Negishi cross coupling

Substituted ferrocenyl groups are useful asymmetric building groups for stereoselective syntheses. Hayashi and co-workers have discovered a novel class of ferrocenyl catalysts, allowing the kinetic resolution of benzylic zinc derivatives, such as 85. a The racemic mixture of the benzylic zinc reagent 85 obtained by transmetallation 

R = aryl, alkenyl, allyl, benzyl homoallyl, homopropargyl X = Cl, Br, I 

L = PPhs, P(o-tolyl)3, dppe, dppp, dppb, dppf, BINAP, diop, chiraphos 

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. 

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KUMADA NEGISHI Cross coupling Stsreospecific alkenyl aluminum-alkenyl halide cross coupling catalyzed by Pd or Ni... 

Knochel et al. described Pd-catalyzed Negishi cross-coupling reactions between zinc organometallics and aryl iodides in [BMMlM][Bp4]. Scheme 5.2-20 illustrates the reaction for the formation of a 3-substituted cyclohexenone from 3-iodo-2-cyclo-hexen-l-one [82]. 

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

Sequential arylzinc formation and Negishi cross-coupling. 

Scheme 6.42 Synthesis of enantiopure 2,2 -diarylated 1,1 -binaphthyls utilizing stereoconservative Negishi cross-coupling reactions.

When the metallic additive to the intermediate 374 was zinc dihalide (or another Lewis acid, such as aluminum trichloride, iron trichloride or boron trifluoride), a conjugate addition to electrophilic olefins affords 381 . In the case of the lithium-zinc transmetallation, a palladium-catalyzed Negishi cross-coupling reaction with aryl bromides or iodides allowed the preparation of arylated componnds 384 ° in 26-77% yield. In addition, a Sn2 allylation of the mentioned zinc intermediates with reagents of type R CH=CHCH(R )X (X = chlorine, bromine) gave the corresponding compounds 385 in 52-68% yield. ... 

However, while this procedure was acceptable on a laboratory scale, it was unsuitable for scale-up due to difficulties with the preparation of the dialdehyde 987 in bulk quantities. Therefore, an alternative procedure was developed that involved a Negishi cross-coupling approach. Thus, coupling of 2-pyridylzinc chloride 990 and 2-chloro-5-iodopyrimidine 991 in the presence of a catalytic amount of Pd(PPh3)4 was able to be achieved in 60-70% yield with a product purity for 989 of greater than 95% <20070PD237>. 

Banwell has developed a new approach to the core associated with several members of the lamellarin class of marine natural products. This approach utilized some interesting pyrrole arylation reactions including a Negishi. cross coupling of the iodopyrrole 46 followed by a double-barrelled Heck cyclization of the resultant arylpyrrole 47 yielding the core structure 48... 

SCHEME 106. Synthesis of a-aniino acids by Negishi cross-couplings... 

SCHEME 110. Negishi cross-coupling with heterocyclic zinc reagents... 

Zhou, J. Fu, G. C. Palladium-catalyzed Negishi cross-coupling reactions of unactivated alkyl iodides, bromides, chlorides, and tosylates. I. Am. Chem. Soc. 2003, 125, 12527-12530. 

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