Development and Mechanistic Study of an Iron-Catalyzed Intramolecular Nitroso Ene Reaction of Nitroarenes

An intramolecular iron-catalyzed nitroso ene reaction was developed to afford six- or seven-membered N-heterocycles from nitroarenes using an earth abundant iron catalyst and phenylsilane as the terminal reductant. The reaction can be triggered using as little as 3 mol % of iron(II) acetate and 3 mol % of 4,7-dimethoxyphenanthroline as the ligand. The scope of the reaction is broad tolerating a range of electron-releasing or electron-withdrawing substituents on the nitroarene, and the ortho-substituent can be modified to diastereoselectively construct benzoxazines, dihydrobenzothiazines, tetrahydroquinolines, tetrahydroquinoxalines, or tetrahydrobenzooxazepines. Mechanistic investigations indicated that the reaction proceeds via a nitrosoarene intermediate, and kinetic analysis of the reaction revealed a first-order rate dependence in catalyst-, nitroarene-, and silane concentration, and an inverse kinetic order in acetate was observed. The difference in rates between PhSiH3 and PhSiD3 was found to be 1.50 ± 0.09, and investigation of the temperature dependence of the reaction rate revealed that the activation parameters to be ΔH‡ = 13.5 kcal•mol-1 and ΔS‡ = -39.1 cal•mol-1•K-1. These data were interpreted to indicate that the turnover-limiting step to be hydride transfer from iron to the coordinated nitroarene, which occurs through an ordered transition state with little Fe-H bond breaking.