The Bifunctional Silyl Reagent Me2(CH2Cl)SiCF3 Enables Highly Enantioselective Ketone Trifluoromethylation and Related Tandem Processes

作者：Mu, Bo-Shuai; Gao, Yang; Yang, Fu-Ming; Wu, Wen-Biao; Zhang, Ying; Wang, Xin^*; Yu, Jin-Sheng^*; Zhou, Jian^*

来源：Angewandte Chemie - International Edition, 2022, 61(38): e202208861.

DOI：10.1002/anie.202208861

• Asymmetric Synthesis
• Fluorine
• Tandem Synthesis
• Tertiary Alcohols
• Trifluoromethylation

We report the development of bifunctional trifluoromethylsilyl reagents for selective trifluoromethylation. The newly developed reagent, Me-2(CH2Cl)SiCF3, allows highly enantioselective trifluoromethylations of ketones with broad scope. Notably, by taking advantage of the chloromethyl group, a tandem synthesis of chiral trifluoromethylated oxasilacyclopentanes is developed, paving way to alpha-CF3 tertiary alcohols with vicinal tertiary or quaternary stereocenters. Theoretical studies revealed the important role of nonclassical C-H center dot center dot center dot F-C interactions in stabilizing the transition state, and that the presence of the chlorine atom enhances such interactions for better enantiofacial control.

• 单位
  四川大学; 中国科学院