Hydrogen-bond promoted nucleophilic fluorination: concept, mechanism and applications in positron emission tomography

Due to the tremendous interest in carbonfluorine bond-forming reactions, research efforts in this area have been dedicated to the development of facile processes to synthesize small fluorine-containing organic molecules. Among others, PET (Positron Emission Tomography) is one of the most important a...

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Bibliographic Details
Published in:Chemical Society reviews 2016-08, Vol.45 (17), p.4638-465
Main Authors: Lee, Ji-Woong, Oliveira, Maria Teresa, Jang, Hyeong Bin, Lee, Sungyul, Chi, Dae Yoon, Kim, Dong Wook, Song, Choong Eui
Format: Article
Language:English
Subjects:
Alkali metals
Bonding
Fluorides
Fluorination
Hydrogen bonding
Positron emission
Solvents
Tomography
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Summary:Due to the tremendous interest in carbonfluorine bond-forming reactions, research efforts in this area have been dedicated to the development of facile processes to synthesize small fluorine-containing organic molecules. Among others, PET (Positron Emission Tomography) is one of the most important applications of fluorine chemistry. Recognizing the specific requirements of PET processes, some groups have focused on fluorination reactions using alkali metal fluorides, particularly through S N 2-type reactions. However, a common misconception about the role of protic solvents and hydrogen bonding interactions in this class of reactions has hampered the employment of these excellent promoters. Herein, we would like to review recent discoveries in this context, showing straightforward nucleophilic fluorination reactions using alkali metal fluorides promoted by protic solvents. Simultaneous dual activation of reacting partners by intermolecular hydrogen bonding and the enhancement of the effective fluoride nucleophilicity, which is Nature's biocatalytic approach with the fluorinase enzyme, are the key to this unprecedentedly successful nucleophilic fluorination. This Tutorial Review summarizes the recent breakthroughs in S N 2-type nucleophilic fluorination reactions using alkali metal fluorides promoted by protic solvents, inducing excellent selectivity and high reaction rates.
ISSN:0306-0012
1460-4744
DOI:10.1039/c6cs00286b