The stereochemistry of electrolysis and samarium diiodide-induced cyclization between carbonyl and enone system in inter- and intramolecular coupling

Article abstract of DOI:10.3987/com-06-s(k)45

Both the inter- and intramolecular cyclization of the carbonyl compounds with α,β-unsaturated carbonyl system using samarium diiodide and electrolysis were carried out. The stereochemistry of the products was compared each other.

Full text of DOI:10.3987/com-06-s(k)45

HETEROCYCLES, Vol. 72, 2007
517
HETEROCYCLES, Vol. 72, 2007, pp. 517 - 528. © The Japan Institute of Heterocyclic Chemistry
Received, 13th December, 2006, Accepted, 25th January, 2007, Published online, 26th January, 2007. COM-06-S(K)45
THE STEREOCHEMISTRY OF ELECTROLYSIS AND SAMARIUM
DIIODIDE-INDUCED CYCLIZATION BETWEEN CARBONYL AND
ENONE SYSTEM IN INTER- AND INTRAMOLECULAR COUPLING
Masakazu Sono,* Tsutomu Shoji, Tatsuya Tamaki, Satoko Kishi, and Motoo
Tori
Faculty of Pharmaceutical Sciences, Tokushima Bunri University,
Yamashiro-cho, Tokushima, 770-8514, Japan. e-mail:sono@ph.bunri-u.ac.jp
Abstract – Both the inter- and intramolecular cyclization of the carbonyl
compounds with ꢀ,ꢁ-unsaturated carbonyl system using samarium diiodide and
electrolysis were carried out. The stereochemistry of the products was
compared each other.
INTRODUCTION
Electrolysis can be carried out in water as a solvent without expensive reagents at ambient temperature
costing only electricity.1 Thus, it is cost-effective and environmentally benign.1 The reaction
mechanism is thought to be through a radical or an anion.1 Samarium (II) also induces radical coupling
of various carbonyl groups, which is well documented.2 Cyclohexanone was reacted with methyl
acrylate to form a lactone by the action of SmI2, which was reported by Inanaga et al.3 We are interested
in carrying out this type of reaction using electrolysis. At the same time we have already reported
several cyclization reactions using SmI2 to form hydrindanones4-6 and perhydronaphthalenones.7 We are
interested in carrying out these reactions using electrolysis in order to compare them with the reaction by
SmI2. Now we report our results in detail.
RESULTS AND DISCUSSION
Although cyclohexanone was reported to afford a lactone with methyl acrylate under reductive
cyclization conditions,3 stereoselectivity of the reaction was not studied. We would like to know the
stereochemistry (relative to the existing substituents) of the coupling reactions. Therefore, we applied
this reaction to 2-methylcyclohexanone (1) to study the stereochemistry of the lactone ring and found the
isomer ratio was 3:2, whose stereochemistry was determined by derivatization of the products into the

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HETEROCYCLES, Vol. 72, 2007
acetate.8 The selectivity of addition of an alkyl group to the carbonyl group of 2-methylcyclohexanone
(1) is well known,9 that is, the alkyl groups always approach from the backside of a 2-methyl group to
yield 1,2-trans-dialkylated cyclohexanol derivatives. Yamamoto et al. used an aluminium complex to
prevent the predominant attack by coordination to the carbonyl group.10 However, this methodology
works only in the case of methyl and other small alkyl groups. Large alkyl groups do not work very
well. In the SmI2-induced coupling, syn-product 3 was obtained in ca. 40% yield (Scheme 1), which is
the highest yield of the syn-product, to the best of our knowledge. We carried out electrolysis of
2-methylcyclohexanone (1) with methyl acrylate in tBuOH-H2O (2:3) with Et4NOTs as an electrolyte.
However, the yield was not so high as expected and the ratio of syn-product 3 was similar to that of
addition of an alkyl group to 2-methylcyclohexanone (1).9 3-Methylcyclohexanone (4) was next reacted
with methyl acrylate. The yield of electrolysis was almost the same as that of 1, but the ratio was
completely opposite to that of 1. SmI2-induced cyclization afforded 5 and 6 in poor yield and the ratio
was opposite to that of electrolysis. The stereochemistry of the products was determined by analysis of
the NOESY spectrum.11
COOMe
COOMe
+
O
+
O
O
O
O
O
O
O
2
O
3
O
5
6
a) - Zn--Pt +
-100 mA CCE
b) SmI2, THF
tBuOH (2 eq)
a) - Zn--Pt +
1
:
:
94
60
6
4
23%
98%
:
:
-100 mA CCE
b) SmI2, THF
tBuOH (2 eq)
30
80
70
20
32%
40
30%
Scheme 1.
Scheme 2.
COOMe
O
+
O
O
O
O
8
9
a) - Zn--Pt +
-100 mA CCE
7
55
9
:
45
91
28%
76%
:
b) SmI2, THF
tBuOH (2 eq)
Scheme 3.
Next, we carried out the reaction of 4-t-butylcyclohexanone (7) and methyl acrylate with the aid of SmI2
and electrolysis. It is very interesting to note that SmI2-induced reaction gave two lactones, 8 and 9, in
the ratio of 9:91 in 76% yield. However, electrolysis yielded the same products in the ratio of 55:45 in
28% yield. The stereochemistry was determined by analysis of the 2D NMR spectra and also by
derivatization.12

