10.1002/chem.201903702
Chemistry - A European Journal
COMMUNICATION
2015, 47, 2554-2569; c) B. Lantaño, A. Postigo, Org. Biomol. Chem. 2017,
15, 9954-9973.
spectrum of the reaction mixture. Furthermore, when UV/Vis
spectra were recorded with increasing concentrations of
Selectfluor® vs 1 (from 0.5 to 2.5 equiv.) an increase in absorption
was observed, suggesting the formation of an EDA-complex.[14]
[25] There is a better overlap between the absorption spectrum of
the reaction mixture and the emission spectrum of blue LEDs with
lmax = 405 nm than with the blue LEDs with lmax = 440 nm.[14]
Therefore, to further test the influence of light on the
transformation, we followed the standard reaction under different
wavelengths of irradiation (lmax = 365, 405 and 440 nm).[14] These
studies revealed that regardless of the lmax of irradiation, all
reactions reached completion after 30 min. However, at shorter
reaction times the highest yields were observed when blue LEDs
with lmax = 405 nm were employed. At this wavelength of
irradiation the reaction likely proceeds via pathway A (Scheme 3).
Light ON/OFF experiments confirmed that the reaction only
proceeds when irradiated, thus further confirming the crucial role
of the light in the reaction.[14]
[9] For selected references see: a) Q. Michaudel, D. Thevenet, P. S. Baran, J.
Am. Chem. Soc. 2012, 134, 2547-2550; b) S. Bloom, C. R. Pitts, D. C. Miller,
N. Haselton, M. G. Holl, E. Urheim, T. Lectka, Angew. Chem. Int. Ed. 2012,
51, 10580-10583; c) S. Bloom, C. R. Pitts, D. C. Miller, N. Haselton, M. G.
Holl, E. Urheim, T. Lectka, Angew. Chem. 2012, 124, 10732-10735; d) S.
Bloom, J. L. Knippel, T. Lectka, Chem. Sci. 2014, 5, 1175-1178; e) C. R.
Pitts, S. Bloom, R. Woltornist, D. J. Auvenshine, L. R. Ryzhkov, M. A.
Siegler, T. Lectka, J. Am. Chem. Soc. 2014, 136, 9780-9791; f) D. D. Bume,
C. R. Pitts, R. T. Jokhai, T. Lectka, Tetrahedron 2016, 72, 6031-6036; g) D.
D. Bume, S. A. Harry, T. Lectka, C. R. Pitts, J Org Chem 2018, 83, 8803-
8814; h) C. R. Pitts, D. D. Bume, S. A. Harry, M. A. Siegler, T. Lectka, J.
Am. Chem. Soc. 2017, 139, 2208-2211.
[10] G. B. Boursalian, W. S. Ham, A. R. Mazzotti, T. Ritter, Nat. Chem. 2016, 8,
810.
[11] C. R. Pitts, B. Ling, J. A. Snyder, A. E. Bragg, T. Lectka, J. Am. Chem. Soc.
2016, 138, 6598-6609.
[12] For selected references see: a) J. M. R. Narayanam, C. R. J. Stephenson,
Chem. Soc. Rev. 2011, 40, 102-113; b) C. K. Prier, D. A. Rankic, D. W. C.
MacMillan, Chem. Rev. 2013, 113, 5322-5363; c) D. Ravelli, S. Protti, M.
Fagnoni, Chem. Rev. 2016, 116, 9850-9913; d) M. D. Kärkäs, J. A. Porco,
C. R. J. Stephenson, Chem. Rev. 2016, 116, 9683-9747; e) N. A. Romero,
D. A. Nicewicz, Chem. Rev. 2016, 116, 10075-10166; f) J. Twilton, C. Le,
P. Zhang, M. H. Shaw, R. W. Evans, D. W. C. MacMillan, Nature Rev.
Chem. 2017, 1, 0052; g) J. Xie, H. Jin, A. S. K. Hashmi, Chem. Soc. Rev.
2017, 46, 5193-5203.
[13] For selected examples of oxalate salts as radical precursors see: a) C. C.
Nawrat, C. R. Jamison, Y. Slutskyy, D. W. C. MacMillan, L. E. Overman, J.
