Silver-Catalyzed Nitration/Annulation of α-Alkynyl Arylols toward 3-Nitrated Benzofurans

Article abstract of DOI:10.1002/asia.201901400

A silver-catalyzed nitration/annulation of α-alkynyl arylols is reported by using tert-butyl nitrite (TBN) as a NO₂ radical precursor, from which a set of 3-nitrated benzofurans were synthesized with moderate to good yields. This transformation

Full text of DOI:10.1002/asia.201901400

DOI: 10.1002/asia.201901400
Full Paper
Silver-Catalyzed Nitration/Annulation of a-Alkynyl Arylols toward
3-Nitrated Benzofurans
Tian-Shu Zhang,[a] Lei Yang,[b] Pei-Jun Cai,*[a] Shu-Jiang Tu,[b] and Bo Jiang*[b]
Abstract: A silver-catalyzed nitration/annulation of a-alkynyl
arylols is reported by using tert-butyl nitrite (TBN) as a NO2
radical precursor, from which a set of 3-nitrated benzofurans
were synthesized with moderate to good yields. This trans-
formation initiated by an in situ generated NO2 radical pro-
ceeds efficiently under mild and neutral redox conditions,
which provides a new pathway toward the 3-nitrobenzofur-
an framework via catalytic difunctionalization of internal al-
kynes.
Introduction
Catalytic addition of alkynes toward their functionalization re-
mains one of the hot topics in modern organic synthesis,[1]
providing economical and efficient methods for numerous
functionalized molecular libraries. Specifically, difunctionaliza-
tion of alkynes via addition of heteroatoms across carbon-
carbon multiple bond has been recognized as a step- and
atom-economic synthetic strategy for the assembly of heteroa-
tom-containing molecules with high stereoselectivity.[2] Among
them, radical-induced addition/intramolecular annulations of
internal alkynes have been one of the most attractive targets
in the organic community since such transformations not only
realize alkyne difunctionalization but also construct bioactive
heterocyclic system in a highly regioselective manner, and thus
has drawn considerable attention from chemists.[3] On the
other hand, tert-butyl nitrite (TBN) emerges as a powerful NO2
radical precursor, which have been widely applied in the syn-
thesis of nitrogen-containing compounds including nitroar-
enes.[4] Recently, our group reported a silver-catalyzed nitra-
tion-annulation of 2-alkynylanilines with TBN, leading to the se-
lective generation of a variety of C5/7-nitroindoles (Scheme 1,
path a).[5] However, NO2 radical-triggered difunctionalization of
internal alkynes remains almost unexplored,[6] probably be-
cause of their strong bond energy and difficulty in the regiose-
lectivity.[7]
Scheme 1. Profiles of nitration-annulation of TBN.
a remarkable biological and pharmacological activities.[8] For in-
stance, 3-nitrobenzofurans have been found to show antibac-
terial, parasiticidal[9] and antimicrobial[10] activities. With these
contributions in mind, considerable effort has been made to
identify efficient methods for the synthesis of these 3-nitroben-
zofurans, including traditional electrophilic substitution of ben-
zofurans using HNO3 as nitrating reagents[11] and cyclization of
benzoquinones with nitro compounds.[12] However, these
methods often suffer from over-nitration and poor regioselec-
tivity, narrow substrate scope and limited functional group tol-
erance, thereby limiting their further applications to a certain
extent. To search a new entry to construct 3-nitrobenzofuran
skeleton and to continue our efforts on radical transforma-
tions,[13] we found that by using a-alkynyl arylols 1 as internal
alkynes[14] and TBN as a nitrating reagent, a silver-catalyzed re-
action proceeded readily in a highly regioselective manner, en-
abling nitro radical addition/intramolecular annulation to
access a vast array of structurally diverse 3-nitrobenzofurans 2
in moderate to good yields (Scheme 1, path b). Herein, we
elaborate this attractive transformation for the achievement of
NO2 radical difunctionalization of internal alkynes.
