An approach to the synthesis of naphtho[b]furans from allyl bromonaphthyl ethers employing sequential photoinduced radical cyclization and dehydrohalogenation reactions

Article abstract of DOI:10.1016/j.tetlet.2014.04.056

A simple method has been developed for the efficient synthesis of naphtho[b]furans from allyl bromonaphthyl ethers. The approach utilizes a novel photochemical process involving sequential radical cyclization and dehydrohalogenation. Because light is a readily available, environmentally friendly reagent that produces no by-products, the new process serves as a green synthetic method.

Full text of DOI:10.1016/j.tetlet.2014.04.056

Accepted Manuscript
An Approach to the Synthesis of Naphtho[b]furans from Allyl Bromonaphthyl
Ethers Employing Sequential Photoinduced Radical Cyclization and Dehydro-
halogenation Reactions
Yusuke Suzuki, Yoshiki Okita, Toshio Morita, Yasuharu Yoshimi
PII:
S0040-4039(14)00668-6
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.04.056
TETL 44518
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
14 March 2014
8 April 2014
15 April 2014
Please cite this article as: Suzuki, Y., Okita, Y., Morita, T., Yoshimi, Y., An Approach to the Synthesis of
Naphtho[b]furans from Allyl Bromonaphthyl Ethers Employing Sequential Photoinduced Radical Cyclization and
Dehydrohalogenation Reactions, Tetrahedron Letters (2014), doi: http://dx.doi.org/10.1016/j.tetlet.2014.04.056
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Graphical Abstract
An Approach to the Synthesis of Naphtho[b]-
furans from Allyl Bromonaphthyl Ethers
Employing Sequential Photoinduced Radical
Cyclization and Dehydrohalogenation Reactions
Leave this area blank for abstract info.
Yusuke Suzuki, Yoshiki Okita, Toshio Morita, Yasuharu Yoshimi*
R2
Br
R2
Br
R1
R1

h

h
O
R2
O
O
- HBr
R1
R1=H or CH3
R2=CH3 or Ph or CO2CH3
35-72%

1
Tetrahedron Letters
journal homepage: www.elsevier.com
An Approach to the Synthesis of Naphtho[b]furans from Allyl Bromonaphthyl
Ethers Employing Sequential Photoinduced Radical Cyclization and
Dehydrohalogenation Reactions
Yusuke Suzuki, Yoshiki Okita, Toshio Morita, Yasuharu Yoshimi*
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, University of Fukui, 3-9-1 Bunkyo, Fukui 910-8507, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
A simple method has been developed for the efficient synthesis of naphtho[b]furans from allyl
bromonaphthyl ethers. The approach utilizes a novel photochemical process involving sequential
Received in revised form
Accepted
Available online
radical cyclization and dehydrohalogenation. Because light is a readily available,
environmentally friendly reagent that produces no by-products, the new process serves as a
green synthetic method.
2009 Elsevier Ltd. All rights reserved.
Keywords:
Naphtho[b]furan
Allyl bromonaphthyl ether
Photoinduced radical cyclization
Photoinduced dehydrohalogenation
Naphtho[b]furans are structural components of a large number
of interesting natural and synthetic compounds (Figure 1).1 Some
naturally occurring substances in this family exhibit a variety of
interesting pharmacological properties.2 Common methods
developed for the synthesis of naphtho[b]furans usually involve
cyclization reactions of allyl naphthols or allyl iodonaphthyl
ethers promoted using metal catalysts such as Cu and Pd.3 In an
exploratory study aimed at uncovering synthetic approaches that
rely on the use of less toxic and more readily available reagents,
we observed that photochemical reductive radical cyclization
reactions of allyl 2-bromoaryl ethers in i-PrOH containing NaOH
produce dihydrobenzofurans.4 In this study, we also found that
photoreactions of allyl bromonaphthyl ethers in the absence of
NaOH generate naphtho[b]furans. Below, we present the results
mercury lamp and Pyrex glass filter (>280 nm) and an argon
atmosphere, at room temperature for 3 h leads to formation of 2-
methylnaphtho[2,1-b]furan 2a in 72% yield (Entry 1).5 The
efficiency of this process is significantly lowered when
irradiation is carried out on a solution of 1a under an air
atmosphere (Entry 2). This observation suggests that a molecular
oxygen quenchable triplet state of 1a is participates in this
process.6 In addition, the yield of 2a decreases when higher
concentrations of 1a (5 or 10 mM) in acetonitrile are employed in
the photoreaction (Entries 3 and 4). While a variety of solvents
including hexane, benzene, diethyl ether, and acetone can be
Table 1. Photoreactions of Allyl 1-Bromo-2-naphthyl Ether 1aa
Br
of an effort in which we have developed
a simple,