HETEROCYCLES, Vol. 72, 2007
519
Samarium diiodide transfers one-electron to the carbonyl group to yield a radical in the axial manner, in
which samarium still coordinates to the carbonyl oxygen atom. Thus, acrylate attacks the radical from
the axial side to give compounds 5 and 9 as the major product. In the case of 2-methylcyclohexanone
(1), the samarium-coordinated group is close to the 2-methyl group, and thus, the selectivity is not as high
as 4 and 7. However, electrolysis provides a radical or an anion of acrylate and it attacks the carbonyl
group from the equatorial side to yield an axial alcohol followed by lactonization.9,13,14
We have previously reported SmI2-induced intramolecular cyclization to yield hydrindanones4-6 and
perhydronaphthalenones.7 Aldehyde 10 cyclized under the SmI2 conditions with a proton source
(MeOH) into four kinds of hydrindanones 11, 12, 14, 15 in the ratio of 32:12:17:39 in moderate yield as
reported in the literature (Table 1).5 Here, we carried out electrolysis of compound 10 to yield 11, 14,
and 15 in the ratio of 17:64:19 in 31% yield. Unfortunately, the yield was much less than that of
SmI2-induced cyclization. The predominant compound 14 had cis-ring junction with the ethyl and
hydroxy groups in the opposite side. Thus, the results are very diverse and complicated, and different in
each case.15
Table 1. Cyclization of compound 10 to bycyclic ketols 11-15.
O
O
O
O
O
O
H
H
H
H
H
+
+
+
+
CHO
10
H
H
H
H
H
OH
OH
Additive
OH
OH
OH
11
12
13
15
14
Reagent
Solvent
Time(h) Ratio (11:12:13:14:15)
Yield(%)
31
electrolysis tBuOH-H2O
Et4NTsO
4
17:0:0:64:19
(4:6)
SmI2
THF
2
1
47:20:21:12:0
32:12:0:17:39
64
69
-
SmI2
THF
MOH (10 equiv.)
Table 2. Cyclization of compound 16 to bicyclic ketols 17-19.
O
O
O
H
O
H
H
+
+
CHO
H
OH
H
H
16
OH
17
OH
19
18
Reagent
Solvent
Additive
Time(h)
3
Ratio (17:18:19) Yield(%)
electrolysis tBuOH-H2O
Et4NTsO
22:14:63
60
(4:6)
SmI2
THF
1
4
28:61:11
55:45:0
100
98
-
NiI2
SmI2
THF
Next, we studied the reaction of compounds having a 6-membered ring. Aldehyde 16 was reported to
give 17, 18, and 19 in quantitative yield in the ratio of 28:61:11 by the action of SmI2 without additive.7

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HETEROCYCLES, Vol. 72, 2007
Electrolysis afforded three products as well, in the ratio of 22:14:63 in favor of compound 19, which was
a remarkable contrast to the results of SmI2. Compound 19 has trans stereochemistry concerning the
hydroxy group and the juncture proton, while compounds 17 and 18 have cis-arrangement.
The next two examples are the case of compounds having a methyl group at the juncture position.
Compound 2016 cyclized into cis-arranged hydrindanolone 2117 in 80% yield by SmI2, and in 39% yield
by electrolysis (Scheme 4). Similar results were obtained in the case of compound 22 (Scheme 5).18,19
Therefore, the 6-Endo Trig mode or 5-Endo Trig mode of cyclization reaction by electrolysis and SmI2
both gave the same product in these examples.
O
O
O
H
O
H
OHC
OHC
HO
OH
20
21
23
a) - Zn--Pt +
-100 mA CCE
b) SmI2, THF
22
a) - Zn--Pt +
39%
80%
65%
57%
-100 mA CCE
b) SmI2, THF
Scheme 4.
Scheme 5.
The last two examples are the case of reaction between ketone and the ꢀ,ꢁ-unsaturated ketone system
having a methyl group at the juncture position (Table 3).20 Electrolysis did not give a good yield, but the
predominant product was compound 26 in the ratio of 1:4. SmI2-induced reaction also afforded
compound 26 as a major product without an additive. SmI2 reduces the carbonyl group to give -OSm
group and it coordinates to the oxygen atom of the enone carbonyl group to yield compound 26.
However, SmI2 with a proton source (MeOH) gave an almost 1:1 mixture of diastereomeric products 25
and 26.21 In this case, the -OSm group does not coordinate to the carbonyl oxygen atom to afford
compounds 25 and 26, in almost 1:1 ratio.4
Table 3. Cyclization of compound 24 to bicyclic ketols 25 and 26.
O
O
O
H
H
+
HO
HO
24
Solvent
26
25
O
Reagent
Additive
Et4NTsO
Time(h) Ratio (25:26) Yield(%)
electrolysis tBuOH-H2O
3
20:80
34
(4:6)
-
SmI2
SmI2
1
11:89
55:45
50
THF
THF
MOH (20 equiv.) 1.5
100
In the case of perhydronaphthalenones, the yield of the electrolysis reaction was excellent and the
products were only 28 and 29, in the ratio of ca. 1:1 (Table 4). SmI2-induced reaction of compound 27
gave four kinds of products as reported.7 Since compounds 28 and 29 are the isomers concerning the

