Electrochemical Sulfonylation of Lysine Residues in Continuous Flow Microreactors.

Projektinformationen

ELECTROSULF

ID Finanzhilfevereinbarung: 840724

DOI

10.3030/840724

Projekt abgeschlossen

EK-Unterschriftsdatum 17 April 2019

Startdatum 5 September 2019

Enddatum 4 September 2021

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 175 572,48

EU-Beitrag

€ 175 572,48

Koordiniert durch

TECHNISCHE UNIVERSITEIT EINDHOVEN
Netherlands

Periodic Reporting for period 1 - ELECTROSULF (Electrochemical Sulfonylation of Lysine Residues in Continuous Flow Microreactors.)

Berichtszeitraum: 2019-09-05 bis 2021-09-04

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Electrochemistry has become an important tool for organic chemists as it allows to selectively functionalize molecules by tuning the applied voltage, without the addition of strong oxidant/reductant agents. As electrons are considered green reagents and not harsh conditions are generally involved, synthetic electrochemistry can be seen environmentally friendly. Although known for centuries, this technique has only recently become an intriguing possibility for scientists, and it gets explored more and more, due to modern technological advances.
In this sense, continuous-flow chemistry with its benefits (better heat- and mass transfer, higher productivity, etc.) can significantly contribute to the development of new more efficient transformations, also in a bigger scale. The combination of electrochemistry and continuous-flow technology could have a strong impact in synthetic chemistry, with important consequences for the industrial sets up too. In fact, the development of new electrochemical synthesis in flow is important as it might contribute to an industrial shift towards more efficient processes and thus to a more sustainable society.
Taking this in consideration, the aim of my project was to learn how to use the electrochemical microflow reactor to find and tune new reactivities. Although the first attempts were unsuccessful, I finally managed to optimize and develop the electrochemical azolation of arenes in flow, proving once more the great potential of electrochemistry in flow. Compared to other azolation methods, electrochemistry does not require neither metal nor organic catalyst; moreover, the reaction time can be reduced to 10 min in flow, instead of several hours in batch.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Electrochemical sulfonylation of lysine: Considering that the electrochemical sulfonylation in flow of protected lysine was already pubished by the time I started the project (J. Am. Chem. Soc. 2019, 141, 5664−5668), I focused on the sulfonylation of unprotected lysine in dipeptides. Unluckily, the obtained the results were not good enough for publication.

Electrochemical azolation of arenes in flow: this is an important reaction which allows the formation of a new C–N bond between unactivated substrates. This transformation has already been studied in batch electrochemical systems, but often required higher temperature/longer reaction times. Our microflow reactor allow to accelerate the reaction which could take place in 10 min residence time and at room temperature. A scale-up on 1.54 mmol was still feasible. In total, 22 substrates were prepared in moderate to excellent yields. This project was finally published (J. Org. Chem. 2021, DOI: https://doi.org/10.1021/acs.joc.1c01409). The paper was advertised in Twitter where it received a good feedback (15 retweets, 111 “likes” on September, 10 2021).

Photocatalytic azolation of arenes in flow (in collaboration with prof. Erwin Reisner’s group): parallelly to the previous works, I collaborated with some group members (Zhenghui Wan and others) who performed the same reaction but using a heterogeneous recyclable carbon nitride as the photocatalyst to start the reaction. The transformation proved efficient with 30 different substrates. It was possible to translate the system in a continuous-flow reactor and to scale-up the process. This paper was published in ChemSusChem (https://doi.org/10.1002/cssc.202101767).

Preparation of a review about technology in photochemistry: the review was written together with 4 other group members (Fabian Raymenants and others) and it was published in Chem. Rev. (DOI: https://doi.org/10.1021/acs.chemrev.1c00332). The work was advertised on Twitter (35 retweets, 138 “likes” on September, 10 2021).

Organophotoredox hydrodefluorination of trifluoromethylarenes (in collaboration with prof. Véronique Gouverneur’s group): during this collaboration about organophotocatalysis, which resulted in a paper, my role was to measure to study the mechanism of the transformation by performing the cyclic voltammetry of various substrates (J. Am. Chem. Soc. 2020, 142, 9181–9187)

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The results of ELECTROSULF, though different from what expected at the beginning, are very notable, as proven by the record of publications (4 papers in 4 major journals). Moreover, the international collaborations started during my MSCA-IF prove the importance of the obtained results and will lead to the development of new projects.
This will result in a strong feedback in the future from the scientific community. In particular, the results published in the J. Org. Chem. paper show the wide applicability of electrochemistry in flow, thus paving the path for future industrial applications which should be more sustainable. This should eventually help in building a greener society.

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