N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanides
Abstract Both the pyrroloindoline core and N–CF3 moiety hold significant importance in medicinal chemistry. However, to date, no instances of constructing N–CF3-containing pyrroloindolines have been reported. Herein, we present a robust and operationally simple approach to assembling such intriguing...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53271-9 |
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| author | Jun-Yunzi Wu Long-Ling Huang Jia-Luo Fu Jia-Yi Li Shuang Lin Shuang Yang Zhi-Shu Huang Honggen Wang Qingjiang Li |
| author_facet | Jun-Yunzi Wu Long-Ling Huang Jia-Luo Fu Jia-Yi Li Shuang Lin Shuang Yang Zhi-Shu Huang Honggen Wang Qingjiang Li |
| author_sort | Jun-Yunzi Wu |
| collection | DOAJ |
| description | Abstract Both the pyrroloindoline core and N–CF3 moiety hold significant importance in medicinal chemistry. However, to date, no instances of constructing N–CF3-containing pyrroloindolines have been reported. Herein, we present a robust and operationally simple approach to assembling such intriguing skeletons from tryptamine-derived isocyanides through a cascade sequence, which includes an oxidative trifluorination and a subsequent halogenative cyclization. Key to the success lies in the development of a facile conversion of isocyanides to N–CF3 moiety with commercially available reagents N-halosuccinimide and Et3N·HF. The protocol features mild reaction conditions, broad functional group tolerance, good to excellent yields, and high diastereoselectivities. In addition, we demonstrate that the halide substituent within the products serves as a versatile functional handle for accessing diverse C3-quaternary-substituted N–CF3-pyrroloindolines. |
| format | Article |
| id | doaj-art-c2f779f2c1d84c99a1b19e35f7edd985 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c2f779f2c1d84c99a1b19e35f7edd9852025-08-20T01:50:38ZengNature PortfolioNature Communications2041-17232024-10-011511810.1038/s41467-024-53271-9N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanidesJun-Yunzi Wu0Long-Ling Huang1Jia-Luo Fu2Jia-Yi Li3Shuang Lin4Shuang Yang5Zhi-Shu Huang6Honggen Wang7Qingjiang Li8State Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityAbstract Both the pyrroloindoline core and N–CF3 moiety hold significant importance in medicinal chemistry. However, to date, no instances of constructing N–CF3-containing pyrroloindolines have been reported. Herein, we present a robust and operationally simple approach to assembling such intriguing skeletons from tryptamine-derived isocyanides through a cascade sequence, which includes an oxidative trifluorination and a subsequent halogenative cyclization. Key to the success lies in the development of a facile conversion of isocyanides to N–CF3 moiety with commercially available reagents N-halosuccinimide and Et3N·HF. The protocol features mild reaction conditions, broad functional group tolerance, good to excellent yields, and high diastereoselectivities. In addition, we demonstrate that the halide substituent within the products serves as a versatile functional handle for accessing diverse C3-quaternary-substituted N–CF3-pyrroloindolines.https://doi.org/10.1038/s41467-024-53271-9 |
| spellingShingle | Jun-Yunzi Wu Long-Ling Huang Jia-Luo Fu Jia-Yi Li Shuang Lin Shuang Yang Zhi-Shu Huang Honggen Wang Qingjiang Li N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanides Nature Communications |
| title | N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanides |
| title_full | N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanides |
| title_fullStr | N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanides |
| title_full_unstemmed | N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanides |
| title_short | N-Halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine-derived isocyanides |
| title_sort | n halosuccinimide enables cascade oxidative trifluorination and halogenative cyclization of tryptamine derived isocyanides |
| url | https://doi.org/10.1038/s41467-024-53271-9 |
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