Synthesis of Furo[3,2-c]benzopyrans via an Intramolecular [4 + 2] Cycloaddition Reaction of o-Quinonemethides

Article abstract of DOI:10.1021/acs.joc.5b01641

An intramolecular [4 + 2] cycloaddition reaction of o-quinonemethides generated from salicylaldehydes and α-prenylated alcohols is described. In the presence of a catalytic amount of benzenesulfonic acid (BSA), the reaction proceeded smoothly in EtOH to afford furo[3,2-c]benzopyrans through a three-bond forming process in moderate to excellent yields with high diastereoselectivity. This reaction provides a simple and straightforward protocol to efficiently construct furo[3,2-c]benzopyran skeletons. A possible mechanism involving hemiacetal formation/hetero-Diels-Alder reaction is proposed to rationalize the observed results.

Full text of DOI:10.1021/acs.joc.5b01641

Note
pubs.acs.org/joc
Synthesis of Furo[3,2‑c]benzopyrans via an Intramolecular [4 + 2]
Cycloaddition Reaction of o‑Quinonemethides
Li-Ming Zhao,* Ai-Li Zhang, Hua-Shuai Gao, and Jie-Huan Zhang
School of Chemistry and Chemical Engineering and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials,
Jiangsu Normal University, Xuzhou 221116, Jiangsu, China
S
* Supporting Information
ABSTRACT: An intramolecular [4 + 2] cycloaddition reaction of o-quinonemethides generated from salicylaldehydes and α-
prenylated alcohols is described. In the presence of a catalytic amount of benzenesulfonic acid (BSA), the reaction proceeded
smoothly in EtOH to afford furo[3,2-c]benzopyrans through a three-bond forming process in moderate to excellent yields with
high diastereoselectivity. This reaction provides a simple and straightforward protocol to efficiently construct furo[3,2-
c]benzopyran skeletons. A possible mechanism involving hemiacetal formation/hetero-Diels−Alder reaction is proposed to
rationalize the observed results.
inflammatory,6 antiosteoporotic,7 ER antagonistic or agonistic,8
olycyclic oxygen heterocycles are an important class of
and so forth.
Pfused heterocycles found in numerous natural products
and are reported to possess interesting biological activity.1 In
particular, the furan-fused heterocycle furo[3,2-c]benzopyran is
the key structural motif of many natural products and
biologically active molecules.2 For example, pterocarpans and
cordigol have this central motif of furo[3,2-c]benzopyran
(Figure 1). The furo[3,2-c]benzopyran derivatives are also
known for their wide range of biological activities, such as
antifungal,3 antibacterial,3 antisnake venom,4 anti-HIV,5 anti-
The hetero-Diels−Alder (HDA) reaction is an efficient and
powerful method for the construction of polycyclic oxygen
heterocycles.9 o-Quinonemethides as important intermediates
have a special position in the synthesis of polycyclic ring
systems by means of an HDA reaction. They can act as
heterodiene cycloaddition partners in inter- and intramolecular
Diels−Alder [4 + 2] cylcoadditions with alkenes to afford
various oxygenated heterocycles.10 However, the synthesis of
fused polycyclic oxygen heterocycles utilizing [4 + 2]
cycloaddition reactions of o-quinonemethides is mostly limited
to the synthesis of pyranobenzopyrans,11 and there are only
limited cases with limited examples (that hinders diversifica-
tion) reporting the synthesis of furo[3,2-c]benzopyrans in this
manner.11b,d Furthermore, the reported reactions require the
use of stoichiometric quantities of combined reagents (e.g.,
CH(OMe)3/p-TsOH11b or CH(OMe)3/I211d) and toxic
solvents (e.g., benzene11b), thus increasing the cost and limiting
their applications. Recently, Spivey et al. reported the synthesis
of the core 2,3-cis-THF ring system of cordigol via oxonium-
Prins cyclization.12 However, despite its elegance, low temper-
ature (−78 °C) and stoichiometric SnCl4 (1.1 equiv) were
required. In a chemical reaction, the reagent and the solvent are
the major source of waste, and therefore, minimizing the use of
chemical reagents and substituting a toxic solvent with a less
Figure 1. Representative molecules containing furo[3,2-c]benzopyran
motifs.
Received: July 16, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b01641
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
Table 1. Optimization of the Reaction Conditions
b
c
b
b
b
entry
acid (mol %)
solvent
temp
t (h)
3a (%)
dr
4a (%)
recovery of 1a (%)
recovery of 2a (%)
1
SnCl4 (100)
CH2Cl2
CH2Cl2
benzene
CH2Cl2
MeOH
EtOH
r.t.
0.5
6
0
0
45
34
21
12
0
80
90
0
0
2
In(OTf)3 (100)
p-TsOH (30)
p-TsOH (30)
p-TsOH (30)
p-TsOH (30)
C6H5SO3H (30)
CF3SO3H (30)
CH3SO3H (30)
H2SO4 (10)
r.t.
3
r.t.
4
30
60
42
73
87
50
0
92:8
30
8
d
4
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
4
ND
ND
10
0
5
5
21
0
6
5
91:9
90:10
95:5
0
12
0
7
EtOH
5
0
trace
30
0
8
EtOH
8
0
23
60
0
9
EtOH
24
24
24
5
0
57
10
11
12
13
EtOH
0
36
0
84
CH3COOH (100)
C6H5SO3H (15)
C6H5SO3H (50)
EtOH
0
100
37
100
25
0
EtOH
48
90
ND
88:12
0
EtOH
5
0
trace
a
b
c
Reactions were carried out with 1a (0.5 mmol), 2a (0.5 mmol), and acid in solvent (5 mL). Isolated yield. The diastereomeric ratio (dr) was
d
1
determined by H NMR. Not determined.
toxic solvent are the crucial points in designing environmentally
improved methods toward functionalized heterocycles. There-
fore, it remains a challenging, but very attractive, task to find
more economical and practical methods with a broader
substrate scope for the preparation of furo[3,2-c]benzopyran
derivatives from inexpensive and simple reagents and
conditions. Moreover, the development of methodology that
uses simple reagents and conditions that lead to convenient
procedures and better yields is highly desirable.
