Chemoselective cascade reaction of glycidic esters with 2-naphthol derivatives initiated by stable radical cation salt

Article abstract of DOI:10.1016/j.tet.2013.05.109

A novel and efficient chemoselective tandem Friedel-Crafts alkylation/cyclization reaction of glycidic esters with 2-naphthol derivatives initiated by stable radical cation salt (0.5 mol %) has been developed.

Full text of DOI:10.1016/j.tet.2013.05.109

Tetrahedron 69 (2013) 6375e6380
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Chemoselective cascade reaction of glycidic esters with 2-naphthol
derivatives initiated by stable radical cation salt
*
Congde Huo , Jinzhu An, Wenju Chang, Xiaodong Jia, Lisheng Kang, Mingxia Wu
Key Laboratory of Eco-Environment-Related Polymer Materials Ministry of Education, College of Chemistry and Chemical Engineering,
Northwest Normal University, Lanzhou, Gansu 730070, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel and efficient chemoselective tandem FriedeleCrafts alkylation/cyclization reaction of glycidic
esters with 2-naphthol derivatives initiated by stable radical cation salt (0.5 mol %) has been developed.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 13 February 2013
Received in revised form 23 May 2013
Accepted 26 May 2013
Available online 7 June 2013
Keywords:
Glycidic esters
Naphthol
Radical cation
FriedeleCrafts alkylation
Cascade reaction
1. Introduction
and the initiator is commercially available and inexpensive. (2)
a,b-epoxy ketones are used as valuable halogen-free pre-electro-
As one of the cornerstone reactions for the construction of
carbonecarbon bonds, FriedeleCrafts (FC) alkylation is a significant
fundamental reaction in organic chemistry, and it has been widely
used to generate important classes of building blocks.1,2 With
the increasing economic and environmental awareness, the de-
velopment of greener and/or sustainable methods for this basic
transformation has emerged in recent years.2 During our studies on
philes due to their ready availability and highly atom-economical
character. (3) one-pot protocol is operationally simple.3b,3c As part
of our ongoing program to expand the scope and generality of this
chemistry, we decided to investigate a,b-epoxy esters, also known
as glycidic esters, easily derived from a Darzens-type process,4 as
pre-electrophiles in the reaction with 2-naphthol derivatives.
the radical cation mediated transformations of a,b
-epoxy ketones,3
2. Results and discussion
we have demonstrated that stable triarylaminium salt [tris(4-
bromophenyl)aminium hexachloroantimonate, TBPAþꢀSbCl6ꢁ] is
a highly efficient nonmetallic initiator for the FC alkylation reaction
between chalcone epoxides and heteroarenes to construct complex
Our investigation started with the reaction between glycidic
ester (1a) and 2-naphthol (2a) (Table 1). 1a was taken as a model
substrate because of the extra stability of benzylic cation in-
termediate (Scheme 2, intermediate A) provided by 4-methoxyl
substituent. To our delight, after adding 5 mol % of TBPAþꢀSbCl6ꢁ,
1a and 2a were consumed in a few minutes, and one major product
3aa (68%) and one minor product 4aa (22%) were produced (Table
1, entry 1). Compounds 1, 2-dihydronaphtho-[2,1-b]furan de-
rivative5 3aa and splitomicin derivative6 4aa were isolated and fully
characterized by HRMS, 1H NMR, 13C NMR, and their stereochem-
istry was determined by X-ray crystallographic analysis.7 Lewis
acids AlCl3, InCl3, FeCl3, and I2 were also evaluated. All of them can
catalyze the reaction between glycidic ester 1a and 2-naphthol
(Table 1, entries 2e7) to give the products 3aa and 4aa. But
TBPAþꢀSbClꢁ6 as the catalyst gave the best yield and showed the best
chemoselectivity. These results encouraged us to optimize the
b
-heteroaryl a
-ketols3a and for the novel FC alkylation/annulation
cascade reaction between chalcone epoxides and 2-naphthols or
2-naphthyl ethers to construct polysubstituted 1,2-dihydronaphtho
[2,1-b]furans.3b,3c And TBPAꢀSbClꢁ6 could also efficiently induce the
cycloaddition of chalcone epoxides with olefins to form tetrahy-
drofurans3d and the cycloaddition of chalcone epoxides with ary-
limines to form 1,3-oxazolidines.3e These reactions initiated by
TBPAþꢀSbClꢁ6 have several advantages: (1) no metal is needed for
the reaction. Only catalytic amount of organo initiator is used
* Corresponding author. Tel.: þ86 0931 7971533; fax: þ86 0931 7971989; e-mail
addresses: huocongde1978@hotmail.com, huocongde@nwnu.edu.cn (C. Huo).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.109

6376
C. Huo et al. / Tetrahedron 69 (2013) 6375e6380
Table 1
Under the optimized conditions (Table 1, entry 12), the gener-
Screening of reaction conditions
ality and scope of this procedure was investigated using a variety of
glycidic esters and 2-naphthol derivatives. Initially, different gly-
cidic esters (R¼OMe, OEt, OtBu) were tested and the reaction pro-
ceeded smoothly to afford the desired products in good yields
(Table 2, entries 1e3). Glycidic esters with electron-rich aryl groups
(such as 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, and piperonyl)
