Synthesis of Heterocycles via One-Pot Sequential Reactions Using Recyclable Heterogeneous Metallic Multi-Task Catalysts – SYNTH ONE POT

One of the major aim of this project was to design and prepare new heterogeneous bimetallic catalysts displaying uncovered reactivities in various reactions. More specifically, we have developed simple methods for adsorbing metallic NPs onto carbon materials. Metallic NPs were generated from Pd(OAc)2, Cu(OAc)2 and KAuCl4 for respectively Pd NPs, Cu NPs, and Au NPs in MeOH under an atmosphere of H2. The addition of activated charcoal or graphite to this solution provided the heterogeneous catalyst with an excellent control of the NPs morphology and size

In this project we obtained three major results. The first one is the discovery of the first Heck-Matsuda reaction using a substoichiometric amount of diazonium salt through an uncovered double catalytic cycle. Our concept features very mild conditions, and generates only environmentally benign byproduct such as t-BuOH, H2O, and N2. The second one is a novel concept to increase the recyclability of palladium on carbon-based catalysts for the Sonogashira reaction. The origin of the reusability enhancement can be found in the stabilisation of Pd nanoparticles through the formation of an alloy with gold atoms, without altering its initial shape. The third one is the design of a multi-task Pd-Cu/C catalyst for sequential reactions allowing the preparation of original heterocycles.

The ANR “SYNTH ONE POT” has been successful on many points and led, among others, to two exiting results: (1) the cooperative bicatalysis for the coupling aryl diazonium salts with olefin, and (2) the use of supported alloys as robust and recyclable catalysts.
These studies led to promising perspectives:
(1) the developement of an asymmetric version of the cooperative bicatalytic process. Due to a constrained timing, this point has not been adressed in the «SYNTH ONE POT« project.
(2) The discovery of new supported alloy for several catalytic processes.

This project led to 12 publications in highly rated journals including the following four most significant papers:
1. An Unprecedented Substoichiometric Use of Hazardous Aryl Diazonium Salts in the Heck-Matsuda Reaction via a Double Catalytic Cycle. Le Callonnec, F.; Fouquet, E.; Felpin, F.-X. Org. Lett. 2011, 13, 2646-2649
2. Sustainable Heck-Matsuda Reaction with Catalytic Amounts of Diazonium Salts: An Experimental and Theoritical Study. Susperregui, N.; Miqueu K.; Sotiropoulos, J.-M.; Le Callonnec, F.; Fouquet, E.; Felpin, F.-X. Chem. Eur. J. 2012, 18, 7210-7218.
3. Stabilization of carbon-supported palladium nanoparticles through the formation of an alloy with gold. Application to the Sonogashira reaction. Rossy, C.; Majimel, J.; Fouquet, F.; Delacôte, C.; Boujtita, M. Labrugère, C.; Tréguer, M.; Felpin, F.-X. Chem. Eur. J. 2013, 19, 140124-14029.
4. Palladium and Copper-Supported on Charcoal: A Heterogeneous Multi-Task Catalyst for Sequential Sonogashira-Click and Click-Heck Reactions. Rossy, C.; Majimel, J.; Tréguer-Delapierre, M.; Fouquet, F.; Tréguer, M.; Felpin, F.-X. J. Organomett. Chem. 2014, 755C, 78-85.

The development of modern sustainable chemistry will be a major factor challenge of the 21th century in industrialized countries. Being at the heart of many discoveries in various scientific areas from physic to medicine, chemical sciences must play a pivotal role to solve many environmental issues we must face. The minimization of depletive resources in favor of renewable feedstock, the reduction of waste, and the use of environmental friendly reagents are some of the issues that chemists must address in a near future.
In this prospect, heterogeneous catalysis and one-pot reactions represent fertile and innovative fields that meet many of the twelve principles of green chemistry. Although these fields have independently been the subject of many scientific research programs, the combination of both in chemical synthesis is, quite surprisingly, largely unexplored. Indeed, this promising association should enable a breakthrough toward sustainable chemistry. In this proposal, we expect to take advantage of the heterogeneization of one or more transition metals on carbon material (charcoal and graphite) able to catalyze many transformations in only one reaction vessel for the construction of complex molecular architectures. Tandem transformations catalyzed by metallic catalysts can be divided in two classes of reactions:
• One-pot reactions mediated by a single metallic complex
• One-pot reactions mediated by a multimetallic catalyst
In this proposal, we will expose our interest for these two classes of reactions in the context of heterogeneous catalysis:
(1) Quite surprisingly, one-pot reactions catalyzed by palladium catalysts have almost been exclusively used for consecutive reactions having related mechanism. In the first part of this project, we envisage to take advantage of the various properties of heterogeneous palladium catalysts for executing one-pot fundamentally different reactions. Enantioselective approaches will be also evaluated.
(2) In a second time, we will propose to devise one-pot multi-step sequences using supported bimetallic catalysts. This area of research is of recent interest, and much work needs to be done to develop efficient and useful transformations.
These two different approaches for executing one-pot reactions will be applied to the synthesis of relevant and quite complex heterocycles whose structures could be interesting for biological purposes. One of the main goals of the present proposal is to prepare, fully characterize and test the catalytic activity of new catalysts supported on carbon material.
A careful analysis of each new catalyst will provide useful information for a better understanding, as well as for the optimization, of the heterogeneous catalysts with regard to the expected catalytic activity. The recycling of the catalysts will be also studied in depth. Although almost unexploited in catalysis for C-C or C-X bonds formation, we expect that the unique properties of these carbon-based materials could be of interest for one-pot reactions. This proposal involves two researchers and two technicians whose competences are clearly complementary. The coordinator of the project, François-Xavier Felpin, specialized in organic synthesis and palladium catalysis will study new one-pot reactions using multi-tasks catalysts supported on graphenes. The catalysts will be prepared by Mona Tréguer who has a strong background in the preparation of metallic nanoparticles on a support and in solution. Catalysts characterization will be realized by Jerôme Majimel who is a specialist in microcospy and nanometric characterization.