10.1002/anie.202005181
Angewandte Chemie International Edition
FULL PAPER
[3]
H.-J. Böhme, D. Banner, M. Kansy, B. Kuhn, K. Müller, U. Obst-Sander,
M. Stahl, ChemBioChem. 2004, 5, 637-643.
[4]
[5]
T. Liang, T. Ritter, Angew. Chem. Int. Ed. 2013, 52, 8214-8264.
(a) B. Zajc, M. Zupan, J. Org. Chem. 1990, 55, 1099-1102. (b) G.
Haufe, U. Wessel, K. Schulze, G. Alvernhe, J. Fluorine Chem. 1995,
74, 283-291. (c) T. B. Patrick, U. P. Dahal, J. Fluorine Chem. 2009,
130, 470-473.
[6]
(a) V. Rauniyar, A. D. Lackner, G. L. Hamilton, F. D. Toste, Science
2011, 334, 1681-1684. (b) F. Romanov-Michailidis, L. Guénée, A.
Alexakis, Angew. Chem. Int. Ed. 2013, 52, 9266-9270. (c) F. Romanov-
Michailidis, M. Romanova-Michaelides, M. Pupier, A. Alexakis, Chem.
Eur. J. 2015, 21, 5561-5583.
[7]
Y. Lu, H. Nakatsuji, Y. Okumura, L. Yao, K. Ishihara, J. Am. Chem.
Soc. 2018, 140, 6039-6043.
[8]
[9]
H. C. Shen, Tetrahedron 2009, 65, 3931-3952.
(a) C. Thiehoff, Y. P. Rey, R. Gilmour, Isr. J. Chem. 2017, 57, 92-100.
(b) I. G. Molnár, C. Thiehoff, M. C. Holland, R. Gilmour, ACS Catal.
2016, 6, 7167-7173. (f) F. Scheidt, P. Selter, N. Santschi, M. C.
Holland, D. V. Dudenko, C. D. Daniliuc, C. Mück-Lichtenfeld, M. R.
Hansen, R. Gilmour, Chem. Eur. J. 2017, 23, 6142-6149.
Scheme 4. A tentative catalytic cycle and induction model invoking a type IIinv
pathway.
In conclusion, an operationally simple, direct fluoro-cyclization of
aryl allyl ethers to access biologically relevant enantio-enriched
3-fluorochromanes is disclosed. Selectivities up to 7:93 e.r. can
be obtained using a simple C2-symmetric iodoresorcinol catalyst
in combination with Selectfluor® and simple amine:HF
combinations. X-ray crystallographic analyses of representative
products reveal conformations that enable stabilizing
[10] G. Valsamakis, S. Kumar, Exp. Opin. Pharmacother. 2000, 1, 1413-
1421.
[11] (a) M.-J. Xu, X.-J. Lui, Y.-L. Zhao, D. Lui, Z.-H. Xu, X.M.- Lang, P. Ao,
W.-H. Lin, S.-L. Yang, Z.-G. Zhang, J. Xu, Mar. Drugs 2012, 10, 639-
654. (b) X.-J. Liu, M.-J. Xu, S.-T. Fan, Z. Wu, J. Li, X.-M. Yang, Y.-H.
Wang, J. Xu, Z.-G. Zhang, J. Investig. Dermatol. 2013, 133, 1351-1360.
(c) X. Jiao, Y. Yao, B. Yang, X. Lui, X. Li, H. Yang, L. Li, J. Xu, M. Xu, P.
Xie, Org. Biomol. Chem. 2016, 14, 1805-1813.
stereoelectronic
interactions.
This
physicochemical
consideration renders these materials potentially valuable as
drug discovery modules. Mechanistic interrogation of the
reaction using deuterated probes reveals that the process is
stereospecific and likely follows a type IIinv pathway.
[12] R. Brigelius-Flohé, M. G. Traber, FASEB J. 1999, 13, 1145-1155.
[13] M. J. Weyant, A. M. Carothers, A. J. Dannenberg, M. M. Bertagnolli,
Cancer Res. 2001, 61, 118-125.
[14] For selected examples of catalytic fluorocyclizations via I(I)/I(III)
catalysis, see (a) S. Suzuki, T. Kamo, K. Fukushi, T. Hiramatsu, E.
Tokunaga, T. Dohi, Y. Kita, N. Shibata, Chem. Sci. 2014, 5, 2754–2760.
(b) E. M. Woerly, S. M. Banick, E. N. Jacobsen, J. Am. Chem. Soc.
2016, 138, 13858-13861. (c) K. Kitamura, A. Miyake, K. Muta, J.
Oyamada, J. Org. Chem. 2017, 82, 11721-11726. (d) K. M. Mennie, S.
M. Banik, E. C. Reichert, E. N. Jacobsen, J. Am. Chem. Soc. 2018, 140,
4797-4802. (e) F. Scheidt, C. Thiehoff, G. Yilmaz, S. Meyer, C. G.
Daniliuc, G. Kehr, R. Gilmour, Beilstein J. Org. Chem. 2018, 14, 1021-
1027.
Experimental Section
Full details are provided in the Supporting Information.
Acknowledgements
We acknowledge generous financial support from the WWU
[15] For selected stoichiometric fluorocyclizations with I(III) reagents, see (a)
M. Sawaguchi, S. Hara, N. Yoneda, J. Fluorine Chem. 2000, 105, 313-
317. (b) W. Kong, P. Feige, T. de Haro, C. Nevado, Angew. Chem. Int.
Ed. 2013, 52, 2469–2473. (c) G. C. Geary, E. G. Hope, A. M.
Stuart, Angew. Chem. Int. Ed. 2015, 54, 14911–14914. (d) W. Yuan, K.
J. Szabó, Angew. Chem. Int. Ed. 2015, 54, 8533-8537. (e) C. Brunner,
A. Andries-Ulmer, G. M. Kiefl, T. Gulder, Eur. J. Org. Chem. 2018,
2615-2621. (f) J. Zhang, K. J. Szabó, F. Himo, ACS Catal. 2017, 7,
1093-1100. (g) L. Li, S. Cao, F. Lin, P. Liao, Y. Ning, Eur. J. Org. Chem.
2020, 693–696.
Münster and the German Research Council
Forschungsgemeinschaft (DFG).
/ Deutsche
Keywords: chromanes • fluorine • gauche effect •
organocatalysis • stereospecificity
[1]
(a) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem.
Soc. Rev. 2008, 37, 320-330. (b) D. O'Hagan, J. Fluorine Chem. 2010,
131, 1071–1081. (c) E. P. Gillis, J. K. Eastman, M. D. Hill, D. J.
Donnelly, N. A. Meanwell, J. Med. Chem. 2015, 58, 8315-8359. (d) N.
A. Meanwell, J. Med. Chem. 2018, 61, 5822-5880.
[16] (a) S. V. Kohlhepp, T. Gulder, Chem. Soc. Rev. 2016, 45, 6270-6288.
(b) A. M. Arnold, A. Ulmer, T. Gulder, Chem. Eur. J. 2016, 22, 8728-
8739.
[2]
(a) D. O´Hagan, Chem. Soc. Rev. 2008, 37, 308-319. (b) L. E. Zimmer,
C. Sparr, R. Gilmour, Angew. Chem. Int. Ed. 2011, 50, 11860-11871.
(c) M. Aufiero, R. Gilmour, Acc. Chem. Res. 2018, 51, 1701-1710.
[17] (a) 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,
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