NIS-Induced Enone Difunctionalization for the Synthesis of Naphtho[2,3-b]furan-4,9-diones

Article abstract of DOI:10.1002/ejoc.201601291

An efficient synthesis of naphtho[2,3-b]furan-4,9-diones has been developed by N-iodosuccinimide (NIS)-induced enone difunctionalization with 2-hydroxy-1,4-naphthoquinones. This reaction involved sequential Michael addition, intramolecular oxidative cycli

Full text of DOI:10.1002/ejoc.201601291

A Journal of
Accepted Article
Title: NIS-Induced Enones Difunctionalization for the Synthesis of
Naphtho[2,3-b]furan-4,9-diones
Authors: Yun Liu, Wenhui Ge, Youquan Zhu, Huayou Hu, Hui Fan,
Yanhui Shi, and Hui Wu
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
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content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601291
Link to VoR: http://dx.doi.org/10.1002/ejoc.201601291
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10.1002/ejoc.201601291
European Journal of Organic Chemistry
PER
uced Enones Difunctionalization for the Synthesis of
o[2,3-b]furan-4,9-diones
Wen-Hui Ge,[a] You-Quan Zhu,[b] Hua-You Hu,[c] Hui Fan,[a] Yan-Hui Shi[a] and Hui Wu*[a]
ficient synthesis of naphtho[2,3-b]furan-4,9-diones
oped via N-Iodosuccinimide (NIS)-induced enones
with alkenes or alkynes;13 three-component reaction with
aromatic aldehydes and pyridinium salt;14 or with isocyanides
and aldehydes;15 and domino reaction with β-nitrostyrenes.16
However, there are some shortcomings associated with these
methods such as limited substituent scope, not easily available
substrates, or low yields. Therefore, it is still highly desirable to
develop more convenient synthetic protocols for the preparation
of diverse naphtho[2,3-b]furan-4,9-diones from 2-hydroxy-1,4-
naphthoquinone.
n
reaction with 2-hydroxy-1,4-naphthoquinones.
volved sequential Michael addition, intramolecular
ion and dehydrogenative aromatization to form new
nds at α- and β-position of enones. Various enones
the reaction conditions and the corresponding
btained in moderate to excellent yields.
O
O
OMe
(1) CAN
(2) DBU
O
ref. 12
ref. 13
ref. 14
+
+
n
OH
OH
OH
O
OMe
O
O
O
R1
O
O
R1
R2
curring quinones constitute an important class of
s.1,2 As annulated quinones, naphtho[2,3-b]furan-
e been found in many natural plants.3 For
pounds A, B and C were isolated from Tabebuia
cheme 1).3a-3c Furthermore, naphtho[2,3-b]furan-
e exhibited significant biological activities, such
antitumoral,5 antiproliferative,6 trypanocidal,7 and
wth of human keratinocyte.8 Consequently, the
naphtho[2,3-b]furan-4,9-dione derivatives have
ention in the past decades.9-17
(1) hv, acetone, N2
(2) air
R1
O
O
O
O
O
Ar
NHH4OAc, H2O
1000oC, 10h
O
COAr1
+
ArCHO
RCHO
+
N
Ar1
O
O
O
O
R
O
Toluenee
reflux
NHR1
R1
N C
ref. 15
ref. 16
+
+
OH
O
O
O
O
O
R
OH
O
O
NO2
NH4OAc
H2O, 100oC
NH2
+
OH
R
O
O
O
O
OH
OH
O
O
O
B
C
Scheme 2 Previous routes to naphtho[22,3-b]furan-4,9-diones from 2-hydroxy-
1,4-naphthoquinone
les of natural products bearing naphtho[2,3-b]furan-4,9-
Iodine or low valent iodine(I)-promoted C-H oxidative
coupling in tandem reaction has been reported as an effective
approach for the construction of heterocyclic compounds.18-19
Recently, Gao uncovered the synthesis of 2,3-dihydropyrroles
by I2-mediated reaction of chalcones with enamine ketones;19a
Park developed a mild synthesis of 3-arylimidazo[1,2-a]pyridines
via NIS-oxidation;19b and Huang described I2‑mediated oxidative
cyclization for the synthesis of indolizines.19c From our own
interest in iodine and N-iodosuccinimide (NIS)-mediated reaction,
herein, we report an effective synthesis of naphtho[2,3-b]furan-
4,9-diones via NIS-induced difunctionalization reaction of
enones with 2-hydroxy-1,4-naphthoquinones.
4-naphthoquinone is an important precursor for
uran-4,9-diones synthesis. As shown in Scheme
nthetic protocols include CAN-mediated oxidative
th special alkene;12 photochemical cycloaddition
[a]
Yun Liu, Wen-Hui Ge, Jun-Wen Han, Hui Fan, and Hui Wu
Jiangsu Key Laboratory of Green Synthetic for Functional Materials
School of Chemistry and Chemical Engineering, and School of
Mechanical and Electrical Engineering, Jiangsu Normal University,
Xuzhou 221116, Jiangsu, P. R. China
E-mail: liu__yun3@sina.com; wuhui1972@126.com
http://202.195.67.55/chemcourse/Teacher.aspx?id=87
You-Quan Zhu
[b]
[c]
State Key Laboratory of Elemento-Organic Chemistry, Nankai
University, Tianjin, 300071, P. R. China
Hua-You Hu
Results and Discussion
The reaction of 2-hydroxy-1,4-naphthoquinone 1a with
chalcone 2a was studied initially. To our delight, by heating the
mixture of 1a (0.5 mmol) and 2a (0.5 mmol), NIS (0.5 mmol) and
Et3N (1.0 equiv) in acetonitrile at 100 C for 12 h, we obtained
3a in 48% yield (entry 1 in Table1).
Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials,
School of Chemistry and Chemical Engineering, Huaiyin Normal
University, Huaian 223300, Jiangsu, P. R. China
o
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejoc.201601291
European Journal of Organic Chemistry
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n of reaction conditions[a]
O
O
PPh
O
Ph
O
Ph
COPh
additive
OH
+
COPh
+
COPh
1a
2a
O
+
base, solvent
100 oC, 12 h
OOH
O
O
O
O
Ph
O
COPh
5
3a
4
Additive (equiv)
Solvent
Base (equiv)
2a
3a
4
5
(% conversion)
(% yield)[b]
48
38
43
0
(%% yield)[b]
(% yield)[b]
NIS (1)
NIS (0.5)
NIS (1.5)
none
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Dioxane
benzene
DMF
Et3N (2)
55
53
56
52
52
54
0
0.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
288
0
0
Et3N (2)
trace
Et3N (2)
0
Et3N (2)
45
I2 (1)
Et3N (2)
42
46
0
0
ICl (1)
Et3N (2)
0
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
NIS (1)
none
0
K2CO3 (2)
Cs2CO3 (2)
Pyridine (2)
DABCO (2)
DABCO (2.5)
DABCO (1.5)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
DABCO (2)
8
0
trace
10
54
66
68
50
33
28
41
32
10
90
91
91
88
87
17
0
trace
46
59
59
36,
26
22
33
25
trace
78
78
77
23
51
0
0
0
0
trace
0
0
0
C2H5OH
DCE
0
0
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
0
0
0
51
0
10
o
ons: 1a (0.5 mmol), 2a (0.5 mmol), additive, base, solvent (5 mL), sealed tube, 100 C, 12 h. [b] Isolateed yields based on added 2a. [c] 0.75
mmol of 1a. [e] Under O2. [f] Under N2. [g] 80 oC. [h] 60 oC.
