Etude de la réactivité des allénylcuivres vis-à-vis des aldéhydes, application à la synthèse diastéréosélective et énantiosélective d'alcools homopropargyliques

Ce manuscrit de thèse décrit la mise au point d une nouvelle voie de synthèse d alcools homopropargyliques par le biais de dérivés organométalliques de type allénylcuivre qui n avaient jamais été utilisés dans cette réaction. La méthodologie utilisée pour préparer ces composés consiste à additionner ces allénylcyanocuprates, issus d amines, d éthers et d alkyles propargyliques métallés, sur un aldéhyde pour conduire aux isomères anti avec une excellente sélectivité. Il est également possible d inverser la stéréochimie de ces réactions en utilisant des allénylalkylcuprates. Des calculs de modélisation ont permis une meilleure compréhension de la réactivité de ces espèces et aussi de montrer le rôle crucial du cation lithium. Une version asymétrique de cette réaction a été mise au point à partir d une oxazolidinone optiquement pure. Nous avons par la suite montré, par le biais du test d Hoffmann, que les allénylcuivres sont configurationnellement instables à basse température.This manuscript describes a new strategy for the synthesis of homopropargylic alcohols by using allenyl copper reagents. The addition of allenylcyanocuprates onto aldehydes gives anti propargylic alcohols with a good selectivity. We have found that it is possible to reverse the stereochemical course of this reaction by using allenylalkylcuprates which give the syn alcohols. Calculations have allowed us to understand the reactivity of all these species and the crucial effect of the lithium cation associated. An asymmetric version of these reactions has been developed starting from an optically pure oxazolidinone. The allenyl copper species have been found to be configurationnally unstable at low temperature by using the Hoffman test.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Preparation of anti-1,2-Disubstituted Homopropargylic Alcohols by Addition of Allenyl(cyano)cuprates to Aldehydes

International audienceThe generality of the addition of allenyl(cyano)cuprates to aldehydes to afford anti-1,2-disubstituted homopropargylic alcohols was studied. The reaction is general, regardless of the nature of the cyanocuprate, although with alkyl-substituted derivatives the anti selectivity is dependent upon the nature of the aldehyde

Remarkably Efficient Charcoal-Promoted Ring-Closing Carbonylations

International audienceAn efficient, versatile and practical gram-scale preparation of oxazolidinone, imidazolidinone and dioxolanone is achieved

1,3-Li/H Shift of 1-Aryl-1,2-alkadienyl Reagents: An Experimental and Theoretical Study

International audienceA-Li shuffle: Experimental and computational data are employed to elucidate the mechanistic aspects of the 1,3-lithium shift occurring in the allenyllithium complexes derived from 1-aryl-1-alkynes. A central role is shown to be played by proton donors, resulting in the in situ formation of a transient allene. This highlights the role of water in the reaction mechanism and explains the disconcerting non-reproducibility of proton-free reaction procedures

Addition of a Chiral Copper Reagent Derived from Propargylic Oxazolidininone to Aldehydes

International audienceThe copper reagent arising from an optically pure propargylic oxazolidinone was found to react regio- and diastereoselectively with aldehydes, leading, in a one-pot procedure, to the anti homopropargylic amino alcohols derivatives in good yields

Diastereodivergent Behavior of Alkyl- versus Cyano- Allenylcuprates towards Aldehydes: a Key Role for Lithium

International audienceThe stereodivergent behavior of allenyl(cyano)- and allenyl(alkyl)- cuprates toward aldehydes, providing a selective preparation of both syn or anti homopropargylic alcohols, is described. This study, which combines both experimental and theoretical support, shows that the copper non-transferred "dummy ligand" controls the localization of the lithium cation with respect to the allenylcuprate moiety. As a consequence, Li+ acts as a Lewis acid activator but also controls the diastereoselectivity during the addition of allenylcuprates onto aldehydes. The combined high selectivity, efficiency and versatility of these cuprate compounds open the way to new one-pot synthetic procedures as illustrated by the combined Klein rearrangement / transmetallation methodology described herein

Dynamic Kinetic Resolution Processes Based on the Switchable Configurational Instability of Allenyl Copper Reagents

International audienceThe configurational instability of allenyl copper reagents is unveiled. An experimental study highlights the crucial role of Li+ and of the reaction temperature in the control of the configurational stability of allenyl copper reagents. A judicious choice of the reaction conditions allows efficient dynamic kinetic resolution processes and gives a one-pot access to homopropargylic alcohols or amines bearing up to four contiguous defined stereogenic centers