In the continuation of our interest on homoallylic
compounds13 and oxygen heterocycles,14 we report herein a
novel method for the synthesis of angularly fused furo[3,2-
c]benzopyrans through an HDA reaction of salicylaldehydes
with α-prenylated alcohols. The present method features a
broad substrate scope on furo[3,2-c]benzopyrans synthesis,
ease of manipulation, high degree of synthetic flexibility, and
eliminates the requirement of complex and stoichiometric
reagents as well as toxic solvents.
Optimization of the reaction conditions was performed with
salicylaldehyde 1a and 4-methyl-1-phenylpent-3-en-1-ol 2a as
model substrates, and the results are presented in Table 1.
Spivey and co-workers previously reported similar cyclization
using salicylaldehyde as the aldehyde component and (E)-4-
phenylbut-3-en-1-ol as the homoallylic alcohol component in
the presence of stoichiometric SnCl4 in CH2Cl2 at −78 °C.12
Analogous to this procedure, we initially employed equimolar
amounts of 1a and 2a and 100 mol % of SnCl4 as a catalyst in
CH2Cl2. To avoid using harsh reaction conditions, we
performed the reaction at room temperature. Disappointingly,
the reaction at room temperature led to the recovery of the
starting precursor salicylaldehyde 1a and significant amounts of
eliminated byproduct 4a (Table 1, entry 1). When indium
triflate, a new type of Lewis acid that differs from typical Lewis
acids, such as AlCl3 and SnCl4, was used, a similar result was
observed (entry 2). These observations suggest that the Lewis
acids might not be ideal catalysts for this reaction. Thus, we
attempted the reaction in the presence of Brønsted acids
instead of Lewis acids. The reaction was first studied with a
catalytic amount of Brønsted acid p-toluene sulfonic acid (p-
TsOH) in benzene at room temperature. To our delight, our
attempts to catalyze the cyclization using 30 mol % p-TsOH
between 1a and 2a in the absence of any additive resulted in the
desired 3a in 30% yield, albeit with the dehydration byproduct
4a (entry 3). It is noteworthy that trimethyl orthoformate
(TMOF) was found to be vital to this kind of cycloaddition
reaction when using acid or iodine as the catalyst.11b,d,15
However, our experiment in the absence of TMOF afforded the
cyclized product, suggesting that TMOF is not an essential
requirement for the desired transformation. Subsequently,
screening with different solvents (CH2Cl2, MeOH, and
EtOH) using 30 mol % catalyst loading led to further
improvement in the yield (entries 4−6). Ethanol was the
most efficient among the tested solvents (entry 6). From the
viewpoint of green chemistry, this is of relevance because
ethanol is a safe and cheap solvent, whereas the majority of the
solvents are organic chemicals with hazardous, toxic, and costly
properties. In a quest to improve the conversion of 1a, other
Brønsted acids, such as C6H5SO3H (BSA), CH3SO3H,
CF3SO3H, H2SO4, and CH3COOH, were used in lieu of p-
TsOH (entries 7−11). Gratifyingly, the reaction was found to
not only lead to the complete conversion of starting precursor
1a but also successfully avoided the formation of dehydration
byproduct 4a and gave 3a in an improved yield of 87% with
slightly lower diastereoselectivity when the acid p-TsOH was
replaced by BSA (entry 7). Other acids, such as CF3SO3H,
CH3SO3H, H2SO4, and CH3COOH, all gave disappointing
results. For example, the use of CF3SO3H as the catalyst led to
a significant decrease in efficiency of the catalytic system with
even the reaction time prolonged to 8 h (entry 8). Moreover,
no desired product 3a was observed when the reaction was
conducted in the presence of CH3SO3H, H2SO4, and
CH3COOH (entries 9−11, respectively). Finally, the amount
of BSA was examined, and the results showed that the reaction
efficiency was obviously lower with decreased catalyst loading
(entry 12). The use of higher catalyst loading did not result in
significant improvement in the yield or diastereoselectivity of
the reaction (entry 13). Therefore, the optimized conditions for
B
DOI: 10.1021/acs.joc.5b01641
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The Journal of Organic Chemistry
Note
this cycloaddition reaction are as follows: 30 mol % of BSA as
the acid and EtOH as the solvent at reflux.
With the optimized reaction conditions in hand, the substrate
scope with respect to various kinds of substituted salicylalde-
hydes 1 and α-prenylated alcohols 2 was examined, and the
results are summarized in Table 2. The influence of the
products 3i−q in moderate to good yields (entries 8−16).
Similarly, examples of the electron-withdrawing chloro group at
the 5-position (1c) of salicylaldehyde led to good yields for 3r
(81%) and 3s (76%) (entries 17 and 18, respectively).
Particularly noteworthy was that 5-nitro salicylaldehyde 1d
reacted well with α-prenylated alcohols 2a and 2f to deliver
products 3t and 3u in 93 and 70% yields (entries 19 and 20,
respectively). This is particularly important because many
reactions are incompatible with nitro substituents due to their
strong electron-withdrawing characteristics. Gratifyingly, the
substituent on the salicylaldehyde is not limited to electron-
withdrawing substituents. The salicylaldehyde substrate bearing
an electron-donating methyl group substituted at the 5-position
(1e) proceeded smoothly to afford corresponding products
3v−x in synthetically useful yields (51−67%). These outcomes
from the successful formation of products 3i−x thus
emphasized the usefulness of this catalytic method for the
synthesis of furo[3,2-c]benzopyran scaffold, which could easily
lead to analogues of biologically active pterocarpans. Moreover,
the halogen groups in the product offer useful handles for
further functionalization. Besides the wide substrate scope,
another impressive feature of the current reaction is its high
diastereoselectivity. For instance, in most cases, salicylaldehydes
1 and α-prenylated alcohols 2 gave furo[3,2-c]benzopyran
derivatives 3 as single diastereomers (entries 2, 4, 5, 7, 9, 11, 12,
14, 16, 17, and 19−23). In the case of 1a and 2b (entry 1), 1a
and 2d (entry 3), 1a and 2g (entry 6), 1b and 2a (entry 8), 1b
and 2c (entry 10), 1b and 2j (entry 13), 1b and 2f (entry 15),
and 1c and 2j (entry 18), the reaction yielded mixtures of
diastereomers 3b, 3d, 3g, 3i, 3k, 3n, 3p, and 3s with a ratio
ranging from 78:22 to 94:6, respectively. All the products were
identified through their NMR and HRMS. The structure of 3g
was further confirmed by X-ray crystallography (CCDC ref.