o
o
this promising result, we began to optimize the
ons (Table 1). It was found the amount of NIS,
e and solvent, the ratio of reactants, as well as
rature all played critical roles on the reaction
his reaction, one equiv of NIS was needed but
e of its amount could not provide better yield
hout NIS, only Michael adduct 5 was generated
iodine or ICl instead of NIS also led to low yields
. Organic bases could promote this reaction, and
ABCO (1,4-diazabicyclo[2.2.2]octane) gave the
hem (entry 7-13). With 2.0 equiv of DABCO as
solvents were screened and acetonitrile was
uperior solvent compared to dioxane, benzene,
and DCE (entry 11, 14-18). For the ratio of
equiv of 1a worked most effectively and the yield
proved to 78% (entry 19-20). Under oxygen
similar yield of 3a was given (entry 21). While
atmosphere, a significant amount of Michael
detected (entry 22). Reducing the reaction
temperature to 80 C or 60 C led to mixture of 3 and 420 or
Michael adduct (entry 23-24). Therefore, the optimal conditions
were set to heating 1a (0.75 mmol), 2a (0.5 mmol) and NIS (0.5
mmol) in acetonitrile at 100 oC for 12 h using DABCO (1.0 mmol)
as base.
With the optimized reaction conditions in hand, the scope of
enone was then surveyed (Table 2). The result showed that a
range of chalcones 2 reacted with 1a smoothly under the optimal
conditions. For instance, chalcones with electron-deficient
groups (F, Cl and Br) on ortho-, meta-, or para-position of Ar2
ring provided the desired products 3b-3g in good to excellent
yields (73-88%). Meanwhile, chalocones with electron-donating
groups (Me, Et and OMe) on Ar2 ring gave the products 3h-3k in
moderate yields (50%-62%). Similarly, for chalcones with
different groups at Ar1 ring, products 3l-3w were formed in 68%
to 85% yields. Using chalcone 2a to react with substituted 2-
hydroxy-1,4-naphthoquinone 1b gave satisfied result as well (3x,
82%). Except for NMR and HRMS, the structure of the products
was further supported by X-ray crystallographic structure of 3q.
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10.1002/ejoc.201601291
European Journal of Organic Chemistry
PER
halcone 2[a,b]
O
O
O
O
O
O
O
Ar1
O
O
O
O
O
NIS (1 equiv)
O
R
O
O
C2H5
O
DABCO (2 equiv)
Ar1
O
COAr2
O
CH3
O
COAr2
O
CH3CN
O
F
7d,
68%
100 oC, 12 h
7c,
66%
7b,
66%
7a, 75%
2
3
O
S
O
O
O
S
O
O
O
O
O
O
O
O
O
O
O
O
O
O
7e,
OCH3
F
7h, 66%
Cl
7g, 63%
O
O
O
O
65%
7f,
62%
O
Br
O
O
O
F
O
O
O
O
O
S
O
O
O
H3CO
O
O
O
O
O
O
Br
F
3d, 73%
Cl
OCH3
3c, 75%
3b, 76%
O
O
O
O
O
O
O
Cl
CH3
7l,
62%
7k, 64%
7i
7j,
58%
61%
O
O
Br
O
O
O
F
O
O
O
Cl
O
O
O
O
Cl
O
H3CO
O
O
O
H3CO
O
O
Cl
CH3
O
O
3f,
3g, 83%
88%
3h, 56%
Cl
F
Cl
7m, 69%
7n, 72%
O
O
O
O
[a] Reaction conditions: 1 (0.75 mmol), 66 (0.5 mmol), NIS (0.5 mmol), DABCO
(1.0 mmol), acetonitrile (5 mL), sealed ttube, 100 oC, 12 h. [b] Isolated yields
based on added 6..
O
O
O
O
O
O
O
O
3j,
55%
C2H5
3l, 71%
3k,
OCH3
50%
To demonstrate the feasibility of this method in practical
organic synthesis, we carried out this reaction on gram scale
(Scheme 3). Heating 1a (7.5 mmol, 1.31 g), 2a (5 mmol, 1.04 g)
under the optimal reaction conditions, 1.34 g of 3a was obtained,
meaning a 71% yield.
Br
NO2
Cl
O
O
O
O
O
O
O
O
O
O
O
O
3p,
68%
3o,
74%
3n,
76%
O
O
Cl
Ph
NIS (1 equiv)
CH3
DABCCOO (2 equiv)
Br
Ph
Cl
COPh
+
OH
O
O
O
COPh
CH 3CN
100 ooC, 12 h
O
O
O
O
O
O
O
O
O
O
3a
1a
2a
1.04 g
O
O
1.34 g, 71%
1.31 g
3s, 79%
3t, 82%
3r,
83%
OCH3
Scheme 3 Gram-scale synthesis
O
O
O
OCH3
H3CO
O
O
O
OO
O
O
O
To shed light on the reaction mechanism, three control
experiments were carried out. Firstly, Michael adduct 5 prepared
under basic condition without NIS could be tansformed
completely under the standard conditions, and 3a was isolated
in 92% yield (Scheme 4a, 4b). This illustrated that 5 was a
possible intermediate of this reaction. Secondly, preparing 4
O
O
3w,
81%
Cl
3x, 82%
3v, 78%
ons: 1 (0.75 mmol), 2 (0.5 mmol), NIS (0.5 mmol), DABCO
itrile (5 mL), sealed tube, 100 oC, 12 h. [b] Isolated yields
o
xtend the utility of this reaction, we then turned
other enones, including benzalacetone, penten-
ryl-, thienyl-, and naphthyl-substituted enones
s observed that various enones 6 participated in
well, forming the corresponding naphtho[2,3-
es 7a-7n in 58%-75% yields.
from 1a and 2a at 80 C (entry 23, Table 1) and then heating 4
with DABCO but without NIS in acetonitrile provided 3a in 98%
yield, which confirmed that NIS is not involved in the
aromatization step (Scheme 4c). Thirdly, mixing chalcone 2a
with NIS and DABCO, no reaction occurred after heating in
o
acetonitrile at 100 C for 12 h (Scheme 4d). This ruled out the
possibility of initial chalcone iodination.
Based on these results and previous literatures,19 a possible
mechanism for this reaction is suggested (Scheme 5). At first,
Michael addition of 2-hydroxy-1,4-naphthoquinone 1a with
chalcone 2a yielded the tautomeric intermediate 5.
