Pyrimidines zincation

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 are available by transmetallation reactions as discussed in Section 6.02.5.6.4. Most work has been done with pyridines, but coupling reactions seem equally feasible with pyrimidines. An example is provided by 2-iodo-4,6-dimethylpyrimidine which is zincated in the 2-position and Pd-coupled with iodobenzene to furnish the 2-phenyl derivative in 26% yield <93T9713). 

The direct synthesis of arylzinc halides from the halide and activated zinc <90TL4413,9lJOCl445> can also be applied to heteroaromatic systems, (e.g. bromo- and iodopyridines). In the electrophilic pyrimidine 2-position zincation and coupling of the iodo derivative took place to the extent of 26%... 

Zinc Derivatives. Zincated and Al-protected 6-iodouracil 155 can be used under Negishi conditions for the preparation of 6-arylated uracil derivatives (Scheme 63). The conversion of the 6-iodouracil derivative is best performed using highly active zinc dust in DMAC.f The oxidative addition of active zinc has also been applied to a number of other iodo- and bromo-substituted 7r-deficient heteroarenes such as pyridine, pyrimidine, and quinoline, giving the corresponding heteroarylzinc halides 156, which are transformed to arylated derivatives by palladium catalysis. ... 

Metalation of Sensitive Heterocycles and Functional Group Tolerance. Several sensitive heteroarenes such as pyridazines, pyrimidines, and pyrazines can be cleanly zincated at 25 °C using the nuld hase TMPZnCl-LiCl (eq 2). Thus, the treatment of 3,6-dichloropyridazine with TMPZnCl-LiCl (1.1 equiv, 25 °C, 30 min) readily leads to the corresponding zincated species with full conversion. Similarly, the zincation of other sensitive chloro-diazines such as 4,6-dichloropyrimidine or 2,6-dichloropyrazine furnishes the corresponding zincated arene at room temperature, also in excellent conversion. ... 

Even more complex pyrimidine derivatives such as thienopy-rimidines can be zincated. Interestingly, they display a similar re-gioselectivity switch, as already seen with the chromones. Thus, the treatment with TMPZnCl LiCl (1.2 equiv, 25 °C, 12 h) leads to a smooth deprotonation of the most acidic proton in position 6 (eq 16). Complementarily, addition of BF3-OEt2 (1.1 equiv, 0°C, 15 min) to thienopyrimidines followed by TMPZnCl-LiCI (1.5 equiv, 0°C, 2 h) leads to a regioselective zincation at position 2. ... 

Seggio A, ChevallierF, Vaultier M, Mongin F (2(X)7) Lithium-mediated zincation of pyrazine, pyridazine, pyrimidine, and quinoxaline. J Org Chem 72 6602-6605. doi 10.1021/jo0708341... 

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