gave the corresponding products in good yields (Table 2, entries 1,
4, 5). The scope of the 2-naphthol counterpart in this reaction was
also evaluated. 2-Naphthols with electron donating groups or
electron withdrawing groups at C2, C6 and C7 all worked well with
glycidic esters under the present reaction conditions (Table 2, en-
tries 6e11). It is noteworthy that halo-substituted 2-naphthol was
tolerated well, thus leading to halo-substituted complex hetero-
cyclic products, which could be used for further transformations
(Table 2, entry 8). In addition, the relative sensitive formyl-
substituted 2-naphthol was also tolerated in this transformation,
thus generating 3ae in 67% yield (Table 2, entry 9). However, gly-
cidic esters without strong electron donating R1 group gave no
desired products with 2-naphthol under the same experimental
conditions (Table 2, entries 12, 13). But when Fraeseol was used,
3ha was achieved in good yield. This may be attributed to the extra
Entry
Conditions
Yield of 3aab (%)
Yield of 4aab (%)
5% TBPAþ , CHCl3
68
32
41
27
38
30
31
72
62
32
29
72
22
38
36
34
39
34
35
21
18
12
11
20
ꢀ
1
2
3
4
5
6
7
8
5% AlCl3, CHCl3
5% FeCl3, CHCl3
5% FeCl3$6H2O, CHCl3
5% InCl3, CHCl3
5% InCl3$6H2O, CHCl3
5% I2, CHCl3
5% TBPAþ , CH2Cl2
ꢀ
5% TBPAþ , ClCH2CH2Cl
ꢀ
9
5% TBPAþ , MeCN
ꢀ
10
11
12
5% TBPAþ , Acetone
ꢀ
0.5% TBPAþ , CH2Cl2
ꢀ
aReaction conditions: 1a (0.1 mmol), 2a (0.1 mmol), Catalyst, Solvent (1 mL), rt, 0.5 h.
b
Yields were determined by NMR spectroscopy.
stability of cation intermediate provided by a-methyl group (Table
2, entry 14). When 2-naphthyl ethers were employed as nucleo-
philes, it is of importance to note that the same FC alkylation/cy-
clization cascade reaction took place smoothly to give 1,2-
dihydronaphtho[2,1-b]furans (Table 2, entries 15e19). However,
when 2-naphthalenethiol was used as a nucleophile, only S-alkyl-
ation product was obtained (Table 2, entry 20), perhaps due to
higher nucleophilicity of the sulfur atom of 2-naphthalenethiol.8
Unfortunately, the reaction between glycidic esters 1a and
4-XC6H4OH (X¼MeO, Me, Br, NO2) gave no designed benzofuran
analogs.
Scheme 1. One-pot preparation of naphtho[2,1-b]furan in large scale.
To evaluate the practical application of our method,9 the re-
action between glycidic ester 1a and 2-naphthol has been per-
formed on a 20 mmol scale in a single batch. And to our delight, no
yield loss was observed and the reaction still completed within half
an hour (Scheme 1). Furthermore, after subsequent aerobic oxida-
tive aromatization,10,3b,3c polysubstituted naphtho[2,1-b]furans
were delivered in excellent yield (Scheme 1). The direct trans-
formation of glycidic ester with 2-naphthol into naphtho[2,1-b]
furans could also be carried out in one-pot. That is, to say, here we
present a practical and scalable synthetic entry to polysubstituted
1,2-dihydronaphtho[2,1-b]furans and naphtho[2,1-b]furans using
easily available glycidic esters and 2-naphthol derivatives.
Although the mechanistic details of this transformation are not
clear at this stage, we illustrated a tentative radical cation mediated
chain mechanism for this TBPAþꢀSbClꢁ6 induced transformation in
Scheme 2. The glycidic ester (1) was first activated by single elec-
tron oxidation to give distonic11 radical cation intermediate A.
2-Naphthol (2a as an example) was then attacked by the benzylic
cation of intermediate A to form the dihydrofurylium distonic
radical cation intermediate B. Then there were two options. Route
1: Oxygen radical combined with the carbocation to construct
radical cation intermediate C. And then the radical cation in-
termediate D was formed by eliminating a molecule of water from
intermediate C. Intermediate D would then undergo single electron
transfer from substrate 1 to produce the major product 3 and re-
generate intermediate A at the same time. Chain propagation
continued until all substrates were converted into the products.
Route 2: Oxygen radical abstracted a hydrogen atom to afford in-
termediate E. After sequential SET and intramolecular ester ex-
Scheme 2. Proposed mechanism.
reaction conditions based on TBPAþꢀSbCl6ꢁ. A screening of solvents
revealed that chlorinated solvents were more efficient to the re-
action and the best result was obtained by the use of CH2Cl2 as the
solvent (Table 1, entry 8). And to our delight, when the catalyst
loading was lowered from 5 to 0.5 mol %, the reaction still worked
well and gave the same yield of 3aa (Table 1, entry 12). Control
experiments rꢁevealed that no reaction was observed in the absence
of TBPAþꢀSbCl6 . To avoid the influence of the trace amount of SbCl5
or any other possibly existing trace amounts of Lewis acids or
change process, minor product
4 was produced. That the
þ
ꢁ
Bronsted acids in TBPA ꢀSbCl6 , an equimolar amount of hindered
non-nucleophilic base 2,6-di-tert-butylpyridine (DBP) was added
as an acid scavenger. No obvious inhibition was observed.
combination of the oxygen radical with carbocation (Route 1) is
easier than hydrogen abstraction (Route 2) may lead to the
chemoselectivity.