Subsequently, in the aid of NIS, 5 was transformed into
iodinated intermediate I. Finally, in the presence of base,
intermediate I underwent intramolecular nucleophilic cyclization
to afford 4, which generated 3a via air oxidation.
ther enone 6[a,b]
R1
O
NIS (1 equiv)
R
DABCO (2 equiv)
R1
COR2
COR2
CH3CN
100 oC, 12 h
O
O
7
6
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10.1002/ejoc.201601291
European Journal of Organic Chemistry
PER
O
Ph
General Procedure for the Preparation of Naphtho[2,3-b]furan-4,9-
COPh
(a)
DABCO (2 equiv)
dione
3 (Table 2): 2-Hydroxy-1,4-naphthoquinone 1 (0.75 mmol),
COPh
CH3CN
chalcone 2 (0.5 mmol), NIS (0.5 mmol), and DABCO (1.0 mmol) were
mixed in 5 mL of CH3CN in a sealed tube and heated at 100 oC for 12 h.
After completion of the reaction, the mixture was cooled to room
temperature and separated by flash column chromatography (ethyl
acetate/hexane) on silica gel to afford product 3.
OH
100 oC, 12 h
O
a (1 equiv)
5 (83%)
O
Ph
NIS (1 equiv)
h
DABCO (2 equiv)
COPh
(b)
CH3CN (5 mL)
100 oC, 12 h
O
O
2-Benzoyl-3-phenylnaphtho[2,3-b]furan-4,9-dione (3a): Yellow solid;
mp 140–142 oC; yield 147 mg, 78%. 11H NMR (400 MHz, CDCl3) δ 7.38–
7.43 (m, 5H), 7.48–7.49 (m, 2H), 7.55 (t, J = 7.6 Hz, 1H), 7.78–7.80 (m,
3a
(92%)
O
Ph
DABCO (2 equiv)
2H), 7.89 (d, J = 8.0 Hz, 2H), 8.16–8.18 (m, 1H), 8.25–8.28 (m, 1H). 13
C
(c)
COPh
Ph
O
CH3CN
100 oC, 12 h
NMR (100 MHz, CDCl3) δ 183.8, 180.0, 174.1, 152.4, 150.5, 135.9,
134.6, 134.1, 133.8, 133.7, 132.3, 132.0, 130.2, 129.9, 129.2, 128.5,
128.2, 128.0, 127.8, 127.4, 126.9. HRMS (ESI) m/z calcd for C25H15O4
[M+H]+ 379.0970, found 379.0966.
O
3a (98%)
NIS (1 equiv)
ABCO (2 equiv)
(d)
no reaction
CH3CN
100 oC, 12 h
2-(4-Fluorobenzoyl)-3-phenylnaphtho[2,3-b]furan-4,9-dione
(3b):
Yellow solid; mp 133–135 oC; yield 151 mg, 76%. 1H NMR (400 MHz,
CDCl3) δ 7.09 (t, J = 8.4 Hz, 2H), 7.39–7.41 (m, 3H), 7.47–7.49 (m, 2H),
7.78–7.81 (m, 2H), 7.94–7.97 (m, 2H), 8.15–8.17 (m, 1H), 8.25–8.27 (m,
1H). 13C NMR (100 MHz, CDCl3) δ 181.7, 179.5, 173.7, 165.6 (d, J = 250
Hz), 152.1, 149.9, 134.2, 133.8, 133.3, 132.3 (d, J = 9 Hz), 131.9, 131.8,
131.7, 129.8, 128.9, 127.7, 127.6, 127.4, 127.0, 126.6, 115.4 (d, J = 22
Hz). HRMS (ESI) m/z calcd for C225H14FO4 [M+H]+ 397.0876, found
397.0870.
experiments
O
Ph
O
Ph
COPh
COPh
COPh
NIS
addition
OH
O
O
O
5
O
O
Ph
O
Ph
2-(4-Chlorobenzoyl)-3-phenylnaphtho[2,3-b]furan-4,9-dione
(3c):
air
Yellow solid; mp 194–195 oC; yield 154 mg, 75%. 1H NMR (400 MHz,
CDCl3) δ 7.38–7.43 (m, 5H), 7.47–7.49 (m, 2H), 7.79–7.81 (m, 2H), 7.86
(d, J = 8.8 Hz, 2H), 8.16–8.18 (m, 1H), 8.26–8.28 (m, 1H). 13C NMR (100
MHz, CDCl3) δ 182.3, 179.7, 174.0, 152.4, 150.1, 140.2, 134.5, 134.2,
134.1, 133.6, 132.3, 132.1, 131.2, 130.6, 130.1, 129.3, 129.2, 128.8,
127.9, 127.7, 127.3, 126.9. HRMS (ESI) m/z calcd for C25H14ClO4 [M+H]+
413.0581, found 413.0569.
ABCOH+
- I-
COPh
COPh
oxidation
O
O
O
O
4
3a
d mechanism
s
2-(4-Bromobenzoyl)-3-phenylnaphtho[2,3-b]furan-4,9-dione
(3d):
Yellow solid; mp 190–192 oC; yield 166 mg, 73%. 1H NMR (400 MHz,
CDCl3) δ 7.41–7.50 (m, 5H), 7.57 (d, J = 8.4 Hz, 2H), 7.78–7.82 (m, 4H),
8.16–8.19 (m, 1H), 8.27–8.29 (m, 1H). 13C NMR (100 MHz, CDCl3) δ
182.6, 179.8, 174.1, 152.5, 150.1, 134.7, 134.6, 134.2, 133.7, 132.5,
132.2, 131.9, 131.3, 130.1, 130.0, 1294, 129.1, 128.1, 128.0, 127.8,
127.4, 127.3, 127.0. HRMS (ESI) m/z calcd for C25H14BrO4 [M+H]+
457.0075, found 457.0077.
we have described an efficient methodology for
of naphtho[2,3-b]furan-4,9-dione derivatives via
ones difunctionalization reaction with 2-hydroxy-
nones. In this reaction process, new C-C and C-
formed in one pot. This synthesis enjoys easy
arting materials, wide substrate scope and mild
ons. A variety of enones tolerated the reaction
the corresponding products were obtained in
cellent yields.
2-(3-Bromobenzoyl)-3-phenylnaphtho[2,3-b]furan-4,9-dione
(3e):
Yellow solid; mp 131–133 oC; yield 180 mg, 79%. 1H NMR (400 MHz,
CDCl3) δ 7.28 (t, J = 8.0 Hz, 1H), 7.39–7.48 (m, 5H), 7.65 (d, J = 8.0 Hz,
1H), 7.80–7.82 (m, 3H), 7.96 (d, J = 1.6 Hz, 1H), 8.17–8.19 (m, 1H),
8.27–8.29 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 182.3, 179.8, 174.0,
152.6, 149.8, 137.5, 136.4, 134.6, 134.1, 133.7, 132.7, 132.5, 132.2,
130.1, 130.0, 129.3, 128.3, 128.0, 127.9, 127.7, 127.3, 126.9, 122.6.
