Lewis acid-mediated highly regioselective ring-expansion of methyl 2-phenyl-1-(arylhydroxymethyl)cyclopropanecarboxylates

Article abstract of DOI:10.1246/cl.2010.194

A novel ring-expansion of methyl (arylhydroxymethyl)- cyclopropanecarboxylates 1 using Sc(OTf)₃ or BF₃· OEt₂ afforded 1,2-dihydronaphthalene-3-carboxylic acid ester 2 in high to excellent yields. In the reaction, highly regioselective ring opening of cyclopropane and sequential cyclization occurred.

Full text of DOI:10.1246/cl.2010.194

doi:10.1246/cl.2010.194
194
Published on the web January 30, 2010
Lewis Acid-mediated Highly Regioselective Ring-expansion of
Methyl 2-Phenyl-1-(arylhydroxymethyl)cyclopropanecarboxylates
Eri Yoshida, Kazufumi Nishida, Kei Toriyabe, Ryouta Taguchi, Jiro Motoyoshiya, and Yoshinori Nishii*
Department of Chemistry, Faculty of Textile Science and Technology, Shinshu University, Ueda 386-8567
(Received November 16, 2009; CL-091004; E-mail: nishii@shinshu-u.ac.jp)
A novel ring-expansion of methyl (arylhydroxymethyl)-
lene-3-carboxylic acid in 71% yield. The use of CF3CO2H
decreased the yield of ring-expansion (Entry 6). A similar
reaction with BF3¢Et2O proceeded in good yields (Entries 7 and
8). The use of lanthanide triflates, Yb(OTf)3 and Sc(OTf)3, at
83 °C promoted ring-expansion in high yields (Entries 10 and
12). Similar reactions at room temperature resulted in a decrease
in the yield (Entries 9 and 11). Thus, the use of Sc(OTf)3 at
83 °C in EDC (1,2-dichloroethane) is the most efficient
condition for this ring-expansion.6 The structures of 2a were
determined by analogy with a known compound, based on
spectral data.7
Next we investigated the ring-expansion of (arylhydroxy-
methyl)cyclopropanecarboxylates 1b-1e with Sc(OTf)3 at 83 °C.
As expected, the ring-expansion of ester 1b-1e proceeded
smoothly to afford dihydronaphthalene 2b-2e in good to high
yields (Table 2, Entries 1-4). In the case of 1d, hydrolysis of
ester 2d occurred as a side reaction (Entry 3). In addition, we
also investigated similar reaction of diaryl analogs 1f-1i
(Table 3). Every case of ester 1f-1i underwent the desired
ring-expansion to give dihydronaphthalene 2f-2i in good to
excellent yields. Treatment of 1f with Sc(OTf)3 at 83 °C afforded
dihydronaphthalene 2f in high yield (Entry 1). The use of
Yb(OTf)3 or TiCl4 decrease the yield of ring-expansion (Entries
2 and 3). In the case of diaryl analog 1f, BF3¢Et2O also
promoted the ring-expansion in excellent yield (Entry 4).
cyclopropanecarboxylates 1 using Sc(OTf)3 or BF3¢OEt2 afford-
ed 1,2-dihydronaphthalene-3-carboxylic acid ester 2 in high to
