Reaction of methylenecyclopropanes and diphenyl diselenide under visible-light irradiation

Article abstract of DOI:10.1055/s-2006-948210

The reaction of methylenecyclopropanes with diphenyl diselenide promoted by visible light was investigated and a series of 2,4-diphenylselenyl-1-butenes was prepared under mild conditions. Interestingly, with the addition of oxidant such as dibenzoyl peroxide, 1-(phenylselenyl)cyclobutanols were obtained. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-948210

2136
LETTER
Reaction of Methylenecyclopropanes and Diphenyl Diselenide under
Visible-Light Irradiation
R
eaction of Met
e
hylenecyc
l
i
opropanes
an
Y
d Diphenyl
D
iseleunide ,a Xian Huang*a,b
a
Department of Chemistry, Zhejiang University(Campus Xixi), Hangzhou 310028, P. R. of China
b
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai, 200032, P. R. of China
Fax +86(571)88807077; E-mail: huangx@mail.hz.zj.cn
Received 28 March 2006
Table 1 Reaction of MCPs and Diphenyl Diselenide under Visible-
Light Irradiation in Different Solvents
Abstract: The reaction of methylenecyclopropanes with diphenyl
diselenide promoted by visible light was investigated and a series of
2,4-diphenylselenyl-1-butenes was prepared under mild conditions.
Interestingly, with the addition of oxidant such as dibenzoyl perox-
ide, 1-(phenylselenyl)cyclobutanols were obtained.
Ph
Ph
hν
N2
PhSe
+ PhSeSePh
PhSe
2a
Ph
Ph
Key words: methylenecyclopropanes, selenium, radicals, radical
1a
reactions
Entry
Solventa
PhH
Time (h)b
Yield (%)c
1
2
3
4
5
5
3.5
12
8
77
87
39
72
70
Methylenecyclopropanes, which are highly strained but
readily accessible molecules, are of current interest in
synthetic organic chemistry.1 The relief of their ring strain
provides a potent thermodynamic driving force, which
facilitates the construction of complex and interesting
organic molecules under mild conditions.2 During the last
decade, much attention has been paid to the reactions of
MCPs catalyzed by transition metal3 or Lewis acid.4
Recently, our group reported several free radical reactions
of MCPs, providing a useful synthetic method for 1,2-di-
hydronaphthalenes.5
PhMe
MeCN
CCl4
EtOH
9
a Amounts of MCP and diphenyl diselenide were both 0.3 mmol, the
amount of solvent was 5 mL.
b The reaction was monitored by TLC.
c Isolated yields.
In the research on MCPs’ free-radical-mediated reactions,
Shi6 reported heat-promoted free radical reaction of
MCPs and diphenyldiselenide to synthesize 2,4-diphen-
ylselenyl-1-butenes, which could be further transformed
to 3-phenylselenyl-2,5-dihydrofuran derivatives. How-
ever, this reaction requires a high temperature (150 °C),
which might limit its application in organic synthesis. It is
well known that diphenyl diselenide has its maximum ab-
sorption in the near-UV range, thus irradiation with the
light of wavelength longer than 300 nm can also induce
homolytic cleavage of the selenium–selenium bond to
generate phenylseleno radical.7 In this paper, we wish to
present the reaction of MCPs with diphenyl diselenide
under visible-light irradiation.
strated that toluene was a better solvent, and the yield of
2a could be improved to 87% (Table 1, entry 2).
Under these conditions, a series of MCPs was employed
and the corresponding products 2,4-diphenylselenyl-1-
butenes were prepared in good yields8 (Table 2). In this
reaction, high temperature was not required and the reac-
tion conditions were much milder.
Interestingly, when the reaction was proceeded without
nitrogen protection in EtOH, in addition to 1,1-diphenyl-
2,4-diphenylselenyl-1-butene (2a), an unexpected ring-
expansion product 2,2-diphenyl-1-phenylselenylcyclo-
butanol (3a) was obtained in 37% yield (Scheme 1).
Further screening demonstrated that addition of dibenzoyl
peroxide could avoid the formation of 2a and the yield of
3a could be increased to 66%. Under similar reaction
conditions, various 1-(phenylselenyl)cyclobutanols were
prepared in moderate yields9 (Table 3).
