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

We report the development of bifunctional trifluoromethylsilyl reagents for selective trifluoromethylation. The newly developed reagent, Me2(CH2Cl)SiCF3, allows highly enantioselective trifluoromethylations of ketones with broad scope. Notably, by taking advantage of the chloromethyl group, a tandem...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2022-09, Vol.61 (38), p.e202208861-n/a
Main Authors: Mu, Bo‐Shuai, Gao, Yang, Yang, Fu‐Ming, Wu, Wen‐Biao, Zhang, Ying, Wang, Xin, Yu, Jin‐Sheng, Zhou, Jian
Format: Article
Language:English
Subjects:
Alcohols
Asymmetric Synthesis
Chlorine
Enantiomers
Fluorine
Ketones
Organic chemistry
Reagents
Tandem Synthesis
Tertiary Alcohols
Trifluoromethylation
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Summary:We report the development of bifunctional trifluoromethylsilyl reagents for selective trifluoromethylation. The newly developed reagent, Me2(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 α‐CF3 tertiary alcohols with vicinal tertiary or quaternary stereocenters. Theoretical studies revealed the important role of nonclassical C−H⋅⋅⋅F−C interactions in stabilizing the transition state, and that the presence of the chlorine atom enhances such interactions for better enantiofacial control. A novel bifunctional trifluoromethylsilyl reagent (BTR), Me2(CH2Cl)SiCF3 is prepared, which enables ketone trifluoromethylations with excellent enantioselectivity and broad scope. Notably, by taking advantage of the chloromethyl group, a tandem synthesis of chiral trifluoromethylated oxasilacyclopentanes and α‐CF3 tertiary alcohols with vicinal tertiary or quaternary stereocenters was developed.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202208861