Repurposing the novel DATB catalyst for the direct catalytic cross-coupling of carboxylic acids

2020 Fiscal Year Research-status Report

• Project/Area Number: 20K15292
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: OPIE Christopher 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 (90858531)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: heterocycle / catalyst / DATB

Outline of Annual Research Achievements

Unfortunately the known DATB heterocycle-containing molecules have not yet provided a means to catalyze different reaction classes other that known in the literature. Even our plan to use the amide-forming ability of DATB in tandem with a separate catalytic system has not been shown to be practical at this stage.
The replacement of the terphenyl scaffold with other structures had appeared to be straightforward, however it was found to be crucial for DATB ring formation. Despite this, variants elaborating the terphenyl scaffold were designed, and it was seen that dimerization to DATB could be hindered to such an extent that a reactive intermediate could be isolated.
This intermediate can react with other molecules to give novel heterocycles, which are potentially catalytically active.

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

The status for the project, 'slightly delayed', was selected for two main reactions. Firstly, the lack of success in our initial plan for the use of the already-established DATB-containing molecules in catalyzing other reaction types has forced us to investigate the synthesis of new catalysts. We had hoped to avoid this very time-consuming process, but as it unexpectedly let to some interesting but unforeseen compounds, it was not time wasted.
Secondly, the research institute where this research is being conducted is located in Tokyo, which, due to the spread of COVID-19, has been in and out of various forms of 'State of Emergency' for over a year. Various policies are in place at the research institute in order to combat the spread of the infection, which has naturally resulted in a reduced number of working hours.

Strategy for Future Research Activity

The original DATB-containing molecules have not yet been exhaustively investigated for their applicability to other reaction classes, and thus more experiments and reaction conditions need to be considered.
Additionally, the novel heterocycles recently developed - and indeed the key intermediates themselves - have the potential to be catalytically active. Even in the case that they do not harbor catalytic activity, these compounds are intellectually compelling, and ideally will be investigated by X-ray crystallography.
Finally, using the same synthetic platform, the development of other novel heterocycles will be investigated. The ideal scenario involves the introduction of Lewis acidic heteroatoms, giving rise to a new - or perhaps simply stronger - catalytic system than that of DATB.

Causes of Carryover

The budgeting materials for the first year of funding was predicated on finding an applicable catalytic system, then enhancing this catalytic system with various, often quite expensive, metal additives and ligands. Instead, systematic modifications of the catalyst itself was found to be necessary, which was performed with more typical reagents.
Having produced some interesting and novel compounds, we are in the fortunate position of having the means to scale up their synthesis, as well as exploring their use in the aforementioned desired catalytic systems.