The development of new and efficient methods, reagents, and catalysts for the introduction of fluorine atoms or fluorinated moieties in molecular scaffolds has become a topic of paramount importance in organic synthesis. In this framework, the incorporation of the SCF₃ group into organic molecule has often led to beneficial effects on the drug’s metabolic stability and bioavailability. Here we report our studies aimed to the stereoselective synthesis of chiral α-SCF₃-β−ketoesters featuring a tetrasubstituted stereocenter. The use of a chiral auxiliary was crucial to synthesize enantiopure enamines that were reacted with N-trifluoromethylthio saccharin or phthalimide, to afford enantioenriched α-SCF₃-tetrasubstitued β-keto esters. By using a readily available, inexpensive chiral diamine, such as trans-1,2-diaminocyclohexane, the fluorinated products could be obtained in modest to good yields, and, after the removal of the chiral auxiliary, α-substituted- α trifluoromethylthio-β−ketoesters were isolated with high enantioselectivity (up to 91% ee).

中文翻译：

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具有四元立体中心的手性α-SCF3-β-酮酸酯的立体选择性合成

在分子支架中引入氟原子或氟化部分的新的有效方法，试剂和催化剂的开发已成为有机合成中最重要的主题。在此框架中，将SCF ₃基团并入有机分子通常会导致对药物代谢稳定性和生物利用度的有益影响。在这里，我们报告我们研究的目的是手性α-SCF的立体选择性合成₃ -β-酮酯设有四取代立体。使用的手性助剂是到用反应合成对映体纯的烯胺关键Ñ -trifluoromethylthio糖精或邻苯二甲酰亚胺，得到对映体富集α-SCF ₃-四取代的β-酮酯。通过使用容易获得的便宜的手性二胺，例如反式-1,2-二氨基环己烷，可以适度地获得良好的氟化产物，并且在除去手性助剂后，可以得到α-取代的-α三氟甲硫基-β。以高对映选择性（高达91％ee）分离出-酮酸酯。