Mg-promoted facile and selective intramolecular cyclization of aromatic δ-ketoesters

Article abstract of DOI:10.1016/j.tet.2010.12.030

Treatment of various types of aromatic δ-ketoesters 2, 7, and 9 with Mg-turnings for Grignard reaction at -5 to 0 °C in N,N-dimethylformamide (DMF) containing trimethylsilyl chloride (TMSCl) brought about selective and reductive intramolecular cyclization

Full text of DOI:10.1016/j.tet.2010.12.030

Tetrahedron 67 (2011) 1598e1602
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Mg-promoted facile and selective intramolecular cyclization of aromatic
d-ketoesters
*
Takeshi Miyazaki, Hirofumi Maekawa , Kazuaki Yonemura, Yoshimasa Yamamoto, Yoshiko Yamanaka,
*
Ikuzo Nishiguchi
Department of Chemistry, Nagaoka University of Technology, 1603-1, Kamitomioka-cho, Nagaoka, Niigata 940-2188, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 October 2010
Received in revised form 9 December 2010
Accepted 10 December 2010
Available online 16 December 2010
Treatment of various types of aromatic d-ketoesters 2, 7, and 9 with Mg-turnings for Grignard reaction
at ꢀ5 to 0 ꢁC in N,N-dimethylformamide (DMF) containing trimethylsilyl chloride (TMSCl) brought about
selective and reductive intramolecular cyclization to give the corresponding
a-aryl-a-hydrox-
ycyclopentanones 5, 8, and 10, respectively, in moderate to good yields. Similar reductive intramolecular
cyclization of aromatic -ketodiesters 14, followed by acidic hydrolysis and decarboxylation easily gave
d
the corresponding 2-aryl-2-cyclopenten-1-ones 15. The present facile coupling may be initiated through
electron transfer from Mg metal to the aromatic carbonyl groups of 2, 7, 9, and 14 to generate the cor-
responding radical anions, followed by their intramolecular nucleophilic attack to the ester groups to
give the corresponding five-membered ring compounds 5, 8, 10, and 15, respectively.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Aromatic d-ketoesters
Mg-turnings
Electron transfer
Reductive intramolecular cyclization
a
a
-Aryl-
-Aryl-
a
a
-cyclopentenones
-hydroxycyclopentanones
1. Introduction
In this study, we wish to report selective, facile, effective, and
general Mg-promoted intramolecular cyclization of four types of
Selective and facile cross coupling between different electro-
philes through electron transfer, mainly promoted by electro-
chemical or metal-promoted reactions, may provide unique and
useful methodology in organic synthesis.1 Among them, cross
coupling involving aromatic carbonyl groups with other electro-
philic functional groups has extensively studied to give many types
of interesting reactions.2,6 For example, we have already reported
electroreductive coupling of aromatic acid anhydride with aliphatic
acid anhydrides,3 and Mg-promoted coupling of aromatic ketones
with aliphatic ketones4 and acid chloride.5
easily available aromatic d-ketoesters to give 2-aryl-2-hydrox-
ycyclopentan-1-ones or 2-aryl-2-cyclopenten-1-ones in good to
moderate yields. Use of inexpensive Mg turning for Grignard
reaction and wide generality of the reaction may be emphasized as
feature and advantage of the present methods.
2. Results and discussion
2.1. Mg-promoted reductive intramolecular cyclization of
aromatic
g
-,
d
-, and
3
-ketoesters, 1, 2aeg, 3, 7aec, and 9
On the other hand, it was reported that intramolecular cycliza-
tion of aromatic d- and 3-ketoesters, 2-alkyl-indanone-2-acetate
The starting aromatic
g
-, -, and -ketoesters, 1, 2aeg, and 3,
d
3
and/or 2-acyloxymethyl-1-indanones by electrochemical,6e8 and
Sm-promoted reduction.9,10 These methods may be interesting and
noteworthy from the standpoint of organic reactions, although
there may be some limitations as organic synthetic methods,
especially in a large scale, because of necessity of more than an
equivalent mole of expensive SmI2 and/or some problems
regarding inevitable necessity of particular reaction equipments for
electroreduction.
were easily prepared by FriedeleCrafts acylation of substituted
benzene with succinic, glutaric, and adipic anhydrides, respectively,
followed by acid-catalyzed esterification according to the usual
procedure.11
Treatment of aromatic
d- and 3-ketoesters, 2a and 3, with
excess of Mg turning for Grignard reaction at ꢀ5 to 0 ꢁC in N,N-
dimethylformamide(DMF) containing trimethylsilyl chloride
(TMSCl) as an activator of Mg turning,12 followed by acid-hydro-
lysis using 5% aqueous H2SO4 in methanol, brought about re-
ductive intramolecular cyclization between the keto and the ester
groups to give the corresponding cyclization products,
a-phenyl-
* Corresponding authors. Tel.: þ81 (258) 47 9307; fax: þ81 (258) 47 9300; e-mail
address: nishiiku@vos.nagaokaut.ac.jp (I. Nishiguchi).
