Catalyst-controlled directing group translocation in the site selective C–H functionalization of 3-carboxamide indoles and metallocarbenes
Abstract Complementary methods toward the selective functionalization of indole and oxindole frameworks employing an alternative strategy in heteroaryl C–H functionalizations are presented herein. This work focuses on a catalyst-controlled, site selective C–H activation/functionalization of 3-acyl i...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55246-2 |
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| author | Kuang Gu Mary T. Hall Zachary D. Tucker Gregory M. Durling Brandon L. Ashfeld |
| author_facet | Kuang Gu Mary T. Hall Zachary D. Tucker Gregory M. Durling Brandon L. Ashfeld |
| author_sort | Kuang Gu |
| collection | DOAJ |
| description | Abstract Complementary methods toward the selective functionalization of indole and oxindole frameworks employing an alternative strategy in heteroaryl C–H functionalizations are presented herein. This work focuses on a catalyst-controlled, site selective C–H activation/functionalization of 3-acyl indoles, wherein an amide serves as a robust and versatile directing group capable of undergoing concomitant 1,2-acyl translocation/C–H functionalization in the presence of a RhI/AgI co-catalysts to provide the cross-coupled adducts in high yields. In contrast, the use of IrIII/AgI catalysts subverted the 1,2-acyl migration to afford the corresponding C2-functionalized products in good to excellent yields. A notable feature of the catalyst systems was the exceptional level of site selectivity observed in which the corresponding C–H functionalized indoles were obtained exclusively. Mechanistic experiments indicate a concerted 1,2-acyl migration step and indole metallation occurring through an electrophilic aromatic substitution process. |
| format | Article |
| id | doaj-art-21d32052f68d4ac1a202e9fbc6c97b86 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-21d32052f68d4ac1a202e9fbc6c97b862025-01-05T12:39:03ZengNature PortfolioNature Communications2041-17232025-01-011611910.1038/s41467-024-55246-2Catalyst-controlled directing group translocation in the site selective C–H functionalization of 3-carboxamide indoles and metallocarbenesKuang Gu0Mary T. Hall1Zachary D. Tucker2Gregory M. Durling3Brandon L. Ashfeld4Department of Chemistry and Biochemistry, University of Notre DameDepartment of Chemistry and Biochemistry, University of Notre DameDepartment of Chemistry and Biochemistry, University of Notre DameDepartment of Chemistry and Biochemistry, University of Notre DameDepartment of Chemistry and Biochemistry, University of Notre DameAbstract Complementary methods toward the selective functionalization of indole and oxindole frameworks employing an alternative strategy in heteroaryl C–H functionalizations are presented herein. This work focuses on a catalyst-controlled, site selective C–H activation/functionalization of 3-acyl indoles, wherein an amide serves as a robust and versatile directing group capable of undergoing concomitant 1,2-acyl translocation/C–H functionalization in the presence of a RhI/AgI co-catalysts to provide the cross-coupled adducts in high yields. In contrast, the use of IrIII/AgI catalysts subverted the 1,2-acyl migration to afford the corresponding C2-functionalized products in good to excellent yields. A notable feature of the catalyst systems was the exceptional level of site selectivity observed in which the corresponding C–H functionalized indoles were obtained exclusively. Mechanistic experiments indicate a concerted 1,2-acyl migration step and indole metallation occurring through an electrophilic aromatic substitution process.https://doi.org/10.1038/s41467-024-55246-2 |
| spellingShingle | Kuang Gu Mary T. Hall Zachary D. Tucker Gregory M. Durling Brandon L. Ashfeld Catalyst-controlled directing group translocation in the site selective C–H functionalization of 3-carboxamide indoles and metallocarbenes Nature Communications |
| title | Catalyst-controlled directing group translocation in the site selective C–H functionalization of 3-carboxamide indoles and metallocarbenes |
| title_full | Catalyst-controlled directing group translocation in the site selective C–H functionalization of 3-carboxamide indoles and metallocarbenes |
| title_fullStr | Catalyst-controlled directing group translocation in the site selective C–H functionalization of 3-carboxamide indoles and metallocarbenes |
| title_full_unstemmed | Catalyst-controlled directing group translocation in the site selective C–H functionalization of 3-carboxamide indoles and metallocarbenes |
| title_short | Catalyst-controlled directing group translocation in the site selective C–H functionalization of 3-carboxamide indoles and metallocarbenes |
| title_sort | catalyst controlled directing group translocation in the site selective c h functionalization of 3 carboxamide indoles and metallocarbenes |
| url | https://doi.org/10.1038/s41467-024-55246-2 |
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