No. 1426296; see the Supporting Information).
a
Table 2. Substrate Scope
yield
b
c
entry
1
R1
2
R2
3
(%)
trans:cis
1
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1c
1c
1d
1d
1e
1e
1e
H
H
H
H
H
H
H
2b
2c
2d
2e
2f
3-FC6H4
4-FC6H4
4-BrC6H4
2,6-Cl2C6H3
2-MeC6H4
4-MeC6H4
3-MeOC6H4
Ph
3b
3c
3d
3e
3f
89
83
79
80
73
52
44
64
72
85
65
74
68
76
63
57
81
76
93
70
67
66
51
94:6
>99:1
94:6
2
3
4
>99:1
>99:1
5
6
2g
2h
2a
2b
2c
2i
3g
3h
3i
82:18
>99:1
92:8
7
8
5-Br
9
5-Br
3-FC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
3,4-Cl2C6H3
2,6-Cl2C6H3
2-MeC6H4
4-MeC6H4
2-BrC6H4
3,4-Cl2C6H3
Ph
3j
>99:1
78:22
>99:1
>99:1
87:13
>99:1
90:10
>99:1
>99:1
85:15
>99:1
>99:1
>99:1
>99:1
>99:1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
5-Br
3k
3l
5-Br
5-Br
2d
2j
3m
3n
3o
3p
3q
3r
5-Br
5-Br
2e
2f
5-Br
5-Br
2g
2k
2j
5-Cl
5-Cl
3s
3t
On the basis of these results and previous reports,11b,16
a
5-NO2
5-NO2
5-Me
5-Me
5-Me
2a
2f
plausible explanation of the reaction mechanism is depicted in
Scheme 1. First, hemiacetal I is formed in situ from aldehyde 1
and α-prenylated 2 after activation with BSA. Subsequent
elimination of H2O from I would generate o-quinonemethide
II. Then, an intramolecular HDA reaction occurs via transition
state A (TS-A) with the simultaneous formation of the C−C
and C−O bonds or in a stepwise manner to provide trans-fused
3. The excellent diaseteroselectivity of this reaction to yield
trans-fused 3 can be explained on the basis of the transition
state proposed in Scheme 1. Because of the nonbonded
interaction between the hydrogen at 6-position of the phenyl
ring and an axial hydrogen of the homoallylic moiety,
cycloaddition via TS-B appears to be disfavored. Conversely,
such steric interaction is absent in TS-A, and thus, it seems to
be more stable than TS-B. Consequently, trans-3 is
predominantly formed.
In conclusion, the use of salicylaldehydes in [4 + 2]
cycloaddition with α-prenylated alcohols affords rapid access to
furo[3,2-c]benzopyrans in good yields with high diastereose-
lectivity. The reaction sequence involved an acetal reaction
under catalytic Brønsted acid conditions followed by intra-
molecular Diels−Alder cyclization to create three new bonds in
one process. Inexpensive BSA could be used as the catalyst, and
EtOH was the best solvent. The catalytic method uses readily
available substrates, avoids the use of combined reagents, toxic
solvents, and drastic reaction conditions, and a variety of
synthetically useful yet sensitive functional groups are well-
tolerated under the reaction conditions used. Thus, this novel
2-MeC6H4
Ph
3u
3v
3w
3x
2a
2d
2l
4-BrC6H4
3-MeC6H4
a
Reactions were carried out at the 0.5 mmol scale and catalyzed by 30
b
c
mol % BSA in EtOH (5 mL) at reflux for 5 h. Isolated yield. The
ratio was determined by H NMR.
1
substituents at the α-prenylated alcohol moiety was first
investigated by submitting salicylaldehyde 1a with various α-
prenylated alcohols 2. In this event, the reaction could proceed
well using diverse α-prenylated alcohols 2b−h with an electron-
withdrawing group (F, Cl, or Br) or an electron-donating group
(Me or MeO) on the phenyl ring to give the corresponding
products 3b−h in moderate to good yields (entries 1−7).
Generally, the phenyl ring with electron-withdrawing sub-
stituents were relatively more reactive than those with electron-
donating ones and thus gave relatively higher yields (entries 1−
4). Lower yields are observed for substrates bearing electron-
donating substituents on the phenyl ring, as observed for the
reactions of 2f−h (entries 5−7, respectively). Subsequently, the
influence of the substituent at the salicylaldehyde on the
cycloaddition reaction was also examined. Both electron-rich
and -deficient salicylaldehyde participated in the reaction
efficiently. For example, salicylaldehydes bearing an electron-
withdrawing bromo group at the 5-position (1b) could react
well with various α-prenylated alcohols to afford cyclized
C
DOI: 10.1021/acs.joc.5b01641
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The Journal of Organic Chemistry
Note
Scheme 1. Proposed Reaction Mechanism
49.4, 36.0, 29.7, 22.0. HRMS (APCI): m/z calcd for C19H20FO2 [M +
H]+, 299.1447; found, 299.1468.
BSA-catalyzed reaction offers good economic and environ-
mental benefits and can be an alternative protocol for the
synthesis of valuable furo[3,2-c]benzopyrans.
2-(4-Fluorophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo-
[3,2-c]chromene (3c). White solid (124 mg, 83% yield); mp 78−80
1
°C; H NMR (400 MHz, CDCl3): δ 7.53 (d, J = 3.5 Hz, 1H), 7.33−
EXPERIMENTAL SECTION
7.22 (m, 4H), 7.02 (t, J = 8.7 Hz, 2H), 6.73 (d, J = 8.7 Hz, 1H), 5.39
(dd, J = 9.4, 2.7 Hz, 1H), 4.63 (d, J = 11.2 Hz, 1H), 2.37−2.25 (m,
1H), 2.15−2.08 (m, 1H), 1.96−1.90 (m, 1H), 1.41 (s, 3H), 1.34 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 162.3 (J = 243.8 Hz), 152.2,
139.3, 131.7, 127.6 (J = 44.0 Hz), 127.5, 126.3, 118.5, 115.4 (J = 21.4
Hz), 112.1, 81.0, 80.2, 75.2, 49.43, 35.9, 29.6, 22.0. HRMS (APCI): m/
z calcd for C19H20FO2 [M + H]+, 299.1447; found, 299.1464.
