27 research outputs found
Heterohelicenes through 1,3-Dipolar Cycloaddition of Sydnones with Arynes: DFT-optimized structures
No full textHeterohelicenes through 1,3-Dipolar Cycloaddition of Sydnones with Arynes: Synthesis, Origins of Selectivity, and Application to pH-Triggered Chiroptical Switch with CPL Sign Reversal
Expédite Yen-Pon, Floris Buttard, Lucas Frédéric, Pierre Thuéry, Frédéric Taran, Grégory Pieters*, Pier Alexandre Champagne*, and Davide Audisio*
DOI: 10.1021/jacsau.1c00084
Gaussian 16 output files for all the computed structure
3-Vinyl-1,2,4-triazines comme plateformes bifonctionnelles pour la synthèse de nouvelles structures tétrahydro-[1,6]-naphthyridines
No full textThe development of new methods for the synthesis of original heterocyclic molecules represents a current concern in organic chemistry, aiming to furnish medicinal chemistry and chemical biology with new chemical tools and contribute to the exploration of chemical space.In this context, the work which was carried out during this PhD thesis focused on the elaboration of new approaches for the synthesis of tetrahydro-[1,6]-naphthyridine scaffolds. The original use of 3-vinyl-1,2,4-triazines as bifunctional synthetic platforms, able to react both as Michael acceptor and as aza-diene in inverse-electron-demand Diels-Alder cycloadditions, is the keystone our methodology is based upon. The development of domino reactions – allowing quick and efficient synthesis of targeted compounds – remaineda perpetual concern evolving along side our preoccupation to access enantioselective transformations relying on organocatalysis.The synthesis of new 3-vinyl-1,2,4-triazines platforms and the elaboration of domino conjugate addition/cycloadditions and orgonocatalyzed one-pot synthesis strategies enabled to synthetize a wide panelof new diversly substituted tetrahydro-[1,6]-naphthyridines compounds.Le développement de nouvelles méthodes de synthèse de molécules hétérocycliques originales représente un enjeu actuel majeur en chimie organique. L’objectif est de fournir de nouveaux outils chimiques pour le développement de molécules actives en chimie médicinale et/ou pour l’étude de la biologie chimique, tout en contribuant à l’exploration de l’espace chimique.Dans ce contexte, le travail effectué au cours de cette thèse de doctorat a visé à élaborer de nouvelles voies de synthèse de motifs tétrahydro-[1,6]-naphtyridines. La pierre angulaire des méthodologies développées réside dans l’utilisation des 3-vinyl-1,2,4-triazines comme des plateformes synthétiques bifonctionnelles. Ces composés ont été développés pour réagir à la fois comme accepteurs de Michael et comme aza-diènes dansdes cycloadditions de Diels-Alder à demande électronique inverse. Un intérêt tout particulier a été porté à lamise au point de stratégies synthétiques innovantes, par des réactions en cascade permettant une synthèse rapide et efficace des molécules cibles, et des approches de catalyse organique visant des transformations énantiosélectives.La synthèse de nouvelles 3-vinyl-1,2,4-triazines et le développement de stratégies de réactions d’addition conjuguée/cycloadditions en cascade et de synthèses monotopes organocatalysées ont fournis l’accès à une vaste gamme de nouvelles tétrahydro-[1,6]-naphthyridines diversement substituées
3-vinyl-1,2,4-triazines as bifunctional platforms towards new tetrahydro-[1,6]-naphthyridines scaffolds synthesis
No full textLe développement de nouvelles méthodes de synthèse de molécules hétérocycliques originales représente un enjeu actuel majeur en chimie organique. L’objectif est de fournir de nouveaux outils chimiques pour le développement de molécules actives en chimie médicinale et/ou pour l’étude de la biologie chimique, tout en contribuant à l’exploration de l’espace chimique.Dans ce contexte, le travail effectué au cours de cette thèse de doctorat a visé à élaborer de nouvelles voies de synthèse de motifs tétrahydro-[1,6]-naphtyridines. La pierre angulaire des méthodologies développées réside dans l’utilisation des 3-vinyl-1,2,4-triazines comme des plateformes synthétiques bifonctionnelles. Ces composés ont été développés pour réagir à la fois comme accepteurs de Michael et comme aza-diènes dansdes cycloadditions de Diels-Alder à demande électronique inverse. Un intérêt tout particulier a été porté à lamise au point de stratégies synthétiques innovantes, par des réactions en cascade permettant une synthèse rapide et efficace des molécules cibles, et des approches de catalyse organique visant des transformations énantiosélectives.La synthèse de nouvelles 3-vinyl-1,2,4-triazines et le développement de stratégies de réactions d’addition conjuguée/cycloadditions en cascade et de synthèses monotopes organocatalysées ont fournis l’accès à une vaste gamme de nouvelles tétrahydro-[1,6]-naphthyridines diversement substituées.The development of new methods for the synthesis of original heterocyclic molecules represents a current concern in organic chemistry, aiming to furnish medicinal chemistry and chemical biology with new chemical tools and contribute to the exploration of chemical space.In this context, the work which was carried out during this PhD thesis focused on the elaboration of new approaches for the synthesis of tetrahydro-[1,6]-naphthyridine scaffolds. The original use of 3-vinyl-1,2,4-triazines as bifunctional synthetic platforms, able to react both as Michael acceptor and as aza-diene in inverse-electron-demand Diels-Alder cycloadditions, is the keystone our methodology is based upon. The development of domino reactions – allowing quick and efficient synthesis of targeted compounds – remaineda perpetual concern evolving along side our preoccupation to access enantioselective transformations relying on organocatalysis.The synthesis of new 3-vinyl-1,2,4-triazines platforms and the elaboration of domino conjugate addition/cycloadditions and orgonocatalyzed one-pot synthesis strategies enabled to synthetize a wide panelof new diversly substituted tetrahydro-[1,6]-naphthyridines compounds
