Zn(CF3SO3)2 - Mediated domino hydroamination-ring cleavage of 2,5-dihydrofuran

Article abstract of DOI:10.1016/j.tetlet.2013.05.058

By using Zn(CF₃SO₃)₂ as the catalyst, series of 2-arylamino-3-buten-1-ols (3) were successfully synthesized via domino hydroamination-ring cleavage of 2,5-dihydrofuran (1) with aromatic amines (2). A proton-induced and Zn(CF₃SO₃)₂-assisted mechanism is proposed on the experimental basis, during which the proton is generated by the interaction between aniline and Zn(CF₃SO ₃)₂.

Full text of DOI:10.1016/j.tetlet.2013.05.058

Tetrahedron Letters 54 (2013) 3937–3939
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Zn(CF3SO3)2—mediated domino hydroamination-ring cleavage
of 2,5-dihydrofuran
⇑
Xiao-juan Shen, Hong-zhong Bu, Jie Shi, Zheng-guang Wu, Hong-fei Ma, Yu-feng Li
College of Science, Nanjing University of Technology, Puzhu South Road, No. 30, Nanjing 211816, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
By using Zn(CF3SO3)2 as the catalyst, series of 2-arylamino-3-buten-1-ols (3) were successfully synthe-
sized via domino hydroamination-ring cleavage of 2,5-dihydrofuran (1) with aromatic amines (2). A pro-
ton-induced and Zn(CF3SO3)2-assisted mechanism is proposed on the experimental basis, during which
the proton is generated by the interaction between aniline and Zn(CF3SO3)2.
Received 9 March 2013
Revised 3 May 2013
Accepted 13 May 2013
Available online 21 May 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Hydroamination
Ring cleavage
2,5-Dihydrofuran
2-Arylamino-3-buten-1-ols
Hydroamination of olefin has attracted much attention during
the past decades due to its high atom economy in C–N construc-
tion.1 Muller, Ackermann and many groups made great contribu-
tions to both intramolecular and intermolecular hydroamination.
During the latest fifteen years, many catalysts such as several
groups of metal, solid acids, Lewis acids, and Bronsted acids, have
been employed to improve the selectivity of hydroamination.2 In
the literature, we notice that specifically functionalized substrates
have often been adopted in intramolecular hydroamination to ob-
tain molecular diversity,3 because a specific latent group can usu-
ally arouse a domino or synergistic reaction to allow the formation
of complicated compounds. This trend is also presented in the rel-
atively limited intermolecular system. For instance, several groups
reported the one-step synthesis of tetrahydroquinolines starting
from 2,3-dihydrofuran and aromatic amines.4 Matsubara and co-
workers assembled a series of 2-alkylquinolines through the reac-
tion of aromatic amines with vinyl ethers or allyl ethers in the
presence of Palladium catalyst.5
Herein we describe our recent work on the hydroamination of
2,5-dihydrofuran (1) mediated by Zn(CF3SO3)2. In the cyclic ally
ether (1), the ether bond serves as a latent group allowing us to
develop a practical one step method for the synthesis of ring
opened 2-arylamino-3-buten-1-ol derivatives (3). This skeleton
has been widely employed as a synthetic precursor for numerous
heterocycles such as oxazolidines,6 2-oxazolidinones,7 2-oxazoli-
dinethiones,8 1,4-diphenylpiperazines,9 1,2,3-oxathiazolidines,10
2H-1,4-oxazines,11 1,3,2-oxazaphospholidines,12 et al. To the best
of our knowledge, several literatures have reported the synthesis
of compounds bearing this skeleton,13 including Rhodium-catalyzed
asymmetric ring-opening reactions of tetrahydroquinolines which
is most likely to our work.13c
The hydroamination of 2,5-dihydrofuran (1) with aniline (2a)
was performed initially for catalyst screening and condition opti-
mization. Seven classic Lewis acids and three noble metal catalysts
15
[Pd(PPh3)4,14 Pd(OAc)2, and RhCl3],16 were tested respectively in
a 1 mol % loading. Toluene was selected as the first trial solvent
for its stability as well as a broad adjustable temperature range, ex-
cept that dichloromethane was used instead in AlCl3-catalyzed
reaction concerning probable Friedel–Crafts alkylation of toluene.