One the other hand, benzofurans are an important structural
scaffold in the pharmaceutical application and have exhibited
[a] Dr. T.-S. Zhang, Prof. Dr. P.-J. Cai
School of Chemical Engineering&Technology
China University of Mining and Technology
Xuzhou, 221116 (P. R. China)
E-mail: pjcai@cumt.edu.cn
[b] L. Yang, Prof. S.-J. Tu, Prof. Dr. B. Jiang
School of Chemistry & Materials Science
Jiangsu Normal University
Xuzhou 221116 (P. R. China)
E-mail: jiangchem@jsnu.edu.cn
Results and Discussion
Supporting information and the ORCID identification number(s) for the au-
thor(s) of this article can be found under:
We initiated our investigations with 1-(phenylethynyl)naphtha-
https://doi.org/10.1002/asia.201901400.
len-2-ol (1a) and commercially available TBN as the nitrating
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agent. The reaction of 1a with in a 1:1 mol ratio worked in the
presence of AgNO3 (10 mol%) at 108C in tetrahydrofuran (THF)
under air conditions. To our delight, 1-nitronaphtho[2,1-b]furan
product 2a was obtained in 45% yield (Table 1, entry 1). With-
out AgNO3, the reaction did not proceed, indicating silver salts
are crucial for this transformation (entry 2). Reducing reaction
temperature to 08C resulted in a slightly dropped yield of 2a
(43%, entry 3). In contrast, the yield of 2a remarkably de-
Table 1. Optimization Conditions for Forming 2a.[a]
Entry Ag-cat. [mol%] Ratio [1a/TBN] Solvent
t [8C] Yield [%][b]
1
2
3
4
5
6
7
8
AgNO3 (0.1)
–
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:2
1:1
1:1
1:1
1:1
1:1
THF
THF
THF
THF
10
10
0
45
N.R.
43
17
50
N.R.
N.D.
24
N.D.
51
AgNO3 (0.1)
AgNO3 (0.1)
AgNO3 (0.1)
AgNO3 (0.1)
AgNO3 (0.1)
AgNO3 (0.1)
AgNO3 (0.1)
AgNO3 (0.1)
AgNO3 (0.5)
AgNO3 (1.0)
AgBF4 (0.5)
AgOTf (0.5)
Ag2CO3 (0.5)
25
1,4-dioxane 10
toluene
DMF
DCE
CH3CN
1,4-dioxane 10
1,4-dioxane 10
1,4-dioxane 10
1,4-dioxane 10
1,4-dioxane 10
1,4-dioxane 10
10
10
10
10
9
10
11
12
13
14
15
53
53
42
76
40
[a] Reaction conditions: 1a (0.2 mmol), solvent (2.0 mL), 0.5 h in a sealed
tube. [b] Isolated yield.
creased when the temperature was raised to 258C (entry 4). As
the next optimization step, we examined the solvent effect by
adjusting reaction media, including 1,4-dioxane, toluene, dime-
thylformamide (DMF), dichloroethane (DCE) and acetonitrile
(entries 5–9). After carful screening of these solvents, we found
that 1,4-dioxane was proven to be the best one, affording 2a
in 50% yield (entry 5). The yield of 2a levelled off by increasing
the amount of TBN (entry 10). Subsequently, an increase in the
loading of AgNO3 to 0.5 equivalent facilitated the transforma-
tion, providing 2a in 53% yield (entry 11). Further increasing
AgNO3 loading to 1.0 equivalent did not show any improve-
ment on the yield of 2a (entry 12). The following screening of
other silver catalysts such as AgBF4, AgOTf and Ag2CO3 (en-
tries 13–15) revealed that AgOTf was the best choice, deliver-
ing a higher yield than AgNO3 (entry 14 vs. entry 11).
Scheme 2. Synthesis of 3-nitrofurans.
yields. Obviously, the radical system can readily endure various
substituents, such as methyl (1b, 1c and 1d), ethyl (1e), n-
propyl (1 f), tert-butyl (1g), fluoro (1i and 1j), chloro (1k, 1l
and 1h), and bromo (1n). Among them, both Cl and Br groups
provide the possibility for further functionalization. Alternative-
ly, 2-thienyl analogue 1o did not influence the reaction
output, affording product 2o in 81% yield. Moreover, sterically
more demanding 1-naphthyl (1-Np) 1p and 2-methoxynaph-
thalen-1-yl (1-(2-MeO)Np) 1q were suitable surrogates for the
alkyne difunctionalization, albeit with remarkably declining
yields of products 2p and 2q. However, a-alkynyl arylol 1r
bearing an ethyl group did not work in this transformation.
