Couverture : Function-Oriented Synthesis toward Peloruside A Analogs

A convergent and rapid synthesis of original C2,C3-unsaturated, C11,C13-keto-enol macrocycles with peloruside A skeleton has been developed. These original unsaturated macrocycles constitute valuable platforms to access peloruside A analogues with high diversity. The four-fragment strategy implemented features two aldol-type couplings with the central C12-C14 building-block TES-diazoacetone and a late-stage ring-closing metathesis. Enantiopure analogue 18ab showed antiproliferative activity in the low micromolar range on NCI and MCF7 tumor cell lines.

A.-C. Chany, F. Legros, H. Haroun, U. K. Kundu, B. Biletskyi, S. Torlak, M. Mathé-Allainmat, J. Lebreton, A. Macé, B. Carboni, B. Renoux, P. Gosselin, G. Dujardin, C. Gaulon-Nourry, Org. Lett. 2019 ASAP.

https://pubs.acs.org/doi/10.1021/acs.orglett.9b00413

Publication : Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

A new access to several chiral 3-aminoglycals as potential precursors for glycosylated natural products is reported from a common starting material, (−)-methyl-L-lactate. The stereodivergent strategy is based on the implementation of a ring-closing metathesis of vinyl ethers as key step of reaction sequences developed.

Nocquet, P.-A.; Macé, A.; Legros, F.; Lebreton, J.; Dujardin, G.; Collet, S.; Martel, A.; Carboni, B.; Carreaux, F. Beilstein J. Org. Chem. 2018, 14, 2949-2955.

https://www.beilstein-journals.org/bjoc/articles/14/274

Publication : Stereospecific C‐Glycosylation by Mizoroki–Heck Reaction: A Powerful and Easy‐to‐Set‐Up Synthetic Tool to Access α‐ and β‐Aryl‐C‐Glycosides

Stereospecific C‐Glycosylation by Mizoroki–Heck Reaction: A Powerful and Easy‐to‐Set‐Up Synthetic Tool to Access α‐ and β‐Aryl‐C‐Glycosides

A stereospecific Mizoroki–Heck cross‐coupling of differently substituted glycals with haloarenes resulting in the exclusive formation of either α‐ or β‐aryl‐C‐glycosides depending solely on the configuration at C3 was achieved. The reaction was easy to set up because no specific precautions were required concerning moisture or oxygen, and it proceeded by a chirality transfer from C3 to C1. After optimization of cross‐coupling conditions, various prepared glycals (7 examples) and arenes (10 examples) were tested, leading stereospecifically to the corresponding aryl‐C‐glycosides with a carbonyl group at C3, thus opening up new horizons for the total synthesis of glycosylated natural products.

Mabit, T.; Siard, A.; Legros, F.; Guillarme, S.; Martel, A.; Lebreton, J.; Carreaux, F.; Dujardin, G.; Collet, S. Chemistry – A European Journal 2018, 24, 14069-14074.

https://onlinelibrary.wiley.com/doi/10.1002/chem.201803674

Publication : Transition-Metal-Free Enantioselective Reactions of Organo­magnesium Reagents Mediated by Chiral Ligands

Transition-Metal-Free Enantioselective Reactions of Organo­magnesium Reagents Mediated by Chiral Ligands

Organomagnesium reagents are among the most important reagents in organic chemistry because of their great utility in forming carbon–carbon bonds. Although most enantioselective reactions using these organometallics involve transmetalation, the past decade has witnessed impressive advances in directchiral-ligand-mediated reactions of organomagnesiums­. This short review presents an overview of these achievements in enantioselective nucleophilic additions and substitutions.

Guyon, H.; Boussonnière, A.; Castanet, A.-S. Synthesis 2018, 50, 3589-3602.

https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0037-1610135

Publication: Addition of Organozinc Reagents to Glycopyranosyl Cyanides: Access to Keto Ester‐C‐glycosides or Unsaturated Acyl‐C‐glycosides

Addition of Organozinc Reagents to Glycopyranosyl Cyanides: Access to Keto Ester‐C‐glycosides or Unsaturated Acyl‐C‐glycosides

Original keto ester‐C‐glycosides or unsaturated acyl‐C‐glycosides have been prepared in moderate to excellent yields in the galactose, glucose and mannose series by reactions involving addition of Reformatsky‐type or allylic zinc reagents to 2,3,4,6‐tetra‐O‐benzylglycopyranosyl cyanides.

