10.1002/anie.201813708
Angewandte Chemie International Edition
COMMUNICATION
41%. Efforts to prepare [18F]Tiflorex applying halex 18F-
fluorination with a more advanced N-Boc precursor were not
successful.
A. Pees, A. J. Poot, R. V. A. Orru, A. D. Windhorst, D. J. Vugts, Chem.
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766.
1) reagent 1 (1.2 equiv)
1) HOCH2CH2OH
PTSA (10 mol%)
(DPPE)CuCl (10 mol%)
NaOtBu (30 mol%)
toluene, 50 °C, 2 h
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O
HC(OEt)3
CH2Cl2, 70 °C, 12 h
BrF2CS
O
Bpin
Br
O
O
2) PTSA (10 mol%)
Acetone/H2O (5:1)
60 °C, 24 h
2) Pd(dppf)Cl2
B2pin2, KOAc
DMSO, 80 °C, 12 h
10
11, 77%
12, 87%
[
18F]KF/K222
CH3CH2NH2
NaB(OAc)3H
AcOH
H
18FF2CS
AgOTf (2.0 equiv)
pyridine (4.0 equiv)
N
18FF2CS
O
1,2-dichloroethane
1,2-dichloroethane
60 °C, 20 min
[
18F]Tiflorex
60 °C, 20 min
13, RCC: 49% ± 13% (n = 4)
RCC: 84% (n = 1)
Overall RCC: 41%
Scheme 5. Synthesis of [18F]Tiflorex.
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In
summary,
we
have
developed
the
first
bromodifluoromethylthiolating reagent, -cumyl bromodifluoro-
methanesulfenate 1, and have demonstrated its applicability for
the conversion of (hetero)aryl boronic pinacol esters into
bromodifluoromethylthiolated (hetero)arenes under copper
catalysis. This protocol provides facile access to a large range of
BrCF2S-substituted (hetero)arenes including molecules relevant
to material science and drug discovery. This chemistry enabled
the validation of a new retrosynthetic route to 18F-labeled
arylSCF3 featuring (hetero)aryl–SCF3 instead of (hetero)arylS–
CF3 bond construction. This advance expands the range of
precursors available for 18F-trifluoromethylthiolation, provides
access to molecules difficult to obtain by other routes, and
therefore expands the radiochemical space available to
radiochemists for PET imaging studies.
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Acknowledgements
The authors gratefully acknowledge the financial support from
National Natural Science Foundation of China (21625206,
21632009, 21572258, 21572259, 21421002), the Strategic
Priority Research Program of the Chinese Academy of Sciences
(XDB20000000), the EPSRC (EP/L025604/1, NS/A000024/1)
and CRUK (C5255/A16466). We also thank Dr. Tao Yang of
Shanghai Institute of Organic Chemistry (SIOC) for some initial
work and insightful discussion.
quality-guidelines.html
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Keywords: bromodifluoromethylthiolation • boron reagents •
PET • fluorine • radiolabeling
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