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Controlling Regioselectivity in the Enantioselective N‐Alkylation of Indole Analogues Catalyzed by Dinuclear Zinc‐ProPhenol
Author(s) -
Trost Barry M.,
Gnanamani Elumalai,
Hung ChaoI Joey
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201705315
Subject(s) - regioselectivity , enantioselective synthesis , indole test , alkylation , zinc , catalysis , chemistry , combinatorial chemistry , stereochemistry , organic chemistry
The enantioselective N‐alkylation of indole and its derivatives with aldimines is efficiently catalyzed by a zinc‐ProPhenol dinuclear complex under mild conditions to afford N‐alkylated indole derivatives in good yield (up to 86 %) and excellent enantiomeric ratio (up to 99.5:0.5 e.r.). This method tolerates a wide array of indoles, as well as pyrrole and carbazole, to afford the corresponding N‐alkylation products. The reaction can be run on a gram scale with reduced catalyst loading without impacting the efficiency. The chiral aminals were further elaborated into various chiral polyheterocyclic derivatives. The surprising stability of the chiral N‐alkylation products will open new windows for asymmetric catalysis and medicinal chemistry.