Department of Chemistry, Stanford University, Stanford, California 94305, United States.
Org Lett. 2020 Mar 20;22(6):2437-2441. doi: 10.1021/acs.orglett.0c00646. Epub 2020 Mar 6.
Enantioselective incorporation of trifluoromethyl (-CF) and trifuoromethylthio (-SCF) groups in small molecules is of high interest to modulate the potency and pharmacological properties of drug candidates. Herein, we report a Zn-ProPhenol catalyzed diastereo- and enantioselective Mannich addition of α-trifluoromethyl- and α-trifuoromethylthio-substituted ketones. This transformation uses cyclic and acyclic ketones and generates quaternary trifluoromethyl and tetrasubstituted trifuoromethylthio stereogenic centers in excellent yields and selectivities.
对映选择性地在小分子中引入三氟甲基（-CF）和三氟甲硫基（-SCF）基团，可以调节候选药物的效力和药理学性质。在此，我们报告了 Zn-ProPhenol 催化的 α-三氟甲基和 α-三氟甲硫基取代酮的非对映选择性和对映选择性 Mannich 添加。该转化使用环状和非环状酮，并以优异的产率和选择性生成季碳三氟甲基和四取代三氟甲硫基手性中心。