To broaden the scope of this protocol, representative a-alky-
nylphenols 1s–1u were employed to react with TBN. All these
reactions worked well under standard conditions. In cases of
1s and 1t, products 2s and 2t were offered in 81% and 60%
With the optimized reaction conditions in hands, we then in-
vestigated the scope of this nitration-annulation reaction by
examining various a-alkynyl arylols under standard conditions
(Scheme 2). The presence of substituents on the aryl ring (R)
relative to the alkynyl moiety did not hamper the reaction pro-
cess. Both electronically rich and poor groups at different posi-
tions could show highly reactive profiles, delivering the corre-
sponding 1-nitronaphtho[2,1-b]furans 2b–2q in 40–82%
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yields, respectively. The desired product 2u was observed but
extremely decomposed during purification process and failed
to be isolated. The structures of products 2 have been fully
characterized by NMR and HRMS analyses. Furthermore, the
structure of 2k has been determined by X-ray diffraction analy-
sis (Figure 1, see the Supporting Information).[15]
Combining the above experimental results and literature
survey, a reasonable mechanism for forming 3-nitrofurans was
proposed (Scheme 4). Initially, the decomposition of TBN yields
C
tBuO together with NO radical (·NO), followed oxidized by O2
from air to give NO2 radical (·NO2). Next, addition of NO2 radical
to carbon-carbon triple bond of 1 activated by silver catalyst
Figure 1. X-ray Structure of 2k.
In order to gain insights on the mechanistic pathway, several
control experiments were conducted. 2.0 Equivalents of
2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) as the radical
scavenger was first subjected to the reaction mixture of 1a
and TBN under the standard conditions, the reaction was com-
pletely inhibited. The similar outcome was observed as the an-
tioxidant butylated hydroxytoluene (BHT) was used
(Scheme 3a). These results show that the mechanism may in-
clude a radical process. Next, the reaction of 1a with TBN
under argon (Ar) conditions failed to generate the desired
product 2a with the starting materials remaining unconsumed
(Scheme 3b), showing that O2 may participate in the reaction
process. To further confirm the sequence of nitration and an-
nulation, subjecting the preformed 2-phenylnaphtho[2,1-
b]furan 3 to the standard conditions failed to generate any de-
sired product 2a with the starting materials remaining uncon-
sumed (Scheme 3c), indicating that the nitration drove annula-
tion reaction.
Scheme 4. Plausible mechanism.
gives alkenyl radical intermediate A, which undergoes 1,5-hy-
drogen atom transfer (HAT) to give alkenyl O-centered radical
intermediate B. Subsequent intramolecular 5-endo-trig cycliza-
tion of intermediate B occurs, providing C-centered radical in-
C
termediate C. Finally, tBuO abstracts hydrogen atom to afford
the desired products 2.
Conclusions
In summary, we have successfully established an efficient radi-
cal-enabled difunctionalization of internal alkynes with TBN via
a silver-catalyzed nitration–annulation cascade, providing a
wide range of 3-nitrated benzofurans with moderate to good
yields. The transformation offered a new entry to prepare the
3-nitrobenzofuran skeleton, avoiding the use of traditional
HNO3 as a NO2 source. Further investigation and application of
this nitration–annulation reaction is underway in our laborato-
ry.
Experimental Section
General Information
All one-pot reactions were carried out in a 10-mL Schlenk tube
equipped with a magnetic stir bar under air. All melting points are
uncorrected. The NMR spectra were recorded in CDCl3 on a
400 MHz instrument with TMS as internal standard. Chemical shifts
(d) were reported in ppm with respect to TMS. Data are presented
as follows: chemical shift, multiplicity (s=singlet, d=oublet, m=
multiples), coupling constant (J, Hz) and integration. HRMS analy-
ses were carried out using a TOF-MS instrument with an APCI
source. X-Ray crystallographic analysis was performed with a
SMART CCD and a P4 diffractometer.
Scheme 3. Control experiments.
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General Procedure for the Synthesis of Products 2.
2-(4-ethylphenyl)-1-nitronaphtho[2,1-b]furan (2e)
Light yellow solid, 52 mg, 82% yield; mp 113–1158C. 1H NMR
(400 MHz, CDCl3): d=8.41 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.0 Hz,
1H), 7.88–7.78 (m, 3H), 7.68–7.61 (m, 2H), 7.60–7.54 (m, 1H), 7.36
(d, J=8.0 Hz, 2H), 2.79–2.70 (m, 2H), 1.31 ppm (t, J=7.8 Hz, 3H).
