Stereospecific Intramolecular Arylation of 2- and 3-Pyridyl Substituted Alkylamines via Configurationally Stable α-Pyridyl Organolithiums

Julien Maury; Wojciech Zawodny; Jonathan Clayden

doi:10.1021/acs.orglett.6b03603

Stereospecific Intramolecular Arylation of 2- and 3-Pyridyl Substituted Alkylamines via Configurationally Stable α-Pyridyl Organolithiums

Julien Maury, Wojciech Zawodny, Jonathan Clayden^*

^*Corresponding author for this work

School of Chemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Treatment of N'-aryl urea derivatives of enantiomerically-enriched α-(2-pyridyl) and α-(3-pyridyl)alkylamines with base leads to the migration of the N'-aryl substituent from N to C in a 'non-classical' intramolecular nucleophilic aro-matic substitution reaction. Both electron-rich and electron-poor rings migrate successfully. A new quaternary stereo-genic centre is formed adjacent to the pyridine ring with high stereospecificity, even when the intermediate anion is a presumably planar 2-picolyllithium. Base hydrolysis of the urea gives enantiomerically enriched α-pyridylalkylamines.

Original language	English
Pages (from-to)	472-475
Number of pages	4
Journal	Organic Letters
Volume	19
Issue number	3
Early online date	18 Jan 2017
DOIs	https://doi.org/10.1021/acs.orglett.6b03603
Publication status	Published - 3 Feb 2017

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Organic & Biological

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10.1021/acs.orglett.6b03603

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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via ACS at http://pubs.acs.org/doi/abs/10.1021/acs.orglett.6b03603. Please refer to any applicable terms of use of the publisher.
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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via ACS at http://pubs.acs.org/doi/suppl/10.1021/acs.orglett.6b03603. Please refer to any applicable terms of use of the publisher.
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title = "Stereospecific Intramolecular Arylation of 2- and 3-Pyridyl Substituted Alkylamines via Configurationally Stable α-Pyridyl Organolithiums",

abstract = "Treatment of N'-aryl urea derivatives of enantiomerically-enriched α-(2-pyridyl) and α-(3-pyridyl)alkylamines with base leads to the migration of the N'-aryl substituent from N to C in a 'non-classical' intramolecular nucleophilic aro-matic substitution reaction. Both electron-rich and electron-poor rings migrate successfully. A new quaternary stereo-genic centre is formed adjacent to the pyridine ring with high stereospecificity, even when the intermediate anion is a presumably planar 2-picolyllithium. Base hydrolysis of the urea gives enantiomerically enriched α-pyridylalkylamines.",

author = "Julien Maury and Wojciech Zawodny and Jonathan Clayden",

year = "2017",

month = feb,

day = "3",

doi = "10.1021/acs.orglett.6b03603",

language = "English",

volume = "19",

pages = "472--475",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society",

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T1 - Stereospecific Intramolecular Arylation of 2- and 3-Pyridyl Substituted Alkylamines via Configurationally Stable α-Pyridyl Organolithiums

AU - Maury, Julien

AU - Zawodny, Wojciech

AU - Clayden, Jonathan

PY - 2017/2/3

Y1 - 2017/2/3

N2 - Treatment of N'-aryl urea derivatives of enantiomerically-enriched α-(2-pyridyl) and α-(3-pyridyl)alkylamines with base leads to the migration of the N'-aryl substituent from N to C in a 'non-classical' intramolecular nucleophilic aro-matic substitution reaction. Both electron-rich and electron-poor rings migrate successfully. A new quaternary stereo-genic centre is formed adjacent to the pyridine ring with high stereospecificity, even when the intermediate anion is a presumably planar 2-picolyllithium. Base hydrolysis of the urea gives enantiomerically enriched α-pyridylalkylamines.

AB - Treatment of N'-aryl urea derivatives of enantiomerically-enriched α-(2-pyridyl) and α-(3-pyridyl)alkylamines with base leads to the migration of the N'-aryl substituent from N to C in a 'non-classical' intramolecular nucleophilic aro-matic substitution reaction. Both electron-rich and electron-poor rings migrate successfully. A new quaternary stereo-genic centre is formed adjacent to the pyridine ring with high stereospecificity, even when the intermediate anion is a presumably planar 2-picolyllithium. Base hydrolysis of the urea gives enantiomerically enriched α-pyridylalkylamines.

UR - https://www.scopus.com/pages/publications/85011340347

U2 - 10.1021/acs.orglett.6b03603

DO - 10.1021/acs.orglett.6b03603

M3 - Article (Academic Journal)

C2 - 28099031

AN - SCOPUS:85011340347

SN - 1523-7060

VL - 19

SP - 472

EP - 475

JO - Organic Letters

JF - Organic Letters

IS - 3

ER -

Stereospecific Intramolecular Arylation of 2- and 3-Pyridyl Substituted Alkylamines via Configurationally Stable α-Pyridyl Organolithiums

Abstract

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alpha-Arylation and alpha-Vinylation of Enolates: New Reactivity from the Urea Linkage.

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Stereospecific Intramolecular Arylation of 2- and 3-Pyridyl Substituted Alkylamines via Configurationally Stable α-Pyridyl Organolithiums

Abstract

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alpha-Arylation and alpha-Vinylation of Enolates: New Reactivity from the Urea Linkage.

3-month Core Capability for Chemistry Research

Cite this