Synthesis of β-amino alcohols using the tandem reduction and ring-opening reaction of nitroarenes and epoxides

Article abstract of DOI:10.1016/j.tet.2016.04.083

A high yield one-pot synthesis of β-amino alcohols from nitroarenes and 1,2-epoxides was developed, which utilizes inexpensive iron dust as a reducing agent and NH₄Cl as the only additive in a 50% (v/v) ethanol solution. This new efficient synthetic approach tolerates a wide range of functionalities. The mild reaction conditions (e.g., 60?°C), together with the use of low cost and readily available starting materials, make this synthetic approach an attractive alternative to the current synthesis of β-amino alcohols.

Full text of DOI:10.1016/j.tet.2016.04.083

Accepted Manuscript
Synthesis of β-amino alcohols using the tandem reduction and ring-opening reaction
of nitroarenes and epoxides
Chongyang Shi, Cheng Ren, Erlei Zhang, Huile Jin, Xiaochun Yu, Shun Wang
PII:
S0040-4020(16)30377-5
10.1016/j.tet.2016.04.083
TET 27731
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 21 December 2015
Revised Date: 26 April 2016
Accepted Date: 28 April 2016
Please cite this article as: Shi C, Ren C, Zhang E, Jin H, Yu X, Wang S, Synthesis of β-amino alcohols
using the tandem reduction and ring-opening reaction of nitroarenes and epoxides, Tetrahedron (2016),
doi: 10.1016/j.tet.2016.04.083.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Leave this area blank for abstract info.
One-pot tandem reduction and ring-opening
reaction of nitroarenes and epoxides: A
simple and effective approach to
alcohols
β-amino
Chongyang Shi, Cheng Ren, Erlei Zhang, Huile Jin, Xiaochun Yu* and Shun Wang*
College of Chemistry and Materials Engineering, Wenzhou University, Chashan University Town, Wenzhou,
Zhejiang Province 325035, People’s Republic of China.

ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Synthesis of β-amino alcohols using the tandem reduction and ring-opening reaction
of nitroarenes and epoxides
Chongyang Shi, Cheng Ren, Erlei Zhang, Huile Jin, Xiaochun Yu* and Shun Wang*
College of Chemistry and Materials Engineering, Wenzhou University, Chashan University Town, Wenzhou, Zhejiang Province 325035, People’s Republic of
China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A high yield one-pot synthesis of β-amino alcohols from nitroarenes and 1,2-
epoxides was developed, which utilizes inexpensive iron dust as a reducing agent and
NH4Cl as the only additive in a 50% (v/v) ethanol solution. This new efficient
synthetic approach tolerates a wide range of functionalities. The mild reaction
conditions (e.g., 60℃), together with the use of low cost and readily available starting
materials, make this synthetic approach an attractive alternative to the current
synthesis of β-amino alcohols.
Available online
Keywords:
β-Amino alcohols
Nitroarenes
1,2-Epoxides
2009 Elsevier Ltd. All rights reserved.
Iron
Reduction and ring-opening tandem reaction
1. Introduction
comparatively
inexpensive,
relatively
non-toxic
and
environment-friendly. A number of methods based on iron have
been reported, which include Fe/CH3COOH,15a Fe/NH4Cl,15b, 15c
β-Amino alcohols are important organic intermediates in the
synthesis of a wide range of biologically active natural, amino
acids and chiral auxiliaries.1 One of the most practical and widely
used routes for the preparation of β-amino alcohols is the direct
ring-opening of epoxides with amines. The aminolysis protocols
of 1,2-epoxides, which have been greatly developed and reported
in literature in the past years, mainly involve monohaptic
nucleophiles in different reaction media such as hexafluoro-2-
propanol,2a ionic liquids,2b supercritical carbon dioxide
(scCO2),2c water2d and solvent-free conditions.2e-g Different
catalysts such as metal triflates,2d, 2g, 3 metal halides2f, 4 and other
metal salts,5 and organic reagents6 including β-cyclodextrin,2c
Bu3P,6b DABCO6c have also been used in those processes.
