Coupling, metal mediated, alkyl halides

Barbier coupling reaction Metal-mediated addition of alkyl, allyl or benzyl halides to carbonyl compounds. 38... 

As in the case of quinolines, isoquinolines can be prepared by metal-mediated annotation processes. Reaction of t-butylimines of iodo-benzaldehydes with acetylenes in the presence of palladium catalyst affords 3,4-disubstituted isoquinolines. The power of this reaction relies on its ability to introduce different type of substituents on 4-position of the heterocycle by using the formed intermediate palladium complex in the cross-coupling reaction with aryl and alkyl halides or alkenes. This methodology was successfully applied to the total synthesis of decumbenine... 

In general, the compounds of the Group 4 metals, such as halides and alkoxides, are well known as Lewis acids to catalyze two-electron electrophilic reactions, and their metallocenes coupled with alkylation and/or reduction agents were effective catalysts for the coordination polymerization of olefins. For the transition metal-catalyzed radical polymerization, their alkoxides, such as Ti(Oi-Pr)4, have also been employed as an additive for a better control of the products. Contrary to the common belief that the Group 4 metals rarely undergo a one-electron redox reaction under mild conditions, there have been some reports on the controlled radical polymerization catalyzed or mediated by titanium complexes, although the conflict in the mechanism between the (reverse) ATRP and OMRP is also the case with the Group 4 metal complexes. 

Pletcher and associates [155, 159, 160] have studied the electrochemical reduction of alkyl bromides in the presence of a wide variety of macrocyclic Ni(II) complexes. Depending on the substrate, the mediator, and the reaction conditions, mixtures of the dimer and the disproportionation products of the alkyl radical intermediate were formed (cf. Section 18.4.1). The same group [161] reported that traces of metal ions (e.g., Cu2+) in the catholyte improved the current density and selectivity for several cathodic processes, and thus the conversion of trichloroacetic acid to chloroacetic acid. Electrochemical reductive coupling of organic halides was accompanied several times by hydrodehalogena-tion, especially when Ni complexes were used as mediators. In many of the reactions examined, dehalogenation of the substrate predominated over coupling [162-165]. 

The possibilities for the formation of carbon-carbon bonds involving arenes have been dramatically increased in recent years by the use of transition metal catalysis. Copper-mediated reactions to couple aryl halides in Ulknann-type reactions [12, 13] have been known for many years, and copper still remains an important catalyst [14, 15]. However, the use of metals such as palladium [16,17] to effect substitution has led to such an explosion of research that in 2011 transition metal-catalyzed processes comprised more than half of the reactions classified as aromatic substitutions in Organic Reaction Mechanisms [18]. The reactions often involve a sequence outlined in Scheme 6.6 where Ln represents ligand(s) for the palladium. Oxidative addition of the aryl halide to the paiiadium catalyst is followed by transmetalation with an aryl or alkyl derivative and by reductive elimination to give the coupled product and legeuCTate the catalyst. Part 6 of this book elaborates these and related processes. 

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