Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

Wen-Bin Yi,Zijuan Zhang,Wei Zhang,Xin Huang,Dian-Rong Zhu,Chun Cai

doi:10.3762/bjoc.8.138

Abstract

A fluorous cinchona alkaloid ester has been developed as a chiral promoter for the asymmetric fluorination of β-ketoesters. It has comparable reactivity and selectivity to the nonfluorous versions of cinchona alkaloids and can be easily recovered from the reaction mixture by simple fluorous solid-phase extraction (F-SPE) and used for the next round of reaction without further purification.

Highlights

Fluorinated organic compounds have unique properties because fluorine forms a strong carbon–fluorine bond with a small covalent radius and high electronegativity
The synthesis of fluorous quinine ester C-1 was accomplished by the reaction of quinine with a fluorous acid chloride (Scheme 1). This compound was purified by fluorous-solid phase extraction (F-SPE) with a cartridge charged with fluorous silica gels [29,30]
A fluorous cinchona alkaloid-ester has been introduced as a promoter for Selectfluor-based asymmetric fluorination of β-ketoesters

Summary

Introduction

Fluorinated organic compounds have unique properties because fluorine forms a strong carbon–fluorine bond with a small covalent radius and high electronegativity. With the fluorous quinine ester C-1 in hand, we explored the fluorination reaction using ethyl 2-methyl-3-oxo-3-phenylpropanoate (1a) as a model compound. It was found that using MeCN as a solvent with 1 equiv of C-1 gave fluorinated product 2a in 49% yield and 65% ee (Table 1, entry 1).

Results

Conclusion