Organo-selenium induced radical ring-opening intramolecular cyclization or electrophilic cyclization of 2- (arylmethylene) cyclopropylaldehyde: A tunable synthesis of 1-naphthaldehydes or 3-oxabicyclo[3.1.0]hexan-2-ols

Article abstract of DOI:10.1021/jo900805a

(Chemical Equation Presented) 1-Naphthaldehydes and 3-oxabicyclo[3.1.0] hexan-2-ols can be prepared, respectively, by the intramolecular alkylation and cyclization of (E)-2-(arylmethylene)cyclopropylaldehyde 1 mediated by different organo-selenium reagent

Full text of DOI:10.1021/jo900805a

pubs.acs.org/joc
complex and interesting organic molecules.1 In the past
Organo-Selenium Induced Radical Ring-Opening
Intramolecular Cyclization or Electrophilic
Cyclization of 2- (Arylmethylene)
cyclopropylaldehyde: A Tunable Synthesis of
1-Naphthaldehydes or 3-Oxabicyclo[3.1.0]hexan-2-ols
decades, much attention has been paid to the transition metal2
and Lewis acid3 catalyzed reactions of MCPs through three
different reaction pathways, namely, addition to CdC bond,
distal, and proximal C-C bond cleavages. A troublesome
feature of unfunctional MCPs is their multiform reactivities
that may lead to formation of a variety of products.
Maozhong Miao† and Xian Huang*,†,‡
Recently, MCPs with functional groups attached to a
cyclopropyl ring have received considerable attention.4 Ma
previously reported a highly selective ring-opening cyclo-
isomerization of methylene- or alkylidenecyclopropyl ke-
tones catalyzed by Pd(II) catalyst,4a and Lautens has shown
a novel ring expansion of secondary methylenecyclopropyl
amides in the presence of MgI2,4c leading to useful com-
pounds with synthetic and biological importance. Wang has
presented the Friedel-Crafts reaction initiated by the direct
generation of a carbocation at the C3 position of MCP 1,1-
diesters through distal bond cleavage.4e Recently, we re-
ported substrate-controlled selective proximal and distal
C-C bond cleavage via Lewis acid mediated O-acylation
of 2-(arylmethylene)cyclopropylaldehyde.4f In principle, the
presence of functional groups may facilitate the selective
cleavage of C-C bonds of MCPs, thus delicately tuning the
regioselectivity of the reactions.
†Department of Chemistry, Zhejiang University
(Xixi Campus), Hangzhou 310028, People’s Republic of
China, and ‡State Key Laboratory of Organometallic
Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032,
People’s Republic of China
huangx@mail.hz.zj.cn
Received April 18, 2009
Organo-selenium compounds are now commonly em-
ployed as very useful and powerful reagents, which allow
the chemo-, regio-, and stereoselective introduction of new
functional groups into complex organic substrates.5 Sele-
nium can be introduced as an electrophile, a nucleophile, or a
radical.6 Shi and we have disclosed the reactions of MCPs
with various selenium reagents to afford useful selenium-
containing compounds.7 In this paper, we wish to report an
organo-selenium promoted reaction of formyl-substituted
MCPs, providing a selective synthesis of 1-naphthaldehydes
and 3-oxabicyclo[3.1.0]hexan-2-ols.
1-Naphthaldehydes and 3-oxabicyclo[3.1.0]hexan-2-ols
can be prepared, respectively, by the intramolecular
alkylation and cyclization of (E)-2-(arylmethylene)cyclo-
propylaldehyde 1 mediated by different organo-selenium
reagents. The properties of selenium reagents may play an
important role in the reactions. A rationale for these
transformations is proposed.