a
-hydroxy-cyclopentanones (5a)6 from
d-ketoesters 2a, and
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.12.030

T. Miyazaki et al. / Tetrahedron 67 (2011) 1598e1602
1599
a
-phenyl-
and 43% yields, respectively. However, similar treatment of
-ketoesters, methyl benzoylpropionate (1), resulted in simple
reduction to give only non-cyclization product, methyl -hydroxy-
-phenylbutyrate (4)13 in a 30% yield.
These phenomena may be considerably attributed to combined
a
-hydroxycyclohexanone (6)6 from
3
-ketoesters 3 in 78%
Also it may be noteworthy that the present Mg-promoted
intramolecular cyclization shows rough tendency that an electron-
withdrawing group on aromatic ring of 2aeg mostly led to
increased yields of the corresponding cyclization products com-
pared with an electron-donating group.
It may be quite interesting and noteworthy that Mg-promoted
method, possessing more facility and wider generality, may gener-
ally give the better yield of the corresponding same products from
g
g
g
effects of ring-strain of the products and proximity between the
keto and the ester groups in the cyclization steps.
Furthermore, facile and effective intramolecular cyclization took
place to afford 2-aryl-2-hydroxycyclo-pentanones 5beg in good
yields from the corresponding aromatic
according to the similar procedures under the similar reaction
conditions, as shown in Table 1.
the same starting d-ketoester than electroreduction, promoted by
the similar electron-transfer reaction. For instance, the former
method gave the corresponding product 5a from 2a in a 78% yield
while the latter method gave the same product 5a in a 56% yield.6
This effective ring-closure may be successfully applied to the
related bicyclic systems. Thus, similar Mg-promoted intramolecular
ketoester coupling were successfully accomplished in the system of
d
-ketoesters 2beg14
Table 1
2-carbomethoxyethyl-a
-indanones 7aec,15 giving 1-hydrox-
Mg-promoted intramolecular cyclization of d-ketoesters
ybicyclo[3.3.0]octan-8-ones 8aec,16 as shown in Table 2.
Table 2
Mg-promoted intramolecular cyclization of aromatic ketoester
Ar of
d
-ketoesters 2aeg
Yielda (%) of products 5aeg
C6H5 (2a)
3-CH3OC6H4 (2b)
4-ClC6H4 (2c)
78 (5a)
90 (5b)
72 (5c)
70 (5d)
67 (5e)
47 (5f)
43 (5g)
3-ClC6H4 (2d)
4-CH3C6H4 (2e)
2,5-(CH3O)2C6H3 (2f)
4-CH3OC6H4 (2g)
R2
R1
Yield (%) of 8aec
endo/exo
H
CH3
H
H (7a)
H (7b)
CH3 (7c)
64
57
48
d
56/44
65/35
a
Isolated yields.
It may be quite noteworthy that use of 2-carbomethoxyethyl-a-
In these reactions, the reaction mixtures were usually treated
with 5% aqueous H2SO4 in methanol to obtain hydrolysis products
5aeg (Scheme 1). Careful attempts for isolation of the trimethylsi-
lylated products before acid-catalyzed hydrolysis of the reaction
mixture of 2a led to successful identification of 1,2-bis(trimethylsi-
lyloxy)-1-methoxy-2-phenylcyclopentane (5a0)6 and 2-trime-
thylsilyloxy-2-phenylcyclopentanone (5a00),6 as shown in Fig. 1.
tetralone(9)6 as the starting compound in the present Mg-promoted
intramolecular ketoester coupling brought about stereoselective
and efficient formation of cis-1-hydroxybicyclo[4.3.0]nonan-9-one
system (10)6 (Scheme 2).
O
O
O
HO
1) Mg / TMSCl / DMF
OCH3
H
CH OH
3
2) 5% H2SO4aq. /
O
O
O
OH
1) Mg / TMSCl / DMF
OMe
OMe
OMe
OMe
10 : Y=83%
9
2) 5% H2SO4 aq. / MeOH
O
O
O
O
1
Scheme 2. Mg-promoted intramolecular cyclization of 2-carbomethoxyethyl-
a-tetra-
4 : Y = 30%
HO
lone (9).