15d
Fe/CaCl2,
nickel-iron oxide/NH2NH2·H2O,15e Fe3O4/
NH2NH2·H2O,15f,15g Fe nanoparticles/H2O, 15h Fe–phenanthroline-
C/ NH2NH2·H2O,15i Fe(acac)3/TMDS (1,1,3,3-tetramethyl
disiloxane),15j and γ-Fe2O3/2-propanol15k
.
Here we report a strategy for the direct aminolysis of
nitroarenes with 1,2-epoxides through a tandem reduction and
ring-opening process to prepare β-amino alcohols, which uses
iron/NH4Cl in a mixture of water and ethanol. The key of our
proposed method is to choose a suitable reducing agent that is
just strong enough to reduce the target functional group without
affecting 1,2-epoxides and other functional groups. As a result, it
ensures the selective reduction of nitro group and the subsequent
reaction of ring-opening of nitroarenes and epoxides.
Arylamines are widely used as important intermediates in the
synthesis of dyes, antioxidants, conducting polymers,
photographic, pharmaceutical, agricultural chemicals, etc.7 The
most important method to obtain primary anilines is based on the
selective reduction of nitroarenes, since nitroarenes are relatively
cheap, stable and readily available. The reduction of nitro group
2. Results and discussion
The optimization of the reduction and ring-opening tandem
reaction of nitroarenes and epoxides was accomplished by
employing the reaction of nitrobenzene 1a with 7-oxa-
bicyclo[4.1.0]heptane 2a. The results in Table 1 illustrate how
selected additives of CaCl2, MgSO4, BaCl2, NH4Cl, NaH2PO4,
KH2PO4 and NaCl were screened to improve this transformation
(entry 1- 7). NH4Cl was found to be the best one, giving the
highest isolated yield of the product (87%) in a mixture of
ethanol and water in the presence of 3 equiv iron. The system
with NaH2PO4 or KH2PO4, could not reduce nitrobenzene
effectively and only afforded the product with unsatisfied yield
(entries 5, 6). Moreover, when iron was decreased to 2 equiv, it
is
a key step in the preparation of nitrogen-containing
pharmaceutical agents and fine chemicals.8 Traditionally, the
hydrogenation of nitroarenes has employed metal catalysts of
Ru9 and Pd,10 combined with stoichiometric amount of various
reducing reagents. Clearly, the high cost and limited availability
of these noble metals make it desirable to search for more
economic and environmentally friendly alternatives. Procedures
based on bio-relevant metals, such as copper11, iron,12 zinc13 and
similar other metals14 have thus been developed. Especially, more
attention has been paid to iron since it is an abundant,

2
Tetrahedron
Table 2. The reduction and ring-opening tandem reaction of
slowed reaction rates and failed to achieve 100% conversion of
ACCEPTED MANUSCRIPT
nitroarenes with 7-oxa-bicyclo[4.1.0]heptane 1a.
nitrobenzene with resulted 51% isolated yield only (entry 8). This
result is consistent with what was suggested in literature.15e, 15i
Table 1. Condition optimization for the reduction and ring-option
tandem reaction of nitrobenzene 1a with 7-oxa-
bicyclo[4.1.0]heptane 2a.
Entrya
1
2
3
4
5
6
7
8
R1
1a(H)
1b(4-Br)
1c(3-Br)
1d(4-Cl)
1e(2-Cl)
1f(3-Cl)
1g(2-F)
Yield(%)b
3a,87
3b,63
3c,59
3d,68
3e,65
3f,62
3g,72
3h,81
3i,86
3j,86
3k,71
Entrya
1
2
3
4
5
6
Additive
CaCl2
MgSO4
BaCl
Solvent
Yield(%)b
72
H2O/EtOH(1:1)
H2O/EtOH(1:1)
H2O/EtOH(1:1)
H2O/EtOH(1:1)
H2O/EtOH(1:1)
H2O/EtOH(1:1)
H2O/EtOH(1:1)
H2O/EtOH(1:1)
H2O
76
78
87
13
Trace
Trace
51
63
NR
79
1h(4-F)
9
10
11
1i(4-CH3)
1j(4-OCH3)
1k(3-CH3)
NH4Cl
NaH2PO4
KH2PO4
NaCl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
aAll reactions were carried out using 2a (0.75mmol), 1
(0.5mmol), NH4Cl (1.0equiv), iron (3.0equiv), Solvent (1.0ml) at
60℃ for 12h. bIsolated yields.
