Zinc catalysts Negishi reaction

Alkylzinc halides have also been prepared under microwave irradiation. The Reformatsky reagents (2-t-butoxy-2-oxoethyl)zinc bromide and [(2-dibenzylamino)-2-oxoethyl]zinc bromide were synthesized from the corresponding bromides via reaction with zinc in THF (Scheme 5) [24], The oxidative addition was executed at 100 °C in 5 min. The obtained reagents were subsequently used in Negishi reactions on 2-bromopyridine, 3-bromopyridine, 2-bromo-5-nitropyridine, and 2-bromo-5-trifluoromethyl-pyridine using Pd(PPh3)4 as a catalyst (Scheme 5). 

Knochel showed that 2-thiazolylzinc species 42 cross-coupled with aromatic or aliphatic electrophiles to give the corresponding products 43 and 44, respectively, in the presence of copper and palladium catalysts. 2,4-Dibromothiazole has been used as halide in Negishi reactions the crosscoupling took place selectively in the 2-position in 50-62% yield. The formation of zinc species in the 5-position of thiazole can also be prepared if the 2-position was protected with a trimethylsilyl group as in 45 before the organozinc derivative 46 was formed in the 5-position. The subsequent... 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

A cross-coupling reaction (Negishi coupling) between A -SEM-pyrrol-2-yl-zinc chloride 618 and the appropriate dibromo derivative catalyzed by a Ni catalyst leads to 2-[4-(l//-pyrrol-2-yl)phenyl]-l//-pyrroles 619 (Scheme 125) <1997CM2876>. The SEM-protecting group can be easily removed by reaction with BU4NF. 

A special case of a Negishi coupling was performed with 1-hydroxy-imidazole (92), which could be etherified with Merrifield and Wang resin (91) [210]. Upon treatment with Bull, the H-2 is removed giving a stabilized carbanion, which can react with various electrophiles such as aryl iodides (2). Both ZnCh and Pd(PPh3)4 were required for the reaction. The Z.riCL was used in excess and displaces the Li from the imidazole. The Pd catalyst was added in small quantities (0.1 equiv.) and performs an insertion into the aryl-iodine bond creating the electrophile to be trapped by the zinc imidazolide. Several 2-arylated 1-hydroxyimidazoles (95) were obtained by this method in almost quantitative yields (Scheme 21). 

Unsymmetrical biaryh and diarylmethanes. Negishi et al have used a nickel-(0) complex or a palladium(0) complex as catalyst for the cross-coupling of aryl-or benzylzinc halides with aryl halides at room temperature to form biaryls or diarylmethanes. The zinc derivatives are prepared by reaction of aryl- or benzyl-lithium with zinc chloride or bromide. 

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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