€

C. Huo et al. / Tetrahedron 69 (2013) 6375e6380
6377
Table 2
Reaction of chalcone epoxides with 2-naphthyl ethers
Entry
1
Substrate 1
Substrate 2
Products
Yield %b (trans:cis)
(3aa)
70 (1.8:1)
62 (1.6:1)
51 (1.5:1)
2
3
(3ba)
(3ca)
4
(3da)
68 (1.4:1)
5
6
(3ea)
(3ab)
67 (1.4:1)
68 (1.5:1)
7
8
9
(3ac)
(3ad)
(3ae)
65 (1.7:1)
70 (1.8:1)
67 1.9:1)
10
11
12
13
(3af)
(3ag)
(3fa)
(3ga)
57 (1.6:1)
62 (1.5:1)
Trace
Trace
14
15
(3ha)
(3aa)
62
70 (1.6:1)
48 (1.2:1)
16
17
(3ca)
(3da)
65 (1.4:1)
(continued on next page)

6378
C. Huo et al. / Tetrahedron 69 (2013) 6375e6380
Table 2 (continued )
Entry
Substrate 1
Substrate 2
Products
Yield %b (trans:cis)
18
19
20
(3ea)
64 (1.5:1)
(3aa)
(3aj)
61 (1.8:1)
aStandard reaction conditions: 1 (1.0 mmol), 2 (1.0 mmol), TBPAþ (0.005 mmol), CH2Cl2 (10 mL), rt, 0.5 h.
ꢀ
b
Isolated yields of the isolated products.
3. Conclusions
exact mass calcd for C21H19O4 [MþH] m/z 335.1283, found
335.1285.
In summary, we have demonstrated a novel triarylaminium salt
catalyzed FriedeleCrafts alkylation/cyclization cascade reaction
between glycidic esters and 2-naphthol derivatives. The practica-
bility of this transformation was demonstrated and a one-pot tan-
dem FC alkylation/cyclization/aerobic oxidative aromatization
procedure was carried out for the synthesis of aromatic naphtho
[2,1-b]furans. A possible radical cation mediated chain mechanism
was proposed. Further mechanistic studies of this reaction are
underway in our laboratory.
4.2.2. Methyl 1-(4-methoxyphenyl)-1,2-dihydronaphtho[2,1-b]furan-
2-carboxylate (Compound 3aa, cis isomer). White solid, mp
148e149 ꢂC. 1H NMR (400 MHz, CDCl3)
d
7.74 (t, J¼7.6 Hz, 2H), 7.21
(m, 4H), 6.93 (d, J¼8.4 Hz, 2H), 6.68 (d, J¼8.6 Hz, 2H), 5.56
(d, J¼9.9 Hz, 1H), 5.14 (d, J¼9.9 Hz, 1H), 3.65 (s, 3H), 3.30 (s, 3H). 13C
NMR (101 MHz, CDCl3)
d 168.91, 158.89, 156.85, 130.47, 130.39,
130.32, 130.08, 130.04, 129.96, 129.69, 128.84, 128.76, 128.69,
126.91, 123.31, 122.77, 120.18, 113.63, 112.28, 112.19, 112.10, 85.51,
55.08, 51.81, 50.51.
4. Experimental section
4.1. General
4.2.3. Ethyl 1-(4-methoxyphenyl)-1,2-dihydronaphtho[2,1-b]furan-
2-carboxylate (Compound 3ba, trans isomer). Colorless oil. 1H NMR
(400 MHz, CDCl3)
d
7.81 (t, J¼7.5 Hz, 2H), 7.30 (m, 5H), 7.17
The starting materials and reagents, purchased from commer-
cial suppliers, were used without further purification. Darzens
condensation was used for the preparation of glycidic esters.
TBPAþꢀSbClꢁ6 was synthesized according to literature and used as
freshly prepared. Solvents were purified by standard methods.
Analytical TLC was performed with silica gel GF254 plates, and the
products were visualized by UV detection. Flash chromatography
was carried out using silica gel 200e300. 1H NMR (400 MHz) and
13C NMR (100 MHz) spectra were measured with TMS as internal
standard when CDCl3 was used as solvent. High-resolution elec-
trospray ionization (HRESI) mass spectra were recorded by a QTOF-
2 Micromass spectrometer.
(d, J¼8.2 Hz, 2H), 6.85 (d, J¼8.6 Hz, 2H), 5.12 (m, 2H), 4.30 (m, 2H),
3.80 (s, 3H), 1.37 (t, J¼7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3)
d
170.89, 158.84, 157.24, 134.26, 130.48, 130.24, 130.08, 128.82,
128.74, 126.85, 123.26, 122.91, 119.34, 114.31, 112.16, 88.20, 61.75,
55.25, 51.84, 14.24. HRMS (ESI) exact mass calcd for C22H21O4
[MþH] m/z 349.1440, found 349.1437.
