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.