Design and application of intramolecular arylogous nitroaldol condensation to access 2-aryl-benzofuran and -indole derivatives and formal synthesis of saprisartan

Abstract

This study presents the design and application of intramolecular arylogous nitroaldol (Henry) condensation. A transition metal-free, base-mediated reaction of ortho-heteroatom-substituted aryl aldehydes/ketones and 2-nitrobenzyl (pseudo)halides has been developed to access a wide range of 2-(2-nitroaryl)benzofuran/2-(2-nitroaryl)indole derivatives in high yields. The reaction appears to proceed through O-/N-benzylation and intramolecular arylogous nitroaldol condensation. The application potential of the presented strategy has been demonstrated in the formal synthesis of anti-hypertensive agent saprisartan through the efficient synthesis of an advanced key intermediate, which has been accomplished in a ten-fold high overall yield by using resourceful, inexpensive and less-toxic reagents compared to the known methods.