Organic Letters
Letter
ORCID
Scheme 6. Manipulation of α-Fluoroepoxides and Aziridines
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the University of Vienna and Bari for
financial support. This research was supported by the project
Laboratorio Sistema code PONa300369 financed by MIUR,
MISE, Horizon 2020 − PON 2014/2020 FARMIDIAB “code
338”. S.M. acknowledges the University of Vienna for a
Unidocs fellowship. We thank A. Roller and D. Dobusch
(University of Vienna) for X-ray analysis and HRMS
measurements, respectively. The authors are indebted to
Albemarle Corporation and ABCR Germany for generous gifts
of organolithiums and fluoroiodomethane.
a
b
Isolated yields. Diasteromeric ratio determined by 19F NMR
c
analysis. Otherwise indicated: isolated yields. Diasteromeric ratio
(dr) determined by 19F-NMR analysis.
REFERENCES
■
with full preservation of the sensitive α-fluorinated three-
membered heterocyclic units.
(1) O’Hagan, D. Chem. Soc. Rev. 2008, 37, 308−319.
(2) For leading reviews, see: (a) Wang, J.; Sanchez-Rosello, M.;
̃
Acena, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok,
V. A.; Liu, H. Chem. Rev. 2014, 114, 2432−2506. (b) Gillis, E. P.;
Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. J. Med.
Chem. 2015, 58, 8315−8359. (c) Meanwell, N. A. J. Med. Chem. 2018,
61, 5822−5880. (d) Purser, S.; Moore, P. R.; Swallow, S.;
Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320−330. See also:
(e) Dammacco, M.; Degennaro, L.; Florio, S.; Luisi, R.; Musio, B.;
Altomare, A. J. Org. Chem. 2009, 74, 6319−6322.
́
́
In conclusion, we have developed an expeditious synthesis of
α-fluoroepoxides and α-fluoroaziridines starting from ketones
and imine-type derivatives (aldimines and ketimines),
respectively. The proposed strategy relies on the introduction
of an unknown fluorocarbenoid−fluoroiodomethyllithium
which acting in nucleophilic mode selectively attacks the
carbonyl-like electrophilic center. The inherent different
reactivities of the two C−halogen bonds connected to the
inserted carbon allow the exclusive expulsion of iodine, thus
leavingafter the ring closurethe fluorine atom in the final
compound. In the case of imines, a two-step sequence is
required, with the ring-closure step occurring on the (isolable)
fluoroiodoamines. Remarkably, fluoroiodomethyllithium acts
with superb chemoselectivity as evidenced in the presence of
additional electrophilic sites across the molecular core: the full
preservation of an aldehyde, a ketone, a nitrile, or an alkene
nicely highlights the unique reactivity pattern of this new
mixed, bis-functionalized carbenoid.
(3) For authoritative references, see: (a) Furuya, T.; Kamlet, A. S.;
Ritter, T. Nature 2011, 473, 470. (b) Liang, T.; Neumann, C. N.;
Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214−8264. (c) Yang, X.;
Wu, T.; Phipps, R. J.; Toste, F. D. Chem. Rev. 2015, 115, 826−870.
(d) Zhu, Y.; Han, J.; Wang, J.; Shibata, N.; Sodeoka, M.; Soloshonok,
V. A.; Coelho, J. A. S.; Toste, F. D. Chem. Rev. 2018, 118, 3887−3964.
(e) Neumann, C. N.; Ritter, T. Angew. Chem., Int. Ed. 2015, 54,
3216−3221.
(4) For reviews, see: (a) Prakash, G. K. S.; Hu, J. Acc. Chem. Res.
2007, 40, 921−930. (b) Hu, J.; Zhang, W.; Wang, F. Chem. Commun.
2009, 7465−7478. (c) Farnham, W. B. Chem. Rev. 1996, 96, 1633−
́
1640. (d) Zhang, Z.; Puente, A.; Wang, F.; Rahm, M.; Mei, Y.; Mayr,
H.; Prakash, G. K. S. Angew. Chem., Int. Ed. 2016, 55, 12845−12849.
(e) Burton, D. J.; Yang, Z.-Y.; Morken, P. A. Tetrahedron 1994, 50,
2993−3063.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
■
S
(5) Shimizu, M.; Hata, T.; Hiyama, T. Heterocycles 2000, 52, 707−
717.
(6) (a) Ni, C.; Li, Y.; Hu, J. J. Org. Chem. 2006, 71, 6829−6833.
(b) Zhang, W.; Ni, C.; Hu, J. Top. Curr. Chem. 2011, 308, 25.
(c) Shen, X.; Zhang, W.; Zhang, L.; Luo, T.; Wan, X.; Gu, Y.; Hu, J.
Angew. Chem., Int. Ed. 2012, 51, 6966−6970. (d) Fukuzumi, T.;
Shibata, N.; Sugiura, M.; Yasui, H.; Nakamura, S.; Toru, T. Angew.
Chem., Int. Ed. 2006, 45, 4973−4977. (e) Furukawa, T.; Shibata, N.;
Mizuta, S.; Nakamura, S.; Toru, T.; Shiro, M. Angew. Chem., Int. Ed.
2008, 47, 8051−8054. (f) Prakash, G. K. S.; Chacko, S.; Vaghoo, H.;
Shao, N.; Gurung, L.; Mathew, T.; Olah, G. A. Org. Lett. 2009, 11,
1127−1130. (g) Shen, X.; Miao, W.; Ni, C.; Hu, J. Angew. Chem., Int.
Ed. 2014, 53, 775−779. (h) Gessner, V. H. Chem. Commun. 2016, 52,
12011−12023. (i) Molitor, S.; Gessner, V. H. Angew. Chem., Int. Ed.
2016, 55, 7712−7716. (j) Molitor, S.; Feichtner, K.-S.; Gessner, V. H.
Chem. - Eur. J. 2017, 23, 2527−2531.
Experimental procedure, NMR spectra, and analytical
data for all the compounds (PDF)
Accession Codes
tallographic data for this paper. These data can be obtained
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
(7) Shimizu, M.; Hata, T.; Hiyama, T. Tetrahedron Lett. 1997, 38,
4591−4594.
(8) Shen, X.; Zhou, M.; Ni, C.; Zhang, W.; Hu, J. Chem. Sci. 2014, 5,
117−122.
D
Org. Lett. XXXX, XXX, XXX−XXX