A facile access to medium- and large-size naphthalenacarbocycles via Lewis acid mediated ring-expansion reaction of bicyclic vinylidenecyclopropanes

Article abstract of DOI:10.1055/s-2007-1000844

Ring-expansion reactions of bicyclic vinylidenecyclopropanes in the presence of Lewis acid was investigated, providing an efficient method for the synthesis of naphthalenes with annulated carbocycles of various ring sizes in good to excellent yields under

Full text of DOI:10.1055/s-2007-1000844

LETTER
229
A Facile Access to Medium- and Large-Size Naphthalenacarbocycles via Lewis
Acid Mediated Ring-Expansion Reaction of Bicyclic Vinylidenecyclopropanes
F
acile Access toM
i
edium
-
and
L
arge
n
-Size
N
aphthalenac
H
a
rbocycles uang,*a,b Chenliang Su,a Qingyang Liu,a Yuetong Songa
a
Department of Chemistry, Zhejiang University (Campus Xixi), Hangzhou 310028, P. R. of China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, P. R. of China
b
Fax +86(571)88807077; E-mail: huangx@mail.hz.zj.cn
Received 25 September 2007
tention from theoretical, spectroscopic, synthetic and
mechanistic viewpoints.10
Abstract: Ring-expansion reactions of bicyclic vinylidenecyclo-
propanes in the presence of Lewis acid was investigated, providing
an efficient method for the synthesis of naphthalenes with annulated
carbocycles of various ring sizes in good to excellent yields under
mild conditions.
Recently, Shi et al. have developed the reaction of vi-
nylidenecyclopropanes catalyzed by Lewis acids to afford
a series of naphthalene and indene derivatives.10g–i Herein,
we wish to report a ring-expansion reaction of bicyclic vi-
nylidenecyclopropanes mediated by TiCl4 for the synthe-
sis of medium- and large-size naphthalenacarbocycles
(Scheme 1).
Key words: bicyclic vinylidenecyclopropanes, ring expansion,
Lewis acids
The synthesis of medium- and large-size ring systems is
still a challenge for organic chemists as they are wide-
spread, ranging from naturally occurring compounds to
macrocyclic synthetic receptors or ligands.1 A number of
reactions such as Wurtz coupling,2 Friedel–Crafts reac-
tion,3 acyloin condensation,4 samarium diiodide promoted
reaction5 and metal-mediated coupling reactions6 were
applied to synthesize carbocyclic skeletons. Ring-expan-
sion reaction from smaller cyclic units is also a facile
method for the synthesis of medium- and large-size ring
compounds. Many interesting and useful medium- and
large-size ring compounds have been synthesized through
these methods.7
Initially, we examined the reaction of 0.5 mmol of bicy-
clic vinylidenecyclopropane 1a with 10% of BF3·OEt2 as
a catalyst in CH2Cl2 at room temperature. After stirring
for 12 hours, the desired product 2a was obtained in 55%
yield (Table 1, entry 1). To optimize the reaction condi-
tions, a series of Lewis acids and solvents were employed.
Table 1 Optimization of Conditions for the Synthesis of Naphtha-
lenacarbocycle 2aa
Ph
Ph
conditions
r.t.
Methylenecyclopropanes (MCPs) are highly strained but
readily available molecules which have served as useful
building blocks in organic synthesis.8 Recently, we have
investigated the cyclization reactions of MCPs to synthe-
size aromatic compounds.9 Compared with MCPs, vi-
nylidenecyclopropanes (VCPs) have an allene structure
unit instead of the vinyl bonds adjacent to the cyclopropyl
ring, which might lead to more possible reactive positions
than classical MCPs, and yet they are thermally stable and
reactive substances. Therefore, thermal and photochemi-
cal skeletal conversions of VCPs have attracted much at-
1a
2a
Entry
Lewis acid
Solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
THF
Time (h) Yield (%)b
1
2
10% BF3⋅EtO2
10% AlCl3
10% CF3COOH
10% ZrCl4
10% TiCl4
20% TiCl4
30% TiCl4
30% TiCl4
30% TiCl4
30% TiCl4
12
48
48
24
5
55
10
3
33
4
58
5
66
R
6
2
74
30% TiCl4
Ar
Ar
7
2
85
n
CH2Cl2
r.t., 2 h
R
8
2
78
n
9
5
tracec
traced
Ar =
R
10
MeCN
5
Scheme 1
SYNLETT 2008, No. 2, pp 0229–0232
a The reaction was carried under a nitrogen atmosphere on a 0.5-mmol
scale.
x
x.
x
x.
2
0
0
7
b Isolated yield.
Advanced online publication: 21.12.2007
DOI: 10.1055/s-2007-1000844; Art ID: W18007ST
© Georg Thieme Verlag Stuttgart · New York
c Compound 1a (83%) was recovered.
d Compound 1a (77%) was recovered.

