Copper(II) acetate mediated reactions of methylenecyclopropane and diphenyl diselenide

Article abstract of DOI:10.1055/s-2007-980361

Phenylselenyl-substituted cyclobutenes and 1,3-butadienes were obtained from a copper(II) acetate mediated reaction between methylenecyclopropanes and diphenyl diselenide. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-980361

LETTER
1371
Copper(II) Acetate Mediated Reactions of Methylenecyclopropane and
Diphenyl Diselenide
C
opper(II) Acet
e
a
te Mediate
i
d
R
eactions
Y
of Methylenecycloupropane and a
,
D
iphenyl
D
iselenid
X
e
ian 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 20 December 2006
CH2
Abstract: Phenylselenyl-substituted cyclobutenes and 1,3-buta-
dienes were obtained from a copper(II) acetate mediated reaction
between methylenecyclopropanes and diphenyl diselenide.
R1
R2
R1
R2
R1
R2
PhSe
PhSe
PhSe
Key words: methylenecyclopropane, free radical, selenium, cop-
per, electron transfer
1
3
2
R1
R2
PhSe
Methylenecyclopropanes 1 (MCPs), which are highly
strained but readily accessible molecules, are of current
interest in synthetic organic chemistry.1 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 metals3 or
Lewis acids.4 Recently, free-radical reactions of MCPs
have also been widely investigated.5
PhSe
PhSe
4
Cu(II)
?
Scheme 1
44% yield, respectively (Table 1, entry 2). When the reac-
tion was performed in DMSO, it proceeded very slowly
and only trace amounts of 4a were obtained (Table 1,
entry 3). Interestingly, when acetic acid was employed, 2-
phenylselenyl-3,3-diphenylcyclobutene 6a could be ob-
tained in 65% yield (Table 1, entry 4).
Free-radical addition of diphenyl diselenide to methyl-
enecyclopropanes has been reported.5c,g In this reaction, a
phenylselenyl radical, generated from the homolytic
cleavage of diphenyl diselenide, was added to the MCP to
give the phenylselenyl-substituted homoallylic free radi-
cal 3, which then reacted with another molecule of di-
phenyl diselenide to produce 2,4-diphenylselenylbut-1-
ene (4) as the final product (Scheme 1). It is well known
that carbonium ions can be generated from alkyl radicals
by electron transfer in the presence of copper(II) acetate to
produce organocopper intermediates, which could poten-
tially produce some interesting compounds via further re-
actions.6 Hence, it is of interest to investigate the reaction
of MCPs and diphenyl diselenide in the presence of
copper(II) acetate.
Table 1 Reaction of Diphenylmethylenecyclopropane (1a), Di-
phenyl Diselenide and Copper(II) Acetate under Visible-Light
Irradiationa
Ph
PhSe
+
PhSe
Ph
Ph
Ph
Cu(OAc)2·H2O
4a
+ (PhSe)2
hν (> 300 nm)
Ph
Ph
Ph
HO
Ph
solvent, N2
+
1a
SePh
SePh
5a
6a
Initially, we examined the reaction of diphenylmethyl-
enecyclopropane (1a), diphenyl diselenide and copper(II)
acetate under visible light irradiation using chloroform as
the solvent. After two hours, only free-radical adduct 4a
was obtained in 72% yield (Table 1, entry 1). This unsuc-
cessful result was possibly due to the poor solubility of
copper(II) acetate in chloroform. We therefore tried using
acetonitrile as solvent as it has a higher polarity. Under
similar conditions, 4a and 5a were produced in 15% and
Entry Solvent
Time
(h)b
Yield of 4a Yield of 5a Yield of 6a
(%)c
(%)c
(%)c
1
2
3
4
CHCl3
MeCN
DMSO
AcOH
2
5
8
5
72
0
0
15
44
0
0
trace
0
0
0
65
a 1a (0.3 mmol), (PhSe)2 (0.3 mmol), Cu(OAc)2 (0.3 mmol) and
solvent (2 mL) were employed.
SYNLETT 2007, No. 9, pp 1371–1374
Advanced online publication: 23.05.2007
DOI: 10.1055/s-2007-980361; Art ID: W25706ST
© Georg Thieme Verlag Stuttgart · New York
0
1.
