling reactions. Coupling reactions lead to cinnamate esters and styrenyl ketones. Arylstannanes and arylsilanols can be used as substrates. Oxidative cross-coupling of 2-hydoxybiaryls with alkenes under aeration gives benzochromene derivatives." ... 

Oxidative cross-coupling. a-Stannylalkanoic esters and amides undergo oxidation, and the resulting free radicals can be trapped in situ by electron-rich alkenes such as silyl enol ethers and allylsilanes. Thus y-keto esters are accessible by this reaction. Note that a-germanylalkanoic esters are less reactive toward the oxidant and the a-silylalkanoic esters do not undergo oxidation at all. 

The iron-catalyzed oxidative cross-coupling of phenols with alkenes was developed for the preparation of the pharmacologically important 2,3-dihydrobenzofurans (Scheme 9.25) [30]. The reaction was applicable to a variety of alkenes including styrene, a-alkyl- and a-arylstyrenes, /i-alkyl styrenes, and stilbenes. 

Palladium salts will attack C-H bonds in functionalised aromatics such as acetoaniline to form palladium-carbon bonds that subsequently undergo insertion of alkenes [31], (3-Hydride elimination gave styryl derivatives and palladium hydride, which requires re-oxidation of palladium by benzoquinone. The reaction can be regarded as a combined Murai reaction (C-H activation, if electrophilic) and a Heck reaction (arylalkene formation), notably without the production of salts as the cross-coupling reactions do. An example is shown in Figure 19.15. 

The cross-coupling reaction of diaryl tellurides with alkenes in MeOH in the presence of Pd " catalyst, EtjN and AgOAc as oxidant, gives the corresponding aryl-substituted (Z)-aUcenes in good yields. ... 

Palladium(0)-catalyzed cross-coupling of aryl halides and alkenes (i.e., the Heck reaction) is widely used in organic chemistry. Oxidative Heck reactions can be achieved by forming the Pd -aryl intermediate via direct palladation of an arene C - H bond. Intramolecular reactions of this type were described in Sect. 4.1.2, but considerable effort has also been directed toward the development of intermolecular reactions. Early examples by Fu-jiwara and others used organic peroxides and related oxidants to promote catalytic turnover [182-184]. This section will highlight several recent examples that use BQ or dioxygen as the stoichiometric oxidant. 

Despite its apparent noble character, gold catalysts have been recently found to be active in many homogeneous and heterogeneous catalytic processes such as oxidation reactions, nucleophilic additions, cross-coupling reactions, and alkene and imine hydrogenations (69—71). Corma and co-workers showed that Au... 

Cross-coupling of allylic compounds occurs by transmetallation between 7i-allyl intermediates and organometallic compounds of Mg, Zn, B, Al, Si and Sn, and subsequent reductive elimination. Reaction of the allylic dithioacetal 180 with MeMgBr in the presence of an Ni catalyst affords alkenes 184 bearing a tert-butyl group [90]. In this reaction, generation of the 7i-allylnickel 181 by oxidative addition and subsequent transmetallation with MeMgBr afford 182. Then the methylated product 183 is formed by reductive elimination, and finally the dimethylated product 184 is formed by the sequence of similar reactions. 

Alkylpalladium complexes generated by oxidative addition of Pd(0) to alkyl halides with a /3 hydrogen can undergo /3-elimination to yield an alkene and a Pd-hydrido complex (as in the Heck reaction Scheme8.7). Nevertheless, this process is relatively slow compared with transmetalations and reductive eliminations, and simple alkyl halides or tosylates with /3 hydrogen can be cross-coupled with carbon nucleophiles under optimized conditions if the nucleophile is sufficiently reactive [9, 73-75] (Scheme8.6). 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

If the alkyne in the second step is a 1-aryl propargyl alcohol the product is a bischalcone as a consequence of a CIR-CIR sequence. Furthermore, it is also possible to perform CIR-Heck and CIR-Suzuki sequences if alkenes or boronates and potassium carbonate are added after completion of the initial CIR step. Here again, the gradual differences in reactivity in the oxidative addition between an electron-deficient and an electro-neutral carbon-bromine bond can be readily exploited for selective cross-coupling, first to furnish an aryl propargyl alcohol that is slowly isomerized upon base catalysis to give the bromo chalcone for further cross-coupling. 

The mechanism for this palladium-catalyzed cross-coupling reaction comprises the initial oxidative addition of the electrophile 37 to the palladium(O) catalyst followed by transmetallation of triethylsilane to yield the corresponding bis(organo)palladium(II) complex 39, which then undergoes reductive elimination to form the alkene 40 and to regenerate the palladium(O) catalyst. 

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