HETEROCYCLES, Vol. 72, 2007
521
juncture position, it is easier to isomerize 28 into the trans-fused ketone 29. In this respect, the whole
process of electrolysis is highly selective and gives high yield, which can be utilized in the synthesis.
Table 4. Cyclization of compound 27 to bicyclic ketols 28-31.
O
O
O
O
O
H
H
H
H
+
+
+
HO
HO
HO
HO
27
Reagent
O
29
30
28
31
Solvent
Additive
Et4NTsO
Time(h) Ratio (28:29:30:31) Yield(%)
electrolysis tBuOH-H2O
4.5
3.5
43:57:0:0
100
(4:6)
100
91
-
SmI2
SmI2
THF
69:19:3:9
THF
MOH (20 equiv.) 1.5
30:51:11:8
Here, we reported three examples of intermolecular coupling and six examples of intramolecular
cyclization by both electrolysis and SmI2-induced reaction. Since the enone system is more susceptible
to reduction, the resulting anion or radical attacks the other carbonyl group. Samarium can coordinate to
both carbonyl groups and it adopts an equatorial or energetically more stable position leading to the
stereoselective products. Electrolysis can provide high stereoselectivity and high yield of products, if
the conditions fit the reaction system. It should be noted here again, water can be used as a solvent for
electrolysis without expensive reagents at ambient temperature costing only electricity and it is
cost-effective and environmentally benign.1
EXPERIMENTAL
GENERAL
1
13
IR spectra were measured on a JASCO FT/IR-5300 spectrophotometer. The H and C NMR spectra
were taken on a Varian Unity 600 (600 MHz and 150 MHz, respectively) and a Varian Unity 200 (200
MHz and 50 MHz, respectively) spectrometer. MS spectra including high-resolution mass spectra were
recorded on a JEOL JMS-700 MStation. Chemcopak Nucleosil 50-5 (4.8ꢀ250 mm) was used for HPLC
(JASCO pump system). Silica gel 60 (70-230 mesh, Fuji Sylisia) was used for column chromatography
and silica gel 60 F254 plates (Merck) were used for TLC.
General procedure for electrolysis
Zn and Pt were used for cathode and anode, respectively, with Et4NOTs in tBuOH-H2O (2:3) (20 mL), at
100 mA and 13.94 V at rt. Work-up: Benzene was added and most of the water was removed under