7
8c
9
10
11
12
13
14
15d
16e
EtOH
H2O/EtOH(4:1)
H2O/EtOH(3:2)
H2O/EtOH(2:3)
H2O/EtOH(1:4)
H2O/EtOH(1:1)
H2O/EtOH(1:1)
And different unsymmetrical 1,2-epoxides were also
investigated under the optimized conditions in order to examine
the practicality and synthetic potential of the reduction and ring-
opening tandem reaction. The results were summarized in Table
3, which illustrate that the reaction of styrene oxide as an active
epoxide (table 3, entries 1–12) has been completed with all
nitroarenes in the presence of iron and NH4Cl with a moderate to
good yields. As expected, in the case of styrene oxide primary
alcohols were obtained as the major product. The ratio of 3/3’
was determined by 1H NMR. And it is reasonable that
regioselectivity is not specific since the benzyl position of
epoxide 2b is more positive and easy to be attacked by
nucleophiles. With the reaction of styrene oxide, substituent
steric effect was significant, and more hindered ortho-substituted
nitroarenes (table 3, entry 5, 7) provided products only with
moderate yield, while electronic effect was not significant,
nitroarenes containing various electron-donor or electron-
withdraw groups (table 3, entry 2–11), reacted efficiently with 2b
in good isolated yields.
79
72
59
53
80
aAll reactions were carried out using 2a (0.75 mmol), 1a
(0.5mmol), Additive (1.0equiv), iron (3.0equiv), solvent (1.0ml)
at 60℃ for 12h. bIsolated yields, c2equiv was added, c30℃. e80℃
.
In the next step, the solvent effect was investigated, in which
very good yields were obtained in water or a mixture of
water/ethanol. The mixture of water/ethanol (1:1) was found to
be the best. This is likely because most of the nitro substrates
were insoluble in water, but become soluble in water/ethanol
solution. In the process, we also found that the optimum reaction
temperature was 60oC.
Using the above optimized conditions various nitroarenes
were subsequently employed in the reduction and ring-opening
tandem reactions with 7-oxa-bicyclo [4.1.0] heptane 2a to extend
the scope of this method. Results summarized in Table 2 show
that the expected β-amino alcohols were formed with a moderate
to good yield. Those with reactive functional groups such as
fluoro, chloro, and bromo were compatible with the reaction
conditions, and no dehalogenated product was detected by GC-
MS (table 2, entry 2 -8). Substituent electronic effect was not
significant in the reactions. Various electron-donate (CH3-, and
CH3O-) or electron-withdraw groups (F-, Cl-, and Br-)
substituted nitroarenes (table 2, entry 2–11), reacted efficiently
with 2a to afford the corresponding β-amino alcohols in good
yields. Moreover, substitutent steric effect was not significant
either, and more hindered ortho-substituted nitroarenes reacted
smoothly and provided products with a high yield (table 2, entry
5, 7). It is useful to point out that the epoxide 2a did not undergo
cleavage by chloride ion of NH4Cl, and no vicinal chlorohydrin
product was observed.
In the case of unsymmetrically substituted epoxides 2c and 2d,
highly regioselectivity with the attack of nucleophile on the less
substituted epoxide carbon was observed (table 3, entry 13, 14),
though their product yields were not satisfied. Moreover, in case
of the reaction of 2c, we did not detect the epoxide formation
(eliminate a chloride anion). And we did not detect the product
which the chloride anion was substituted by aromatic amine,
either.
NO2
OH
H
Fe (3equiv),
NH4Cl(1equiv)
N
O
+
EtOH-H2O(1:1),
60oC
1a
2a
3a
100 mmol 150 mmol
Scheme 1
Finally, the reaction was carried out on much larger scale.