0
6.
2
0
0
7
b The reaction was monitored by TLC (eluent: PE).
c Isolated yields.

1372
L. Yu, X. Huang
LETTER
Cyclobutene derivatives, which are not very easy to
prepare, are pivotal skeletons in many natural products
with an unusual spectrum of biological activities.7 They
are also useful building blocks in synthetic organic chem-
istry.7 Selenium compounds are of great interest because
of their synthetic applications and biological activities
including antitumor, antibacterial activities and other
properties.8 2-Phenylselenyl-3,3-diarylcyclobutene (6),
containing both a cyclobutene structural unit and a
selenium atom, may have potential biochemical activity
and applications in organic synthesis.9 Thus, a series of
2-phenylselenyl-3,3-diarylcyclobutenes 6 were prepared
R
R
R
R
H2C
PhSe
R
R
PhSe
PhSe
1
2
3
Cu(OAc)2
CuIIOAc
CuIOAc
R
R
R
R
H2C
PhSe
R
R
SePh
PhSe
CuOAc
PhSe
R
R
6
10
9
from various MCPs
1 under similar conditions
Scheme 2
(Table 2).10
Table 2 Synthesis of 2-Phenylselenyl-3,3-diarylcyclobutenesa
1e) were employed, only trace amounts of 2-phenylsele-
nyl-3,3-diarylcyclobutenes were obtained.11 Hence, the
present method provides a facile entry to various 2-phen-
ylselenyl-3,3-diarylcyclobutenes.
R
R
R
Cu(OAc)2·H2O
+ (PhSe)2
SePh
hν (> 300 nm)
R
AcOH, N2
1
6
A possible mechanism for the formation of cyclobutene 6
is shown in Scheme 2. The phenylselenyl free radical,
generated from the homolytic cleavage of diphenyl di-
selenide, adds to MCP 1 to form the intermediate 2, which
immediately undergoes homoallylic rearrangement to
give 3.5a,c Compound 3 then reacts with copper(II) acetate
to generate an organocopper intermediate 9,6 which
undergoes an intramolecular insertion of C=C to C–Cu to
produce an intermediate 10 followed by b-elimination to
afford the final product 6.6
Entry
R
Yield of 6 (%)b
65 (6a)
1
2
3
4
5
Ph (1a)
p-FC6H4 (1b)
60 (6b)
p-ClC6H4 (1c)
p-MeC6H4 (1d)
p-MeOC6H4 (1e)
62 (6c)
53 (6d)
50 (6e)
When monosubstituted MCP 1f was employed, 7f was ob-
tained instead of the expected 6f (Scheme 3). This was
presumably due to less steric hindrance around the free-
radical intermediate 2, which allowed for the attack of the
copper species prior to the homoallylic rearrangement.
Similarly, when alkyl-substituted MCP 1g was employed,
attack of the copper species occurred before the homoal-
lylic rearrangement. Subsequent b-elimination then gave
the final product 8g.
a 1 (0.3 mmol), (PhSe)2 (0.3 mmol), Cu(OAc)2 (0.3 mmol) and AcOH
(2 mL) were employed.
b Isolated yields.
Previous literature has indicated that the reaction of MCPs
and phenylselenyl chloride would produce 2-phenylsele-
nyl-3,3-diarylcyclobutenes and 2-phenyl-4-chloro-1,1-di-
arylbut-1-enes. However, the yields of 2-phenylselenyl-
3,3-diarylcyclobutenes were low, and when MCPs with
an electron-donating group on the benzene ring (1d and
AcOCuII
AcO
AcO–
p-BrC6H4
Cu(OAc)2·H2O
p-BrC6H4
p-BrC6H4
SePh
+ (PhSe)2
hν (> 300 nm)
AcOH, N2
– CuOAc
SePh
1f
7f (58%)
AcOCuII
Cu(OAc)2·H2O
Ph
Ph
Ph
+ (PhSe)2
hν (> 300 nm)
AcOH, N2
PhSe
SePh
8g (66%)
1g
Scheme 3
Ph
Ph
Ph
Ph
Ph
Cu(OAc)2·H2O
AcOCuII
+
(PhSe)2
110 °C
AcOH, N2
PhSe
Ph
PhSe
1a
9
11a (42%)
Scheme 4
Synlett 2007, No. 9, 1371–1374 © Thieme Stuttgart · New York

LETTER
Copper(II) Acetate Mediated Reactions of Methylenecyclopropane and Diphenyl Diselenide
1373
Interestingly, when the reaction was undertaken under In conclusion, we have found that the copper(II) acetate
heat instead of visible light, the result was quite different. mediated reactions of MCPs and diphenyl diselenide or
Under these conditions, b-elimination occurred on the diphenyl disulfide gave different results under different
intermediate 9 to give the phenylselenyl-substituted buta- reaction conditions. Under visible light irradiation, phen-
1,3-diene 11 (Scheme 4).