Initially, the reaction of (E)-1a and diphenyl diselenide
was performed in the presence of K2S2O8 in CH3CN at 70 °C,
Methylenecyclopropanes (MCPs), which are highly strained
but readily accessible carbocyclic molecules, have been exten-
sively studied and are usually employed for the construction of
(4) (a) Ma, S.; Zhang, J. Angew. Chem., Int. Ed. 2003, 42, 184. (b) Ma, S.;
Lu, L.; Zhang, J. J. Am. Chem. Soc. 2004, 126, 9645. (c) Lautens, M.; Han,
W.; Liu, J. H.-C. J. Am. Chem. Soc. 2003, 125, 4028. (d) Nakamura, M.;
Toganoh, M.; Ohara, H.; Nakamura, E. Org. Lett. 1999, 1, 7. (e) Hu, B.;
Xing, S.; Wang, Z. Org. Lett. 2008, 10, 5481. (f) Huang, X.; Miao, M. J. Org.
Chem. 2008, 73, 6884. (g) Chen, J; Lu, L; Ma, S. Tetrahedron 2008, 64, 8899.
(5) For the applications of selenium contained compounds, see: (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.
(6) (a) Wirth, T; Kulicke, K. J.; Fragale, G. J. Org. Chem. 1996, 61, 2686.
(b) Hassner, A; Amarasekara, A. Tetrahedron Lett. 1987, 58, 5185. (c)
Nicolaou, K. C.; Lysenko, Z. J. Am. Chem. Soc. 1977, 99, 3185. (d)
Masamune, S; Kaiho, T; Garvey, D. S. J. Am. Chem. Soc. 1982, 104, 5521.
(e) McKittrick, B. A.; Ganem, B. J. Org. Chem. 1985, 50, 5897. (f) Clive, D. L.
J.; Daigneault, S. J. Org. Chem. 1991, 56, 3801. (g) Ogawa, A.; Ogawa, I.;
Obayashi, R.; Umezu, K.; Doi, M.; Hirao, T. J. Org. Chem. 1999, 64, 86.
(7) (a) Liu, L.-P.; Shi, M. J. Org. Chem. 2004, 69, 2805. (b) Shi, M.; Lu,
J.-M. J. Org. Chem. 2006, 71, 1920. (c) Tian, G.-Q.; Li, J.; Shi, M. J. Org.
Chem. 2008, 73, 673. (d) Shi, M; Lua, J.-M.; Xu, G.-C. Tetrahedron Lett.
2005, 46, 4745. (e) Liu, L.; Shi, M. Chem. Commun. 2004, 2878. (f) Yu, L.;
Huang, X. Synlett 2007, 1371. (g) Yu, L.; Huang, X. Synlett 2006, 2136.
(1) Synthesis of MCPs: (a) Brandi, A.; Goti, A. Chem. Rev. 1998, 98, 589.
Recent reviews of MCPs: (b) Brandi, A.; Cicchi, S.; Cordero, F. M.; Goti, A.
Chem. Rev. 2003, 103, 1213. (c) Nakamura, I.; Yamamoto, Y. Adv. Synth.
Catal. 2002, 2, 111. (d) Nakamura, E.; Yamago, S. Acc. Chem. Res. 2002, 35,
867.
(2) Selected recent articles about transition-metal-catalyzed reactions of
MCPs: (a) Camacho, D. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. J. Org.
Chem. 2001, 66, 270. (b) Camacho, D. H.; Nakamura, I.; Saito, S.; Yama-
moto, Y. Angew. Chem., Int. Ed. 1999, 38, 3365. (c) Nakamura, I.; Itagaki,
H.; Yamamoto, Y. J. Org. Chem. 1998, 63, 6458. (d) Lautens, M.; Meyer, C.;
€
Lorenz, A. J. Am. Chem. Soc. 1996, 118, 10676. (e) Furstner, A.; Aissa, C.
J. Am. Chem. Soc. 2006, 128, 6306. (f) Saito, S.; Masuda, M.; Komagawa, S.
J. Am. Chem. Soc. 2004, 126, 10540. (g) Kawasaki, T.; Saito, S.; Yamamoto,
Y. J. Org. Chem. 2002, 67, 4911. (h) 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. (i) Chiusoli, G. P.; Costa,
M.; Melli, L. J. Organomet. Chem. 1998, 358, 495. (j) Zhao, L.; de Meijere, A.