13C NMR (100 MHz, CDCl3): d=152.9, 150.2, 147.7, 131.4, 129.3,
128.6, 128.4, 128.3, 127.4, 125.9, 125.8, 124.7, 124.0, 115.4, 111.9,
29.0, 15.3 ppm. IR (KBr): n˜ =1496, 1392, 1360, 1213, 1116, 1017,
840, 785 cmÀ1. HRMS (APCI-TOF, m/z): calcd for C20H16NO3 [M+H]+
318.1130, found 318.1141.
Example for the synthesis of 2a:
A suspension of AgNO3 (0.1 mmol, 0.5 equiv), tBuONO (0.2 mmol,
1.0 equiv) in 1.0 mL of 1,4-dioxane was stirred at 108C under air
conditions. Subsequently, 1-(phenylethynyl)naphthalen-2-ol 1a
(0.2 mmol, 1.0 equiv) in 1,4-dioxane (1.0 mL) was added into the
suspension over 30 min via a syringe pump. Next, the mixture was
sealed and stirred for 30 min until TLC (petroleum ether: ethyl ace-
tate=1:15, v/v) revealed that conversion of the starting material
1a was completed. The reaction system was evaporated under
vacuum and purified by flash column chromatography (silica gel,
mixtures of petroleum ether/ ethyl acetate=1:50, v/v) to afford
the desired product 2a.
1-nitro-2-(4-propylphenyl)naphtho[2,1-b]furan (2 f)
Light yellow solid, 50 mg, 75% yield; mp 80–828C. 1H NMR
(400 MHz, CDCl3): d=8.41 (d, J=8.4 Hz, 1H), 8.01–7.94 (m, 1H),
7.90–7.84 (m, 1H), 7.82 (d, J=8.0 Hz, 2H), 7.70–7.61 (m, 2H), 7.60–
7.54 (m, 1H), 7.34 (d, J=8.0 Hz, 2H), 2.71–2.64 (m, 1H), 1.76–1.65
(m, 2H), 0.99 ppm (t, J=7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): d=
152.9, 150.2, 146.2, 131.5, 129.3, 129.0, 128.6, 128.2, 127.4, 125.9,
125.8, 124.8, 124.0, 115.4, 111.9, 38.1, 24.3, 13.9 ppm. IR (KBr): n˜ =
1506, 1383, 1341, 1219, 1187, 1007, 835, 769 cmÀ1. HRMS (APCI-
TOF, m/z): calcd for C21H18NO3 [M+H]+ 332.1287, found 332.1282.
1-nitro-2-phenylnaphtho[2,1-b]furan (2a)
Light yellow solid, 44 mg, 76% yield; mp 104–1058C. 1H NMR
(400 MHz, CDCl3): d=8.40 (d, J=8.4 Hz, 1H), 7.98 (d, J=7.6 Hz,
1H), 7.91–7.85 (m, 3H), 7.70–7.62 (m, 2H), 7.61–7.56 (m, 1H), 7.56–
7.51 ppm (m, 3H). 13C NMR (100 MHz, CDCl3): d=152.4, 150.4,
131.5, 130.9, 129.3, 128.9, 128.8, 128.2, 127.5, 127.4, 125.9, 125.9,
123.9, 115.3, 111.9 ppm. IR (KBr): n˜ =1507, 1453, 1388, 1356, 1200,
1131, 1020, 802, 750 cmÀ1
. HRMS (APCI-TOF, m/z): calcd for
C18H12NO3 [M+H]+ 290.0817, found 290.0835.
2-(4-(tert-butyl)phenyl)-1-nitronaphtho[2,1-b]furan (2g)
Light yellow solid, 44 mg, 63% yield; mp 85–878C. 1H NMR
(400 MHz, CDCl3): d=8.41 (d, J=8.4 Hz, 1H), 7.97 (d, J=8.0 Hz,
1H), 7.89–7.82 (m, 3H), 7.68–7.61 (m, 2H), 7.60–7.52 (m, 3H),
1.39 ppm (s, 9H). 13C NMR (100 MHz, CDCl3): d=154.5, 152.9, 150.2,
131.4, 129.3, 128.6, 128.0, 127.4, 125.9, 125.8, 124.5, 124.0, 115.4,
111.9, 35.1, 31.2 ppm. IR (KBr): n˜ =1573, 1508, 1393, 1357, 1210,
1143, 1014, 827, 802, 754 cmÀ1. HRMS (APCI-TOF, m/z): calcd for
C22H20NO3 [M+H]+ 346.1443, found 346.1429.