h
O
O
environmentally friendly photochemical method to prepare
naphtho[b]furans from allyl bromonaphthyl ethers.
1a
2a
O
1
O
b
Solvent Concentration of /mM Yield of 2a/%b
1a
Entry
a
2
3
CH3CN
1
3
72
11
2c
naphtho[1,2-b]furan
naphtho[2,1-b]furan
3
4d
57
51
70
5
10
3
Figure 1. Structures of naphtho[2,1-b] and [1,2-b]furans.
5
hexane
6
7
8
benzene
64
61
58
Initial exploratory studies were carried out using allyl 1-
bromo-2-naphthyl ether 1a (Table 1). Irradiation of an
acetonitrile solution of 1a (3 mM), using a 100 W high-pressure
diethyl ether
acetone
aPhotoreactions were carried out for 3 h under Ar atmosphere.
bIsolated yield. cUnder air atmosphere. dIrradiation time is 6 h.
Corresponding author. Tel.: +81-776-27-8633; fax: +81-776-
27-8747; e-mail: yyoshimi@u-fukui.ac.jp. (Y. Yoshimi)

2
Tetrahedron
Br
absorption spectra of 1a and 1b are observed (Supplementary
Material, Fig. S1). In addition, the efficiency of the second
photochemical step involving dehydrohalogenation of 3b is
lower than that of 3a. Finally, the low efficiencies of both steps
in the reaction of 1c leads to a low yield of both 2a and 3c and
high recovery of 1c even when a 3 h irradiation period is
employed. These observations suggest that 2-halomethyl
substituted naphthodihydrofurans 3 are the primary products
formed from the triplet excited states of the allyl 1-halo-2-
naphthyl ethers 1 and that these substances undergo secondary

h , 3 h
O
1a
2a
(3 mM)
+
t-BuOH
32%
3a
27%
Scheme 1. Photoreaction of 1a in t-BuOH
photoinduced
dehydrohalogenation
to
generate
2-
utilized for this process (Entries 5–8), irradiation of 1a in THF
and alcohols such as methanol, ethanol and i-PrOH gives rise to
complex product mixtures. Interestingly, when t-BuOH is
employed as solvent, photoreaction of 1a generates 2a (32%)
along with the 2-bromomethyl substituted naphthodihydrofuran
3a (27%) (Scheme 1). Similarly, the respective 2-halomethyl
substituted naphthodihydrofurans 3a-c are generated along with
2a when acetonitrile solutions of the ethers 1a-c are irradiated for
1 or 3 h (Scheme 2). Moreover, iodo-ether 1b is entirely
transformed to 3b (79%) along with 2a (8%) after a 1 h
irradiation time whereas only 62% of chloro-ether 1c is
converted to 2a (22%) and 3c (17%) using a longer 3 h
irradiation period.
methylnaphtho[2,1-b]furan 2a. In addition, the efficiency of the
first photocyclization is governed in the expected manner by the
nature of the halogen substituent on the naphthalene ring of the
substrate (I > Br > Cl)6; however, the efficiency of the second
photochemical dehydrohalogenation is not reasonable (Br > I >
Cl). The investigation of the detailed mechanism of the second
photoinduced dehydrohalogenation is underway in our laboratory.
Table 2. Photoreactions of 1d–g in CH3CNa
R2
Br
R1

