Enantioconvergent nucleophilic substitution via synergistic phase-transfer catalysis
Catalytic enantioconvergent nucleophilic substitution reactions of alkyl halides are highly valuable transformations, but they are notoriously difficult to implement. Specifically, nucleophilic fluorination is a renowned challenge, especially when inexpensive alkali metal fluorides are used as fluor...
| প্রধান লেখক: | , , , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Nature Research
2025
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| _version_ | 1826317806181810176 |
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| author | Dooley, C Ibba, F Botlik, BB Palladino, C Goult, CA Gao, Y Lister, A Paton, RS Lloyd-Jones, GC Gouverneur, V |
| author_facet | Dooley, C Ibba, F Botlik, BB Palladino, C Goult, CA Gao, Y Lister, A Paton, RS Lloyd-Jones, GC Gouverneur, V |
| author_sort | Dooley, C |
| collection | OXFORD |
| description | Catalytic enantioconvergent nucleophilic substitution reactions of alkyl halides are highly valuable transformations, but they are notoriously difficult to implement. Specifically, nucleophilic fluorination is a renowned challenge, especially when inexpensive alkali metal fluorides are used as fluorinating reagents due to their low solubility, high hygroscopicity and Brønsted basicity. Here we report a solution by developing the concept of synergistic hydrogen bonding phase-transfer catalysis. Key to our strategy is the combination of a chiral bis-urea hydrogen bond donor (HBD) and an onium salt—two phase-transfer catalysts essential for the solubilization of potassium fluoride—as a well-characterized ternary HBD–onium fluoride complex. Mechanistic investigations indicate that this chiral ternary complex is capable of enantiodiscrimination of racemic benzylic bromides and α-bromoketones, and upon fluoride delivery affords fluorinated products in high yields and enantioselectivities. This work provides a foundation for enantioconvergent fluorination chemistry enabled through the combination of a HBD catalyst with a co-catalyst specifically curated to meet the requirement of the electrophile. |
| first_indexed | 2025-03-11T16:59:45Z |
| format | Journal article |
| id | oxford-uuid:a1a3fa71-06be-4dba-b764-0704a00bf4ea |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-03-11T16:59:45Z |
| publishDate | 2025 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:a1a3fa71-06be-4dba-b764-0704a00bf4ea2025-03-08T20:03:34ZEnantioconvergent nucleophilic substitution via synergistic phase-transfer catalysisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a1a3fa71-06be-4dba-b764-0704a00bf4eaEnglishJisc Publications RouterNature Research2025Dooley, CIbba, FBotlik, BBPalladino, CGoult, CAGao, YLister, APaton, RSLloyd-Jones, GCGouverneur, VCatalytic enantioconvergent nucleophilic substitution reactions of alkyl halides are highly valuable transformations, but they are notoriously difficult to implement. Specifically, nucleophilic fluorination is a renowned challenge, especially when inexpensive alkali metal fluorides are used as fluorinating reagents due to their low solubility, high hygroscopicity and Brønsted basicity. Here we report a solution by developing the concept of synergistic hydrogen bonding phase-transfer catalysis. Key to our strategy is the combination of a chiral bis-urea hydrogen bond donor (HBD) and an onium salt—two phase-transfer catalysts essential for the solubilization of potassium fluoride—as a well-characterized ternary HBD–onium fluoride complex. Mechanistic investigations indicate that this chiral ternary complex is capable of enantiodiscrimination of racemic benzylic bromides and α-bromoketones, and upon fluoride delivery affords fluorinated products in high yields and enantioselectivities. This work provides a foundation for enantioconvergent fluorination chemistry enabled through the combination of a HBD catalyst with a co-catalyst specifically curated to meet the requirement of the electrophile. |
| spellingShingle | Dooley, C Ibba, F Botlik, BB Palladino, C Goult, CA Gao, Y Lister, A Paton, RS Lloyd-Jones, GC Gouverneur, V Enantioconvergent nucleophilic substitution via synergistic phase-transfer catalysis |
| title | Enantioconvergent nucleophilic substitution via synergistic phase-transfer catalysis |
| title_full | Enantioconvergent nucleophilic substitution via synergistic phase-transfer catalysis |
| title_fullStr | Enantioconvergent nucleophilic substitution via synergistic phase-transfer catalysis |
| title_full_unstemmed | Enantioconvergent nucleophilic substitution via synergistic phase-transfer catalysis |
| title_short | Enantioconvergent nucleophilic substitution via synergistic phase-transfer catalysis |
| title_sort | enantioconvergent nucleophilic substitution via synergistic phase transfer catalysis |
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