2020 Fiscal Year Annual Research Report
Hybrid Metal Catalysis for C-H Functionalization of Simple Arenes
Publicly Offered Research
| Project Area | Hybrid Catalysis for Enabling Molecular Synthesis on Demand |
|---|
| Project/Area Number |
20H04830
|
|---|
| Research Institution | Institute of Physical and Chemical Research |
|---|
Principal Investigator |
イリエシュ ラウレアン 国立研究開発法人理化学研究所, 環境資源科学研究センター, チームリーダー (40569951)
|
|---|
| Project Period (FY) |
2020-04-01 – 2022-03-31
|
| Keywords | organic synthesis |
|---|
| Outline of Annual Research Achievements |
The purpose of this research is the development of a hybrid strategy for C-H functionalization of simple arenes: activation of an arene substrate by catalytic pi-coordination to a metal such as Cr, causing a strong decrease in electron density on the arene, and thus increasing the reactivity towards nucleophilic attack of a reagent or electron-rich metal catalyst.
During FY2020, we tested this hypothesis for the transition-metal-catalyzed borylation of arenes, which typically proceeds well for electron-deficient arenes, but it is more difficult for electron-neutral and -rich arenes. Initial experiments showed that pi-coordination of xylene or anisole to chromium does accelerate the cobalt/terpyridine-catalyzed borylation of these substrates, and the reactivity was improved by the addition of KF. To our surprise, control experiments revealed that the cobalt catalyst is not necessary, and KF is enough to activate the boron reagent.
We also investigated the pi-coordination strategy for the activation of aryl chlorides. Initial trials for activating aryl chlorides towards Pd- or Fe-catalyzed couplings were unsuccessful, but we found that an aryl chloride coordinated to chromium carbonyl reacts with a solvent amount of arene in the presence of an alcoxide and a bipyridine ligand, probably through a radical pathway.
|
| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Based on the hypothesis of activating arenes or arene chlorides through pi-coordination to a Cr complex, we discovered two new reactivities: the uncatalyzed borylation of arenes in the presence of a KF activator, and the radical reaction of arene chlorides with arenes. These results demonstrate the potential of pi-coordination strategy for organic synthesis, and especially C-H functionalization reactions.
|
| Strategy for Future Research Activity |
Activation of arenes: we next plan to design a chromium complex precursor that can undergo ligand exchange with an arene substrate, and thus activate the arene towards borylation. Moreover, we plan to investigate the possibility of catalytic reactions in chromium complex. Once the reaction parameters are established, we plan to apply the new reaction for the functionalization of simple and complex arenes, with a focus on electron-rich ones, typically less reactive under transition metal catalysis. We also plan to investigate the mechanism of the borylation reaction through experiment and computation.
Activation of chloroarenes: we plan to optimize the reaction conditions for the reaction with arenes, especially the possibility of decreasing the amount of arene substrate. Next, we plan to investigate the scope of this reaction, then perform mechanistic studies to confirm the radical nature of the reaction.
|