Adv. Synth. Catal. 2006, 348, 2484.
(3) Selected recent articles about Lewis acid mediated reactions of MCPs:
(a) Nakamura, I.; Kamada, M.; Yamamoto, Y. Tetrahedron Lett. 2004, 45,
2903. (b) Patient, L.; Berry, M. B.; Kiburn, J. D. Tetrahedron Lett. 2003, 44,
1015. (c) Shi, M.; Xu, B. Org. Lett. 2002, 4, 2145. (d) Shi, M.; Liu, L.-P.;
Tang, J. Org. Lett. 2006, 8, 4043.
5636 J. Org. Chem. 2009, 74, 5636–5639
Published on Web 06/26/2009
DOI: 10.1021/jo900805a
r
2009 American Chemical Society

Miao and Huang
JOCNote
TABLE 1. Reaction of (E)-1a with Various Selenium Reagents under Different Conditionsa
entry
selenium reagants (equiv)
temp (°C)
solvent
time (min)b
yield (%)c
1
2
3
4
5
6
7
8
9
K2S2O8 (1.5) PhSeSePh (0.5)
(NH4)2S2O8 (1.5) PhSeSePh (0.5)
(NH4)2S2O8 (1.5) PhSeSePh (0.5)
(NH4)2S2O8 (1.5) PhSeSePh (0.5)
(NH4)2S2O8 (1.0) N-PSP (1.2)
(NH4)2S2O8 (1.0) N-PSP (1.2)
(NH4)2S2O8 (1.0) N-PSP (1.2)
(NH4)2S2O8 (1.0) PhSeBr (1.2)
(NH4)2S2O8 (1.0) PhSeCl (1.2)
70
70
reflux
70
70
45
100
70
CH3CN
CH3CN
THF
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
20
20
30
5
5
5
5
10
30
26
47
NRd
55
61
52
21
trace
trace
70
aUnless otherwise specified, the reaction was carried out using (E)-1a (0.2 mmol) in 3 mL of solvent at N2 atmosphere. bThe reaction was monitored by
TLC. cIsolated yields. dNo reaction.
TABLE 2. Reaction of (E)-1 with N-PSP
SCHEME 1. Establishment of the Structure of 3a
entrya
Ar1
Ar2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
products
yield (%)b
affording 3-(phenylselanyl)-1-naphthaldehyde (3a) in 26%
(Table 1, entry 1). The structure of 3a was established by the
NOESY analysis of 5a, which was reduced by treatment of 3a
with NaBH4 (Scheme 1). Using (NH4)2S2O8 instead of
K2S2O8 led to the increased yield of 47% (Table 1, entry 2).
The yield could be further improved to 55% when the reaction
was conducted in DMSO (Table 1, entry 4). Screen of the
selenium reagents proved that the use of N-(phenylseleno)
phthalimide (N-PSP) gave better results than diphenyl disel-
enide (Table 1, entry 5). Phenylselenyl bromide and phenylse-
lenyl chloride weretotally ineffective for thisreaction(Table 1,
entries 8 and 9).
1
2
3
4
5
6
7
8
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
61
73
80
56
39
53
42
45
67
42c
p-MePh
p-OMePh
p-ClPh
p-BrPh
p-FPh
o-BrPh
o-OMePh
Ph
Ph
p-MePh
Ph
9
10
Ph
3a
aUnless otherwise specified, the reaction was carried out using (E)-1
(0.2 mmol), N-PSP (0.24 mmol) in 3 mL of DMSO at N2 atmosphere.
bIsolated yields. c(Z)-1a was applied to this reaction.
With the optimized conditions in hand, we next probed the
reaction of a variety of (E)-1 with N-PSP, and the experi-
mental results showed that the corresponding adducts 3 were
obtained in moderate yields. The yields of the (E)-1a with
electron-donating groups on the aromatic rings appear to
be higher than those with electron-withdrawing groups
(Table 2, entries 1-8). In the synthesis of (E)-1a, a small
amount of (Z)-1a isomer was obtained. The reaction of (Z)-
1a with N-PSP gave the same product (Table 2, entry 10).
