PhD position in organic chemistry: Regioselective strategies for the multiformation of C-C bond through metallotropic rearrangement and valorisation of CO2

Offer Description

Context:

Historically, academic research efforts in organic synthesis have always been directed towards the development of reactions leading to the selective formation of only one carbon-carbon bond in a predictive manner. Since organic structures of interest for fine chemistry and pharmacy are usually strongly different from commercially available compounds, this philosophy inevitably results in proposing time-consuming multi-step synthetic sequences to reach the desired molecular targets. As these targets are obtained at the cost of titanic efforts and in tiny amounts, the relative synthetic approaches are often inadequate for the industry.  This is why a growing number of synthetic chemists are focusing on the development of reaction processes allowing the one-pot formation of several carbon-carbon bonds without the need of usual intermediary treatment and purification operations. This is in line with the concept of “pot-economy”1 which enables to approach the ‘ideal synthesis’ when associated with the use of abundant, biocompatible and/or renewable resources. We reckon that a strategy based on the concept of “remote functionalisation through internal induction”2 would offer the pot-economy concept a new dimension. Although seldom highlighted, the former enables to regioselectively generate several C-C bonds at distant sites if creatively implemented.3 As it were, it becomes possible to reach the molecular complexity from the simplicity in a record time.

Research objectives:

Recently, we have disclosed an original example of consecutive reactions based on the concept of remote functionalisation ‘through internal induction’ using para-iodobenzyl mesylate as substrate.4 Moreover, the reported methodology required a combination of abundant metals as a unique reagent (a lithium organozincate,5 (R1)3ZnLi) and a bio-sourced solvent which was identified as a promoter of all elementary steps of the reported reaction sequence. Our synthetic tactic allows the regioselective formation of two C-C bonds, namely a C(sp3)-C(Sp2) and a C(sp3)-C(sp3) bond at sites distant by 5 atoms in a single operation. The project entrusted to the PhD candidate will be the brand-new extension of this remote transformation to halogenated heterocycles possessing a benzylic leaving group. Two or even three new C-C bonds should be formed, including at a non preactivated site, in single process and using only one reagent. Thereafter, he will develop the first asymmetric versions of this transformation. Finally, the products resulting from the previously developed synthetic sequence will be functionalized by incorporation of a CO2 or CO molecule in order to access added-value molecules. Abundant metal-based catalytic/photocatalytic processes will be used in this regard.7

References:

(a) Y. Hayashi, Chem. Sci.2016, 7, 866−880. DOI : 10.1039/C5SC02913A ; (b) N. J. Green, M. S. Sherburn, Aust. J. Chem.2013, 66, 267–283. DOI : 10.1071/CH13003.

A. Vasseur, J. Bruffaerts, I. Marek, Nat. Chem. 2016, 8, 209–219. DOI : 10.1038/nchem.2445

A. Vasseur, I. Marek, Nat. Protoc.2017, 12, 74–87. DOI : 10.1038/nprot.2016.161

(a) A. Pierret, C. Denhez, P. C. Gros, A. Vasseur, Adv. Synth. Catal. 2022, 364, 3805–3816. DOI:    10.1002/adsc.202200475 ; (b) Premier volet mécanistique, voir : A. Pierret, C. Lefebvre, P. C. Gros, C. Denhez, A. Vasseur, Eur. J. Org. Chem.2023, 26, e202300954. DOI : 10.1002/ejoc.202300954

Pour une revue sur la réactivité des organozincates de lithium en synthèse organique, voir : M. Uchiyama, C. Wang, Top. Curr. Organomet. Chem. 2014, 47, 159–202. DOI : 10.1007/3418_2013_72

Exemple de stratégie pour une fonctionnalisation sur position non péactivée de ce type de substrat, voir R. Gaertner, J. Am. Chem. Soc. 1951, 73, 3934–3937. DOI : 10.1021/ja01152a112

(a) X. Yan, L. Fan, X. Zhang, G. Liu, Org. Chem. Front.2022, 9, 6749–676. DOI : 10.1039/D2QO01419J ; (b) S. Wang, P. Xu, X. Zhu, ChemCatChem2023, 15, e202300695. DOI : 10.1002/cctc.202300695

Requirements

Research Field Chemistry » Organic chemistry

Education Level Master Degree or equivalent

Skills/Qualifications

The PhD candidate must hold a master degree in organic chemistry, organometallic chemistry or catalysis with a good average grade (at least 12 out of 20). He must be familiar with the usual treatment and purification techniques for organic compounds as well as the typical characterisation tools (NMR, IR, HRMS).

Specific Requirements

Application must be sent to Dr. Alexandre VASSEUR, (alexandre.vasseur@univ-lorraine.fr) and Pr. Jr. Ibrahim ABDELLAH (ibrahim.abdellah@univ-lorraine.fr) and must include a letter of motivation, a resume, the transcripts of his/her master degree (first and second year) and a letter of recommendation from his/her placement supervisor.

Level Good

Research Field Chemistry » Organic chemistry

Years of Research Experience None

Additional Information

Work Location(s)

Number of offers available 1

Company/Institute University of Lorraine, L2CM UMR CNRS 7053

Country France

State/Province Grand Est

City Vandoeuvre-lès-Nancy

Postal Code 54500

Street Boulevard des aiguillettes

Where to apply

E-mail alexandre.vasseur@univ-lorraine.fr

Contact

City Vandoeuvre les Nancy

Website http://www.l2cm.univ-lorraine.fr/l2cm/?page_id=53&amp%3Bcategorie_actualites=all

Street Bvd des Aiguillettes

Postal Code 54506

E-Mail andreea.pasc@univ-lorraine.fr