Functionalization by Metallation of Fluoropyrazine. Diazines XXI

Lithiation of fluoropyrazine followed by quenching with various electrophiles was successfully achieved and was used to synthesize new pyrazine derivatives. A further lithiation of 2-fluoro-3-substituted pyrazines allowed access to 2,3,6-trisubstituted pyridazine derivatives. As an application, a one-pot synthesis of a quinuclidinylfluoropyrazine has been performed. When the 3-substituent bears a TMS protected alcohol, functionalization via metallation at C5 position provides tetrasubstituted pyrazines in good yield.