We initially examined the reaction of (diphenylmethyl-
ene)cyclopropane (1a) and diphenyl diselenide in nitro-
gen under visible-light irradiation with benzene as
solvent. After five hours, the expected product 1,1-di-
phenyl-2,4-diphenylselenyl-1-butene (2a) was obtained
in 77% yield (Table 1, entry 1). Further screening demon-
Cyclobutane derivatives, which are not easily accessible,
are pivotal skeletons in many natural products with inter-
esting biological activities and are useful building blocks
in synthetic organic chemistry.10 Selenium compounds
are of great interest because of their biological activities
such as antitumor, antibacterial and other properties.11
SYNLETT 2006, No. 13, pp 2136–2138
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7
.0
8
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0
0
6
Advanced online publication: 09.08.2006
DOI: 10.1055/s-2006-948210; Art ID: W06506ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Reaction of Methylenecyclopropanes and Diphenyl Diselenide
2137
Table 2 Preparation of 2,4-Diphenylselenyl-1-butenes
A plausible mechanism was suggested as follows: the
diphenyl diselenide was first oxidized to benzeneselen-
enic anhydride 4,13 which added to the C=C double bound
of the MCPs to form the cyclopropyl cationic intermedi-
ates 5 and 6. Rearrangement of carbonium ion 6 gave
ring-expanded cyclobutyl cation 7,14 which reacted with
benzeneselenenic anion to give the intermediate 8. Alco-
holysis of 8 gave the final product 3 (Scheme 2).
R1
R1
R2
hν >300 nm
+
PhSeSePh
PhSe
toluene, N2
R2
PhSe
1
2
Entry
R1, R2
Ph, Ph (1a)
Yield (%)a
87 (2a)
80 (2b)
75 (2c)
72 (2d)
71 (2e)
90 (2f)
1
2
3
4
5
6
7
8
R1
R1
R2
p-MeC6H4, p-MeC6H4 (1b)
p-MeOC6H4, p-MeOC6H4 (1c)
p-FC6H4, p-FC6H4 (1d)
p-ClC6H4, p-ClC6H4 (1e)
-CH2CH2CH(Ph)CH2CH2- (1f)
-(CH2)5- (1g)
R2
[O]
"PhSeOSePh"
PhSeSePh
Se
SePh
OH
R1
4
5
Ph
R2
R1
SePh
EtOH
3
SePh
R1
OSePh
R1
R2
72 (2g)
76b (2h)
SePh
R2
R2
8
7
6
p-BrC6H4, H (1h)
Scheme 2
a Isolated yields.
b Z/E = 1:1 as determined by 1H NMR.
For proving the above mechanism that benzeneselenenic
anhydride (4) was formed at first and then underwent
electrophilic addition to carbon–carbon double bond. We
examined the reaction of styrene under the same reaction
conditions. Experimental results showed that the expected
product a-phenylselenyl acetophenone (9) was produced
in 50% yield after irradiation for three hours. Obviously,
the diphenyl diselenide was firstly oxidized to benzene-
selenenic anhydride (4), then added to the double bond of
the olefin, further elimination of PhSeH produced a-phen-
ylselenyl acetophenone (9)13 (Scheme 3).
OH
Ph
Ph
Ph
hν >300 nm
SePh
Ph
+ PhSeSePh
PhSe
PhSe
+
in air
Ph
Ph
3a
1a
2a
25%
37%
Scheme 1
Table 3 Preparation of 1-(Phenylselenyl)cyclobutanols
OH
R
hν >300 nm
SePh
R
+
PhSeSePh
O
dibenzoyl peroxide
dibenzoyl peroxide
PhSeSePh
+
SePh
R
Ph
Ph
hν >300 nm
EtOH, 3 h
R
9
1
3
50%
Entry
R, R
Yield (%)a
1
2
3
4
5
Ph (1a)
66
69
60
54
58
O
"PhSeOSePh"
PhSe
SePh
Ph
SePh
Ph
H
p-MeC6H4 (1b)
p-MeOC6H4 (1c)
p-FC6H4 (1d)
4
Scheme 3
p-ClC6H4 (1e)
In order to gain more mechanistic insights into this ring-
expansion reaction, we employed monosubstituted MCP
1-bromo-4-(cyclopropylidenemethyl)benzene (1h) as
substrate. However, when dibenzoyl peroxide was em-
ployed as oxidant in this reaction, a series of unidentified
products was obtained instead of the expected 4-bro-
mophenyl 1-(phenylselenyl)cyclopropyl ketone (10h),
this was probably because that the oxidizability of diben-
zoyl peroxide was too strong. Thus, we used air as weaker
oxidant. Even as we expected, 4-bromophenyl 1-(phen-
ylselenyl)cyclopropyl ketone (10h) was obtained when
monosubstituted MCP 1-bromo-4-(cyclopropylidene-
a Isolated yields.
1-(Phenylselenyl)cyclobutanols, containing both cyclo-
butane structural unit and selenium atom, may have po-
tential biochemical activity and applications in organic
synthesis.12
This methodology is only suitable for diaryl-substituted
MCPs. When alkyl-substituted MCPs were employed, a
series of side products was obtained instead of the desired
1-(phenylselenyl)cyclobutanols.