The catalyst screening results are shown in Table 1.
When the mixture of 1 and 2a was treated with the five Lewis
acids, respectively, an identical compound was isolated with a pre-
parative thin layer process (Table 1, entries 1–5). Even the ESI-MS
result states its molecular weight to be 163.0 in line with the as-
sumed adduct (N-phenyl-3-furanamine), the chemical shifts at d
5.77 (ddd, J = 17.3, 10.4, 5.5 Hz, 1H), 5.29 (dt, J = 17.3, 1.3 Hz, 1H),
and 5.22 (dt, J = 10.4, 1.2 Hz, 1H) in the 1H NMR spectrum reveal
the existence of a –CH@CH2 moiety in the structure, relative to
which distinct correlation signals in HMQC are shown between
1H (d 5.77) and 13C (d 113.98), 1H (d 5.26) and 13C (d 117.40).
Another methylene group is distinguished in the DEPT–135 spectrum.
Two corresponding correlations between this 13C signal and
the two 1H signals (respectively at d 3.75, 3.59) are clearly
demonstrated in the HMQC spectrum. The compound is thus
confirmed as 3a despite an attempt of single crystal fostering being
fruitless due to its low melting point.17
⇑
Corresponding author.
E-mail address: yufengli@njut.edu.cn (Y. Li).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.05.058

3938
X. Shen et al. / Tetrahedron Letters 54 (2013) 3937–3939
Table 1
up to 68% (Table 3, entries 1–9), whereas electron poor amines
2k–m were inactive under the reaction condition (Table 3, entries
10–12). Secondary amine 2n reacted smoothly with 1 to give 3n
without formation of any undesired products (Table 3, entry 13).
To better understand the behaviors of the catalyst, some exper-
iments were consciously designed and conducted. Firstly, in order
to examine whether Bronsted acids are effective on the reaction,
hydrochloric acid (10% aq), trifluoromethanesulfonic acid, aniline
hydrochloride, and N,N-dimethylaniline hydrochloride were,
respectively, used with a catalytic loading (2 mol %) to catalyze
the reaction of 1 with 2a in toluene at 20–60 °C. The former two
reactions stopped soon after the initial hour and just generated
inseparable mixtures containing very low contents of 3a. However,
isolatable 3a was obtained in yields of 31% and 35% in aniline
hydrochloride and N,N-dimethylaniline hydrochloride-catalyzed
The catalyst screening for the hydroamination of 2,5-dihydrofuran (1) with aniline
(2a)
H
NH
2 catalyst
N
O
OH
2a
1
3a
Entry
Catalyst
Conditions
Conversiona (%)
Yieldb (%)
1
FeCl3
AlCl3
HfCl4
Zn(CF3SO3)2
ZnCl2
CuCl
CuI
Pd(PPh3)4
Pd(OAc)2
RhCl3
10 h, 25 °C
10 h, 25 °C
10 h, 25 °C
10 h, 25 °C
24 h, 25 °C
24 h, 60 °C
24 h, 60 °C
10 h, 60 °C
10 h, 60 °C
10 h, 25 °C
42
28
75
70
45
17
10
0
27
20
45
49
22
0e
0e
0
2c
3d
4
5
6
7
8d
9d
10
reactions, respectively. Second,
1 was directly treated with
23
15
0e
0e
Zn(CF3SO3)2 at 60 °C for 6 h in an anhydrous argon atmosphere
to examine whether it was effective to catalyze the ring-cleavage
of 1 or the isomerization of 1 to 2,3-dihydrofuran. After that treat-
ment, the mixture was carefully distilled and only one fraction was
collected, which was proved to be the material itself having purity
more than 99% based on GC analysis. So we deduce that the forma-
tion of 3a should not be only ascribed to Zn(II) itself and a proton-
induced and Zn(CF3SO3)2-assisted mechanism is proposed as
shown in Scheme 1. The interaction between aniline and
Zn(CF3SO3)2 generates an ammonium salt. The protonation of the
complex of 1 by the ammonium salt gives a carbon cation interme-
diate (4). Compound 4 is attacked by aniline and a domino type
ring cleavage is induced with the help of Zn(CF3SO3)2 to afford 6.
