Negishi coupling

The Negishi coupling is a cross coupling reaction in organic chemistry involving an organozinc compound, an organic halide and a nickel or palladium catalyst creating a new carbon-carbon covalent bond :


 * [[Image:Negishi_coupling.png|400px|The Negishi coupling]]


 * The halide X can be chloride, bromine or iodine but also a triflate or acetyloxy group with as the organic residue R alkenyl, aryl, allyl, alkynyl or propargyl.
 * The halide X' in the organozinc compound can be chloride, bromine or iodine and the organic residue R' is alkenyl, aryl, allyl or alkyl.
 * The metal M in the catalyst is nickel or palladium
 * The ligand L in the catalyst can be triphenylphosphine, dppe, BINAP or CHIRAPHOS

Palladium catalysts in general have higher chemical yields and higher functional group tolerance.

Reaction mechanism
The active catalyst in this reaction is zerovalent (M0) and the reaction in general proceeds through an oxidative addition step of the organic halide followed by transmetalation with the zinc compound and then reductive elimination:


 * [[Image:NegishiCouplingMechanism.png|300px|Negishi Coupling Mechanism]]

Both organozinc halides and diorganozinc compounds can be used as starting materials. In one model system it was found that in the transmetalation step the former give the cis-adduct R-Pd-R' resulting in fast reductive elimination to product while the latter gives the trans-adduct which has to go through a slow trans-cis isomerization first.

Scope
The Negishi coupling has been applied in the synthesis of a 2,2'-bipyridine from 2-bromopyridine with  Tetrakis(triphenylphosphine)palladium(0), the synthesis of a biphenyl from  o-tolylzinc chloride and  o-iodotoluene and Tetrakis(triphenylphosphine)palladium(0) , the synthesis of 5,7-Hexadecadiene from 1-decyne and (Z)-1-hexenyl iodide

The Negishi coupling has been applied in the synthesis of hexaferrocenylbenzene :
 * [[Image:Hexaferrocenylbenzene.png|400px|Hexaferrocenylbenzene]]

with hexaiodidobenzene, diferrocenylzinc and tris(dibenzylideneacetone)dipalladium(0) in tetrahydrofuran. The yield is only 4% signifying substantial crowding around the aryl core.

In a novel modification palladium is first oxidized by the haloketone 2-chloro-2-phenylacetophenone 1 and the resulting palladium OPdCl complex then accepts both the organozinc compound 2 and the organotin compound 3 in a double transmetalation :


 * [[Image:DoubleTransmetallationcrosscoupling.png|400px|Double Transmetallation crosscoupling]]