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Structure Ligation Relationship of Amino Acids for the Selective Indole C−H Arylation Reaction: L‐Aspartic acid as Sustainable Alternative of Phosphine Ligands
Author(s) -
Lokhande† Shyam Kumar,
Vaidya† Gargi Nikhil,
Satpute Dinesh Parshuram,
Venkatesh Ashwini,
Kumar Sanjeev,
Kumar Dinesh
Publication year - 2020
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.202000426
Subject(s) - chemistry , indole test , decarboxylation , regioselectivity , phosphine , tandem , amino acid , catalysis , combinatorial chemistry , aryl , aspartic acid , medicinal chemistry , stereochemistry , organic chemistry , biochemistry , alkyl , composite material , materials science
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.