The elimination of LH from 6 produces the target product 3a as
well as Zn(II) catalyst to complete a catalytic cycle. As a good leav-
ing group, the anion takes an important role in the reaction to im-
prove the efficiency. Zn(II)-catalyst may also be helpful to the
a
b
c
Conversion of 2a determined by HPLC.
Isolated yield of 3a.
CH2Cl2 as the solvent.
Experiment was conducted under strict anhydrous and oxygen-free condition.
3a was observable in TLC but inseparable due to its low content.
d
e
Returning to the catalyst screening question, among the seven
Lewis acids, only HfCl4 and Zn(CF3SO3)2 gave comparably inspiring
results (Table 1, entries 3 and 4). When FeCl3, AlCl3, and ZnCl2 were
used, lowered yields of 3a were obtained (Table 1, entries 1, 2, and
5). While Cu(I) catalysts were employed in the reaction under a
more drastic condition, no 3a was isolated for its low contents
(Table 1, entries 6 and 7). Pd(PPh3)4 and Pd(OAc)2 showed no
activation on the reaction though the temperature was raised to
60 °C (Table 1, entries 8 and 9). While RhCl3 was used (Table 1,
entry 10), an inseparable mixture was obtained but no 3a was
found. Based on the results, Zn(CF3SO3)2 is clearly the most
suitable since it is less expensive and gives a reasonable yield of
3a requiring no strict anhydrous and oxygen-free condition.
The solvent and temperature factor were then examined with
Zn(CF3SO3)2 as the catalyst (shown in Table 2). Toluene was found
to be the best solvent in which 49% yield of 3a was achieved
(Table 2, entry 1). Other solvents such as methanol, N,N-dimethyl-
formamide (DMF), acetonitrile, tetrahydrofuran (THF), and
dichloromethane were not suitable for this conversion (Table 2,
entries 4–9). The reaction temperature was also examined when
toluene was used. Raising temperature is not useful but harmful
to the yield. When the reaction was conducted under 150 °C in a
sealed tube, just an inseparable mixture was produced containing
only a trace of 3a according to the TLC analysis (Table 2, entry 3).
A series of aromatic amines were then examined for the amina-
tion-ring cleavage feasibility (Table 3). The catalytic system
worked well with primary amines 2b–j to afford 3b–j with yields
reaction for the weakening of p–p conjugation between oxygen
and carbon cation in 5 and thus inhibiting or partially inhibiting
the isomerization of 4 to 5. The reaction could not be induced by
Pd(PPh3)4 and Pd(OAc)2 because no active proton was generated
there, while RhCl3 could interact with 2a to produce active proton,
the reaction did take place though the selectivity of 3a is almost
zero.
