Cross Kumada coupling

The enantioselective total synthesis of (+)-ambruticin was accomplished in the laboratory of E.N. Jacobsen. The Kumada cross-coupling was utilized to convert an ( )-vinyl iodide intermediate to the corresponding conjugate diene in good yield. The stereochemistry of the vinyl iodide was completely preserved. 

Research by M. Ikunaka showed that C2-symmetrical chiral quaternary ammonium salts can serve as asymmetric phase-transfer catalysts. To prepare significant quantities of (R)-3,5-dihydro-4/-/-dinaphth[2,1-c T,2 -e]azepine, a novel short and scalable synthetic approach was undertaken. The synthesis commenced with the triflation of (R)-binol to give the b/s-O-triflate. The Kumada cross-coupling was used to install two methyl groups in good yield. 

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Scheme 6.40 Negishi and Kumada cross-coupling reactions.

The Kumada cross-coupling reaction (also occasionally known as the Kharasch cross-coupling reaction) is a nickel- or palladium-catalyzed cross-coupling reaction of a Grignard reagent with an organic halide, triflate, etc. 

Scheme 21 Microwave-assisted Kumada cross-coupling...

The use of a functionalized silica-supported salen-nickel complex has allowed Kumada cross-couplings to be performed in flow the corresponding polystyrene supported complex was shown to be inferior for a number of reasons. Catalyst 33 (Figure 4.7) with the longer tether was found to be more active than the benzyl ether tether used for catalyst 34. This was postulated to be due to the fact that catalyst 33 resided further away from the silica surface and hence was more available for reaction. Under the conditions used a maximum conversion of 65% was found for the 1 1 reaction of 4-bromoanisole and phenylmagnesium chloride, which was found to be comparable to that obtained in batch mode. However, during the reaction catalyst degradation was observed and the conversion reduced from 60% in the first hour to 30% in the fifth hour of the reaction [155,156]. 

In symmetrically substituted 3,4-dihalothiophenes, several stepwise cross-coupling reactions have been performed <2005T2245>. Thus, 3,4-dibromothiophene undergoes a Negishi coupling with benzylzinc bromide to yield the monobromothiophene 84. This can be subjected to a Kumada cross-coupling to give the unsymmetrically substituted thiophenes 85. 

Pd- or Ni-catalyzed Kumada cross-coupling Cross-coupling of alkenyl- or aryl halides and Grignard reagents or organolithium species. 258... 

Related reactions Kumada cross-coupling, Stille cross-coupling, Suzuki cross-coupling ... 

Walla, P., Kappe, C. O. Microwave-assisted Negishi and Kumada cross-coupling reactions of aryl chlorides. Chem. Common. 2004, 564-565. 

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... 

A bimetallic oxidative addition mechanism involving radical intermediates has been proposed for allqrl-allq l Kumada cross-coupling catalysed by complex 18 (Figure 14.2). In this catalytic cycle, the oxidative addition of allq l halide involves two nickel centres, and the key intermediate for the activation of allqrl halide is the complex [(N2N)Ni-R](R-MgCl). The formation of this species is the turnover-limiting step of the catalysis. ... 

Scheme 14.32 Stereospecific Kumada cross-couplings of henzylic ethers.

Scheme 14.33 Kumada cross-couplings of benzylic alcohols.

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