1) Mg / TMSCl / DMF
Cyclic voltammetric study17 of methyl benzoyl pentanoate (3a),
acetophenone, methyl acetate, and TMSCl showed their reduction
potential ꢀ2.09 V, ꢀ2.20 V, ꢀ2.80 V, and no peak up to 3.00 V (vs
Ag/AgCl), respectively, indicating that the first electron transfer
may take place from Mg metal to the carbonyl group of the benzoyl
2
2) 5% H2SO4 aq. / MeOH
O
2a
5a : Y = 78%
HO
1) Mg / TMSCl / DMF
group of aromatic d-ketoesters 9 to give the corresponding anion
3
radical 11a, in which the generated Mgþꢂcation radical reasonably
makes some of strong participation with the oxygen atom of the
keto group of 11a from the opposite site against the (2-carbome-
thoxy)ethyl group because of its large steric effect. Furthermore,
2) 5% H2SO4 aq. / MeOH
O
3
6 : Y = 43%
Scheme 1. Mg-promoted reductive intramolecular cyclization of
ketoesters 1, 2a, and 3.
g-, d-, and aromatic
the anionic a-carbon atom of the anion radical 11a may attack to
the carbonyl carbon atom of the carbomethoxy group, accompa-
nying another electron transfer from Mgþꢂcation radical to form the
cis-condensed bicyclic intermediate 11b, in which a Mg2þ-cation
may possess some of ionic bonding with the two oxygen anions.
The subsequent electrophilic attack of TMSCl to these oxygen an-
ions of the intermediate may give the bicyclic cis-condensed cis-bis
(trimethylsilyloxy) compound 12. The following acid-catalyzed
hydrolysis may give the product 10 in a stereoselective manner, as
shown in the following Scheme 3.
TMSO
C6H5
TMSO
C6H5
TMSO
MeO
O
5a''
5a'
Fig. 1. Trimethylsilylated products.

1600
T. Miyazaki et al. / Tetrahedron 67 (2011) 1598e1602
Mg+
Table 3
O
Novel synthesis of 2-aryl-2-cyclopenten-1-ones 15aef through Mg-promoted
reductive cyclization of -ketodiesters, followed by acid-catalyzed reactions
O
O
d
O
OMe
H
Mg (+e)
OMe
9
11a
TMS-
Mg2+
O
OMe
H
O
O
OMe
H
Entry
X
R
Isolated yield (%)
TMS-
O
1
2
3
4
5
6
H
Ph
Ph
Ph
Ph
Me
Ph
51 (15a)
23 (15b)
31 (15c)
32 (15d)
43 (15e)
14 (15f)
+e
2 TMSCl
p-OMe
p-Cl
p-Me
H
Å|MgCl2
m-OMe
12
11b
Reaction condition: (First Step) substrate (5 mmol), Mg (10.0 equiv), TMSCl
(5.0 equiv), DMF (100 mL): (Second Step) 10% H2SO4 (25 mL), EtOH (75 mL), 4 h.
O
H+
HO
O
Å|MeOH
Å|2TMSOH
EtOOC
O
COOEt
COOEt
EtO
H
Mg+
O
+e
Mg (+e)
10
X
X
Scheme 3. Proposed reaction mechanism for stereoselective cyclization of d-ketoesters.
14a-f
16a-f
COOEt
OEt
O
COOEt
2.2. Novel synthesis of 2-aryl-2-cyclopenten-1-ones 15aef
through Mg-promoted reductive cyclization of aromatic d-
ketodiesters 14aef followed by acid-catalyzed hydrolysis
Mg2+
O
1) TMSCl
2) H3O+
HO
O
X
X
The present interesting Mg-promoted reductive cyclization of
aromatic -ketoesters were successfully applied to development of
new synthetic methods of 2-aryl-2-cyclopenten-1-ones 15aef18
18a-f
X
d
O
17a-f
H3O+
- CO2, -H2O
starting from
d-ketodiesters, diethyl 2-(3-oxo-1,3-diarylpropyl)
malonates 14aef,19 which were easily prepared through conju-
gated addition of diethyl malonate anion to the corresponding
chalcone derivatives 13aef according to the usual procedure, as
shown in Scheme 4.
R
15a-f
Scheme 5. Proposed reaction mechanism for intramolecular cyclization of ketoesters
14aef.
EtOOC
O
COOEt
O
In these over-all steps, the substituent effects may be too com-
plex to mention because many steps, such as cyclization, acid-cat-
alyzed hydrolysis, and decarboxylation were involved.
CH2(COOEt)2
R
R
KOH / PhCH2Me3NCl
In conclusion, the present Mg-promoted intramolecular cycli-
X
X
zation of aromatic d-ketoesters may be characterized by simple
13a-f
14a-f
procedure, reasonable yields, and high utility of the products, giv-
ing new, important, and useful methodology in organic synthesis.
Especially, use of inexpensive and easily available Mg-turnings for
Grignard reaction, much facility in a large scale synthesis, and wide
generality of the reaction and wide generality of the reaction as
well as satisfactory yields and selectivities may be strongly
emphasized as features and advantages of the present methods.
