Asymmetric Sequential Cu-Catalyzed 1,6/1,4-Conjugate Additions of Hard Nucleophiles to Cyclic Dienones: Determination of Absolute Configurations and Origins of Enantioselectivity
Asymmetric Sequential Cu-Catalyzed 1,6/1,4-Conjugate Additions of Hard Nucleophiles to Cyclic Dienones: Determination of Absolute Configurations and Origins of Enantioselectivity
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DOI：
10.1002/chem.201606034
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发表时间：
2017-06-01
影响因子：
4.3
通讯作者：
Mauduit, Marc
中科院分区：
文献类型：
--
作者：
Blons, Charlie;Morin, Marie S. T.;Mauduit, Marc
首次报道了Cu催化的C-金属化硬亲核试剂与环二烯酮的立体控制连续1，6/1，4-不对称共轭加成反应（ACA）。使用DiPPAM（二苯基膦基偶氮甲磺酸酯），然后作为立体诱导配体的亚磷酰胺促进高ee值的1，6-ACA和高de值的1，4-ACA反应组分，从而得到对映体富集的1，3-二烷基化部分。用振动圆二色性（VCD）和旋光色散（ORD）光谱，结合密度泛函（DFT）计算和X射线分析确定了它们的绝对构型。有趣的是，DFT计算的对映选择性1，6-加成的机制，通过使用前所未有的Cu-Zn双金属催化体系证实了这一属性。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提供了具有挑战性的补身烷骨架的途径。
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 dichro-ism (VCD) and optical rotatory dispersion (ORD) spectroscopy, in combination with DFT calculations and X-ray analysis. Interestingly, DFT calculations for the mechanism of enantio-selective 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.