230
X. Huang et al.
LETTER
Table 2 Synthesis of Medium- and Large-Size Naphthalenacarbocyclesa
R
30% TiCl4
Ar
Ar
n
CH2Cl2
r.t., 2 h
R
n
2
1
Ar =
R
Entry
Vinylidenecyclopropanes
Product
Yield (%)b
R
R
R
R
1
2
1a (R = H)
1b (R = Cl)
2a (R = H)
2b (R = Cl)
85
87
R
R
R
R
3
4
1c (R = H)
1d (R = Cl)
2c (R = H)
2d (R = Cl)
82
83
Ph
Ph
5
6
7
78
86
85
1e
1f
2e
2f
Ph
Ph
Ph
Ph
1g
2g
Ph
Ph
8
82
1h
2h
a The reaction was carried out under nitrogen atmosphere on a 0.5-mmol scale.
b Isolated yield.
Synlett 2008, No. 2, 229–232 © Thieme Stuttgart · New York

LETTER
Facile Access to Medium- and Large-Size Naphthalenacarbocycles
231
The experimental results showed that TiCl4 was a better leased via a 1,4-proton shift to give the corresponding in-
Lewis acid than the other Lewis acid tested and in this termediate E, while a further 1,3-proton shift finally
case, the corresponding product 2a was obtained in 66% affords the aromatic product F (Scheme 2).
yield (Table 1, entry 5). Further investigations indicated
that when the catalyst amount was enhanced to 30%, the
yield of product was efficiently improved and CH2Cl2 was
found to be the best solvent (Table 1, entry 7).
When the bicyclic vinylidenecyclopropane 1i was em-
ployed, a similar ring-expansion reaction happened to
give the intermediate B. However, chlorination of B in-
stead of the intramolecular Friedel–Crafts reaction oc-
With these results in hand, the scope of this reaction was curred to give the intermediate H, which could be
investigated and the typical results are summarized in transformed to the final product 3,6-dihydro-2H-pyran
Table 2.11 As can be seen from Table 2, the corresponding derivative 2i in 71% yield when quenched with water
rearranged product 2, six-membered ring and medium- (Scheme 3).12
size naphthalenacarbocycles derivatives were obtained in
In conclusion, we have disclosed that the Lewis acid me-
good to high yields (Table 2, entries 1–6). For bicyclic vi-
diated ring-expansion reaction of bicyclic vinylidenecy-
nylidenecyclopropane 1g, the corresponding product 2g
clopropanes would give a convenient approach to the
was obtained in 85% yield (Table 2, entry 7), which
synthesis of naphthalenes with annulated carbocycles of
showed that the C=C double bond was tolerated in this re-
various ring sizes. Due to the easily accessible starting
action. For large-size bicyclic vinylidenecyclopropane
materials, the simple reaction procedure and the mild con-
ditions, this method could prove very attractive for the
building of common-, medium- and large-size rings. The
1h, the reaction happened smoothly to afford 2h in 82%
yield (Table 2, entry 8).
A plausible mechanism for the ring-expansion reaction is reaction mechanism and synthetic applications of this
shown in Scheme 2.10i Coordination of compound 1 to methodology are being further studied in our laboratory.
Lewis acid gives the intermediate A, which produces the
ring-expansion intermediate B. The intramolecular
Friedel–Crafts reaction of B gives the cyclized intermedi-
ate C, which is smoothly transformed to the intermediate
D through further rearrangement. The Lewis acid is re-
0.5 mmol TiCl4
O
O
CH2Cl2, r.t.
71%
1i
Cl
Ar
Ar
Ar
Ar
LA
2i
0.5 mmol
+
n
n
CH2Cl2, r.t.
LA
H2O
A
R
Ar =
R
Cl3Ti
Ar
LA–
+
O
+
n
O
TiCl3
Ar
–Cl
Cl
LA
+
B
B
H
n
C
R
Scheme 3
R
R
Acknowledgment
LA–
We are grateful to the National Natural Science Foundation of Chi-
na (Project No. 20472072, 20332060 and 20672095) for financial
support.
[1,4]-H shift
– LA
[1,3]-H shift
+
n
R
n
R
References and Notes
E
D
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R
LA = Lewis acid
n
R
F
Scheme 2
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Synlett 2008, No. 2, 229–232 © Thieme Stuttgart · New York