Synlett 2006, No. 13, 2136–2138 © Thieme Stuttgart · New York

2138
L. Yu, X. Huang
LETTER
(4) (a) Shi, M.; Xu, B. Tetrahedron Lett. 2003, 44, 3839.
methyl)benzene (1h) and diphenyl diselenide were irradi-
ated in air with EtOH as solvent (Scheme 4). Elimination
of PhSeH became feasible because of the presence of a
hydrogen atom adjacent to the carbocation. When diaryl-
substituted MCPs were employed, there was no hydrogen
atom linked to the cationic carbon, so elimination of
PhSeH was impossible and the rearrangement of carboni-
um ion happened.
(b) Huang, J.; Shi, M. Tetrahedron Lett. 2003, 44, 9343.
(c) Shao, L.; Shi, M. Eur. J. Org. Chem. 2004, 426. (d) Shi,
M.; Xu, B. Org. Lett. 2002, 4, 2145. (e) Shi, M.; Chen, Y.;
Xu, B.; Tang, J. Tetrahedron Lett. 2002, 43, 8019. (f) Shi,
M.; Shao, L.; Xu, B. Org. Lett. 2003, 5, 579. (g) Xu, B.;
Shi, M. Org. Lett. 2003, 5, 1415.
(5) (a) Zhou, H.; Huang, X.; Chen, W. J. Org. Chem. 2004, 69,
5471. (b) Huang, X.; Yu, L. Synlett 2005, 2953. (c) Yu, L.;
Huang, X.; Xie, M. Synlett 2006, 423.
(6) Liu, L.; Shi, M. Chem. Commun. 2004, 2878.
(7) Schmidt, U.; Müller, A.; Markau, K. Chem. Ber. 1964, 97,
405.
Br
O
hν >300 nm
+ PhSeSePh
Br
+
Br
(8) 2,4-Diphenylselenyl-1-butenes 2 – Typical Procedure.
A solution of(diphenylmethylene)cyclopropane (1a, 0.062
g, 0.3 mmol) and diphenyl diselenide (0.094 g, 0.3 mmol) in
5 mL of toluene was irradiated with a tungsten lamp (300 W)
under nitrogen atmosphere. The temperature rose to 40 °C
because of the irradiation. The reaction was monitored by
TLC (eluent: PE). After 3.5 h, the reaction terminated, the
solvent was evaporated under vacuum and the residue was
subjected to preparative TLC (eluent: PE) to afford 2a
(0.135 g, 87%). The melting point and spectra data were
consistent with literature.6 Other 2,4-diphenylselenyl-1-
butenes were prepared in a similar way.
(9) 1-Phenylselenylcyclobutanol 3 – Typical Procedure.
A solution of(diphenylmethylene)cyclopropane (1a, 0.062
g, 0.3 mmol), diphenyl diselenide (0.094 g, 0.3 mmol) and
dibenzoyl peroxide (0.073 g, 0.3 mmol) in 5 mL of EtOH
was irradiated with a tungsten lamp (300 W) in air. The
temperature rose to 40 °C because of the irradiation. The
reaction was monitored by TLC (eluent: PE). After 5 h, the
reaction terminated, the solvent was evaporated under
vacuum and the residue was subjected to preparative TLC
(eluent: EtOAc) to afford 3a (0.075 g, 66%). Other 1-
(phenylselenyl)cyclobutanols were prepared in a similar
way.
in air
SePh
SePh
SePh
1h
2h
20%
10h
46%
Scheme 4
In conclusion, we reported here an efficient transforma-
tion of MCPs to the corresponding 2,4-diphenylselenyl-1-
butenes under visible-light irradiation. We also developed
a novel and convenient method for the synthesis of 1-
(phenylselenyl)cyclobutanols. The reaction mechanism
and synthetic applications of this methodology are under
further investigations in our laboratory.
Acknowledgment
This work was supported by the National Natural Science Founda-
tion of China (20332060, 20472072) and Academic Foundation of
Zhejiang Province.
Selected Data for 3a: White solid, mp 106–107 °C. 1H
NMR (400 MHz, CDCl3): d = 7.23–7.57 (m, 15 H), 5.80 (s,
1 H, exchanged with D2O), 1.26–1.32 (m, 1 H), 0.64–0.70
(m, 2 H), 0.42–0.46 (m, 1 H). 13C NMR (100 MHz, CDCl3):
d = 6.1, 9.0, 51.1, 81.3, 127.0, 127.1, 127.3, 127.5, 127.7,
128.0, 128.2, 129.1, 131.0, 131.1, 140.1, 143.8. IR (KBr):
d = 3057, 1491, 1044, 806, 745, 703 cm–1. MS (EI, 70 eV):
m/z (%) = 380 (4) [M+ + H], 379 (1) [M+], 198 (33), 183 (40),
105 (100).
References and Notes
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Synlett 2006, No. 13, 2136–2138 © Thieme Stuttgart · New York