1-nitro-2-(p-tolyl)naphtho[2,1-b]furan (2b)
Light yellow solid, 41 mg, 68% yield; mp 116–1188C. 1H NMR
(400 MHz, CDCl3): d=8.41 (d, J=8.4 Hz, 1H), 7.97 (d, J=8.0 Hz,
1H), 7.89–7.83 (m, 1H), 7.79 (d, J=8.0 Hz, 2H), 7.69–7.60 (m, 2H),
7.60–7.54 (m, 1H), 7.33 (d, J=8.0 Hz, 2H), 2.45 ppm (s, 3H).
13C NMR (100 MHz, CDCl3): d=152.9, 150.2, 141.5, 131.4, 129.6,
129.3, 128.6, 128.2, 127.4, 125.9, 125.8, 124.6, 124.0, 115.4, 111.9,
2-(4-ethylphenyl)-1-nitronaphtho[2,1-b]furan (2h)
21.7 ppm. IR (KBr): n˜ =1506, 1389, 1356, 1213, 1015, 801, 736 cmÀ1
HRMS (APCI-TOF, m/z): calcd for C19H14NO3 [M+H]+ 304.0974,
.
Light yellow solid, 35 mg, 55% yield; mp 143–1448C. 1H NMR
(400 MHz, CDCl3): d=8.43 (d, J=8.0 Hz, 1H), 7.97 (d, J=7.6 Hz,
1H), 7.90–7.82 (m, 3H), 7.67–7.61 (m, 2H), 7.59–7.54 (m, 1H), 7.06–
7.01 (m, 2H), 3.89 ppm (s, 3H). 13C NMR (100 MHz, CDCl3): d=
161.7, 153.2, 150.0, 131.5, 130.2, 129.3, 128.4, 127.3, 125.9, 125.7,
124.1, 119.8, 115.5, 114.3, 111.8, 55.5 ppm. IR (KBr): n˜ =1608, 1506,
1389, 1351, 1256, 1176, 1021, 825, 796 cmÀ1. HRMS (APCI-TOF, m/z):
calcd for C19H14NO4 [M+H]+ 320.0923, found 320.0930.
found 304.0981.
1-nitro-2-(m-tolyl)naphtho[2,1-b]furan (2c)
Light yellow solid, 30 mg, 50% yield; mp 139–1418C. 1H NMR
(400 MHz, CDCl3): d=8.40 (d, J=8.4 Hz, 1H), 7.98 (d, J=8.0 Hz,
1H), 7.87 (d, J=9.2 Hz, 1H), 7.71–7.66 (m, 3H), 7.66–7.61 (m, 1H),
7.61–7.55 (m, 1H), 7.45–7.39 (m, 1H), 7.34 (d, J=7.6 Hz, 1H),
2.46 ppm (s, 3H). 13C NMR (100 MHz, CDCl3): d=152.7, 150.3, 138.7,
131.8, 131.4, 129.3, 128.8, 128.7, 128.6, 127.5, 127.3, 125.9, 125.3,
123.9, 115.4, 111.9, 21.5 ppm. IR (KBr): n˜ =1565, 1505, 1392, 1362,
1192, 1089, 1007, 812, 745 cmÀ1. HRMS (APCI-TOF, m/z): calcd for
C19H14NO3 [M+H]+ 304.0974, found 304.0970.
2-(4-fluorophenyl)-1-nitronaphtho[2,1-b]furan (2i)
Light yellow solid, 37 mg, 60% yield; mp 125–1268C. 1H NMR
(400 MHz, CDCl3): d=8.41 (d, J=8.4 Hz, 1H), 7.98 (d, J=7.6 Hz,
1H), 7.93–7.86 (m, 3H), 7.68–7.63 (m, 2H), 7.61–7.56 (m, 1H), 7.26–
7.19 ppm (m, 2H). 13C NMR (100 MHz, CDCl3): d=164.1 (1JCF
=
251.6 Hz), 151.75, 150.32, 131.49, 130.72, 130.64, 129.33, 128.94,
127.55, 125.95, 125.85, 124.01, 123.65, 123.61, 116.2 (2JCF =22.0 Hz),
115.24, 111.81 ppm. IR (KBr): n˜ =1606, 1508, 1362, 1237, 1164, 1102,
831, 795, 752 cmÀ1. HRMS (APCI-TOF, m/z): calcd for C18H11FNO3
[M+H]+ 308.0723, found 308.0719.