232
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LETTER
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(11) Typical Procedure for the Preparation of 2: To a solution
of bicyclic vinylidenecyclopropanes (0.5 mmol) in anhyd
CH2Cl2 (3 mL) under N2 was added TiCl4 (28.4 mg, 0.15
mmol) under a nitrogen atmosphere. The mixture was stirred
at r.t. for 2 h. After the reaction was complete, the mixture
was concentrated and the residue was purified by flash
chromatography to afford medium- and large-size
naphthalenacarbocycles 2. Selected spectral data for 2h: 1H
NMR (400 MHz, CDCl3): d = 8.07 (d, J = 8.0 Hz, 1 H), 7.87
(d, J = 8.4 Hz, 1 H), 7.42–7.53 (m, 5 H), 7.36–7.42 (m, 1 H),
7.30–7.36 (m, 1 H), 7.25 (s, 1 H), 3.00–3.09 (m, 2 H), 2.70–
2.80 (m, 2 H), 1.74–1.89 (m, 4 H), 1.64–1.73 (m, 2 H), 1.48–
1.64 (m, 6 H), 1.34–1.48 (m, 6 H). 13C NMR (100 MHz,
CDCl3): d = 23.2, 23.4, 24.5, 24.6, 26.4, 26.6, 26.9, 27.0,
27.1, 27.8, 32.3, 123.9, 124.5, 125.6, 126.6, 126.9, 128.1,
129.8, 130.2, 130.6, 132.8, 135.1, 137.4, 138.2, 141.1. IR
(KBr): 2929, 2856, 1461, 1383, 762, 707 cm–1. MS (70 eV,
EI): m/z = 356 [M+], 356 (100). HRMS (EI): m/z [M+] calcd
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(12) Spectral data for 2i: 1H NMR (400 MHz, CDCl3): = 7.33–
7.41 (m, 3 H), 7.27–7.32 (m, 7 H), 6.42 (s, 1 H), 5.57 (t, J =
2.6 Hz, 1 H), 4.24 (d, J = 2.2 Hz, 1 H), 4.17 (dd, J1 = 3.7 Hz,
J2 = 18.0 Hz, 1 H), 4.08 (dd, J1 = 1.8 Hz, J2 = 17.8 Hz, 1 H),
3.98 (dd, J1 = 2.9 Hz, J2 = 12.4 Hz, 1 H), 3.87 (dd, J1 = 3.0
Hz, J2 = 12.4 Hz, 1 H). 13C NMR (100 MHz, CDCl3): d =
54.0, 65.5, 70.0, 125.1, 127.4, 127.5, 127.6, 128.1, 128.3,
129.8, 132.7, 140.0, 142.5, 143.9. IR (film): 3056, 3024,
2925, 2852, 1658, 1598, 1491, 1445, 1380, 1135, 1080, 758,
700 cm–1. MS (70 eV, EI): m/z = 296 [M+], 231 (100).
Synlett 2008, No. 2, 229–232 © Thieme Stuttgart · New York

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