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HETEROCYCLES, Vol. 72, 2007
reduced pressure. The residue was extracted with AcOEt and the organic layer was washed with Sat.
NaCl solution. The organic layer was dried (MgSO4), and the filtrate was evaporated to give a residue,
which was purified by silica-gel column chromatography or HPLC.
General procedure for SmI2 reduction
A solution of substrate in dry THF was introduced into a solution of SmI2 at a certain temperature.
Saturated solution of sodium potassium tartrate was added and the solvent was evaporated. The mixture
was extracted with ether and worked up as usual. The residue was purified by silica-gel column
chromatography.
1
2: colorless oil; IR (FT) 1770 cm-1; H NMR (200 MHz, CDCl3): ꢀ 0.94 (3H, d, J = 6.2 Hz), 1.30-1.93
(10H, m), 2.20 (1H, m), 2.58 (2H, m); 13C NMR (50 MHz, CDCl3) ꢀ 14.9 (CH3), 22.3 (CH2), 24.8 (CH2),
29.0 (CH2), 30.7 (CH2) 31.5 (CH2), 38.3 (CH2), 39.9 (CH), 88.0 (C), 177.4 (CO); MS m/z 168 (M+), 150,
139, 125, 111 (base), 98, 83; HRMS Found m/z 168.1150. Calcd for C10H16O2 168.1150.
1
3: colorless oil; IR (FT) 1765 cm-1; H NMR (200 MHz, CDCl3): ꢀ 0.91 (3H, d, J = 6.6 Hz), 1.30-1.93
(10H, m), 2.12 (1H, m), 2.56 (2H, m); 13C NMR (50 MHz, CDCl3) ꢀ 14.8 (CH3), 23.1 (CH2), 24.2 (CH2),
26.0 (CH2), 29.3 (CH2), 31.0 (CH2), 37.1 (CH2), 39.5 (CH), 89.6 (C), 177.0 (CO); MS (EI) m/z 168 (M+),
150, 139, 125, 111 (base), 98, 83; HRMS Found m/z 168.1159. Calcd for C10H16O2 168.1150.
5: colorless oil; IR (FT): 1770 cm-1; 1H NMR (200 MHz, CDCl3): ꢀ 0.89 (1H, dddd, J = 13.2, 11.5, 11.5,
3.6 Hz), 0.96 (3H, d, J = 6.6 Hz), 1.34 (1H, qt, J = 13.2, 3.6 Hz), 1.39 (1H, t, J = 12.4 Hz), 1.50 (1H, m),
1.62 (1H, td, J = 13.2, 3.6 Hz), 1.66 (1H, m), 1.77 (1H, m), 1.75 (1H, m), 1.79 (1H, dquint, J = 13.2, 3.6
13
Hz), 2.06 (2H, td, J = 8.8, 2.2 Hz), 2.59 (2H, t, J = 8.8 Hz); C NMR (150 MHz, CDCl3) ꢀ 22.1 (CH3),
22.6 (CH2), 28.7 (CH2), 29.9 (CH) 30.7 (CH2), 33.5 (CH2), 36.1 (CH2), 45.1 (C), 87.3 (C), 176.7 (CO);
MS (EI) m/z 168 (M+), 153, 140, 125 (base), 111, 95; HRMS Found m/z 168.1158. Calcd for C10H16O2
167.1150.
6: colorless oil; IR (FT): 1775 cm-1; 1H NMR (600 MHz, CDCl3): ꢀ 0.86 (1H, m), 0.89 (3H, d, J = 6.6 Hz)
1.09 (1H, t, J = 12.4 Hz) 1.36 (1H, ddd, J = 13.2, 13.2, 4.9 Hz), 1.64 (1H, m), 1.67 (1H, m), 1.74 (1H, m),
1.80 (1H, m), 1.84 (1H, m), 1.97 (2H, m), 2.59 (2H, t, J = 8.40 Hz); 13C NMR (150 MHz, CDCl3) ꢀ 22.0
(CH2), 22.3 (CH3), 28.4 (CH), 28.6 (CH2), 33.8 (CH2), 34.5 (CH2) 36.6 (CH2), 45.5 (CH2), 86.4 (C), 176.9
(CO); MS (EI) m/z 168 (M+), 140, 125 (base), 111, 95; HRMS Found m/z 168.1149. Calcd for C10H16O2
168.1150
8: colorless amorphous; IR (FT): 1760 cm-1; 1H NMR (600 MHz, CDCl3) ꢀ 0.86 (9H, s), 1.02 (1H, tt, J =
11.8, 3.0 Hz), 1.38-1.49 (4H, m), 1.65-1.68 (2H, m), 1.93-1.96 (2H, m), 1.97 (2H, t, J = 8.4 Hz), 2.59 (2H,
t, J = 8.40 Hz); 13C NMR (150 MHz, CDCl3) ꢀ 23.1 (CH2), 27.5 (CH3), 28.7 (CH2), 32.4 (C), 34.1 (CH2),
37.6 (CH2), 47.2 (CH), 85.6 (C), 177.0 (C); MS (EI) m/z 210 (M+), 195, 154 (base), 136, 94, 81, 57;
HRMS Found m/z 210.1600. Calcd for C13H22O3 210.1620.