2-(3,4-dimethylphenyl)-1-nitronaphtho[2,1-b]furan (2d)
Light yellow solid, 33 mg, 52% yield; mp 120–1218C. 1H NMR
(400 MHz, CDCl3): d=8.40 (d, J=8.4 Hz, 1H), 7.96 (d, J=7.6 Hz,
1H), 7.83 (d, J=8.8 Hz, 1H), 7.67–7.61 (m, 4H), 7.59–7.54 (m, 1H),
7.27 (d, J=8.4 Hz, 1H), 2.35 (s, 3H), 2.34 ppm (s, 3H). 13C NMR
(100 MHz, CDCl3): d=153.1, 150.1, 140.2, 137.3, 131.4, 130.1, 129.3,
129.0, 128.5, 127.4, 125.9, 125.8, 125.7, 124.9, 124.0, 115.4, 111.9,
20.0, 19.9 ppm. IR (KBr): n˜ =1506, 1391, 1359, 1255, 1212, 1180,
2-(3-chloro-4-fluorophenyl)-1-nitronaphtho[2,1-b]furan (2j)
Light yellow solid, 38 mg, 56% yield; mp 152–1548C. 1H NMR
(400 MHz, CDCl3): d=8.39 (d, J=8.4 Hz, 1H), 8.02–7.95 (m, 2H),
7.90 (d, J=8.8 Hz, 1H), 7.83–7.77 (m, 1H), 7.70–7.64 (m, 2H), 7.62–
7.57 (m, 1H), 7.33–7.27 ppm (m, 1H). 13C NMR (100 MHz, CDCl3):
d=159.5 (1JCF =253.8 Hz), 150.5, 150.1, 131.5, 130.9, 129.4, 129.4,
1006, 817, 795, 748 cmÀ1
C20H16NO3 [M+H]+ 318.1130, found 318.1125.
. HRMS (APCI-TOF, m/z): calcd for
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128.5 (3JCF =7.9 Hz), 127.7, 126.1, 125.8, 124.6 (4JCF =4.1 Hz), 124.0,
122.2, 122.0, 117.3, 117.11 (2JCF =21.7 Hz), 115.1, 111.8 ppm. IR (KBr):
n˜ =1508, 1392, 1363, 1266, 1212, 1122, 1061, 900, 817 cmÀ1. HRMS
(APCI-TOF, m/z): calcd for C18H10ClFNO3 [M+H]+ 342.0333, found
342.0335.
2-(naphthalen-1-yl)-1-nitronaphtho[2,1-b]furan (2p)
Light yellow solid, 28 mg, 41% yield; mp 161–1638C. 1H NMR
(400 MHz, CDCl3): d=8.74 (d, J=8.4 Hz, 1H), 8.08 (d, J=8.4 Hz,
1H), 8.04 (d, J=8.0 Hz, 1H), 7.97 (m, 2H), 7.84 (m, 1H), 7.77 (d, J=
8.0 Hz, 1H), 7.71 (m, 2H), 7.63 (m, 2H), 7.60–7.50 ppm (m, 2H).
13C NMR (100 MHz, CDCl3): d=154.6, 151.2, 133.5, 131.7, 131.7,
131.5, 129.6, 129.3, 129.0, 128.8, 127.6, 126.7, 126.1, 126.0, 125.2,
125.0, 124.9, 124.7, 114.6, 112.1 ppm. IR (KBr): n˜ =1506, 1447, 1320,
1301, 1219, 1134, 829 cmÀ1. HRMS (APCI-TOF, m/z): calcd for
C22H13NO3 [M+H]+ 340.0974, found 340.1012.
2-(4-chlorophenyl)-1-nitronaphtho[2,1-b]furan (2k)
Light yellow solid, 38 mg, 58% yield; mp 153–1558C. 1H NMR
(400 MHz, CDCl3): d=8.39 (d, J=8.4 Hz, 1H), 7.98 (d, J=8.0 Hz,
1H), 7.89 (d, J=9.2 Hz, 1H), 7.86–7.81 (m, 2H), 7.69–7.63 (m, 2H),
7.62–7.56 (m, 1H), 7.53–7.47 ppm (m, 2H). 13C NMR (100 MHz,
CDCl3): d=151.2, 150.5, 137.2, 131.5, 129.5, 130.0, 129.2, 129.1,
127.6, 126.0, 125.8, 123.9, 115.3, 111.8 ppm. IR (KBr): n˜ =1510, 1483,
1392, 1354, 1199, 1093, 1012, 805, 747 cmÀ1. HRMS (APCI-TOF, m/z):
calcd for C18H11ClNO3 [M+H]+ 324.0427, found 324.0430.