HRMS (ESI) m/z calcd for C25H14BrO44 [M+H]+ 457.0075, found 457.0083.
al Section
points are uncorrected. 1H NMR spectra were
MHz with CDCl3 as solvent. The chemical shifts (δ) are
per million relative to the residual deuterated solvent
ng constants (J) are given in Hertz. 13C NMR spectra
n 100 MHz with CDCl3 as solvent. HRMS (ESI) data
he electron impact (EI) mode. All reagents and solvent
ed commercially and used without further purification
otherwise. Chalcones 2, furyl-, thienyl-, or naphthyl-
s 6, and 2-hydroxy-6-methoxy-1,4-naphthoquinone 1b
cording to literature 21 and 22.
2-(3,4-Dichlorobenzoyl)-3-phenylnaphtho[2,3-b]furan-4,9-dione (3f):
Yellow solid; mp 210–212 oC; yield 196 mg, 88%. 1H NMR (400 MHz,
CDCl3) δ 7.41–7.50 (m, 6H), 7.75 (dd, J = 8.4, 2.0 Hz, 1H), 7.80–7.82 (m,
2H), 7.95 (d, J = 2.0 Hz, 1H), 8.16–8.18 (m, 1H), 8.27–8.29 (m, 1H). 13
C
NMR (100 MHz, CDCl3) δ 181.2, 179.7, 174.0, 152.6, 149.6, 138.3,
135.4, 134.6, 134.2, 133.7, 133.2, 132.9, 132.2, 131.7, 130.6, 130.0,
129.4, 128.7, 128.0, 127.8, 127.7, 127.4, 127.0. HRMS (ESI) m/z calcd
for C25H13Cl2O4 [M+H]+ 447.0191, found 447.0197.
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10.1002/ejoc.201601291
European Journal of Organic Chemistry
PER
oyl)-3-(4-methoxyphenyl)naphtho[2,3-b]furan-4,9-
8.25–8.28 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 183.6, 180.0, 174.0,
152.4, 150.5, 135.8, 135.4, 134.6, 134.2, 133.9, 133.6, 132.2, 131.6,
130.9, 130.0, 128.7, 128.3, 127.7, 127.4, 127.0, 126.6. HRMS (ESI) m/z
calcd for C25H14ClO4 [M+H]+ 413.0581, found 413.0569.
w solid; mp 185–187 oC; yield 183 mg, 83%. 1H NMR
δ 3.83 (s, 3H), 6.86 (d, J = 8.8 Hz, 2H), 7.29 (t, J = 7.2
J = 7.2, 0.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 3H), 7.77–7.80
7 (m, 1H), 8.24–8.26 (m, 1H). 13C NMR (100 MHz,
80.0, 174.1, 160.3, 152.9, 149.9, 136.9, 134.5, 134.1,
2.5, 132.3, 132.1, 131.7, 130.2, 130.1, 127.9, 127.3,
.5, 113.3, 55.3. HRMS (ESI) m/z calcd for C26H16ClO5
found 443.0679.
2-(4-Chlorobenzoyl)-3-(4-chlorophenyl)naphtho[2,3-b]furan-4,9-
dione (3n): Yellow solid; mp 225–226 oC; yield 169 mg, 76%. 1H NMR
(400 MHz, CDCl3) δ 7.40–7.48 (m, 6H), 7.81–7.83 (m, 2H), 7.93 (dd, J =
6.8, 1.6 Hz, 2H), 8.16–8.19 (m, 1H), 8.26–8.29 (m, 1H). 13C NMR (100
MHz, CDCl3) δ 182.0, 179.8, 173.9, 152.3, 150.0, 140.5, 135.5, 134.7,
134.2, 134.1, 133.6, 132.1, 131.5, 131.3, 130.7, 129.5, 129.4, 129.0,
128.3, 127.4, 127.0, 126.4. HRMS (ESI) m/z calcd for C25H13Cl2O4
[M+H]+ 447.0191, found 447.0191.
oyl)-3-phenylnaphtho[2,3-b]furan-4,9-dione
(3h):
178–180 oC; yield 110 mg, 56%. 1H NMR (400 MHz,
3H), 7.22 (d, J = 8.0 Hz, 2H), 7.39–7.42 (m, 3H), 7.49–
8–7.84 (m, 4H), 8.16–8.18 (m, 1H), 8.25–8.28 (m, 1H).
Hz, CDCl3) δ 183.4, 180.0, 174.1, 152.3, 150.8, 144.9,
3.8, 133.4, 132.3, 131.5, 130.2, 129.3, 129.1, 128.3,
7.3, 126.9, 21.8. HRMS (ESI) m/z calcd for C26H17O4
found 393.1136.
2-Benzoyl-3-(4-bromophenyl)naphtho[2,3-b]furan-4,9-dione
(3o):
Yellow solid; mp 244–246 oC; yield 168 mg, 74%. 1H NMR (400 MHz,
CDCl3) δ 7.39 (d, J = 8.4 Hz, 2H), 7.47 (t, J = 8.0 Hz, 2H), 7.54 (d, J = 8.4
Hz, 2H), 7.61 (t, J = 7.6 Hz, 1H), 7.80–7.82 (m, 2H), 7.94 (d, J = 8.0 Hz,
2H), 8.16–8.19 (m, 1H), 8.26–8.29 (m, 1H). 13C NMR (100 MHz, CDCl3)
δ 182.6, 179.8, 174.1, 152.5, 150.1, 134.7, 134.2, 133.7, 132.5, 132.2,
131.9, 131.3, 130.1, 129.4, 1291.1, 128.0, 127.9, 127.8, 127.4, 127.0.
HRMS (ESI) m/z calcd for C25H14BrO44 [M+H]+ 457.0075, found 457.0079.
yl)-2-(4-methylbenzoyl)naphtho[2,3-b]furan-4,9-
w solid; mp 215-216 oC; yield 127 mg, 62%. 1H NMR
δ 2.42 (s, 3H), 7.10 (t, J = 8.8 Hz, 2H), 7.25 (d, J = 7.6
3 (m, 2H), 7.80–7.85 (m, 4H), 8.17–8.19 (m, 1H), 8.26–
NMR (100 MHz, CDCl3) δ 183.2, 180.1, 174.0, 163.1 (d,
2, 150.8, 145.0, 134.5, 134.1, 133.7, 133.2, 132.2 (d, J
0.1, 129.3, 127.7, 127.3, 126.9, 124.1, 115.1 (d, J = 22
(ESI) m/z calcd for C26H16FO4 [M+H]+ 411.1033, found
2-Benzoyl-3-(4-nitrophenyl)naphtho[2,3-b]furan-4,9-dione
(3p):
Yellow solid; mp 234–236 oC; yield 143 mg, 68%. 1H NMR (400 MHz,
CDCl3) δ 7.50 (t, J = 8.0 Hz, 2H), 7.64 (t, J = 7.6 Hz, 1H), 7.70 (d, J = 8.8
Hz, 2H), 7.82–7.84 (m, 2H), 7.99 (d, J = 7.2 Hz, 2H), 8.15–8.18 (m, 1H),
8.27–8.30 (m, 3H). 13C NMR (100 MHz, CDCl3) δ 182.6, 179.3, 173.4,
151.9, 150.3, 147.6, 135.0, 134.8, 134.3, 134.0, 133.8, 133.0, 131.7,
130.8, 129.5, 129.4, 128.4, 127.1, 127.0, 126.6. 122.7. HRMS (ESI) m/z
calcd for C25H14NO6 [M+H]+ 424.0821, found 424.0828.