h , 1 h

h , 3 h
O
R2
2a
1a (3 mM)
+
3a
O
CH3CN
42%
CH3CN
9%
R1
Recovery of 1a; 38%
I
1d; R1=H, R2=CH3
1e
2d-g
; R1=CH3, R2=CH3
I
1f; R1=H, R2=Ph

h
1g
O
; R1=H, R2=CO2CH3
Entry
O
2a
+
CH3CN
b
2
1
Yield of /%
3b
1b
(3 mM)
1
2
3
4
1d
1e
68
61
50
35
1h;
3h;
8%
38%
79%
45%
1f
Cl
1g
aIrradiation of solutions for 3 h under Ar atmosphere. bIsolated
yields.
Cl
O

h , 3 h
O
2a
22%
+
CH3CN
In order to gain information about the substrate scope of the
3c
1c
(3 mM)
1c
Recovery of ; 38%
new
2-methylnaphtho[2,1-b]furan
forming
process,
17%
photoreactions of allyl bromonaphthyl ethers 1d–g, 5 and 7 in
acetonitrile were investigated. The results show that irradiation of
solutions of ethers 1d–g (3 mM) for 3 h periods leads to the
production of the respective naphtho[2,1-b]furans 2d–g in
moderate yields (Table 2). Actually, irradiation of an acetonitrile
solution of 1e for the short time period of 0.5 h leads mainly to
formation of the dihydrofuran 4, which is then converted to 2e
upon prolonged irradiation (Scheme 4). Moreover, a prolonged
irradiation period of 12 h is required to transform the
regioisomeric allyl 2-bromo-1-naphthyl ether 5 to the 2-
methylnaphtho[1,2-b]furan 6 (62%) (Scheme 5). In contrast,
irradiation of a solution of allyl 3-bromo-2-naphthyl ether 7 for
Scheme 2. Photoreactions of 1a-c in CH3CN.
Significantly, irradiation of acetonitrile solutions of the 2-
bromomethyl, 2-iodomethyl, 2-chloromethyl substituted
naphthodihydrofurans (3a–c) for 1 h results in the production of
2-methylnaphtho[2,1-b]furan 2a in respective 76%, 16%, and 5%
(67% 3b and 90% 3c recovery) yields (Scheme 3). Moreover, the
efficiency (reflected in irradiation time) of the initial
photocyclization step in reaction of 1b to generate 3b is greater
than that of the first step in reaction of 1a, even the similar
12
h does not promote formation of the corresponding

h , 1 h
naphthofuran and leads to quantitative recovery of the starting
material.
2a
3a (3 mM)
3b (3 mM)
CH3CN
76%

h , 1 h
2a
CH3CN
16%
3b
Recovery of
; 67%

h , 0.5 h
O
1e
2e
(3 mM)
+

h , 1 h
CH3CN
25%
3c
2a
(3 mM)
CH3CN
5%
4
61%
Recovery of 3c; 90%
Scheme 4. Photoreaction of 1e in short irradiation (0.5 h).
Scheme 3. Photoreactions of 3a–c for 1 h in CH3CN.

