Interception of enamine intermediates in reductive functionalization of lactams by sodium hydride: synthesis of 2-cyano-3-iodo piperidines and pyrrolidines
Facile conversion of 2-piperidones and 2-pyrrolidones into 2-cyano-3-iodo piperidines or pyrrolidines has been accomplished by the sequence of 1) controlled hydride reduction of lactams using sodium hydride (NaH) in the presence of sodium iodide (NaI); 2) silylation of anionic hemiaminal intermediat...
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2022
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| Online Access: | https://hdl.handle.net/10356/161610 |
| _version_ | 1811677178891337728 |
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| author | Chen, Jiahua Lim, Jun Wei Chiba, Shunsuke |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Chen, Jiahua Lim, Jun Wei Chiba, Shunsuke |
| author_sort | Chen, Jiahua |
| collection | NTU |
| description | Facile conversion of 2-piperidones and 2-pyrrolidones into 2-cyano-3-iodo piperidines or pyrrolidines has been accomplished by the sequence of 1) controlled hydride reduction of lactams using sodium hydride (NaH) in the presence of sodium iodide (NaI); 2) silylation of anionic hemiaminal intermediates to facilitate deoxygenation to form an equilibrium mixture of iminium cations and enamines-silanol pair; 3) interception of enamine intermediates by electrophilic iodination to generate iodonium ions; 4) nucleophilic cyanation of the resultant iminium cations. The overall transformation proceeded in highly diastereoselective fashion. The resultant 2-cyano-3-iodo piperidines were converted into 2-cyanotetrahydropyridines, which could be used for [2 + 2]-annulation or ring-expansion reactions with reactive benzyne or alkyne species, respectively. |
| first_indexed | 2024-10-01T02:33:15Z |
| format | Journal Article |
| id | ntu-10356/161610 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:33:15Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1616102023-02-28T20:07:54Z Interception of enamine intermediates in reductive functionalization of lactams by sodium hydride: synthesis of 2-cyano-3-iodo piperidines and pyrrolidines Chen, Jiahua Lim, Jun Wei Chiba, Shunsuke School of Physical and Mathematical Sciences Science::Chemistry Sodium Hydride Lactams Facile conversion of 2-piperidones and 2-pyrrolidones into 2-cyano-3-iodo piperidines or pyrrolidines has been accomplished by the sequence of 1) controlled hydride reduction of lactams using sodium hydride (NaH) in the presence of sodium iodide (NaI); 2) silylation of anionic hemiaminal intermediates to facilitate deoxygenation to form an equilibrium mixture of iminium cations and enamines-silanol pair; 3) interception of enamine intermediates by electrophilic iodination to generate iodonium ions; 4) nucleophilic cyanation of the resultant iminium cations. The overall transformation proceeded in highly diastereoselective fashion. The resultant 2-cyano-3-iodo piperidines were converted into 2-cyanotetrahydropyridines, which could be used for [2 + 2]-annulation or ring-expansion reactions with reactive benzyne or alkyne species, respectively. Ministry of Education (MOE) Nanyang Technological University Submitted/Accepted version This work was supported by funding from Nanyang Technological University, Singapore (NTU) and Ministry of Education, Singapore (Academic Research Fund Tier 2: MOE2019-T2-1-089) (for S.C.). 2022-09-12T01:27:53Z 2022-09-12T01:27:53Z 2022 Journal Article Chen, J., Lim, J. W. & Chiba, S. (2022). Interception of enamine intermediates in reductive functionalization of lactams by sodium hydride: synthesis of 2-cyano-3-iodo piperidines and pyrrolidines. Tetrahedron, 114, 132779-. https://dx.doi.org/10.1016/j.tet.2022.132779 0040-4020 https://hdl.handle.net/10356/161610 10.1016/j.tet.2022.132779 2-s2.0-85129891115 114 132779 en MOE2019-T2-1-089 Tetrahedron © 2022 Elsevier Ltd. All rights reserved. This paper was published in Tetrahedron and is made available with permission of Elsevier Ltd. application/pdf |
| spellingShingle | Science::Chemistry Sodium Hydride Lactams Chen, Jiahua Lim, Jun Wei Chiba, Shunsuke Interception of enamine intermediates in reductive functionalization of lactams by sodium hydride: synthesis of 2-cyano-3-iodo piperidines and pyrrolidines |
| title | Interception of enamine intermediates in reductive functionalization of lactams by sodium hydride: synthesis of 2-cyano-3-iodo piperidines and pyrrolidines |
| title_full | Interception of enamine intermediates in reductive functionalization of lactams by sodium hydride: synthesis of 2-cyano-3-iodo piperidines and pyrrolidines |
| title_fullStr | Interception of enamine intermediates in reductive functionalization of lactams by sodium hydride: synthesis of 2-cyano-3-iodo piperidines and pyrrolidines |
| title_full_unstemmed | Interception of enamine intermediates in reductive functionalization of lactams by sodium hydride: synthesis of 2-cyano-3-iodo piperidines and pyrrolidines |
| title_short | Interception of enamine intermediates in reductive functionalization of lactams by sodium hydride: synthesis of 2-cyano-3-iodo piperidines and pyrrolidines |
| title_sort | interception of enamine intermediates in reductive functionalization of lactams by sodium hydride synthesis of 2 cyano 3 iodo piperidines and pyrrolidines |
| topic | Science::Chemistry Sodium Hydride Lactams |
| url | https://hdl.handle.net/10356/161610 |
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