E
Synlett
M. Minakawa et al.
Letter
(
d) Cho, C. S.; Kim, D. T.; Kim, T.-J.; Shim, S. C. Bull. Korean Chem.
(11) (a) Zhang, M.; Xie, F.; Wang, X.-T.; Yan, F.; Wang, T.; Chen, M.;
Ding, Y. RSC Adv. 2013, 3, 6022. (b) Kasuga, T.; Takamura, K.;
Hara, R.; Takagi, U. Jpn. Kokai Tokkyo Koho 1996, 08319273.
(c) Joule, J. A. Sci. Synth. 2001, 10, 361. (d) Nisida, T.; Tokuda, Y.;
Tsuchiya, M. J. Chem. Soc., Perkin Trans. 2 1995, 4, 823.
Soc. 2003, 24, 1026. (e) Lee, D. Y.; Cho, C. S.; Kim, J. H.; Youn, Y.
Z.; Shim, S. C.; Song, H. Bull. Korean Chem. Soc. 1996, 17, 1132.
(f) Shan, S. P.; Xiaoke, X.; Gnanaprakasam, B.; Dang, T. T.;
Ramalingam, B.; Huynh, H. V.; Seayad, A. M. RSC Adv. 2015, 5,
4434. (g) Xia, J.; Huang, Z.; Yang, X.; Wang, F.; Li, X. Org. Lett.
(12) General Procedure and Characterization Data:
2
018, 20, 740. (h) Shi, Z.; Boultadakis-Arapinis, M.; Glorius, F.
Ir-catalyzed direct cyclization of 3-fluoro-aniline (4e) with 1,3-
propanediol (2a) (Table 3, entry 5): To a vial was added 3-fluoro-
aniline (111.1 mg, 1.0 mmol), IrCl ·3H O (11.5 mg, 5.0 mol%),
Chem. Commun. 2013, 49, 6489. (i) Yu, S.; Li, X. Org. Lett. 2014,
6, 1200.
4) (a) Tsuji, Y.; Huh, K.-T.; Watanabe, Y. Tetrahedron Lett. 1986, 27,
1
3
3
(
and rac-BINAP (30.4 mg, 7.5 mol%) under air. Furthermore,
mesitylene (0.5 mL) and then 1,3-propanediol (98.9 mg, 1.3
mmol) were added and the reaction mixture was stirred at
165 °C for 18 h. After the reaction, the resulting mixture was
diluted with hexane. Then, the reaction mixture was filtrated
with a filter paper and concentrated in vacuo. The resulting
residue was purified by flash column chromatography on SiO2
377. (b) Tsuji, Y.; Huh, K.-T.; Watanabe, Y. J. Org. Chem. 1987, 52,
1673. (c) Amamoto, H.; Obora, Y.; Ishii, Y. J. Org. Chem. 2009, 74,
628. (d) Lee, H.; Yi, C. S. Organometallics 2016, 35, 1973.
(e) Labed, A.; Jiang, F.; Labed, I.; Lator, A.; Peters, M.; Achard, M.;
Kabouche, A.; Kabouche, Z.; Sharma, G. V. M.; Brujneu, C. Chem-
CatChem 2015, 7, 1090. (f) Pan, S.; Shibata, T. ACS Catal. 2013, 3,
t
7
04.
5) Minakawa, M.; Okubo, M.; Kawatsura, M. Bull. Chem. Soc. Jpn.
015, 88, 1680.
6) Minakawa, M.; Okubo, M.; Kawatsura, M. Tetrahedron Lett.
016, 57, 4187.
( BuOMe/hexane 1:15) to yield 2,3,6,7-tetrahydro-8-fluoro-
(
(
(
1H,5H-benzo[ij]quinolizine (5e) in 59% yield (73.2 mg) as a pale
2
yellow solution.
1
H NMR (500 MHz, CDCl ): δ = 1.92−1.98 (m, 4 H), 2.68−2.72 (m,
3
2
4 H), 3.09−3.12 (m, 4 H), 6.24 (t, J = 8.8 Hz, 1 H), 6.70 (t, J
=
=
HF
HF
13
3
7) (a) Abura, T.; Ogo, S.; Watanabe, Y.; Fukuzumi, S. J. Am. Chem.
Soc. 2003, 125, 4149. (b) Ogo, S.; Uehara, K.; Abura, T.;
Fukuzumi, S. J. Am. Chem. Soc. 2004, 126, 3020.
7.5 Hz, 1 H) ppm. C NMR (125 MHz, CDCl ): δ = 20.3 (d, J
3
CF
2
5.9 Hz), 21.3, 22.2, 27.3, 49.6, 50.0, 102.0 (d, JCF = 22.9 Hz),
2
4
3
108.5 (d, JCF = 21.7 Hz), 116.8 (d, JCF = 2.4 Hz), 126.8 (d, JCF
=
3
1
(
8) In entry 11, 2a was not detected in 1H NMR analysis (conver-
sion: 100%). The main product seems to be N,N'-diphenyl-1,3-
propanediamine (45% NMR yield).