2-(2-methoxynaphthalen-1-yl)-1-nitronaphtho[2,1-b]furan (2q)
Light yellow solid, 30 mg, 40% yield; mp 169–1708C. 1H NMR
(400 MHz, CDCl3): d=8.81 (d, J=8.4 Hz, 1H), 8.07 (d, J=9.2 Hz,
1H), 8.03 (d, J=8.0 Hz, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.89 (d, J=
8.0 Hz, 1H), 7.73 (d, J=9.2 Hz, 1H), 7.69 (d, J=7.2 Hz, 1H), 7.64–
7.58 (m, 2H), 7.51–7.45 (m, 1H), 7.43 (d, J=8.0 Hz, 1H), 7.38 (d, J=
9.2 Hz, 1H), 3.93 ppm (s, 3H). 13C NMR (100 MHz, CDCl3): d=156.5,
151.6, 133.3, 133.1, 131.6, 129.2, 128.8, 128.6, 128.5, 128.0, 127.4,
126.2, 125.8, 125.1, 124.3, 124.0, 112.7, 112.2, 56.5 ppm. IR (KBr): n˜ =
1506, 1411, 1357, 1329, 1183, 1131, 1042, 865, 746 cmÀ1. HRMS
(APCI-TOF, m/z): calcd for C23H16NO4 [M+H]+ 370.1079, found
370.1054.
2-(3-chlorophenyl)-1-nitronaphtho[2,1-b]furan (2l)
Light yellow solid, 37 mg, 57% yield; mp 135–1368C. 1H NMR
(400 MHz, CDCl3): d=8.37 (d, J=8.4 Hz, 1H), 7.98 (d, J=7.6 Hz,
1H), 7.91–7.85 (m, 2H), 7.78–7.74 (m, 1H), 7.69–7.62 (m, 2H), 7.61–
7.56 (m, 1H), 7.51–7.43 ppm (m, 2H). 13C NMR (100 MHz, CDCl3):
d=150.5, 150.5, 135.0, 131.5, 130.9, 130.2, 129.4, 129.3, 129.0,
128.1, 127.7, 126.2, 126.1, 125.8, 123.9, 115.2, 111.8 ppm. IR (KBr):
n˜ =1560, 1509, 1475, 1359, 1145, 1080, 997, 792 cmÀ1. HRMS (APCI-
TOF, m/z): calcd for C18H11ClNO3 [M+H]+ 324.0427, found 324.0435.
3-nitro-2-phenylbenzofuran (2s)
Light yellow solid, 39 mg, 81% yield; mp 70–728C. 1H NMR
(400 MHz, CDCl3): d=8.51 (d, J=2.0 Hz, 1H), 8.25–8.20 (m, 1H),
7.91–7.86 (m, 2H), 7.60 (d, J=9.2 Hz, 1H), 7.53–7.47 (m, 2H), 7.46–
7.40 (m, 1H), 7.14 ppm (s, 1H). 13C NMR (100 MHz, CDCl3): d=
159.3, 157.6, 144.3, 129.7, 129.7, 129.2, 129.1, 125.3, 120.1, 117.3,
111.5, 101.6 ppm. IR (KBr): n˜ =1514, 1440, 1348, 1262, 1069, 1016,
862 cmÀ1. HRMS (APCI-TOF, m/z): calcd for C14H10NO3 [M+H]+
240.0661, found 240.0670.
2-(2-chlorophenyl)-1-nitronaphtho[2,1-b]furan (2m)
Light yellow solid, 33 mg, 51% yield; mp 140–1428C. 1H NMR
(400 MHz, CDCl3): d=8.36 (d, J=8.4 Hz, 1H), 7.98 (d, J=7.6 Hz,
1H), 7.92–7.85 (m, 2H), 7.79–7.73 (m, 1H), 7.69–7.62 (m, 2H), 7.61–
7.56 (m, 1H), 7.51–7.43 ppm (m, 2H). 13C NMR (100 MHz, CDCl3):
d=150.5, 150.4, 135.0, 131.5, 130.9, 130.2, 129.4, 129.3, 129.0,
128.1, 127.7, 126.2, 126.1, 125.8, 123.9, 115.2, 111.8 ppm. IR (KBr):
n˜ =1560, 1509, 1475, 1359, 1211, 1145, 1080, 997, 804 cmÀ1. HRMS
(APCI-TOF, m/z): calcd for C18H11ClNO3 [M+H]+ 324.0427, found
324.0436.
