Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene: Application in the Total Synthesis of 10‐Deoxymethynolide

Kristian J. Chambers; Patthadon Sanghong; Daniel carter Martos; Giorgia Casoni; Rory c. Mykura; Durga prasad Hari; Adam Noble; Varinder kumar Aggarwal

doi:10.1002/anie.202312054

Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene: Application in the Total Synthesis of 10‐Deoxymethynolide

Kristian J. Chambers, Patthadon Sanghong, Daniel carter Martos, Giorgia Casoni, Rory c. Mykura, Durga prasad Hari, Adam Noble, Varinder kumar Aggarwal

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

4 Citations (Scopus)

Abstract

Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three-carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated-methoxyallene, protonation triggers a stereospecific 1,2-migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2-migration and give a much broader range of α-functionalized enones. Finally, the methodology was applied to a 14-step synthesis of the enone-containing polyketide 10-deoxymethynolide.

Original language	English
Article number	e202312054
Journal	Angewandte Chemie - International Edition
Volume	62
Issue number	50
Early online date	25 Oct 2023
DOIs	https://doi.org/10.1002/anie.202312054
Publication status	E-pub ahead of print - 25 Oct 2023

Bibliographical note

Funding Information:
K. J. C. thanks EPSRC (EP/T517872/1) for support. R. C. M. thanks the Bristol Chemical Synthesis Centre for doctoral training funded by the EPSRC (EP/L015366/1) and AstraZeneca (Thomas G. Hayhow). P. S. thanks the Development and Promotion of Science and Technology Talent Project (DPST), Thailand for financial support. We thank Craig Butts (UoB) for helpful discussions.

Publisher Copyright:
© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

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Chambers, K. J., Sanghong, P., Martos, D. C., Casoni, G., Mykura, R. C., Hari, D. P., Noble, A., & Aggarwal, V. K. (2023). Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene: Application in the Total Synthesis of 10‐Deoxymethynolide. Angewandte Chemie - International Edition, 62(50), Article e202312054. Advance online publication. https://doi.org/10.1002/anie.202312054

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abstract = "Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three-carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated-methoxyallene, protonation triggers a stereospecific 1,2-migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2-migration and give a much broader range of α-functionalized enones. Finally, the methodology was applied to a 14-step synthesis of the enone-containing polyketide 10-deoxymethynolide.",

author = "Chambers, {Kristian J.} and Patthadon Sanghong and Martos, {Daniel carter} and Giorgia Casoni and Mykura, {Rory c.} and Hari, {Durga prasad} and Adam Noble and Aggarwal, {Varinder kumar}",

note = "Funding Information: K. J. C. thanks EPSRC (EP/T517872/1) for support. R. C. M. thanks the Bristol Chemical Synthesis Centre for doctoral training funded by the EPSRC (EP/L015366/1) and AstraZeneca (Thomas G. Hayhow). P. S. thanks the Development and Promotion of Science and Technology Talent Project (DPST), Thailand for financial support. We thank Craig Butts (UoB) for helpful discussions. Publisher Copyright: {\textcopyright} 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",

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Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene: Application in the Total Synthesis of 10‐Deoxymethynolide. / Chambers, Kristian J.; Sanghong, Patthadon; Martos, Daniel carter et al.
In: Angewandte Chemie - International Edition, Vol. 62, No. 50, e202312054, 25.10.2023.

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

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T1 - Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene: Application in the Total Synthesis of 10‐Deoxymethynolide

AU - Chambers, Kristian J.

AU - Sanghong, Patthadon

AU - Martos, Daniel carter

AU - Casoni, Giorgia

AU - Mykura, Rory c.

AU - Hari, Durga prasad

AU - Noble, Adam

AU - Aggarwal, Varinder kumar

N1 - Funding Information: K. J. C. thanks EPSRC (EP/T517872/1) for support. R. C. M. thanks the Bristol Chemical Synthesis Centre for doctoral training funded by the EPSRC (EP/L015366/1) and AstraZeneca (Thomas G. Hayhow). P. S. thanks the Development and Promotion of Science and Technology Talent Project (DPST), Thailand for financial support. We thank Craig Butts (UoB) for helpful discussions. Publisher Copyright: © 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

PY - 2023/10/25

Y1 - 2023/10/25

N2 - Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three-carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated-methoxyallene, protonation triggers a stereospecific 1,2-migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2-migration and give a much broader range of α-functionalized enones. Finally, the methodology was applied to a 14-step synthesis of the enone-containing polyketide 10-deoxymethynolide.

AB - Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three-carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated-methoxyallene, protonation triggers a stereospecific 1,2-migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2-migration and give a much broader range of α-functionalized enones. Finally, the methodology was applied to a 14-step synthesis of the enone-containing polyketide 10-deoxymethynolide.

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DO - 10.1002/anie.202312054

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