Phenylselenyl bromide and phenylselenyl chloride are a
class of typical phenylselenyl cation sources and have wide
application in the electrophilc addition reaction.8 However,
as indicated in Table 1, when phenylselenyl bromide and
phenylselenyl chloride were used, the reaction of (E)-1a only
gave a trace amount of the expected product, which may
SCHEME 2. Controlled Experiments
(8) (a) Tingoli, M.; Tiecco, M.; Testaferri, L.; Temperini, A. Synth.
Commun. 1998, 28, 1769. (b) Murata, S.; Suzuki, T. Tetrahedron Lett.
1987, 28, 4415. (c) Tiecco, M.; Testaferri, L.; Santi, C. Eur. J. Org. Chem.
1999, 797.
exclude the cation process. The reaction of (E)-1a and N-PSP
did not occur with no (NH4)2S2O8 added (eq 1, Scheme 2).
On the other side, when the reaction was carried out in the
J. Org. Chem. Vol. 74, No. 15, 2009 5637

Miao and Huang
JOCNote
TABLE 3. Reaction of (E)-1a with Various Electrophilic Selenium Reagents under Different Conditionsa
entry
electrophilic selenium reagants (equiv)
solvent
base
yield (%)c
1
2
3
4
5
6
7
8
PhSeCl (1.2)
PhSeBr (1.2)
PhSeBr (1.2)
PhSeBr (1.2)
PhSeBr (1.2)
PhSeBr (1.2)
PhSeBr (1.2)
N-PSP (1.2)
DMSO þ 0.1 mL H2O
DMSO þ 0.1 mL H2O
CH3CN þ 0.1 mL H2O
CH2Cl2 þ 0.1 mL H2O
CH3CN þ 0.1 mL H2O
CH3CN þ 0.2 mL H2O
CH3CN þ 0.01 mL H2O
CH3CN þ 0.1 mL H2O
61
66
73
46
89
85
61
NRd
K2CO3
K2CO3
K2CO3
K2CO3
aUnless otherwise specified, the reaction was carried out using (E)-1a (0.2 mmol) in 3 mL of solvent. bReaction was monitored by TLC. cIsolated
yields. dNo reaction.
SCHEME 3. Proposed Mechanism for the Reaction
TABLE 4. Reaction of (E)-1a with H2O in the Presence of Phenylse-
lenyl Bromide
entrya
Ar
products
yield (%)b
1
2
3
4
5
6
Ph
4a
4b
4c
4d
4e
4f
89
86
91
75
88
79
p-BrPh
p-MePh
p-OMePh
p-ClPh
o-BrPh
presence of 1.0 equiv of 2,20-azo-bis-isobutyronitrile (AIBN)
and air, the corresponding product was also formed in 27%
yield (eq 2, Scheme 2), albeit in low yield with long reaction
time, comparatively. When radical inhibitor was added in
the reaction system, the yield of 3a significantly dropped to
6% (eq 3, Scheme 2). These results may indicate that the
radical process may be the main pathway in this reaction.
On the basis of the above results, a plausible mechanism
was proposed, as shown in Scheme 3. The reaction of N-PSP
aUnless otherwise specified, the reaction was carried out using (E)-1
(0.2 mmol), PhSeBr (0.24 mmol), and K2CO3 (0.24 mmol) in 3 mL of
CH3CN and 0.1 mL of H2O in an air atmosphere. bIsolated yields.