Thus, Thus, as shown in Scheme 1, a 100-mmol scale reaction of
1a and 2a successfully afforded 73% isolated yield of 3a under
the standard conditions. The result clearly revealed the

To a mixture of nitro compound (0.5 mmol) and epoxide (0.75
generality, practicality and synthetic potential of the present
method.
ACCEPTED MANUSCRIPT
mmol) in H2O/C2H5OH (v:v=1:1, 1mL) was added Fe (1.5
mmol), NH4Cl (0.5 mmol) and the mixture was magnetically
stirred at 60 oC under air for 12 h. After completion of the
reaction (TLC, GC-MS) the reaction mixture was extracted by
EtOAc and dried over anhydrous Na2SO4. The solvent was
evaporated in vacuo and the crude isolate was purified by flash
chromatography using silica gel (300-400 mesh) and eluted with
EtOAc/petroleum ether to gave the pure product.
Table 3. The reduction and ring-opening tandem reaction of
nitroarene with unsymmetrical epoxides.
4.2.1. Compound 3a16: a white solid. 1H NMR (500 MHz,
CDCl3): δ 7.19-7.16 (m, 2H), 6.76-6.70 (m, 3H), 3.36-3.31 (m,
1H), 3.14-3.02 (m, 3H), 2.12-2.10 (m, 2H), 1.78-1.70 (m, 2H),
1.43-1.25 (m, 3H), 1.07-1.00 (m, 1H). 13C NMR (125 MHz,
CDCl3): δ 147.8, 129.3, 118.3, 114.3, 74.5, 60.1, 33.1, 31.6, 25.0,
24.2.
4.2.2 Compound 3b17: Yellow solid. 1H NMR (500 MHz,
CDCl3): δ 7.25 (d, J = 8.5 Hz, 2H), 6.59 (d, J = 8.5 Hz, 2H),
3.37-3.32 (m, 1H), 3.11-3.06 (m, 1H), 2.63 (b, 1H), 2.12-2.07 (m,
2H), 1.78-1.72 (m, 2H), 1.40-1.25 (m, 3H), 1.09-1.01 (m, 1H).
13C NMR (125 MHz, CDCl3): δ 146.9, 132.0, 115.8, 109.8, 74.5,
60.2, 33.2, 31.5, 24.9, 24.2.
4.2.3 Compound 3c18: Colorless liquid. 1H NMR (500 MHz,
CDCl3): δ 7.00 (t, J = 8.5 Hz, 1H), 6.83-6.82 (m, 2H), 6.61-6.58
(m, 1H), 3.49 (b, 1H), 3.35-3.30 (m, 1H), 3.11-3.06 (m, 1H), 2.72
(b, 1H), 2.10-2.04 (m, 2H), 1.77-1.70 (m, 2H), 1.39-1.24 (m,
3H), 1.08-1.00 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 149.2,
130.5, 123.2, 120.8, 116.5, 112.7, 74.4, 59.8, 33.2, 31.5, 24.8,
24.1.
Entrya
1(R1)
2
3:3’
Yield(%)b
1
2
1a
1b
2b
2b
87:13
88:12
3l,98
3m,76
3
4
1c
1d
1e
1f
2b
2b
2b
2b
2b
2b
2b
2b
2b
82:18
92:8
3n,76
3o,87
3p,53
3q,80
3r,56
3s,87
3t,93
3u,74
3v,89
5
93:7
6
83:17
89:11
88:12
84:16
97:3
7
1g
1h
1i
8
9
10
11
1l
1k
1l
90:10
12
13
2b
2c
81:19
2:98
3w,80
3x,66
1
4.2.4 Compound 3d19: White solid. H NMR (500 MHz, CDCl3):
(3-Me-4-F)
δ 7.10 (d, J = 8.5 Hz, 2H), 6.61 (d, J = 8.5 Hz, 2H), 3.35-3.30 (m,
2H), 3.08-3.03 (m, 1H), 2.82 (b, 1H), 2.10-2.06 (m, 2H), 1.77-
1.69 (m, 2H), 1.41-1.24 (m, 3H), 1.06-1.00 (m, 1H). 13C NMR
(125 MHz, CDCl3): δ 146.4, 129.0, 122.6, 115.3, 74.4, 60.2,
33.2, 31.4, 24.8, 24.2.