HETEROCYCLES, Vol. 72, 2007
523
1
9: colorless amorphous; IR (FT): 1770 cm-1; H NMR (600 MHz, CDCl3) ꢀ 0.87 (9H, s), 1.05-1.13 (3H,
13
m), 1.74 (2H, m), 1.82 (4H, m), 2.06 (2H, t, J = 8.2 Hz), 2.58 (2H, t, J = 8.2 Hz); C NMR (150 MHz,
CDCl3) ꢀ 24.1 (CH2), 27.5 (CH3), 28.6 (CH2), 30.2 (CH2), 32.2 (C), 36.8 (CH2), 46.7 (CH), 87.2 (C),
176.7 (C); MS (EI) m/z 210 (M+), 195, 167, 155, 136, 111, 94, 81, 57 (base); HRMS Found m/z 210.1597.
Calcd for C13H22O3 210.1620.
Preparation of 4-(2-methyl-5-oxocyclopent-1-enyl)butanal (20)
To a stirred solution of tBuOK in THF (72.6 mL) was added 3-methylcyclopent-2-en-1-one (2.90 g, 30.2
mmol) and the mixture was stirred for 30 min at rt. 1-Bromo-3-(t-butyldimethylsilyloxy)propane (12.0
g, 45.2 mmol) was added and the mixtrure was heated at 100ꢀ under reflux for 1 h. After cooling,
NH4Cl solution was added and the solvent was evaporated. The residue was extracted with ether and the
organic phase was washed with brine. The organic layer was dried (MgSO4), and evaporated under
reduced pressure to afford a residue. The residue was purified by silica-gel column chromatography to
give 2-(4-t-butyldimethylsilyloxybutyl)-3-methylcyclopent-2-en-1-one (20b) (1.20 g, 9.2%): oil; IR (FT):
1700, 1640 cm-1; 1H NMR (200 MHz, CDCl3) ꢀ -0.01 (6H, s), 0.84 (9H, s), 1.20-1.52 (4H, m), 2.00 (3H,
s), 2.14 (2H, t, J = 7.0 Hz), 2.25-2.32 (2H, m), 2.42-2.47 (2H, m), 3.55 (2H, t, J = 6.2 Hz); 13C NMR (200
MHz, CDCl3) ꢀ –5.4 (CH3), 17.1 (CH3), 18.2 (C), 22.6 (CH2), 24.5 (CH2), 25.8 (CH3), 31.4 (CH2), 32.6
(CH2), 34.2 (CH2), 62.8 (CH2), 140.5 (C), 170.2 (C), 209.6 (CO); MS (EI) m/z 282 (M+), 267, 225 (base);
HRMS Found m/z 282.2017. Calcd for C16H30O2Si 282.2015.
Compound 20b (1.20 g) was dissolved in THF (8 mL) and TBAF (8.5 mL, 2 equiv.) was added and the
mixture was stirred for 1 h at rt. Work-up as usual and purification by silica-gel column
chromatography afforded 4-(2-methyl-5-oxocyclopent-1-enyl)butanol (20c) (479 mg, 73%): oil; IR (FT):
1
3450, 1680, 1640 cm-1 ; H NMR (200 MHz, CDCl3) ꢀ 1.34-1.66 (4H, m), 2.07 (3H, s), 2.20 (2H, t, J =
13
7.6 Hz), 2.32-2.41 (2H, m), 2.42-2.56 (3H, m), 3.64 (2H, t, J = 6.2 Hz); C NMR (200 MHz, CDCl3) ꢀ
17.1 (CH3), 22.4 (CH2), 24.4 (CH3), 31.5 (CH2), 32.2 (CH2), 34.2 (CH2), 62.3 (CH2), 140.4 (C), 171.0 (C),
210.2 (CO); MS (EI) m/z 168 (M+), 150, 135 (base), 123, 109, 93, 79, 67, 55; HRMS Found m/z 168.1158.
Calcd for C10H16O2 168.1152.
The alcohol 20c (617 mg, 3.68 mmol) was oxidized with PDC (2.77 g, 7.36 mmol) and molecular sieves
(3A, 615 mg) in CH2Cl2 (64 mL) at rt for 7 h. Work-up and purification afforded aldehyde 20 (409 mg,
71%): oil; IR (FT): 1720, 1690, 1640 cm-1; 1H NMR (200 MHz, CDCl3) ꢀ 1.65-1.82 (2H, m), 2.07 (3H, s),
2.23 (2H, t, J = 7.2 Hz), 2.26-2.58 (6H, m), 9.75 (1H, t, J = 1.4 Hz); 13C NMR (150 MHz, CDCl3) ꢀ 17.1
(CH3), 20.6 (CH2), 22.1 (CH2), 31.5 (CH2), 34.2 (CH2), 43.3 (CH2), 139.5 (C), 171.4 (C), 202.3 (CO),
209.6 (CO); MS (EI) m/z 166 (M+), 137, 123 (base), 110; HRMS Found m/z 166.0989. Calcd for
C10H14O2 166.0994.

