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De Novo Fatty Acid Synthesis from Alkane Feedstocks and CO2

Periodic Reporting for period 1 - FAT-FEEDOX (De Novo Fatty Acid Synthesis from Alkane Feedstocks and CO2)

Reporting period: 2019-05-01 to 2021-04-30

Fatty acids and short-chain aliphatic acids can be widely found in nature, playing significant roles in different areas of our daily life. In addition, fatty acids are important building blocks in synthetic chemistry to build up molecular complexity. Current industrial production of fatty acids is based on the fermentation of sugar or starch, oxidation of biomass or carbonylation reactions with carbon monoxide (such as Monsanto process or Cativa process for acetic acid production). Employing CO2 as an abundant C-1 building block in organic synthesis to prepare carboxylic acids has been emerged as a straightforward alternative to classical synthetic routes. However, most of the recent advancements in the activation/carboxylation require prefunctionalized starting materials. Despite the high levels of sophistication realized, FAT-FEEDOX introduces a more favorable scenario: the direct combination of abundant chemical feedstocks with CO2 en route to fatty acids. The conceptual novelty of FAT-FEEDOX lies on the merger of alkane borylation and catalytic carboxylation for the selective incorporation of CO2 into C(sp3)–H bonds. This project will make use of simple, unfunctionalized precursors, avoiding the need for stoichiometric halogenated precursors or excess of metal reagents that typically plague the current catalytic carboxylation portfolio.

Although the implementation of CO2 fixation in synthetic methods will unlikely reduce its concentration in the atmosphere, we cannot underestimate its value in synthetic endeavors by using CO2 as an abundant, inexpensive and renewable C1 feedstock, as it provides an added value that might be able to compensate the potential costs of its capture and recyclability. This new approach will be translated into a better use of energy and carbon, reducing waste, representing a step-forward for our circular economy. Therefore, this project is closely aligned with the H2020 priorities, especially within the societal challenge 5: Climate action, environment, resource efficiency and raw materials.

The main objective of FAT-FEEDOX is to develop efficient protocols that enable the direct carboxylation of alkane feedstocks via synergistic C(sp3)–H borylation/CO2 insertion, thus allowing to obtain in essentially one-step fatty acids, key building blocks on the manufacture of detergents, soaps, dyes, animal feed, plastics, agrochemicals or pharmaceuticals.
The specific objectives are the following:
1. To prepare a library of catalysts and ligands to promote terminal C(sp3)–H functionalization
2. To study the reactivity of the corresponding alkyl metal boryl species with CO2
3. To develop a one-pot carboxylation of alkanes via the intermediacy of alkyl metal boryl species

• Conclusions of the action:
The initial plan for direct or cascade route to sp3 carboxylation with CO2 did not give any corresponding product. The unsuccessful results on the study of the initial direct carboxylation of hexane with CO2 prompted us to come up with another pathway for sp3 C-H activation. The experience of the ER in dealing with Ir containing complexes and the recent resurge of photoredox arena with Ir sensitizer directed us to step into photoredox regime for sp3 C-H activation. In combination with the ample knowledge on nickel catalysis from the Martin group, we started the Ir/Ni dual catalysis journey. This part has been finished and published in a top catalysis journal in collaboration with another world-leading group in nickel catalysis, the Montgomery group in the US.

• Research endeavours with the project have produced:
FAT-FEEDOX has resulted into 1 publication, which has been published in high ranking catalysis journal (ACS Catal. 2020, 10, 4671–4676; DOI: 10.1021/acscatal.0c01318). It has been broadly disseminated by publishing in Open Access. In collaboration with the Communications and Outreach unit at ICIQ, the result has been uploaded to the twitter accounts of ICIQ (@ICIQchem) and the Martin group (MartinLab_ICIQ).
In the Martin group at ICIQ, Dr. Yin has led the project FAT-FEEDOX by planning, conducting the research, monitoring the milestones time to time. The results obtained in FAT-FEEDOX are important to the field of organometallic chemistry, inert bond activation and sustainable organic synthesis. The unsuccessful results on the study of the initial direct carboxylation of hexane with CO2 prompted us to come up with another pathway for direct sp3 C-H activation, which is a vital path for structural modifications of feedstock materials containing sp3 C-H.

In combination with the ample knowledge on nickel catalysis from the Martin group and the resurgence of using Ir sensitizers in photocatalysis, we started the Ir/Ni dual catalysis journey. A dual catalytic sp3 alfa C–H arylation and alkylation of benzamides with organic halides has been developed. This protocol exhibits an exquisite site-, chemo- and enantioselectivity pattern, offering a complementary reactivity mode to existing sp3 arylation or alkylation events via transition metal catalysis or photoredox events. This work has been collaboratively published between the host group and the Montgomery group in the university of Michigan, US in one of the top ranked catalysis journals, ACS Catalysis (ACS Catal. 2020, 10, 4671–4676; DOI: 10.1021/acscatal.0c01318.
With the advancement of FAT-FEEDOX, Dr. Yin gained several new knowledge in handling new techniques through the training in ICIQ, such as HTE, NMR, MS and EPR trainings. Furthermore, Dr. Yin participated several workshops and skill learning courses, such as the Grant Writing workshop, the Intellectual Property workshop and the leadership courses, where he enriched his professional presenting skills and developed creative problem solving ability, which will definitely be valuable for his future career development. Moreover, the current results achieved in FAT-FEEDOX will have a significant impact on the contribution of visible light photocatalysis/nickel dual catalysis area for the preparation of substituted benzamides under mild conditions. The method developed by Dr. Yin has been widely disseminated on the twitter of the Martin Lab, also been presented by the ER in a prestigious international conference, 9th Pacific Symposium on Radical Chemistry (PSRC-9, California, US). The participation in the international conference has offered Dr. Yin great opportunities to initiate networks with the world leading scientists both from academia and also from industry partners, which will be a great fortune for the ER to build his recognition in his future career. With the advancement of FAT-FEEDOX, Dr. Yin has gained deeper understanding about independent scientific research and have experienced unforgettable exciting moments, which will be a powerful engine to promote the ER to pursue more in the research direction in his future career path.

Dr. Yin has a long standing aim at joining a pharmaceutical company, where he can combine his organic chemistry backgroud and medicinal chemistry backgroud together. To this end, the ER has accepted an offer from a company in China, where he will get hands on API synthesis and early drug development.
Dual Catalytic Platform for Enabling sp3 α C–H Arylation & Alkylation of Benzamides