Nickel‐Catalyzed Coupling of Aryl Bromides in the Presence of Alkyllithium Reagents

Abstract

Transition-metal-catalyzed coupling reactions of halogenated molecules leading to formation of new carbon-carbon bonds are a very important category of reactions used in the synthesis of complex compounds and conjugated polymers. [1][2][3] Within the past decade, this methodology has evolved into a powerful synthetic tool for the preparation of a wide range of specialty polymers, composite materials, and pharmaceutically active compounds both in the laboratory and on the industrial scale. It is also widely appreciated in the context of parallel synthesis and combinational chemistry. [4,5] We desired to develop an improved catalytic method for transition-metal-catalyzed aryl coupling reactions and report herein the one-pot, one-step, nickel-catalyzed coupling of aryl bromides in the presence of alkyllithium reagents [Eq. (1)].Metallic reagents including palladium and nickel complexes have demonstrated to be quite effective in C À C coupling reactions. Typically, coupling reactions of aryl halides involving the use of catalytic amounts of nickel(II) complexes require the addition of either magnesium or zinc to facilitate efficient coupling and regeneration of active nickel(0) catalytic species. For example, Kumada coupling reactions use magnesium for the formation of active alkyl/ aryl magnesium bromide species (Grignard formation), which is generally a substrate-and solvent-specific reaction (working optimally in tetrahydrofuran or diethyl ether as solvents). [6][7][8][9][10] Nickel reactions facilitated by the addition of zinc powder have been utilized in a similar fashion in organic synthesis, [11][12][13] as well as in efficient condensation polymerizations. [14][15][16] These reactions are not always well controlled, require prolonged heating at high temperatures, and the products have high levels of metal impurities that can be difficult and costly to remove. This trace-metal contamination is especially problematic if the end use is in pharmaceutical or microelectronic applications in which safety, performance, and reliability require stringent control of purity. Another known aryl-halide coupling reaction involves the use of highly reactive zinc (Rieke zinc), which is prepared by reduction of ZnCl 2 with lithium naphthalenide and has been shown to readily undergo oxidative addition with alkyl, aryl, and vinyl halides under mild conditions to generate the corresponding organozinc compounds. These reactive organozinc compounds are then cross-coupled with other aryl or vinyl halides using palladium(0) catalysts. [17] Recently, homocoupling of bromide compounds has been facilitated through the combination of metallic magnesium and a catalytic amount of iron salts.[18] Coupling reactions involving activated dihalogenated thiophene molecules catalyzed by nickel(II) complexes have also been demonstrated in the presence of reactive zinc (Rieke zinc) [19] or an alkylmagnesium reagent (GRIM/McCullough method) [20] to form regioregular polythiophenes.Coupling reactions of halogenated molecules involving nickel(0) compl...

Nickel‐Catalyzed CH Arylation of Azoles with Haloarenes: Scope, Mechanism, and Applications to the Synthesis of Bioactive Molecules

“…However, we must stress that even if this is the case, the deprotonation/protonation shuttle of azoles (which avoids azole substrate decomposition) is essential for achieving the heterobiaryl coupling. [29] In this regard, the present Ni-catalyzed azole arylation is not merely an in situ Kumada-Tamao-Corriu type coupling.…”

Lithium Compounds in Cross‐Coupling Reactions

“…molar equivalent of t-BuLi, was achieved using a flask, that is, the conventional batch system (Scheme 16.11) [14]. The producing biaryls were isolated in good to high yields without forming t-butylated arenes.…”

Poly(vinylpyridine)‐Grafted Silica Containing Palladium or Nickel Nanoparticles as Heterogeneous Catalysts for the Sonogashira Coupling Reaction

“…[15,[31][32][33] Nickel is a promising and cheaper alternative to the use of palladium as a transition-metal catalyst in coupling reactions. There are many reports in the literature on the use of nickel as an alternative to palladium in homocoupling [34][35][36] and crosscoupling reactions such as Heck, Suzuki, and Kumada, [37][38][39][40][41][42][43] but there are only a few reports on Ni-catalyzed Sonogashira reactions. [22][23][24][25][26][27][28] A nickel-catalyzed Sonogashira reaction was reported by Beletskaya et al using homogeneous Ni II species.…”