Am. Chem. Soc. 2015, 137, 11270-11273; b) X. Zhang, D. W. C. MacMillan,
J. Am. Chem. Soc. 2016, 138, 13862-13865; c) Y. Slutskyy, C. R. Jamison,
G. L. Lackner, D. S. Müller, A. P. Dieskau, N. L. Untiedt, L. E. Overman, J.
Org. Chem. 2016, 81, 7029-7035; d) B. Lipp, A. M. Nauth, T. Opatz, J. Org.
Chem. 2016, 81, 6875-6882; e) Y. Slutskyy, C. R. Jamison, P. Zhao, J. Lee,
Y. H. Rhee, L. E. Overman, J. Am. Chem. Soc. 2017, 139, 7192-7195; f) S.
Y. Abbas, P. Zhao, L. E. Overman, Org Lett 2018, 20, 868-871.
[14] See Supporting Information for further details.
In conclusion, a light-mediated, catalyst-free, mild and general
strategy to tackle the challenging deoxyfluorination of tertiary
alcohols has been developed. Preliminary mechanistic
investigations support the proposed radical chain mechanism,
where the key species TEDA2+• is likely generated via irradiation
of an EDA-complex between Selectfluor® and the corresponding
oxalate.
[15] Product 11 decomposes in acidic media via fluoride elimination to give the
corresponding olefin. When the 1H and 13C NMR of 11 were recorded in
CDCl3, after ca. 18 h complete conversion to the olefinic product was
observed. This observation might also explain the difference between the
NMR and the isolated yields, as the column chromatography was carried
out in silica gel. Similar issues were observed for products 4, 18, 24 and 26.
[16] The stereoretention of the reaction was demonstrated by formation of the
corresponding Mosher’s amide after Boc deprotection. See the supporting
information for further details.
[17] M. B. van Niel, I. Collins, M. S. Beer, H. B. Broughton, S. K. F. Cheng, S.
C. Goodacre, A. Heald, K. L. Locker, A. M. MacLeod, D. Morrison, C. R.
Moyes, D. O'Connor, A. Pike, M. Rowley, M. G. N. Russell, B. Sohal, J. A.
Stanton, S. Thomas, H. Verrier, A. P. Watt, J. L. Castro, J. Med. Chem.
1999, 42, 2087-2104.
Acknowledgements
This work was supported by the Fonds der Chemischen Industrie
(Liebig scholarship to A.G.S. and Ph.D. scholarship to F.J.A.T.).
We thank Dr Lisa Candish, Jun.-Prof. Matthew N. Hopkinson, Dr
Michael Teders and Dr David J. Nelson for fruitful discussions and
proofreading of the manuscript. Prof. Stefan Kirsch (BUW) is
greatly acknowledged for his continuous support.
[18] a) T. Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2013, 52,
8214-8264; b) T. Liang, C. N. Neumann, T. Ritter, Angew. Chem. 2013,
125, 8372-8423; c) C. N. Neumann, T. Ritter, Angew. Chem. 2015, 127,
3261-3267.
[19] A. Hachem, D. Grée, S. Chandrasekhar, R. Grée, Synthesis 2017, 49,
2101-2116.
Keywords: Fluorination • Photochemistry • Radicals
[1] For reviews on deoxyfluorination methodologies see: a) N. Al-Maharik, D.
O’Hagan, Aldrichimica Acta 2011, 44, 65-75; b) W. L. Hu, X. G. Hu, L.
Hunter, Synthesis-Stuttgart 2017, 49, 4917-4930.
[20] a) L. J. Cheng, C. J. Cordier, Angew. Chem. Int. Ed. 2015, 54, 13734-
13738; b) L.-J. Cheng, C. J. Cordier, Angew. Chem. 2015, 127, 13938-
13942.
[21] For the seminal work on EDA-complexes see: a) R. S. Mulliken, J. Am.
Chem. Soc. 1952, 74, 811-824; For reviews on the use of EDA-complexes
in organic synthesis see: b) C. G. S. Lima, T. de M. Lima, M. Duarte, I. D.
Jurberg, M. W. Paixão, ACS Catal. 2016, 6, 1389-1407.
[22] For selected examples on the use of excited iminium species as electron
acceptors see: a) Y. Q. Zou, F. M. Hormann, T. Bach, Chem. Soc. Rev.
2018, 47, 278-290; b) M. Silvi, C. Verrier, Y. P. Rey, L. Buzzetti, P.
