Kumada coupling biaryl synthesis

The coupling of Grignard reagents with alkyl, vinyl or aryl halides under Ni-catalysis provides an economic transformation, but the reaction is limited to halide partners that do not react with organomagnesium compounds. One example is in the industrial-scale production of styrene derivatives, and the Kumada Coupling is the method of choice for the low-cost synthesis of unsymmetrical biaryls. 

Of the various possible asymmetric cross-coupling reactions, (1) asymmetric alkylation with secondary alkylmetals, (2) asymmetric biaryl synthesis, and (3) asymmetric allylation with allylic electrophiles have been most extensively studied with chiral Ni and Pd complexes [166]. The initial study in this area was reported as early as 1974 by Kumada and his co-workers, but only a meager range of 8-15% ee was reported [167]. By the end of the 1970s, however, the cross-coupling reaction had been sufficiently developed so that its application to the asymmetric synthesis was already practically attractive, as indicated by an asymmetric total sythesis of (R)-(—)-a-curcumene in five steps in 66% ee and 34% overall yield shown in Scheme 1-47 [168]. 

Kumada coupling. A report of biaryl synthesis from ArMgBr and Ar Cl highlights the use of a Ni carbenoid (1). Both bis(Ti -allyl)nickel and palladium complexes are also useful catalysts for the cross-coupling." ... 

Biaryl synthesis through Kumada coupling has employed a recyclable catalyst in which PdCl2 is anchored in a mesoporous silica with an appended bipyridyl unit." It also has addressed the steric hindrance issue. Choice of ligands appears to be important. One report describes the use of a PdCl2 complex of both l,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene and 3-chloropyridine, another indicates the effectiveness of (t-Bu2POH)2PdCl2. ... 

Cazin and coworkers investigated the activity of dimers analog to 10 as catalysts for Kumada coupling reactions [32]. Of the four complexes tested (NHC = IPr, SlPr, IMes, and SlMes) the SlPr-bearing complex proved to be the most effective for the synthesis of tri- and tetra-ori//o-substituted biaryls, under relatively mild reaction conditions and in good yields. 

The Stille reaction is arobust choice for the synthesis of biaryls, including heteroaryl systems (Scheme 2.61). Despite trying Suzuki, Hiyama and Kumada couplings and others, only Stille coupling (M = -BusSn) proved reliable on a large scale (302 g) for the synthesis of a heteroaryl-substituted imidazole 2.180, needed for the synthesis of an angiogenesis inhibitor (Scheme 2.62). ... 

It was not until Cazin and co-workers introduced the well-defined dimer complex [Pd( J,-Cl)(Cl)(SIPr)]2 that the Kumada-Tamao-Corriu cross-coupling between severely sterically hindered partners was pursued, allowing the synthesis of tri- and tetra-orf/io substituted biaryls [81] (Scheme 6.20). 

An alternate approach to the asymmetric synthesis of axially chiral biaryls has been developed based on the nickel-catalysed Kumada cross coupling of dibenzothiophenes. Cleavage of the carbon—sulfur bond of achiral dibenzoth-iophene (10.25) with the nickel catalyst generated from ligand (10.26) leads to the... 

In Chapter 1, the authors present a general overview of the classical cross-coupling methods, such as Heck-Mizoroki, Suzuki-Miyaura, Sonogashira, Kumada, Negishi, Ullmann coupling, and modern methods for biaryl unit synthesis, with metals such as Fe and Co. This is a very extensive chapter. 

---