A general catalyzed direct C-H functionalization of s-tetrazines is reported. Under mild reaction conditions, N-directed ortho-C-H activation of tetrazines allows the introduction of various functional groups, thus forming carbon-heteroatom bonds: C-X (X=I, Br, Cl) and C-O. Based on this methodology, we developed electrophilic mono- and poly-ortho-fluorination of tetrazines. Microwave irradiation was optimized to afford fluorinated s-aryltetrazines, with satisfactory selectivity, within only ten minutes. This work provides an efficient and practical entry for further accessing highly substituted tetrazine derivatives (iodo, bromo, chloro, fluoro, and acetate precursors). It gives access to ortho-functionalized aryltetrazines which are difficult to obtain by classical Pinner-like syntheses.

Ag eneral protocolf or palladium-catalysed C À Hm ono-and di-fluorination of highly substituted arylpyrazoles is reported. Coupling pathways and substrate limitations are discussedi nt he light of complementary mechanistic experimental and density functional theory (DFT) studies.T he mono-a nd di-ortho-fluorination of arylpyrazoles having substituted pyrazole groups and ortho-, meta-, or para-substituteda rene moieties is achieved.V arious pyrazole groups can efficiently promote the direct C À Ha ctivation/fluorination of substrates bearing valuable reactive ester, cyano,h alide and nitro functions.T he presence of methoxy,m ethyl and trifluoromethyl is tolerated on the pyrazole directing groups.H owever, steric substituent effects have am arked influence which is evidencedb yc alculations.D FT modelling suggested also ap reviously unseen outer-sphereo xidative addition of N-fluorobenzenesulfonimide (NFSI) to Pd(II) as an alternative mechanism to the commonly assumed Pd(II)/Pd(IV)p rocess.T his unprecedented proposal, which is supported by the mass spectrometry identification of ak ey Pd(II) monomer under the stoichiometric conditions deserves more attention. Thei nfluence of elaborateh ighly substituted directing groups on the course of Pd-catalysed fluorination has generally received limited attentiona lthough this questionh as ac rucial synthetic utility;h erein, appropriate conditions for isolating pure productsare reported.