Organocatalytic stereoselective C–H diazenylation of active methylenes with arenediazonium salts

Abstract

Herein, we report the unveiling of the first organocatalytic sp3 C–H diazenylation of active methylenes with arenediazonium salts under ambient conditions, affording diverse hydrazones. The reaction features mild and additive-free conditions, excellent regio- and chemoselectivity, the use of readily available substrates with a broad scope, and excellent yields up to 99%. In addition, with ethyl 4,4,4-trifluoroacetoacetate as active methylene, exclusively Z-selective hydrazones were isolated. Moreover, the green chemistry metrics calculated for the reaction, such as the atom economy, E-factor, TON, and TOF, are promising. In contrast to the classical Japp–Klingemann reaction, no removal of any molecular fragment was observed. Application to the synthesis of valuable targets was also carried out. Mechanistic experiments revealed a polar pathway for the reaction. Furthermore, the role of intramolecular H-bonding was found to be crucial not only in stabilizing the reaction product but also in determining the observed Z-stereoselectivity. Such a substituent-switched H-bonding-driven induction of stereoselectivity, which affords stereoselective trifluoroacetyl-substituted Z-hydrazones, is remarkable and unprecedented in aminocatalysis.