Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon
Abstract A robust and practical difluoroalkylation synthon, α,α‐difluoroenol species, which generated in situ from trifluoromethyl diazo compounds and water in the presence of dirhodium complex, is disclosed. As compared to the presynthesized difluoroenoxysilane and in situ formed difluoroenolate un...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-04-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202307520 |
| _version_ | 1827190462035787776 |
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| author | Xiongda Xie Shanliang Dong Kemiao Hong Jingjing Huang Xinfang Xu |
| author_facet | Xiongda Xie Shanliang Dong Kemiao Hong Jingjing Huang Xinfang Xu |
| author_sort | Xiongda Xie |
| collection | DOAJ |
| description | Abstract A robust and practical difluoroalkylation synthon, α,α‐difluoroenol species, which generated in situ from trifluoromethyl diazo compounds and water in the presence of dirhodium complex, is disclosed. As compared to the presynthesized difluoroenoxysilane and in situ formed difluoroenolate under basic conditions, this difluoroenol intermediate displayed versatile reactivity, resulting in dramatically improved enantioselectivity under mild conditions. As demonstrated in catalytic asymmetric aldol reaction and Mannich reactions with ketones or imines in the presence of chiral organocatalysts, quinine‐derived urea, and chiral phosphoric acid (CPA), respectively, this relay catalysis strategy provides an effective platform for applying asymmetric fluorination chemistry. Moreover, this method features a novel 1,2‐difunctionalization process via installation of a carbonyl motif and an alkyl group on two vicinal carbons, which is a complementary protocol to the metal carbene gem‐difunctionalization reaction. |
| first_indexed | 2024-04-24T11:27:27Z |
| format | Article |
| id | doaj.art-24be90e74b9d43fd84634a71cc1b5cb1 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2025-03-21T08:10:14Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-24be90e74b9d43fd84634a71cc1b5cb12024-07-12T14:21:04ZengWileyAdvanced Science2198-38442024-04-011114n/an/a10.1002/advs.202307520Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged SynthonXiongda Xie0Shanliang Dong1Kemiao Hong2Jingjing Huang3Xinfang Xu4School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 P. R. ChinaSchool of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 P. R. ChinaSchool of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 P. R. ChinaSchool of Chemistry Sun Yat‐Sen University Guangzhou Guangdong 510275 P. R. ChinaSchool of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 P. R. ChinaAbstract A robust and practical difluoroalkylation synthon, α,α‐difluoroenol species, which generated in situ from trifluoromethyl diazo compounds and water in the presence of dirhodium complex, is disclosed. As compared to the presynthesized difluoroenoxysilane and in situ formed difluoroenolate under basic conditions, this difluoroenol intermediate displayed versatile reactivity, resulting in dramatically improved enantioselectivity under mild conditions. As demonstrated in catalytic asymmetric aldol reaction and Mannich reactions with ketones or imines in the presence of chiral organocatalysts, quinine‐derived urea, and chiral phosphoric acid (CPA), respectively, this relay catalysis strategy provides an effective platform for applying asymmetric fluorination chemistry. Moreover, this method features a novel 1,2‐difunctionalization process via installation of a carbonyl motif and an alkyl group on two vicinal carbons, which is a complementary protocol to the metal carbene gem‐difunctionalization reaction.https://doi.org/10.1002/advs.2023075201,2‐difunctionalizationasymmetric catalysisdifluoroalkylationmetal carbenemulti‐component reaction |
| spellingShingle | Xiongda Xie Shanliang Dong Kemiao Hong Jingjing Huang Xinfang Xu Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon Advanced Science 1,2‐difunctionalization asymmetric catalysis difluoroalkylation metal carbene multi‐component reaction |
| title | Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon |
| title_full | Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon |
| title_fullStr | Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon |
| title_full_unstemmed | Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon |
| title_short | Catalytic Asymmetric Difluoroalkylation Using In Situ Generated Difluoroenol Species as the Privileged Synthon |
| title_sort | catalytic asymmetric difluoroalkylation using in situ generated difluoroenol species as the privileged synthon |
| topic | 1,2‐difunctionalization asymmetric catalysis difluoroalkylation metal carbene multi‐component reaction |
| url | https://doi.org/10.1002/advs.202307520 |
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