Melchiorre, Nat. Chem. 2017, 9, 868-873; c) D. Mazzarella, G. E. M.
Crisenza, P. Melchiorre, J. Am. Chem. Soc. 2018, 140, 8439-8443; d) C.
Verrier, N. Alandini, C. Pezzetta, M. Moliterno, L. Buzzetti, H. B. Hepburn,
A. Vega-Peñaloza, M. Silvi, P. Melchiorre, ACS Catal. 2018, 8, 1062-1066;
e) G. Goti, B. Bieszczad, A. Vega-Peñaloza, P. Melchiorre, Angew. Chem.
2019, 131, 1226-1230; f) G. Goti, B. Bieszczad, A. Vega-Peñaloza, P.
Melchiorre, Angew. Chem. Int. Ed. 2019, 58, 1213-1217; g) T. Morack, C.
Mück-Lichtenfeld, R. Gilmour, Angew. Chem. 2019, 131, 1221-1225; h) T.
Morack, C. Muck-Lichtenfeld, R. Gilmour, Angew. Chem. Int. Ed. 2019, 58,
1208-1212.
[2] R. P. Singh, J. n. M. Shreeve, Synthesis 2002, 2002, 2561-2578.
[3] a) M. K. Nielsen, C. R. Ugaz, W. Li, A. G. Doyle, J. Am. Chem. Soc. 2015,
137, 9571-9574; b) M. K. Nielsen, D. T. Ahneman, O. Riera, A. G. Doyle,
J. Am. Chem. Soc. 2018, 140, 5004-5008.
[4] a) F. Sladojevich, S. I. Arlow, P. Tang, T. Ritter, J. Am. Chem. Soc. 2013,
135, 2470-2473; b) X. Shen, C. N. Neumann, C. Kleinlein, N. W. Goldberg,
T. Ritter, Angew. Chem. Int. Ed. 2015, 54, 5662-5665; c) X. Shen, C. N.
Neumann, C. Kleinlein, N. W. Goldberg, T. Ritter, Angew. Chem. 2015, 127,
5754-5757; d) T. Fujimoto, T. Ritter, Org. Lett. 2015, 17, 544-547; e) C. N.
Neumann, J. M. Hooker, T. Ritter, Nature 2016, 534, 369; f) C. N. Neumann,
T. Ritter, Acc. Chem. Res. 2017, 50, 2822-2833.
[5] N. W. Goldberg, X. Shen, J. Li, T. Ritter, Org. Lett. 2016, 18, 6102-6104.
[6] a) Su, J. Y.; Grunenfelder, D. C.; Takeuchi, K.; Reisman, S. E., Org Lett
2018, 20, 4912-4916; b) J. Brioche, Tetrahedron Lett. 2018, 59, 4387-
4391; and c) M. González-Esguevillas, J. Miró, J. L. Jeffrey, D. W. C.
MacMillan, Tetrahedron 2019, 75, 4222-4227
[7] a) P. T. Nyffeler, S. G. Durón, M. D. Burkart, S. P. Vincent, C. H. Wong,
Angew. Chem. Int. Ed. 2004, 44, 192-212; b) P. T. Nyffeler, S. G. Durón,
M. D. Burkart, S. P. Vincent, C.-H. Wong, Angew. Chem. 2005, 117, 196-
217.
[23] a) L. Niu, J. Liu, X.-A. Liang, S. Wang, A. Lei, Nat. Commun. 2019, 10, 467;
b) X. A. Liang, L. Niu, S. Wang, J. Liu, A. Lei, Org Lett 2019, 21, 2441-2444.
[24] H. Zhao, J. Jin, Org Lett 2019, DOI: 10.1021/acs.orglett.9b01635.
[25] Attempts to calculate the association constant or the stoichiometry of this
species via Job’s plot proved unsuccessful.
[8] For the seminal contribution on fluorine transfer to alkyl radicals see: a) M.
Rueda-Becerril, C. Chatalova Sazepin, J. C. T. Leung, T. Okbinoglu, P.
Kennepohl, J.-F. Paquin, G. M. Sammis, J. Am. Chem. Soc. 2012, 134,
4026-4029; For selected reviews on radical fluorination see: b) C.
Chatalova-Sazepin, R. Hemelaere, J.-F. Paquin, G. M. Sammis, Synthesis
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