A Plausible Mechanism for the Iridium-Catalyzed Hydrogenation of a Bulky <i>N</i>-Aryl Imine in the (<i>S</i>)-Metolachlor Process
The hydrogenation of <i>N</i>-(2-ethyl-6-methylphenyl)-1-methoxypropan-2-imine is the largest-scale asymmetric catalytic process for the industrial production of agrochemical (<i>S</i>)-metolachlor. The challenging hydrogenation across the sterically crowded carbon–nitrogen d...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/16/5106 |
| _version_ | 1827617686386900992 |
|---|---|
| author | Amanda L. Kwan Robert H. Morris |
| author_facet | Amanda L. Kwan Robert H. Morris |
| author_sort | Amanda L. Kwan |
| collection | DOAJ |
| description | The hydrogenation of <i>N</i>-(2-ethyl-6-methylphenyl)-1-methoxypropan-2-imine is the largest-scale asymmetric catalytic process for the industrial production of agrochemical (<i>S</i>)-metolachlor. The challenging hydrogenation across the sterically crowded carbon–nitrogen double bond was achieved using a mixture of [IrCl(COD)]<sub>2</sub>, (<i>R</i>,<i>S<sub>Fc</sub></i>)-Xyliphos, NBu<sub>4</sub>I and acetic acid. Acetic acid was critical in achieving excellent productivity and activity. Despite its industrial significance, a mechanism that explains how the sterically hindered bond in the imine is reduced has yet to be proposed. We propose a plausible proton-first, outer-sphere mechanism based on density functional theory calculations that is consistent with the experimentally observed activity and the enantioselectivity of the industrial process. Key findings include transition states involving acetate-assisted dihydrogen splitting, and a hydride transfer from a five-coordinate iridium trihydride directed by a C-H∙∙∙Ir interaction. This article was submitted to a Special Issue in honor of Professor Henri Kagan. |
| first_indexed | 2024-03-09T09:51:31Z |
| format | Article |
| id | doaj.art-0471ef031b564b23b7f4b68ccf92549c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T09:51:31Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0471ef031b564b23b7f4b68ccf92549c2023-12-02T00:04:01ZengMDPI AGMolecules1420-30492022-08-012716510610.3390/molecules27165106A Plausible Mechanism for the Iridium-Catalyzed Hydrogenation of a Bulky <i>N</i>-Aryl Imine in the (<i>S</i>)-Metolachlor ProcessAmanda L. Kwan0Robert H. Morris1Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, CanadaDepartment of Chemistry, University of Toronto, Toronto, ON M5S 3H6, CanadaThe hydrogenation of <i>N</i>-(2-ethyl-6-methylphenyl)-1-methoxypropan-2-imine is the largest-scale asymmetric catalytic process for the industrial production of agrochemical (<i>S</i>)-metolachlor. The challenging hydrogenation across the sterically crowded carbon–nitrogen double bond was achieved using a mixture of [IrCl(COD)]<sub>2</sub>, (<i>R</i>,<i>S<sub>Fc</sub></i>)-Xyliphos, NBu<sub>4</sub>I and acetic acid. Acetic acid was critical in achieving excellent productivity and activity. Despite its industrial significance, a mechanism that explains how the sterically hindered bond in the imine is reduced has yet to be proposed. We propose a plausible proton-first, outer-sphere mechanism based on density functional theory calculations that is consistent with the experimentally observed activity and the enantioselectivity of the industrial process. Key findings include transition states involving acetate-assisted dihydrogen splitting, and a hydride transfer from a five-coordinate iridium trihydride directed by a C-H∙∙∙Ir interaction. This article was submitted to a Special Issue in honor of Professor Henri Kagan.https://www.mdpi.com/1420-3049/27/16/5106asymmetric catalysisdensity functional calculationshydrogenationiridiumreaction mechanisms |
| spellingShingle | Amanda L. Kwan Robert H. Morris A Plausible Mechanism for the Iridium-Catalyzed Hydrogenation of a Bulky <i>N</i>-Aryl Imine in the (<i>S</i>)-Metolachlor Process Molecules asymmetric catalysis density functional calculations hydrogenation iridium reaction mechanisms |
| title | A Plausible Mechanism for the Iridium-Catalyzed Hydrogenation of a Bulky <i>N</i>-Aryl Imine in the (<i>S</i>)-Metolachlor Process |
| title_full | A Plausible Mechanism for the Iridium-Catalyzed Hydrogenation of a Bulky <i>N</i>-Aryl Imine in the (<i>S</i>)-Metolachlor Process |
| title_fullStr | A Plausible Mechanism for the Iridium-Catalyzed Hydrogenation of a Bulky <i>N</i>-Aryl Imine in the (<i>S</i>)-Metolachlor Process |
| title_full_unstemmed | A Plausible Mechanism for the Iridium-Catalyzed Hydrogenation of a Bulky <i>N</i>-Aryl Imine in the (<i>S</i>)-Metolachlor Process |
| title_short | A Plausible Mechanism for the Iridium-Catalyzed Hydrogenation of a Bulky <i>N</i>-Aryl Imine in the (<i>S</i>)-Metolachlor Process |
| title_sort | plausible mechanism for the iridium catalyzed hydrogenation of a bulky i n i aryl imine in the i s i metolachlor process |
| topic | asymmetric catalysis density functional calculations hydrogenation iridium reaction mechanisms |
| url | https://www.mdpi.com/1420-3049/27/16/5106 |
| work_keys_str_mv | AT amandalkwan aplausiblemechanismfortheiridiumcatalyzedhydrogenationofabulkyiniarylimineintheisimetolachlorprocess AT roberthmorris aplausiblemechanismfortheiridiumcatalyzedhydrogenationofabulkyiniarylimineintheisimetolachlorprocess AT amandalkwan plausiblemechanismfortheiridiumcatalyzedhydrogenationofabulkyiniarylimineintheisimetolachlorprocess AT roberthmorris plausiblemechanismfortheiridiumcatalyzedhydrogenationofabulkyiniarylimineintheisimetolachlorprocess |