Selective synthesis of fluorinated organic compounds and investigation of their properties have become a major topic in all fields of chemical sciences and in technological applications. While methods of formation of C–F bonds have been developed from the beginning of organic fluorine chemistry, application of C–F bond cleavage in poly-fluorinated carbon compounds for the preparation of partially fluorinated molecules was less developed. This is apparently due to the fact that C–F bonds are the strongest that carbon can form. Research for the activation of C–F bonds of arylfluorides has a long history. On the other hand, aliphatic fluorides have been less frequently involved in such processes and quite forced conditions such as organometallic reagents or strong nucleophiles have to be applied. Thus the development of mild and effective methods for the activation of an aliphatic C-F bond has become a stimulating topic in general organic chemistry. Recently, we reported the cleavage of a non-activated aliphatic C–F bond by utilizing the fluorophilicity of silicon and the formation of a strong (~140 kcal/mol) silicon-fluorine bond. Using this reaction, 3,5-diaryl-5-fluoromethyl-oxazolidin-2-ones 1 were synthesized by a conceptually new desymmetrization of non-activated aliphatic 1,3-difluorides 2 with silicon-induced C–F bond-activation as a key step under mild reaction conditions with bis(trimethylsilyl)acetamide (BSA) and catalytic CsF (Scheme 1). To extend this chemistry, we set our next goal to “asymmetric desymmetrization” via C–F bond activation. Herein, we succeeded in asymmetric synthesis of 3,5-diaryl-5-fluoromethyl-oxazolidin-2-ones 1 with quaternary carbon center with high enantioselectivities via cleavage of the much more challenging non-activated aliphatic Csp3–F bond of 2 (Scheme 1). The use of chiral ammonium bifluoride catalyst and ortho-effect on the stereogenic aryl group play key roles for success.

Asymmetric desymmetrization via non-metallic C-F bond activation: Synthesis of 3,5-diaryl-5-fluoromethyl-oxazolidin-2-ones with quaternary carbon center

253rd National Meeting (2017)

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