4.2.5 Compound 3e17: Colorless liquid. 1H NMR (500 MHz,
CDCl3): δ 7.27-7.25 (m, 1H), 7.14-7.11 (m, 1H), 6.85 (d, J = 8.5
Hz, 1H), 6.67-6.64 (m, 1H), 4.06 (b, 1H), 3.48-3.43 (m, 1H),
3.20 (s, 1H), 2.63 (s, 1H), 2.14-2.07 (m, 2H), 1.80-1.66 (m, 2H),
1.46-1.26 (m, 3H), 1.18-1.09 (m, 1H). 13C NMR (125 MHz,
CDCl3): δ 143.8, 129.3, 127.8, 120.2, 118.0, 112.8, 74.5, 59.8,
33.1, 31.7, 24.9, 24.2.
4.2.6 Compound 3f20: Colorless liquid. 1H NMR (500 MHz,
CDCl3): δ 7.06 (t, J = 8.0 Hz, 1H), 6.70-6.67 (m, 2H), 6.56-6.54
(m, 1H), 3.49 (b, 1H), 3.36-3.31 (m, 1H), 3.12-3.07 (m, 1H), 2.66
(b, 1H), 2.11-2.07 (m, 2H), 1.79-1.71 (m, 2H), 1.42-1.25 (m,
3H), 1.09-1.00 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 149.1,
135.0, 130.2, 117.9, 113.7, 112.4, 74.4, 59.9, 33.3, 31.5, 24.8,
24.2.
1a
2d
14
1a
>1:99
3y,51
aAll reactions were carried out using 2 (0.75mmol), 1 (0.5mmol),
Fe (1.5mmol), NH4Cl (0.5mmol) in EtOH-H2O (1:1) (1.0ml) at
60℃ for 12h. bIsolated yields.
3. Conclusion
In conclusion, a new and efficient procedure has been
developed for the one-pot synthesis of β-amino alcohols from
nitroarenes and 1,2-epoxides. It uses iron as the reducing agent
and NH4Cl as the only additive. The advantages of this method
include readily available starting materials, good substrate
generality, inexpensive Fe as reducing agent under mild
conditions, which offers great potential of being economic and
environmentally benign alternative to the synthesis of β-amino
alcohols.
4.2.7 Compound 3g3d: Colorless liquid. 1H NMR (500 MHz,
CDCl3): δ 7.00-6.95 (m, 2H), 6.88-6.84 (m, 1H), 6.68-6.63 (m,
1H), 3.63 (b, 1H), 3.43-3.39 (m, 1H), 2.75 (b, 1H), 2.14-2.06 (m,
2H), 1.80-1.70 (m, 2H), 1.45-1.26 (m, 3H), 1.14-1.05 (m, 1H).
13C NMR (125 MHz, CDCl3): δ 152.2 (d, JC-F = 237.4 Hz), 136.2
(d, JC-F = 11.4 Hz), 124.6 (d, JC-F = 3.5 Hz), 117.6 (d, JC-F =7.1
Hz), 114.7 (d, JC-F = 18.9 Hz), 113.8 (d, JC-F = 2.8 Hz), 74.5,
59.8, 33.1, 31.6, 25.0, 24.2.
4. Experimental section
4.1 General remarks.
1H and 13C NMR spectra were recorded on a Bruker Avance
AV-II 300 MHz or Bruker Avance AV-III 500 MHz
spectrometer for solution in CDCl3 with tetramethylsilane (TMS)
as an internal standard; J-values are in Hz. Commercially
obtained reagents were used without further purification. Flash
column chromatography was carried out using Huanghai 300-400
mesh silica gel at increased pressure.
