Iodine‐DMSO‐Catalyzed Chemoselective Biomimetic Aromatization of Tetrahydro‐β‐carbolines‐3‐carboxylic Acid: Mechanism Study with DFT‐Calculation

A new protocol for the chemoselective aromatization of tetrahydro‐β‐carboline‐3‐carboxylic acids to direct biomimetic one step synthesis of β‐carboline‐3‐carboxylic acids 2 A‐L using catalytic amount of I2 in DMSO/H+ produces very good yield. This method was also successfully extended for the aromatization of tetrahydro‐β‐carboline‐3‐methyl esters 5 A‐G as well as one‐step synthesis of Marinacarbolines‐D analog, respectively. Further, the mechanism and role of iodine–DMSO in aromatization has been studied by Density Functional Theory Calculation. This paper described a unique I2‐DMSO catalyzed chemoselective aromatization of easily accessible THβC‐carboxylic acids for the synthesis of β‐carboline‐3‐carboxylic acid. The use of DMSO, I2 is as a HI source and greener solvent. Further, this method can be extended for the aromatization of tetrahydro‐β‐carboline methyl esters and novel hybrid β‐carboline derivatives with excellent yield. The mechanism was supported by DFT calculations.