New routes to L-iduronic acid derivatives

L’objectif de ce travail est le développement de nouvelles voies d’accès à des dérivés de l’acide L-iduronique à partir d’un sucre abondant et peu couteux, le méthyl a-D-glucopyranoside. Plusieurs approches de synthèse ont été envisagées. Tout d’abord, l’obtention d’un composé 1,6-anhydro-5-ulose a été réalisée avec fixation de la configuration L-ido en C-5 et une fonctionnalisation adéquate en C-4. Par la suite, la désoxygénation de ce composé a fait l’objet d’une étude approfondie en employant diverses méthodes (radicalaires, ioniques…). Dans la troisième partie, la chimie (formation et réactivité) des septanosides a été également explorée comme une nouvelle stratégie vers les dérivés L-ido. Enfin, la quatrième partie concerne l’étude de trois voies annexes potentielles qui utilisent des intermédiaires précédemment obtenus afin de préparer des dérivés du L-idose.This work deals with the development of new routes to L-iduronic acid derivatives from a cheap and abundant sugar, the methyl a-D-glucopyranoside. Many approaches were studied. First, the 1,6-anhydro-5-ulose compound preparation was achieved with the right configuration L-ido at C-5 and the adequat protection at C-4. Then, a large study of its deoxygenation was made by using different methods (radicals, ions…). The third part is focused on the septanoside chemistry (preparation and reactivity) as a new strategy to the L-ido compound derivatives. To finish, three auxiliary routes are tested from different molecules obtained previously in order to prepare L-idose derivatives

Nouvelles voies d'accès à des dérivés de l'acide L-iduronique

This work deals with the development of new routes to L-iduronic acid derivatives from a cheap and abundant sugar, the methyl a-D-glucopyranoside. Many approaches were studied. First, the 1,6-anhydro-5-ulose compound preparation was achieved with the right configuration L-ido at C-5 and the adequat protection at C-4. Then, a large study of its deoxygenation was made by using different methods (radicals, ions...). The third part is focused on the septanoside chemistry (preparation and reactivity) as a new strategy to the L-ido compound derivatives. To finish, three auxiliary routes are tested from different molecules obtained previously in order to prepare L-idose derivativesL'objectif de ce travail est le développement de nouvelles voies d'accès à des dérivés de l'acide L-iduronique à partir d'un sucre abondant et peu couteux, le méthyl a-D-glucopyranoside. Plusieurs approches de synthèse ont été envisagées. Tout d'abord, l'obtention d'un composé 1,6-anhydro-5-ulose a été réalisée avec fixation de la configuration L-ido en C-5 et une fonctionnalisation adéquate en C-4. Par la suite, la désoxygénation de ce composé a fait l'objet d'une étude approfondie en employant diverses méthodes (radicalaires, ioniques...). Dans la troisième partie, la chimie (formation et réactivité) des septanosides a été également explorée comme une nouvelle stratégie vers les dérivés L-ido. Enfin, la quatrième partie concerne l'étude de trois voies annexes potentielles qui utilisent des intermédiaires précédemment obtenus afin de préparer des dérivés du L-idos

Nouvelles voies d'accès à des dérivés de l'acide L-iduronique

L objectif de ce travail est le développement de nouvelles voies d accès à des dérivés de l acide L-iduronique à partir d un sucre abondant et peu couteux, le méthyl a-D-glucopyranoside. Plusieurs approches de synthèse ont été envisagées. Tout d abord, l obtention d un composé 1,6-anhydro-5-ulose a été réalisée avec fixation de la configuration L-ido en C-5 et une fonctionnalisation adéquate en C-4. Par la suite, la désoxygénation de ce composé a fait l objet d une étude approfondie en employant diverses méthodes (radicalaires, ioniques ). Dans la troisième partie, la chimie (formation et réactivité) des septanosides a été également explorée comme une nouvelle stratégie vers les dérivés L-ido. Enfin, la quatrième partie concerne l étude de trois voies annexes potentielles qui utilisent des intermédiaires précédemment obtenus afin de préparer des dérivés du L-idose.This work deals with the development of new routes to L-iduronic acid derivatives from a cheap and abundant sugar, the methyl a-D-glucopyranoside. Many approaches were studied. First, the 1,6-anhydro-5-ulose compound preparation was achieved with the right configuration L-ido at C-5 and the adequat protection at C-4. Then, a large study of its deoxygenation was made by using different methods (radicals, ions ). The third part is focused on the septanoside chemistry (preparation and reactivity) as a new strategy to the L-ido compound derivatives. To finish, three auxiliary routes are tested from different molecules obtained previously in order to prepare L-idose derivatives.NANCY1-Bib. numérique (543959902) / SudocSudocFranceF