2-(4-Bromophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo-
[3,2-c]chromene (3d). White solid (141 mg, 79% yield); mp 123−125
■
1
General Methods. Melting points are uncorrected. H NMR and
13C NMR spectra were recorded at 400 and 100 MHz in CDCl3 with
chemical shift (δ) given in ppm relative to TMS as the internal
standard. Multiplicities were indicated as s (singlet), d (doublet), t
(triplet), q (quartet), m (multiplet), dd (doublet of doublets), and so
forth; coupling constants (J) were given in Hertz (Hz). High
resolution mass spectra (HRMS) were recorded using atmospheric
pressure chemical ionization (APCI) and time-of-flight (TOF) mass
analysis. α-Prenylated alcohols 2 were prepared according to the
procedure described previously by our group.13a
1
°C. H NMR (400 MHz, CDCl3): δ 7.46−7.39 (m, 3H), 7.23−7.16
(m, 3H), 6.93 (t, J = 7.0 Hz, 1H), 6.85 (d, J = 8.2 Hz, 1H), 5.37 (dd, J
= 9.5, 2.6 Hz, 1H), 4.68 (d, J = 11.2 Hz, 1H), 2.38−2.27 (m, 1H),
2.18−2.08 (m, 1H), 1.94−1.87 (m, 1H), 1.41 (s, 3H), 1.34 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 153.1, 142.9, 131.6, 128.8, 127.6,
124.8, 124.4, 121.2, 119.9, 116.6, 80.8, 79.6, 75.8, 49.4, 36.0, 29.7, 22.0.
HRMS (APCI): m/z calcd for C19H20BrO2 [M + H]+, 359.0647;
found, 359.0673.
General Procedure for the Synthesis of Furo[3,2-c]benzopyran 3
from Salicylaldehydes 1 and α-Prenylated Alcohols 2. To a round-
bottom flask (25 mL) were added salicylaldehydes (0.5 mmol) and α-
prenylated alcohols (0.5 mmol) in EtOH (5.0 mL), and then,
benzenesulfonic acid (30 mol %) was added. The mixture was heated
to reflux for 5 h. After being cooled to room temperature, the solvent
was evaporated in vacuum, water was added, and it was then extracted
with ethyl acetate (3 × 5.0 mL). The combined organic layer was
washed with brine, dried with MgSO4, and concentrated in vacuo. The
residue was purified by flash column chromatography (petroleum
ether/ethyl acetate = 40:1) to afford corresponding product 3.
2-Phenyl-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo[3,2-c]-
2-(2,6-Dichlorophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-
1
furo[3,2-c]chromene (3e). Yellow oil (139 mg, 70% yield). H NMR
(400 MHz, CDCl3): δ 7.47 (s, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.26 (d, J
= 3.8 Hz, 2H), 7.17 (t, J = 8.0 Hz, 1H), 6.73 (d, J = 8.7 Hz, 1H), 5.95
(dd, J = 9.8, 5.9 Hz, 1H), 4.58 (d, J = 11.5 Hz, 1H), 2.74−2.65 (m,
1H), 2.23−2.14 (m, 2H), 1.47 (s, 3H), 1.38 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 152.3, 135.6, 134.7, 131.6, 129.7, 129.6, 127.4, 126.1,
118.4, 112.0, 80.7, 78.2, 75.7, 50.7, 31.8, 29.8, 22.0. HRMS (APCI):
m/z calcd for C19H19Cl2O2 [M + H]+, 349.0762; found, 349.0733.
2-o-Tolyl-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo[3,2-c]-
chromene (3f). White solid (107 mg, 73% yield); mp 145−148 °C. 1H
NMR (400 MHz, CDCl3): δ 7.52 (d, J = 7.5 Hz, 1H), 7.19 (t, J = 7.3
Hz, 2H), 7.06−6.97 (m, 4H), 6.79 (d, J = 8.2 Hz, 1H), 5.28 (dd, J =
10.5, 5.7 Hz, 1H), 5.18 (d, J = 7.9 Hz, 1H), 2.74−2.67 (m, 1H), 2.50−
2.43 (m, 1H), 2.29 (s, 3H), 1.69 (q, J = 10.8 Hz, 1H), 1.37 (s, 3H),
1.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.1, 140.7, 134.1,
130.3, 130.0, 129.1, 127.0, 126.4, 125.4, 123.0, 121.1, 117.4, 78.9, 75.9,
73.6, 47.7, 35.3, 26.8, 26.0, 19.4. HRMS (APCI): m/z calcd for
C20H23O2 [M + H]+, 295.1698; found, 295.1684.
1
chromene (3a). White solid (122 mg, 87% yield); mp 83−84 °C. H
NMR (400 MHz, CDCl3): δ 7.44 (d, J = 7.6 Hz, 1H), 7.36−7.28 (m,
4H), 7.28−7.16 (m, 2H), 6.93 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 8.2 Hz,
1H), 5.43 (dd, J = 9.4, 2.7 Hz, 1H), 4.69 (d, J = 11.1 Hz, 1H), 2.37−
2.29 (m, 1H), 2.23−2.15 (m, 1H), 1.99−1.93 (m, 1H), 1.41 (s, 3H),
1.35 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 153.2, 143.9, 128.7,
128.5, 127.4, 125.9, 124.9, 124.6, 119.9, 116.6, 81.5, 79.7, 75.7, 49.5,
36.0, 29.8, 22.0. HRMS (APCI): m/z calcd for C19H21O2 [M + H]+,
281.1542; found, 281.1545.
