2020 Fiscal Year Research-status Report
The Development of Direct Vinylogous Michael Addition of Butenolides to Chromones and Its Application to the Total Synthesis of Natural Products
| Project/Area Number |
20K15966
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| Research Institution | Microbial Chemistry Research Foundation |
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Principal Investigator |
崔 進 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (20839120)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | vinylogous addition / chromone / atom-economy / natural product |
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| Outline of Annual Research Achievements |
In this work, a direct catalytic asymmetric vinylogous Michael-type reaction of chromones and β,γ-butenolides to afford anti-adducts with high enantioselectivity has been developed successfully. The synthetic method developed for the reaction was characterized by (1) tuning of the steric and electronic environment within the stereocontrolling transition state using (R)-3,4,5-(MeO)3-MeOBIPHEP as a chiral ligand to invert diastereoselection, and (2) improvement of the catalyst turnover by a coordinative phenoxide additive to increase the chemical yield. This method is useful for the syntheses of natural product-like libraries with high levels of stereoselectivity.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The current progress is generally in line with initial expectations. A novel catalytic synthetic method has been identified successfully to generate chromone lactones with high enantioselectivity (most >99% ee) and moderate diastereoselectivity (up to 7/1). An unexpected selectivity reversal of the reaction was observed. The results achieved have been published in the journal (Chem. Sci. 2020, 11, 7170.).
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| Strategy for Future Research Activity |
Although the developed synthetic method worked well for the generation of simplified chromone lactones, the synthesis of natural products using chromone substrate bearing ester group at the β position of enone remain difficult. Thus, the identification of a more robust catalytic system suitable for the sterically hindered chromone is highly desirable, and is the next work for this project.
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| Remarks |
https://www.bikaken.or.jp/
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