Organic Letters
Funding
Letter
2012, 48, 7738. (c) Onys’ko, P. P.; Kyselyova, O. I.; Zamulko, K. A.;
Shalimov, O. O.; Kurilchyk, S. M. Synthesis and some transformations
of 1-chloro-2,2,2-trifluoroethyl isocyanate. J. Fluorine Chem. 2015,
National Natural Science Foundation of China (No.
21801083, to D. Lu, and No. 21472053, to Y. Gong) and
Hubei Provincial Natural Science Foundation of China (No.
0216013067, to D. Lu) provided funding of this research work.
́
173, 1. (d) Aparici, I.; Guerola, M.; Dialer, C.; Simon-Fuentes, A.;
́
́
Sanchez-Rosello, M.; del Pozo, C.; Fustero, S. Diastereodivergent
synthesis of fluorinated cyclic β3-amino acid derivatives. Org. Lett.
2015, 17, 5412. (e) Parise, L.; Pelagalli, A.; Pellacani, L.; Sciubba, F.;
Vergari, M. C.; Fioravanti, S. Ethyl nitroacetate in aza-Henry addition
on trifluoromethyl aldimines: a solvent-free procedure to obtain chiral
Notes
The authors declare no competing financial interest.
trifluoromethyl α,β-diamino esters. J. Org. Chem. 2016, 81, 2864.
́
ACKNOWLEDGMENTS
́
́
́
(f) Sanz-Vidal, A.; Miro, J.; Sanchez-Rosello, M.; del Pozo, C.;
Fustero, S. Gold-catalyzed Povarov-type reaction of fluorinated imino
esters and furans. J. Org. Chem. 2016, 81, 6515. (g) Wei, L.; Li, Q.-H.;
Wang, C.-J. Copper(I)-catalyzed asymmetric 1,3-dipolar cyclo-
addition of azomethine ylides with fluorinated imines: the expanded
scope and mechanism insights. J. Org. Chem. 2018, 83, 11814.
(h) Crousse, B.; Bonnet-Delpon, D. N-Benzyltrifluoroacetaldimine. In
Encyclopedia of Reagents for Organic Synthesis; Wiley, 2015.
■
Financial support from Huazhong University of Science &
Technology and the Natural Science Foundation of Hubei
Committee (No. 2016CFA001) are gratefully acknowledged.
We also thank Huazhong University of Science & Technology
Analytical & Testing Center for characterizing new com-
pounds.
(7) (a) Kagayama, T.; Sakaguchi, S.; Ishii, Y. Synthesis of α-hydroxy-
γ-butyrolactones from acrylates and 1,3-dioxolanes using N-hydrox-
yphthalimide (NHPI) as a key catalyst. Tetrahedron Lett. 2005, 46,
3687. (b) Liu, D.; Liu, C.; Li, H.; Lei, A. Copper-catalysed oxidative
C−H/C−H couling between olefins and simple ethers. Chem.
Commun. 2014, 50, 3623. (c) Du, P.; Li, H.; Wang, Y.; Cheng, J.;
Wan, X. Radical−polar crossover reactions: oxidative coupling of 1,3-
dioxolanes with electron-deficient alkenes and vinylarenes based on a
radical addition and Kornblum−DeLaMare Rearrangement. Org. Lett.
2014, 16, 6350. (d) Chu, X.-Q.; Meng, H.; Zi, Y.; Xu, X.-P.; Ji, S.-J.
Metal-free oxidative direct C(sp3)−H bond functionalization of ethers
with α,α-diaryl allylic alcohols. Chem. Commun. 2014, 50, 9718.
(e) Nielsen, M. K.; Shields, B. J.; Liu, J.; Williams, M. J.; Zacuto, M. J.;
Doyle, A. G. Mild, Redox-neutral formylation of aryl chlorides
through the photocatalytic generation of chlorine radicals. Angew.
Chem., Int. Ed. 2017, 56, 7191.
(8) For a review and selected examples of oxidative cross-coupling of
ethers, see: (a) Yi, H.; Zhang, G.; Wang, H.; Huang, Z.; Wang, J.;
Singh, A. K.; Lei, A. Recent advances in radical C−H activation/
radical cross-coupling. Chem. Rev. 2017, 117, 9016. (b) Zhang, L.; Yi,
H.; Wang, J.; Lei, A. Visible-light mediated oxidative C−H/N−H
cross-coupling between tetrahydrofuran and azoles using air. J. Org.
Chem. 2017, 82, 10704. (c) Liu, D.; Liu, C.; Li, H.; Lei, A. Direct
functionalization of tetrahydrofuran and 1,4-dioxane: nickel-catalyzed
oxidative C(sp3)−H arylation. Angew. Chem., Int. Ed. 2013, 52, 4453.
(d) Liu, D.; Liu, C.; Li, H.; Lei, A. Copper-catalysed oxidative C−H/
C−H coupling between olefins and simple ethers. Chem. Commun.
2014, 50, 3623.
REFERENCES
■
(1) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.;
Meanwell, N. A. Applications of fluorine in medicinal chemistry. J.
Med. Chem. 2015, 58, 8315.
