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Synthesis of Enantiopure ( S )‐Indolylglycine by Organocatalyzed Friedel–Crafts Alkylation of Indole
Author(s) -
Wanner Martin J.,
Hauwert Peter,
Schoemaker Hans E.,
de Gelder René,
van Maarseveen Jan H.,
Hiemstra Henk
Publication year - 2008
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200700886
Subject(s) - chemistry , enantiopure drug , friedel–crafts reaction , indole test , phosphoric acid , alkylation , yield (engineering) , organic chemistry , carbon atom , medicinal chemistry , catalysis , enantioselective synthesis , alkyl , materials science , metallurgy
Tritylsulfenyl‐ and 2‐nitrophenylsulfenyl‐substituted glyoxyl imines were used in chiral phosphoric acid catalyzedFriedel–Crafts (FC) reactions with indole. High yields and ee values ranging from 86 % for Nps‐protected ( S )‐indolylglycine to 88 % for Trs‐protected ( R )‐indolylglycine were obtained. On a preparative scale, a FC product with 99.5 % ee and 71 % yield was readily obtained by crystallization of the reaction mixture. Removal of the Nps protecting group under mild acidic conditions did not affect the stereochemical integrity of the α‐carbon atom and ( S )‐indolylglycine was afforded in ≥98 % ee .(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)