ylselenyl-substituted cyclobutenes were generated, while
under heating conditions, phenylselenyl- or phenyl-
sulfanyl-substituted buta-1,3-dienes were obtained. All of
these analogues are extremely useful in organic synthesis.
Further screening demonstrated that using less solvent
decreased the amount of solvent adduct and enhanced the
yield of 11a (Table 3, entry 2).
Table 3 Reaction of Diphenylmethylenecyclopropane (1a),
Acknowledgment
Diphenyl Diselenide and Copper(II) Acetate under Heata
This work was supported by the National Natural Science Founda-
tion of China (20332060, 20472072) and Academic Foundation of
Zhejiang Province.
Ph
Ph
Cu(OAc)2·H2O
+
(PhSe)2
110 °C
solvent, N2
Ph
PhSe
11a
Ph
1a
References and Notes
Entry
Solvent (volume)
HOAc (2 mL)
HOAc (0.2 mL)
–
Time (h)b Yield of 11a (%)c
(1) For the preparation of the MCPs, see: Brandi, A.; Goti, A.
Chem. Rev. 1998, 98, 589; and references cited therein.
(2) (a) Brandi, A.; Cicchi, S.; Cordero, F. M.; Goti, A. Chem.
Rev. 2003, 103, 1213. (b) Nakamura, I.; Yamamoto, Y. Adv.
Synth. Catal. 2002, 344, 111; and references cited therein.
(3) (a) Camacho, D. H.; Nakamura, I.; Saito, S.; Yamamoto, Y.
J. Org. Chem. 2001, 66, 270. (b) Tsukada, N.; Shibuya, A.;
Nakamura, I.; Yamamoto, Y. J. Am. Chem. Soc. 1997, 119,
8123. (c) Nakamura, I.; Saito, S.; Yamamoto, Y. J. Am.
Chem. Soc. 2000, 122, 2661. (d) Nakamura, I.; Siriwardana,
A. I.; Saito, S.; Yamamoto, Y. J. Org. Chem. 2002, 67,
3445. (e) Nakamura, I.; Itagaki, H.; Yamamoto, Y. J. Org.
Chem. 1998, 63, 6458. (f) Nakamura, I.; Oh, B. H.; Saito, S.;
Yamamoto, Y. Angew. Chem. Int. Ed. 2001, 40, 1298.
(g) Lautens, M.; Ren, Y.; Delanghe, P. H. M. J. Am. Chem.
Soc. 1994, 116, 8821. (h) Lautens, M.; Ren, Y. J. Am. Chem.
Soc. 1996, 118, 9597. (i) Lautens, M.; Ren, Y. J. Am. Chem.
Soc. 1996, 118, 10668. (j) Suginome, M.; Matsuda, T.; Ito,
Y. J. Am. Chem. Soc. 2000, 122, 11015. (k) Lautens, M.;
Meyer, C.; Lorenz, A. J. Am. Chem. Soc. 1996, 118, 10676.
(l) Bessmertnykh, A. G.; Blinov, K. A.; Grishin, Y. K.;
Donskaya, N. A.; Tveritinova, E. V.; Yur'eva, N. M.;
Beletskaya, I. P. J. Org. Chem. 1997, 62, 6069.
(4) (a) Shi, M.; Xu, B. Tetrahedron Lett. 2003, 44, 3839.
