10.1002/chem.201901176
Chemistry - A European Journal
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Program(16QA1404600), and the Youth Innovation Promotion
Association CAS (2014231) is gratefully acknowledged.
Scheme 3. Mechanistic Considerations
Conflict of interest
The authors declare the following financial interest: J.H., J.G. and C.N.
have filed a patent application based on the results of this study.
Keywords: deoxyfluorination · alcohols · SulfoxFluor
(1) Q. A. Huchet, B. Kuhn, B. Wagner, N. A. Kratochwil, H. Fischer, M. Kansy,
D. Zimmerli, E. M. Carreira, K. Müller, J. Med. Chem. 2015, 58, 9041.
(2) P. A. Champagne, J. Desroches, J.-D. Hamel, M. Vandamme, J.-F. Paquin,
Chem. Rev. 2015, 115, 9073; and references therein.
(3) a) R. P. Singh, J. M. Shreeve, Synthesis 2001, 34, 2561; b) N. Al-Maharik, D.
O’Hagan, Aldrichimica Acta 2011, 44, 65; c) M.-O. Turcotte-Savard, O. Mahe,
J.-F. Paquin, Chim. Oggi 2013, 31, 14; d) C. N. Neumann, T. Ritter, Acc. Chem.
Res. 2017, 50, 2822.
(4) a) N. N. Yarovenko, M. A. Raksha, V. N. Shemanina, A. S. Vasileva, J. Gen.
Chem. USSR 1957, 27, 2246; b) A. Takaoka, K. Iwamoto, T. Kitazume, N.
We envisioned that DBU may serve as a base to deprotonate the
alcohol, thus promoting the formation of the sulfonimidate ester via
replacing the fluorine atom in SulfoxFluor, which is similar to
previously reported reaction of PyFluor.14a According to above results
Ishikawa, J. Fluorine Chem. 1979, 14, 421.
(5) W. R. Hasek, W. C. Smith, V. A. Engelhardt, J. Am. Chem. Soc. 1960,
82, 543.
(6) W. J. Middleton, J. Org. Chem. 1975, 40, 574.
and rationalization,
a
proposed reaction pathway for the
(7) G. S. Lal, G. P. Pez, R. J. Pesaresi, F. M. Prozonic & H. Cheng, J. Org.
Chem. 1999, 64, 7048.
deoxyfluorination of alcohols with SulfoxFluor is shown in Scheme 3b.
First, DBU deprotonates the alcohol to generate the alcoholate anion,
which undergoes very fast nucleophilic addition to the SulfoxFluor to
afford a pentacoordinated intermediate 7. Then the stabilization effect
of the protonated DBU on fluoride promotes the quick release of the
fluorine substituent from intermediate 7 to afford the sulfonimidate
ester 6. Finally, the nucleophilic displacement of the sulfonimidate
group by DBU-HF provided the alkyl fluoride products and the salt 8.
We believe that the excellent leaving ability of the sulfonimidate group
can be attributed to the electron-withdrawing nature of the N-
substuituitent. The further activation of the leaving group by
protonation on nitrogen20d is less likely due to the weak acidity of the
DBU-HF complex.
(8) F. Beaulieu, L.-P. Beauregard, G. Courchesne, M. Couturier, F. LaFlamme,
A. L’Heureux, Org. Lett. 2009, 11, 5050.
(9) T. Umemoto, R. P. Singh, Y. Xu, N. Saito, J. Am. Chem. Soc. 2010, 132,
18199.
(10) N. Ishikawa, H. Iwakiri, A. Takaoka, Bull. Chem. Soc. Jpn. 1979, 52, 3377.
(11) F. Sladojevich, S. I. Arlow, P. Tang, T. Ritter, J. Am. Chem. Soc. 2013, 135,
2470.
(12) N. W. Goldberg, X. Shen, J. Li, T. Ritter, Org. Lett. 2016, 18, 6102.
(13) a) B. Bennua-Skalmowski, H. Vorbrüggen, Tetrahedron Lett. 1995, 36,
2611; b) H. Vorbrüggen, Synthesis 2008, 1165.
In summary, we have developed a bench-stable and crystalline
sulfonimidoyl fluoride compound, SulfoxFluor, as a safe and practical
reagent for rapid and efficient deoxyfluorination of alcohols.
SulfoxFluor can be readily accessible from inexpensive materials and
handled without special techniques. Its reaction with alcohols not only
tolerates a wide range of functionalities, but also shows high selectivity
against elimination. Therefore, this new deoxyfluorination protocol
with SulfoxFluor reagent promises to find many industrial applications.
Our results also provides new insights into the chemistry of fluorinated
sulfoximines as well as the different reactivities of various
deoxyfluorination reagents. Further investigation on the synthetic
application of SulfoxFluor by utilizing its unique activation ability is
underway in our laboratory.
(14) a) M. K. Nielsen, C. R. Ugaz, W. Li, A. G. Doyle, J. Am. Chem. Soc. 2015,
137, 9571; b) For a most recent report on deoxyfluorination with various
sulfonyl fluorides, see: M. K. Nielsen, D. T. Ahneman, O. Riera, A. G. Doyle, J.
Am. Chem. Soc. 2018, 140, 5004.
(15) L. Li, C. Ni, F. Wang, J. Hu, Nat. Commun. 2016, 7, 13320.
(16) S. J. Tavener, J. H. Clark, In Fluorine and the Environment: Agrochemicals,
Archaeology, Green Chemistry & Water (Advances in Fluorine Science; Vol. 2),
A. Tressaud, Ed.; Elsevier: Amsterdam, 2006; p 177.
(17) a) M. Reggelin, C. Zur, Synthesis 2000, 1, 1; b) U. Lücking, Angew. Chem.,
Int. Ed. 2013, 52, 9399; c) V. Bizet, R. Kowalczyk, C. Bolm, Chem. Soc. Rev.
2014, 43, 2426.
(18) For reviews, see: a) X. Shen, J. Hu, Eur. J. Org. Chem. 2014, 4437; b) V.
Bizet, R. Kowalczyk, C. Bolm, Chem. Soc. Rev. 2014, 43, 2426. For a recent
example, see: c) Q. Liu, X. Shen, C. Ni, J. Hu, Angew. Chem., Int. Ed. 2017, 56,
619.
Acknowledgements
Financial support of this work by the National Basic Research Program
of China (2015CB931900), the National Key Research and
Development Program of China (2016YFB0101200), the National
Natural Science Foundation of China (21632009, 21372246, 21421002,
21472221), the Key Program of the Chinese Academy of Sciences
(KGZD-EW-T08), the Key Research Program of Frontier Sciences of
CAS (QYZDJ-SSW-SLH049), the Shanghai Academic Research
Leader Program (15XD1504400), the Shanghai Rising-Star
(19) J. Dong, L. Krasnova, M. G. Finn, K. B. Sharpless, Angew., Chem. Int. Ed.
2014, 53, 9430.
(20) a) T. J. Maricich, R. A. Jourdenais, T. A. Albright, J. Am. Chem. Soc. 1973,
95, 5831; b) C. R. Johnson, E. U. Jonsson, C. C. Bacon, J. Org. Chem. 1979, 44,
2055; c) B. C. Challis, J. N. Iley, J. Chem. Soc., Perkin Trans. 2 1985, 699; d) T.
J. Maricich, M. J. Allan, B. S. Kislin, A. I-T. Chen, F.-C. Meng, C. Bradford, N.-
C. Kuan, J. Wood, O. Aisagbonhi, A. Poste, D. Wride, S. Kim, T. Santos, M.
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