4.2.8 Compound 3h19: White solid. 1H NMR (500 MHz, CDCl3):
δ 6.88 (t, J = 8.5 Hz, 2H), 6.65-6.62 (m, 2H), 3.35-2.99 (m, 4H),
2.11-2.07 (m, 2H), 1.78-1.70 (m, 2H), 1.39-1.26 (m, 3H), 1.05-
4.2 Experimental procedures
0.98 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 156.2 (d, JC-F
=
239.3 Hz), 144.0 (d, JC-F = 1.6 Hz), 115.6 (d, JC-F = 22.3 Hz),
115.5 (d, JC-F = 7.4 Hz), 74.3, 61.1, 33.2, 31.4, 24.9, 24.2.
General procedure for the reduction and ring-opening
tandem reaction of epoxide and nitrocompound.

4
Tetrahedron
ACCEPTED MANUSCRIPT
1
4.2.9 Compound 3i17: White solid. 1H NMR (500 MHz, CDCl3):
4.2.19 Compound 3s24: Colorless liquid. H NMR (500 MHz,
CDCl3): δ 7.37-7.22 (m, 5H), 6.77 (t, J = 9.0 Hz, 2H), 6.47-6.44
(m, 2H), 4.38-4.36 (m, 1H), 3.88-3.84 (m, 1H), 3.68-3.64 (m,
1H). 13C NMR (125 MHz, CDCl3): δ 156.0 (d, JC-F = 234.7 Hz),
143.5 (d, JC-F = 1.8 Hz), 139.9, 128.8, 127.6, 126.7, 115.5 (d, JC-F
= 22.3 Hz), 114.7 (d, JC-F = 7.4 Hz), 114.4 (d, JC-F = 18.4 Hz),
113.6 (d, JC-F = 3.0 Hz), 67.2, 60.5.
δ 6.99 (d, J = 8.5 Hz, 2H), 6.62 (d, J = 8.5 Hz, 2H), 3.33-3.28 (m,
1H), 3.09-3.04 (m, 3H), 2.34 (s, 3H), 2.11-2.07 (m, 2H), 1.77-
1.67 (m, 2H), 1.41-1.23 (m, 3H), 1.03-0.95 (m, 1H). 13C NMR
(125 MHz, CDCl3): δ 145.4, 129.7, 127.6, 114.7, 74.3, 60.5,
33.0, 31.5, 25.0, 24.2, 20.3.
4.2.10 Compound 3j17: Yellow solid. 1H NMR (500 MHz,
CDCl3): δ 6.77 (d, J = 9.0 Hz, 2H), 6.68 (d, J = 8.5 Hz, 2H), 3.74
(s, 3H), 3.33-3.28 (m, 1H), 3.01-2.96 (m, 3H), 2.11-2.06 (m, 2H),
1.77-1.68 (m, 2H), 1.41-1.21 (m, 3H), 1.03-0.95 (m, 1H). 13C
NMR (125 MHz, CDCl3): δ 152.7, 141.6, 116.2, 114.7, 74.2,
61.5, 55.6, 33.0, 31.4, 25.0, 24.2.
4.2.20 Compound 3t16: Colorless liquid. H NMR (500 MHz,
1
CDCl3): δ 7.35-7.21 (m, 5H), 6.88 (d, J = 8.0 Hz, 2H), 6.45 (d, J
= 8.0 Hz, 2H), 4.40-4.38 (m, 1H), 3.84-3.81 (m, 1H), 3.64-3.60
(m, 1H), 2.17 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 144.9,
140.3, 129.6, 128.6, 127.4, 127.0, 126.6, 114.0, 67.2, 60.1, 20.3.
4.2.11 Compound 3k3d: Yellow liquid. 1H NMR (500 MHz,
CDCl3): δ 7.08-7.05 (m, 1H), 6.58-6.51 (m, 3H), 6.61-6.58 (m,
1H), 3.34-3.29 (m, 1H), 3.14-2.95 (m, 3H), 2.27 (s, 3H), 2.12-
2.08 (m, 2H), 1.79-1.69 (m, 2H), 1.43-1.25 (m, 3H), 1.06-0.99
(m, 1H). 13C NMR (125 MHz, CDCl3): δ 147.8, 139.1, 129.1,
119.2, 115.1, 111.5, 74.5, 60.1, 33.1, 31.6, 25.0, 24.2, 21.5.