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HETEROCYCLES, Vol. 72, 2007
1
21: colorless oil; IR (FT): 3450, 1740 cm-1; H NMR (600 MHz, CDCl3) ꢀ 1.17 (1H, m), 1.19 (3H, s),
1.39 (1H, m), 1.44 (1H, 1H, m), 1.51 (1H, m), 1.58 (1H, m), 1.64 (1H, m), 1.99 (1H, br d, J = 14 Hz),
2.04 (1H, m), 2.24-2.37 (3H, m), 3.28 (1H, dd, J = 12, 4.2 Hz); 13C NMR (150 MHz, CDCl3) ꢀ 18.7 (CH3),
19.7 (CH2), 21.8 (CH2), 30.1 (CH2), 34.6 (CH2), 43.7 (C), 57.3 (CH), 71.0 (CH), 219.3 (CO); MS (EI) m/z
168 (M+), 150, 135, 111, 97 (base); HRMS Found m/z 168.1152. Calcd for C10H16O2 168.1150.
Preparation of 3-(2-methyl-6-oxocyclohex-1-enyl)propanal (22)
Compound 22 was prepared following the procedure for 20 starting from 3-methylcyclohex-2-en-1-one.
1
22b: oil; IR (FT): 1660, 1620 cm-1; H NMR (200 MHz, CDCl3) ꢀ 0.02 (6H, s), 0.87 (9H, s), 1.43-1.57
(2H, m), 1.93 (3H, s), 1.82-1.95 (2H, m), 2.27-2.37 (6H, m), 3.57 (2H, t, J = 6.2 Hz); 13C NMR (50 MHz,
CDCl3) ꢀ -5.3 (CH3ꢀ2), 18.3 (C), 21.1 (CH3), 21.6 (CH2), 22.3 (CH2), 25.9 (CH3ꢀ3), 32.2 (CH2), 32.8
(CH2), 37.9 (CH2), 62.9 (CH2), 135.4 (C), 155.3 (C), 198.7 (C); MS (CI) m/z 283 [M+H]+ , 282, 281, 267,
225 (base), 151, 133, 107, 91; CI-HRMS Found m/z 283.2063. Calcf for C16H31SiO2 283.2093. 22c:
oil; IR (FT): 3400,1660, 1620 cm-1; 1H NMR (200 MHz, CDCl3) ꢀ 1.59 (2H, quint, J = 6.0 Hz), 1.98 (3H,
13
s), 1.88-2.01 (2H, m), 2.34-2.45 (6H, m), 3.75 (2H, t, J = 6.2 Hz); C NMR (200 MHz, CDCl3) ꢀ 20.3
(CH2), 21.2 (CH3), 22.3 (CH2), 31.6 (CH2), 32.9 (CH2), 37.6 (CH2), 60.9 (CH2), 134.8 (C), 157.6 (C),
200.6 (CO); MS (CI) m/z 169 [M+H]+, 151 (base), 135, 123, 79; CI-HRMS Found m/z 169.1214. Calcd
1
for C10H17O2 169.1228. 22: oil; IR (FT) 2710, 1720, 1660, 1630 cm-1; H NMR (200 MHz, CDCl3) ꢀ
1.98 (3H, s), 1.87-2.00 (2H, m), 2.31-2.66 (8H, m), 9.55 (1H, t, J = 1.6 Hz); 13C NMR (50 MHz, CDCl3 )
ꢀ 18.3 (CH2), 21.2 (CH3), 32.8 (CH2), 37.6 (CH2), 43.0 (CH2), 133.7 (C), 156.8 (C), 198.6 (C), 202.3
(CH); MS (EI) m/z 166 (M+), 138 (base), 110, 95, 79, 67; HRMS Found m/z 166.0979. Calcd for
C10H14O2 166.0994.
23: oil; IR (FT): 3420, 1700 cm-1; 1H NMR (600 MHz, CDCl3) ꢀ 1.09 (3H, s), 1.52 (1H, ddd, J = 14.0, 7.4,
4.1 Hz), 1.61 (1H, m), 1.67 (1H, ddd, J = 14.0, 8.5, 4.1 Hz), 1.87 (1H, m), 1.90 (1H, m), 1.95 (1H, m),
2.07 (1H, m), 2.19 (1H, m), 2.26 (1H, m), 2.43 (1H, m), 2.46 (1H, dd, J = 8.1, 6.0 Hz), 3.81 (1H, t, J =
5.4 Hz); 13C NMR (150 MHz, CDCl3) ꢀ 20.2 (CH3), 21.9 (CH2), 22.6 (CH2), 31.2 (CH2), 31.6 (CH2), 38.9
(CH2), 50.2 (C), 57.1 (CH), 77.8 (CH), 213.2 (CO); MS (EI) m/z 168 (M+), 153, 138, 124, 111 (base), 97;
HRMS Found m/z 168.1158. Calcd for C10H16O2 168.1150.
Preparation 5-(2-methyl-5-oxocyclopent-2-enyl)-2-pentanone (24)
Compound 24 was prepared from 2-methyl-2-(3-bromopropyl)-1,3-dioxolane in two steps.
3-Methylcyclopent-2-en-1-one was alkylated in the presence of tBuOK in THF to afford 24a: oil; IR (FT)
1
1700, 1650 cm-1; MS m/z 224 (M+), 209, 115, 87 (base); H NMR (200 MHz, CDCl3) ꢀ 1.29 (3H, s),
1.42-1.48 (4H, m), 2.05 (3H, br s), 2.18 (2H, m), 2.37 (2H, m), 2.63 (2H, m), 3.92 (4H, m); 13C NMR (50
MHz, CDCl3) ꢀ 17.2 (CH3), 22.7 (CH2), 22.8 (CH2), 23.7 (CH3), 31.4 (CH2), 34.2 (CH2), 38.8 (CH2), 64.4