l)-3-(4-chlorophenyl)naphtho[2,3-b]furan-4,9-dione
mp 195–196 oC; yield 121 mg, 55%. 1H NMR (400 MHz,
J = 7.6 Hz, 3H), 2.71 (q, J = 7.6 Hz, 2H), 7.27 (d, J = 8.0
J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.79–7.81 (m,
2-Benzoyl-3-(3-fluorophenyl)naphtho[2,3-b]furan-4,9-dione
(3q):
8.4 Hz, 2H), 8.16–8.18 (m, 1H), 8.26–8.28 (m, 1H). 13
C
Yellow solid; mp 202–204 oC; yield 158 mg, 80%. 1H NMR (400 MHz,
CDCl3) δ 7.13 (td, J = 8.0, 1.6 Hz, 1H), 7.24–7.28 (m, 2H), 7.35–7.41 (m,
1H), 7.47 (t, J = 7.6 Hz, 2H), 7.61 (t, J = 7.2 Hz, 1H), 7.81–7.85 (m, 2H),
7.94 (d, J = 7.6 Hz, 2H), 8.18–8.21 (m, 1H), 8.28–8.30 (m, 1H). 13C NMR
(100 MHz, CDCl3) δ 183.5, 179.8, 174.0, 162.2 (d, J = 250 Hz), 152.3,
150.7, 135.8, 134.6, 134.2, 133.9, 133.6, 132.2, 130.5, 130.4, 130.2 (d, J
= 9 Hz), 129.9, 129.4 (d, J = 8 Hz), 128.6, 127.7, 127.4, 127.0, 125.9 (d,
J = 3 Hz), 117.3 (d, J = 23 Hz), 116.1 (d, J = 21 Hz). HRMS (ESI) m/z
calcd for C25H14FO4 [M+H]+ 397.0876, found 397.0865.
CDCl3) δ 183.2, 180.0, 174.0, 152.2, 151.2, 150.9,
4.2, 133.6, 133.4, 132.2, 131.6, 130.5, 130.2, 128.2,
.3, 126.9, 126.7, 29.1, 15.2. HRMS (ESI) m/z calcd for
+ 441.0894, found 441.0890.
yl)-2-(4-methoxybenzoyl)naphtho[2,3-b]furan-4,9-
w solid; mp 219–220 oC; yield 111 mg, 50%. 1H NMR
δ 3.89 (s, 3H), 6.94 (d, J = 8.8 Hz, 2H), 7.39 (d, J = 8.4
J = 8.4 Hz, 2H), 7.80–7.82 (m, 2H), 7.98 (d, J = 8.8 Hz,
m, 1H), 8.26–8.28 (m, 1H). 13C NMR (100 MHz, CDCl3)
74.0, 164.4, 152.1, 151.1, 135.2, 134.5, 134.1, 133.7,
1.5, 130.1, 128.6, 128.2, 127.7, 127.3, 126.9, 114.0,
I) m/z calcd for C26H16ClO5 [M+H]+ 443.0686, found
2-Benzoyl-3-(3-chlorophenyl)naphtho[2,3-b]furan-4,9-dione
(3r):
Yellow solid; mp 144–146 oC; yield 171 mg, 83%. 1H NMR (400 MHz,
CDCl3) δ 7.34–7.40 (m, 3H), 7.44–7.49 (m, 3H), 7.59 (t, J = 7.2 Hz, 1H),
7.80–7.82 (m, 2H), 7.93 (d, J = 8.4 Hz, 2H), 8.17–8.19 (m, 1H), 8.26–
8.28 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 183.5, 179.8, 174.0, 152.3,
150.7, 135.8, 134.7, 134.3, 133.9, 133.8, 133.6, 132.2, 130.5, 130.2,
130.0, 129.9, 129.3, 129.2, 128.7, 128.4, 127.7, 127.4, 127.0. HRMS
(ESI) m/z calcd for C25H14ClO4 [M+H]++ 413.0581, found 413.0579.
uorophenyl)naphtho[2,3-b]furan-4,9-dione
(3l):
166–167 oC; yield 140 mg, 71%. 1H NMR (400 MHz,
J = 8.8 Hz, 2H), 7.40–7.49 (m, 5H), 7.79–7.81 (m, 2H),
), 8.15–8.18 (m, 1H), 8.25–8.28 (m, 1H). 13C NMR (100
3.7, 180.0, 174.1, 163.0 (d, J = 250 Hz), 152.4, 150.5,
4.2, 133.9, 133.7, 132.3, 132.2 (d, J = 9 Hz), 131.1,
.5 (d, J = 26 Hz), 127.0, 124.1, 124.0, 115.1 (d, J = 22
) m/z calcd for C25H14FO4 [M+H]+ 397.0876, found
2-Benzoyl-3-(3-bromophenyl)naphtho[2,3-b]furan-4,9-dione
(3s):
Yellow solid; mp 179–181 oC; yield 180 mg, 79%. 1H NMR (400 MHz,
CDCl3) δ 7.28 (t, J = 8.0 Hz, 1H), 7.45 (t, J = 8.0 Hz, 3H), 7.52–7.64 (m,
3H), 7.80–7.82 (m, 2H), 7.92 (dd, J = 8.4, 1.2 Hz, 2H), 8.16–8.19 (m, 1H),
8.26–8.28 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 183.7, 180.1, 174.2,
152.6, 150.9, 136.0, 134.9, 134.5, 134.2, 133.9, 133.3, 132.5, 132.4,
130.6, 130.5, 130.2, 129.7, 129.2, 129.1, 128.9, 127.9, 127.7, 127.3,
122.1. HRMS (ESI) m/z calcd for C225H14BrO4 [M+H]+ 457.0075, found
457.0070.
hlorophenyl)naphtho[2,3-b]furan-4,9-dione
(3m):
240–242 oC; yield 151 mg, 73%. 1H NMR (400 MHz,
J = 8.0 Hz, 2H), 7.45–7.47 (m, 4H), 7.60 (t, J = 7.6 Hz,
m, 2H), 7.93 (d, J = 7.6 Hz, 2H), 8.16–8.18 (m, 1H),
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601291
European Journal of Organic Chemistry
PER
ylnaphtho[2,3-b]furan-4,9-dione (3t): Yellow solid;
2-Propionylnaphtho[2,3-b]furan-4,9-dione (7b): Red solid; mp 189–
191 oC; yield 84 mg, 66%. 1H NMR (400 MHz, CDCl3) δ 1.26 (t, J = 7.2
Hz, 3H), 3.06 (q, J = 7.2 Hz, 2H), 7.61 (s, 1H), 7.80–7.82 (m, 2H), 8.22–
8.27 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 190.8, 179.8, 173.9, 155.4,
152.7, 134.4, 134.3, 133.1, 132.6, 130.7, 127.3, 127.2, 111.9, 32.6, 7.4.
