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Solvent‐Mediated C3/C7 Regioselective Switch in Chiral Phosphoric Acid‐Catalyzed Enantioselective Friedel‐Crafts Alkylation of Indoles with α‐Ketiminoesters
Author(s) -
Zhao Yunlong,
Cai Lu,
Huang Tongkun,
Meng Shanshui,
Chan Albert S. C.,
Zhao Junling
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.201901380
Subject(s) - regioselectivity , chemistry , stereocenter , enantioselective synthesis , alkylation , indole test , friedel–crafts reaction , catalysis , phosphoric acid , organic chemistry , organocatalysis , combinatorial chemistry
The first solvent‐mediated tunable C3/C7 regio‐ and enantioselective Friedel‐Crafts alkylation of 4‐aminoindoles with α‐ketimino esters has been developed. This catalysis allows the highly regioselective formation of indole C3 and C7 alkylation products, both in high yields (up to 96%) and excellent enantioselectivities (up to 99% ee). Mechanism study revealed that the hydrogen‐bonding interactions of the solvents with the catalyst played a vital role for the regioselectivity switch. Furthermore, the corresponding products are indole containing unnatural α‐amino acid derivatives bearing a quaternary stereocenter and enable many further elaborations.