14a (X = H, R = Ph: Y = 37%),
14c (X = p-Cl, R = Ph: Y = 58%), 14d (X = p-Me, R = Ph: Y = 75%),
14e (X = H, R = Me: Y = 77%), 14f (X = m-OMe, R = Ph: Y = 38%)
Scheme 4. Preparation of -ketodiesters 14aef.
14b (X = p-OMe, R = Ph: Y = 63%),
d
Mg-promoted intramolecular coupling of aromatic d-ketoesters,
followed by acid-catalyzed hydrolysis, also smoothly proceeded to
give 2-aryl-2-cyclopenten-1-ones 15aef as the sole products, possi-
bly useful fragrant substances, in 51e14% yields, as shown in Table 3.
3. Experimental section
3.1. Typical procedure for Mg-promoted reductive
These conversion of the
penten-1-ones 15 may be explained by the following Scheme 5, as
shownbelow. The firstelectrontransferfromMgmetaltothe benzoyl
d
-aryl ketodiesters 14 to 2-aryl-2-cyclo-
intramolecular coupling of aromatic
9, 14aef, and -ketoester 3
d-ketoesters, 2aeg, 7aec,
3
carbonyl group of
d
-aryl ketodiesters 14 gave the corresponding an
Into a 50-mL three-necked flask were introduced 30 mL of an-
hydrous N,N-dimethylformamide (DMF) as solvent, 10 equiv mol
Mg turning for Grignard reaction, and 2.5 equiv of trimethylsilyl
chloride (TMSCl) were added under nitrogen atmosphere, and the
solution was stirred at room temperature for 0.5 h. Then the mix-
anion radical 16, whose anionic carbon may attack to a carbonyl
carbonof the ester groupsaccompanyingthesecondelectrontransfer
from Mg metal to generate a five-membered ring dianion 17.
Trapping of the dianion 17aef with TMSCl followed by acid-
catalyzed hydrolysis, decarboxylation, and dehydration may finally
give 2-aryl-2-cyclopenten-1-ones 15aef as the final products.
ture of an aromatic
d-ketoesters, 2aeg, 7aec, 9, 14aef, or
3-ketoester 3 (5.0 mmol) and the additional 2.5 equiv of TMSCl

T. Miyazaki et al. / Tetrahedron 67 (2011) 1598e1602
1601
dissolved in 15 mL of anhydrous DMF were added dropwise to the
above DMF solution at ꢀ5 to 0 ꢁC over 20 min. The reaction mixture
was stirred at room temperature for 12 h. After the reaction, the
mixture was poured into satd NaHCO3 solution. Organic materials
were extracted with three 150-mL portions of ethyl ether. The
combined ethereal solution was concentrated under reduced
pressure to give the residual oil, which was then treated with 5%
sulfuric acid in 50% aqueous methanol at room temperature for 3 h.
In the case of the reaction of 14aef, each of the reaction mixture
was found to consist of a complex mixture of several components.
Then, the mixture was further treated with 10% aqueous sulfuric
acid for another 3 h. The organic components were then extracted
with ethyl ether three times, and the combined ethereal solution
was dried over anhydrous MgSO4. After removal of MgSO4 by fil-
tration and evaporation of the solvent, isolation by column chro-
matography gave the corresponding cyclization products in
satisfactory yield.
cmꢀ1): 3425 (OH), 3046 (AreH), 2947 (CeH), 1734 (C]O), 1229
(CeOeC), 734. MS (EI): m/z 236 (Mþ). Mp: 99.8102.6 ꢁC. Anal. Calcd
for C13H16O4: C, 66.09; H, 6.83, found: C, 66.12; H, 6.86.
3.2.6. Methyl-3-(1-oxo-2-indanyl) butanoate (7b). Diastereomers
ratio¼6:4. Mixture of isomers. 1H NMR (400 MHz, CDCl3, ppm):
d
0.86 (d, J¼6.8 Hz, 1.8H), 1.00 (d, J¼7.1 Hz, 1.2H), 2.29e2.95 (m, 5H),
3.20 (dd, J¼7.6 , 17.6 Hz, 0.6H), 3.29 (dd, J¼8.1 , 17.3 Hz, 0.4H), 3.64
(s, 1.2H), 3.69 (s, 1.8H), 7.34e7.38 (m, 1H), 7.46e7.48 (m, 1H),
7.56e7.60 (m, 1H), 7.71e7.75 (m, 1H). IR (neat, cmꢀ1): 3077 (AreH),
2953 (CeH), 1735 (ester), 1709 (C]O). MS (EI): m/z 232 (Mþ). Anal.