excellent yields. In the reaction, highly regioselective ring
opening of cyclopropane and sequential cyclization occurred.
1-Aryl-1,2-dihydronaphthalene analogs are attracting con-
siderable attention due to their distribution in nature (for
examples, trilobatin A, B, cyclogalgravin, and magnoshinin,
Scheme 1), multiple biological activities, and usefulness as
important synthetic intermediates.1 As a part of our ongoing
program of synthetic studies on the transformation of gem-
dihalocyclopropanes,2 we have recently reported highly stereo-
selective SmI2-promoted Reformatsky-type reactions of 1-
chlorocyclopropanecarboxylate to afford (arylhydroxymethyl)-
cyclopropanecarboxylates 1 (Scheme 2).3 Here we report a
Lewis acid-mediated highly regioselective ring expansion of
methyl (arylhydroxymethyl)cyclopropanecarboxylates 14 to give
1-aryl-1,2-dihydronaphthalene-3-carboxylic acid esters 2.5
Initially, we investigated the reaction of cyclopropanecar-
boxylate 1a with various Lewis acids. Table 1 lists the results of
the ring-expansion. TiCl4, SnCl4, or TBDMSOTf promoted ring-
expansion to afford dihydronaphthalene 2a in low to moderate
yields (Entries 1-4). These results are inconsistent with those for
benzannulation of gem-dichlorocyclopropylmethanol.2b Under
Seebach’s condition,5 no amount of ester 2a was obtained
(Entry 5). In this case, hydrolysis of ester occurred along with
the ring-expansion to give corresponding 1,2-dihydronaphtha-
Table 1. Highly regioselective ring-expansion of methyl
(phenylhydroxymethyl)cyclopropanecarboxylates 1aa-d
Ph
CO2Me
CO2Me
Lewis Acid
O
HO
HO
OH
Ph
OH
*
HO
HO
OR1
Trilobatin A R1
TrilobatinB R1
=
=
CO2H
CO2H
1a
2a
O
*
Yielde/%
OH
Entry
Acid
Temp/°C
Solvent
OH
R2
HO
HO
OH
1
2
3
4
5
6
7
8
9
TiCl4
TiCl4
SnCl4
rt
83
rt
rt
35
rt
rt
83
rt
83
rt
83
CH2Cl2
EDC
CH2Cl2
CH2Cl2
Et2O
none
CH2Cl2
EDC
CH2Cl2
EDC
CH2Cl2
EDC
43
36
25
54
0
10
70
62
10
90
66
95
R3
Me
OH
MeO
Me
R2
Cyclogalgravin I:
2 = H, R3 = OMe, R4 = H
Magnoshinin:
2 = OMe, R3 = H, R4 = OMe
R4
TBDMSOTf
R
f
H2SO4
MeO
R
CF3CO2H
BF3¢Et2O
BF3¢Et2O
Yb(OTf)3
Yb(OTf)3
Sc(OTf)3
Sc(OTf)3
OMe
Scheme 1.
CO2Me
Ph
CO2Me
10
11
12
SmI2
Ph
HMPA, THF
R2
CHO
R1
Ph
CO2Me
Cl
Lewis Acid
OH
Ring-expansion
?
aReactions were carried out under an Ar atmosphere. bReaction
time is 1 h. 1.1 equiv of Lewis acid was used. A mixture of
diastereo isomers (ratio = 1/1) was used for the reactions of 1a.
eIsolated. Based on Ref. 5, 1000 equiv of H2SO4 was used.
R1
R2
R1
R2
c
d
1
2
f
Scheme 2.
Chem. Lett. 2010, 39, 194-195
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