4.2.4. tert-Butyl 1-(4-methoxyphenyl)-1,2-dihydronaphtho[2,1-b]fu-
ran-2-carboxylate (Compound 3ca, trans isomer). White solid, mp
131e132 ꢂC. 1H NMR (400 MHz, CDCl3)
d
7.84 (t, J¼7.5 Hz, 2H),
7.31 (m, 4H), 7.17 (d, J¼8.7 Hz, 2H), 6.90 (d, J¼8.7 Hz, 2H), 5.08
(d, J¼5.7 Hz, 1H), 5.02 (d, J¼5.7 Hz, 1H), 3.85 (s, 3H), 1.57 (s, 9H).
13C NMR (101 MHz, CDCl3)
d 169.89, 158.83, 157.53, 134.54,
4.2. General procedure for TBPADꢀSbCl6L induced reaction of
glycidic esters with 2-naphthols
130.46, 130.35, 130.07, 128.85, 128.76, 126.78, 123.15, 122.92,
119.25, 114.31, 112.21, 88.48, 82.46, 55.24, 52.10, 28.11. HRMS
(ESI) exact mass calcd for C24H25O4 [MþH] m/z 377.1753, found
377.1756.
Glycidic esters (1, 1 mmol) and 2-naphthols (2, 1 mmol) werꢁe
dissolved in CH2Cl2 (10 mL) at ambient temperature; TBPAþꢀSbCl6
(0.005 mmol, 0.5 mol %) was then added in portion under stirring.
The reaction completed within half an hour as monitored by TLC.
The diastereomer products were isolated by column chromato-
graphic separation with the rapidly eluting the trans isomer and the
slowly eluting the cis isomer.
4.2.5. tert-Butyl 1-(4-methoxyphenyl)-1,2-dihydronaphtho[2,1-b]fu-
ran-2-carboxylate (Compound 3ca, cis isomer). White solid, mp
145e146 ꢂC. 1H NMR (400 MHz, CDCl3)
d
7.79 (t, J¼8.8 Hz, 2H), 7.28
(m, 4H), 7.09 (d, J¼8.4 Hz, 2H), 6.77 (d, J¼8.8 Hz, 2H), 5.52
(d, J¼9.9 Hz, 1H), 5.15 (d, J¼9.9 Hz, 1H), 3.74 (s, 3H), 1.16 (s, 9H). 13C
NMR (101 MHz, CDCl3)
d 167.37, 158.94, 156.61, 130.96, 130.22,
4.2.1. Methyl 1-(4-methoxyphenyl)-1,2-dihydronaphtho[2,1-b]furan-
130.08, 130.03, 130.00, 128.78, 126.87, 123.18, 122.67, 121.18, 113.74,
112.34, 85.41, 82.09, 55.26, 50.30, 27.55.
2-carboxylate (Compound 3aa, trans isomer). White solid, mp
123e125 ꢂC. 1H NMR (400 MHz, CDCl3)
d
7.80 (t, J¼7.5 Hz, 2H), 7.28
(m, 4H), 7.12 (d, J¼8.6 Hz, 2H), 6.83 (d, J¼8.6 Hz, 2H), 5.12 (m, 2H),
3.83 (s, 3H), 3.79 (s, 3H). 13C NMR (101 MHz, CDCl3)
171.38, 158.84,
4.2.6. Methyl 1-(3,4,5-trimethoxyphenyl)-1,2-dihydronaphtho[2,1-b]
d
furan-2-carboxylate (Compound 3da, trans isomer). White solid, mp
157.10, 134.14, 130.48, 130.20, 130.08, 128.79, 128.67, 126.87, 123.29,
122.88, 119.36, 114.31, 112.09, 88.15, 55.22, 52.65, 51.76. HRMS (ESI)
131e133 ꢂC. 1H NMR (400 MHz, CDCl3)
d
7.81 (m, 2H), 7.30 (m, 4H),
6.44 (s, 2H), 5.14 (m, 2H), 3.86 (s, 3H), 3.81 (s, 3H), 3.74 (s, 6H).

C. Huo et al. / Tetrahedron 69 (2013) 6375e6380
6379
HRMS (ESI) exact mass calcd for C23H23O6 [MþH] m/z 395.1495,
(t, J¼7.3 Hz, 1H), 7.20 (m, 4H), 7.03 (d, J¼8.4 Hz, 2H), 6.78 (d,
J¼8.8 Hz, 2H), 5.69 (d, J¼10.1 Hz, 1H), 5.34 (m, 2H), 5.26 (d,
J¼10.1 Hz, 1H), 3.76 (s, 3H), 3.38 (s, 3H). 13C NMR (101 MHz, CDCl3)
found 395.1499.
4.2.7. Methyl 1-(3,4,5-trimethoxyphenyl)-1,2-dihydronaphtho[2,1-b]
d 168.63, 158.97, 148.64, 144.70, 136.48, 131.08, 129.85, 129.59,
furan-2-carboxylate (Compound 3da, cis isomer). White solid, mp
128.61, 128.06, 127.69, 127.50, 125.33, 124.65, 123.92, 122.70, 121.74,
113.67, 109.88, 86.06, 70.84, 55.14, 51.73, 51.00.
