Synthesis of indenes by ytterbium-catalyzed carboalkoxylation/Friedel- Crafts reaction of arylidenecyclopropanes with acetals

Article abstract of DOI:10.1016/j.tetlet.2004.02.066

Ytterbium-catalyzed tandem carboalkoxylation/Friedel-Crafts reaction of arylidenecyclopropanes 1 with acetals 2 afforded the corresponding indene derivatives 3 in good to high yields. For example, in the presence of 10mol% of Yb(OTf)₃ the react

Full text of DOI:10.1016/j.tetlet.2004.02.066

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2903–2906
Synthesis of indenes by ytterbium-catalyzed carboalkoxylation/
Friedel–Crafts reaction of arylidenecyclopropanes with acetals
Itaru Nakamura, Michiru Kamada and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science, Tohoku University, Aramaki Aza Aoba, Sendai 980-8578, Japan
Received 28 December 2003; revised 3 February 2004; accepted 13 February 2004
Abstract—Ytterbium-catalyzed tandem carboalkoxylation/Friedel–Crafts reaction of arylidenecyclopropanes 1 with acetals 2
afforded the corresponding indene derivatives 3 in good to high yields. For example, in the presence of 10 mol % of Yb(OTf) the
3
reaction of 1-phenylbenzylidenecyclopropane 1a with the dimethyl acetals of benzaldehyde 2a, p-tolualdehyde 2b, and p-anisal-
dehyde 2c gave 1,3-diphenyl-2-(2-methoxyethyl)indene 3a, 2-(2-methoxyethyl)-3-phenyl-1-(p-tolyl)indene 3b, and 1-(p-anisyl)-2-
(
2-methoxyethyl)-3-phenylindene 3c in 82%, 80%, and 80% yields, respectively.
Ó 2004 Elsevier Ltd. All rights reserved.
Methylenecyclopropanes have been widely utilized as a
1
four carbon unit in organic synthesis. Recently, tran-
proceeds via distal bond cleavage between C3 and C4
(type b), to give the allylated pronucleophiles. Lewis
acidic transition metal-catalyzed addition of pronucleo-
sition metal-catalyzed addition to methylenecyclopro-
panes has been widely investigated and become a
powerful tool to construct new carbon–carbon and
11
12
13
philes, such as alcohols, water, amines, and aro-
matic rings, to methylenecyclopropanes have also been
14
2
15
carbon–heteroatom bonds. The addition of metal
3
hydrides, such as H–Sn and H–Si, and bismetallic
reported (type c). These reactions proceed predomi-
4
nantly through proximal bond cleavage, affording the
homoallylated pronucleophiles. To the best of our
knowledge, however, the catalytic addition of a carbon–
oxygen bond, so-called carboalkoxylation, to methyl-
enecyclopropanes is not known. Herein, we report that
the ytterbium-catalyzed tandem carboalkoxylation/
5
6
compounds, such as B–B and B–Si, to methylene-
cyclopropanes proceeds through ring opening at
the proximal bond between C2 and C3 (Scheme 1,
type a). The addition of pronucleophiles, such as active
7
8
9
10
methynes, amines, alcohols, and hetero-aromatics,
R'
R 1
R
3
4
cat. TM
R
(
a)
b)
+
R'
M
M
2
2
R' = H, B, Sn
M = B, Si, Sn
R
R 1
3
R
cat. TM
cat. LA
Nu
(
+
+
H–Nu
R
R
4
3
4
H
Nu = CR3, NR2, OR
H
R 1
R
R
(c)
H–Nu
Nu
2
R
Nu = NR2, OR, OH
Scheme 1. Catalytic addition to methylenecyclopropanes.
Keywords: Indene; Lewis acid catalysis; Ytterbium triflate; exo-Methylenecyclopropane; Carboalkoxylation; Friedel–Craft reaction; Ytterbium
catalyzed reaction.
*
Corresponding author. Tel.: +81-22-217-6581; fax: +81-22-217-6784; e-mail: yoshi@yamamoto1.chem.tohoku.ac.jp
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.066

