Asymmetric Sequential Cu-Catalyzed 1,6/1,4-Conjugate Additions of Hard Nucleophiles to Cyclic Dienones: Determination of Absolute Configurations and Origins of Enantioselectivity

Charlie Blons (1) , Marie S. T. Morin (1) , Thibault E. Schmid (1) , Thomas Vives (1) , Sophie Colombel-Rouen (1) , Olivier Baslé (1) , Thibault Reynaldo (1) , Cody L. Covington (2) , Stéphanie Halbert (3) , Sean N. Cuskelly (4) , Paul V. Bernhardt (4) , Craig M. Williams (4) , Jeanne Crassous (1) , Prasad L. Polavarapu (2) , Christophe Crevisy (1) , Hélène Gérard (3) , Marc Mauduit (1)

1 ISCR - Institut des Sciences Chimiques de Rennes
2 Vanderbilt University [Nashville]
3 LCT - Laboratoire de chimie théorique
4 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland

The first stereocontrolled Cu-catalyzed sequential 1,6/1,4-asymmetric conjugate addition (ACA) of C-metalated hard nucleophiles to cyclic dienones is reported. The use of DiPPAM (diphenylphosphinoazomethinylate) followed by a phosphoramidite as the stereoinducing ligands facilitated both high ee values for the 1,6-ACA and high de values for the 1,4-ACA reaction components, which thus gave enantioenriched 1,3-dialkylated moieties. The absolute configurations were determined by using vibrational circular dichroism (VCD) and optical rotatory dispersion (ORD) spectroscopy, in combination with DFT calculations and X-ray analysis. Interestingly, DFT calculations for the mechanism of enantioselective 1,6-addition by using an unprecedented Cu-Zn bimetallic catalytic system confirmed this attribution. Lastly, exploring intramolecular cyclization avenues for enantioenriched 1,3-dialkylated products provided access to the challenging drimane skeleton.

Mots clés: Copper; asymmetric catalysis; Circular Dichroism; configuration determination; conjugate addition

Domaines: Chimie organique; Catalyse

Charlie Blons, Marie S. T. Morin, Thibault E. Schmid, Thomas Vives, Sophie Colombel-Rouen, et al.. Asymmetric Sequential Cu-Catalyzed 1,6/1,4-Conjugate Additions of Hard Nucleophiles to Cyclic Dienones: Determination of Absolute Configurations and Origins of Enantioselectivity. Chemistry - A European Journal, 2017, 23 (31), pp.7515-7525. ⟨10.1002/chem.201606034⟩. ⟨hal-01533324⟩