Uncommon Phosphonylation of Pyrazine‐2,3‐dicarbonitrile Derivatives via C(sp²)−CN Bond Cleavage

Abstract A direct phosphonylation of the C(sp 2 )−CN bond under mild catalytic and non‐catalytic reaction conditions is disclosed. Pyrazine‐2,3‐dicarbonitriles are readily coupled with HPO(OEt) 2 to produce the corresponding dialkoxyphosphoryl‐substituted pyrazines. The phosphonylation reaction occurs in the presence of a base (Et 3 N, Cs 2 CO 3 ) as nucleophilic substitution of the CN groups. The yield of target diphosphonates depends on the nature of substituents in the 5,6‐positions of the pyrazine ring: it exceeds 90 % for di‐5,6‐aryl‐substituted pyrazines and is significantly lower when electron‐donating alkyl ( n ‐propyl) groups are attached to the 5,6‐positions. It should be noted that for pyrazine‐2,3‐dicarbonitriles bearing vicinal 4‐bromophenyl groups, the nucleophilic phosphonylation leading to C−CN/P−H coupling in the pyrazine ring is predominant over Pd‐catalyzed Hirao's C−Br/P−H coupling reaction in phenyl rings. Detailed structural characterization, both in solution by means of 1 H, 13 C and 31 P NMR spectroscopy and in the solid state by single crystal X‐ray diffraction, of a series of newly synthesized pyrazine phosphonates is reported.