Communications
corrected RCY of 18% (Table 1, entry 8; n = 3).[11] The
[1] a) Handbook of Radiopharmaceuticals (Eds.: M. J. Welch, C. S.
Redvanly), Wiley, New York, 2003; b) S. M. Ametamey, M.
[2] For monographs, see: R. D. Chambers, Fluorine in Organic
Chemistry, Blackwell, Oxford, 2004; K. Uneyama, Organofluor-
ine Chemistry, Wiley, New York, 2006.
remaining radioactivity was observed at the solvent front
and was attributed to unreacted [18F]-2 and [18F]fluoride ion.
The less electron-rich stannylated precursor 7 also reacted
under similar conditions and gave [18F]fluoroanisole ([18F]-10)
in
a similar RCY (Table 1, entry 9). Most pleasingly,
[18F]fluorophenol 11 was accessible upon fluorodestannyla-
tion of 8 with a RCY of 14% (Table 1, entry 10; n = 3).
In summary, [18F]Selectfluor bis(triflate) 2 was prepared
successfully and used for the synthesis of 18F-labeled material.
This labeled reagent has a unique reactivity profile in the
sense that it is much milder and selective than elemental
fluorine and suitable for the fluorination of electron-rich
substrates that cannot be fluorinated using alternative N–F
reagents. These characteristics are highly sought after,
especially for the 18F labeling of precursors that are not
suitable for nucleophilic fluorination. The applicability of
[18F]Selectfluor bis(triflate) 2 was demonstrated with the
radiolabeling of representative substrates. The silver-triflate-
mediated 18F fluorination of the electron-rich arylstannanes is
of particular interest because this transformation can now be
conducted selectively and rapidly under very mild conditions
(room temperature; “shake and mix” type protocol). Signifi-
cantly, the unprotected alcohol functionality of arylstannane 8
is well tolerated in this process. It was previously suggested
that “the development of 18F-labeled Selectfluor would
revolutionize electrophilic fluorination in much the same
way as the development of the unlabeled reagent”.[7] This
statement certainly stands true if the reagent allows for the
preparation of high SA 18F-labeled compounds. With the
preparation of [18F]-2 from high SA [18F]F2, we have shown
that the 18F-labeled compound 5 was formed with SA in the
range of 20 GBqmmolÀ1. This work demonstrated that we are
one significant step closer to the ultimate goal in the field,
which is the availability of the electrophilic fluorinating
reagent of tailored reactivity such as 18F-labeled Selectfluor,
suited for the preparation of radiotracers with SA matching
the level currently attainable using [18F]fluoride ion
(in practice 8 CimmolÀ1 or ꢀ300 GBqmmolÀ1). Ongoing
work in our laboratories investigates further the applicability
of [18F]-2 with the preparation of clinically useful radiotracers,
including [18F]-6-fluoro-l-DOPA.
[3] a) P. W. Miller, N. J. Long, R. Vilar, A. D. Gee, Angew. Chem.
[4] For the radiosynthesis of [18F]-labeled l-tyrosine and l-DOPA,
Bida, J. R. Barrio, Appl. Radiat. Isot. 1992, 43, 989; c) A. Luxen,
M. Guillaume, W. P. Melega, V. W. Pike, O. Solin, R. Wagner,
Nucl. Med. Biol. 1992, 19, 149; d) E. Hess, S. Sichler, A. Kluge,
Gillet, S. Guillout, A. Plenevaux, J. Aerts, A. Luxen, Eur. J. Org.
L. Christiaens, J. Nucl. Med. 1990, 31, 1247; g) E. Hess, G.
Kuroda, A. Ochi, N. Nakane, T. Umeyama, N. Muto, N. Nimura,
Hinnen, D. Fournier, F. Vaufrey, C. Crouzel, J. Labelled Compd.
Radiopharm. 1998, 41, 105; j) S. Forsback, O. Eskola, M.
[5] a) F. Oberdorfer, E. Hofman, W. Maier-Borst, J. Labelled
Hofman, W. Maier-Borst, Appl. Radiat. Isot. 1988, 39, 685;
c) N. Satyamurthy, G. T. Bida, M. E. Phelps, J. R. Barrio, Appl.
Radiat. Isot. 1990, 41, 733; d) F. Oberdorfer, G. Dietzel, J.
Labelled Compd. Radiopharm. 2003, 46, S216.
[6] H. Teare, E. G. Robins, E. ꢁrstad, S. K. Luthra, V. Gouverneur,
[7] P. T. Nyffeler, S. G. Durꢂn, M. D. Burkart, S. P. Vincent, C.-H.
Wong, Angew. Chem. 2004, 116, 194; Angew. Chem. Int. Ed.
2004, 43, 192.
[8] S. P. Vincent, M. D. Burkart, C.-Y. Tsai, Z. Zhang, C.-H. Wong, J.
[10] a) R. E. Banks, M. K. Besheesh, S. N. Mohialdin-Khaffaf, I.
S. N. Mohialdin-Khaffaf, G. S. Lal, I. Sharif, R. G. Syvret, J.
Products and Chemicals, Inc. USA), US 5,086,178, 1992, p. 9.
[11] The RCY will be calculated based on the use of crude stock
solution containing both [18F]-2 (50% of the activity) and Li18F
(50% of the activity). The maximum radiochemical yield
achievable is therefore 50%.
Experimental Section
Typical procedure for the preparation of [18F]-9 from [18F]Selectfluor
bis(triflate) 2: Compound 6 (0.01 mmol) was added to [18F]-2
(0.2 mL) in a solution of acetone and AgOTf (0.02 mmol). The
reaction mixture was stirred at RT for 20 min. Analysis was
performed by radio-HPLC of 0.1 mL of the reaction mixture diluted
in 0.9 mL of CH3CN/H2O (1:1).
[12] For a nucleophilic 18F fluorination protocol using diaryliodonium
salts as precursors, see: V. W. Pike, F. I. Aigbirhio, J. Chem. Soc.
Chem. Commun. 1995, 21, 2215 – 2216; for recent work on
palladium-catalyzed nucleophilic 19F fluorination of electron-
rich aromatic compounds, see: S. D. A. Watson, M. N. Su, G.
Teverovskiy, Y. Zhang, J. Garcꢃa-Fortanet, T. Kinzel, S. L.
Received: April 19, 2010
Published online: August 16, 2010
[13] For electrophilic fluorination of vinyl or arylstannanes in the
presence of AgOTf, see: a) M. A. Tius, J. K. Kawakami,
Keywords: electrophilic substitution · fluorination ·
.
positron emission tomography · radiochemistry · Selectfluor
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 6821 –6824