Anionic Amino-Cope Rearrangement Cascade Synthesis of 2,4-Substituted Benzoate Esters from Acyclic Building Blocks

M. Haziq Qureshi; Jon T. Njardarson

doi:10.1021/acs.orglett.2c03134

Anionic Amino-Cope Rearrangement Cascade Synthesis of 2,4-Substituted Benzoate Esters from Acyclic Building Blocks

M. Haziq Qureshi
, Jon T. Njardarson

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

3 Scopus citations

Abstract

We report a new anionic cascade for assembling 2,4-substituted benzoate esters in one pot from racemic β-fluoro-substituted conjugated tert-butylsulfinyl imines and 3-substituted methyl 2-butenoates. Dienolate formation triggers a Mannich addition followed by an amino-Cope like rearrangement, which results in immediate elimination of fluoride by a lithiated enamine. The newly formed 1,4-diene intermediate contains a highly acidic proton which is spontaneously deprotonated, leading to a facile intramolecular cyclization followed by sulfinamide group elimination and aromatization.

Original language	English (US)
Pages (from-to)	7978-7982
Number of pages	5
Journal	Organic Letters
Volume	24
Issue number	43
DOIs	https://doi.org/10.1021/acs.orglett.2c03134
State	Published - Nov 4 2022
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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10.1021/acs.orglett.2c03134

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title = "Anionic Amino-Cope Rearrangement Cascade Synthesis of 2,4-Substituted Benzoate Esters from Acyclic Building Blocks",

abstract = "We report a new anionic cascade for assembling 2,4-substituted benzoate esters in one pot from racemic β-fluoro-substituted conjugated tert-butylsulfinyl imines and 3-substituted methyl 2-butenoates. Dienolate formation triggers a Mannich addition followed by an amino-Cope like rearrangement, which results in immediate elimination of fluoride by a lithiated enamine. The newly formed 1,4-diene intermediate contains a highly acidic proton which is spontaneously deprotonated, leading to a facile intramolecular cyclization followed by sulfinamide group elimination and aromatization.",

author = "Qureshi, \{M. Haziq\} and Njardarson, \{Jon T.\}",

note = "Funding Information: We would like to thank the National Science Foundation (CHE-1855708 and CHE-2153657) for financial support of this research program and for supporting the purchase of an NMR spectrometer (MRI-grant CHE-1920234) and a single-crystal X-ray diffractometer (MRI-grant CHE-2117516). We are most grateful to Nicholas R. Lauta (Department of Chemistry and Biochemistry, University of Arizona) for the synthesis of the phenylthio-substituted nucleophile and to Dr. Vlad Kumirov (Department of Chemistry and Biochemistry, University of Arizona) with his assistance in determining the stereochemistry of the intermediate compounds in the cascade. Publisher Copyright: {\textcopyright} 2022 Authors. All rights reserved.",

year = "2022",

month = nov,

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doi = "10.1021/acs.orglett.2c03134",

language = "English (US)",

volume = "24",

pages = "7978--7982",

journal = "Organic Letters",

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publisher = "American Chemical Society",

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T1 - Anionic Amino-Cope Rearrangement Cascade Synthesis of 2,4-Substituted Benzoate Esters from Acyclic Building Blocks

AU - Qureshi, M. Haziq

AU - Njardarson, Jon T.

N1 - Funding Information: We would like to thank the National Science Foundation (CHE-1855708 and CHE-2153657) for financial support of this research program and for supporting the purchase of an NMR spectrometer (MRI-grant CHE-1920234) and a single-crystal X-ray diffractometer (MRI-grant CHE-2117516). We are most grateful to Nicholas R. Lauta (Department of Chemistry and Biochemistry, University of Arizona) for the synthesis of the phenylthio-substituted nucleophile and to Dr. Vlad Kumirov (Department of Chemistry and Biochemistry, University of Arizona) with his assistance in determining the stereochemistry of the intermediate compounds in the cascade. Publisher Copyright: © 2022 Authors. All rights reserved.

PY - 2022/11/4

Y1 - 2022/11/4

N2 - We report a new anionic cascade for assembling 2,4-substituted benzoate esters in one pot from racemic β-fluoro-substituted conjugated tert-butylsulfinyl imines and 3-substituted methyl 2-butenoates. Dienolate formation triggers a Mannich addition followed by an amino-Cope like rearrangement, which results in immediate elimination of fluoride by a lithiated enamine. The newly formed 1,4-diene intermediate contains a highly acidic proton which is spontaneously deprotonated, leading to a facile intramolecular cyclization followed by sulfinamide group elimination and aromatization.

AB - We report a new anionic cascade for assembling 2,4-substituted benzoate esters in one pot from racemic β-fluoro-substituted conjugated tert-butylsulfinyl imines and 3-substituted methyl 2-butenoates. Dienolate formation triggers a Mannich addition followed by an amino-Cope like rearrangement, which results in immediate elimination of fluoride by a lithiated enamine. The newly formed 1,4-diene intermediate contains a highly acidic proton which is spontaneously deprotonated, leading to a facile intramolecular cyclization followed by sulfinamide group elimination and aromatization.

UR - https://www.scopus.com/pages/publications/85140834278

UR - https://www.scopus.com/pages/publications/85140834278#tab=citedBy

U2 - 10.1021/acs.orglett.2c03134

DO - 10.1021/acs.orglett.2c03134

M3 - Article

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AN - SCOPUS:85140834278

SN - 1523-7060

VL - 24

SP - 7978

EP - 7982

JO - Organic Letters

JF - Organic Letters

IS - 43

ER -

Anionic Amino-Cope Rearrangement Cascade Synthesis of 2,4-Substituted Benzoate Esters from Acyclic Building Blocks

Abstract

ASJC Scopus subject areas

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