Activation/Cyclization of 2H‐Azirines and 3‐Amino‐2‐fluoropyridines Towards 2‐Aryl‐Pyrido[2,3‐b]pyrazines

The electrophilic activation of 2H‐azirines with triflic anhydride (Tf2O) for an addition/cyclization reaction producing 2‐aryl‐pyrido[2,3‐b]pyrazines regioselectively is described. This reaction proceeds via nucleophilic addition of 3‐amino‐2‐fluoropyridines onto 1‐trifloyl‐aziridin‐2‐yl triflates and subsequent cyclization via SNAr. Desulfonylation and oxidation provides a single regioisomer of the aza‐bicyclic heterocycle after treatment with Et3N. Optimization of the reaction conditions lead to a range of 2‐aryl‐pyrido[2,3‐b]pyrazines in isolated yields of 20 % to 60 %. A general method to prepare 2‐aryl‐pyrido[2,3‐b]pyrazines from 3‐amino‐2‐fluoropyridine is described. The method relies on 2H‐azirine electrophilic activation via a Tf2O/DTBMP combination. Variation of the pyridine substitution pattern along with 2H‐azirines provided single regioisomers of the bicyclic heterocycles