Direct Sₙ2 or Sₙ2X manifold─mechanistic study of ion-pair-catalyzed carbon(sp³)-carbon(sp³) bond formation
Density functional theory (DFT) is used in this work to predict the mechanism for constructing congested quaternary-quaternary carbon(sp3)-carbon(sp3) bonds in a pentanidium-catalyzed substitution reaction. Computational mechanistic studies were carried out to investigate the proposed SN2X manifold,...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2023
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| Online Access: | https://hdl.handle.net/10356/164028 |
| _version_ | 1811689497025314816 |
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| author | Lee, Richmond Chao, Chi Bong Eric Ban, Xu Tan, Siu Min Yu, Haibo Hyland, Christopher J. T. Tan, Choon-Hong |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Lee, Richmond Chao, Chi Bong Eric Ban, Xu Tan, Siu Min Yu, Haibo Hyland, Christopher J. T. Tan, Choon-Hong |
| author_sort | Lee, Richmond |
| collection | NTU |
| description | Density functional theory (DFT) is used in this work to predict the mechanism for constructing congested quaternary-quaternary carbon(sp3)-carbon(sp3) bonds in a pentanidium-catalyzed substitution reaction. Computational mechanistic studies were carried out to investigate the proposed SN2X manifold, which consists of two primary elementary steps: halogen atom transfer (XAT) and subsequent SN2. For the first calculated model on original experimental substrates, XAT reaction barriers were more kinetically competitive than an SN2 pathway and connect to thermodynamically stable intermediates. Extensive computational screening modeling was then done on various substrate combinations designed to study the steric influence and to understand the mechanistic rationale, and calculations reveal that sterically congested substrates prefer the SN2X manifold over SN2. Different halides as leaving groups were also screened, and it was found that the reactivity increases in the order of I > Br > Cl > F, in agreement with the strength of C-X bonds. However, DFT modeling suggests that chlorides can be a viable substrate for the SN2X process, which should be further explored experimentally. ONIOM calculations on the full catalyst model predicted the correct stereochemical outcome, and further catalyst screening with cationic Me4N+ and K+ predicted that pentanidium is still the choice for SN2X C-C bond formation. |
| first_indexed | 2024-10-01T05:49:02Z |
| format | Journal Article |
| id | ntu-10356/164028 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:49:02Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1640282023-01-03T03:44:38Z Direct Sₙ2 or Sₙ2X manifold─mechanistic study of ion-pair-catalyzed carbon(sp³)-carbon(sp³) bond formation Lee, Richmond Chao, Chi Bong Eric Ban, Xu Tan, Siu Min Yu, Haibo Hyland, Christopher J. T. Tan, Choon-Hong School of Physical and Mathematical Sciences Science::Chemistry Leaving-Group Basis-Sets Density functional theory (DFT) is used in this work to predict the mechanism for constructing congested quaternary-quaternary carbon(sp3)-carbon(sp3) bonds in a pentanidium-catalyzed substitution reaction. Computational mechanistic studies were carried out to investigate the proposed SN2X manifold, which consists of two primary elementary steps: halogen atom transfer (XAT) and subsequent SN2. For the first calculated model on original experimental substrates, XAT reaction barriers were more kinetically competitive than an SN2 pathway and connect to thermodynamically stable intermediates. Extensive computational screening modeling was then done on various substrate combinations designed to study the steric influence and to understand the mechanistic rationale, and calculations reveal that sterically congested substrates prefer the SN2X manifold over SN2. Different halides as leaving groups were also screened, and it was found that the reactivity increases in the order of I > Br > Cl > F, in agreement with the strength of C-X bonds. However, DFT modeling suggests that chlorides can be a viable substrate for the SN2X process, which should be further explored experimentally. ONIOM calculations on the full catalyst model predicted the correct stereochemical outcome, and further catalyst screening with cationic Me4N+ and K+ predicted that pentanidium is still the choice for SN2X C-C bond formation. Ministry of Education (MOE) Nanyang Technological University We gratefully acknowledge financial support from the Australian Research Council (DE210100053, R.L.), UOW RITA Grant 2021 (H.Y. and R.L.), and a UOW Vice Chancellor's Research Fellowship (R.L.). We would also like to acknowledge Nanyang Technological University for Tier 1 grants (RG1/19 and RG2/20) and Ministry of Education (Singapore) Tier 2 grants (MOE2019-T2-1-091, C.H.T.). 2023-01-03T03:44:38Z 2023-01-03T03:44:38Z 2022 Journal Article Lee, R., Chao, C. B. E., Ban, X., Tan, S. M., Yu, H., Hyland, C. J. T. & Tan, C. (2022). Direct Sₙ2 or Sₙ2X manifold─mechanistic study of ion-pair-catalyzed carbon(sp³)-carbon(sp³) bond formation. Journal of Organic Chemistry, 87(6), 4029-4039. https://dx.doi.org/10.1021/acs.joc.1c02782 0022-3263 https://hdl.handle.net/10356/164028 10.1021/acs.joc.1c02782 35245425 2-s2.0-85126106746 6 87 4029 4039 en RG1/19 RG2/20 MOE2019-T2-1-091 Journal of Organic Chemistry © 2022 American Chemical Society. All rights reserved. |
| spellingShingle | Science::Chemistry Leaving-Group Basis-Sets Lee, Richmond Chao, Chi Bong Eric Ban, Xu Tan, Siu Min Yu, Haibo Hyland, Christopher J. T. Tan, Choon-Hong Direct Sₙ2 or Sₙ2X manifold─mechanistic study of ion-pair-catalyzed carbon(sp³)-carbon(sp³) bond formation |
| title | Direct Sₙ2 or Sₙ2X manifold─mechanistic study of ion-pair-catalyzed carbon(sp³)-carbon(sp³) bond formation |
| title_full | Direct Sₙ2 or Sₙ2X manifold─mechanistic study of ion-pair-catalyzed carbon(sp³)-carbon(sp³) bond formation |
| title_fullStr | Direct Sₙ2 or Sₙ2X manifold─mechanistic study of ion-pair-catalyzed carbon(sp³)-carbon(sp³) bond formation |
| title_full_unstemmed | Direct Sₙ2 or Sₙ2X manifold─mechanistic study of ion-pair-catalyzed carbon(sp³)-carbon(sp³) bond formation |
| title_short | Direct Sₙ2 or Sₙ2X manifold─mechanistic study of ion-pair-catalyzed carbon(sp³)-carbon(sp³) bond formation |
| title_sort | direct sₙ2 or sₙ2x manifold─mechanistic study of ion pair catalyzed carbon sp³ carbon sp³ bond formation |
| topic | Science::Chemistry Leaving-Group Basis-Sets |
| url | https://hdl.handle.net/10356/164028 |
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