12 research outputs found
ContrĂŽle de la chiralitĂ© axiale Ă lâaide dâarynes et en absence de mĂ©taux de transition
International audienceThe modular construction of enantioenriched biaryl derivatives is presented. This approach is based on (a) an almost quantitative access to polybrominated precursors via a transition metal-free aryl-aryl coupling, the ARYNE-coupling, (b) the regioselective introduction of a traceless chiral auxiliary (an enantiopure para-tolylsulfinyl group), (c) the chemoselective functionalization of this auxiliary and (d) subsequent regioselective functionalization of the remaining bromine atoms without any racemization during these steps. Next, the atropo-selective coupling of in situ generated arynes and aryllithiums bearing various chiral auxiliaries (tert-butylsulfoxide, para-tolylsulfoxide, tartrate-derived chiral diethers and oxazolines) is described and applied to the formal synthesis of (-)-steganacin. La construction modulaire de dérivés biaryliques énantioenrichis est présentée. Cette approche est basée sur (a) un accÚs quasi quantitatif aux précurseurs polybromés via un 2 couplage aryle-aryle sans métaux de transition, le couplage ARYNE, (b) l'introduction régiosélective d'un auxiliaire chiral (un groupe para-tolylsulfinyl énantiopur), (c) la fonctionnalisation chimiosélective de cet auxiliaire et (d) la fonctionnalisation régiosélective subséquente des atomes de brome restants sans racémisation au cours de ces étapes. Ensuite, le couplage atropo-sélectif à l'aide d'arynes générés in situ et d'aryllithiums portant divers auxiliaires chiraux (tert-butylsulfoxyde, para-tolylsulfoxide, diéthers dérivés du tartrate et des oxazolines chirales) est décrit et appliqué à la synthÚse formelle de la (-)-stéganacine
Transition-Metal-Free Synthesis of a Known Intermediate in the Formal Synthesis of (-)-Steganacin
International audienceThe formal synthesis of both enantiomers of a natural axially chiral biaryl, steganacin is reported. The previously developed atropo-diastereoselective coupling of an aryne and an aryllithium (the 'ARYNE coupling') allows for this synthesis. In each step, the axial configuration of the biaryl could be maintained. The key intermediate of literature was accessed without using transition metals, demonstrating the interest of the ARYNE coupling as a complement or an alternative to transition metal-catalyzed couplings
SynthÚses de biaryles atropoenrichis et de biphénylÚnes via des arynes substitués
This work consisted in the study of the âaryne couplingâ, a transition-metal free process to access biaryl moieties, which involves the reaction between two in situ generated intermediates: a nucleophilic aryllithium derivative and an electrophilic aryne. This work resided in the optimization of the atropoenantioselective version of the aryne coupling and its application to the formal synthesis of (-)-steganacin. We then moved to the atropoenantioselective version of the reaction, by introducing chiral ligands in the reaction mixture, which aim was to coordinate the aryllithium species and to transfer their chiral information to the biaryl axis. After optimization of various reaction parameters, some enantiomeric excesses were obtained as well as various side products in some cases, among which biphenylene derivatives. According to the potential applications of these compounds, another part of this work was dedicated to their synthesis by means of aryne dimerization reactions.Les travaux prĂ©sentĂ©s dans ce manuscrit ont eu pour but dâĂ©tudier le « couplage aryne », une technique de synthĂšse qui produit des biaryles sans lâintervention de mĂ©taux de transition, grĂące Ă la rĂ©action entre deux intermĂ©diaires rĂ©actionnels gĂ©nĂ©rĂ©s in situ : un aryllithien nuclĂ©ophile et un aryne Ă©lectrophile. Les travaux rĂ©alisĂ©s ont consistĂ© en lâoptimisation de la version diastĂ©rĂ©osĂ©lective du couplage, ensuite appliquĂ©e Ă la synthĂšse formelle de la (-)-stĂ©ganacine. Dans un second temps, les premiĂšres Ă©tudes sur la version Ă©nantiosĂ©lective du couplage ont Ă©tĂ© rĂ©alisĂ©es, en introduisant des ligands chiraux Ă la rĂ©action et en Ă©valuant lâinfluence de diffĂ©rents paramĂštres rĂ©actionnels. Les premiers excĂšs Ă©nantiomĂ©riques ont ainsi Ă©tĂ© obtenus, parfois accompagnĂ©s de la formation de divers sous-produits, parmi lesquels des dĂ©rivĂ©s de biphĂ©nylĂšne. Devant lâintĂ©rĂȘt que reprĂ©sentent ces composĂ©s, une partie des travaux a Ă©tĂ© consacrĂ©e Ă leur synthĂšse par dimĂ©risation des arynes
Synthesis of biphenylenes and atropoenriched biaryls via substituted arynes
Les travaux prĂ©sentĂ©s dans ce manuscrit ont eu pour but dâĂ©tudier le « couplage aryne », une technique de synthĂšse qui produit des biaryles sans lâintervention de mĂ©taux de transition, grĂące Ă la rĂ©action entre deux intermĂ©diaires rĂ©actionnels gĂ©nĂ©rĂ©s in situ : un aryllithien nuclĂ©ophile et un aryne Ă©lectrophile. Les travaux rĂ©alisĂ©s ont consistĂ© en lâoptimisation de la version diastĂ©rĂ©osĂ©lective du couplage, ensuite appliquĂ©e Ă la synthĂšse formelle de la (-)-stĂ©ganacine. Dans un second temps, les premiĂšres Ă©tudes sur la version Ă©nantiosĂ©lective du couplage ont Ă©tĂ© rĂ©alisĂ©es, en introduisant des ligands chiraux Ă la rĂ©action et en Ă©valuant lâinfluence de diffĂ©rents paramĂštres rĂ©actionnels. Les premiers excĂšs Ă©nantiomĂ©riques ont ainsi Ă©tĂ© obtenus, parfois accompagnĂ©s de la formation de divers sous-produits, parmi lesquels des dĂ©rivĂ©s de biphĂ©nylĂšne. Devant lâintĂ©rĂȘt que reprĂ©sentent ces composĂ©s, une partie des travaux a Ă©tĂ© consacrĂ©e Ă leur synthĂšse par dimĂ©risation des arynes.This work consisted in the study of the âaryne couplingâ, a transition-metal free process to access biaryl moieties, which involves the reaction between two in situ generated intermediates: a nucleophilic aryllithium derivative and an electrophilic aryne. This work resided in the optimization of the atropoenantioselective version of the aryne coupling and its application to the formal synthesis of (-)-steganacin. We then moved to the atropoenantioselective version of the reaction, by introducing chiral ligands in the reaction mixture, which aim was to coordinate the aryllithium species and to transfer their chiral information to the biaryl axis. After optimization of various reaction parameters, some enantiomeric excesses were obtained as well as various side products in some cases, among which biphenylene derivatives. According to the potential applications of these compounds, another part of this work was dedicated to their synthesis by means of aryne dimerization reactions
Access to Atropisomerically Enriched Biaryls by the Coupling of Aryllithiums with Arynes under Control by Homochiral Oxazolines
We report the preparation of axially stereoenriched biphenyls by the coupling of in situ generated aryllithiums and arynes using chiral oxazoline auxiliaries. The design of the aryne precursors, the choice of oxazoline and the reaction conditions were key to accessing the desired, highly substituted, atropisomerically enriched biarylic products. In one case, the two atropo-diastereomers could be obtained in isomerically pure form by column chromatographic separation and their absolute configurations established by X-ray crystallography. The stereoselectivity of the reaction seems to be governed by subtle parameters