Table 3
Zn(CF3SO3)2–catalyzed hydroamination-ring cleavage of 2,5-dihydrofuran with aro-
matic amines
R1
H
N
N
R1 Zn(CF3SO3)2
+
OH
toluene
O
1
R
R
2
3
Entry
2
3
Conditions
Yielda (%)
1
2
3
4
5
6
7
8
2b, R = 2-Me, R1 = H
2c, R = 3-Me, R1 = H
2d, R = 4-Me, R1 = H
2e, R = 4-OMe, R1 = H
2f, R = 2,6-Me2, R1 = H
2g, R = 3,5-Me2, R1 = H
2h, R = 2-Et-6-Me, R1 = H
2i, R = 4-OCF3, R1 = H
2j, R = 4-Cl, R1 = H
3b
3c
3d
3e
3f
3g
3h
3i
8 h, 25 °C
8 h, 25 °C
8 h, 25 °C
8 h, 25 °C
6 h, 25 °C
6 h, 25 °C
6 h, 25 °C
6 h, 25 °C
10 h, 25 °C
24 h, 60 °C
24 h, 60 °C
24 h, 60 °C
6 h, 25 °C
61
58
55
59
64
66
68
63
45
0
Table 2
The condition optimization of the reaction of 1 and 2a in the presence of Zn(CF3SO3)2
Entry Solvent
Temperature (°C) Time (h) Conversiona (%) Yield (%)
1
2
3
4
5
6
7
8
9
Toulene
Toulene
25
60
10
10
1
70
77
73
17
14
51
45
40
27
49
40
Toulene 150
––b
––b
––b
38
9
3j
MeOH
DMF
CH3CN
THF
Dioxane
CH2Cl2
25
25
25
25
25
25
10
24
10
10
10
10
10
11
12
13
2k, R = 4-NO2, R1 = H
2l, R = 3-NO2, R1 = H
2m, R = 2-COOMe, R1 = H
2n, R = H, R1 = Me
––b
––b
––b
3n
0
0
33
65c
32
––b
a
b
c
Isolated yield of 3.
No reaction.
Without side product.
a
Conversion of 2a determined by HPLC.
Inseparable due to the low content of 3a.
b

X. Shen et al. / Tetrahedron Letters 54 (2013) 3937–3939
3939
5, 227–231; (d) Breitenlechner, S.; Fkeck, M.; Muller, T. E.; Suppan, A. J. Mol.
Catal. A: Chem. 2004, 214, 175–179; (e) Ouh, L. L.; Muller, T. E.; Yan, Y. K. J.
Organomet. Chem. 2005, 690, 3774–3782; (f) Kaspar, L. T.; Fingerhut, B.;
Ackermann, L. Angew. Chem., Int. Ed. 2005, 44, 5972–5974; (g) Ackermann, L.;
Born, R. Tetrahedron Lett. 2004, 45, 9541–9544; (h) Rueping, M.; Koenigs, R.
M.; Atodiresei, I. Chem. Eur. J. 2010, 16, 9350–9365.
2 PhNH2
-
PhNHZnL
PhNH3+L-
-PhNH2
ZnL2
O
1
PhNH
ZnL2
3. (a) Van Otterlo, W. A. L.; Pathak, R.; De Koning, C. B.; Fernandes, M. A.
Tetrahedron Lett. 2004, 45, 9561–9563; (b) Llauger, L.; Bergami, C.; Kinzel, O. D.;
Lillini, S.; Pescatore, G.; Torrisi, C.; Jones, P. Tetrahedron Lett. 2009, 50, 172–177.
4. (a) Jia, X. D.; Ren, Y.; Huo, C. D.; Wang, W. J.; Chen, X. N.; Fu, Q.; Wang, X. C.
Chin. Chem. Lett. 2011, 22, 671–674; (b) Lin, X.-F.; Cui, S.-L.; Wang, Y.-G.
Tetrahedron Lett. 2006, 47, 4509–4512; (c) Zhang, J.; Li, C. J. J. Org. Chem. 2002,
6(11), 3969–3971.
OH
3a
O
O
L
L
L
Zn
Zn
H
PhNH
-H+
L
5
4
5. Matsubara, Y.; Hirakawa, S.; Yamaguchi, Y.; Yoshida, Z. Angew. Chem., Int. Ed.
2011, 50, 7670–7673.
6. Kon, G. A. R.; Roberts, J. J. J. Chem. Soc. 1950, 978–982.
7. Wang, Y.; Liu, J.; Xia, C. Chin. J. Catal. 2011, 32, 1782–1786.
8. Teruaki, M.; Isao, K.; Kinya, M. J. Org. Chem. 1966, 31(1), 32–34.
9. Alain, V.; Armand, L. Compt. Rend. 1963, 256, 2635–2637.
L
-
O
L= CF3SO3
6
ZnL
Scheme 1. The mechanism of Zn(CF3SO3)2-mediated reaction of 1 and 2a.