yield with excellent stereoselectivity (Table 3, entry 1). Using
(E)-1a as the substrate, we examined the reaction under a
variety of reaction conditions to develop the best one. The
results are summarized in Table 3. Using phenylselenyl
bromide instead of phenylselenyl chloride led to the in-
creased yield of 66% (Table 3, entry 2). The following
examination of the solvent effects indicated that CH3CN
was the most suitable solvent (Table 3, entries 2-4). When
the base K2CO3 was used in CH3CN, 4a was obtained in
89% yield (Table 3, entry 5). Moreover, the amount of H2O
also affected the yield of the reaction, and 0.1 mL of H2O is
suitable (Table 3, entries 5-7). Thus, the optimized condi-
tions are to carry the reaction in 3 mL of CH3CN and 0.1 mL
of H2O using 1.2 equiv of phenylselenyl bromide and 1.2
equiv of K2CO3 at room temperature. When the selenium
reagent N-PSP was used instead of phenylselenyl bromide,
no reaction occurred (Table 3, entry 8).
9
with free radical initiator (NH4)2S2O8 may first give the
phenylselenyl radical, which adds to the CdC bond of (E)-1
to produce the radical intermediate A. The presence of a
formyl group may facilitate a highly selective scission of the
proximal C-C bond in the cyclopropane ring to afford
intermediate B, followed by the intramolecular radical cycli-
zation reaction to give 1,2-dihydronaphthalene C with loss of
a hydrogen atom. Finally, 1,2-dihydronaphthalene C is
oxidized by (NH4)2S2O8 to give the more stable 1-naphthal-
dehyde derivative 3.
Interestingly, when the reaction was conducted in 3 mL of
DMSO and 0.1 mL of H2O using phenylselenyl chloride as
the electrophilic selenium reagents, the bicycle derivatives
3-oxabicyclo[3.1.0]hexan-2-ols 4a were obtained in 61%
With the optimized reaction conditions in hand, we next
examined the electrophilic cycloaddition of a variety of (E)-1
with phenylselenylbromide. Theresultsare showninTable4.
The positions and properties of substituents on the aromatic
ring of (E)-1 have little effect on the reaction, and the
(9) (a) Rasmussen, J. K; Smith, H. K. II. J. Am. Chem. Soc. 2004, 126,
9645. (b) Minisci, F.; Fontana, F.; Coppa, F.; Yan, Y.-M. J. Org. Chem.
1995, 60, 5630. (c) Liu, Z.-Q; Sun, L; Wang, J.-G; Han, J; Zhao, Y.-K; Zhou,
B. Org. Lett. 2009, 11, 1437.
5638 J. Org. Chem. Vol. 74, No. 15, 2009

Miao and Huang
JOCNote
SCHEME 4. Proposed Mechanism for the Reaction
with flash chromatography on silica gel (petroleum ether/ethyl
acetate 50:1 v/v) to afford 3.
3-Phenylselanylnaphthalene-1-carbaldehyde (3a): oil; 1H
NMR (400 MHz, CDCl3) δ=10.26 (s, 1H), 9.17 (d, J=8.0 Hz,
1H), 8.17 (s, 1H), 7.98 (d, J=1.6 Hz, 1H), 7.79 (d, J=8.4 Hz, 1H),
7.68-7.70 (m, 1H), 7.50-7.60 (m, 3H), 7.29-7.35 (m, 3H); 13
C
NMR (100 MHz, CDCl3) δ=124.9, 127.5, 127.8, 127.9, 128.0,
129.1, 129.3, 129.6, 130.0, 132.0, 133.3, 134.4, 138.3, 140.5, 192.9;
IR (neat) 1689, 1617, 1574, 1501, 1214, 1061, 736, 689 cm-1; MS
(70 eV, EI) m/z 312 (Mþ); HRMS (EI) m/z calcd for C17H12OSe
(Mþ) 312.0053, found 312.0048.
General Procedure for Synthesis of 3-Oxabicyclo[3.1.0]hexan-
2-ols 4. To a stirred solution of (E)-1 (0.2 mmol) in CH3CN
(3 mL) was added 0.1 mL of H2O and K2CO3 (0.24 mmol) at
room temperature, then the PhSeBr (0.24 mmol) was added.