HETEROCYCLES, Vol. 72, 2007
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(CH2), 109.6 (C), 140.2 (CH), 170.4 (C), 209.5 (CO); HRMS Found m/z 224.1401. Cacld for C13H20O3
224.1412. This was treated with TsOH to afford 24: oil; IR (FT): 1720, 1695, 1650 cm-1; 1H NMR (200
MHz, CDCl3) ꢀ 1.66 (2H, quint, J = 5.2 Hz), 2.07 (3H, s), 2.13 (3H, s), 2.16 (1H, m), 2.34-2.54 (5H, m);
13C NMR (50 MHz, CDCl3) ꢀ 17.2 (CH3), 22.1 (CH2), 22.4 (CH2), 29.8 (CH3), 31.5 (CH2), 34.2 (CH2),
43.1 (CH2), 139.8 (CO), 171.1 (CO), 208.7 (CO), 209.5 (CO); MS (EI) m/z 180 (M+), 137, 123 (base),
110, 96; HRMS Found m/z 180.1162. Calcd for C11H16O2 180.1150.
1
25: oil; H NMR (600 MHz, CDCl3) ꢀ 1.16 (3H, s), 1.17 (3H, s), 1.36 (1H, m), 1.39 (1H, m), 1.46 (1H,
m), 1.53 (1H, ddd, J = 13.2, 11.0, 8.0 Hz), 1.62 (1H, m), 1.64 (1H, m), 1.90 (1H, m), 2.03 (1H, m), 2.20
(1H, dddd, J = 18.1, 11.0, 3.0, 1.6 Hz), 2.31 (1H, ddd, J = 13.2, 10.2, 3.0 Hz), 2.41 (1H, ddd, J = 18.1,
10.2, 8.0 Hz); 13C NMR (150 MHz, CDCl3) ꢀ 18.0 (CH2), 19.4 (CH2), 25.0 (CH3), 26.2 (CH3), 29.5 (CH2),
36.2 (CH2), 36.6 (CH2), 45.0 (C), 55.4 (CH), 74.3 (C), 218.4 (CO); MS m/z 182 (M+), 167, 164, 154, 149,
124, 109, 97 (base), 84; HRMS Found m/z 182.1305. Calcd for C11H18O2 182.1307.
1
26: oil; H NMR (600 MHz, CDCl3) ꢀ 1.03 (3H, s), 1.18 (3H, s), 1.21 (1H, m), 1.55-1.71 (6H, m), 2.02
(1H, dt, J = 12.6, 9.6 Hz), 2.09 (1H, dd, J = 12.2, 6.3 Hz), 2.29 (1H, dt, J = 19.5, 10.4 Hz), 2.38 (1H, ddd,
13
J = 19.5, 9.9, 2.2 Hz); C NMR (150 MHz, CDCl3) ꢀ 19.6 (CH2), 20.7 (CH3), 24.3 (CH2), 24.9 (CH3),
28.8 (CH2), 33.9 (CH2), 35.9 (CH2), 45.2 (C), 54.7 (CH), 71.9 (C), 220.3 (CO); MS m/z 182 (M+), 167,
164, 154, 149, 124, 111, 106, 97 (base), 84; HRMS Found m/z 182.1334. Calcd for C11H18O2 182.1307.
ACKNOWLEDGEMENTS
We thank Miss Yasuko Okamoto, of this University, for measurement of MS spectra.
REFERENCES AND NOTES
* This paper is dedicated to Professor Yoshito Kishi on the occasion of his 70th birthday.
1. a) T. Shono, ‘Electroorganic Synthesis,’ Academic Press, London, 1991. b) R. D. Little, Chem. Rev.,
1996, 96, 93.
2. a) G. A. Molander, Chem. Rev., 1992, 92, 29. b) G. A. Molander and C. R. Harris, Chem. Rev., 1996,
96, 307.
3.
4.
5.
6.
K. Otsubo, J. Inanaga, and M. Yamaguchi, Tetrahedron Lett., 1986, 27, 5763.
M. Sono, Y. Nakashiba, K. Nakashima, and M. Tori, J. Org. Chem., 2000, 65, 3099.
M. Sono, A. Hashimoto, T. Nakashima, and M. Tori, Tetrahderon Lett., 2000, 41, 5115.
M. Sono, Y. Nakashiba, K. Nakashima, S. Takaoka, and M. Tori, Heterocycles, 2001, 54, 101.

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HETEROCYCLES, Vol. 72, 2007
7.
M. Sono, S. Onishi, and M. Tori, Tetrahedron, 2003, 59, 3385.
8. The stereochemistry was established as follows. Grignard reaction of 4-bromo-1-butene to
2-methylcyclohexanone gave 32, whose stereochemistry is well known. Compound 32 was further
derived into acetate 33 by a three step-transformation [(i) O3, CH2Cl2, -78ºC, (ii) NaBH4, MeOH, 0ºC,
(iii) Ac2O, Py, rt]. Then, a lactone mixture of 2 and 3 was reduced (LiAlH4, Et2O) to diol 34 as a
mixture followed by acetylation (Ac2O, Py) and separation to yield 33 as a major compound, with
the same stereochemistry as that from 32. 33: amorphous: IR(FT): 3520, 1730 cm-1; 1H NMR (200
MHz, CDCl3) ꢀ 0.87 (3H, d, J = 6.2 Hz), 1.24-1.74 (14H, m), 2.05 (3H, s), 4.07 (2H, td, J = 6.6, 1.8
Hz); 13C NMR (50 MHz, CDCl3) ꢀ 14.8 (CH3), 20.9 (CH3), 21.7 (CH2), 22.9 (CH2), 25.6 (CH2), 30.5
(CH2), 35.8 (CH2), 36.8 (CH2), 38.2 (CH), 65.0 (CH2), 72.6 (C), 171.2 (CO); MS (EI) m/z 214 (M+),
154, 113, 97 (base); HRMS Found m/z 214.1556 Calcd for C12H22O3 214.1569. 35: amorphous:
1
IR (FT): 3480, 1740, 1720 cm-1; H NMR (200 MHz, CDCl3) ꢀ 0.97 (3H, d, J = 6.6 Hz), 1.14-1.84
13
(14H, m), 2.06 (3H, s), 4.09 (2H, t, J = 6.6 Hz); C NMR (50 MHz, CDCl3) ꢀ 15.0 (CH3), 21.0
(CH3), 21.8 (CH2), 23.1 (CH2), 23.9 (CH2), 30.1 (CH2), 30.9 (CH2), 35.9 (CH2), 41.4 (CH), 65.2
(CH2), 73.8 (C), 171.3 (CO); MS (EI) m/z 214 (M+), 154, 113, 97 (base); HRMS Found m/z
214.1549 Calcd for C12H22O3 214.1569.
1) O3
MgBr
2) NaBH4
3) Ac2O
OH
OH
quant.
O
1
32
OAc
84 %
33
AcO2
LAH
+
O
pyridine
73 %
Et2O
92 %
OH
OH
OH
O
2 and 3
35
OH
33
OAc
OAc
34
9. E. C. Ashby and J. T. Laemmle, Chem. Rev., 1975, 75, 521.
10. K. Maruoka, T, Itoh, M. Sakurai, K. Nonoshita, and H. Yamamoto, J. Am. Chem. Soc., 1998, 110,
3588.
11. The stereochemistry of compounds 5 and 6 was determined by NOESY spectra. The selected
correlations were shown here.
H
H
H
H
H
H
H
O
H
H
O
H
H
H
NOE
O
H
6
5
O

