Diastereoselective synthesis of multi-substituted cyclobutanes via catalyst-controlled regiodivergent hydrophosphination of acyl bicyclobutanes
Abstract Although ring-opening reactions of bicyclo[1.1.0]butanes (BCBs) provide a reliable platform for synthesizing functionalized cyclobutanes, current methods frequently encounter challenges such as poor diastereoselectivity, regioselectivity issues, and a lack of α- and β‘-selective transformat...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61726-w |
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| author | Heng-Xian He Feng Wu Kun-Ju Wang Lei Wang Jian-Jun Feng |
| author_facet | Heng-Xian He Feng Wu Kun-Ju Wang Lei Wang Jian-Jun Feng |
| author_sort | Heng-Xian He |
| collection | DOAJ |
| description | Abstract Although ring-opening reactions of bicyclo[1.1.0]butanes (BCBs) provide a reliable platform for synthesizing functionalized cyclobutanes, current methods frequently encounter challenges such as poor diastereoselectivity, regioselectivity issues, and a lack of α- and β‘-selective transformations. Herein, we report a catalyst-controlled, regiodivergent α- and β‘-selective hydrophosphination of acyl BCBs, which expands the chemical space of tertiary phosphines with multi-substituted cyclobutane backbones derived from identical starting materials. Utilizing a Cu(I) catalytic system, we achieve an α-selective nucleophilic addition to 1,3-disubstituted BCBs. This reaction exhibits a broad substrate scope under mild conditions, yielding valuable 1,1,3-functionalized cyclobutanes predominantly as single diastereoisomers. In contrast, the unusual β‘-selective pathway facilitated by a Cu(II) catalytic system produces 1,2,3-trisubstituted variants with up to >20:1 d.r. The developed method holds promise for accessing structurally diverse cyclobutanes with potential applications in medicinal chemistry and the design of organophosphorus catalysts. |
| format | Article |
| id | doaj-art-64db39177f5f44908a905ea5d67971b4 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-64db39177f5f44908a905ea5d67971b42025-08-20T03:42:55ZengNature PortfolioNature Communications2041-17232025-07-0116111110.1038/s41467-025-61726-wDiastereoselective synthesis of multi-substituted cyclobutanes via catalyst-controlled regiodivergent hydrophosphination of acyl bicyclobutanesHeng-Xian He0Feng Wu1Kun-Ju Wang2Lei Wang3Jian-Jun Feng4State Key Laboratory of Chemo and Biosensing, Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan UniversityState Key Laboratory of Chemo and Biosensing, Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan UniversityState Key Laboratory of Chemo and Biosensing, Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan UniversitySchool of Chemistry & Chemical Engineering, Yangzhou UniversityState Key Laboratory of Chemo and Biosensing, Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan UniversityAbstract Although ring-opening reactions of bicyclo[1.1.0]butanes (BCBs) provide a reliable platform for synthesizing functionalized cyclobutanes, current methods frequently encounter challenges such as poor diastereoselectivity, regioselectivity issues, and a lack of α- and β‘-selective transformations. Herein, we report a catalyst-controlled, regiodivergent α- and β‘-selective hydrophosphination of acyl BCBs, which expands the chemical space of tertiary phosphines with multi-substituted cyclobutane backbones derived from identical starting materials. Utilizing a Cu(I) catalytic system, we achieve an α-selective nucleophilic addition to 1,3-disubstituted BCBs. This reaction exhibits a broad substrate scope under mild conditions, yielding valuable 1,1,3-functionalized cyclobutanes predominantly as single diastereoisomers. In contrast, the unusual β‘-selective pathway facilitated by a Cu(II) catalytic system produces 1,2,3-trisubstituted variants with up to >20:1 d.r. The developed method holds promise for accessing structurally diverse cyclobutanes with potential applications in medicinal chemistry and the design of organophosphorus catalysts.https://doi.org/10.1038/s41467-025-61726-w |
| spellingShingle | Heng-Xian He Feng Wu Kun-Ju Wang Lei Wang Jian-Jun Feng Diastereoselective synthesis of multi-substituted cyclobutanes via catalyst-controlled regiodivergent hydrophosphination of acyl bicyclobutanes Nature Communications |
| title | Diastereoselective synthesis of multi-substituted cyclobutanes via catalyst-controlled regiodivergent hydrophosphination of acyl bicyclobutanes |
| title_full | Diastereoselective synthesis of multi-substituted cyclobutanes via catalyst-controlled regiodivergent hydrophosphination of acyl bicyclobutanes |
| title_fullStr | Diastereoselective synthesis of multi-substituted cyclobutanes via catalyst-controlled regiodivergent hydrophosphination of acyl bicyclobutanes |
| title_full_unstemmed | Diastereoselective synthesis of multi-substituted cyclobutanes via catalyst-controlled regiodivergent hydrophosphination of acyl bicyclobutanes |
| title_short | Diastereoselective synthesis of multi-substituted cyclobutanes via catalyst-controlled regiodivergent hydrophosphination of acyl bicyclobutanes |
| title_sort | diastereoselective synthesis of multi substituted cyclobutanes via catalyst controlled regiodivergent hydrophosphination of acyl bicyclobutanes |
| url | https://doi.org/10.1038/s41467-025-61726-w |
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