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

Abstract

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 PhSiH 3 and PhSiD 3 was found to be 1.50 ± 0.09, and investigation of the temperature dependence of the reaction rate revealed the activation parameters to be Δ H ‡ = 13.5 kcal mol –1 and Δ S ‡ = −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.

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