Calcd for C14H16O3: C, 72.39; H, 6.94, found: C, 72.36; H, 7.07.
3.2.7. Methyl-3-(1-oxo-2-indanyl)-2-methylpropanoate
(7c).
Diastereomers ratio¼1:1. Mixture of isomers. 1H NMR (400 MHz,
CDCl3, ppm):
d
1.25 (d, J¼7.1 Hz, 1.5H), 1.26 (d, J¼7.1 Hz, 1.5H),
1.56e3.70 (m, 5H,), 3.33 (dd, J¼7.8 , 17.1 Hz, 0.5H), 3.39 (dd, J¼7.8 ,
16.8 Hz, 0.5H), 3.39 (d, J＝3.4 Hz， 1.5H), 3.70 (d, J¼3.4 Hz, 1.5H),
7.34e7.38 (m, 1H), 7.43e7.46 (m, 1H), 7.57e7.60 (m, 1H), 7.73e7.75
(m, 1H). IR (neat, cmꢀ1): 3033 (AreH), 2950 (CeH), 1731 (ester).
1711 (C]O). MS (EI): m/z 232 (Mþ). Anal. Calcd for C14H16O3: C,
72.39; H, 6.94, found: C, 72.43; H, 7.16.
In the fivefolded scale reaction of 2a under the similar reaction
conditions, the product 5a was isolated in a 70% yield.
All the cyclization products, 5aeg, 8aec, 10, 15aef, and 6,
obtained in this study were characterized by spectroscopic and
elemental analyses or comparison of spectroscopic and chro-
matographic behaviors with those of authentic samples.
3.2.8. (3aS
drocyclopent[a]inden-3-one (8b). endo:exo¼56:44. Mixture of iso-
mers. 1H NMR (400 MHz, CDCl3, ppm):
*
,8aS )-3a-Hydroxy-1-methyl-1,2,3,3a,8,8a-hexahy-
*
3.2. Analytical data for new compounds among the products
d
1.02 (d, J¼6.7 Hz, 1.68H),
3.2.1. 2-Hydroxy-2-(3-methoxyphenyl)cyclopentanone (5b). 1H NMR
1.13 (d, J¼6.8 Hz, 1.32H), 1.85e3.64 (m, 5H), 3.30 (br s, 1H),
7.21e7.41 (m, 4H). IR (KBr, cmꢀ1): 3443 (OH), 3064 (AreH), 2960
(CeH),1732 (C]O). MS (EI): m/z 202 (Mþ). Anal. Calcd for C13H14O2:
C, 77.20; H, 6.98, found: C, 77.16; H, 6.94.
(400 MHz, CDCl3, ppm):
d 1.81e1.89 (m, 1H), 2.03e2.09 (m, 1H),
2.18e2.25 (m, 1H), 2.44e2.52 (m, 3H), 2.99 (br s, 1H), 3.80 (s, 3H),
6.83e6.94 (m, 3H), 7.25e7.30 (m, 1H). 13C NMR (100 MHz, CDCl3,
ppm): d 17.27, 35.75, 37.82, 55.27, 80.56,111.62,113.43,117.84,129.59,
142.19,159.66, 218.27. IR (neat, cmꢀ1): 3441 (OH), 3066 (AreH), 2965
(CeH), 1742 (C]O), 1265 (CeOeC). MS (EI): m/z 206 (Mþ). Anal.
Calcd for C12H14O3: C, 69.88; H, 6.84, found: C, 69.85; H, 6.77.
3.2.9. (3aS
drocyclopent[a]inden-3-one (8c). endo:exo¼65:35. Mixture of iso-
mers. 1H NMR (400 MHz, CDCl3, ppm):
*
,8aR
*
)-3a-Hydroxy-2-methyl-1,2,3,3a,8,8a-hexahy-
d
1.14 (d, J¼6.8 Hz, 1.05H),
1.22 (d, J¼6.8 Hz, 1.95H), 1.59e3.45 (m, 5H), 3.09 (br s, 0.65H), 3.28
(br s, 0.35H), 7.21e7.41 (m, 4H). IR (neat, cmꢀ1): 3437 (OH), 3065
(AreH), 2931 (CeH),1740 (C]O). MS (EI): m/z 202 (Mþ). Anal. Calcd
for C13H14O2: C, 77.20; H, 6.98, found: C, 77.43; H, 7.08.
3.2.2. 2-Hydroxy-2-(4-chlorophenyl)cyclopentanone (5c). 1H NMR
(400 MHz, CDCl3, ppm):
d 1.80e1.89 (m, 1H), 2.04e2.13 (m, 1H),
2.19e2.27 (m, 1H), 2.39e2.54 (m, 3H), 2.98 (br s, 1H), 7.26e7.35 (m,
4H). 13C NMR (100 MHz, CDCl3, ppm):
d 17.31, 35.75, 37.92, 80.09,
127.17, 128.73, 134.04, 139.13, 217.93. IR (neat, cmꢀ1): 3438 (OH),
3049 (AreH), 2974 (CeH), 1745 (C]O). MS (EI): m/z 210 (Mþ). Anal.
