Enantioselective C2-Alkylation of Indoles through a Redox-Relay Heck Reaction of 2-Indole Triflates

Nicholas J. Race; Qianjia Yuan; Matthew S. Sigman

doi:10.1002/chem.201805416

Enantioselective C2-Alkylation of Indoles through a Redox-Relay Heck Reaction of 2-Indole Triflates

Nicholas J. Race, Qianjia Yuan, Matthew S. Sigman

Chemistry (Twin Cities)

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

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 S1P₁ agonist precursor developed by Merck.

Original language	English (US)
Pages (from-to)	512-515
Number of pages	4
Journal	Chemistry - A European Journal
Volume	25
Issue number	2
DOIs	https://doi.org/10.1002/chem.201805416
State	Published - Jan 7 2019

Bibliographical note

Funding Information:
The work was supported by National Institute of Health (NIGMS R01GM063540). Q.Y. acknowledges Shanghai Jiao Tong University for a postdoctoral fellowship.

Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

Heck reaction
asymmetric catalysis
enantioselective catalysis
indole
palladium

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10.1002/chem.201805416

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342193

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title = "Enantioselective C2-Alkylation of Indoles through a Redox-Relay Heck Reaction of 2-Indole Triflates",

abstract = "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 S1P1 agonist precursor developed by Merck.",

keywords = "Heck reaction, asymmetric catalysis, enantioselective catalysis, indole, palladium",

author = "Race, \{Nicholas J.\} and Qianjia Yuan and Sigman, \{Matthew S.\}",

note = "Funding Information: The work was supported by National Institute of Health (NIGMS R01GM063540). Q.Y. acknowledges Shanghai Jiao Tong University for a postdoctoral fellowship. Publisher Copyright: {\textcopyright} 2019 Wiley-VCH Verlag GmbH \& Co. KGaA, Weinheim",

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doi = "10.1002/chem.201805416",

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AU - Race, Nicholas J.

AU - Yuan, Qianjia

AU - Sigman, Matthew S.

N1 - Funding Information: The work was supported by National Institute of Health (NIGMS R01GM063540). Q.Y. acknowledges Shanghai Jiao Tong University for a postdoctoral fellowship. Publisher Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2019/1/7

Y1 - 2019/1/7

N2 - 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 S1P1 agonist precursor developed by Merck.

AB - 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 S1P1 agonist precursor developed by Merck.

KW - Heck reaction

KW - asymmetric catalysis

KW - enantioselective catalysis

KW - indole

KW - palladium

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U2 - 10.1002/chem.201805416

DO - 10.1002/chem.201805416

M3 - Article

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AN - SCOPUS:85058296586

SN - 0947-6539

VL - 25

SP - 512

EP - 515

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 2

ER -

Enantioselective C2-Alkylation of Indoles through a Redox-Relay Heck Reaction of 2-Indole Triflates

Abstract

Bibliographical note

Keywords

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