(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) Xu, B.; Chen, Y.; Shi, M. Tetrahedron Lett. 2002, 43,
2781. (b) Zhou, H.; Huang, X.; Chen, W. J. Org. Chem.
2004, 69, 5471. (c) Liu, L.; Shi, M. Chem. Commun. 2004,
2878. (d) Huang, X.; Yu, L. Synlett 2005, 2953. (e) Huang,
J.; Shi, M. J. Org. Chem. 2005, 70, 3859. (f) Yu, L.; Huang,
X.; Xie, M. Synlett 2006, 423. (g) Yu, L.; Huang, X. Synlett
2006, 2136.
1
2
3
4
2
2
3
6
42
68
10d
0
DMSO (2 mL)
a 1a (0.3 mmol), (PhSe)2 (0.3 mmol) and Cu(OAc)2 (0.3 mmol) were
employed.
b The reaction was monitored by TLC (eluent: PE).
c Isolated yields.
d Free-radical adduct 4a was obtained as the main product in 45%
yield.
Under the optimized conditions, a series of phenylselenyl-
substituted butadienes were synthesized (Table 4, entries
1–4).12 When diphenyl disulfide was employed, the corre-
sponding phenylsulfanyl-substituted 1,3-butadienes were
obtained (Table 4, entries 5–7). Buta-1,3-dienes are use-
ful building blocks in synthetic organic chemistry.13 Here,
we have developed a convenient method for the synthesis
of phenylselenyl- or phenylsulfanyl-substituted buta-1,3-
dienes.
Table 4 Synthesis of Phenylselenyl- or Phenylsulfanyl-Substituted
Buta-1,3-dienes
R
R
R
Cu(OAc)2·H2O
+
(PhY)2
110 °C
R
PhY
11
AcOH, N2
1
Entry
R
Y
Yield of 11 (%)a
68 (11a)
1
2
3
4
5
6
7
Ph (1a)
Se
Se
Se
Se
S
(6) (a) Kochi, J. K. J. Am. Chem. Soc. 1963, 85, 1958.
(b) Kochi, J. K.; Bemis, A. J. Am. Chem. Soc. 1968, 90,
4038. (c) Kochi, J. K.; Bemis, A.; Jenkins, C. L. J. Am.
Chem. Soc. 1968, 90, 4616. (d) Kochi, J. K. Free Radicals,
Vol. I; Wiley: New York, 1968, 591.
(7) For selected recent articles about cyclobutenes, see:
(a) Delas, C.; Urabe, H.; Sato, F. J. Am. Chem. Soc. 2001,
123, 7937. (b) Tantillo, D. J.; Hoffmann, R. J. Am. Chem.
Soc. 2001, 123, 9855. (c) Winkler, J. D.; McLaughlin, E. C.
Org. Lett. 2005, 7, 227. (d) Murakami, M.; Usui, I.;
Hasegawa, M.; Matsuda, T. J. Am. Chem. Soc. 2005, 127,
1366. (e) Inanaga, K.; Takasu, K.; Ihara, M. J. Am. Chem.
p-FC6H4 (1b)
p-ClC6H4 (1c)
p-MeC6H4 (1d)
Ph (1a)
46 (11b)
40 (11c)
54 (11d)
63 (11e)
p-FC6H4 (1b)
p-MeC6H4 (1d)
S
48 (11f)
S
52 (11g)
a Isolated yields.
Synlett 2007, No. 9, 1371–1374 © Thieme Stuttgart · New York

1374
L. Yu, X. Huang
LETTER
d = 46.9, 61.9, 126.4, 127.4, 127.5, 128.0, 128.1, 129.3,
Soc. 2005, 127, 3668.
(8) (a) Back, T. G. Organoselenium Chemistry: A Practical
Approach; Oxford: UK, 1999. (b) Zeni, G.; Stracke, M. P.;
Nogueira, C. W.; Braga, A. L.; Menezes, P. H.; Stefani, H.
A. Org. Lett. 2004, 6, 1135. (c) Prediger, P.; Moro, A. V.;
Nogueira, C. W.; Savegnago, L.; Menezes, P. H.; Rocha, J.