Spiroindoles as Intermediates/Products in Transition Metal Catalyzed Dearomatization of Indoles
No full textSpirocyclic indole derivatives are fascinating tridimensional molecular scaffolds, from both a synthetic and biological point of view. Among the diversity of strategies developed to access this kind of structures, transition metal catalysis recently led to impressive advances, especially in order to tame the unique reactivity of the dearomatized spirocyclic intermediates. These species can indeed evolve towards both spirocyclic or non-spirocyclic products through rearomatization-driven processes which are at the same time highly challenging to control but also source of a large structural diversity. This review highlights the most prominent methods of the last decade allowing to trigger a spirocyclization on indole derivatives tethered with a transition metal-activable functional group, leading to both spirocyclic and rearomatized products. The discussion is particularly focused on the reactivity and the complex mechanistic features regarding the evolution of the spiroindoleninium intermediate, highly dependent on the catalytic system
Emergent Strategies for Catalytic Enantioselective Direct Thiocyanation and Selenocyanation Reactions
No full textInternational audienc
In the quest for molecular complexity, the direct and selective functionalization of C(sp3) centers is of paramount importance. As sulfur- and/or fluorine-containing molecules are particularly important, the development of methods to (regio)selectively introduce moieties containing these atoms on a C(sp3) center by direct C–H bond functionalization or decarboxylative reaction has garnered our interest in the last few years. Given the challenges that the direct functionalization of C(sp3) centers represents, this account summarizes our recent contributions thanks to strategies based on transition metal catalysis and photochemistry
Binding modes and origins of enantioselectivity in the phase transfer-catalyzed conjugate cyanation of β-trifluoromethylated chalcone.
No full text<p>Gaussian output files of the optimizations and frequency calculations. </p>
Binding Modes and Origins of Enantioselectivity in the Phase-Transfer-Catalyzed Conjugate Cyanation of β‑Trifluoromethylated Chalcones
No full textDespite
their importance in industrial applications, enantioselective
phase-transfer catalyzed reactions are poorly understood, especially
for anionic nucleophiles other than enolates. In this context, we
have studied the quinidinium-catalyzed phase-transfer cyanation of
trifluoromethylated chalcones, reported by Shibata in 2012 and patented
by Syngenta in 2016, using density functional theory (DFT) calculations.
To efficiently sample the conformational space available to the noncovalently
bound systems, we have designed a multistage procedure involving interrupted
constrained optimizations, which identifies the most relevant conformers
while sparing computational resources. A full study of the mechanism
with a model catalyst confirmed that the 1,4-addition step is enantiodetermining
in this reaction. Our calculations predict a 97:3 e.r. favoring the
(R) enantiomer at the B3LYP-D3(BJ)/Def2TZVPP/SMD(i-Pr2O) level of theory, in excellent agreement
with the experimental results. A complete analysis of the available
binding modes of the substrates with the catalyst demonstrates that
the strong stabilization of the two reaction partners by the ammonium
α-hydrogens in the transition structure is critical to lower
the activation barrier for the conjugate addition and that π-stacking
interactions are not the main drivers of the selectivity as previously
thought. These discoveries allowed us to propose a model of selectivity
for the conjugate cyanation of chalcones, which mirrors the previously
reported model for phase-transfer-catalyzed enolate alkylations
Binding Modes and Origins of Enantioselectivity in the Phase-Transfer-Catalyzed Conjugate Cyanation of β‑Trifluoromethylated Chalcones
No full textDespite
their importance in industrial applications, enantioselective
phase-transfer catalyzed reactions are poorly understood, especially
for anionic nucleophiles other than enolates. In this context, we
have studied the quinidinium-catalyzed phase-transfer cyanation of
trifluoromethylated chalcones, reported by Shibata in 2012 and patented
by Syngenta in 2016, using density functional theory (DFT) calculations.
To efficiently sample the conformational space available to the noncovalently
bound systems, we have designed a multistage procedure involving interrupted
constrained optimizations, which identifies the most relevant conformers
while sparing computational resources. A full study of the mechanism
with a model catalyst confirmed that the 1,4-addition step is enantiodetermining
in this reaction. Our calculations predict a 97:3 e.r. favoring the
(R) enantiomer at the B3LYP-D3(BJ)/Def2TZVPP/SMD(i-Pr2O) level of theory, in excellent agreement
with the experimental results. A complete analysis of the available
binding modes of the substrates with the catalyst demonstrates that
the strong stabilization of the two reaction partners by the ammonium
α-hydrogens in the transition structure is critical to lower
the activation barrier for the conjugate addition and that π-stacking
interactions are not the main drivers of the selectivity as previously
thought. These discoveries allowed us to propose a model of selectivity
for the conjugate cyanation of chalcones, which mirrors the previously
reported model for phase-transfer-catalyzed enolate alkylations
