Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids
Abstract The primary objective in synthetic organic chemistry is to develop highly efficient, selective, and versatile synthetic methodologies, which are essential for discovering new drug candidates and agrochemicals. In this study, we present a unified strategy for a one-pot, catalytic enantiosele...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41846-x |
| _version_ | 1827326974263033856 |
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| author | Fang-Fang Xu Jin-Quan Chen Dong-Yang Shao Pei-Qiang Huang |
| author_facet | Fang-Fang Xu Jin-Quan Chen Dong-Yang Shao Pei-Qiang Huang |
| author_sort | Fang-Fang Xu |
| collection | DOAJ |
| description | Abstract The primary objective in synthetic organic chemistry is to develop highly efficient, selective, and versatile synthetic methodologies, which are essential for discovering new drug candidates and agrochemicals. In this study, we present a unified strategy for a one-pot, catalytic enantioselective synthesis of α-alkyl and α,α′-dialkyl pyrrolidine, piperidine, and indolizidine alkaloids using readily available amides and alkynes. This synthesis is enabled by the identification and development of an Ir/Cu/N-PINAP catalyzed highly enantioselective and chemoselective reductive alkynylation of α-unbranched aliphatic amides, which serves as the key reaction. This reaction is combined with Pd-catalyzed tandem reactions in a one-pot approach, enabling the collective, catalytic enantioselective total syntheses of eight alkaloids and an anticancer antipode with 90–98% ee. The methodology’s enantio-divergence is exemplified by the one-step access to either enantiomer of alkaloid bgugaine. |
| first_indexed | 2024-03-07T14:54:13Z |
| format | Article |
| id | doaj.art-27b83d03c61a406abbda38c75652fe25 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:54:13Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-27b83d03c61a406abbda38c75652fe252024-03-05T19:31:01ZengNature PortfolioNature Communications2041-17232023-10-0114111210.1038/s41467-023-41846-xCatalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloidsFang-Fang Xu0Jin-Quan Chen1Dong-Yang Shao2Pei-Qiang Huang3Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen UniversityDepartment of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen UniversityDepartment of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen UniversityDepartment of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen UniversityAbstract The primary objective in synthetic organic chemistry is to develop highly efficient, selective, and versatile synthetic methodologies, which are essential for discovering new drug candidates and agrochemicals. In this study, we present a unified strategy for a one-pot, catalytic enantioselective synthesis of α-alkyl and α,α′-dialkyl pyrrolidine, piperidine, and indolizidine alkaloids using readily available amides and alkynes. This synthesis is enabled by the identification and development of an Ir/Cu/N-PINAP catalyzed highly enantioselective and chemoselective reductive alkynylation of α-unbranched aliphatic amides, which serves as the key reaction. This reaction is combined with Pd-catalyzed tandem reactions in a one-pot approach, enabling the collective, catalytic enantioselective total syntheses of eight alkaloids and an anticancer antipode with 90–98% ee. The methodology’s enantio-divergence is exemplified by the one-step access to either enantiomer of alkaloid bgugaine.https://doi.org/10.1038/s41467-023-41846-x |
| spellingShingle | Fang-Fang Xu Jin-Quan Chen Dong-Yang Shao Pei-Qiang Huang Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids Nature Communications |
| title | Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids |
| title_full | Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids |
| title_fullStr | Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids |
| title_full_unstemmed | Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids |
| title_short | Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids |
| title_sort | catalytic enantioselective reductive alkynylation of amides enables one pot syntheses of pyrrolidine piperidine and indolizidine alkaloids |
| url | https://doi.org/10.1038/s41467-023-41846-x |
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