posted on 2023-11-16, 12:05authored byPankaj Gupta, Surabhi Panday, Amitava Hazra, Joydev K. Laha
A novel intramolecular direct amidation
of unactivated esters with
nitroarenes under a mild, practical, and scalable synthetic protocol
is the subject of this present investigation. The method uses a green,
environmentally friendly, inexpensive, and readily available single-electron
reductant, sodium dithionite (Na2S2O4), as the sole reagent under metal-free, additive-free, mild reaction
conditions. Various nitroarenes containing ortho-ester
functionalities are subjected to tandem chemoselective reductive cyclization/amidation
to deliver high-value azaheterocycles in excellent yields. Notably,
the present method enables the rapid construction of pharmaceutically
relevant azaheterocycles from readily accessible ortho-functionalized nitroarenes. Furthermore, gram-scale synthesis of
several key starting materials and pharmaceuticals demonstrates the
practical utility of the developed protocol.