Origins of the Reactivity in 1,3-Dipolar Cycloadditions of Acyl Isocyanide Ylides

Javier E. Alfonso-Ramos; Ruben Van Lommel; David Hernandez-Castillo; Frank De Proft; Roy Gonzalez-Aleman; Erik V. Van der Eycken; Gerardo M. Ojeda-Carralero

doi:10.1002/ejoc.202201028

Origins of the Reactivity in 1,3-Dipolar Cycloadditions of Acyl Isocyanide Ylides

Javier E. Alfonso-Ramos, Ruben Van Lommel, David Hernandez-Castillo, Frank De Proft, Roy Gonzalez-Aleman, Erik V. Van der Eycken, Gerardo M. Ojeda-Carralero

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

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Abstract

1,3-Dipolar cycloadditions are the preferred method to generate five-membered heterocyclic rings. Surprisingly, cycloadditions based on acyl-isocyanide ylides have remained underexplored by the chemical community. Acyl-isocyanide ylides readily react with dipolarophiles, such as substituted alkenes, to yield Δ¹-pyrroline derivatives. As an explanation for the observed reactivity of this reaction is lacking, extensive density functional theory calculations were performed to scrutinize the mechanistic features of the transformation. Herein we explain the experimental outcome of the reaction using a variety of reactivity theories and predict opposed regioselectivity for electron-poor and electron-rich dipolarophiles. With the insights obtained, we hope to incentivize the design of new cycloaddition reactions based on the acyl-isocyanide ylides motif.

Original language	English
Article number	e202201028
Number of pages	8
Journal	European Journal of Organic Chemistry
Volume	26
Issue number	3
DOIs	https://doi.org/10.1002/ejoc.202201028
Publication status	Published - 17 Jan 2023

Bibliographical note

Funding Information:
G.M.O.C. is grateful to VLIR-UOS for financial support of a Flemish-Cuba cooperation project (CU2018TEA458A101, recipient G.M.O.C., management, conceptualization and writing). J.E.A.R., D.H.C. and R.G.A. acknowledge the support of the International Fund and Project Management Office from the Ministry of Science, Technology and Environment, Republic of Cuba (project PN223LH010-02X, recipient J.E.A.R., experiments, data analysis and writing, and D.H.C. and R.G.A., revision of manuscript and technical support). R.V.L. acknowledges the use of Tier2 computational resources and services provided by the Shared ICT Services Centre funded by the Vrije Universiteit Brussel, the Flemish Supercomputer Center (VSC), and FWO. R.V.L. thanks FWO for the Ph.D. fellowships received (1185221 N, recipient R.V.L., experiments, writing, data analysis and visualization). E.V.V.d.E. is thankful to “RUDN University Strategic Academic Leadership Program” for financial support. The publication has been prepared with the support of the «RUDN University Strategic Academic Leadership Program» (recipient EVdE, supervision and writing). F.D.P. wishes to acknowledge the Vrije Universiteit Brussel for the support through a Strategic Research Program (supervision and revision of manuscript).

Publisher Copyright:
© 2022 Wiley-VCH GmbH.

Copyright:
Copyright 2023 Elsevier B.V., All rights reserved.

Keywords

1
3-dipolar cycloaddition
acyl isocyanide ylides
density functional theory
regioselectivity

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10.1002/ejoc.202201028

Paper_acceptedAccepted author manuscript, 1.18 MBLicence: Unspecified

Cite this

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title = "Origins of the Reactivity in 1,3-Dipolar Cycloadditions of Acyl Isocyanide Ylides",

abstract = "1,3-Dipolar cycloadditions are the preferred method to generate five-membered heterocyclic rings. Surprisingly, cycloadditions based on acyl-isocyanide ylides have remained underexplored by the chemical community. Acyl-isocyanide ylides readily react with dipolarophiles, such as substituted alkenes, to yield Δ1-pyrroline derivatives. As an explanation for the observed reactivity of this reaction is lacking, extensive density functional theory calculations were performed to scrutinize the mechanistic features of the transformation. Herein we explain the experimental outcome of the reaction using a variety of reactivity theories and predict opposed regioselectivity for electron-poor and electron-rich dipolarophiles. With the insights obtained, we hope to incentivize the design of new cycloaddition reactions based on the acyl-isocyanide ylides motif.",

keywords = "1, 3-dipolar cycloaddition, acyl isocyanide ylides, density functional theory, regioselectivity",

author = "Alfonso-Ramos, {Javier E.} and {Van Lommel}, Ruben and David Hernandez-Castillo and {De Proft}, Frank and Roy Gonzalez-Aleman and {Van der Eycken}, {Erik V.} and Ojeda-Carralero, {Gerardo M.}",

