2021 Fiscal Year Research-status Report
Asymmetric Borylation of Remote C(sp3)-H Bonds for the Construction of Compounds with Three-Dimensional Structural Diversity
| Project/Area Number |
20K15269
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| Research Institution | Hokkaido University |
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Principal Investigator |
REYES RONALD・LAZO 北海道大学, 化学反応創成研究拠点, 特任助教 (30845475)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | asymmetric synthesis / borylation / organometallic catalysis / organic synthesis / C-H activation / C-H functionalization |
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| Outline of Annual Research Achievements |
With our interest in the development of novel methodologies for the transformation of C-H bonds in readily available feedstock chemicals, we previously demonstrated the competent activation and subsequent asymmetric borylation of gamma-C(sp3)-H bonds under Ir catalysis. Our collaboration with ICReDD scientists has given us infinite opportunity to further extend the reactivity of our catalytic system.
Furthermore, using our catalytic system we have developed a strategy for the asymmetric desymmetrization of monocyclic saturated ring systems in pharmacologically-relevant heteroarenes including pyridine, quinoline, isoquinoline, and benzo-annulated N-heteroaryl frameworks facilitating the preparation of cycloalkane organoboron derivatives appended on common natural product, bioactive, and medicinally significant heterocyclic cores.
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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
As described, several important paper contributions have been made. Thus, guided by calculation derived transition-state models, we recently succeeded in the asymmetric borylation of more distal C-H bonds in the aliphatic hydrocarbon chain of common and readily available chemical feedstocks including biomass resources allowing for a more sustainable and efficient organic synthesis. Thereby, the borylation of epsilon-C-H bonds, located five carbons away from the carbonyl group of the substrate, has been achieved - a direct functionalization realized using a modularly designed supramolecular catalytic assembly.
Moreover, an enantioselective desymmetrization of monocyclic saturated ring systems using a chiral Ir-monophosphite catalyst through a directed C(sp3)-H borylation was developed. The methodology provides access to enantioenriched cycloalkane boronate derivatives encompassing synthetically significant small to intermediate-sized rings from cyclopropane to cycloheptane. The catalytic system efficiently discriminates between methylene C-H bonds located on two different prochiral carbon centers leading to the generation of highly desired structural cycloalkane motifs bearing contiguous chiral centers. Further transformations of the cycloalkane boronate products were also demonstrated
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| Strategy for Future Research Activity |
It is my plan and goal to conclude and publish our work on the asymmetric desymmetrization of cycloalkyls appended unto privileged heterocyclic cores. This project has been started last year and I believe that our findings merit publication at this stage. Moreover, for the year 2022, I am working on the development of a supramolecular catalytic system consists of a metal catalyst and chiral ligand platform in generating an asymmetric field or a substrate binding cavity that will enable the activation and functionalization of remote C-H bonds.
Our project collaboration in ICReDD is on-going and it looks into the possibility of achieving site-selectivity and stereocontrol in C-H bond activation by carefully considering catalyst design combining experimental, theoretical, and information science. We envisioned that computational information will help to expedite the development of effective catalyst to realize our goal in functionalizing remote C-H bonds in readily available starting materials such as hydrocarbon derivatives, fatty acids, and bioactive compounds. This strategy will provide a unifying theme for the diversification of molecules generating 3D complexities to enable facile access to important compounds.
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| Causes of Carryover |
Due to the onset and continuous surge of COVID-19 pandemic several conferences were cancelled. Laboratory spending is likewise affected due to some restrictions enforced to prevent the spread of the infection. For the next fiscal year, research activities will be promptly continued. Research expenses will be devoted in purchasing necessary chemicals for reaction optimization. Essential equipment and glassware will be purchased in line with the need of the research. Attendance in prominent conferences will also be prioritized.
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[Presentation] Asymmetric Remote C-H Bond Borylation with a Modular Iridium Catalyst2021
Author(s)
Reyes, R. L., Sato, M., Iwai, T., Suzuki, K., Maeda, S., and Sawamura, M.
Organizer
101st Chemistry Society of Japan (CSJ) Annual Meeting
Int'l Joint Research
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[Presentation] Catalytic Enantioselective Remote C-H Borylation of Aliphatic Carboxylic Amides and Esters2021
Author(s)
Reyes, R. L., Sato, M., Masuda, Y., Higashida, K., Iwai, T., Suzuki, K., Maeda, S., and Sawamura, M.
Organizer
67th Organometallic Chemistry Symposium
Int'l Joint Research
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[Presentation] Synthesis of Biologically-Relevant Organoboron Compounds through Asymmetric C-H Borylation2021
Author(s)
Reyes, R. L., Sato, M., Chong, S.-G, Higashida, K., Iwai, T., Suzuki, K., Maeda, S., and Sawamura, M.
Organizer
13th International Medicinal Chemistry Symposium
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