Ella Obame, I.; Ireddy, P.; Guisot, N.E.S.; Nourry, A.; Saluzzo, C.; Dujardin, G.; Dubreuil, D.; Pipelier, M.; Guillarme, S. Eur. J. Org. Chem. 2018, 2018, 1735-1738.

https://onlinelibrary.wiley.com/doi/10.1002/ejoc.201800090

Publication : Successive addition of two different Grignard reagents to nitriles: access to α,α-disubstituted propargylamine derivatives

Publication : Successive addition of two different Grignard reagents to nitriles: access to α,α-disubstituted propargylamine derivatives

The successive addition of two different Grignard reagents to acyl cyanohydrins was performed with success by taking advantage of the low reactivity of alkynyl Grignard reagents. The experimental conditions were adjusted so that they were not reactive during the first addition step, but reactive only in the second one. The synthetic utility of the prepared compounds was validated by the preparation of chiral quaternary α-amino acids.

Caille, J.; Boukattaya, F.; Boeda, F.; Pearson-Long, M.S.M.; Ammar, H.; Bertus, P. Org. Biomol. Chem. 2018, 1519.

https://pubs.rsc.org/en/content/articlelanding/2018/ob/c7ob03047a#!divAbstract

Séminaire Gaëlle Blond
Séminaire Gaëlle Blond

Le docteur Gaëlle BLOND (Laboratoire d'innovation thérapeutique - UMR CNRS 7200 - Strasbourg) donnera une présentation le jeudi 05 juillet 2018 à 14h00 à l'IUT Chimie (Amphi vert).
Cette conférence sera intitulée:"Synthesis of Complex Molecules via Metal-Mediated Domino Reactions".

Séminaire François Carreaux
Séminaire François Carreaux

Le docteur François CARREAUX (Institut des Sciences chimiques de Rennes - UMR CNRS 6226) donnera une présentation le lundi 02 juillet 2018 à 14h00 en salle IAM.
Cette conférence sera intitulée:"Séquences réactionnelles impliquant une allylboration: Quelques applications en synthèse de produits naturels".

Séminaire - Florence Mongin / William Erb
Séminaire - Florence Mongin / William Erb

Séminaire de Florence Mongin et William Erb de l'Institut des Sciences Chimiques de Rennes :
"A chaque aromatique son LiTMP : de la déprotonation des hétérocycles à celle des ferrocènes"
Le vendredi 15 juin 11h - Salle IAM

Offres de thèse - Rentrée 2018
Offres de thèse - Rentrée 2018

 

Sujet(s) à télécharger :

Télécharger le fichier «Offre de thèse MESR 2018-Anne Boussonniere.pdf» (123.2 KB)

Publication : Enantioselective Access to Robinson Annulation Products and Michael Adducts as Precursors

The Robinson annulation is a reaction that has been useful for numerous syntheses since its discovery in 1935, especially in the field of steroid synthesis. The products are usually obtained after three consecutive steps: the formation of an enolate (or derivative), a conjugate addition, and an aldol reaction. Over the years, several methodological improvements have been made for each individual step or alternative routes have been devised to access the Robinson annulation products. The first part of this Review outlines the most relevant developments towards the formation of monocarbonyl-derived Robinson annulation products (MRA products, MRAPs) and activated monocarbonyl-derived Robinson annulation products (AMRA products, AMRAPs). The following sections are then devoted to the diastereoselective and enantioselective synthesis of these products, while the last section describes the enantiomeric resolution of racemic mixtures.

Gallier, F.; Martel, A.; Dujardin, G., Angew. Chem. Int. Ed. 2017, 56, 12424-12458. 