Calcd for C11H11ClO2: C, 62.72; H, 5.26, found: C, 62.78; H, 5.45.
3.2.10. Diethyl-2-[3-(3-methoxyphenyl)-1-phenyl-3-oxopropyl]-mal-
onate (14f). 1H NMR (400 MHz, CDCl3, ppm):
d
1.00 (t, J¼7.3 Hz, 3H),
1.24 (t, J¼7.3 Hz, 3H), 3.44 (dd, J¼7.3 , 16.5 Hz, 1H), 3.57 (dd, J¼4.3 ,
16.5 Hz,1H), 3.81 (d, J¼9.9 Hz,1H), 3.82 (s, 3H), 3.95(q, J¼7.3 Hz, 2H),
4.14e4.23 (m, 3H), 7.07e7.51 (m, 9H). 13C NMR (100 MHz, CDCl3,
3.2.3. 2-Hydroxy-2-(3-chlorophenyl)cyclopentanone (5d). 1H NMR
(270 MHz, CDCl3, ppm):
d
1.81e1.92 (m, 1H), 2.04e2.14 (m, 1H),
ppm): d 13.73, 14.00, 40.87, 42.75, 55.40, 57.56, 61.32, 61.64, 112.17,
2.20e2.28 (m,1H), 2.39e2.55(m, 3H), 3.03(brs,1H),7.17e7.36 (m, 4H).
119.86, 120.74, 127.12, 128.23, 128.37, 129.50, 140.39, 159.75, 167.71,
168.32, 197.35. IR (neat, cmꢀ1): 3020 (AreH), 2992 (CeH), 1725 (C]
O),1676 (C]O) 1240 (CeOeC). MS (EI): m/z 398 (Mþ). Anal. Calcd for
C23H26O6: C, 69.33; H, 6.58, found: C, 69.30; H, 6.51.
13C NMR (67.5 MHz, CDCl3, ppm):
d 17.38, 35.75, 35.88, 80.14, 123.78,
126.04, 128.22, 129.80, 134.51, 142.83, 217.69. IR (neat, cmꢀ1): 3435
(OH), 3052 (AreH), 2972 (CeH), 1743 (C]O). MS (EI): m/z 210 (Mþ).
Anal. Calcd for C11H11ClO2: C, 62.72; H, 5.26, found: C, 62.82; H, 5.12.
3.2.11. 2-(4-Methoxyphenyl)-4-phenyl-2-cyclopenten-1-one (15b).
3.2.4. 2-Hydroxy-2-(4-methylphenyl)cyclopentanone (5e). 1H NMR
1H NMR (400 MHz, CDCl3, ppm):
d
2.54 (dd, J¼1.8 ,18.6 Hz,1H), 3.10
(270 MHz, CDCl3, ppm):
d
1.71e1.88 (m, 1H), 1.96e2.10 (m, 1H),
(dd, J¼6.8 , 18.6 Hz, 1H), 3.82 (s, 3H), 4.11e4.14 (m, 1H), 6.92e6.94
2.13e2.45 (m, 1H), 2.14 (s, 3H), 2.39e2.53 (m, 3H), 3.15 (br s, 1H),
(m, 2H), 7.18e7.35 (m, 5H), 7.68e7.76 (m, 3H) ppm. 13C NMR
7.12 (d, J¼8.5 Hz, 2H) 7.24 (d, J¼8.5 Hz, 2H). 13C NMR (67.5 MHz,
(100 MHz, CDCl3):
d 43.58, 45.65, 55.22, 113.86, 123.66, 127.11,
CDCl3, ppm):
d
17.17, 21.10, 35.56, 37.57, 80.41, 125.59, 129.18, 137.35,
127.20, 128.37, 128.94, 129.09, 142.05, 142.12, 158.67, 207.43. IR
(neat, cmꢀ1): 3020 (AreH), 2982 (CH), 1733 (C]O), 1246 (CeOeC)
cmꢀ1. MS (EI): m/z 264 (Mþ). Anal. Calcd for C18H16O2: C, 86.79; H,
6.10, found: C, 86.80; H, 6.12.
137.82, 218.45. IR (neat, cmꢀ1): 3435 (OH), 3054 (AreH), 2978
(CeH), 1744 (C]O). MS (EI): m/z 190 (Mþ). Anal. Calcd for C12H14O2:
C, 75.76; H, 7.42, found: C, 75.86; H, 7.12.