note = "Funding Information: G.M.O.C. is grateful to VLIR-UOS for financial support of a Flemish-Cuba cooperation project (CU2018TEA458A101, recipient G.M.O.C., management, conceptualization and writing). J.E.A.R., D.H.C. and R.G.A. acknowledge the support of the International Fund and Project Management Office from the Ministry of Science, Technology and Environment, Republic of Cuba (project PN223LH010-02X, recipient J.E.A.R., experiments, data analysis and writing, and D.H.C. and R.G.A., revision of manuscript and technical support). R.V.L. acknowledges the use of Tier2 computational resources and services provided by the Shared ICT Services Centre funded by the Vrije Universiteit Brussel, the Flemish Supercomputer Center (VSC), and FWO. R.V.L. thanks FWO for the Ph.D. fellowships received (1185221 N, recipient R.V.L., experiments, writing, data analysis and visualization). E.V.V.d.E. is thankful to “RUDN University Strategic Academic Leadership Program” for financial support. The publication has been prepared with the support of the «RUDN University Strategic Academic Leadership Program» (recipient EVdE, supervision and writing). F.D.P. wishes to acknowledge the Vrije Universiteit Brussel for the support through a Strategic Research Program (supervision and revision of manuscript). Publisher Copyright: {\textcopyright} 2022 Wiley-VCH GmbH. Copyright: Copyright 2023 Elsevier B.V., All rights reserved.",

year = "2023",

month = jan,

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doi = "10.1002/ejoc.202201028",

language = "English",

volume = "26",

journal = "Eur. J. Org. Chem.",

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Origins of the Reactivity in 1,3-Dipolar Cycloadditions of Acyl Isocyanide Ylides. / Alfonso-Ramos, Javier E.; Van Lommel, Ruben; Hernandez-Castillo, David; De Proft, Frank; Gonzalez-Aleman, Roy; Van der Eycken, Erik V.; Ojeda-Carralero, Gerardo M.

In: European Journal of Organic Chemistry, Vol. 26, No. 3, e202201028, 17.01.2023.

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

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AU - Van Lommel, Ruben

AU - Hernandez-Castillo, David

AU - De Proft, Frank

AU - Gonzalez-Aleman, Roy

AU - Van der Eycken, Erik V.

AU - Ojeda-Carralero, Gerardo M.

N1 - Funding Information: G.M.O.C. is grateful to VLIR-UOS for financial support of a Flemish-Cuba cooperation project (CU2018TEA458A101, recipient G.M.O.C., management, conceptualization and writing). J.E.A.R., D.H.C. and R.G.A. acknowledge the support of the International Fund and Project Management Office from the Ministry of Science, Technology and Environment, Republic of Cuba (project PN223LH010-02X, recipient J.E.A.R., experiments, data analysis and writing, and D.H.C. and R.G.A., revision of manuscript and technical support). R.V.L. acknowledges the use of Tier2 computational resources and services provided by the Shared ICT Services Centre funded by the Vrije Universiteit Brussel, the Flemish Supercomputer Center (VSC), and FWO. R.V.L. thanks FWO for the Ph.D. fellowships received (1185221 N, recipient R.V.L., experiments, writing, data analysis and visualization). E.V.V.d.E. is thankful to “RUDN University Strategic Academic Leadership Program” for financial support. The publication has been prepared with the support of the «RUDN University Strategic Academic Leadership Program» (recipient EVdE, supervision and writing). F.D.P. wishes to acknowledge the Vrije Universiteit Brussel for the support through a Strategic Research Program (supervision and revision of manuscript). Publisher Copyright: © 2022 Wiley-VCH GmbH. Copyright: Copyright 2023 Elsevier B.V., All rights reserved.

PY - 2023/1/17

Y1 - 2023/1/17

N2 - 1,3-Dipolar cycloadditions are the preferred method to generate five-membered heterocyclic rings. Surprisingly, cycloadditions based on acyl-isocyanide ylides have remained underexplored by the chemical community. Acyl-isocyanide ylides readily react with dipolarophiles, such as substituted alkenes, to yield Δ1-pyrroline derivatives. As an explanation for the observed reactivity of this reaction is lacking, extensive density functional theory calculations were performed to scrutinize the mechanistic features of the transformation. Herein we explain the experimental outcome of the reaction using a variety of reactivity theories and predict opposed regioselectivity for electron-poor and electron-rich dipolarophiles. With the insights obtained, we hope to incentivize the design of new cycloaddition reactions based on the acyl-isocyanide ylides motif.

AB - 1,3-Dipolar cycloadditions are the preferred method to generate five-membered heterocyclic rings. Surprisingly, cycloadditions based on acyl-isocyanide ylides have remained underexplored by the chemical community. Acyl-isocyanide ylides readily react with dipolarophiles, such as substituted alkenes, to yield Δ1-pyrroline derivatives. As an explanation for the observed reactivity of this reaction is lacking, extensive density functional theory calculations were performed to scrutinize the mechanistic features of the transformation. Herein we explain the experimental outcome of the reaction using a variety of reactivity theories and predict opposed regioselectivity for electron-poor and electron-rich dipolarophiles. With the insights obtained, we hope to incentivize the design of new cycloaddition reactions based on the acyl-isocyanide ylides motif.

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KW - 3-dipolar cycloaddition

KW - acyl isocyanide ylides

KW - density functional theory

KW - regioselectivity

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DO - 10.1002/ejoc.202201028

M3 - Article

VL - 26

JO - Eur. J. Org. Chem.

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SN - 1434-193X

IS - 3

M1 - e202201028

ER -

Origins of the Reactivity in 1,3-Dipolar Cycloadditions of Acyl Isocyanide Ylides

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Keywords

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