HRMS (ESI) m/z calcd for C15H11O4 [M+H]+ 255.0657, found 255.0661.
ield 161 mg, 82%. 1H NMR (400 MHz, CDCl3) δ 2.39 (s,
8.0 Hz, 2H), 7.39–7.45 (m, 4H), 7.57 (t, J = 7.2 Hz, 1H),
), 7.92 (dd, J = 8.8, 1.6 Hz, 2H), 8.17–8.19 (m, 1H),
). 13C NMR (100 MHz, CDCl3) δ 184.1, 180.3, 174.4,
9.5, 136.3, 134.8, 134.3, 134.1, 133.9, 132.6, 130.3,
9.3, 129.0, 128.8, 127.8, 127.6, 127.2, 125.4, 21.8.
calcd for C26H17O4 [M+H]+ 393.1127, found 393.1118.
2-Benzoyl-3-(furan-2-yl)naphtho[2,3-b]furan-4,9-dione (7c): Red solid;
o
mp 167–169 C; yield 122 mg, 66%. 11H NMR (400 MHz, CDCl3) δ 6.50–
oyl)-3-p-tolylnaphtho[2,3-b]furan-4,9-dione
(3u):
6.52 (m, 1H), 7.32 (d, J = 1.6 Hz, 1H), 7.47 (t, J = 8.0 Hz, 2H), 7.52 (d, J
= 3.2 Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.82–7.84 (m, 2H), 7.90 (d, J = 7.6
Hz, 2H), 8.26–8.28 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 184.3, 179.6,
173.8, 152.6, 150.0, 143.8, 142.1, 136.1, 134.5, 134.0, 133.8, 133.7,
132.0, 129.7, 128.6, 127.4, 126.9, 126.2, 119.6, 115.3, 111.8. HRMS
(ESI) m/z calcd for C23H13O5 [M+H]+ 369.0763, found 369.0752.
232–234 oC; yield 182 mg, 85%. 1H NMR (400 MHz,
3H), 7.21 (d, J = 8.0 Hz, 2H), 7.39 (t, J = 8.0 Hz, 4H),
), 7.87 (d, J = 8.4 Hz, 2H), 8.15–8.18 (m, 1H), 8.25–
NMR (100 MHz, CDCl3) δ 182.3, 179.7, 174.0, 152.3,
9.3, 134.5, 134.2, 134.0, 133.6, 132.5, 132.1, 131.2,
6, 127.7, 127.4, 127.3, 126.8, 124.8, 21.4. HRMS (ESI)
16ClO4 [M+H]+ 427.0737, found 427.0739.
2-(4-Fluorobenzoyl)-3-(furan-2-yl)naphtho[2,3-b]furan-4,9-dione (7d):
Red solid; mp 190–191 oC; yield 132 mg, 68%. 1H NMR (400 MHz,
CDCl3) δ 6.52–6.53 (m, 1H), 7.15 (t, J = 8.4 Hz, 2H), 7.34 (s, 1H), 7.52 (d,
J = 3.2 Hz, 1H), 7.81–7.83 (m, 2H), 7.94–7.97 (m, 2H), 8.25–8.27 (m,
2H). 13C NMR (100 MHz, CDCl3) δ 182.6, 179.5, 173.8, 166.1 (d, J = 255
Hz), 152.7, 149.6, 143.9, 142.0, 134.6, 134.1, 133.7, 132.6 (d, J = 2.9
Hz), 132.4 (d, J = 10 Hz), 131.9, 127.5, 126.9, 126.2, 119.8, 115.9 (d, J =
22 Hz), 115.5, 111.9. HRMS (ESI) m/z calcd for C23H12FO5 [M+H]+
387.0669, found 387.0672.
ethoxyphenyl)naphtho[2,3-b]furan-4,9-dione (3v):
164–165 oC; yield 159 mg, 78%. 1H NMR (400 MHz,
3H), 6.92 (d, J = 8.8 Hz, 2H), 7.41–7.48 (m, 4H), 7.56 (t,
7.79–7.81 (m, 2H), 7.90 (d, J = 8.0 Hz, 2H), 8.18–8.20
8 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 183.9, 180.1,
2.4, 150.3, 136.1, 134.5, 134.0, 133.8, 133.6, 132.3,
9.9, 128.6, 128.5, 127.7, 127.3, 126.9, 120.0, 113.4,
I) m/z calcd for C26H17O5 [M+H]+ 409.1076, found
2-(4-Chlorobenzoyl)-3-(furan-2-yl)naphtho[2,3-b]furan-4,9-dione (7e):
Red solid; mp 177–179 oC; yield 130 mg, 65%. 1H NMR (400 MHz,
CDCl3) δ 6.53–6.54 (m, 1H), 7.34 (s, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.54
(d, J = 3.6 Hz, 1H), 7.81–7.84 (m, 2H), 7.86 (d, J = 8.8 Hz, 2H), 8.25–
8.27 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 183.0, 179.5, 173.8, 152.7,
149.5, 143.9, 142.0, 140.4, 134.6, 134.5, 134.1, 133.7, 131.9, 131.0,
129.0, 127.5, 126.9, 115.6, 112.0. HMRS (ESI) m/z calcd for C23H12ClO5
[M+H]+ 403.0373, found 403.0381.
nyl)-2-(4-chlorobenzoyl)naphtho[2,3-b]furan-4,9-
w solid; mp 178 mg, 85–86 oC; yield 81%. 1H NMR (400
63 (s, 3H), 6.85 (d, J = 8.8 Hz, 1H), 7.01 (t, J = 7.2 Hz,
, 4H), 7.78–7.84 (m, 4H), 8.14–8.16 (m, 1H), 8.26–8.28
(100 MHz, CDCl3) δ 182.5, 179.7, 174.0, 156.5, 152.5,
4.4, 134.2, 133.9, 133.7, 132.3, 131.3, 130.9, 130.8,
4, 127.2, 126.9, 120.3, 117.5, 110.6, 55.2. HRMS (ESI)
16ClO5 [M+H]+ 443.0686, found 443.0691.
