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Asymmetric cooperative catalysts constructed on supramolecular helices

Periodic Reporting for period 1 - SupraCopCat (Asymmetric cooperative catalysts constructed on supramolecular helices)

Reporting period: 2018-08-01 to 2020-07-31

Novel robust catalysts are key to improve the efficiency and reduce the environmental impact of industrial processes, which provide crucial chemical intermediates/products in modern society. In particular, asymmetric catalysis (AC) is regarded as the most important approach to synthesize enantiomerically pure compounds, which have attracted intense interest from industry and academia. For example, a catalytic asymmetric synthesis of Remdesivir as one of the anti-COVID-19 drug was reported, in which a chiral bicyclic imidazole catalyst played a key role in the chiral induction. Besides this, prominent anti-inflammatory drugs, Ibuprofen and Naproxen, were also successfully synthesized via asymmetric hydroformylation (AHF)/oxidation or asymmetric hydrogenation. These compounds are indispensable intermediates of pharmaceuticals, natural products, and fine chemicals in modern society.
However, the development of catalysts is traditionally a time-consuming step because it requires synthesizing and testing a large number of systems. The main benefit of this project is to revolutionize the synthesis of novel catalysts via a supramolecular strategy that consists in mixing two or three building blocks (taken from a vast library) that self-assemble to form the catalyst. In this way catalyst optimization is vastly facilitated.
More specifically, the aim of the SupraCopCat project is to provide new asymmetric cooperative catalysts, by anchoring different catalytic functions (such as dimethylaminopyridine and thiourea) at the periphery of a supramolecular helix and test them in various enantioselective catalytic reactions.
The main results achieved are:
i) New methods for the synthesis of novel SupraCopCats were developed.
ii) 14 novel building blocks were synthesized and fully characterized by 1H NMR and HR-MS.
iii) The supramolecular self-assembly of the obtained building blocks were fully investigated by UV, IR, CD spectroscopies and Small Angle Neutron Scattering (SANS), and the structures for the assemblies were determined.
iv) The catalytic activity of these catalysts was evaluated in:
1) the enantioselective Michael addition of malonate ester to nitroalkenes and
2) the ring opening polymerization of rac-lactide.

In the latter reaction, a two-fold increase in the rate of the polymerization was observed with the SupraCopCat catalyst relatively to a catalytic system of reference.

Exploitation: the results are highly encouraging but more investigations are necessary to improve the catalysts selectivity. Excellent catalyst performances are required for publication.

Dissemination: one of us (Matthieu Raynal) delivered a 2h lesson to ca. 30 Master students on the topic of supramolecular catalysis.
Novel catalytic systems have been developed by using asymmetric cooperative supramolecular catalysts.

After further detailed optimization of reaction conditions, excellent selectivities and activities can be expected in various asymmetric reactions such as enantioselective Michael addition and ring open polymerization.

This achievement will provide a new asymmetric synthetic method, with practical potential utility in the synthesis of drugs or fine products in modern society.

Most importantly, this project proved the novel concept for the design of chiral supramolecular catalysts, which will largely enrich the field of asymmetric catalysis