3.2.5. 2-Hydroxy-2-(2,5-dimethoxyphenyl)cyclopentanone (5f). 1H
3.2.12. 2-(4-Chlorophenyl)-4-phenyl-2-cyclopenten-1-one (15c). 1H
NMR (400 MHz, CDCl3, ppm):
d
2.03e2.14 (m, 3H), 2.31e2.34 (m,
NMR (400 MHz, CDCl3, ppm):
(dd, J¼4.0 , 16.0 Hz, 1H), 4.15e4,18 (m, 1H), 7.19e7.38 (m, 7H),
7.71e7.85 (m, 3H). 13C NMR (100 MHz, CDCl3, ppm):
43.73, 45.52,
d
2.57 (dd, J¼4.0 , 16.0 Hz, 1H), 3.12
1H), 2.45 (br s, 1H), 2.48e2.50 (m, 1H), 2.55e2.62 (m, 1H), 3.69 (s,
3H), 3.79 (s, 3H), 6.72e6.85 (m, 2H) 7.10e7.21 (m, 1H). 13C NMR
d
(100 MHz, CDCl3, ppm):
112.44, 112.63, 113.33, 132.62, 148.98, 154.01, 217.92. IR (neat,
d
19.69, 36.49, 37.81, 55.70, 55.78, 78.42,
127.23, 127.27, 128.50, 128.69, 129.02, 131.13, 141.90, 142.86, 153.01,
160.51, 207.09. IR (neat, cmꢀ1): 3029 (AreH), 2990 (CeH), 1706 (C]

1602
T. Miyazaki et al. / Tetrahedron 67 (2011) 1598e1602
O). MS (EI): m/z 268 (Mþ). Anal. Calcd for C17H13ClO: C, 75.98; H,
4.88, found: C, 75.87; H, 4.85.
2. (a) Kise, N.; Shirozawa, Y.; Ueda, N. Tetrahedron Lett. 2004, 45, 7599; (b) Kise, N.;
Shirozawa, Y.; Ueda, N. Tetrahedron 2007, 63, 5415.
3. Nishiguchi, I.; Matsunami, M.; Mizoguchi, S.; Maekawa, H. Electrochem. Soc.
Trans. 2007, 2, 29.
3.2.13. 2-(4-Methyl phenyl)-4-phenyl-2-cyclopenten-1-one (15d). 1H
4. Maekawa, H.; Yamamoto, Y.; Shimada, H.; Yonemura, Y.; Nishiguchi, I. Tetra-
hedron Lett. 2004, 45, 3869.
5. Nishiguchi, I.; Sakai, M.; Maekawa, H.; Ohno, T.; Yamamoto, Y.; Ishino, Y. Tet-
rahedron Lett. 2002, 43, 635.
6. Kise, N.; Arimoto, K.; Ueda, N. Tetrahedron Lett. 2003, 44, 6281.
7. For intramolecular coupling between imino and ester groups, see Kise, N.;
Ozaki, H.; Moriyama, N.; Kitagishi, Y.; Ueda, N. J. Am. Chem. Soc. 2003, 125, 11591.
8. For intramolecular coupling between keto and amide groups, see Kise, N.;
Sakurai, T. Tetrahedron Lett. 2010, 51, 70.
NMR (400 MHz, CDCl3, ppm):
1H), 3.57 (dd, J¼7.6 , 18.8 Hz, 1H), 3.80 (dd, J¼3.0 , 7.6 Hz, 1H),
7.11e7.64 (m, 10H). 13C NMR (100 MHz, CDCl3, ppm):
21.03, 39.24,
d
2.33 (s, 3H), 3.16 (dd, J¼3.0 ,18.8 Hz,
d
51.39, 127.29, 127.57, 127.67, 127.79, 129.58, 131.47, 133.71, 135.61,
136.90, 140.47, 202.93. IR (neat, cmꢀ1): 3030 (AreH), 2992 (CeH),
1702 (C]O). MS (EI): m/z 248 (Mþ). Anal. Calcd for C18H16O: C,
87.06; H, 6.41, found: C, 87.05; H, 6.33.
9. Iwaya, K.; Tamura, M.; Nakamura, M.; Hasegawa, E. Tetrahedron Lett. 2003, 44,
9317.
10. Hasegawa, E.; Okamoto, K.; Tanigawa, N.; Nakamura, M.; Iwaya, K.; Hoshi, T.;
Suzuki, T. Tetrahedron Lett. 2006, 47, 7715.