190e191 ꢂC. 1H NMR (400 MHz, CDCl3)
d
7.80 (m, 2H), 7.31 (m, 4H),
6.33 (s, 2H), 5.64 (d, J¼10.0 Hz, 1H), 5.18 (d, J¼10.0 Hz, 1H), 3.79 (s,
3H), 3.72 (s, 6H), 3.41 (s, 3H). 13C NMR (101 MHz, CDCl3)
168.79,
d
4.2.14. Methyl 7-bromo-1-(4-methoxyphenyl)-1,2-dihydronaphtho
156.80, 152.92, 133.69, 130.51, 130.05, 129.97, 128.70, 126.92, 123.33,
122.67, 119.72, 112.12, 105.79, 85.37, 60.69, 56.02, 51.75, 51.54.
[2,1-b]furan-2-carboxylate (Compound 3ad, trans isomer). Pale yel-
low solid, mp 90e92 ꢂC. 1H NMR (400 MHz, CDCl3)
d 7.95 (s, 1H),
7.70 (d, J¼8.9 Hz, 1H), 7.35 (m, 2H), 7.14 (m, 3H), 6.85 (d, J¼8.6 Hz,
4.2.8. Methyl 1-(benzo[d][1,3]dioxol-5-yl)-1,2-dihydronaphtho[2,1-
2H), 5.14 (s, 2H), 3.87 (s, 3H), 3.78 (s, 3H). 13C NMR (101 MHz, CDCl3)
b]furan-2-carboxylate (Compound 3ea, trans isomer). White solid,
d 171.13,159.02,157.46,133.78,131.24,130.77,130.16,129.66,128.72,
mp 179e180 ꢂC. 1H NMR (400 MHz, CDCl3)
d
7.82 (t, J¼7.9 Hz, 2H),
7.32 (m, 5H), 6.76 (s, 2H), 6.66 (s,1H), 5.93 (d, J¼9.6 Hz, 2H), 5.12 (m,
2H), 3.85 (s, 3H). 13C NMR (101 MHz, CDCl3)
171.29, 157.13, 148.21,
128.67, 124.58, 119.84, 116.93, 114.46, 113.22, 88.24, 55.25, 52.76,
51.64. HRMS (ESI) exact mass calcd for C21H18BrO4 [MþH] m/z
413.0388, found 413.0393.
d
146.90, 135.94, 130.64, 130.06, 128.81, 126.96, 123.37, 122.81, 120.89,
119.11, 112.11, 108.46, 107.87, 101.10, 87.97, 52.73, 52.18. HRMS (ESI)
exact mass calcd for C21H17O5 [MþH] m/z 349.1076, found 349.1071.
4.2.15. Methyl 7-bromo-1-(4-methoxyphenyl)-1,2-dihydronaphtho
[2,1-b]furan-2-carboxylate (Compound 3ad, cis isomer). White
solid, mp 147e149 ꢂC. 1H NMR (400 MHz, CDCl3)
d 7.97 (s, 1H), 7.71
4.2.9. Methyl 1-(benzo[d][1,3]dioxol-5-yl)-1,2-dihydronaphtho[2,1-
(d, J¼8.9 Hz, 1H), 7.35 (m, 2H), 7.16 (d, J¼8.9 Hz, 1H), 6.98 (d,
J¼8.3 Hz, 2H), 6.77 (d, J¼8.7 Hz, 2H), 5.64 (d, J¼10.0 Hz, 1H), 5.21 (d,
J¼10.0 Hz, 1H), 3.75 (s, 3H), 3.38 (s, 3H). 13C NMR (101 MHz, CDCl3)
b]furan-2-carboxylate (Compound 3ea, cis isomer). White solid, mp
146e148 ꢂC. 1H NMR (400 MHz, CDCl3)
d
7.82 (t, J¼7.8 Hz, 2H), 7.31
(m, 4H), 6.66 (m, 2H), 6.51 (s, 1H), 5.89 (d, J¼12.0 Hz, 2H), 5.62 (d,
d 168.75, 159.03, 157.25, 131.23, 130.76, 130.23, 129.70, 129.64,
J¼9.8 Hz, 1H), 5.18 (d, J¼9.8 Hz,1H), 3.48 (s, 3H). 13C NMR (101 MHz,
129.59, 128.55, 124.51, 120.56, 116.99, 113.75, 113.33, 85.52, 55.14,
51.84, 50.40.
CDCl3)
d 168.74, 156.73, 147.58, 146.87, 131.70, 130.50, 130.03,
129.93, 128.76, 126.97, 123.37, 122.66, 121.97, 120.04, 112.18, 108.87,
107.92, 100.95, 85.36, 51.81, 50.79.
4.2.16. Methyl 7-formyl-1-(4-methoxyphenyl)-1,2-dihydronaphtho
[2,1-b]furan-2-carboxylate (Compound 3ae, trans isomer). Pale red
4.2.10. Methyl 8-methoxy-1-(4-methoxyphenyl)-1,2-dihydronaphtho
solid, mp 138e139 ꢂC. 1H NMR (400 MHz, CDCl3)
d 10.03 (s, 1H),
[2,1-b]furan-2-carboxylate (Compound 3ab, trans isomer). White
8.28 (s, 1H), 7.95 (d, J¼8.9 Hz, 1H), 7.78 (d, J¼8.9 Hz, 1H), 7.39 (m,
solid, mp 133e134 ꢂC. 1H NMR (400 MHz, CDCl3)
d 7.71 (m, 2H), 7.18
2H), 7.14 (d, J¼8.6 Hz, 2H), 6.87 (d, J¼8.6 Hz, 2H), 5.17 (m, 2H), 3.86
(m, 3H), 6.93 (d, J¼9.0 Hz, 1H), 6.86 (d, J¼8.6 Hz, 2H), 6.57 (s, 1H),
(s, 3H), 3.78 (s, 3H). 13C NMR (101 MHz, CDCl3)
d 191.76, 170.78,
5.15 (d, J¼5.5 Hz, 1H), 5.09 (d, J¼5.5 Hz, 1H), 3.86 (s, 3H), 3.79 (s,
159.78, 158.97, 135.32, 133.48, 132.51, 131.88, 129.07, 128.57, 124.08,
123.77, 120.40, 114.42, 113.27, 88.40, 55.15, 52.76, 51.27. HRMS (ESI)
exact mass calcd for C22H18O5 [MþH] m/z 362.1154, found 362.1150.