2904
I. Nakamura et al. / Tetrahedron Letters 45 (2004) 2903–2906
Friedel–Crafts reaction of arylidenecyclopropanes 1
with acetals 2 gives the corresponding indenes 3 in good
to high yields (Eq. 1).
acetal of benzaldehyde (2f or 2g) proceeded much more
slowly and it took 24 h for completion; the corre-
sponding indenes 3f or 3g were obtained in 71% and
8
5% yields, respectively (entries 6 and 7). The reaction of
bis(p-tolyl)methylenecyclopropane 1b with 2a produced
3h in a high yield, while the reaction of 1-methylbenz-
ylidenecyclopropane 1c with 2a gave 3i in a lower yield
(entries 8 and 9). The reaction of bis[m-(trifluoro-
methyl)benzyl]methylenecyclopropane 1d and 2a gave a
R1
R1
OR4
OR4
R3
10 mol% Yb(OTf)3
neat, 80 ˚C
+
R3
OR4
R2
R2
0
2
3
2:1 mixture of 3j and 3j (Eq. 2).
1
a (R1 = H, R2 = Ph)
(2 equiv)
1
1
1
b (R = Me, R2 = p-tolyl)
1
c (R = H, R2 = Me)
1
H
Ph
ð1Þ
OMe
Ph
4
The results are summarized in Table 1. In the presence
of 10 mol % of Yb(OTf) , the reaction of 1-phenylbenz-
3
ylidenecyclopropane 1a and 2 equiv of benzaldehyde
dimethyl acetal 2a proceeded at 80 °C without solvent
for 1 h and 1,3-diphenyl-2-(2-methoxyethyl)indene 3a
was obtained in 82% yield (entry 1). In this reaction the
homoallylic ether 4 was obtained as a byproduct in 5%
F3C
OMe
+
Ph
OMe
F3C
2
a
1d
3
yield. Sc(OTf) promoted the reaction of 1a and 2a as
well, giving 3a in 80% yield The reaction of 1a and 2a
CF3
Ph
F3C
Ph
using AgBF as catalyst was much slower (24 h, 76%
4
+
OMe
yield). The reaction of 1a and 2a using Zn(OTf)2,
afforded 3a in a lower
did not promote the
OMe
Sn(OTf)
yield and Cu(OAc)
2
, Cu(OTf)
2
, or La(OTf)
and PdCl
3
F3C
F3C
2
2
3j' (19%)
reaction at all. The reaction of 1a and 2a in solvents,
such as 1,2-dichloroethane or toluene, gave only a trace
amount of 3a and considerable amounts of the starting
materials were recovered. The reaction of 1a and 2a did
not proceed at 30 °C; it took 12 h to complete the
reaction of 1a and 2a at 50 °C, affording 3a in 70% yield.
The reaction of 1 equiv of 2a with 1a gave 3a in 60%
yield. The dimethyl acetals of p-tolualdehyde 2b, p-anis-
aldehyde 2c, and p-trifluoromethylbenzaldehyde 2d re-
acted with 1a and the corresponding indene derivatives
3j (41%)
ð2Þ
The structures of compounds 3 were confirmed by
spectroscopic methods. Furthermore, the structure of 3e
was unambiguously determined by an X-ray crystallo-
graphic analysis. The ORTEP drawing of 3e is shown
in Figure 1.
16
3
b–d were obtained in 80%, 80%, and 73% yields,
A plausible mechanism for this reaction is illustrated in
Scheme 2. The acetal group of 2 would coordinate to
respectively (entries 2–4). The reaction of 1a with 2-
naphthylaldehyde dimethyl acetal 2e afforded 3e in 69%
yield (entry 5). The reaction of the diethyl or dibutyl
Table 1. Yb(OTf)
3
-catalyzed tandem carboalkoxylation/Friedel–
a
Crafts reaction of arylidenecyclopropanes 1 with acetals 2
3
4
Entry
1
2
R
R
3
Yield (%)
b
1
2
3
4
1a
1a
1a
1a
1a
1a
1a
1b
1c
2a
2b
2c
2d
2e
2f
Ph
p-Tolyl
p-Anisyl
Me
Me
Me
Me
3a
3b
3c
3d
3e
3f
82
80
b
b
80
p-CF
3
C
6
H
4
73
69
71
85
80
42
c
5
2-Naphthyl Me
d
6
d
Ph
Ph
Ph
Ph
Et
7
2g
2a
2a
Bu
Me
Me
3g
3h
3i
8
9
a
The reaction of 1 (0.5 mmol) and 2 (1 mmol) was carried out in the
presence of 10 mol % of Yb(OTf)
A trace amount (5–6%) of the homoallylic ether 4 was obtained as a
3
without solvent at 80 °C for 1 h.
b
byproduct.
For 6 h.
For 24 h.
c
d
Figure 1. ORTEP drawing of 3e.