4.2.21 Compound 3u21: Yellow liquid. 1H NMR (500 MHz,
CDCl3): δ 7.33-7.30 (m, 4H), 7.26-7.23 (m, 1H), 6.68 (d, J = 9.0
Hz, 2H), 6.52 (d, J = 9.0 Hz, 2H), 4.40-4.38 (m, 1H), 3.88-3.85
(m, 1H), 3.68-3.64 (m, 4H). 13C NMR (125 MHz, CDCl3): δ
152.3, 141.3, 140.3, 128.7, 127.5, 126.7, 115.3, 114.7, 67.2, 60.8,
55.6.
1
1
4.2.12 Compound 3l21: Colorless liquid. H NMR (500 MHz,
4.2.22 Compound 3v5a: Colorless liquid. H NMR (500 MHz,
CDCl3): δ 7.36-7.15 (m, 5H), 7.09-7.06 (m, 2H), 6.68-6.63 (m,
3H), 6.54-6.52 (m, 2H), 4.44-4.42 (m, 1H), 3.86-3.83 (m, 1H),
3.67-3.64 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 147.2, 140.1,
129.1, 128.7, 127.4, 126.7, 117.8, 113.8, 67.2, 59.8.
4.2.13 Compound 3m21: Red liquid. 1H NMR (500 MHz, CDCl3):
δ 7.37-7.23 (m, 5H), 7.14 (d, J = 9.0 Hz, 2H), 6.39 (d, J = 9.0 Hz,
2H), 4.40-4.37 (m, 1H), 3.90-3.86 (m, 1H), 3.70-3.66 (m, 1H).
13C NMR (125 MHz, CDCl3): δ 146.1, 139.5, 131.8, 128.8,
127.7, 126.6, 115.3, 109.4, 67.1, 59.7.
4.2.14 Compound 3n22: Yellow solid. 1H NMR (500 MHz,
CDCl3): δ 7.38-7.21 (m, 5H), 6.91 (t, J = 8.0 Hz, 1H), 6.77 (d, J
= 7.0 Hz, 1H), 6.69 (s, 1H), 6.43-6.41 (m, 1H), 4.63 (b, 1H),
4.42-4.40 (m, 1H), 3.89-3.86 (m, 1H), 3.71-3.67 (m, 1H), 2.06 (b,
1H). 13C NMR (125 MHz, CDCl3): δ 148.5, 139.4, 130.4, 128.8,
127.7, 126.6, 123.0, 120.5, 116.5, 112.2, 67.1, 59.5.
CDCl3): δ 7.38-7.22 (m, 5H), 6.97 (t, J = 7.5 Hz, 1H), 6.50 (d, J
= 7.5 Hz, 1H), 6.42 (s, 1H), 6.35-6.33 (m, 1H), 4.48-4.45 (m,
1H), 3.90-3.87 (m, 1H), 3.71-3.67 (m, 1H), 2.20 (s, 3H). 13C
NMR (125 MHz, CDCl3): δ 147.2, 140.2, 138.9, 129.0, 128.7,
127.5, 126.7, 118.8, 114.7, 110.8, 67.2, 59.8, 21.5.
4.2.23 Compound 3w: Yellow liquid. 1H NMR (500 MHz,
CDCl3): δ 7.36-7.20 (m, 5H), 6.80-6.77 (m, 2H), 6.62-6.58 (m,
1H), 6.24-6.21 (m, 1H), 4.41-4.39 (m, 1H), 3.90-3.87 (m, 1H),
3.71-3.67 (m, 1H), 2.22 (s, 3H). 13C NMR (125 MHz, CDCl3): δ
155.5 (d, JC-F = 234.2 Hz), 141.4 (d, JC-F = 1.8 Hz), 140.0, 128.8,
127.6, 126.6, 124.4 (d, JC-F = 7.1 Hz), 116.8 (d, JC-F = 22.3 Hz),
112.6 (d, JC-F = 21.4 Hz), 112.2 (d, JC-F = 7.8 Hz), 67.3, 60.3,
17.6. HRMS Calcd for C15H17FNO (M+H)+: 246.1289; found:
246.1295.