3H), 3.64 (s, 3H). 13C NMR (101 MHz, CDCl3)
d 171.39, 158.74, 158.23,
157.53, 133.85, 131.43, 130.25, 130.10, 130.07, 128.72, 128.69, 125.32,
118.60, 115.72, 114.24, 114.21, 109.39, 101.43, 88.05, 55.17, 54.94,
52.66, 51.74. HRMS (ESI) exact mass calcd for C22H21O5 [MþH] m/z
365.1389, found 365.1394.
4.2.17. Methyl 7-formyl-1-(4-methoxyphenyl)-1,2-dihydronaphtho
[2,1-b]furan-2-carboxylate (Compound 3ae, cis isomer). Pale yellow
solid, mp 174e175 ꢂC. 1H NMR (400 MHz, CDCl3)
d 10.07 (s, 1H), 8.31
4.2.11. Methyl 8-methoxy-1-(4-methoxyphenyl)-1,2-dihydronaphtho
(s, 1H), 7.97 (d, J¼8.5 Hz, 1H), 7.77 (d, J¼8.5 Hz, 1H), 7.39 (m, 3H),
7.00 (d, J¼8.4 Hz, 2H), 6.78 (d, J¼8.8 Hz, 2H), 5.69 (d, J¼10.0 Hz, 1H),
5.27 (d, J¼10.0 Hz, 1H), 3.75 (s, 3H), 3.39 (s, 3H).
[2,1-b]furan-2-carboxylate (Compound 3ab, cis isomer). White
solid, mp 214e215 ꢂC. 1H NMR (400 MHz, CDCl3)
d 7.71 (m, 2H), 7.27
(s, 1H), 7.16 (d, J¼8.8 Hz, 1H), 7.03 (d, J¼8.4 Hz, 2H), 6.93 (d,
J¼9.0 Hz, 1H), 6.77 (d, J¼8.6 Hz, 2H), 6.54 (s, 1H), 5.63 (d, J¼9.9 Hz,
1H), 5.16 (d, J¼9.9 Hz, 1H), 3.75 (s, 3H), 3.65 (s, 3H), 3.39 (s, 3H). 13C
4.2.18. Methyl 7-cyano-1-(4-methoxyphenyl)-1,2-dihydronaphtho
[2,1-b]furan-2-carboxylate (Compound 3af, trans isomer). White
NMR (101 MHz, CDCl3)
d
168.99, 158.82, 158.28, 157.36, 131.31,
solid, mp 58e60 ꢂC. 1H NMR (400 MHz, CDCl3)
d 8.19 (s, 1H), 7.88 (d,
130.29, 130.01, 129.66, 125.37, 119.37, 115.62, 113.62, 109.51, 101.50,
101.39, 85.36, 55.01, 51.81, 50.57.
J¼8.9 Hz, 1H), 7.41 (m, 3H), 7.12 (d, J¼8.7 Hz, 2H), 6.90 (d, J¼8.7 Hz,
2H), 5.18 (d, J¼5.4 Hz,1H), 5.14 (d, J¼5.4 Hz,1H), 3.87 (s, 3H), 3.81 (s,
3H). 13C NMR (101 MHz, CDCl3)
d 170.73, 159.62, 159.16, 134.93,
4.2.12. Methyl 4-(benzyloxy)-1-(4-methoxyphenyl)-1,2-
dihydronaphtho[2,1-b]furan-2-carboxylate (Compound 3ac, trans
isomer). White solid, mp 132e133 ꢂC. 1H NMR (400 MHz, CDCl3)
133.27, 131.84, 131.40, 128.90, 128.61, 127.55, 124.02, 120.30, 119.36,
114.57, 114.05, 106.62, 88.53, 76.70, 55.28, 52.87, 51.33, 29.69. HRMS
(ESI) exact mass calcd for C22H17NO4 [MþH] m/z 359.1158, found
359.1164.
d
7.68 (d, J¼8.7 Hz, 1H), 7.56 (d, J¼7.4 Hz, 2H), 7.38 (m, 3H), 7.22 (m,
6H), 6.83 (d, J¼8.6 Hz, 2H), 5.34 (m, 2H), 5.23 (d, J¼5.4 Hz, 1H), 5.16
(d, J¼5.4 Hz, 1H), 3.85 (s, 3H), 3.77 (s, 3H). 13C NMR (101 MHz,
4.2.19. Methyl 7-cyano-1-(4-methoxyphenyl)-1,2-dihydronaphtho
CDCl3)
d
171.18, 158.94, 148.80, 144.65, 136.54, 133.80, 131.08,
[2,1-b]furan-2-carboxylate (Compound 3af, cis isomer). White
128.73, 128.65, 128.07, 127.66, 127.55, 125.49, 124.66, 123.91, 122.73,
121.26, 114.38, 110.07, 88.70, 77.39, 77.07, 76.75, 70.88, 55.26, 52.69,
52.34. HRMS (ESI) exact mass calcd for C28H25O5 [MþH] m/z
441.1702, found 441.1700.