3-(Furan-2-yl)-2-(4-methoxybenzoyl)naphtho[2,3-b]furan-4,9-dione
(7f): Red solid; mp 60–62 oC; yield 123 mg, 62%. 1H NMR (400 MHz,
CDCl3) δ 3.89 (s, 3H), 6.50–6.51 (m, 1H), 6.94 (d, J = 8.8 Hz, 2H), 7.36
(s, 1H), 7.50 (d, J = 3.6 Hz, 1H), 7.79–7.81 (m, 2H), 7.92 (d, J = 8.4 Hz,
2H), 8.23–8.25 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 182.7, 179.6,
173.8, 164.3, 152.3, 150.5, 143.7, 142.3, 134.4, 134.0, 133.7, 132.3,
132.0, 129.0, 127.4, 126.8, 126.2, 118.8, 115.0, 114.0, 111.7, 55.6.
HMRS (ESI) m/z calcd for C24H15O6 [M+H]+ 399.0869, found 399.0876.
hoxy-3-phenylnaphtho[2,3-b]furan-4,9-dione
(3x):
182–184 oC; yield 167 mg, 82%. 1H NMR (400 MHz,
3H), 7.22 (dd, J = 8.4, 2.4 Hz, 1H), 7.38–7.43 (m, 5H),
, 7.55 (t, J = 7.6 Hz, 1H), 7.61 (d, J = 2.8 Hz, 1H), 7.90
), 8.20 (d, J = 7.6 Hz, 1H). 13C NMR (100 MHz, CDCl3)
73.3, 164.7, 152.9, 150.2, 136.1, 136.0, 133.6, 132.0,
9.4, 129.1, 128.5, 128.3, 127.9, 127.6, 127.5, 125.6,
. HRMS (ESI) m/z calcd for C26H17O5 [M+H]+ 409.1076,
2-Benzoyl-3-(thiophen-2-yl)naphtho[2,3-b]furan-4,9-dione (7g): Red
1
solid; mp 150–152 oC; yield 121 mg, 63%. H NMR (400 MHz, CDCl3) δ
7.06 (t, J = 8.0 Hz, 1H), 7.43–7.47 (m, 3H), 7.52 (d, J = 3.6 Hz, 1H), 7.59
(t, J = 7.6 Hz, 1H), 7.80–7.82 (m, 2H), 7.91 (d, J = 7.6 Hz, 2H), 8.21–8.23
(m, 1H), 8.25–8.27 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 183.8, 179.7,
174.0, 152.4, 150.6, 135.9, 134.6, 134.1, 133.9, 133.8, 132.0, 131.8,
129.9, 128.6, 128.5, 127.6, 127.5, 127.4, 126.9, 126.8, 124.5. HRMS
(ESI) m/z calcd for C23H13O4S [M+H]+ 385.0535, found 385.0539.
ure for the Preparation of Naphtho[2,3-b]furan-4,9-
3): 2-Hydroxy-1,4-naphthoquinones 1 (0.75 mmol),
ol), NIS (0.5 mmol), and DABCO (1.0 mmol) were mixed
o
N in a sealed tube and heated at 100 C for 12 h. After
reaction, the mixture was cooled to room temperature
flash column chromatography (ethyl acetate/hexane)
ord product 7.
2-(4-Fluorobenzoyl)-3-(thiophen-2-yl)naphtho[2,3-b]furan-4,9-dione
(7h): Red solid; mp 125–127 oC; yield 133 mg, 66%. 1H NMR (400 MHz,
CDCl3) δ 7.07–7.15 (m, 3H), 7.48 (d, J = 5.2 Hz, 1H), 7.52 (d, J = 3.6 Hz,
1H), 7.81–7.83 (m, 2H), 7.96–7.99 (m, 2H), 8.22–8.24 (m, 1H), 8.26–8.28
(m, 1H). 13C NMR (100 MHz, CDCl3) δ 182.1, 179.7, 173.9, 166.1 (d, J =
255 Hz), 152.4, 150.3, 134.6, 134.1, 133.8, 132.6 (d, J = 10 Hz), 132.3,
132.2, 132.0, 131.9, 128.7, 127.5, 127.4, 127.3, 126.9, 126.8, 124.7,
115.9 (d, J = 22 Hz). HRMS (ESI) m/z calcd for C23H12FO4S [M+H]+
403.0440, found 403.0449.
lnaphtho[2,3-b]furan-4,9-dione (7a): Yellow solid; mp
118 mg, 75%. 1H NMR (400 MHz, CDCl3) δ 2.56 (s,
7.78–7.80 (m, 2H), 8.13–8.15 (m, 1H), 8.25–8.28 (m,
00 MHz, CDCl3) δ 188.0, 179.8, 174.2, 152.0, 149.9,
3.7, 132.2, 130.8, 129.9, 129.4, 128.0, 127.9, 127.3,
S (ESI) m/z calcd for C20H13O4 [M+H]+ 317.0814, found
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601291
European Journal of Organic Chemistry
PER
oyl)-3-(thiophen-2-yl)naphtho[2,3-b]furan-4,9-dione
Procedure for the Preparation of 4: 2-Hydroxy-1,4-naphthoquinone 1a
(0.75 mmol), chalcone 2a (0.5 mmol), NIS (0.5 mmol), and DABCO (1.0
mmol) were mixed in 5 mL of CH3CN in a sealed tube and heated at 80
oC for 12 h. After completion of the reaction, the mixture was cooled to
room temperature and separated by flash column chromatography (ethyl
acetate/hexane) on silica gel to afford product 4.
1
p 157–159 oC; yield 115 mg, 58%. H NMR (400 MHz,
3H), 7.07 (t, J = 4.8 Hz, 1H), 7.25 (d, J = 8.0 Hz, 2H),
Hz, 1H), 7.53 (d, J = 3.6 Hz, 1H), 7.79–7.84 (m, 4H),
), 8.25–8.27 (m, 1H). 13C NMR (100 MHz, CDCl3) δ
4.0, 152.3, 150.9, 145.1, 134.5, 134.1, 133.8, 133.3,
0.1, 129.4, 128.5, 127.6, 127.4, 126.9, 124.0, 21.8.
calcd for C24H15O4S [M+H]+ 399.0691, found 399.0681.
trans-2-Benzoyl-3-phenyl-2,3-dihydronaphtho[2,3-b]furan-4,9-dione
(4): Yellow solid; mp 168–170 oC; yield 54 mg, 28%. 1H NMR (400 MHz,
CDCl3) δ 4.96 (d, J = 5.2 Hz, 1H), 6.08 (d, J = 5.2 Hz, 1H), 7.33–7.41 (m,
5H), 7.49 (t, J = 8.0 Hz, 2H), 7.64 (t, J = 7.2 Hz, 1H), 7.68–7.70 (m, 2H),
7.93 (d, J = 7.2 Hz, 2H), 7.95–7.97 (m, 1H), 8.12–8.14 (m, 1H). 13C NMR
(100 MHz, CDCl3) δ 191.7, 181.2, 177.6, 159.2, 139.3, 134.5, 134.4,
133.2, 132.9, 131.7, 129.4, 129.3, 129.1, 128.3, 127.7, 126.4, 126.3,
126.2, 91.5, 49.6. HRMS (ESI) m/z calcd for C25H17O4 [M+H]+ 381.1127,
found 381.1128.
