Sulfur-based solutions for the selective functionalization of organic substrates

Project Information

SULFOSOL

Grant agreement ID: 771295

DOI

10.3030/771295

Project closed

EC signature date 30 January 2018

Start date 1 May 2018

End date 31 January 2024

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 997 500,00

EU contribution

€ 1 997 500,00

Coordinated by

GEORG-AUGUST-UNIVERSITAT GOTTINGEN STIFTUNG OFFENTLICHEN RECHTS
Germany

Periodic Reporting for period 4 - SULFOSOL (Sulfur-based solutions for the selective functionalization of organic substrates)

Reporting period: 2022-11-01 to 2024-01-31

Summary of the context and overall objectives of the project

During the course of this research project a series of novel sulfur-based reagents depicting unique electronic properties have been prepared. These reagents allow the late stage functionalization of complex organic molecules or important synthetic intermediates; thus, facilitating the identification of new targets in areas such as drug discovery and crop science. Group transfer reagents are often based in platforms such as hypervalent I(III) reagents or pyridinium salts, but these reagents depict limitations. Either the groups that can be transferred are limited to some functionalities, or their implementation in industrial processes is seriously limited due to their high reactive nature. The reagents we have prepared in SULFOSOL partially solve some of these problems. They are much much more thermally stable than the I(III) counterparts, but at the same time more reactive ant atom economic than pyridinium ones. This allows their handling in big scale, and enables functional group manipulations to be carried out on these reagents after incorporation of the sulfonium moiety. Moreover, most of the new transformations we have developed are metal free, allowing their implementation in the last steps of complex syntheses where traces of transition metal impurities are not tolerated for safety issues.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

-We have identified the dibenzosulfonium platform as the most appropriate one to develop electrophilic group transfer reagents. This group provides thermal stability, something that hypervalent iodine salts lack, while it does not reduce the reactivity of the resulting reagent (work package 1 of the DoA)
-Making use of this platform we have already synthesized four new reagents able to transfer cyano- alkyne and diazomethyl and pentafluorocyclopropyl groups, respectively, under metal free conditions. A fith reagent has been designed that is able to transfer N-atoms under Rh catalysis (work package 1 of the DoA).
-We have also developed a new methodology for the halocyanation of alkynes (work package 2 of the DoA) and we are studying the compatibility of our reagents with C-H activation processes (work package 2 of the DoA).
-We have tried to develop asymmetric versions of the reactions studied. The enantiomeric excesses are still moderate, but promising (work package 3 of the DoA).
-We have also explored S-based platforms different than dibenzothiophene to design our reagents (work package 4 of the DoA).
-Most of the reagent prepared have been patented, and some are already commercially available.
-We plan now the optimization of large scale syntheses for such reagents.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

- We have developed during the last period an electrophilic amination reagent that is able to transfer nitrogen atoms under Rh-catalysis.
- We have used our new reagents for the modification of proteines and other biomolecules under biological conditions.
- Some success has been obtained in the development of cyclisation cascades, in which after the initial functionalization, the intramolecular cyclisation of the substrates is promoted. This is a topic we will continue to investigate after SULFOSOL

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