Malonates electrophilic fluorination

Newer QM/MM simulations of the electrophilic fluorination of a malonate coordinated to a titanium center with a simplified Selectfluor (F-TEDA) analog [189] throw a new light on the electron transfer/fluorine transfer mechanism. During the approach of the electrophilic fluorine toward the carbon nucleophile an electron is transferred from the nucleophile to Selectfluor, then fluorine is transferred to the nucleophile. Interestingly, the transition state for transfer of the fluorine radical is formed only if a polar solvent (acetonitrile) is used. If the simulation is carried out in vacuo, the reaction stops after the initial electron transfer. 

Trifluoroacetamidine (585) is most widely used for the principal synthesis of pyrimidines. Compound 585 can be prepared from ethyl trifluoroacetate by ammo-nolysis, followed by dehydration with P2O5 and reaction with ammonia (Scheme 124) [335,336]. Amidine 585 has been introduced into reaction with various p-dicarbonyl compounds and their synthetic equivalents (Table 27), including p-ketoesters (Entries 1-6), in particular p-ketopyruvates (Entry 3) and a-alkoxymethylene-p-ketoesters (Entries 4-6), p-enaminocarbonyl compounds (Entries 7-9), malonic acid derivatives (Entry 10), fluorinated p-diketones (Entry 11), vinamidinium salts (Entry 12), a,p-unsaturated nitriles with leaving group at p position (Entries 13-15) and other bis-electrophiles (Entries 16, 17). Usually, the reaction gives moderate yields of the target 2-CF3-pyrimidines (ca. 50 %). 

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