After the reaction was complete (20 min), the mixture was
quenched with 5 mL of water and extracted with EtOAc (3ꢀ5
mL). The combined organic layers were dried over anhydrous
MgSO4. After filtration and removal of the solvent in vacuo, the
residues were purified with flash silica chromatography (petro-
leum ether/ethyl acetate 6:1 v/v) to afford 4.
products 4 were obtained in good to high yields (Table 4,
entries 1-6). Here, it should be mentioned that oxabicyclo-
[3.1.0]hexan-2-ols are important structural motifs frequently
found in pharmacologically interesting structures.10
Obviously, the reaction mechanism in CH3CN and H2O is
different from that in dry DMSO. In the CH3CN and H2O
system, the phenylselenium first adds to the double bonds
to form a seleniranium ion intermediate D. Then a molecule
of H2O nucleophilically attacks at the carbonyl group of the
intermediate D, and simultaneously, the oxygen in the
carbonyl group undergoes intramolecular nucleophilic at-
tack to form the bicycle derivatives 4 with excellent stereo-
selectivity (Scheme 4).
In summary, we have observed a ring-opening intramole-
cular radical cyclization and an electrophilic cyclization
reaction of 2-(arylmethylene)cyclopropylaldehyde, afford-
ing a controlled synthesis of 1-naphthaldehydes and 3-oxa-
bicyclo[3.1.0]hexan-2-ols from (E)-2-(arylmethylene)cyclo-
propylaldehyde. The properties of organo-selenium reagents
may play an important role in the reactions. Further studies
on this transformation are being carried out in our labora-
tory.
4-Phenyl-5-phenylselanyl-3-oxabicyclo[3.1.0]hexan-2-ol (4a):
oil; H NMR (400 MHz, CDCl3) δ=7.38-7.46 (m, 4H), 7.28-
1
7.33 (m, 3H), 7.16-7.22 (m, 3H), 5.42 (d, J=1.6 Hz, 1H), 5.32
(s, 1H), 3.05-3.18 (m, 1H), 2.05 (dd, J1=4.4 Hz, J2=8.4 Hz, 1H),
1.19-1.23 (m, 1H) 1.00-1.06 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ= 13.8, 29.7, 32.9, 81.5, 98.0, 126.7, 127.2, 128.0, 128.1,
129.0, 129.3, 132.2, 137.3; IR (neat) 3396, 1468, 1086, 1060,
962, 816, 733, 689 cm-1; MS (70 eV, EI) m/z 332 (Mþ); HRMS
(EI) m/z calcd for C17H16O2Se (Mþ) 332.0316, found 332.0312.
Acknowledgment. We are grateful to the National Natur-
al Science Foundation of China (Project Nos. 20732005 and
20872127) and National Basic Research Program of China
(973 Program, 2009CB825300) for financial support.
Experimental Section
General Procedure for Synthesis of 1-Naphthaldehydes 3.
Under an atmosphere of dry nitrogen, 1.0 equiv of (NH4)2S2O8
(0.2 mmol) was added to a solution of N-PSP (0.24 mmol) in 3
mL of dry DMSO at 70 °C. Then 1.0 equiv of (E)-1 (0.2 mmol)
was added. After being stirred for 5-20 min (monitored by
TLC), the mixture was quenched with 5 mL of water and
extracted with EtOAc (3 ꢀ 10 mL). The combined organic
layers were dried over anhydrous MgSO4. After filtration and
removal of the solvent in vacuo, the residues were purified
Note Added after ASAP Publication: The version of this
paper published on June 26, 2009, had errors in the text and the
Supporting Information. The corrected version was published
on July 31, 2009.
Supporting Information Available: General experimental
procedures and spectroscopic data for all compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(10) (a) Koft, E. R.; Smith, A. B. III. J. Am. Chem. Soc. 1982, 104, 2659.
(b) Smith, A. B. III; Yokoyama, Y.; Dunlap, N. K. Tetrahedron Lett. 1987,
28, 3663.
J. Org. Chem. Vol. 74, No. 15, 2009 5639