DOI 10.1002/anie.201701401

 

 

Publication : Enantioselective 1,3‐DC reactions of C‐Carboxy Ketonitrones and Enals with MacMillan catalyst: Evidence of a non‐concerted mechanism

Highly diastereo- and enantioselective 1,3-dipolar cycloadditions between functional ketonitrones and β-substituted enals are promoted by organocatalysis with the imidazolidinium catalyst of MacMillan. Study of the scope of the reaction shows that high selectivities are conserved by varying the N-protecting group or the ester function. However it is sensitive to sterical interaction with the C-substituent of the nitrone. Reaction proceeds in all cases with a high exo selectivity. In most cases, a third diastereomer, not compatible with a concerted mechanism, was observed, although in minute amount. DFT calculations evidence that the cycloaddition proceeds in a non-concerted fashion by a first oxa Michael-type addition of the nitrone to the double bond followed by a cyclization. This mechanism explains the formation of the observed minor diastereomers. In addition, the diastereo- and enantioselectivities of the reaction were shown to be intermediately thermodynamically controlled and the diastereomeric ratio is modulated by the kinetics of iminium hydrolysis.

 

Ayed, K. B.; Laurent, M. Y.; Martel, A.; Selim, K. B.; Abid, S.; Dujardin, G., Eur. J. Org. Chem. 2017, 6763.

http://doi.org/10.1002/ejoc.201701307

 

Publication : Chemo-, Regio-, and Stereoselective Synthesis of Polysusbtituted Oxazolo[3,2-d][1,4]oxazepin-5(3H)ones via a Domino oxa-Michael/aza-Michael/Williamson Cycloetherification Sequence

The access to new oxazolo[3,2-d][1,4]oxazepin-5(3H)-ones starting from α-bromoamido alcohols and Michael acceptors under mild conditions is presented. This domino process proved to be chemo-, regio-, and stereoselective and allows the formation of a large diversity of highly functional 7-membered rings in good yields up to 95%. The complete shift of the regioselectivity of the intermediate enolate from a C–C to a C–O bond formation, contrary to the already known alkylations of such ambident nucleophiles, is mostly triggered by steric effects. The last step of the sequence was modeled by DFT giving some important insights for this C–C vs C–O bond shift.

El Bouakher, A.; Tasserie, J.; Le Goff, R.; Lhoste, J.; Martel, A.; Comesse, S.,  J. Org. Chem. 2017, 82, 5798-5809.

 http://dx.doi.org/10.1021/acs.joc.7b00629

 

Publication :Total Synthesis of γ-Indomycinone and Kidamycinone by Means of Two Regioselective Diels–Alder ReactionsTotal Synthesis of γ-Indomycinone and Kidamycinone by Means of Two Regioselective Diels–Alder Reactions

An efficient access for the synthesis of pluramycinones is described. Total syntheses of racemic γ-indomycinone and kidamycinone were achieved by means of two Diels–Alder reactions. A first Diels–Alder condensation followed by a Stille cross-coupling is used for the elaboration of the desired substituted dienes which will be involved in the second pericyclic reaction with juglone to construct the tetracyclic core of pluramycinones.

Mabit, T.; Siard, A.; Pantin, M.; Zon, D.; Foulgoc, L.; Sissouma, D.; Guingant, A.; Mathé-Allainmat, M.; Lebreton, J.; Carreaux, F.; Dujardin, G.; Collet, S., J. Org. Chem. 2017, 82, 5710-5719.

 http://dx.doi.org/10.1021/acs.joc.7b00544

Publication : Double Addition of Organometallics to Nitriles: Toward an Access to Tertiary Carbinamines

As depicted in many textbooks, the addition of organometallics to nitriles is generally limited to a single addition, providing ketones after acidic hydrolysis. However, the double addition, leading to tertiary carbinamines is also possible, as demonstrated as early as 1939 by the double addition of allyl Grignard reagents to α-ethoxyacetonitrile. Since this seminal result, and stimulated by the biological importance of the so-obtained carbinamines, efforts were devoted to expand the scope of the double addition of organometallics to nitriles. This review presents these different approaches which have led to short accesses to tertiary carbinamine derivatives. Particularly interesting is the double addition of different organometallics, which opens the way towards the straightforward asymmetric synthesis of tertiary carbinamines from nitriles.

Pearson-Long, M. S. M.; Boeda, F.; Bertus, P., Adv. Synth. Catal. 2017, 359, 179-201.

http://dx.doi.org/10.1002/adsc.201600727 

Publication : Readily Accessible 1,2-Amino Ether Ligands for Enantioselective Intramolecular Carbolithiation

A new class of chiral 1,2-amino ether ligands, readily accessible from naturally occurring α-amino- or α-hydroxy acids, was found to provide high levels of both conversion and stereocontrol (up to 95:5 er) in intramolecular carbolithiation reactions, outperforming the benchmark ligand (−)-sparteine. The ligand could be used in a substoichiometric amount (0.25 equiv) without significant loss of enantioselectivity.

