2016 Fiscal Year Annual Research Report
Iron-Catalyzed C-H Activation using Organoboron Compounds
| Project/Area Number |
26708011
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| Research Institution | The University of Tokyo |
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Principal Investigator |
イリエシュ ラウレアン 東京大学, 理学(系)研究科(研究院), 准教授 (40569951)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Keywords | 合成化学 |
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| Outline of Annual Research Achievements |
The purpose of this project is the development of iron-catalyzed C-H activation using mild organometallic reagents such as organoboron compounds. During FY2016, we developed an iron-catalyzed activation of the sp3 C-H bond in aliphatic propionamides possessing an 8-quinolylamide group, followed by arylation, heteroarylation, and alkenylation with organoborate reagents. Notably, the use of the mild organoborate reagents allowed for the first time the alkenylation of an aliphatic C-H bond, which has been achieved to date only for activated alkenyl groups. Notably, the alkenyation did not proceed when an organozinc reagent was used, demonstrating the importance of using a mild organoboron compound.
Also, we found that trimethylaluminum effects the methylation of simple aromatic and heteroaromatic carbonyl compounds such as carboxylic acids, esters, amides, and ketones, in the presence of an iron catalyst and a triphosphine ligand. The mild reaction conditions tolerated sensitive functional groups such as boroester, bromide, acetamide, or enolizable ketone, and heteroatoms such as sulfide, thiophene, or pyridine did not poison the catalyst. Notably, this reaction proceeded only with an aluminum reagent, and methylmagnesium or methylzinc reagents were completely ineffective.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Transition-metal-catalyzed alkenylation of an aliphatic C-H bond has met limited success, only for special cases using activated alkenyl groups. The use of mild organoboron reagents in combination with an iron/diphosphine catalyst allowed introduction of simple alkenyl groups to an aliphatic amide for the first time.
The use of a mild trimethylaluminum reagent in the presence of an iron/triphosphine catalyst enabled for the first time the iron-catalyzed C-H activation of simple, weakly coordinating substrates such as carbonyl compounds.
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| Strategy for Future Research Activity |
The research during this project uncovered important guidelines for the design of mild bases and efficient ligands for iron-catalyzed C-H activation. The aluminum reagents were especially effective, enabling C-H activation with high catalyst turnover, tolerance of various sensitive groups, and in combination with a triphosphine ligand allowed for the first time activation of simple carbonyl compounds. I plan to further engineer the aluminum reagents in order to achieve activation of various weakly-coordinating substrates, followed by coupling with neutral molecules such as alkynes, alkenes, alkyl halides, etc. I also plan to investigate other mild organometallic reagents such as organosilicon compounds as a base for C-H bond activation, and other inexpensive bases such as metal alkoxides for C-H bond activation.
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| Causes of Carryover |
During FY2016, the laboratory moved to a new building, and during April-May 2016, the research activity largely stopped because of set up of the new laboratory. Thus, I plan to recover the research time during FY2017.
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| Expenditure Plan for Carryover Budget |
During FY2017, the research funds will be used for further investigating organometallic bases for iron-catalyzed C-H bond activation. A large part of the research funds will be used for the purchase of chemicals such as organometallic reagents and their precursors, pohosphine ligands, and other consumables required for synthetic organic chemistry experiments.
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