Catalyse par un acide Brønsted assistée par les composés nitro : activation des liaisons C(sp3)–O and C(sp3)–F

Alcohols are attractive electrophilic partners for nucleophilic substitution reactions as water is the only by-product in a reaction with protic nucleophiles. Despite being a highly desirable reaction, the scope of useful catalytic transformations remains limited to specific alcohol-nucleophile pairs and a general set of catalytic conditions remains elusive. This thesis describes the development of a general and mild catalyst system for the activation of a broad range of π-activated and aliphatic alcohols to address key limitations in the field. B(C6F6)3•H2O, a strong Brønsted acid, when combined with nitromethane has been found as a widely useful catalyst system for chemoselective alcohol substitution in the presence of acid sensitive functionalities and protecting groups without the typical compromises in reaction rates, substrate/nucleophile scope and catalyst loading. In particular, a co-catalytic effect of nitro compounds is described for the B(C6F6)3•H2O catalyzed azidation of tertiary aliphatic alcohols, enabling catalyst turnover for the first time. On the basis of kinetic, electronic, and spectroscopic investigations, higher order hydrogen-bonded aggregates of nitro compounds and acids are proposed as kinetically competent Brønsted acid catalysts at the origin of the enhanced reactivity. The utility of the new catalytic conditions has been extended beyond alcohol activation and applied to the cleavage of strong C–F bonds in defluorinative Friedel-Crafts reactions of tertiary aliphatic fluorides.Les alcools sont des partenaires électrophiles attractifs pour des réactions de substitution nucléophile puisque l'eau est le seul sous-produit de la réaction en présence de nucléophiles protiques. Malgré le fait que la réaction soit fortement intéressante, la portée des transformations catalytique reste limitée à une combinaison spécifique alcool/nucléophile, ce qui rend l’emploi d’un ensemble général de conditions catalytiques fortement élusif. Cette thèse décrit le développement d'un système général de catalyse doux pour l'activation d'une large gamme d’alcools π-activés ainsi que d’alcools aliphatiques abordant ainsi les limitations clés dans le domaine. B(C6F6)3•H2O, un acide de Brønsted fort quand il est combiné avec le nitrométhane, a été découvert comme étant un système catalytique idéal pour la substitution chimiosélective d'alcools en présence de fonctionnalités et de groupements protecteurs sensibles aux conditions acides sans le compromis typique entre vitesse de réaction, réactivité substrat/nucléophile et quantité de catalyseur. Plus particulièrement, un effet co-catalytique de composés nitro est décrit pour la réaction d’azidation des alcools aliphatiques tertiaires en employant B(C6F6)3•H2O, permettant, pour la première fois, un turnover catalytique. Sur la base des investigations cinétiques, électroniques et spectroscopiques qui ont été menées, des agrégats de composés nitro et d’acides liés par des intéractions hydrogènes sont proposé comme étant l’espèce catalytiques responsables de la cinétique de la catalyse observée. L'utilité des nouvelles conditions catalytiques a été étendue au-delà de l'activation d'alcool et appliquée au clivage des liaisons fortes C-F dans les réactions de Friedel-Crafts défluorinatives de fluorures aliphatiques tertiaires

Autocatalytic Friedel–Crafts Reactions of Tertiary Aliphatic Fluorides Initiated by B(C₆F₅)₃·H₂O

The C–F bond is the strongest single bond to carbon, constituting an intrinsic challenge for selective catalytic activation in the presence of other functional groups. Existing methods for the activation of tertiary aliphatic fluorides involve stoichiometric abstraction with fluorophilic Lewis acids or by Lewis-acid-catalyzed trapping with Si reagents. Herein, we describe a B­(C₆F₅)₃·H₂O-catalyzed Friedel–Crafts reaction of tertiary alkyl fluorides that proceeds rapidly at room temperature without trapping reagents. The method is completely selective for F^– over traditionally better leaving groups and displays an autocatalytic kinetic profile

Generative model based on junction tree variational autoencoder for HOMO value prediction and molecular optimisation

In this work, we provide further development of the junction tree variational autoencoder (JT VAE) architecture in terms of implementation and application of the internal feature space of the model. Pretraining of JT VAE on a large dataset and further optimization with a regression model led to a latent space that can solve several tasks simultaneously: prediction, generation, and optimization. We use the ZINC database as a source of molecules for the JT VAE pretraining and the QM9 dataset with its HOMO values to show the application case. We evaluate our model on multiple tasks such as property (value) prediction, generation of new molecules with predefined properties, and structure modification toward the property. Across these tasks, our model shows improvements in generation and optimization tasks while preserving the precision of state-of-the-art models

A Supramolecular Model for the Co‐Catalytic Role of Nitro Compounds in Brønsted Acid Catalyzed Reactions

International audienceNitro compounds are known to change reaction rates and kinetic concentration dependence of Brønsted-acid-catalyzed reactions. Yet, no mechanistic model exists to account for these observations. Herein we present an atomistic model for the catalytically active form for an alcohol dehydroazidation reaction, generated by DFT calculations. which consists of an H-bonded aggregate of two molecules of Brønsted acid and two molecules of nitro compound. The computed O-H stretching frequencies for the aggregate indicate they are stronger acids than the individual acid molecules and serve as predictors for experimental reaction rates. Applying the model to a chemically diverse set of potential promoters, we predicted and verified experimentally that sulfate esters induce a similar co-catalytic effect. The important implication is that Brønstedacid catalysis must be viewed from a supramolecular perspective that accounts for not only the pKa of the acid and the bulk properties of a solvent, but also the weak interactions between all molecules in solution

Nitro-Assisted Brønsted Acid Catalysis: Application to a Challenging Catalytic Azidation

A cocatalytic effect of nitro compounds is described for the B­(C₆F₅)₃·H₂O catalyzed azidation of tertiary aliphatic alcohols, enabling catalyst turnover for the first time and with a broad range of substrates. Kinetic investigations into this surprising effect reveal that nitro compounds induce a switch from first order concentration dependence in Brønsted acid to second order concentration dependence in Brønsted acid and second order dependence in the nitro compounds. Kinetic, electronic, and spectroscopic evidence suggests that higher order hydrogen-bonded aggregates of nitro compounds and acids are the kinetically competent Brønsted acid catalysts. Specific weak H-bond accepting additives may offer a new general approach to accelerating Brønsted acid catalysis in solution