Pd-Catalyzed Reductive Cyclization Strategies for the Construction of N–N Bonds

Pd-catalyzed reductive cyclization of nitroarenes using carbon monoxide as the reductant has proven to be a versatile tool for the construction of C–N bonds in a variety of heterocycles [1], including indoles [2], carbazoles [3], quinolones [4], oxazines [5] and phenazines [6]. This strategy was now applied to N–N bond formation, targeting 2H-indazoles and 5,6-dihydroindazolo[3,2-a]isoquinolines. A few previous syntheses of 2H-indazoles from o-alkyliminonitroarenes also employed CO but required high Pd or Rh loadings and stoichiometric additives such as SnCl₂. Using Pd/phenanthroline complexes to catalyze the reductive cyclization reaction, N–alkyl 2H-indazoles were accessed under milder conditions. A one-pot protocol from o-nitrobenzaldehyde and primary amines was also investigated, enabling in situ imine formation and cyclization. The methodology was extended to the synthesis of 5,6-dihydroindazolo[3,2- a]isoquinolines from 1-(2-nitrophenyl)-3,4-dihydroisoquinoline using a CO surrogate instead of pressurized CO. Phenyl formate was found to be the best surrogate, affording the product in up to 99% isolated yield with broad substrate scope.