2-(3-Fluorophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo-
[3,2-c]chromene (3b). Yellow oil (133 mg, 89%). 1H NMR (400
MHz, CDCl3): δ 7.43 (d, J = 7.5 Hz, 1H), 7.29−7.25 (m, 1H), 7.22−
7.17 (m, 1H), 7.07 (dd, J = 14.9, 9.8 Hz, 2H), 6.96−6.90 (m, 2H),
6.89−6.81 (m, 1H), 5.41 (dd, J = 9.5, 2.5 Hz, 1H), 4.69 (d, J = 11.2
Hz, 1H), 2.39−2.29 (m, 1H), 2.18−2.10 (m, 1H), 1.98−1.92 (m, 1H),
1.41 (s, 3H), 1.35 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 163.0 (J =
244.3 Hz), 153.1, 146.6, 130.0 (J = 8.2 Hz), 128.8, 124.8, 124.3, 121.3,
119.9, 116.6, 114.2 (J = 21.1 Hz), 112.8 (J = 22.0 Hz), 80.8, 79.6, 75.8,
2-p-Tolyl-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo[3,2-c]-
1
chromene (3g). White solid (76 mg, 52% yield); mp 93−95 °C. H
NMR (400 MHz, CDCl3): δ 7.43 (d, J = 7.5 Hz, 1H), 7.21 (t, J = 6.7
Hz, 3H), 7.12 (d, J = 8.0 Hz, 2H), 6.92 (t, J = 7.4 Hz, 1H), 6.85 (d, J =
8.1 Hz, 1H), 5.39 (dd, J = 9.3, 2.7 Hz, 1H), 4.67 (d, J = 11.0 Hz, 1H),
2.37−2.27 (m, 4H), 2.23−2.15 (m, 1H), 1.97−1.92 (m, 1H), 1.41 (s,
D
DOI: 10.1021/acs.joc.5b01641
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
3H), 1.35 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 153.1, 140.9,
137.1, 129.4, 129.2, 128.7, 125.9, 125.6, 124.9, 124.7, 119.8, 116.5,
81.5, 79.7, 75.6, 49.6, 36.0, 29.8, 22.0, 21.2. HRMS (APCI): m/z calcd
for C20H23O2 [M + H]+, 295.1698; found, 295.1668.
152.2, 143.8, 132.7, 131.8, 131.4, 130.5, 127.8, 127.6, 125.9, 125.2,
118.6, 112.1, 80.2, 80.0, 75.4, 49.2, 35.8, 29.6, 21.9. HRMS (APCI):
m/z calcd for C19H18BrCl2O2 [M + H]+, 426.9867; found, 426.9850.
8-Bromo-2-(2,6-dichlorophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahy-
dro-2H-furo[3,2-c]chromene (3o). Yellow oil (162 mg, 76% yield).
1H NMR (400 MHz, CDCl3): δ 7.37−7.30 (m, 2H), 7.21−7.12 (m,
2-(3-Methoxyphenyl)-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-
1
furo[3,2-c]chromene (3h). Yellow oil (68 mg, 44% yield). H NMR
(400 MHz, CDCl3): δ 7.44 (d, J = 7.5 Hz, 1H), 7.23−7.17 (m, 2H),
6.94−6.89 (m, 3H), 6.86−6.84 (m, 1H), 6.79−6.77 (m, 1H), 5.40 (dd,
J = 9.4, 2.6 Hz, 1H), 4.69 (d, J = 11.1 Hz, 1H), 3.77 (s, 3H), 2.37−2.28
(m, 1H), 2.21−2.13 (m, 1H), 1.99−1.94 (m, 1H), 1.41 (s, 3H), 1.35
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 159.8, 153.1, 145.6, 129.6,
128.7, 124.9, 124.6, 119.9, 118.2, 116.5, 112.5, 111.7, 81.4, 79.7, 75.7,
55.3, 49.5, 36.0, 29.8, 22.0. HRMS (APCI): m/z calcd for C20H23O3
[M + H]+, 311.1647; found, 311.1673.
8-Bromo-2-phenyl-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo-
[3,2-c]chromene (3i). Yellow oil (115 mg, 64% yield). 1H NMR (400
MHz, CDCl3): δ 7.55 (dd, J = 2.5, 1.1 Hz, 1H), 7.35−7.30 (m, 4H),
7.29−7.24 (m, 2H), 6.73 (d, J = 8.7 Hz, 1H), 5.42 (dd, J = 9.5, 2.8 Hz,
1H), 4.64 (d, J = 11.2 Hz, 1H), 2.37−2.27 (m, 1H), 2.19−2.10 (m,
1H), 1.97 (m, 1H), 1.41 (s, 3H), 1.34 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 152.2, 143.5, 131.6, 128.6, 127.6, 127.6, 126.5, 125.8, 118.4,
112.0, 81.6, 80.2, 75.2, 49.4, 35.8, 29.6, 22.0. HRMS (APCI): m/z
calcd for C19H20BrO2 [M + H]+, 359.0647; found, 359.0667.
8-Bromo-2-(3-fluorophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahydro-
2H-furo[3,2-c]chromene (3j). Yellow oil (135 mg, 72% yield). 1H
NMR (400 MHz, CDCl3): δ 7.54 (dd, J = 2.5, 1.1 Hz, 1H), 7.32−7.27
(m, 2H), 7.09 (d, J = 7.7 Hz, 1H), 7.05−7.02 (m, 1H), 6.97−6.92 (m,
1H), 6.73 (d, J = 8.7 Hz, 1H), 5.40 (dd, J = 9.5, 2.6 Hz, 1H), 4.64 (d, J
= 11.2 Hz, 1H), 2.42−2.26 (m, 1H), 2.14−2.06 (m, 1H), 1.98−1.93
(m, 1H), 1.41 (s, 3H), 1.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
162.3 (J = 244.0 Hz), 152.2, 139.3, 131.7, 127.6, 127.5, 127.5, 126.3,
118.5, 115.5, 115.3, 112.1, 81.0, 80.2, 75.2, 49.4, 35.9, 29.6, 22.0.
HRMS (APCI): m/z calcd for C19H19BrFO2 [M + H]+, 377.0552;
found, 377.0536.
2H), 6.90−6.85 (m, 2H), 5.96 (dd, J = 9.7, 6.0 Hz, 1H), 4.64 (d, J =
11.4 Hz, 1H), 2.78−2.70 (m, 1H), 2.31−2.13 (m, 2H), 1.49 (s, 3H),
1.40 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 153.2, 135.6, 135.1,
129.6, 129.6, 128.7, 124.7, 124.3, 119.8, 116.5, 80.1, 78.2, 76.2, 51.0,
32.0, 29.9, 22.0. HRMS (APCI): m/z calcd for C19H18BrCl2O2 [M +
H]+, 426.9867; found, 426.9849.
