2016 Fiscal Year Annual Research Report
Design of Iron Catalyst for Activation of Simple Arenes and Heteroarenes
Publicly Offered Research
| Project Area | Precise Formation of a Catalyst Having a Specified Field for Use in Extremely Difficult Substrate Conversion Reactions |
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| Project/Area Number |
16H01005
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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, 大学院理学系研究科(理学部), 准教授 (40569951)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 合成化学 |
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| Outline of Annual Research Achievements |
During FY2016, we focused our efforts towards activation of simple substrates, and we hypothesized that a triphosphine ligand may stabilize organoiron enough to enable the activation of weakly coordinating substrates. Despite the fact that easily available triphosphines have been known for a long time, they have never been used for transition metal catalysis. These ligands in combination with an iron salt catalyzed the ortho methylation of aromatic and heteroaromatic carbonyl compounds such as carboxylic acids, esters, amides, and ketones. Notably, this reaction proceeded only with the triphosphine ligand, and other ligands were ineffective. Also, the use of a mild organoaluminum reagent was important, and the corresponding magnesium and zinc reagents did not afford the product at all. 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, as it is often the case with late transition metal catalysts such as palladium. The catalytic system was powerful enough to selectively tetramethylate benzophenone. An indoleamine 2,3-dioxygenase-1 inhibitor was also smoothly methylated.
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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
The reaction developed in FY2016 is the first demonstration of the utility of triphosphine ligands for transition metal catalysis, and is expected to open new horizons for ligand design. Also, this reaction is the first example of iron-catalyzed C-H activation of simple, weakly coordinating substrates such as carbonyl compounds.
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| Strategy for Future Research Activity |
1) The iron/triphosphine-catalyzed reaction of carbonyl compounds with aluminum reagents was restricted to methylation. In order to expand the scope of this reaction, I will design new aluminum reagents capable of functioning as a base for the activation of carbonyl compounds, following reaction with a variety of electrophiles such as alkynes, alkenes, alkyl halides, etc.
2) I also plan to investigate the coupling of two C-H substrates: directed coupling of amides, followed by coupling of the resulting iron intermediate with a heteroarene or arene. Based on this reaction, I next plan to design a ligand that enables the direct activation of (hetero)arenes, without the need of a directing group.
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Research Products
(16 results)