solid, mp 86e87 ꢂC. 1H NMR (400 MHz, CDCl3)
d 8.21 (s, 1H), 7.86 (d,
J¼8.9 Hz, 1H), 7.37 (m, 3H), 6.99 (d, J¼8.8 Hz, 2H), 6.78 (d, J¼8.8 Hz,
2H), 5.69 (d, J¼10.1 Hz, 1H), 5.28 (d, J¼10.1 Hz, 1H), 3.76 (s, 3H), 3.38
(s, 3H).
4.2.13. Methyl 4-(benzyloxy)-1-(4-methoxyphenyl)-1,2-
4.2.20. Dimethyl
furan-2,7-dicarboxylate (Compound 3ag, trans isomer). White solid,
mp 135e136 ꢂC. 1H NMR (400 MHz, CDCl3)
8.57 (s, 1H), 7.88 (m,
2H), 7.33 (m, 2H), 7.13 (d, J¼8.6 Hz, 2H), 6.84 (d, J¼8.6 Hz, 2H), 5.14
1-(4-methoxyphenyl)-1,2-dihydronaphtho[2,1-b]
dihydronaphtho[2,1-b]furan-2-carboxylate (Compound 3ac, cis iso-
mer). White solid, mp 161e163 ꢂC. 1H NMR (400 MHz, CDCl3)
d
7.69
d
(d, J¼8.1 Hz, 1H), 7.57 (d, J¼7.3 Hz, 2H), 7.42 (t, J¼7.4 Hz, 2H), 7.35

6380
C. Huo et al. / Tetrahedron 69 (2013) 6375e6380
(m, 2H), 3.93 (s, 3H), 3.85 (s, 3H), 3.77 (s, 3H). 13C NMR (101 MHz,
CDCl3) 171.00, 167.13, 159.11, 159.02, 133.70, 132.59, 132.27, 131.99,
131.97, 129.11, 128.65, 126.45, 124.93, 123.00, 119.83, 114.46, 113.02,
88.43, 77.39, 77.08, 76.76, 55.20, 52.81, 52.13, 51.49. HRMS (ESI)
exact mass calcd for C23H20O6 [MþH] m/z 392.1260, found
392.1266.
References and notes
d
1. For first example, see: (a) Friedel, C.; Crafts, J. M. J. Chem. Soc. 1877, 32, 725 For
recent reviews, see: (b) Rueping, M.; Nachtsheim, B. J. Beilstein J. Org. Chem.
2010, 6, 6; (c) Bandini, M.; Tragni, M. Org. Biomol. Chem. 2009, 7, 1501; (d)
Poulsen, T. B.; Jørgensen, K. A. Chem. Rev. 2008, 108, 2903.
ꢀ
2. For selected recent examples, see: (a) Liebert, C.; Brinks, M. K.; Capacci, A. G.;
Fleming, M. J.; Lautens, M. Org. Lett. 2011, 13, 3000; (b) Nicolaou, K. C.; Re-
ingruber, R.; Sarlah, D.; Brase, S. J. Am. Chem. Soc. 2009, 131, 2086; (c) Stadler, D.;
Bach, T. Angew. Chem., Int. Ed. 2008, 47, 7557; (d) Li, C.; Liu, H.; Liao, J.; Cao, Y.;
Liu, X.; Xiao, W. Org. Lett. 2007, 9, 1847; (e) Mertins, K.; Iovel, I.; Kischel, J.; Zapf,
A.; Beller, M. Angew. Chem., Int. Ed. 2004, 44, 238; (f) Huo, C.; Sun, C.; Wang, C.;
Jia, X.; Chang, W. ACS Sustainable Chem. Eng. 2013, 1, 549; (g) Huo, C.; Wang, C.;
Sun, C.; Jia, X.; Wang, X.; Chang, W.; Wu, M. Adv. Synth. Catal. 2013, 355, http://
dx.doi.org/10.1002/adsc.201300276
3. (a) Huo, C.; Xu, X.; Jia, X.; Wang, X.; An, J.; Sun, C. Tetrahedron 2012, 68, 190; (b)
Huo, C.; Xu, X.; An, J.; Jia, X.; Wang, X.; Wang, C. J. Org. Chem. 2012, 77, 8310; (c)
Huo, C.; An, J.; Xu, X.; Jia, X.; Wang, X.; Kang, L. Tetrahedron Lett. 2013, 54, 1145;
(d) Huo, C.; Jia, X.; Zhang, W.; Yang, L.; Liu, Z. Synlett 2004, 251; (e) Huo, C.; Wei,
R.; Zhang, W.; Yang, L.; Liu, Z. Synlett 2005, 161.
4. Strategic Applications of Named Reactions in Organic Synthesis; Kurti, L., Czako, B.,
Eds.; Elsevier: Burlington, MA, 2005; and references cited therein.