HETEROCYCLES, Vol. 72, 2007
527
12. The structures of 8 and 9 were determined as follows. Both lactones 8 and 9 were reduced with
LiAlH4 to afford 36 and 37, respectively, and their structures were analyzed by NOESY spectra.
36: colorless oil: IR (FT) 3300 cm-1; 1H NMR (600 MHz, CDCl3) ꢀ 0.87 (9H, s), 0.94 (1H, m), 1.28
(2H, m), 1.29 (2H, m), 1.52 (2H, t, J = 6.0 Hz), 1.61 (2H, m), 1.67 (1H, m), 1.69 (1H, m), 1.74 (2H,
m), 3.66 (2H, t, J = 6.0 Hz); 13C NMR (150 MHz, CDCl3) ꢀ 22.4 (CH2), 26.4 (CH2), 27.5 (CH3), 32.4
(C), 37.5 (CH2), 40.9 (CH2), 47.9 (CH), 63.5 (CH2), 70.4 (C); MS (CI) m/z 215 [M+H]+, 214, 19
(base), 179, 155, 115, 97; HRMS Found m/z 214.1914. Calcd for C13H26O2 214.1932. 37:
colorless oil: IR (FT) 3300 cm-1; 1H NMR (600 MHz, CDCl3) ꢀ 0.82 (9H, s), 1.03 (2H, m), 1.05 (1H,
m), 1.37 (2H, m) 1.60-1.69 (6H, m), 1.83 (2H, br d, J = 11.8 Hz), 3.65 (2H, t, J = 5.8 Hz), 13C NMR
(150 MHz, CDCl3) ꢀ 24.4 (CH2), 26.0 (CH2), 27.6 (CH3), 32.2 (C), 33.0 (CH2), 38.7 (CH2), 47.5
(CH), 63.0 (CH2), 71.9(C); MS (CI) m/z 214 (M+), 197 (base), 179, 155, 115, 97; CI-HRMS Found
m/z 214.1951. Calcd for C13H26O2 214.1933.
LAH
Et2O
LAH
Et2O
92 %
O
O
OH
36
OH
37
O
8
O
9
OH
OH
HO
H
HO
H
H
H
H
HO
H
H
H
H
H
H
H
H
HO
H
H
H
H
NOE
H
H
H
37
36
13. D. P. Curran, N. A. Porter, and B. Giese, ‘Stereochemistry of Radical Reactions,’ VCH, Weinheim,
1996.
14. W. Damm, B. Giese, J. Hartung, T. Hasskerl, K. N. Houk, O. Hüter, and H. Zipse, J. Am. Chem. Soc.,
1992, 114, 4067.
15. The reason why compounds 12 and 13 were not produced in electrolysis was not clear now. The
trend of stereoselectivity in SmI2-induced cyclization was discussed in ref. 5.
16. Compound 20 was prepared from 3-methylcyclopent-2-en-1-one in three steps (see Experimental).
O
O
O
O
Br
TBAF
PDC
TBDMSO
tBuOK
THF
OHC
20a
20b
20c
20
OTBDMS
OH

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HETEROCYCLES, Vol. 72, 2007
17. The stereochemistry of 21 was established by NOESY spectrum.
O
H
H
H
NOE
H
OH
21
18. Compound 22 was prepared from 3-methylcyclohex-2-en-1-one in three steps (see Experimental).
O
O
O
O
Swern
oxd.
TBAF
TBDMSO
Br
tBuOK
THF
OHC
HO
TBDMSO
22
22b
22c
22a
19. The stereochemistry of 23 was established by NOESY spectrum.
O
H
NOE
H
HO
H
H
23
20. Compound 24 was prepared from 3-methylcyclopent-2-en-1-one in two steps (see Experimental).
O
O
Br
O
O
TsOH
O
tBuOK
THF
O
O
20a
O
24a
24
21. The stereochemistry of compounds 25 and 26 was established by NOESY spectrum.
O
O
H
H
H
H
H
H
HO
H
HO
NOE
25
26