Structure Ligation Relationship of Amino Acids for the Selective Indole C−H Arylation Reaction: L‐Aspartic acid as Sustainable Alternative of Phosphine Ligands
Shyam Kumar Lokhande, Gargi Nikhil Vaidya, Dinesh Parshuram Satpute, Ashwini Venkatesh, Sanjeev Kumar, Dinesh Kumar
Abstract
Abstract The S tructure L igation R elationship (SLR) of free amino acids (AAs) under Pd‐catalysis were examined for the chemo‐ and regio‐selective indole C−H arylation reactions. While the majority of AAs were minor or ineffective, the L‐aspartic acid (L‐Asp) stands out promising to deliver high‐value C3‐arylated indoles with excellent chemo‐ (C vs N) and regioselectivity (C3 vs C2) with high functional group tolerance. Thus, the protocol offers a cost‐effective and sustainable alternative of phosphine‐based ligands for the indole C3−H arylation reactions. Preliminary mechanistic investigations suggested the simultaneous involvement of −NH 2 , α‐CO 2 H, and β‐CO 2 H functionalities of L‐Asp and found critical for its ligation efficiency. The developed catalytic system was compatible with the tandem decarboxylation/arylation procedure for the chemoselective synthesis of 3‐aryl indoles. magnified image