3-(4-bromophenyl)naphtho[2,3-b]furan-4,9-dione (7j):
194–195 oC; yield 154 mg, 61%. 1H NMR (400 MHz,
J = 8.4 Hz, 2H), 7.52–7.59 (m, 3H), 7.64 (t, J = 7.2 Hz,
, 2H), 7.88–8.00 (m, 4H), 8.18–8.20 (m, 1H), 8.27–8.30
H). 13C NMR (100 MHz, CDCl3) δ 183.3, 180.0, 174.0,
5.8, 134.6, 134.2, 133.7, 133.0, 132.7, 132.2, 131.8,
9.2, 128.7, 127.8, 127.4, 127.2, 127.0, 126.9, 124.7,
SI) m/z calcd for C29H16BrO4 [M+H]+ 507.0232, found
Procedure for the Preparation of 5: 2-Hydroxy-1,4-naphthoquinone 1a
(1.5 mmol), chalcone 2a (1.0 mmol), and DABCO (2.0 mmol) were mixed
in 10 mL of CH3CN in a sealed tube and heated at 100 oC for 12 h. After
completion of the reaction, the mixture was cooled to room temperature
and separated by flash column chromatography (ethyl acetate/hexane)
on silica gel to afford Michael adduct 5.
3-(3-fluorophenyl)naphtho[2,3-b]furan-4,9-dione (7k):
179–180 oC; yield 143 mg, 64%. 1H NMR (400 MHz,
J = 8.0 Hz, 1H), 7.27–7.35 (m, 3H), 7.55 (t, J = 7.2 Hz,
7.6 Hz, 1H), 7.80–7.83 (m, 2H), 7.86–7.99 (m, 4H),
), 8.27–8.30 (m, 1H), 8.48 (s, 1H). 13C NMR (100 MHz,
79.8, 174.0, 162.0 (d, J = 246 Hz), 152.3, 150.9, 135.8,
3.6, 133.0, 132.7, 132.2 (d, J = 3 Hz), 130.4, 129.8,
z), 129.2, 128.6, 127.8, 127.4, 127.0, 126.9, 125.9 (d, J
17.3 (d, J = 23 Hz), 116.1 (d, J = 21 Hz). HMRS (ESI)
16FO4 [M+H]+ 447.1033, found 447.1039.
2-Hydroxy-3-(3-oxo-1,3-diphenylpropyl)naphthalene-1,4-dione
(5):
Yellow solid; mp 138–139 oC; yield 317 mg, 83%. 1H NMR (400 MHz,
CDCl3) δ 3.72 (dd, J = 18.0, 5.6 Hz, 1H), 4.43 (dd, J = 18.0, 10.0 Hz, 1H),
5.16 (dd, J = 10.0, 5.2 Hz, 1H), 7.21 (t, J = 7.2 Hz, 1H), 7.30 (t, J = 7.6
Hz, 2H), 7.44 (t, J = 7.6 Hz, 2H), 7.53–7.65 (m, 5H), 7.72 (t, J = 7.6 Hz,
1H), 7.97–8.03 (m, 3H), 8.10 (d, J = 7.6 Hz, 1H).
oyl)-3-(furan-2-yl)-6-methoxynaphtho[2,3-b]furan-
ed solid; mp 93–95 oC; yield 134 mg, 62%. 1H NMR
) δ 3.99 (s, 3H), 6.52–6.53 (m, 1H), 7.24 (dd, J = 8.4,
(s, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 2.8 Hz,
.0 Hz, 1H), 7.85 (d, J = 8.4 Hz, 2H), 8.19 (d, J = 8.4 Hz,
00 MHz, CDCl3) δ 182.8, 179.4, 172.9, 164.8, 153.2,
2.0, 140.3, 136.0, 134.6, 131.0, 129.4, 129.0, 125.2,
5.6, 111.9, 111.7, 56.0. HMRS (ESI) m/z calcd for
+ 433.0479, found 433.0473.
Procedure for the Preparation of Naphtho[2,3-b]furan-4,9-dione 3a
in Gram Scale: 2-Hydroxy-1,4-naphthoquinone 1a (1.31 g, 7.5 mmol),
chalcone 2a (1.04 g, 5 mmol), NIS (1.13 g, 5 mmol), and DABCO (1.12 g,
10 mmol) were mixed in 30 mL of CH3CN in a sealed tube and heated at
100 oC for 12 h. After completion of the reaction, the mixture was cooled
to room temperature and separated by flash column chromatography
(ethyl acetate/hexane) on silica gel to afford 3a (1.34 g, 71% yield).
3-(4-bromophenyl)-6-methoxynaphtho[2,3-b]furan-
Yellow solid; mp 199–201 oC; yield 185 mg, 69%. 1H
CDCl3) δ 3.96 (s, 3H), 7.24 (dd, J = 8.8, 2.8 Hz, 1H),
z, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.0 Hz, 1H),
), 7.87–7.99 (m, 4H), 8.20 (d, J = 8.8 Hz, 1H), 8.51 (s,
00 MHz, CDCl3) δ 183.3, 179.9, 173.1, 164.8, 152.9,
5.8, 133.1, 132.7, 132.2, 131.8, 131.1, 130.8, 129.8,
8.6, 127.8, 127.3, 127.2, 127.0, 125.6, 124.7, 123.6,
.0. HMRS (ESI) m/z calcd for C30H18BrO5 [M+H]+
37.0328.
Acknowledgements
This work was supported by National Natural Science
Foundation of China and Jiangsu Province (NSFC 21372134,
21571087, 51305178, BK20161307), the Priority Academic
Program Development of Jiangsu Higher Education Institutions
(PAPD), and foundation of Jiangsu Normal University (15XLA06).
Keywords: 2-Hydroxy-1,4-naphthoquinone
• Naphtho[2,3-b]
3-(3-fluorophenyl)-6-methoxynaphtho[2,3-b]furan-
Yellow solid; mp 208–210 oC; yield 171 mg, 72%. 1H
CDCl3) δ 3.96 (s, 3H), 7.03–7.07 (m, 1H), 7.24 (dd, J =
7.27–7.35 (m, 3H), 7.55 (t, J = 7.2 Hz, 1H), 7.60–7.64
8 (m, 4H), 8.21 (d, J = 8.8 Hz, 1H), 8.50 (s, 1H). 13C
CDCl3) δ 183.4, 179.8, 173.2, 164.8, 162.3 (d, J = 245
136.0, 135.8, 133.1, 132.6, 132.2, 130.5 (d, J = 8 Hz),
9.1, 128.6, 127.8, 127.4, 126.9, 125.9 (d, J = 3 Hz),
.0, 117.3 (d, J = 23 Hz), 116.0 (d, J = 21 Hz), 111.5,
I) m/z calcd for C30H18FO5 [M+H]+ 477.1138, found
furan-4,9-diones • Chalcone • NIS • Enones difunctionalization
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