1
4.2.24 Compound 3x16: Colorless liquid. H NMR (500 MHz,
CDCl3): δ 7.19 (t, J = 7.5 Hz, 2H), 6.77-6.74 (m, 1H), 6.64 (d, J
= 8.5 Hz, 2H), 4.06-4.02 (m, 1H), 3.67-3.58 (m, 2H), 3.37-3.33
(m, 1H), 3.21-3.17 (m, 1H), 2.81(b, 1H). 13C NMR (125 MHz,
CDCl3): δ 147.7, 129.3, 118.2, 113.3, 69.8, 47.6, 47.0.
1
4.2.15 Compound 3o23: Colorless liquid. H NMR (500 MHz,
CDCl3): δ 7.37-7.23 (m, 5H), 7.01 (d, J = 9.0 Hz, 2H), 6.44 (d, J
= 9.0 Hz, 2H), 4.55 (b, 1H), 4.41-4.39 (m, 1H), 3.91-3.87 (m,
1H), 3.71-3.68 (m, 1H), 2.02 (b, 1H). 13C NMR (125 MHz,
CDCl3): δ 145.7, 139.6, 128.9, 128.8, 127.7, 126.6, 122.4, 114.9,
67.2, 59.9.
4.2.25 Compound 3y16: Yellow liquid. 1H NMR (500 MHz,
CDCl3): δ 7.19-7.16 (m, 2H), 6.73-6.70 (m, 1H), 6.65-6.63 (m,
2H), 5.95-5.87 (m, 1H), 5.31-5.30 (m, 2H), 4.03-4.02 (m, 3H),
3.56-3.53 (m, 1H), 3.50-3.47 (m, 1H), 3.30-3.27 (m, 1H), 3.16-
3.12 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 148.2, 134.3,
129.2, 117.7, 117.4, 113.1, 72.4, 72.3, 46.7.
1
4.2.16 Compound 3p17: Colorless liquid. H NMR (500 MHz,
CDCl3): δ 7.33-7.22 (m, 5H), 6.96-6.92 (m, 1H), 6.60-6.57 (m,
1H), 6.42-6.40 (m, 1H), 5.15 (b, 1H), 4.52 (s, 1H), 3.95-3.92 (m,
1H), 3.79-3.74 (m, 1H), 2.02 (b, 1H). 13C NMR (125 MHz,
CDCl3): δ 143.0, 139.5, 129.0, 128.8, 127.7, 127.6, 126.6, 119.7,
117.8, 112.8, 67.2, 59.6.
Acknowledgments
4.2.17 Compound 3q24: Yellow liquid. 1H NMR (500 MHz,
CDCl3): δ 7.38-7.22 (m, 5H), 6.97 (t, J = 8.0 Hz, 1H), 6.63-6.61
(m, 1H), 6.52-6.61 (m, 1H), 6.40-6.28 (m, 1H), 4.64 (b, 1H),
4.42-4.40 (m, 1H), 3.90-3.86 (m, 1H), 3.71-3.67 (m, 1H), 2.04 (b,
1H). 13C NMR (125 MHz, CDCl3): δ 148.4, 139.5, 134.8, 130.1,
128.8, 127.7, 126.6, 117.6, 113.5, 111.9, 67.1, 59.6.
Financial support from the National Natural Science
Foundation of China (No. 21302143 and 51572198), Natural
Science Foundation of Zhejiang Province (No. LY13B020006),
and Open Research Fund of Top Key Discipline of Chemistry in
Zhejiang Provincial Colleges is greatly appreciated.
1
4.2.18 Compound 3r21: Colorless liquid. H NMR (500 MHz,
References and notes
CDCl3): δ 7.39-7.20 (m, 5H), 6.98-6.94 (m, 1H), 6.81 (d, J = 7.5
Hz, 1H), 6.61-6.56 (m, 1H), 6.47-6.43 (m, 1H), 4.75 (b, 1H),
4.50-4.48 (m, 1H), 3.93-3.90 (m, 1H), 3.77-3.74 (m, 1H), 2.04 (b,
1H). 13C NMR (125 MHz, CDCl3): δ 151.8 (d, JC-F = 237.9 Hz),
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