An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: generality, applications and mechanistic investigations

Edward Richmond; Kenneth Bruce Ling; Nicolas Fabien Denis Duguet; Lois B. Manton; Nihan Çelebi-Ölçüm; Yu-hong Lam; Sezen Alsancak; Alexandra Martha Zoya Slawin; K. N. Houk; Andrew David Smith

doi:10.1039/c4ob02526a

An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: generality, applications and mechanistic investigations

Edward Richmond
, Kenneth Bruce Ling
, Nicolas Fabien Denis Duguet
, Lois B. Manton
, Nihan Çelebi-Ölçüm
, Yu-hong Lam
, Sezen Alsancak
, Alexandra Martha Zoya Slawin
, K. N. Houk
, Andrew David Smith

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

Abstract

The reaction of L-serine derived N-arylnitrones with alkylarylketenes generates asymmetric 3-alkyl-3-aryloxindoles in good to excellent yields (up to 93%) and excellent enantioselectivity (up to 98% ee) via a pericyclic cascade process. The optimization, scope and applications of this transformation are reported, alongside further synthetic and computational investigations. The preparation of the enantiomer of a Roche anti-cancer agent (RO4999200) 1 (96% ee) in three steps demonstrates the potential utility of this methodology.

Original language	English
Pages (from-to)	1807-1817
Number of pages	11
Journal	Organic & Biomolecular Chemistry
Volume	13
Issue number	6
Early online date	12 Dec 2014
DOIs	https://doi.org/10.1039/c4ob02526a
Publication status	Published - 14 Feb 2015

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Amino acids
Anti-cancer agents
Cascade process
Computational investigation
L-serine
Potential utility

Access to Document

10.1039/c4ob02526a

OxindolepericycliccascadeADS_Final_06_11_2014
© The Royal Society of Chemistry 2014. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at http://pubs.rsc.org/en/Content/ArticleLanding/2015/OB/C4OB02526A#!divAbstract
Accepted author manuscript, 3.68 MB

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Structuring the Future: Structuring the Future - Underpinning world-leading science in EaStCHEM through cutting edge characterisation
Woollins, J. D. (PI), Ashbrook, S. E. (CoI), Morris, R. (CoI) & Slawin, A. (CoI)
EPSRC
1/01/13 → 31/03/13
Project: Standard
N-Heterocyclic Carbenes as Asymmetric: N-Heterocyclic Carbenes as Asymmetric Organocatalysts: Reaction Development
Smith, A. (PI)
EPSRC
1/04/07 → 30/09/10
Project: Standard

An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: generality, applications and mechanistic investigations (dataset)
Richmond, E. (Creator), Ling, K. B. (Creator), Duguet, N. F. D. (Creator), Manton, L. B. (Creator), Çelebi-Ölçüm, N. (Creator), Lam, Y.-H. (Creator), Alsancak, S. (Creator), Slawin, A. M. Z. (Creator), Houk, K. N. (Creator) & Smith, A. D. (Creator), Cambridge Crystallographic Data Centre, 2014
https://dx.doi.org/10.5517/cc13jsp3 and 2 more links, https://dx.doi.org/10.5517/cc13jsq4, https://dx.doi.org/10.5517/cc13jsr5 (show fewer)
Dataset

Cite this

Richmond, E., Ling, K. B., Duguet, N. F. D., Manton, L. B., Çelebi-Ölçüm, N., Lam, Y., Alsancak, S., Slawin, A. M. Z., Houk, K. N., & Smith, A. D. (2015). An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: generality, applications and mechanistic investigations. Organic & Biomolecular Chemistry, 13(6), 1807-1817. https://doi.org/10.1039/c4ob02526a

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title = "An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: generality, applications and mechanistic investigations",

abstract = "The reaction of L-serine derived N-arylnitrones with alkylarylketenes generates asymmetric 3-alkyl-3-aryloxindoles in good to excellent yields (up to 93\%) and excellent enantioselectivity (up to 98\% ee) via a pericyclic cascade process. The optimization, scope and applications of this transformation are reported, alongside further synthetic and computational investigations. The preparation of the enantiomer of a Roche anti-cancer agent (RO4999200) 1 (96\% ee) in three steps demonstrates the potential utility of this methodology.",

keywords = "Amino acids, Anti-cancer agents, Cascade process, Computational investigation, L-serine, Potential utility",

author = "Edward Richmond and Ling, \{Kenneth Bruce\} and Duguet, \{Nicolas Fabien Denis\} and Manton, \{Lois B.\} and Nihan {\c C}elebi-{\"O}l{\c c}{\"u}m and Yu-hong Lam and Sezen Alsancak and Slawin, \{Alexandra Martha Zoya\} and Houk, \{K. N.\} and Smith, \{Andrew David\}",

note = "The authors thank the Royal Society for a URF (ADS), Cancer Research UK (ER), the Leverhulme Trust (ND) and EPSRC (KBL) for funding. We are also grateful to the National Science Foundation (USA) for financial support of the research at UCLA (KNH).",

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doi = "10.1039/c4ob02526a",

language = "English",

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AU - Richmond, Edward

AU - Ling, Kenneth Bruce

AU - Duguet, Nicolas Fabien Denis

AU - Manton, Lois B.

AU - Çelebi-Ölçüm, Nihan

AU - Lam, Yu-hong

AU - Alsancak, Sezen

AU - Slawin, Alexandra Martha Zoya

AU - Houk, K. N.

AU - Smith, Andrew David

N1 - The authors thank the Royal Society for a URF (ADS), Cancer Research UK (ER), the Leverhulme Trust (ND) and EPSRC (KBL) for funding. We are also grateful to the National Science Foundation (USA) for financial support of the research at UCLA (KNH).

PY - 2015/2/14

Y1 - 2015/2/14

N2 - The reaction of L-serine derived N-arylnitrones with alkylarylketenes generates asymmetric 3-alkyl-3-aryloxindoles in good to excellent yields (up to 93%) and excellent enantioselectivity (up to 98% ee) via a pericyclic cascade process. The optimization, scope and applications of this transformation are reported, alongside further synthetic and computational investigations. The preparation of the enantiomer of a Roche anti-cancer agent (RO4999200) 1 (96% ee) in three steps demonstrates the potential utility of this methodology.

AB - The reaction of L-serine derived N-arylnitrones with alkylarylketenes generates asymmetric 3-alkyl-3-aryloxindoles in good to excellent yields (up to 93%) and excellent enantioselectivity (up to 98% ee) via a pericyclic cascade process. The optimization, scope and applications of this transformation are reported, alongside further synthetic and computational investigations. The preparation of the enantiomer of a Roche anti-cancer agent (RO4999200) 1 (96% ee) in three steps demonstrates the potential utility of this methodology.

KW - Amino acids

KW - Anti-cancer agents

KW - Cascade process

KW - Computational investigation

KW - L-serine

KW - Potential utility

U2 - 10.1039/c4ob02526a

DO - 10.1039/c4ob02526a

M3 - Article

C2 - 25501712

SN - 1477-0520

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SP - 1807

EP - 1817

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

IS - 6

ER -

An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: generality, applications and mechanistic investigations

Abstract

UN SDGs

Keywords

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Projects

Structuring the Future: Structuring the Future - Underpinning world-leading science in EaStCHEM through cutting edge characterisation

N-Heterocyclic Carbenes as Asymmetric: N-Heterocyclic Carbenes as Asymmetric Organocatalysts: Reaction Development

Datasets

An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: generality, applications and mechanistic investigations (dataset)

Cite this