Alkenes reductive coupling with alkyl halides

In contrast to each of the above variations, alkyl iodides may also be utihzed directly in nickel-catalyzed conjugate additions. The mechanism of this class of reactions is not well defined however, the related stoichiometric coupling of enals (e.g., 79) with alkyl halides (e.g., 78) has been demonstrated to proceed through nickel-Jt-aUyl intermediates.l The most widely used variant employs nickel(II) chloride hexahydrate in either catal)hic or stoichiometric quantities with activated zinc as a stoichiometric reductant (Scheme g2) [144-148] pjjg organic hahde may be either sp or sp hybridized, and alkene geometry in the final product (e.g., 80) is maintained with alkenyl iodides. 

The electrochemistry of cobalt-salen complexes in the presence of alkyl halides has been studied thoroughly.252,263-266 The reaction mechanism is similar to that for the nickel complexes, with the intermediate formation of an alkylcobalt(III) complex. Co -salen reacts with 1,8-diiodo-octane to afford an alkyl-bridged bis[Co" (salen)] complex.267 Electrosynthetic applications of the cobalt-salen catalyst are homo- and heterocoupling reactions with mixtures of alkylchlorides and bromides,268 conversion of benzal chloride to stilbene with the intermediate formation of l,2-dichloro-l,2-diphenylethane,269 reductive coupling of bromoalkanes with an activated alkenes,270 or carboxylation of benzylic and allylic chlorides by C02.271,272 Efficient electroreduc-tive dimerization of benzyl bromide to bibenzyl is catalyzed by the dicobalt complex (15).273 The proposed mechanism involves an intermediate bis[alkylcobalt(III)] complex. 

In addition to /3-H elimination, olefin insertion, and protonolysis, the cr-metal intermediate has also proved to be capable of undergoing a reductive elimination to bring about an alkylative alkoxylation. Under Pd catalysis, the reaction of 4-alkenols with aryl halides affords aryl-substituted THF rings instead of the aryl ethers that would be produced by a simple cross-coupling mechanism (Equation (126)).452 It has been suggested that G-O bond formation occurs in this case by yy/z-insertion of a coordinated alcohol rather than anti-attack onto a 7r-alkene complex.453... 

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. 

Table 17 Reductive Coupling of Alkenes With Very Easily Reduced Alkyl Halides in Aprotic Medium S [188]...

The macrocycles of nickel and cobalt that stabilize the metal(I) oxidation state allowing the use of M(II)L/M(I)L couples to be used for the catalytic reduction of alkyl halides [13,14]. With alkyl bromides with alkene and alkyne substituents, the reactions can lead to interesting cyclic molecules by intramolecular coupling [15-17]. 

This method is specific for metallacyclopentanes. The alkene-coupling process is favored by metal reduction. A typical synthetic strategy is the in situ reduction of a metal halide precursor in the presence of the alkene see, for example, the synthesis of 79 in Scheme 34.1 An alkylidene precursor may also lead to a metallacycle with elimination of the car-bene ligand as in the synthesis of 81, representing a deactivation pathway for alkene metathesis catalysts. Ilie two alkenes may be generated in situ in the coordination sphere by rearrangement processes, such as intramolecular hydrogen transfer from an alkyl-vinyl precursor. I ... 

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