3.2.14. 2-(3-Methoxyphenyl)-4-phenylcyclopentenon (15f). 1H NMR
11. (a) Creary, X.; Inocencio, P. A.; Underiner, T. L.; Kostromin, R. J. Org. Chem. 1985,
50, 1932; (b) Itoh, K.; Nakanishi, S.; Otsuji, Y. Bull. Chem. Soc. Jpn. 1991, 42, 2965;
(c) Babudri, F.; Fiandanese, V.; Marchese, G.; Punzi, A. Tetrahedron 1996, 42,
13513; (d) Kieslich, K. Indian J. Chem., Sect. B 1984, 23B, 287; (e) EI-Gawad, N. M.;
Abd Al-Azhar. J. Pharm. Sci. 1994, 14, 218.
12. The role of TMSCl may be the following two effects, the first one may be ac-
tivation of Mg metal by refreshment of surface of Mg metal and the second may
be fast trapping of the generating oxygen anions.
(400 MHz, CDCl3, ppm):
J¼8.4 , 18.9 Hz, 1H), 3.79 (s, 3H), 4.25e4,35 (m, 1H), 6.78e7.86 (m,
10H). 13C NMR (100 MHz, CDCl3, ppm):
39.13, 51.68, 55.20, 112.51,
113.73, 114.94, 119.91, 127.38, 127.67, 128.79, 129.901, 131.52, 140.11,
140.11, 159.88, 204.98. IR (neat, cmꢀ1): 3020 (AreH), 2984 (CeH),
1733 (C]O), 1266 (CeOeC). MS (EI): m/z 264 (Mþ). Anal. Calcd for
C18H16O2: C, 86.79; H, 6.10, found: C, 86.80; H, 6.12.
d
3.19 (dd, J¼3.2 , 18.9 Hz, 1H), 3.57 (dd,
d
13. Christopher, T. M.; Koide, K. Org. Lett. 2004, 6, 1785.
14. (a) Itoh, K.; Nakanishi, S.; Otsuji, Y. Bull. Chem. Soc. Jpn. 1991, 64, 2965; (b) Haras,
M. A.; Vaquero, J. J.; Navio, J. G.; Bulla, J. A. Tetrahedron Lett. 1997, 38, 1817; (c)
Kooistra, F. B.; Knol, J.; Kastenberg, F.; Popescu, L. M.; Verhees, W. J. H.; Kroon, J.
M.; Hummelen, J. C. Org. Lett. 2007, 9, 511.
Acknowledgements
15. A reference for 7a: Hashimoto, H.; Tashiro, M. Org. Prep. Proced. Int. 1987,
19, 447.
16. A reference for 8a: Kakiuchi, K.; Fujioka, Y.; Yamaura, H.; Tsutsumi, K.; Mor-
imoto, T.; Kurosawa, H. Tetrahedron Lett. 2001, 42, 7595.
17. Cyclic voltammetry for measurement of reduction potentials of 3a, acetophe-
none, methyl acetate, and trimethylsilyl chloride were performed at room
temperature in a 1% Bu4NClO4 solution of N,N-dimethylforamide using Pt as the
working and counter electrodes, and Ag/AgCl as the reference electrode with
200 mV/s of sweep rate.
18. (a) A reference for 15a: Park, K. H.; Jung, I. G.; Chung, Y. K. Org. Lett. 2004, 6,
1183; (b) A reference for 15e: Jacobson, R. M.; Lahm, G. P. Org. Lett. 1979,
44, 462.
19. (a) A reference for 14aed: Wang, J.; Li, H.; Zu, L. S.; Jiang, W.; Xie, H.; Duan, W.
H.; Wang, W. J. Am. Chem. Soc. 2006, 128, 12652; (b) A reference for 14c: Ooi, T.;
Ohara, D.; Fukumoto, K.; Maruoka, K. Org. Lett. 2005, 7, 3195; (c) A reference for
14e: Wills, M. C.; Chauhan, J.; Whittigham, W. G. Org. Biomol. Chem. 2004, 3,
3094.
The authors wish to express sincere gratitude for partial support
of this research through a Grant-in Aid for Scientific Research (No.
19020018) on Priority Areas “Advanced Molecular Transformation
of Carbon Resources” from the Ministry of Education, Sports, Cul-
ture, Science and Technology, Japan.
References and notes
1. For some of recent reviews for organic synthesis through organic electron
transfer chemistry, see the following reviews. (a) Nishiguchi, I. J. Syn. Org. Chem.
Jpn. 2010, 68, 824; (b) Lund, H.; Hammerich, O. Organic Electrochemistry, 4th ed.;
Marcel Dekker: New York, Basel, 2001; (c) Fuchigami, T.; Konno, A. J. Syn. Org.
Chem. Jpn. 1997, 55, 310; (d) Hisaeda, Y. J. Syn. Org. Chem. Jpn. 1996, 54, 859; (e)
Yoshida, J. J. Syn. Org. Chem. Jpn. 1995, 53, 53.