Où docteurs et entreprises se rencontrent
Menu
Connexion

Vous avez déjà un compte ?

Nouvel utilisateur ?

Functionalization of polyols via the borrowing hydrogen methodology for the synthesis of aza-heterocycles

ABG-100551 Stage master 2 / Ingénieur 5 mois gratification de stage
13/10/2021
ICBMS INSA Lyon
Villeurbanne Auvergne-Rhône-Alpes France
  • Chimie
Organometallic catalysis, Synthetic methodology, Borrowing Hydrogen, Aza-heterocycles
05/11/2021

Établissement recruteur

Situé sur le site de LyonTech-La Doua, l’Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires (ICBMS) dépend de 4 tutelles (l’Université Lyon1, le CNRS, l’Ecole Supérieure de Chimie CPE-Lyon et l’INSA-Lyon). Il est constitué de 10 équipes et comporte 3 plateformes techniques.

L'équipe "Chimie Organique et Bioorganique" de l'Institut National des Sciences Appliquées de Lyon s'intéresse à des projets multidisciplinaires à l'interface chimie-biochimie.

Description

N-Heterocyclic compounds are widely used as synthetic intermediates for the production of pharmaceuticals and bioactive compounds.[1] The development of practical methods for the preparation of saturated aza-heterocycles is an important subject in organic chemistry synthesis.[2]

Over the last decades, borrowing hydrogen (BH) methodology has emerged as an attractive strategy for the construction of novel CN bonds from an alcohol and an amine. A first step of catalytic dehydrogenation converts an unreactive alcohol into the corresponding carbonyl. Subsequent reaction with an amine leads to the imine in situ which upon hydrogenation affords the desired amine. This one pot strategy benefits from metal catalysis (Ir, Ru, Fe…) and affords water as the sole by-product.[3]

Yamaguchi et al. later reported the used of the BH methodology for the synthesis of pyrrolidine and piperidine using a diol and a primary amine catalyzed by a Cp*Ir complex. The amino-alcohol obtained after a first catalytic cycle then undergoes an intramolecular BH cycle affording the corresponding N-heterocyclic product after final reduction.[4] Many articles then reported the synthesis of aza-heterocycles via BH catalysis mediated by Ir, Ru and Fe catalysts. [5] Based on this strategy and taking advantage of our expertise on the direct amination of biobased diols,[6] we envisioned the synthesis of hydroxylated aza-heterocycles, such as 3-pyrrolidinol, starting from a triol and a primary amine, offering the possibility of further functionalization. 

The aim of this M2 internship is twofold: (i) to investigate the direct synthesis of 3-pyrrolidinol using a large scope of primary amines (benzylic, aliphatic, etc.) (ii) to take advantage of the remaining hydroxyl group for further functionalization to form novel CN and CC bonds.

 

-----

 

 

[1] O’Hagan, D. Nat. Prod. Rep. 2000, 17, 435. [2] Felpin, F.-X.; Lebreton, J. Eur. J. Org. Chem. 2003, 3693 and references therein. [3] a) Corma, A.; Navas, J.; Sabater, M. J Chem. Rev. 2018, 118, 1410. [4] Fujita, K.; Fujii, T.; Yamaguchi, R. Org. Lett. 2004, 6, 3525. [5] As an example, see: a) Miao, L.; DiMaggio, S. C.; Shu, H.; Trudell, M. L. Org. Lett. 2009, 11, 1579. b) Marichev, K. O.; Takacs, J. M. ACS Catal. 2016, 6, 2205. c) Yan, T.; Feringa, B. L.; Barta, K. Nat. Commun. 2014, 5, 5602. d) Chamberlain, A. E. R.; Paterson, K. J.; Armstrong, R. J.; Twin, H. C.; Donohoe, T. J. Chem. Commun. 2020, 56, 3563. [6] a) Jacolot, M. ; Moebs-Sanchez, S. ; Popowycz, F. J. Org. Chem. 2018, 83, 9456. b) Bahé, F.; Grand, L.; Cartier, E.; Jacolot, M.; Moebs-Sanchez, S.; Portinha, D.; Fleury, E.; Popowycz, F. Eur. J. Org. Chem. 2020, 2020, 599.

Profil

Nous recherchons un.e étudiant.e de niveau bac+5 (master 2 ou école d'ingénieur) motivé.e, sérieux.se ayant de bonnes connaissances théoriques en chimie organiques et une expérience pratiques des techniques de laboratoire (synthèse et caractérisation structurale). 

Prise de fonction

17/01/2022
Partager via
Postuler
Fermer

Vous avez déjà un compte ?

Nouvel utilisateur ?