I. Nakamura et al. / Tetrahedron Letters 45 (2004) 2903–2906
2905
OR4
R1
YbIII
In conclusion, we are in a position to synthesize multi-
functionalized indenes in a direct and atom economic
manner. The present methodology may be useful for the
4
R3
R3
OR4
R O
H
2
OR4
18
4
R O
R3
YbIII
synthesis of various indene frameworks, which are
often found in research areas, such as biochemistry,
R2
19
O
H+
3
4
YbIII OR4
R
20
21
coordination chemistry, and polymer science.
5
R1
General experimental procedure for the reaction of aryl-
idenecyclopropane 1a and benzaldehyde dimethyl acetal
2a. To the arylidenecyclopropane 1a (103 mg, 0.5 mmol)
H
R3
OR4
R1
R3
OR4
6
R2
3
and Yb(OTf) (31 mg, 0.05 mmol) was added benzalde-
10
hyde dimethyl acetal 2a (0.15 mL, 1.0 mmol) under an
Ar atmosphere in a pressure vial and the mixture was
stirred at 80 °C for 1 h. After completion of the reaction,
which was monitored by GC, the mixture was filtered
through a short silica column with ethyl acetate as elu-
ent. Purification of the crude product by silica gel col-
umn chromatography using a mixture of hexane and
ethyl acetate (10:1) as eluent afforded the indene 3a in
R2
1
R1
R1
R1
R3
R3
R3
R4
OR4
OR4
O
R2
R2
R2
7
8
9
82% yield.
Scheme 2.
ytterbium as shown in 5 and elimination of ytterbium
alkoxide from 5 would give the oxonium cation 6.
Nucleophilic attack of the arylidenecyclopropane 1 to 6
would lead to the cyclopropylcarbinyl cation 7. Cyclo-
propylcarbinyl-homoallyl rearrangement would take
place and following intramolecular electrophilic attack
of the resulting homoallyl cation of 8 to the alkoxy
group would lead to the cyclic oxonium intermediate 9.
Friedel–Crafts type cyclization would then give the
product 3.
References and notes
1
. For reviews see: (a) Binger, P.; B u€ ch, H. M. Top. Curr.
Chem. 1987, 135, 77; (b) Brandi, A.; Goti, A. Chem. Rev.
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. Lautens, M.; Meyer, C.; Lorenz, A. J. Am. Chem. Soc.
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3
lyzed addition of alcohols to methylenecyclopropanes
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11
high yields (Eq. 3). The present reaction produces
4
1
equiv of R OH as a byproduct. However, only a trace
6
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reaction of 1a and 2a. Perhaps, the coordination of
Yb(OTf) to the acetal moiety of 2 is much preferable to
3
that to the alcohol 11 since the acetal group can coor-
dinate to Yb(III) strongly in a bidentate manner
through two oxygen atoms as shown by structure 5 in
Scheme 2.
5
6
7
1
2
8
9
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R
R
Yb(OTf)3
R
+
H
OR'
OR'
R
1
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4
ð3Þ
R O
YbIII
H OR4
YbIII
>>
R3
O
4
R
1
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5
11
1
1
Recently we demonstrated the palladium-catalyzed
intramolecular carboalkoxylation of alkynes with ace-
tals. The present reaction is regarded as the first
intermolecular carboalkoxylation reaction of carbon–
carbon multiple bonds with acetals.
17
1
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1
6. CCDC-230118 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif,
or by emailing data_request@ccdc.cam.ac.uk, or by con-
tacting The Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223
336033.