Organozinc Compounds Negishi Coupling

Tetramethylpiperidine-zincate 1 is a good reagent for directed ortho zincation of various functionalized aromatic and heteroaromatic compounds. For example, benzoate was converted to biphenyl-2-carboxylate 2 by zincation with 1, followed by coupling with iodobenzene [46]. 

A facile and convenient preparative method of alkylzinc reagents is direct reaction of alkyl iodides with activated Zn/Cu couple [47] or Zn dust [48]. Huo reported an efficient, general preparative method of alkylzincs from unactivated 

A new ionic phosphine ligand (1-19) is effective for the coupling of arylzinc 13 with aryl iodide 14 at room temperature to give 15 in a biphasic system containing toluene, THF, and an ionic liquid [bdmim][BF4], The Pd catalyst always stays in the ionic liquid and can be recycled [53]. 

Coupling of the sterically congested arylzinc chloride 21 with 1-cyclopentenyl chloride (22) gave 23 in high yield when Pd[P(t-Bu3)]2 was used as a catalyst in THF-NMP [51], 

Total synthesis of (+)-pumiliotoxin A (39) has been achieved based on the Negishi coupling of the alkylzinc chloride 37, derived from the alkyl iodide, with the alkenyl iodide 38 at room temperature, and subsequent deprotection [58], The alkylzinc reagent 41 was prepared conveniently by the reaction of the alkyl iodide 40 with Zn/Cu couple, and treated with 2-iodoimidazole 42 to afford the adduct 43 [47], 

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Alkenylation and Arylation of Organozinc Compounds (Negishi Couplings) and of Functionalized Organozinc Compounds... 

Scheme 5.2-20 Pd-catalyzed cross-coupling of organozinc compounds (Negishi cross-coupling)...

R = alkenyl, aryl, allyl, benzyl, propargyl R = alkenyl, aryl, alkynyl, alkyl, benzyl, allyl The Negishi Coupling was the first reaction that allowed the preparation of unsymmetrical biaryls in good yields. The versatile nickel- or palladium-catalyzed coupling of organozinc compounds... 

The cross-coupling of organozinc compounds has been accomplished using a number of metal enolate complexes, namely Rh(acac)(H2C=CH2)2 (6) , Co(acac)3 (30) °, Ni(acac)2 (47) , Li(acac) (107) and Cr(acac)3 (108) . For instance, complex 47 proved to be an extremely effective catalyst system for the Negishi cross-coupling of arylzinc halides (109) with aryl (110), heteroaryl and alkenyl halides, triflates and nonaflates to give the corresponding biaryl compounds (111) (equation 30). The solvent played an important role in these reactions and optimal conditions were found with 8 1 mixtures of THF and A-ethylpyrrolidinone (nep). Only 0.05 mol% of the nickel complex... 

The modified Negishi protocoi was used in J.S. Panek s total synthesis of (-)-motuporin to couple the left-hand subunit organozinc compound with the right-hand subunit ( )-vinyl iodide. The left-hand subunit was prepared by the Schwartz hydrozirconation of a disubstituted alkyne to give an ( )-trisubstituted zirconate, which was subsequently transmetalated with anhydrous ZnCl2. The resulting vinylzinc species was immediately treated with one equivalent of the ( )-vinyl iodide in the presence of 5 mol% Pd(PPhs)4 to afford the ( , )-diene coupled product with complete stereoselectivity. 

Yus, M., Gomis, J. Negishi cross-coupling with functionalized organozinc compounds prepared by lithium-zinc transmetallation. 

The Negishi cross-coupling reaction is the nickel- or palladium-catalyzed coupling of organozinc compounds with various halides or triflates (aryl, alkenyl, all nyl, and acyl). 

Negishi and his co-workers have described a new synthetic route to 1,5-dienes (or 1,5-enynes) which is particularly suitable for the construction of head-to-tail coupled isoprene units. The key step involves a regio- and stereo-selective palladium-catalysed cross-coupling of homoallylic (or homopropargylic) organozinc compounds with alkenyl halides (e.g. Scheme 95) homo-coupling... 

Organozinc compounds have been extremely useful reagents in the Negishi cross-coupling reactions with alkyl and aryl halides creating a new C—C bond (Scheme 13.28). The Negishi Ni, Pd, or Fe mediated cross-coupling reactions have proved to be powerful tools in vast areas of synthesis. 

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