B. T.; Zeni, G. J. Org. Chem. 2006, 71, 3786. (d) Soares do
Rego Barros, O.; Nogueira, C. W.; Stangherlin, E. C.;
Menezes, P. H.; Zeni, G. J. Org. Chem. 2006, 71, 1552.
(e) Shafiee, A.; Mazloumi, A.; Cohen, V. I. J. Heterocycl.
Chem. 1979, 16, 1563. (f) Shafiee, A.; Shafaati, A.;
Khamench, B. H. J. Heterocycl. Chem. 1989, 26, 709.
(9) (a) Murakami, M.; Usui, I.; Hasegawa, M.; Matsuda, T.
J. Am. Chem. Soc. 2005, 127, 1366. (b) Shi, M.; Wang, B.;
Li, J. Eur. J. Org. Chem. 2005, 759.
(10) 2-Phenylselenyl-3,3-diarylcyclobutene (6), typical
procedure: Under an N2 atmosphere, a solution of
133.9, 134.8, 141.8, 144.1; MS (EI, 70 eV): m/z (%) = 362
(12) [M+], 281 (14), 205 (100); HRMS (EI): m/z calcd for
C22H18Se: 362.0574; found: 362.0574.
(11) Liu, L.; Shi, M. J. Org. Chem. 2004, 69, 2805.
(12) 1,1-Diaryl-2-phenylselenylbuta-1,3-diene (11), typical
procedure: Under an N2 atmosphere, a solution of
diphenylmethylenecyclopropane (1a, 0.062 g, 0.3 mmol),
diphenyl diselenide (0.094 g, 0.3 mmol) and Cu(OAc)2
(0.060 g, 0.3 mmol) in AcOH (0.2 mL) acid was stirred at
110 °C. The reaction was monitored by TLC (PE). When the
reaction was complete, the solvent was evaporated under
vacuum and the residue was subjected to preparative TLC
(PE) to afford 11a in 68% yield. IR (film): 3054, 1576, 1477,
1440, 737, 697 cm–1; 1H NMR (400 MHz, CDCl3): d = 7.14–
7.34 (m, 15 H), 6.56–6.63 (m, 1 H), 5.81–5.85 (m, 1 H),
5.22–5.25 (m, 1 H); 13C NMR (100 MHz, CDCl3): d = 120.9,
125.8, 127.3, 127.7, 128.1, 128.9, 129.4, 130.0, 130.1,
130.2, 133.0, 135.4, 141.6, 144.1, 151.6; MS (EI, 70 eV):
m/z (%) = 362 (30) [M+], 281 (15), 205 (100); HRMS (EI):
m/z calcd for C22H18Se: 362.0574; found: 362.0567.
(13) For selected recent articles about buta-1,3-dienes, see:
(a) Shi, M.; Wang, B.; Huang, J. J. Org. Chem. 2005, 70,
5606. (b) Wong, K.; Hung, Y. Tetrahedron Lett. 2003, 44,
8033. (c) Taylor, D. K.; Avery, T. D.; Greatrex, B. W.;
Tiekink, E. R. T.; Macreadie, I. G.; Macreadie, P. I.;
Humphries, A. D.; Kalkanidis, M.; Fox, E. N.; Klonis, N.;
Tilley, L. J. Med. Chem. 2004, 47, 1833.
diphenylmethylenecyclopropane (1a, 0.062 g, 0.3 mmol),
diphenyl diselenide (0.094 g, 0.3 mmol) and Cu(OAc)2
(0.060 g, 0.3 mmol) in AcOH (2 mL) was irradiated with a
tungsten lamp (300 W). The temperature rose to 40 °C
because of the irradiation. The reaction was monitored by
TLC (PE). When the reaction was complete, the solvent was
evaporated under vacuum and the residue was subjected to
preparative TLC (PE) to afford 6a in 65% yield. IR (KBr):
3055, 1575, 1491, 1217, 1025, 750, 696 cm–1; 1H NMR (400
MHz, CDCl3): d = 7.22–7.60 (m, 15 H), 6.12 (t, J = 0.8 Hz,
1 H), 3.17 (d, J = 0.8 Hz, 2 H); 13C NMR (100 MHz, CDCl3):
Synlett 2007, No. 9, 1371–1374 © Thieme Stuttgart · New York