The Chemistry of Alkynylaluminum Species

International audienceAmong organoaluminum reagents, alkynylaluminum species exhibit peculiar physicochemical properties and reactivity. Depending on the nature of easily controlled parameters such as substituents on the aluminum center or additives and solvent, their Lewis acidity and nucleophilicity can be independently fine-tuned in a very precise manner. This chapter describes the preparation of alkynylaluminum compounds, their structure, and their reactivity in several synthetic transformations involving the transfer of their alkynyl group such as nucleophilic substitution reactions, additions to C\textendash X multiple bonds, epoxide and aziridine ring-opening reactions, reactions with oxonium and iminium species, metal-assisted cross-coupling reactions, as well as in rearrangements. The reactivity of the triple bond of these reagents is also presented

Direct Synthesis of Polysubstituted Aluminoisoxazoles and Pyrazoles by a Metalative Cyclization

International audienceAlumino-heteroles are obtained from simple precursors in a fully chemo-and regioselective manner by a metalative cyclization. The carbonÀaluminum bond is still able to react further with several electrophiles, without the need of transmetalation. This synthetic route provides a novel entry to heterocyclic organoaluminum reagents as well as a straightforward access to 3,4,5-trisubstituted isoxazoles and 1,3,4,5-tetrasubstituted pyrazoles. The preparation of main-group aryl and heteroaryl organometallics is a very active field, as these reagents are key intermediates in diversity-oriented elaboration of compounds for pharmaceutical and material science applications. 1 In this context, the preparation of aryl-or hetero-cyclic organoaluminum reagents has gained a renewed interest , due to their potential broad functional tolerance 2 and the low cost and toxicity of alanes. 3 A conventional preparative method for aromatic orga-noaluminum compounds has been the transmetalation of the corresponding lithium or magnesium derivatives with various aluminum(III) sources, 4 or in some cases trough aluminumÀtin or boron exchange reactions. 5 However, the transmetalation pathway, generally conducted at low temperature from reactive organolithium reagents, 6 generates salts as side products. These salts have been reported to strongly affect the reactivity 7 of the final organoalumi-num reagent and the enantioselectivity of asymmetric processes. 8 This procedure is very often conducted in ethereal solvents, known to strongly decrease the Lewis acidity of organoaluminum reagents and, therefore, to affect their reactivity. Finally, the potential functional group tolerance of the carbonÀaluminum bond cannot be exploited if (1) (a) Handbook of Functionnalized Organometallics; Knochel, P., Ed.; WILEY-VCH: Weinheim, 2005. (b) Chinchilla, R.; Najera, C.; Yus, M

Copper-Free Asymmetric Allylic Alkylation with a Grignard Reagent: Design of the Ligand and Mechanistic Studies

The Cu-free asymmetric allylic alkylation, catalysed by NHC, with Grignard reagents is reported on allyl bromide derivatives with good results. The enantioselectivity was quite homogeneous (around 85 % ee) on large and various substrates, regardless of the nature of the Grignard reagent. The formation of stereogenic quaternary centres was highly regioselective for both aliphatic and aromatic derivatives with good enantiomeric excess (up to 92 % ee). The methodology developed was found to be complementary with the Cu-catalysed version. Several new NHCs were tested with improved efficiency. In addition, mechanistic studies, using NMR spectroscopy, led to the discovery of the catalytically active species

Carbon\textendashCarbon Bond-Forming Reactions Mediated by Organomagnesium Reagents

International audienceThis chapter contains sections titled: * Introduction * Methods of Preparation of Magnesium Organometallics * Transition-Metal-Catalyzed Cross-Coupling Reactions of Organomagnesium Reagents * Conclusions * Experimental Procedures * Reference

Carbon\textendashCarbon Bond Forming Reactions Mediated by Organozinc Reagents

International audienceThis chapter contains sections titled: * Introduction * Methods of Preparation of\, Zinc Organometallics * Uncatalyzed Cross-Coupling Reactions of Organozinc Reagents * Copper-Catalyzed Cross-Coupling Reactions of Organozinc Reagents * Transition-Metal-Catalyzed Cross-Coupling Reactions of Organozinc Reagents * Conclusions * Experimental Procedures * Reference

The 1,3-dipolar cycloaddition reaction of chiral carbohydrate-derived nitrone and olefin: towards long-chain sugars

International audienceThe thermal and microwave-activated 1,3-dipolar cycloadditions of several alpha, beta-unsaturated esters derived from D-mannose and chiral nitrones derived from threitol have been studied as a model reaction en route to eleven carbon long chain carbohydrates. Very high facial selectivity is observed for the chiral nitrones whereas the olefin facial selectivity varies with the substrate. The presence of a dioxolane ring a to the olefinic bond is beneficial to the facial selectivity of the olefin whereas a pyranose ring is not. The combination of a D-mannose derivative and a L-threitol-derived nitrone is a matched pair suitable for the synthesis of long chain sugars with nine contiguous chiral centres. Finally complete facial selectivity was observed with exo-glycals which gave a single cycloadduct