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 % iron(II) acetate and 3 mol % 4,7-dimethoxyphenanthroline as the ligand. The scope of the reaction is broad and tolerates 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; 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 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 is hydride transfer from iron to the coordinated nitroarene, which occurs through an ordered transition state with little Fe–H bond breaking.