Enantioselective trifluoromethylthiolation of 4-substituted pyrazolones catalyzed by amide-based phase transfer catalysts

We successfully developed the first enantioselective trifluoromethylthiolation of 4-substituted pyrazolones catalyzed by amide-based Cinchona alkaloids with N-trifluoromethylthiosaccharin. A broad variety of chiral CF3S-pyrazolones were obtained in excellent yields with high enantioselectivities. Controlled experiments showed that the multiple hydrogen bonding interactions and the steric hindrance at NH-position were indispensable for high enantioselectivity and reactivity. Furthermore, these amide-based phase transfer catalysts could be easily recovered and reused for such a reaction with almost original reactivity and enantioselectivity.

Automated summary

We have successfully developed an enantioselective trifluoromethylthiolation reaction of 4-substituted pyrazolones using amide-based Cinchona alkaloids catalyzed by N-trifluoromethylthiosaccharin. A variety of chiral CF3S-pyrazolones were obtained with excellent yields and high enantioselectivities. Control experiments revealed that multiple hydrogen bonding interactions and steric hindrance at the NH-position were crucial for achieving high enantioselectivity and reactivity. Moreover, these amide-based phase transfer catalysts could be easily recovered and reused with almost unchanged reactivity and enantioselectivity.