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 BlonsMarie S T MorinThibault E SchmidThomas VivesSophie Colombel-RouenOlivier BasléThibault ReynaldoCody L CovingtonStéphanie HalbertSean N CuskellyPaul V BernhardtCraig M WilliamsJeanne CrassousPrasad L PolavarapuChristophe CrévisyHélène GérardMarc MauduitPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2017)
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.
Keyphrases
- density functional theory
- molecular dynamics
- high resolution
- metal organic framework
- molecular dynamics simulations
- affordable care act
- room temperature
- solid state
- aqueous solution
- molecular docking
- cancer therapy
- heavy metals
- healthcare
- crystal structure
- computed tomography
- drug delivery
- energy transfer
- mass spectrometry
- risk assessment
- dual energy
- ionic liquid
- molecularly imprinted