D
R. A. Ábrahámi et al.
Letter
Synlett
CH3CH2NH2HCl, EtOH
N
NaHCO3, NaBH3CN
AcOH, 20 °C, 3 h
17 (59%, two steps)
NaIO4
THF/H2O
OH
CH3CH2CH2CH2NH2, EtOH
O
N
20 °C, 1 h
NaBH3CN
OH
O
AcOH, 20 °C, 3 h
18 (23%, two steps)
2
I-1
BnNH2, EtOH
N
NaBH3CN
AcOH, 20 °C, 3 h
19 (69%, two steps)
Scheme 4
Funding Information
(j) Stöckigt, J.; Antonchick, A. P.; Wu, F.; Waldmann, H. Angew.
Chem. Int. Ed. 2011, 50, 8538. (k) Liu, W.; Liu, S.; Jin, R.; Guo, H.;
Zhao, J. Org. Chem. Front. 2015, 2, 288.
We are grateful to the Hungarian Research Foundation (NKFIH Nos. K
115731 and K 119282) for financial support. The financial support of
the GINOP-2.3.2-15-2016-00038 project is also acknowledged. This
research was supported by the EU-funded Hungarian grant EFOP-
(3) (a) Wang, J.; Sánchez-Roselló, M.; Aceña, J. L.; del Pozo, C.;
Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem.
Rev. 2014, 114, 2432. (b) Zhou, Y.; Wang, Y.; Gu, Z.; Wang, S.;
Zhu, W.; Aceña, J. L.; Soloshonok, V. A.; Izawa, K.; Liu, H. Chem.
Rev. 2016, 116, 442. (c) Fluorine in Pharmaceutical and Medici-
nal Chemistry: From Biophysical Aspects to Clinical Applications;
Gouverneur, V.; Müller, K., Eds.; Imperial College Press: London,
2012.
3.6.1-16-2016-00008.
)(
Supporting Information
Supporting information for this article is available online at
(4) (a) Fujita, T.; Ichikawa, J. In Vol. 2 Fluorine in Heterocyclic Chem-
istry; Nenajdenko, V., Ed.; Springer International: Cham, 2014,
181. (b) Mormino, M. G.; Fier, P. S.; Hartwig, J. F. Org. Lett. 2014,
16, 1744. (c) Xu, T.; Liu, G. Org. Lett. 2012, 14, 5416.
(d) Kuninobu, Y.; Nagase, M.; Kanai, M. Angew. Chem. Int. Ed.
2015, 54, 10263. (e) Zhang, B.; Studer, A. Org. Biomol. Chem.
2014, 12, 9895. (f) Punirun, T.; Soorukram, D.; Kuhakarn, C.;
Reutrakul, V.; Pohnakotr, M. J. Org. Chem. 2018, 83, 765.
(5) (a) Ábrahámi, R. A.; Kiss, L.; Barrio, P.; Fülöp, F. Tetrahedron
2016, 72, 7526. (b) Kiss, L.; Forró, F.; Fülöp, F. Beilstein J. Org.
Chem. 2015, 11, 596. (c) Ábrahámi, R. A.; Kiss, L.; Fustero, S.;
Fülöp, F. Synthesis 2017, 49, 1206.
(6) Junttila, M. H.; Hormi, O. O. E. J. Org. Chem. 2009, 74, 3038.
(7) Mimura, H.; Kawada, K.; Yamashita, T.; Sakamoto, T.; Kikugawa,
Y. J. Fluorine Chem. 2010, 131, 477.
(8) 1,2,3,4-Tetrahydroquinolines 3–9, 12, and 13: General Proce-
dure
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References
(1) (a) Singh, I. P.; Shah, P. Expert Opin. Ther. Pat. 2017, 27, 17.
(b) Miyazaki, M.; Ando, N.; Sugai, K.; Seito, Y.; Fukuoka, H.;
Kanemitsu, T.; Nagata, K.; Odanaka, Y.; Nakamura, K. T.; Itoh, T.
J. Org. Chem. 2010, 76, 534. (c) Le, V. H.; Inai, M.; Williams, R. M.;
Kan, T. Nat. Prod. Rep. 2015, 32, 328. (d) Freel, R. M. S.; Ogden, K.
K.; Strong, K. L.; Khatri, A.; Chepiga, K. M.; Jensen, H. S.;
Traynelis, S. F.; Liott, D. C. J. Med. Chem. 2013, 56, 5351.
(e) Dzierszinski, F.; Coppin, A.; Mortuaire, M.; Dewally, E.;
Slomianny, C.; Ameisen, J.-C.; DeBels, F.; Tomavo, S. Antimicrob.
Agents Chemother. 2002, 46, 3197. (f) Forró, E.; Megyesi, R.; Paál,
T. A.; Fülöp, F. Tetrahedron: Asymmetry 2016, 27, 1213.
(2) For a recent a comprehensive review, see: (a) Chrzanowska, M.;
Grajewska, A.; Rozwadowska, M. D. Chem. Rev. 2016, 116,
12369. (b) Balamurugan, K.; Jeyachandran, V.; Perumal, S.;
Menéndez, J. C. Tetrahedron 2011, 67, 1432. (c) Hopkins, B. A.;
Wolfe, J. P. Chem. Sci. 2014, 5, 4840. (d) Awuah, E.; Capretta, A.
J. Org. Chem. 2010, 75, 5627. (e) Si, C.; Myers, A. G. Angew. Chem.
Int. Ed. 2011, 50, 10409. (f) Wang, Y.-F.; Toh, K.-K.; Lee, J.-Y.;
Chiba, S. Angew. Chem. Int. Ed. 2011, 50, 5927. (g) Jayakumar, J.;
Parthasarathy, K.; Cheng, C. H. Angew. Chem. Int. Ed. 2012, 51,
197. (h) Chinnagolla, R. K.; Pimparkar, S.; Jeganmohan, M. Org.
Lett. 2012, 14, 3032. (i) Pilgrim, B. S.; Gatland, A. E.; McTernan, C.
T.; Procopiou, P. A.; Donohoe, T. J. Org. Lett. 2013, 15, 6190.
NaIO4 (1.5 equiv) was added to a stirred solution of the dihy-
droxy compound 2 or 11 (4 mmol) in THF–H2O (25 mL + 2 mL),
and the mixture was stirred for 1 h at 20 °C under argon. H2O
(40 mL) was added to dissolve the precipitate, and the mixture
was extracted with CH2Cl2 (3 × 20 mL). The extracts were then
combined and dried (Na2SO4). The crude diformyl product was
immediately used in the reductive cyclization without purifica-
tion. The appropriate fluorinated amine (1 equiv) and NaHCO3
(2 equiv) were added to the solution of the diformyl intermedi-
ate in EtOH (20 mL), and the mixture was stirred at 20 °C for 10
min. NaCNBH3 (1 equiv) and AcOH (2 drops) were added, and
the mixture was stirred for a further 4 h at 20 °C. The mixture
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E