Divergent alkynylative difunctionalization of amide bonds through C–O deoxygenation versus C–N deamination
Abstract The transformation and utilization of amides are significant in organic synthesis and drug discovery. Here we demonstrate a divergent alkynylative difunctionalization of amides in a single transformation. In this reaction, amides react with an organometallic nucleophile to form a tetrahedra...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55618-8 |
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| author | Feng Liu Xueyuan Yan Fangfang Cai Wenjuan Hou Jianyu Dong Shuang-Feng Yin Genping Huang Tieqiao Chen Michal Szostak Yongbo Zhou |
| author_facet | Feng Liu Xueyuan Yan Fangfang Cai Wenjuan Hou Jianyu Dong Shuang-Feng Yin Genping Huang Tieqiao Chen Michal Szostak Yongbo Zhou |
| author_sort | Feng Liu |
| collection | DOAJ |
| description | Abstract The transformation and utilization of amides are significant in organic synthesis and drug discovery. Here we demonstrate a divergent alkynylative difunctionalization of amides in a single transformation. In this reaction, amides react with an organometallic nucleophile to form a tetrahedral intermediate. By altering the N-substitution or the acyl group, the tetrahedral intermediate species selectively undergoes C–O or C–N cleavage with a concomitant capture by an alkynyl nucleophile generated in situ. This process enables the selective introduction of two different functional groups into the amide molecular architecture, producing valuable propargyl amine and propargyl alcohol products. The selectivity between deoxygenation and deamination process has been further elucidated by DFT calculations. Overall, this reaction successfully transforms the traditional mode of nucleophilic acyl addition to amides to a divergent C–O/C–N cleavage. The particularly wide substrate scope, including late-stage modification of bioactive molecules, demonstrates its potential broad applications in organic synthesis. |
| format | Article |
| id | doaj-art-a1072148927d4b0092ee1b1560324233 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a1072148927d4b0092ee1b15603242332025-02-09T12:44:26ZengNature PortfolioNature Communications2041-17232025-02-0116111110.1038/s41467-024-55618-8Divergent alkynylative difunctionalization of amide bonds through C–O deoxygenation versus C–N deaminationFeng Liu0Xueyuan Yan1Fangfang Cai2Wenjuan Hou3Jianyu Dong4Shuang-Feng Yin5Genping Huang6Tieqiao Chen7Michal Szostak8Yongbo Zhou9Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan UniversityDepartment of Chemistry, School of Science, Tianjin UniversityAdvanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan UniversityAdvanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan UniversityAdvanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan UniversityAdvanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan UniversityDepartment of Chemistry, School of Science, Tianjin UniversityCollege of Chemical Engineering and Technology, Hainan UniversityDepartment of Chemistry, Rutgers University, 73 Warren StreetAdvanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan UniversityAbstract The transformation and utilization of amides are significant in organic synthesis and drug discovery. Here we demonstrate a divergent alkynylative difunctionalization of amides in a single transformation. In this reaction, amides react with an organometallic nucleophile to form a tetrahedral intermediate. By altering the N-substitution or the acyl group, the tetrahedral intermediate species selectively undergoes C–O or C–N cleavage with a concomitant capture by an alkynyl nucleophile generated in situ. This process enables the selective introduction of two different functional groups into the amide molecular architecture, producing valuable propargyl amine and propargyl alcohol products. The selectivity between deoxygenation and deamination process has been further elucidated by DFT calculations. Overall, this reaction successfully transforms the traditional mode of nucleophilic acyl addition to amides to a divergent C–O/C–N cleavage. The particularly wide substrate scope, including late-stage modification of bioactive molecules, demonstrates its potential broad applications in organic synthesis.https://doi.org/10.1038/s41467-024-55618-8 |
| spellingShingle | Feng Liu Xueyuan Yan Fangfang Cai Wenjuan Hou Jianyu Dong Shuang-Feng Yin Genping Huang Tieqiao Chen Michal Szostak Yongbo Zhou Divergent alkynylative difunctionalization of amide bonds through C–O deoxygenation versus C–N deamination Nature Communications |
| title | Divergent alkynylative difunctionalization of amide bonds through C–O deoxygenation versus C–N deamination |
| title_full | Divergent alkynylative difunctionalization of amide bonds through C–O deoxygenation versus C–N deamination |
| title_fullStr | Divergent alkynylative difunctionalization of amide bonds through C–O deoxygenation versus C–N deamination |
| title_full_unstemmed | Divergent alkynylative difunctionalization of amide bonds through C–O deoxygenation versus C–N deamination |
| title_short | Divergent alkynylative difunctionalization of amide bonds through C–O deoxygenation versus C–N deamination |
| title_sort | divergent alkynylative difunctionalization of amide bonds through c o deoxygenation versus c n deamination |
| url | https://doi.org/10.1038/s41467-024-55618-8 |
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