Blons Charlie, Morin Marie S T, Schmid Thibault E, Vives Thomas, Colombel-Rouen 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
Ecole Nationale Supérieure de Chimie de Rennes, CNRS UMR 6226, 11 allée de Beaulieu, CS 50837, 35708, Rennes Cedex 7, France.
Université de Rennes 1, CNRS, UMR 6226, Campus de Beaulieu, 35042, Rennes Cedex, France.
Chemistry. 2017 Jun 1;23(31):7515-7525. doi: 10.1002/chem.201606034. Epub 2017 May 16.
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.
首次报道了铜催化的碳金属化硬亲核试剂对环状二烯酮的立体控制的顺序1,6/1,4-不对称共轭加成（ACA）反应。使用二苯基磷基亚甲胺基化物（DiPPAM），随后使用亚磷酰胺作为立体诱导配体，有利于1,6-ACA反应获得高对映体过量值（ee值），以及1,4-ACA反应组分获得高非对映体过量值（de值），从而得到对映体富集的1,3-二烷基化部分。通过振动圆二色性（VCD）和旋光色散（ORD）光谱，结合密度泛函理论（DFT）计算和X射线分析确定了绝对构型。有趣的是，通过使用前所未有的铜-锌双金属催化体系对对映选择性1,6-加成反应机理进行的DFT计算证实了这一归属。最后，探索对映体富集的1,3-二烷基化产物的分子内环化途径，为获得具有挑战性的菖蒲烷骨架提供了途径。