8-Bromo-2-o-tolyl-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo-
[3,2-c]chromene (3p). Yellow oil (117 mg, 63% yield). 1H NMR (400
MHz, CDCl3): δ 7.59 (s, 1H), 7.45−7.43 (m, 1H), 7.29 (d, J = 8.7 Hz,
1H), 7.16 (s, 3H), 6.74 (d, J = 7.5 Hz, 1H), 5.58 (d, J = 9.3 Hz, 1H),
4.66 (d, J = 11.3 Hz, 1H), 2.38−2.29 (m, 4H), 2.14−2.07 (m, 1H),
1.88−1.83 (m, 1H), 1.39 (s, 3H), 1.35 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 152.3, 141.7, 133.6, 131.6, 130.2, 127.7, 127.2, 126.5, 126.2,
125.2, 118.5, 112.1, 80.2, 78.8, 74.9, 49.1, 34.7, 29.6, 22.1, 19.4. HRMS
(APCI): m/z calcd for C20H22BrO2 [M + H]+, 373.0803; found,
373.0775.
8-Bromo-2-p-tolyl-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo-
[3,2-c]chromene (3q). Yellow oil (106 mg, 57% yield). 1H NMR (400
MHz, CDCl3): δ 7.54 (d, J = 2.5 Hz, 1H), 7.28 (d, J = 2.5 Hz, 1H),
7.22−7.20 (m, 2H), 7.15−7.13 (m, 2H), 6.72 (d, J = 8.7 Hz, 1H), 5.38
(dd, J = 9.4, 2.7 Hz, 1H), 4.62 (d, J = 11.1 Hz, 1H), 2.34−2.25 (m,
4H), 2.18−2.10 (m, 1H), 1.99−1.92 (m, 1H), 1.40 (s, 3H), 1.33 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 152.3, 140.6, 137.3, 131.5,
129.6, 129.3, 127.7, 126.6, 125.8, 119.5, 118.4, 112.0, 81.6, 80.2, 75.11,
49.53, 35.9, 29.7, 22.0, 21.3. HRMS (APCI): m/z calcd for
C20H22BrO2 [M + H]+, 373.0803; found, 373.0778.
8-Chloro-2-(2-bromophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahydro-
1
2H-furo[3,2-c]chromene (3r). Yellow oil (158 mg, 81% yield). H
NMR (400 MHz, CDCl3): δ 7.55−7.43 (m, 3H), 7.29 (d, J = 7.5 Hz,
1H), 7.17−7.10 (m, 2H), 6.78 (d, J = 8.7 Hz, 1H), 5.63 (dd, J = 9.5,
2.2 Hz, 1H), 4.68 (d, J = 11.0 Hz, 1H), 2.48−2.39 (m, 1H), 2.04−1.92
(m, 2H), 1.39 (s, 3H), 1.35 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
151.7, 142.7, 132.6, 128.8, 128.7, 127.6, 127.6, 125.9, 124.8, 124.6,
121.1, 118.0, 80.7, 80.2, 75.3, 48.8, 35.0, 29.6, 22.1. HRMS (APCI):
m/z calcd for C19H19BrClO2 [M + H]+, 393.0257; found, 393.0277.
8-Chloro-2-(3,4-dichlorophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahy-
dro-2H-furo[3,2-c]chromene (3s). Yellow oil (145 mg, 76% yield). 1H
NMR (400 MHz, CDCl3): δ 7.39 (d, J = 8.0 Hz, 3H), 7.17−7.14 (m,
2H), 6.78 (d, J = 8.7 Hz, 1H), 5.36 (dd, J = 9.5, 2.5 Hz, 1H), 4.62 (d, J
= 11.2 Hz, 1H), 2.38−2.29 (m, 1H), 2.11−2.02 (m, 1H), 1.96−1.90
(m, 1H), 1.41 (s, 3H), 1.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
151.7, 143.8, 132.7, 131.4, 130.5, 128.9, 127.8, 125.4, 125.2, 124.9,
124.7, 118.1, 80.2, 80.0, 75.5, 49.2, 35.8, 29.6, 21.9. HRMS (APCI):
m/z calcd for C19H18Cl3O2 [M + H]+, 383.0372; found, 383.0362.
8-Nitro-2-phenyl-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo[3,2-
c]chromene (3t). Yellow solid (151 mg, 93% yield); mp 82−85 °C. 1H
NMR (400 MHz, CDCl3): δ 8.45 (d, J = 2.5 Hz, 1H), 8.09 (dd, J =
9.1, 2.8 Hz, 1H), 7.24−7.16 (m, 3H), 7.02−7.01 (m, 2H), 6.87 (d, J =
9.1 Hz, 1H), 5.23 (d, J = 8.0 Hz, 1H), 5.12 (dd, J = 10.7, 5.7 Hz, 1H),
2.82−2.75 (m, 1H), 2.49−2.42 (m, 1H), 1.80 (q, J = 12.0 Hz, 1H),
1.45 (s, 3H), 1.37 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 157.4,
141.9, 141.8, 128.5, 127.7, 126.9, 125.8, 125.0, 123.8, 118.2, 82.4, 77.9,
72.8, 47.1, 36.4, 27.0, 26.0. HRMS (APCI): m/z calcd for C19H20NO4
[M + H]+, 326.1392; found, 326.1418.
8-Bromo-2-(4-fluorophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahydro-
1
2H-furo[3,2-c]chromene (3k). Yellow oil (160 mg, 85% yield). H
NMR (400 MHz, CDCl3): δ 7.53 (d, J = 2.4 Hz, 1H), 7.31−7.26 (m,
3H), 7.02 (t, J = 8.7 Hz, 2H), 6.73 (d, J = 8.7 Hz, 1H), 5.39 (dd, J =
9.4, 2.6 Hz, 1H), 4.63 (d, J = 11.2 Hz, 1H), 2.36−2.27 (m, 1H), 2.16−
2.07 (m, 1H), 1.96−1.90 (m, 1H), 1.41 (s, 3H), 1.33 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 162.2 (J = 243.9 Hz), 152.2, 139.2 (J =
31.0 Hz), 131.6, 127.6 (J = 45.0 Hz), 127.5, 126.3, 118.5, 115.4 (J =
21.3 Hz), 112.1, 81.0, 80.2, 75.2, 49.4, 35.9, 29.6, 22.0. HRMS (APCI):
m/z calcd for C19H19BrFO2 [M + H]+, 377.0552; found, 377.0526.
