Direct Zincation Reactions

Zinc amide 59 shows better chemoselectivity (but lower reactivity) and leads to the formation of aryl- and heteroarylzinc chlorides. Notably, it can be used to achieve [82] directed ortho- and meta-zincation of functionalized aryl nonaflates, thus providing suitable substrates for further Negishi cross-coupling reactions. 

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Also 1,3,4-oxadiazoles are suitable substrates in a new process in which (tmp)2Zn.2MgCl2.2LiCl 173 act as a base for the direct zincation of the heroaromatic compound. Subsequent reaction with an electrophile afforded the corresponding derivatives <07AG(E)7685>. 

Heteroaryl zinc compounds are particularly useful in palladium-catalysed coupling, being compatible with many functional groups. They are often prepared in situ via lithiation, followed by reaction with zinc halides, but direct zincation of halides can be carried out, using either Riecke zinc, as in the example below, or, more conveniently, ordinary zinc dust, with various means of activation. 

Direct zincation of each of the diazines can be achieved using a zinc diamide/lithium amide mixture, pyrazine and pyrimidine (at C-4) in THF at room temperature, pyridazine (at C-3) requiring reaction at reflux. Pyridazine and pyrimidine can also be directly zincated using a phosphazene base (t-Bu-P4) with zinc iodide. ... 

Zinc Derivatives. Direct zincation of 6-bromoxazolo[4,5-b]pyridmes can be effected using activated zinc (Scheme 69). The zincated species 164 and 165 from oxazolo[4,5- ]pyridin-2(3 0-ones or 2-phenyl- or 2-benzyloxyoxazolo[4,5-b]pyridmes were used in Negishi-type coupling in a one-pot reaction with benzyl bromide for the preparation of 6-benzyl derivatives. ... 

Microwave-assisted High-temperature Metalation of Weakly Activated Aromatics and Heteroaromatics. Over the last few decades, microwave irradiation has been used to accelerate numerous organic reactions, including metalations. Organozinc reagents of the type RZnX possess a good thermal stability and tolerate functional groups, even at elevated temperatures. The direct zincation of coumarin requires 7 days at room temperature to achieve 85% conversion. However, under microwave irradiation, the zincation was achieved in over 90% yield (80 °C, 1 h) (eq 7). ... 

Directed zincation of the aromatic diester 244 In a dry and argon-flushed Schlenk flask, 4-bromo-isophthalic acid 244 (248, 1.10 mL, 0.5 m in THF, 0.55 mmol) is added dropwise and the reaction mixture is stirred 10 h at 25 °C until GC analysis of iodolyzed reaction aliquots show completion of the metalation reaction. The reaction mixture with the diorganozinc species 249 is cooled to -20 °C and CuCN-2LiCl (1.1 mL, 1 m in THF, 1.1 mmol) is added. After stirring for 15 min at -20 °C, benzoyl chloride (0.353 g, 2.5 mmol) is added, and the reaction mixture is slowly warmed to 25 °C. The mixture is stirred for 1 h at 25 °C. Usual workup and purification by flash chromatography (pentane/diethyl ether 3 1) furnish the product 250 (0.336 g, 83%) as a colorless solid. 

According to NMR data, reaction of lithium tetramethylpiperidine (TMP) and t-Bu2Zn, in a 1 1 molar ratio (Scheme 6) affords the heteroleptic zincate [f-Bu2Zn(TMP)]Li (36) . An interesting feature of this compound is that it is capable of metalate arenes that contain a directing metalating group (DMG) in ortho-posilion and thus allow further derivatization by reaction of the zincate intermediate with electrophiles (E+). 

Deprotonative zincation and magnesiation have been developed as alternatives for the lithiation of thiophenes. The drawbacks associated with lithiation are that it usually requires the reactions to be performed at —78°C, and the lithium derivatives so formed cannot he directly used for cross-coupling reactions. 

Directed ortho metallation can be carried out with a tetramethylpiperidyl zincate, but the only reported reactions of the resulting heteroarylzincates have been with iodine and benzaldehyde. ... 

Zincate 120g was generated and used directly in Pd-catalyzed cross-coupling reactions leading to... 

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