10.8 Hz), 144.1, (d, J = 8.4 Hz), 159.7 (d, J = 241.3 Hz) ppm.
F-NMR (470 MHz, CDCl ): δ = −124.2 ppm. HRMS: m/z calcd
for C12H14FN [M] : 191.1110; found: 191.1110.
C
F
C
F
19
3
+
4e
(
9) In entry 2, N-methyl-N-propylaniline was also detected. The
1
ratio of 3a to N-methyl-N-propylaniline was 18:1 ( H NMR anal-
R5 R6
ysis). A similar ratio of 3a to N-methyl-N-propylaniline was
observed in entries 3 and 4.
10) (a) The reaction of N-ethylaniline (1g) with 1,3-propanediol
R4
R4
R4
R4
IrCl3 (5.0 mol%)
BINAP (7.5 mol%)
R4
R5
N
(
4a
+
HO
OH
n. d.
(2a) gave 1-ethyl-1,2,3,4-tetrahydroquinoline (3g) in 40% yield.
R5 R6
mesitylene
165 °C
The reaction of N-propylamine (1h) with 1,3 -propanediol (2a)
gave 1-isopropyl-1,2,3,4-tetrahydroquinoline (3h) in <3% yield.
Both reactions included the corresponding diamine compound
R6
R4
5
18 h
4
5
6
4
6
2
2
2
d: R = H, R = H, R = OH
3ad: R = H, R = H, R = OH
4
5
6
4
5
6
e: R = H, R = H, R = Ph
3ae: R = H, R = H, R = Ph
(
like 7) (3g/7g = 1:1 and 3h/7h = 1:39).
f: R = H, R5 = R = Me
4
6
3af: R = H, R5 = R = Me
4
6
10a 1
2g: R = Me, R5 = R6 = Me
4
3ag: R = Me, R5 = R6 = Me
4
Compound 3g:
H NMR (CDCl , 400 MHz): δ = 1.13 (t, J = 7.0
3
Hz, 3 H), 1.92–1.98 (m, 2 H), 2.74 (t, J = 6.2 Hz, 2 H), 3.26 (t, J =
Scheme 7
5.8 Hz, 2 H), 3.34 (q, J = 7.1 Hz, 2 H), 6.54 (tt, J = 0.93 Hz, 7.3 Hz,
1
H), 6.59 (d, J = 8.4 Hz, 1 H), 6.93 (dd, J = 1.2 Hz, 7.2 Hz, 1 H),
+
7.02–7.06 (m, 1 H) ppm. HRMS: m/z calcd for C11H15N [M] :
(13) the reaction 4a with 2d−g, the desired products 3ad−ag were
1
1
61.1204; found: 161.1197.
not detected (Scheme 7) by H NMR analysis
10a 1
Compound 3h:
H NMR (CDCl , 600 MHz): δ = 1.17 (d, J = 6.6
(14) The reaction of 4a with 1,4-butanediol (2c) resulted in a double
N-alkylation to afford 1-phenylpyrrolidine in 76% yield (see
Supporting Information).
3
Hz, 6 H), 1.88–1.92 (m, 2 H), 2.73 (t, J = 6.6 Hz, 2 H), 3.14 (t, J =
.0 Hz, 2 H), 4.10 (sept, J = 6.7 Hz, 1 H), 6.52–6.56 (m, 1 H), 6.68
6
(
d, J = 7.8 Hz, 1 H), 6.94 (d, J = 6.6 Hz, 1 H), 7.03–7.06 (m, 1 H)
(15) Compound 5g was unstable and gradually decomposed under
chromatographic conditions.
+
ppm. HRMS: m/z calcd for C12H17N [M] : 175.1361; found:
1
75.1359. (b) Abarca, B.; Adam, R.; Ballesteros, R. Org. Biomol.
(16) Under similar reaction conditions with 4 Å molecular sieves, the
reaction of aniline (4a) with 1,3-propanediol (2a) gave quino-
line in 7% yield and no tetrahydrobenzoquinolizine 5a.
(17) (a) García-González, M. C.; Hernández-Vázquez, E.; Vengochea-
Gómez, F. A.; Miranda, L. D. Tetrahedron Lett. 2018, 59, 848.
Chem. 2012, 10, 1826.
IrCl3 (5.0 mol%)
BINAP (7.5 mol%)
H
N
R3
N
+
2a
R3
(b) Ouyang, K.; Hao, W.; Zhang, W.-X.; Xi, Z. Chem. Rev. 2015,
mesitylene
1
65 °C
18 h
115, 12045. (c) Ikeda, Y.; Takano, K.; Kodama, S.; Ishii, Y.
Organometallics 2014, 33, 3998, and references therein.
18) For example: LD 490 (Coumarin 6H) [CAS: 58336-35-9].
1
1
g: R3 = Et
h: R = Pr
3g: R3 = Et 40%
3h: R3 = Pr <3%
3
i
i
(
Scheme 6
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E