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Enantioselective C2‐Alkylation of Indoles through a Redox‐Relay Heck Reaction of 2‐Indole Triflates
Author(s) -
Race Nicholas J.,
Yuan Qianjia,
Sigman Matthew S.
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201805416
Subject(s) - indole test , enantioselective synthesis , stereocenter , combinatorial chemistry , chemistry , oxazoline , alkylation , heck reaction , redox , hydride , organic chemistry , palladium , catalysis , hydrogen
A palladium‐catalyzed enantioselective redox‐relay Heck reaction of 2‐indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine‐oxazoline ligand. Tuning the electronics of the indole, through judicious choice of N‐protecting group, is required to ensure selective β‐hydride elimination away from the indole core. Utility of this method is highlighted in a modular formal synthesis of an S1P 1 agonist precursor developed by Merck.