195
Table 2. Highly regioselective Sc(OTf)3-mediated ring-expan-
sion of methyl (arylhydroxymethyl)cyclopropanecarboxylates
1b-1ea-d
MeO
Ph
O
CO2Me
R3
Ph
CO2Me
Ph
Sc(OTf)3
-OH
Sc(OTf)3
OH
R3
OH
R3
CO2Me
CO2Me
Ph
OH
Ph
Sc(OTf)3
R1
R2
R1
R2
R1
R2
EDC
83°C
1
3
4
R1
R2
R1
R2
Ph
CO2Me
R3
CO2Me
R3
1
2
intramolecular
Friedel-Crafts
MeO2C
R3
Entry Substrate
R1
R2
Product Yielde/%
Ph
Ph
1
2
3
4
1b
1c
1d
1e
Cl
Me
OMe
OMe
H
H
H
2b
2c
2d
2e
88
82
60
80
R1
R2
R1
R2
R1
R2
2
5
6
OMe
aReactions were carried out under an Ar atmosphere. bReaction
Scheme 3.
c
d
time is 1 h. 1.1 equiv of Lewis acid was used. A mixture of
diastereo isomers (ratio = 1/1) was used for the reactions of
present method to a total synthesis of natural product is now
being performed.
e
1a. Isolated.
This paper is dedicated to the first principal, Chotaro
Harizuka, on the occasion of 100th anniversary of Faculty of
Textile Science and Technology, Shinshu University. This
research was partially supported by Grant-in-Aids for Scientific
Research on Basic Area (C) “No. 20550036” and for Global
COE Program from MEXT.
Table 3. Highly regioselective ring-expansion of methyl
(diarylhydroxymethyl)cyclopropanecarboxylates 1f-1ia-c
CO2Me
Ph
CO2Me
Lewis Acid
R1
R1
Ph
OH
R1
R1
1f-i
2f-i
References and Notes
Temp
/°C
Yieldd
/%
Entry Substrate R1
Acid
Solvent Product
1
a) J. M. Scher, J. Zapp, H. Becker, Phytochemistry 2003,
62, 769. b) C. Cow, C. Leung, J. L. Charlton, Can. J. Chem.
2000, 78, 553. c) B. L. Yvon, P. K. Datta, T. N. Le, J. L.
Charlton, Synthesis 2001, 1556. d) H. Yoda, Y. Nakaseko, K.
Takabe, Tetrahedron Lett. 2004, 45, 4217. e) L. F. Silva, Jr.,
F. A. Siqueira, E. C. Pedrozo, F. Y. M. Vieira, A. C.
Doriguetto, Org. Lett. 2007, 9, 1433. f) M. Sriram, J. J. Hall,
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8161.
1
2
3
4
5
6
7
1f
1f
1f
1f
1g
1h
1i
H
H
H
H
Sc(OTf)3 83
Yb(OTf)3 83
EDC
EDC
2f
2f
2f
2f
2g
2h
2i
92
85
60
99
68
82
71
TiCl4
rt
rt
rt
rt
rt
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
BF3¢Et2O
Cl BF3¢Et2O
Me BF3¢Et2O
OMe BF3¢Et2O
aReactions were carried out under an Ar atmosphere. bReaction
c
d
time is 1 h. 1.1 equiv of Lewis acid was used. Isolated.
2
a) Y. Nishii, K. Wakasugi, K. Koga, Y. Tanabe, J. Am. Chem.
Soc. 2004, 126, 5358. b) Y. Nishii, T. Yoshida, H. Asano, K.
Wakasugi, J. Morita, Y. Aso, E. Yoshida, J. Motoyoshiya, H.
Aoyama, Y. Tanabe, J. Org. Chem. 2005, 70, 2667. c) Y.
Nishii, T. Nagano, H. Gotoh, R. Nagase, J. Motoyoshiya,
H. Aoyama, Y. Tanabe, Org. Lett. 2007, 9, 563, other
references cited therein.
Similar reaction of diaryl analogs 1g-1i proceeded in good to
high yields (Entries 5-7).
The proposed mechanism of the ring-expansion mediated by
Sc(OTf)3 is as follows (Scheme 3). First, Sc(OTf)3 chelates with
the OH and carbonyl of ¢-hyrdoxyester 1 to give an inter-
mediate 3. Successive Sc(OTf)3-promoted elimination of the
OH group gives the cationic intermediate 4. Then, highly
regioselective ring-opening and Friedel-Crafts-type cyclization
sequentially occur to give dihydronaphthalene 2. Cyclization
proceeds smoothly in the Z-intermediate 5 of the cation. In the
reaction using TiCl4 or SnCl4, the presence of Cl- adversely
affects the cyclization, causing the chlorination of benzyl cation
to occur. BF3¢OEt2 also promotes the ring-expansion of sym-
metrically substituted diaryl analog 1f in excellent yield. In
this case (R3 = p-R1-Ph, R2 = H, intermediate 5 = 6), the
ring-expansion proceeds smoothly without the problem of the
E-intermediate.
3
4
5
6
7
a) T. Nagano, J. Motoyoshiya, A. Kakehi, Y. Nishii, Org.
Lett. 2008, 10, 5453. b) E. Yoshida, T. Nagano, J.
Motoyoshiya, Y. Nishii, Chem. Lett. 2009, 38, 1078.
(Arylhydroxymethyl)cyclopropanecarboxylates 1a-1i were
prepared by the similar method of our previous report: see
Ref. 3a.
As a similar reaction, an example has been reported to
synthesize 3-bromo-1,1-dimethyl-4-phenyl-2-hydronaphtha-
lene: R. Dammann, D. Seebach, Chem. Ber. 1979, 112, 2167.
Procedures were described in Supporting Information, which
is available electronically on the CSJ-Journal Web site,
http://www.csj.jp/journals/chem-lett/index.html.
In conclusion, we developed a novel synthesis of 1-aryl-1,2-
dihydronaphthalene-3-carboxylic acid esters utilizing a Lewis
acid-mediated regioselective ring-expansion of methyl (aryl-
hydroxymethyl)cyclopropanecarboxylate. Application of the
a) J. Vebrel, R. Carrié, Tetrahedron 1983, 39, 4163. b) J.
Vebrel, D. Grée, R. Carrié, Can. J. Chem. 1984, 62, 939. c) J.
Vebrel, R. Carrie, Bull. Chem. Soc. Fr 1982, 3-4, Part II,
116.
Chem. Lett. 2010, 39, 194-195
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/