(2) (a) Pesenti, C.; Arnone, A.; Bellosta, S.; Bravo, P.; Canavesi, M.;
Corradi, E.; Frigerio, M.; Meille, S. V.; Monetti, M.; Panzeri, W.;
Viani, F.; Venturini, R.; Zanda, M. Total synthesis of a pepstatin
analog incorporating two trifluoromethyl hydroxymethylene isosteres
(Tfm-GABOB) and evaluation of Tfm-GABOB containing peptides
as inhibitors of HIV-1 protease and MMP-9. Tetrahedron 2001, 57,
6511. (b) Pesenti, C.; Arnone, A.; Aubertin, A. M.; Bravo, P.; Frigerio,
M.; Panzeri, W.; Schmidt, S.; Viani, F.; Zanda, M. Total synthesis of a
Pepstatin analogue incorporating two trifluoromethyl hydroxy-
methylene isosteres. Tetrahedron Lett. 2000, 41, 7239. (c) Volonterio,
A.; Bravo, P.; Corradi, E.; Fronza, G.; Meille, S. V.; Vergani, B.;
Zanda, M. Unusual nonchelation controlled allylation of a N-
monoprotected α-amino aldehyde: stereoselective entry to non-
racemic trifluoromethyl dipeptide isosteres. J. Fluorine Chem. 2001,
108, 245. (d) Dao Thi, H.; Decuyper, L.; Mollet, K.; Kenis, S.; De
Kimpe, N.; Van Nguyen, T.; D’hooghe, M. Synthesis of Trifluor-
omethylated azetidines, aminopropanes, 1,3-oxazinanes, and 1,3-
oxazinan-2-ones starting from 4-trifluoromethyl-β-lactam building
blocks. Synlett 2016, 27, 1100.
(3) (a) Jurczak, J.; Golebiowski, A. Optically active N-protected α-
amino aldehydes in organic synthesis. Chem. Rev. 1989, 89, 149.
(b) Gryko, D.; Chałko, J.; Jurczak, J. Synthesis and reactivity of N-
protected-α-amino aldehydes. Chirality 2003, 15, 514.
(9) For selected examples of radical addition of 1,3-dioxolane to
imines enabled by stochiometric amounts of oxidant or UV
irradiation, see: (a) Yamada, K.-i.; Fujihara, H.; Yamamoto, Y.;
Miwa, Y.; Taga, T.; Tomioka, K. Radical addition of ethers to imines
(4) For scattered examples of fluoroalkyl amino aldehyde synthesis,
see: (a) Wu, Y.-Y.; Zhang, X.; Meng, W.-D.; Qing, F.-L. Synthesis of
new 2′,3′-Dideoxy-6′,6′-difluoro-3′-thionucleoside from gem-difluor-
ohomoallyl alcohol. Org. Lett. 2004, 6, 3941. (b) Palacios, F.; Ochoa
de Retana, A. M.; Pascual, S.; Oyarzabal, J. Preparation of fluoroalkyl
imines, amines, enamines, ketones, α-amino carbonyls, and α-amino
acids from primary enamine phosphonates. J. Org. Chem. 2004, 69,
8767. (c) Liu, J.; Hu, J. Highly diastereoselective synthesis of α-
difluoromethyl amines from N-tert-butylsulfinyl ketimines and
difluoromethyl phenyl sulfone. Chem. - Eur. J. 2010, 16, 11443.
(5) (a) Gong, Y.; Kato, K.; Kimoto, H. BF3-Promoted aromatic
substitution of N-alkyl α-trifluoromethylated imine: facile synthesis of
1-aryl-2,2,2-trifluoroethylamines. Bull. Chem. Soc. Jpn. 2002, 75, 2637.
(b) Gong, Y.; Kato, K. Convenient preparation of 1-(indol-3-yl)-
2,2,2-trifluoroethylamines via Friedel-Crafts reaction of α-trifluor-
oacetaldehyde hemiaminal. J. Fluorine Chem. 2001, 108, 83.
(6) For recent examples of nucleophilc additions to fluoroalkyl
imines, see: (a) Zhao, Q.-Y.; Yuan, Z.-L.; Shi, M. Highly Diastereo-
and enantioselective vinylogous Mannich reactions of fluorinated
aldimines with siloxyfurans. Adv. Synth. Catal. 2011, 353, 637. (b) Lin,
J.-H.; Zong, G.; Du, R.-B.; Xiao, J.-C.; Liu, S. The asymmetric
synthesis of CF3- or -CF2-substituted tetrahydroquinolines by
employing a chiral phosphoric acid as catalyst. Chem. Commun.
́
initiated by dimethylzinc. Org. Lett. 2002, 4, 3509. (b) Fernandez, M.;
Alonso, R. Diastereoselective intermolecular addition of the 1,3-
dioxolanyl radical to N-acyl aldohydrazones. asymmetric synthesis of
α-amino acid derivatives. Org. Lett. 2003, 5, 2461. (c) Clerici, A.;
Cannella, R.; Panzeri, W.; Pastori, N.; Regolini, E.; Porta, O. TiCl3/
+
PhN2 -mediated radical addition of ethers to aldimines generated in
situ under aqueous conditions. Tetrahedron Lett. 2005, 46, 8351.
(d) Zhang, L.; Deng, Y.; Shi, F. Light promoted aqueous phase amine
synthesis via three-component coupling reactions. Tetrahedron Lett.
2013, 54, 5217. (e) Rossi, B.; Pastori, N.; Prosperini, S.; Punta, C.
Multicomponent versus domino reactions: One-pot free-radical
synthesis of β-amino-ethers and β-amino-alcohols. Beilstein J. Org.
Chem. 2015, 11, 66.
(10) For photoredox-catalyzed redox neutral reaction with imines,
see: (a) Hager, D.; MacMillan, D. W. C. Activation of C−H bonds via
the merger of photoredox and organocatalysis: a coupling of benzylic
ethers with Schiff bases. J. Am. Chem. Soc. 2014, 136, 16986.
(b) Uraguchi, D.; Kinoshita, N.; Kizu, T.; Ooi, T. Synergistic catalysis
of ionic brønsted acid and photosensitizer for a redox neutral
E
Org. Lett. XXXX, XXX, XXX−XXX