Unprecedented Tandem Cyclization on Perlin Aldehyde Towards Stereoselective Synthesis of 1,3-Difunctionalized 2-Deoxy Diindolyl-C-Glycosides

The stereoselective synthesis of 1,3-difunctionalized deoxy sugars remains a synthetic challenge in organic chemistry, despite of significant advancements in modern synthetic methodologies. Herein, we discovered a mild, efficient, highly regio- and stereoselective, transition-metal-free method for the synthesis of 1,3-difunctionalized deoxy sugars using a tandem cyclization reaction between various Perlin aldehydes and a diverse range of indole derivatives, catalyzed by a catalytic amount of indium trichloride within 1-2 hours. This transformation proceeds under mild reaction conditions despite dense carbohydrate functionality, enabling the regio- and stereoselective synthesis of a wide range of intricate 1,3-functionalized 2-deoxy diindolyl-C-glycosides in excellent yield, paving the way for further exploration of their applications in medicinal chemistry and chemical biology. Concurrently, to rationalize the observed regio- and stereoselectivity of these synthetically challenging molecular scaffolds, we also explored the mechanistic details for this transformation by using DFT studies.