3
Supplementary Material
O
O
Br

h , 12 h
Supplementary material (UV absorption spectra of 1a–c, 5 and
7, experimental procedures, and characterization of the
compounds) associated with this article can be found, in the
online version, at doi:###.
CH3CN
6
62%
5 (3 mM)

h
Br
O
CH3CN
References and notes
7 (3 mM)
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(f) Kwiecien, H.; Smist, M.; Kowalewska, M. Curr. Org. Synth.
2012, 9, 529.
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Srivastava, V.; Negi, A. S.; Kumar, J. K.; Faridi, U.; Sisodia, B.
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Scheme 5. Photoreactions of 5 and 7 in CH3CN.
The results described above show that 2-methylnaphtho[2,1-
b]furans and 2-methylnaphtho[1,2-b]furans can be efficiently
prepared by using photochemical reactions of the corresponding
1-bromo-2-naphthyl and 2-bromo-1-naphthyl allyl ethers. In
addition, observations made in this effort suggest that a plausible
mechanism for these photoreactions (Scheme 6) begins with
homolytic C-halogen bond cleavage in the triplet states of the
substrates to generate radical pairs,6 which undergo 5-exo type
cyclization and halogen atom capture to produce the initially
formed 2-halomethyl substituted naphthodihydrofurans 3 similar
3. (a) Hosokawa, T.; Yamashita, S.; Murahashi, S-I.; Sonoda, A. Bull.
Chem. Soc. Jpn. 1976, 49, 3662. (b) Larock, R. C.; Stinn, D. E.
Tetrahedron Lett. 1988, 29, 4687. (c) Roshchin, A. I.; Kel’chevski,
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Xie, X.; Chen, B.; Lu, J.; Han, J.; She, X.; Pan, X. Tetrahedron
Lett. 2004, 45, 4635.
to
photoinduced dehydrohalogenation of 3 takes place to generate
alkylidene dihydrofuran intermediates that undergo
atom-transfer
radical
cyclizations7.
Subsequently,
8
tautomerization to generate the naphthofuran products 2. In the
case of 1e (R1=CH3, R2=CH3), the photochemical
dehydrohalogenation leads to the respective formation of 8 and
the regioisomeric product 4, which is photochemically
tautomerized to 2a. Compared to the conventional methods used
to induce cyclization reactions of substrates similar to 1, which
require the use of Pd and Cu catalysts, the new photochemical
method utilizes light as a less toxic, more readily available, and
non by-product forming reagent. Applications of this
methodology to the synthesis of benzofurans are in progress.
4. Yoshimi, Y.; Kanai, H.; Nishikawa, K.; Ohta, Y.; Okita, Y.;
Maeda, K.; Morita, T. Tetrahedron Lett. 2013, 54, 2419.
5. General procedure for photoreactions of 1; An acetonitrile
solutions containing allyl 1-bromo-2-naphthyl ethers 1 (3 mM) in
Pyrex vessels (18 mm x 180 mm) were purged with argon for 10
min. The solutions were irradiated with 100 W high-pressure
mercury lamp for 3 h, and the resulting mixture was evaporated.
The product was purified by silica gel column chromatography
using hexane and EtOAc as eluents to give 2.
6. (a) Grimshaw, J.; de Silva, A. P. Chem. Soc. Rev. 1981, 10, 181.
(b) Schutt, L.; Bunce, N. J. CRC Handbook of Organic
Photochemistry and Photobiology, 2nd Edition, edited by Horspool,
W.; Leuci, F., CRC Press LLC, 2004, 38-1. (c) Pretali, L.; Albini,
A. CRC Handbook of Organic Photochemistry and Photobiology,
3rd Edition, edited by Griesbeck, A.; Oelgemoller, M.; Ghetti, F.
Taylor & Francis Group, 2012, 369.
Br
3
Intersystem
crossing
*
O
R2

h
1
*
1
1
R1
7. (a) Curran, D. P.; Chen, M.-H.; Kim, D. J. Am. Chem. Soc. 1986,
108, 2489. (b) Clark, A. J. Chem. Soc. Rev. 2002, 31, 1. (c)
Oshima, K. Bull. Chem. Soc. Jpn. 2008, 81, 1.
R2
Br
R1
Radical
cyclization
O
R2
O
+
Br
R1
R2
Br
R2
R1

h
R1


or h
Dehydro-
halogenation
O
Tautomerization
O
2
- HBr
3
8
Scheme 6. Plausible mechanism for photoreactions of 1.