Catalytic asymmetric intermolecular [4 + 2] annulation of benzocyclobutenones with Alkynes and activated carbonyls via C—C activation
Abstract The activation of C—C bonds enables rapid construction of new organic frameworks owing to facile structural reorganization. Nevertheless, enantioselective C—C activation remains heavily underexplored and has been predominantly limited to intramolecular reactions. We herein report two catego...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60109-5 |
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| author | Huilai Liu Zisong Qi Yue Shi Wei Wang Fen Wang Zhi-Wen Ding Ai-Qun Jia Genping Huang Xingwei Li |
| author_facet | Huilai Liu Zisong Qi Yue Shi Wei Wang Fen Wang Zhi-Wen Ding Ai-Qun Jia Genping Huang Xingwei Li |
| author_sort | Huilai Liu |
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| description | Abstract The activation of C—C bonds enables rapid construction of new organic frameworks owing to facile structural reorganization. Nevertheless, enantioselective C—C activation remains heavily underexplored and has been predominantly limited to intramolecular reactions. We herein report two categories of asymmetric intermolecular [4 + 2] annulations between benzocyclobutenones (BCBs) and unsaturated reagents, namely, alkynes and cyclic dicarbonyl compounds. The atroposelective coupling of BCB with several classes of sterically hindered alkynes afford C—N and C—C axially chiral 2-naphthols. The [4 + 2] annulation of BCBs and α-dicarbonyls afford spirocyclic products. Both coupling systems proceed efficiently with excellent regio-, chemo- and enantioselectivity via substrate activation and judicious choice of chiral bidentate phosphine ligands. Synthetic transformations of selected products are demonstrated, and the derived chiral products are shown to be useful additives in C—H bond activation or as ligands in Pd-catalyzed C—C coupling. |
| format | Article |
| id | doaj-art-74b5fbb97e7b4481bfbf3e793112f9b3 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-74b5fbb97e7b4481bfbf3e793112f9b32025-08-20T03:37:38ZengNature PortfolioNature Communications2041-17232025-07-0116111410.1038/s41467-025-60109-5Catalytic asymmetric intermolecular [4 + 2] annulation of benzocyclobutenones with Alkynes and activated carbonyls via C—C activationHuilai Liu0Zisong Qi1Yue Shi2Wei Wang3Fen Wang4Zhi-Wen Ding5Ai-Qun Jia6Genping Huang7Xingwei Li8Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, and School of Chemistry and Chemical Engineering, Shaanxi Normal University (SNNU)Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, and School of Chemistry and Chemical Engineering, Shaanxi Normal University (SNNU)Department of Chemistry, School of Science, Tianjin UniversityKey Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, and School of Chemistry and Chemical Engineering, Shaanxi Normal University (SNNU)Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, and School of Chemistry and Chemical Engineering, Shaanxi Normal University (SNNU)Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical UniversityHainan General Hospital, Hainan Affiliated Hospital of Hainan Medical UniversityDepartment of Chemistry, School of Science, Tianjin UniversityKey Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, and School of Chemistry and Chemical Engineering, Shaanxi Normal University (SNNU)Abstract The activation of C—C bonds enables rapid construction of new organic frameworks owing to facile structural reorganization. Nevertheless, enantioselective C—C activation remains heavily underexplored and has been predominantly limited to intramolecular reactions. We herein report two categories of asymmetric intermolecular [4 + 2] annulations between benzocyclobutenones (BCBs) and unsaturated reagents, namely, alkynes and cyclic dicarbonyl compounds. The atroposelective coupling of BCB with several classes of sterically hindered alkynes afford C—N and C—C axially chiral 2-naphthols. The [4 + 2] annulation of BCBs and α-dicarbonyls afford spirocyclic products. Both coupling systems proceed efficiently with excellent regio-, chemo- and enantioselectivity via substrate activation and judicious choice of chiral bidentate phosphine ligands. Synthetic transformations of selected products are demonstrated, and the derived chiral products are shown to be useful additives in C—H bond activation or as ligands in Pd-catalyzed C—C coupling.https://doi.org/10.1038/s41467-025-60109-5 |
| spellingShingle | Huilai Liu Zisong Qi Yue Shi Wei Wang Fen Wang Zhi-Wen Ding Ai-Qun Jia Genping Huang Xingwei Li Catalytic asymmetric intermolecular [4 + 2] annulation of benzocyclobutenones with Alkynes and activated carbonyls via C—C activation Nature Communications |
| title | Catalytic asymmetric intermolecular [4 + 2] annulation of benzocyclobutenones with Alkynes and activated carbonyls via C—C activation |
| title_full | Catalytic asymmetric intermolecular [4 + 2] annulation of benzocyclobutenones with Alkynes and activated carbonyls via C—C activation |
| title_fullStr | Catalytic asymmetric intermolecular [4 + 2] annulation of benzocyclobutenones with Alkynes and activated carbonyls via C—C activation |
| title_full_unstemmed | Catalytic asymmetric intermolecular [4 + 2] annulation of benzocyclobutenones with Alkynes and activated carbonyls via C—C activation |
| title_short | Catalytic asymmetric intermolecular [4 + 2] annulation of benzocyclobutenones with Alkynes and activated carbonyls via C—C activation |
| title_sort | catalytic asymmetric intermolecular 4 2 annulation of benzocyclobutenones with alkynes and activated carbonyls via c c activation |
| url | https://doi.org/10.1038/s41467-025-60109-5 |
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