8-Bromo-2-(4-chlorophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahydro-
2H-furo[3,2-c]chromene (3l). Yellow oil (127 mg, 65% yield). 1H
NMR (400 MHz, CDCl3): δ 7.53 (d, J = 2.4 Hz, 1H), 7.31−7.24 (m,
5H), 6.73 (d, J = 8.7 Hz, 1H), 5.39 (dd, J = 9.5, 2.5 Hz, 1H), 4.63 (d, J
= 11.2 Hz, 1H), 2.36−2.28 (m, 1H), 2.13−2.04 (m, 1H), 1.97−1.88
(m, 1H), 1.40 (s, 3H), 1.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
152.2, 142.0, 133.3, 131.7, 128.7, 127.6, 127.2, 126.3, 118.5, 112.1,
80.9, 80.1, 75.3, 49.3, 35.9, 29.6, 22.0. HRMS (APCI): m/z calcd for
C19H19BrClO2 [M + H]+, 393.0257; found, 393.0275.
8-Bromo-2-(4-bromophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahydro-
1
2H-furo[3,2-c]chromene (3m). Yellow oil (161 mg, 74% yield). H
NMR (400 MHz, CDCl3): δ 7.52 (d, J = 1.0 Hz, 1H), 7.46−7.42 (m,
2H), 7.30−7.27 (m, 1H), 7.20−7.18 (m, 2H), 6.73 (d, J = 8.7 Hz,
1H), 5.37 (dd, J = 9.5, 2.6 Hz, 1H), 4.63 (d, J = 11.2 Hz, 1H), 2.37−
2.27 (m, 1H), 2.13−2.02 (m, 1H), 1.96−1.87 (m, 1H), 1.40 (s, 3H),
1.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.2, 142.6, 131.7,
131.6, 127.5, 127.5, 126.3, 121.4, 118.5, 112.1, 80.9, 80.1, 75.3, 49.3,
35.8, 29.6, 22.0. HRMS (APCI): m/z calcd for C19H19Br2O2 [M +
H]+, 436.9752; found, 436.9778.
8-Nitro-2-o-tolyl-4,4-dimethyl-3,3a,4,9b-tetrahydro-2H-furo[3,2-
c]chromene (3u). Yellow solid (118 mg, 70% yield); mp 118−120 °C.
1H NMR (400 MHz, CDCl3): δ 8.48 (d, J = 2.7 Hz, 1H), 8.09 (dd, J =
8-Bromo-2-(3,4-dichlorophenyl)-4,4-dimethyl-3,3a,4,9b-tetrahy-
dro-2H-furo[3,2-c]chromene (3n). Yellow oil (145 mg, 68% yield).
1H NMR (400 MHz, CDCl3): δ 7.52 (dd, J = 2.5, 0.9 Hz, 1H), 7.42−
7.37 (m, 2H), 7.29 (dd, J = 9.0, 2.8 Hz, 1H), 7.16 (dd, J = 8.2, 1.8 Hz,
1H), 6.73 (d, J = 8.7 Hz, 1H), 5.35 (dd, J = 9.5, 2.6 Hz, 1H), 4.62 (d, J
= 11.2 Hz, 1H), 2.38−2.28 (m, 1H), 2.11−2.02 (m, 1H), 1.95−1.90
(m, 1H), 1.41 (s, 3H), 1.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
9.1, 2.8 Hz, 1H), 7.11−6.97 (m, 4H), 6.87 (d, J = 9.1 Hz, 1H), 5.31
(dd, J = 10.6, 5.6 Hz, 1H), 5.21 (d, J = 8.0 Hz, 1H), 2.82−2.76 (m,
1H), 2.54−2.46 (m, 1H), 2.29 (s, 3H), 1.64 (q, J = 11.1 Hz, 1H), 1.43
(s, 3H), 1.37 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 157.6, 141.9,
139.8, 134.2, 130.2, 127.3, 126.9, 126.5, 125.1, 124.9, 123.7, 118.2,
79.3, 77.9, 72.5, 47.2, 34.8, 26.7, 26.1, 19.4. HRMS (APCI): m/z calcd
for C20H22NO4 [M + H]+, 340.1549; found, 340.1577.
E
DOI: 10.1021/acs.joc.5b01641
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
2-Phenyl-4,4,8-trimethyl-3,3a,4,9b-tetrahydro-2H-furo[3,2-c]-
(4) Nakagawa, M.; Nakanishi, K.; Darko, L. L.; Vick, J. A. Tetrahedron
Lett. 1982, 23, 3855.
1
chromene (3v). Yellow oil (98 mg, 67% yield). H NMR (400 MHz,
CDCl3): δ 7.36−7.34 (m, 3H), 7.31−7.26 (m, 1H), 6.86 (dd, J = 8.1,
1.9 Hz, 1H), 6.74 (s, 1H), 6.66 (d, J = 8.1 Hz, 1H), 6.13 (s, 1H), 4.47
(dd, J = 8.3, 4.7 Hz, 1H), 3.45−3.28 (m, 2H), 2.64−2.58 (m, 1H),
2.37−2.32 (m, 1H), 2.24 (s, 3H), 1.43 (s, 3H), 1.34 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 149.9, 142.7, 138.3, 130.0, 128.8, 128.6, 127.8,
126.7, 126.3, 122.7, 120.4, 115.8, 81.0, 78.8, 64.4, 40.5, 26.0, 25.9, 20.7,
15.45. HRMS (APCI): m/z calcd for C20H23O2 [M + H]+, 295.1698;
found, 295.1681.
2-(4-Bromophenyl)-4,4,8-trimethyl-3,3a,4,9b-tetrahydro-2H-
furo[3,2-c]chromene (3w). Yellow solid (123 mg, 66% yield); mp
58−60 °C. 1H NMR (400 MHz, CDCl3): δ 7.43 (d, J = 8.5 Hz, 2H),
7.21 (d, J = 8.4 Hz, 3H), 7.00 (dd, J = 8.3, 2.2 Hz, 1H), 6.75 (d, J = 8.3
Hz, 1H), 5.36 (dd, J = 9.5, 2.7 Hz, 1H), 4.65 (d, J = 11.1 Hz, 1H),
2.33−2.27 (m, 4H), 2.17−2.09 (m, 1H), 1.92−1.87 (m, 1H), 1.39 (s,
3H), 1.32 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 150.8, 142.9,
131.6, 129.4, 129.2, 127.7, 125.2, 123.9, 121.3, 116.4, 80.9, 79.3, 75.9,
49.6, 36.0, 29.7, 21.8, 20.7. HRMS (APCI): m/z calcd for C20H22BrO2
[M + H]+, 373.0803; found, 373.0776.
