Organocatalytic stereoselective C-H diazenylation of active methylenes with arenediazonium salts.

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.