tert-BuONO-Promoted Nitrosation of 4-Nitroisoxazole-Based Enamines: Synthesis of 5-Cyanoisoxazoles and Their Application

An efficient approach to previously unknown 5-cyano-4-nitroisoxazoles has been developed using nitrosation of 4-nitroisoxazole-based enamines with tert-butyl nitrite (TBN) followed by a BF3- or TFAA-mediated unusual C═C bond cleavage reaction. This two-step one-pot process is applicable to a broad range of substrates and provides the desired products in mild reaction conditions in moderate to high yields. The dichotomy of reactivity in the SNAr reaction of the resulting 5-cyano-4-nitroisoxazoles has been demonstrated by the cyano-group substitution with N-nucleophiles and the nitro-group substitution with thiophenols and rationalized with DFT-calculations.