TY - JOUR
T1 - Oxidative aliphatic C-H fluorination with manganese catalysts and fluoride ion
AU - Liu, Wei
AU - Huang, Xiongyi
AU - Groves, John Taylor
PY - 2013
Y1 - 2013
N2 - Fluorination is a reaction that is useful in improving the chemical stability and changing the binding affinity of biologically active compounds. The protocol described here can be used to replace aliphatic, C(sp 3)-H hydrogen in small molecules with fluorine. Notably, isolated methylene groups and unactivated benzylic sites are accessible. The method uses readily available manganese porphyrin and manganese salen catalysts and various fluoride ion reagents, including silver fluoride (AgF), tetrabutylammonium fluoride and triethylamine trihydrofluoride (TREAT·HF), as the source of fluorine. Typically, the reactions afford 50-70% yield of mono-fluorinated products in one step. Two representative examples, the fragrance component celestolide and the nonsteroidal anti-inflammatory drug ibuprofen, are described; they produced useful isolated quantities (250-300 mg, ~50% yield) of fluorinated material over periods of 1-8 h. The procedures are performed in a typical fume hood using ordinary laboratory glassware. No special precautions to rigorously exclude water are required.
AB - Fluorination is a reaction that is useful in improving the chemical stability and changing the binding affinity of biologically active compounds. The protocol described here can be used to replace aliphatic, C(sp 3)-H hydrogen in small molecules with fluorine. Notably, isolated methylene groups and unactivated benzylic sites are accessible. The method uses readily available manganese porphyrin and manganese salen catalysts and various fluoride ion reagents, including silver fluoride (AgF), tetrabutylammonium fluoride and triethylamine trihydrofluoride (TREAT·HF), as the source of fluorine. Typically, the reactions afford 50-70% yield of mono-fluorinated products in one step. Two representative examples, the fragrance component celestolide and the nonsteroidal anti-inflammatory drug ibuprofen, are described; they produced useful isolated quantities (250-300 mg, ~50% yield) of fluorinated material over periods of 1-8 h. The procedures are performed in a typical fume hood using ordinary laboratory glassware. No special precautions to rigorously exclude water are required.
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U2 - 10.1038/nprot.2013.144
DO - 10.1038/nprot.2013.144
M3 - Article
C2 - 24177292
AN - SCOPUS:84888349274
VL - 8
SP - 2348
EP - 2354
JO - Nature Protocols
JF - Nature Protocols
SN - 1754-2189
IS - 12
ER -