2-(4-(tert-butyl)phenyl)-3-nitrobenzofuran (2t)
Light yellow solid, 15 mg, 26% yield; mp 65–668C. 1H NMR
(400 MHz, CDCl3): d=8.12–8.07 (m, 1H), 7.91–7.83 (m, 3H), 7.54–
7.49 (m, 2H), 7.37–7.30 (m, 1H), 7.07 (s, 1H), 1.37 ppm (s, 9H).
13C NMR (100 MHz, CDCl3): d=158.9, 153.1, 146.9, 133.8, 133.4,
127.3, 126.3, 126.0, 125.3, 122.8, 120.2, 100.2 ppm. IR (KBr): n˜ =
1516, 1497, 1321, 1150, 1036, 997, 862 cmÀ1. HRMS (APCI-TOF, m/z):
calcd for C18H18NO3 [M+H]+ 296.1287, found 296.1292.
2-(4-bromophenyl)-1-nitronaphtho[2,1-b]furan (2n)
Light yellow solid, 36 mg, 49% yield; mp 160–1618C. 1H NMR
(400 MHz, CDCl3): d=8.39 (d, J=8.4 Hz, 1H), 7.99 (d, J=7.6 Hz,
1H), 7.89 (d, J=9.2 Hz, 1H), 7.79–7.75 (m, 2H), 7.70–7.63 (m, 4H),
7.62–7.57 ppm (m, 1H). 13C NMR (100 MHz, CDCl3): d=151.3, 150.5,
132.2, 131.5, 129.6, 129.4, 129.2, 127.6, 126.3, 126.0, 125.8, 125.6,
123.9, 115.3, 111.8 ppm. IR (KBr): n˜ =1596, 1506, 1356, 1213, 1134,
Acknowledgements
1075, 1012, 833, 802 cmÀ1
. HRMS (APCI-TOF, m/z): calcd for
C18H11BrNO3 [M+H]+ 367.9922, found 367.9917.
We are grateful for financial support from the Fundamental Re-
search Funds for the Central Universities (JH180263), the Post-
graduate Research & Practice Innovation Program of Jiangsu
Province (No. KYCX19_2136) and Postgraduate Research &
Practice Innovation Program of China University of Mining and
Technology (No. KYCX19_2136).
1-nitro-2-(thiophen-2-yl)naphtho[2,1-b]furan (2o)
Light yellow solid, 48 mg, 81% yield; mp 163–1658C. 1H NMR
(400 MHz, CDCl3): d=8.63 (d, J=8.4 Hz, 1H), 8.13–8.08 (m, 1H),
7.97 (d, J=8.0 Hz, 1H), 7.88 (d, J=9.2 Hz, 1H), 7.70–7.62 (m, 3H),
7.61–7.55 (m, 1H), 7.26–7.23 ppm (m, 1H). 13C NMR (100 MHz,
CDCl3): d=150.1, 150.1, 131.7, 131.7, 131.6, 129.3, 129.3, 128.9,
128.2, 127.4, 126.0, 125.9, 125.0, 115.2, 111.6 ppm. IR (KBr): n˜ =
1556, 1493, 1419, 1360, 1224, 1123, 1056, 806 cmÀ1. HRMS (APCI-
TOF, m/z): calcd for C16H10NO3S [M+H]+ 296.0381, found 296.0385.
Conflict of interest
The authors declare no conflict of interest.
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Keywords: annulation · benzofurans · difunctionalization of
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Manuscript received: October 5, 2019
Revised manuscript received: November 3, 2019
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FULL PAPER
Tian-Shu Zhang, Lei Yang, Pei-Jun Cai,*
Shu-Jiang Tu, Bo Jiang*
&& – &&
Silver-Catalyzed Nitration/Annulation
of a-Alkynyl Arylols toward 3-Nitrated
Benzofurans
A silver-catalyzed NO2 radical-trig-
gered nitration/annulation of a-alkynyl
arylols is reported by using tert-butyl ni-
trite (TBN), and a set of 3-nitrated ben-
zofurans were synthesized in moderate
to good yields. The control experiments
suggested that this transformation in-
volved NO2 radical addition, 1,5-HAT, 5-
endo-trig cyclization and H-abstraction,
thus providing a direct pathway for the
formation of 3-nitrobenzofurans via cat-
alytic difunctionalization of internal al-
kynes.
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