(5) Engler, T. A.; Lynch, K. O.; Reddy, J. P.; Gregory, G. S. Bioorg.
Med. Chem. Lett. 1993, 3, 1229.
(6) Njamen, D.; Talla, E.; Mbafor, J. T.; Fomum, Z. T.; Kamanyi, A.;
Mbanya, J.-C.; Cerda-Nicolas, M.; Giner, R. M.; Recio, M. C.; Rios, J.
L. Eur. J. Pharmacol. 2003, 468, 67.
(7) (a) Tyagi, A. M.; Srivastava, K.; Kureel, J.; Kumar, A.;
Raghuvanshi, A.; Yadav, D.; Maurya, R.; Goel, A.; Singh, D.
Osteoporosis Int. 2012, 23, 1151. (b) Bhargavan, B.; Singh, D.;
Gautam, A. K.; Mishra, J. S.; Kumar, A.; Goel, A.; Dixit, M.; Pandey,
R.; Manickavasagam, L.; Dwivedi, S. D.; Chakravarti, B.; Jain, G. K.;
Ramachandran, R.; Chattopadhyay, N.; Sanyal, S. J. Nutr. Biochem.
2012, 23, 27.
(8) van de Schans, M. G. M.; Vincken, J.-P.; Bovee, T. F. H.; David
Cervantes, A.; Logtenberg, M. J.; Gruppen, H. J. Agric. Food Chem.
2014, 62, 10475.
(9) (a) Boger, D. L.; Weinreb, S. M. In Hetero Diels-Alder
Methodology in Organic Synthesis; Academic Press: New York, 1987;
Ch. 7, pp 193−199. For a review, see: (b) Desimoni, G.; Tacconi, G.
Chem. Rev. 1975, 75, 651.
2-m-Tolyl-4,4,8-trimethyl-3,3a,4,9b-tetrahydro-2H-furo[3,2-c]-
1
chromene (3x). Yellow oil (79 mg, 51% yield). H NMR (400 MHz,
(10) For reviews, see: (a) Amouri, H.; Le Bras, J. Acc. Chem. Res.
2002, 35, 501. (b) Van De Water, R. W.; Pettus, T. R. R. Tetrahedron
2002, 58, 5367.
CDCl3): δ 7.29 (d, J = 1.8 Hz, 1H), 7.09 (t, J = 7.6 Hz, 1H), 7.02−
6.97 (m, 2H), 6.86 (d, J = 7.6 Hz, 1H), 6.81 (s, 1H), 6.70 (d, J = 8.3
Hz, 1H), 5.14 (d, J = 7.9 Hz, 1H), 5.02 (dd, J = 10.5, 5.9 Hz, 1H),
2.71−2.60 (m, 1H), 2.43−2.35 (m, 1H), 2.30 (s, 3H), 2.20 (s, 3H),
1.83 (q, J = 11.1 Hz, 1H), 1.37 (s, 3H), 1.32 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 149.8, 142.6, 137.9, 130.5, 130.2, 129.8, 128.2, 128.2,
127.1, 123.3, 122.7, 117.0, 82.3, 75.6, 74.0, 47.8, 36.9, 27.0, 25.8, 21.5,
20.7. HRMS (APCI): m/z calcd for C21H25O2 [M + H]+, 309.1855;
found, 309.1885.
(11) (a) Inoue, S.; Asami, M.; Honda, K.; Miyazaki, H. Chem. Lett.
1996, 889. (b) Miyazaki, H.; Honda, K.; Asami, M.; Inoue, S. J. Org.
Chem. 1999, 64, 9507. (c) Yadav, J. S.; Reddy, B. V. S.; Aruna, M.;
Thomas, M. Synthesis 2002, 2002, 217. (d) Yadav, J. S.; Reddy, B. V.
S.; Rao, C. V.; Rao, K. V. J. Chem. Soc., Perkin Trans. 1 2002, 1401.
(e) Yadav, J. S.; Reddy, B. V. S.; Sadashiv, K.; Padmavani, B. Adv.
Synth. Catal. 2004, 346, 607. (f) Ghosh, A. K.; Kass, J.; Nicponski, D.
R.; Keyes, C. Synthesis 2012, 44, 3579.
ASSOCIATED CONTENT
* Supporting Information
■
(12) Spivey, A. C.; Laraia, L.; Bayly, A. R.; Rzepa, H. S.; White, A. J.
P. Org. Lett. 2010, 12, 900.
S
(13) (a) Zhao, L.-M.; Jin, H.-S.; Wan, L.-J.; Zhang, L.-M. J. Org.
Chem. 2011, 76, 1831. (b) Zhao, L.-M.; Zhang, S.-Q.; Jin, H.-S.; Wan,
L.-J.; Dou, F. Org. Lett. 2012, 14, 886. (c) Zhao, L.-M.; Wan, L.-J.; Jin,
H.-S.; Zhang, S.-Q. Eur. J. Org. Chem. 2012, 2012, 2579. (d) Zhao, L.-
M.; Wan, L.-J.; Zhang, S.-Q.; Sun, R.; Ma, F.-Y. Tetrahedron 2013, 69,
7970. (e) Zhao, L.-M.; Zhang, S.-Q.; Dou, F.; Sun, R. Org. Lett. 2013,
15, 5154. (f) Jin, H.-S.; Zhang, S.-Q.; Sun, R.; Dou, F.; Zhao, L.-M.
RSC Adv. 2014, 4, 21810.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b01641.
1
Copies of H and 13C NMR spectra for all prepared
products and X-ray crystal structure of 3g (PDF)
Crystal data of 3g in CIF format(CIF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: lmzhao@jsnu.edu.cn.
■
(14) Zhao, L.-M.; Dou, F.; Sun, R.; Zhang, A.-L. Synlett 2014, 25,
1431.
(15) Jiang, M.; Shi, M. Org. Lett. 2010, 12, 2606.
(16) Wilson, S. R.; Mao, D. T. J. Am. Chem. Soc. 1978, 100, 6289.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are thankful for financial support from the Natural Science
Foundation of Jiangsu Province (BK2012576), Major Program
of Natural Science Foundation (12KJA150005), and PAPD of
Jiangsu Higher Education Institutions.
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DOI: 10.1021/acs.joc.5b01641
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