10. Uneyama, K.; Namba, H.; Oae, S. Chem. Soc. Jpn. 1968, 41(8), 1928–1937.
11. Klaus, T.; Peter, T. Arch. Pharm. 1979, 312(12), 1042–1045.
12. Pudovik, M. A.; Terenteva, S. A.; Pudovik, A. N. Zh. Obshch. Khim. 1981, 51(3),
518–526.
13. (a) Hayashi, T.; Yamamoto, A.; Ito, Y. Tetrahedron Lett. 1988, 29, 99–102; (b)
Blum, S. A.; Rivera, V. A.; Ruck, R. T.; Michael, F. E.; Bergman, R. G. Organomet.
2005, 24(7), 1647–1659; (c) Lautens, M.; Fagnou, K. J. Am. Chem. Soc. 2001,
123(29), 7170–7171.
In conclusion, as a functional olefin substrate, 2,5-dihydrofuran
tends to take place a domino ring cleavage in Zn(CF3SO3)2-
mediated hydroamination, and thereby a practical method for
the synthesis of 2-arylamino-3-buten-1-ols has been first estab-
lished with theoretically high atomic economy. A further effort will
be made to investigate the application for the construction of
heterocycles as well as the stereochemistry of the reaction.
14. Pahadi, N. K.; Tunge, J. A. Synlett. 2009, 19, 3135–3138.
15. Xu, T.; Qiu, S.; Liu, G. J. Organomet. Chem. 2011, 696, 46–49.
16. (a) Hesp, K. D.; Stradiotto, M. ChemCatChem 2010, 2, 1192–1207; (b) Dorta, R.
Iridium Complexes in Organic Synthesis; Wiley-VCH: Weinheim, 2008; pp 145–
172.
Supplementary data
17. A representative procedure for the synthesis of 3a: To a mixture of aromatic
amines (2a, 0.5 mmol) and Zn(CF3SO3)2 (0.005 mmol) in toluene (10 mL) was
added dropwise 2,5-dihydrofuran (1, 1.0 mmol) within 30 min under room
temperature. The mixture was stirred and detected by GC method. The mixture
was concentrated to give a residue, which was separated and purified to offer
the compound (3a). Product 3a (49%) was obtained as a colorless oil after
preparative thin layer chromatography with petroleum ether/ethyl acetate
(10:1) as eluent. 1H NMR (400 MHz, CDCl3): d = 7.18–7.13 (m, 2H), 6.74–6.69
(m, 1H), 6.64 (dd, J = 8.6, 0.9 Hz, 2H), 5.77 (ddd, J = 17.3, 10.4, 5.5 Hz, 1H), 5.29
(dt, J = 17.3, 1.3 Hz, 1H), 5.22 (dt, J = 10.4, 1.2 Hz, 1H), 3.99 (td, J = 5.7, 1.4 Hz,
1H), 3.75 (dd, J = 11.0, 4.3 Hz, 1H), 3.59 (dd, J = 11.0, 6.4 Hz, 1H) ppm. 13C NMR
(100 MHz, CDCl3): d = 147.36, 136.43, 129.32, 118.08, 117.40, 113.98, 113.48,
64.94, 57.70 ppm. MS (ESI): m/z = 164 [M+H]+. Anal. Calcd for C10H13NO: C,
73.59; H, 8.03; N, 8.58. Found: C, 73.61; H, 7.96; N, 8.62.
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
05.058.
References and notes
1. (a) Hultzsch, K. C.; Gribkov, D. V.; Hampel, F. J. Organomet. Chem. 2005, 690,
4441–4452; (b) Hultzsch, K. C. Org. Biomol. Chem. 2005, 3(10), 1819–1824.
2. (a) Mueller, T. E.; Beller, M. Chem. Rev. 1998, 98(2), 675–703; (b) Jimenez, O.;
Muller, T. E.; Lercher, J. A. In Ionic Liquids in Organic Synthesis; Malhotra, S.,
Ed.; ACS Symposium Series; American Chemical Society: Washington, DC,
2007; pp 267–280; (c) Bodis, J.; Muller, T. E.; Lercher, J. A. Green Chem. 2003,