The aza-Morita-Baylis-Hillman reaction of electronically and sterically deactivated substrates.

The aza-Morita–Baylis–Hillman (azaMBH) reaction has been studied for electronically and sterically deactivated Michael acceptors. It is found that electronically deactivated systems can be converted with electron-rich phosphanes and pyridines as catalysts equally well. For sterically deactivated systems clearly better catalytic turnover can be achieved with pyridine catalysts. This is in accordance with the calculated affinities of the catalysts towards different Michael-acceptors

Reactivity and Steric Parameters from 2D to 3D Bulky Pyridines:Increasing Steric Demand at Nitrogen with Chiral Azatriptycenes

Sterically hindered pyridines embedded in a three-dimensional triptycene framework have been synthesized, and their resolution by chiral HPLC enabled access to unprecedented enantiopure pyridines exceeding the known steric limits. The design principles for new axially chiral pyridine derivatives are then described. To rationalize their associations with Lewis acids and transition metals, a comprehensive determination of the steric and electronic parameters for this new class of pyridines was performed. This led to the general parameterization of the steric parameters (percent buried volume %VBur, Tolman cone angle θ, and He8_steric descriptor) for a large set of two- and three-dimensional pyridine derivatives. These parameters are shown to describe quantitatively their interactions with carbon- and boron-centered Lewis acids and were used to predict the ΔG° of association with the prototypical B(C6F5)3 Lewis acid widely used in frustrated Lewis pair catalysis. This first parameterization of pyridine sterics is a fundamental basis for the future development of predictive reactivity models and for guiding new applications of bulky and chiral pyridines in organocatalysis, frustrated Lewis pairs, and transition-metal catalysis.Sterically hindered pyridines embedded in a three-dimensional triptycene framework have been synthesized, and their resolution by chiral HPLC enabled access to unprecedented enantiopure pyridines exceeding the known steric limits. The design principles for new axially chiral pyridine derivatives are then described. To rationalize their associations with Lewis acids and transition metals, a comprehensive determination of the steric and electronic parameters for this new class of pyridines was performed. This led to the general parameterization of the steric parameters (percent buried volume %VBur, Tolman cone angle θ, and He8_steric descriptor) for a large set of two- and three-dimensional pyridine derivatives. These parameters are shown to describe quantitatively their interactions with carbon- and boron-centered Lewis acids and were used to predict the ΔG° of association with the prototypical B(C6F5)3 Lewis acid widely used in frustrated Lewis pair catalysis. This first parameterization of pyridine sterics is a fundamental basis for the future development of predictive reactivity models and for guiding new applications of bulky and chiral pyridines in organocatalysis, frustrated Lewis pairs, and transition-metal catalysis

Mass Spectrometric Back Reaction Screening of Quasi-Enantiomeric Products as a Mechanistic Tool

In this account, we discuss a mass spectrometric method that enables unambiguous identification of intermediates involved in the enantioselective step of a catalytic cycle. This method, which we originally developed for rapid evaluation of chiral catalysts, is based on monitoring the back reaction of mass-labeled quasi-enantiomeric products by ESI-MS. In this way, the intrinsic enantioselectivity of a chiral catalyst can be determined directly by quantification of catalytically relevant intermediates. By comparing the results from the forward and back reaction, direct evidence for the involvement of a catalytic intermediate in the enantioselective step can be obtained. In addition, insights about the energy profile of the catalytic cycle may be gained. The potential of back reaction screening as a mechanistic tool is demonstrated for organocatalytic aldol reactions, 1,4-additions of aldehydes to nitroolefins, Diels-Alder reactions, Michael additions, and Morita-Baylis-Hillman reactions

HDA cycloadditions of 1-diethoxyphosphonyl-1,3-butadiene with nitroso heterodienophiles: a computational investigation

The hetero Diets-Alder (HDA) reactions of 1-diethoxyphosphony1-1,3-butadiene with various nitroso dienophiles have been studied at the B3LYP/6-31G** level. Structural, energetic and electronic properties are discussed. These cycloadditions with nitroso dienophiles are characterized by a total proximal regioselectivity and an endo selectivity. The influence of the nitroso substitution on the activation barrier and the regiochemistry of the reaction is presented. The analysis of the chemical rearrangement along the intrinsic reaction pathway (IRC), based on bond order and on natural bond orbital (NBO) calculations, emphasizes the polar nature of these cycloadditions. Despite the early and the cyclic nature of the corresponding transition states, a two-center interaction governs this mechanism: these cycloadditions are Polar Diets-Alder reactions (P-DA). (C) 2010 Elsevier B.V. All rights reserved

Développement d'une voie générale d'accès aux dérivés β- et γ-aminophosphoniques par réaction Diels-Alder : approches expérimentale et théorique

Malgré leurs activités nombreuses et variées, les dérivés β-, et γ-aminophosphoniques n'ont été préparés jusqu'à present que de façon ponctuelle selon des stratégies de synthèse particulières. Afin de pallier à ce manque nous nous sommes intéressés, au cours de notre doctorat, au développement d'une voie d'accés générale à ces composés. La stratégie que nous avons sélectionée repose sur la réaction Diels-Alder de partenaires rezspectivement aminés et phosphorés. Nous avons dans la première partie de ce travail de doctorat, mis au point la cycloaddition d'aminodiènes et phosphonodiénophiles; l'utilisation d'aminodiènes chiraux nous a permis d'obtenir des β- et γ-amido-phosphonocyclohexènes optiquement actifs avec une excellente sélectivité. Dans la seconde partie, nous nous sommes intéressés à la possibilité de cycloaddition de phosphonodiènes et d'aminodiénophiles. Cette partie de notre travail nous a conduit au développement d'une nouvelle famille de diènes, les dérivés phosphoniques. Parallèlement à ce travail expérimental, nous avons également réalié une étude approfondie de la fonction phosphonate en utilisant les méthodes ab initio de la chimie quantique. L'analyse de l'influence énergétique, structurale et électronique de la substitution d'un système π et de l'état de transition de la réaction D-A par le groupement phosphonate nous apermis d'identifier et de quantifier les effets de ce groupement sur les doubles liaisons et son influence sur leur réactivité en cycloaddition.Doctorat en sciences (chimie) - UCL, 200