Negishi reaction/cross-coupling

Seheme 3.2 Cross-coupling of bromoindanes with alkylzinc reagents. 

Cross-coupling of TMS-protected secondary propargylic carbonates with arylzinc reagents. 

1) s-BuLi (1.6 equiv), TMEDA (1.5 equiv) Znl2 (0.75 equiv), -78 °C 1-Naph 1-Naph 

3 Hiyama, Kumada, Suzuki, and Related Cross-Coupling Reactions 

In 2011, a related methodology using chiral diamine as ligand was 

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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 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. ... 

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. 

In 2010, a palladium-catalyzed Negishi cross-coupling reaction between the quaternary ammonium charged substrate (p-iodophenyl)-trimethyl-ammonium iodide ([Arl] ) and... 

Recent advances of the Negishi cross-coupling reaction have enabled chemists to catalytically couple two sp carbon centres. These reactions provide the coupled alkane as the final product . A remote double bond in primary halides also enabled the Ni-catalyzed crosscoupling reactions between two Csp centres . ... 

In the area of organometallic chemistry, we begin with a procedure for the palladium-catalyzed animation of aryl halides and aryl triflates, illustrated by syntheses of N-HEXYL-2-METHYL-4-METHOXYANIUNE and N-METHYL-N-<4-CHLOROPHENYL)-ANILINE. The next procedure describes the synthesis of 1,2,3,4-TETRAHYDROCARBAZOLE by the palladium-catalyzed annulation of ketones with o-iodoaniline. Next, a procedure for the synthesis of 2,7-DIMETHYLNAPHTHALENE via the nickel-catalyzed coupling of aryl O-carbamates with Grignard reagents is presented. The fourth procedure in this section describes the synthesis of 5-METHYL-2,2 -BIPYRIDINE by a Negishi cross-coupling reaction... 

In an unusual twist to the Negishi cross-coupling reaction, p-substituted benzyl halides undergo reduction to p-substituted toluenes in the presence of Et2Zn (one or two equivalents) and catalytic amounts of Pd(0).222 Consider the reaction below, and propose a catalytic cycle that explains how it might occur. Assume that a L Pd-H species forms and the by-products of the reaction are ethene and EtZnCl. 

In 2002, Wonnacott published the synthesis and biological evaluation of a pyridazine analog (62) of nicotinic acetylcholine receptor agonist UB-165 [45]. This aza-UB-165 analog (62) was synthesized via Negishi cross-coupling reaction on triflate 60 with pyridazin-3-ylzinc halide (59). Compound 59 could be obtained from 3-bromopyridazine (58) via lithiation and subsequent transmetalation with zinc chloride. 

In the frame of a medicinal chemistry program at Merck Sharp Dohme Ltd, Collins and co-workers reported successful Negishi cross-coupling reaction of 3-aryl-7-bromo-6-[( 1 -methyl-1/7-1,2,4-triazol-5-yl)methoxy][ 1,2,4]triazolo[4,3-/ pyridazines (63) with aliphatic organozinc reagents [35]. 

Table 4 Negishi cross-coupling reactions of alkyl electrophiles and organozinc halides...

Also Pdotalyzed Negishi cross-coupling reactions have been described in ionic liquids. Knochel and coworkers investigated the reaction between organometalhc zinc compounds and aryl iodide in [BMMIM][Bp4] using an ionic phosphine ligand. Scheme 5.3-30 illustrates the reaction for the formation of a 3-substituted cyclohexenone from 3-iodo-cyclohex-2-en-l-one [170]. The reaction vras carried out in an ionic liquid/toluene biphasic system, which allowed easy product recovery from the catalyst by decantation. However, attempts to recycle the ionic catalyst phase resulted in significant catalyst deactivation, after only the third recycle. 

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