Microwave‐Assisted Chemo‐ and Regioselective Synthesis of <i>N</i> ‐arylindoles over Carbazoles Under Phosphine‐Free Conditions

Abstract An efficient method has been devised for selective synthesis of diverse N ‐arylindoles in good to excellent yields (up to 98%) relying on carbopalladation‐cyclization reactions of 2‐halo‐ N ‐arylanilines with alkynes. Compared to conventional heating, microwave assistance significantly reduces the reaction time under phosphine ligand‐free conditions and rules out the competing intramolecular C─H arylation generating carbazole as the side product in the presence of a chloride additive in dry DMF. Reactions exhibit excellent chemoselectivity for C─I bond over other carbon–halogen bonds, and moderate to good C2/C3 regioselectivity with unsymmetrical internal alkynes favoring N ‐arylindoles with substituent bearing the electron‐rich C sp atom of the alkyne at C2 position. A variety of diaryl‐, dialkyl‐, and arylalkylacetylenes having different steric and electronic features reacted smoothly with various 2‐iodo‐ N ‐arylanilines, whereas highly electron‐poor alkynes failed to produce the corresponding N ‐phenylindole under conventional heating conditions. DFT studies revealed that reaction under microwave assistance follows a kinetically controlled path leading to N ‐phenylindole over carbazole. Mulliken charge distribution at the acetylenic carbons and energy difference between the two possible isomeric transition states involved at the carbopalladation‐cyclization steps control the C2/C3 regioselectivity. Utilization of microwave as an efficient green energy source enabled rapid access to forty‐four N ‐arylindoles under mild conditions.