H. Guyon; A. Boussonnière; A.-S. Castanet Readily Accessible 1,2-Amino Ether Ligands for Enantioselective Intramolecular Carbolithiation. J. Org. Chem 2017, 82 (9), 4949-4957.

http://pubs.acs.org/doi/abs/10.1021/acs.joc.7b00423



Publication : Advances in the TBAF-induced aldol-type addition of α-trialkylsilyl-α-diazoacetones: TIPS versus TES

α-Triisopropylsilyl-α-diazoacetone (TIPS-diazoacetone) underwent high-yielding “diazo-side” Mukaiyama aldol-type addition with a range of aryl and alkyl aldehydes when subjected to stoichiometric amount of tetrabutylammonium fluoride at −16 °C, in Et2O. Robustness of the TIPS group makes TIPS-diazoacetone a stable surrogate for α-triethylsilyl-α-diazoacetone, on which generation of the corresponding carbanion can still be efficiently achieved under nucleophilic, weakly basic and practical conditions. These results highlight the synthetic potential that can be expected from TIPS-diazoacetone, promising building block for the convergent elaboration of highly functionalised versatile diazocarbonyl compounds.

Abid, I.; Gavelle, S.; Chany, A.-C.; Legros, F.; Gosselin, P.; Abid, S.; Dujardin, G.; Gaulon-Nourry, C., Comptes Rendus Chimie 2017, 20, 595-600.

http://www.sciencedirect.com/science/article/pii/S1631074816303149 

Publication : Isoxazolidine: A Privileged Scaffold for Organic and Medicinal Chemistry

M. Berthet; T. Cheviet; G. Dujardin; I. Parrot; J. Martinez Isoxazolidine: A Privileged Scaffold for Organic and Medicinal Chemistry. Chemical Reviews 2016, 116 (24), 15235-15283.

http://pubs.acs.org/doi/abs/10.1021/acs.chemrev.6b00543

Publication : short Access to Symmetrically α,α-Disubstituted α-Amino Acids from Acyl Cyanohydrin

Publication :  short Access to Symmetrically α,α-Disubstituted α-Amino Acids from Acyl Cyanohydrin (Synthesis 2016, 48, 906)

A straightforward synthesis of symmetrically α,α-disubstituted α-amino acids is presented. The key step of this process relies on the efficient double addition of Grignard reagents to acyl cyanohydrins to provide N-acyl amino alcohols selectively in good yields. The chemoselectivity of the reaction was modulated by the nature of the acyl moiety. Eleven amino acids were prepared, including the particularly simple divinylglycine, which is not easily accessible by using conventional methods.

 

F. Boukattaya, J. Caillé, H. Ammar, F. Rouzier, F. Boeda, M. Pearson-Long, P Bertus, A short Access to Symmetrically α,α-Disubstituted α-Amino Acids from Acyl Cyanohydrin Synthesis 2016, 48 : p. 906-916.

https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0035-1560404

Publication : Reaction of Glyconitriles with Organometallic Reagents: Access to Acyl β-C-Glycosides

Publication : Reaction of Glyconitriles with Organometallic Reagents: Access to Acyl β-C-Glycosides (J. Org. Chem. 2016, 81 (6), pp 2364–2371)

A new strategy for the synthesis of acyl β-C-glycosides is described. The reactivity of glyconitriles toward organometallic reagents such as organomagnesium or organolithium derivatives was studied, affording acyl β-C-glycosides in moderate to good yields. In this study, glycal formation was efficiently prevented by deprotonating the hydroxyl group in position 2 of the glyconitriles during the process.

N. E. S. Guisot, I. Ella Obame, P. Ireddy, A. Nourry, C. Saluzzo, G. Dujardin, D. Dubreuil, M. Pipelier, S. Guillarme J. Org. Chem. 2016, 81(6), pp 2364–2371

http://pubs.acs.org/doi/abs/10.1021/acs.joc.5b02853

Contact

Animateurs de la thématique Synthèse Organique :

immm-anim-so @ univ-lemans.fr