5. (a) El-Wahab, A. H. F. A.; Al-Fifi, Z. I. A.; Bedair, A. H.; Ali, F. M.; Halawa, A. H. A.;
El-Agrody, A. M. Molecules 2011, 16, 307; (b) Guo, X.; Yu, R.; Li, H.; Li, Z. J. Am.
Chem. Soc. 2009, 131, 17387; (c) Adib, M.; Mahdavi, M.; Bagherzadeh, S.; Bi-
janzadeh, H. Synlett 2009, 2542; (d) Pan, C.; Yu, J.; Zhou, Y.; Wang, Z.; Zhou, M.-
M. Synlett 2006, 1657; (e) Park, K. K.; Jeong, J. Tetrahedron 2005, 61, 545; (f)
Haselgrove, T.; Jevric, M.; Taylor, D. Tetrahedron 1999, 55, 14739; (g) Arrault, A.
Synthesis 1999, 1999, 1241.
4.2.21. Ethyl 1-methyl-1-phenyl-1,2-dihydronaphtho[2,1-b]furan-2-
carboxylate (Compound 3ha, trans isomer). Colorless oil. 1H NMR
(400 MHz, CDCl3)
d
7.78 (m, 2H), 7.44 (d, J¼8.7 Hz, 2H), 7.25 (m, 7H),
7.07 (d, J¼8.3 Hz, 1H), 5.26 (s, 1H), 4.31 (m, 2H), 1.83 (s, 3H), 1.32 (m,
t, J¼7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3)
d 168.71, 156.11, 144.85,
130.71, 130.64, 130.58, 129.41, 129.31, 128.69, 127.30, 127.13, 126.69,
124.56, 123.13, 122.58, 112.51, 92.78, 92.71, 61.30, 54.52, 20.24.
HRMS (ESI) exact mass calcd for C21H18O3 [MþH] m/z 318.1256,
found 318.1259.
4.2.22. Methyl 2-hydroxy-3-(4-methoxyphenyl)-3-(naphthalen-2-
ylthio)propanoate (Compound 3aj, anti isomer). White solid, mp
91e92 ꢂC. 1H NMR (400 MHz, CDCl3)
d 7.74 (m, 4H), 7.45 (m, 5H),
6.87 (d, J¼7.6 Hz, 1H), 4.74 (d, J¼3.0 Hz, 1H), 4.59 (dd, J¼5.6, 2.9 Hz,
1H), 3.80 (s, 3H), 3.57 (s, 3H), 3.37 (d, J¼5.6 Hz, 1H).
6. (a) Freitag, M.; Schemies, J.; Larsen, T.; Gaghlab, K. E.; Schulz, F.; Rumpf, T.; Jung,
M.; Link, A. Bioorg. Med. Chem. 2011, 19, 3669; (b) Neugebauer, R. C.; Uchie-
chowska, U.; Meier, R.; Hruby, H.; Valkov, V.; Verdin, E.; Sippl, W.; Jung, M. J.
Med. Chem. 2008, 51, 1203; (c) Posakony, J.; Hirao, M.; Stevens, S.; Simon, J. A.;
Bedalov, A. J. Med. Chem. 2004, 47, 2635.
7. The X-ray crystal data (excluding structure factors) of compounds 3aa-trans,
3aa-cis & 4aa-cis have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication no CCDC 922031, 922032, and
922033. Copy of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: þ44 (0) 1223 336033 or
e-mail: deposit@ccdc.cam.ac.uk).
4.2.23. Methyl 2-hydroxy-3-(4-methoxyphenyl)-3-(naphthalen-2-
ylthio)propanoate (Compound 3aj, syn isomer). White solid, mp
80e82 ꢂC. 1H NMR (400 MHz, CDCl3)
d 7.92 (s,1H), 7.77 (m, 3H), 7.49
(m, 3H), 7.35 (d, J¼8.0 Hz, 2H), 6.85 (d, J¼8.0 Hz, 2H), 4.72 (d,
J¼3.4 Hz, 1H), 4.61 (dd, J¼6.1, 3.4 Hz, 1H), 3.79 (s, 3H), 3.68 (s, 3H),
2.97 (d, J¼6.1 Hz, 1H).
8. Halimehjani, A. Z.; Aryanasab, F.; Saidi, M. R. Tetrahedron Lett. 2009, 50, 1441.
9. (a) Mendoza, A.; Ishihara, Y.; Baran, P. S. Nat. Chem. 2012, 4, 21; (b) Ley, S. V. In
Practical Synthetic Organic Chemistry; Caron, S., Ed.; John Wiley & Sons: 2011;
foreword.
10. Wang, L.; Li, J.; Yang, H.; Lv, Y.; Gao, S. J. Org. Chem. 2012, 77, 790.
11. Distonic ions are chemical species that contain both a radical and an ionic site
on different atoms of the same molecule. Review see: Stirk, K. M.; Kiminkinen,
L. K. M.; Kenttamaa, H. I. Chem. Rev. 1992, 92, 1649.
Acknowledgements
We thank the National Natural Science Foundation of China
(21262029, 21002080) and the Specialized Research Fund for the
Doctoral Program of Higher Education (20106203120003) of the
Education Ministry for financially supporting this work.