Department of Chemistry and Materials Engineering & High Technology Research Center, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan.
J Org Chem. 2010 Aug 20;75(16):5707-15. doi: 10.1021/jo101147p.
Reversal of enantioselectivity in a Cu-catalyzed asymmetric conjugate addition reaction of dialkylzinc to cyclic enone with use of the same chiral ligand was successfully achieved. The reaction of 2-cyclohexen-1-one (30) with Et(2)Zn catalyzed by Cu(OTf)(2) in the presence of an azolium salt derived from a chiral beta-amino alcohol gave (S)-3-ethylcyclohexanone (31) in good enantioselectivity. Among a series of chiral azolium compounds examined, the benzimidazolium salt (10) having both a tert-butyl group at the stereogenic center and a benzyl substituent at the azolium ring was found to be the best choice of ligand in the Cu(OTf)(2)-catalyzed reaction. Good enantioselectivity was observed when the reaction was conducted by employing a benzimidazolium derivative rather than an imidazolium derivative. The influence of the substituent at the azolium ring on the stereoselectivity of the reaction was also examined. In addition, from the results of the reaction catalyzed by Cu(OTf)(2) combined with an azolium compound derived from (S)-leucine methyl ester, it was found that the hydroxy side chain in the chiral ligand is probably crucial for the enantiocontrol of the conjugate addition reaction. On the other hand, it was discovered from a screening test of copper species that the reversal of enantioselectivity was realized by allowing 30 to react with Et(2)Zn in the presence of Cu(acac)(2) combined with the same ligand precursor to afford (R)-31 as a major product. The influence of the stereodirecting group at the chiral ligand on the stereoselectivity in the Cu(acac)(2)-catalyzed reaction differed completely from that observed in the Cu(OTf)(2)-catalyzed reaction. Reaction with a cyclic enone consisting of a seven-membered ring such as 2-cyclohepten-1-one (40) resulted in increasing the enantioselectivity of the reaction. Thus, treatment of 40 with Et(2)Zn catalyzed by Cu(OTf)(2) combined with a benzimidazolium salt produced the corresponding (S)-conjugate adduct in a 92:8 enantiomer ratio (er), while the Cu(acac)(2)-catalyzed reaction with the same ligand afforded (R)-product in a 9:91 er.
使用相同的手性配体，成功地实现了铜催化的不对称共轭加成反应中，二烷基锌对环状烯酮的对映选择性反转。在手性β-氨基醇衍生的氮唑盐存在下，用 Cu(OTf)(2) 催化 2-环己烯-1-酮（30）与 Et(2)Zn 的反应，得到（S）-3-乙基环己酮（31），具有良好的对映选择性。在所研究的一系列手性氮唑化合物中，在铜（OTf）（2）催化的反应中，发现具有手性中心的叔丁基和氮唑环上的苄基取代基的苯并咪唑鎓盐（10）是配体的最佳选择。当使用苯并咪唑鎓衍生物而不是咪唑鎓衍生物进行反应时，观察到良好的对映选择性。还研究了氮唑环上取代基对反应立体选择性的影响。此外，从铜（OTf）（2）与（S）-亮氨酸甲酯衍生的氮唑化合物催化的反应结果中发现，手性配体中的羟基侧链可能对共轭加成反应的对映控制至关重要。另一方面，通过允许 30 在 Cu(acac)(2) 与相同配体前体存在下与 Et(2)Zn 反应的铜物种筛选测试发现，通过使用 Cu(acac)(2) 与相同配体前体来实现对映选择性的反转，得到（R）-31 作为主要产物。手性配体中的立体导向基团在手性铜（acac）（2）催化的反应中的立体选择性影响与在铜（OTf）（2）催化的反应中观察到的完全不同。与包含例如 2-环庚烯-1-酮（40）的七元环的环状烯酮的反应导致反应的对映选择性增加。因此，用 Cu(OTf)(2) 与苯并咪唑鎓盐组合催化 40 与 Et(2)Zn 的反应以 92:8 的对映体比例（er）生成相应的（S）-共轭加成产物，而用相同的配体进行 Cu(acac)(2) 催化的反应则以 9:91 的 er 生成（R）-产物。
