Premium
Asymmetric Sequential Cu‐Catalyzed 1,6/1,4‐Conjugate Additions of Hard Nucleophiles to Cyclic Dienones: Determination of Absolute Configurations and Origins of Enantioselectivity
Author(s) -
Blons Charlie,
Morin Marie S. T.,
Schmid Thibault E.,
Vives Thomas,
ColombelRouen Sophie,
Baslé Olivier,
Reynaldo Thibault,
Covington Cody L.,
Halbert Stéphanie,
Cuskelly Sean N.,
Bernhardt Paul V.,
Williams Craig M.,
Crassous Jeanne,
Polavarapu Prasad L.,
Crévisy Christophe,
Gérard Hélène,
Mauduit Marc
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201606034
Subject(s) - bimetallic strip , chemistry , enantioselective synthesis , nucleophile , intramolecular force , conjugate , catalysis , absolute configuration , phosphoramidite , circular dichroism , stereochemistry , computational chemistry , combinatorial chemistry , medicinal chemistry , organic chemistry , biochemistry , mathematics , oligonucleotide , dna , mathematical analysis
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.