Mechanism and diastereoselectivity of aziridine formation from sulfur ylides and imines: a computational study.

A computational investigation of the title reaction involving semistabilized (R = Ph) and stabilized (R = CO2Me) sulfur ylides has been performed using DFT methods including a continuum model of solvent. Our results provide support for the generally accepted mechanism and are in very good agreement with observed cis/trans selectivities. This study shows that betaine formation is nonreversible, and that selectivity is thereby determined at the initial addition step, in the case of semistabilized ylides. Our analysis indicates moreover that addition TS structures are governed by the steric strain induced by the N-sulfonyl group, which favors the transoid approach in the case of syn betaine formation and the cisoid mode of addition in anti TSs. The observed low trans selectivity is accounted for by the favorable Coulombic interactions and stabilization by C-H...O hydrogen bonding allowed in the cisoid anti addition TS. In the case of stabilized ylides, the endothermicity of betaine formation combined with the high barrier to ring closure render the elimination step rate- and selectivity-determining. Accordingly, the low cis selectivity observed in stabilized ylide reactions is explained by the lower steric strain in the elimination step generated by the formation of the cis aziridine (as compared to the trans case)

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

Cycloaddition of Cyclopropanes for the Elaboration of Medium-sized Carbocycles

The stereocontrolled formation of medium-sized carbocycles is a major goal in modern organic chemistry due to their widespread occurrence in natural products and pharmaceutically active ingredients. One approach consists in the use of cycloaddition reactions which notably results in high selectivities and atom-economy. To this end, cyclopropanes are ideal substrates since they can provide readily functionalized three- or five-carbon synthons. Herein we report advances made in cycloaddition reactions of cyclopropanes towards the synthesis of medium-sized carbocycles via transition metal catalysis or Lewis acid catalysis

On the Origin of E/Z Selectivity in the Modified Julia Olefination - Importance of the Elimination Step

The mechanism and origin of high E selectivity in the modified Julia olefination of aromatic aldehydes have been explored by computational and experimental means. Reversibility of addition and hence selectivity of the formation of sulfinate 5 is very variable and depends on the nature of the sulfone substrate. However, in all cases, elimination occurs through a concerted antiperiplanar and synperiplanar mechanism for sulfinates anti-5 and syn-5, respectively. Both syn and anti diastereomeric pathways thus lead preferentially to the (E)-alkene. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Formation of four-membered heterocycles

This review focuses on new developments in [2 þ 2] cycloadditions leading to four-membered heterocycles (b-lactams, b-lactones, b-sultams, azetidines, etc.) which appeared between 1992 and 2011. A special attention is drawn to the mechanistic aspects of the reactions and their consequences on the stereochemical outcome of the cycloaddition processes. Accordingly, the subdivision in sections reflects this point of view: the entries are related to reactions of various reagents (ketenes, enolates, ynolates, isocyanates, etc.) with CQX bonds instead of a list of types of heterocycles. The accent is also put on asymmetric catalysis, which is of particular interest for the enantioselective synthesis of biologically active compounds or their precursors

Diastereoselective synthesis of vinylcyclopropanes from dienes and sulfur ylides

The reaction of aryl- and vinyl-stabilized sulfonium ylides with electron-poor dienes has been investigated. Clear] cyclopropanation to 2-aryl- and 2-vinyl-substituted vinylcyclopropanes, with high regio- and stereocontrol, was observed. This new diastereoselective strategy was applied to formal synthesis of lamoxirene and dictyopterene B