Hydrogen-bond promoted nucleophilic fluorination: concept, mechanism and applications in positron emission tomography.
Due to the tremendous interest in carbon-fluorine 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 SN2-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.
Department of Chemistry, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, Korea. s1673@skku.edu.
Ji-Woong
JW
Lee
Department of Chemistry, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, Korea. s1673@skku.edu.
Maria Teresa
MT
Oliveira
Department of Chemistry, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, Korea. s1673@skku.edu.
Hyeong Bin
HB
Jang
Department of Applied Chemistry, Kyung Hee University 1732, Duckyoung-daero 1732, Gihung-gu, Yongin-si, Gyeonggi-do 446-701, Korea. sylee@khu.ac.kr.
Sungyul
S
Lee
Department of Chemistry, Sogang University, 35 Baekbeomro Mapogu, Seoul 121-742, Korea. dychi@sogang.ac.kr.
Dae Yoon
DY
Chi
Department of Chemistry, Inha University, 100 Inha-ro, Nam-gu, Incheon 402-751, Korea. kimdw@inha.ac.kr.
Dong Wook
DW
Kim
Department of Chemistry, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 440-746, Korea. s1673@skku.edu.
Choong Eui
CE
Song