Radical addition of 2-iodoalkanamide or 2-iodoalkanoic acid to alkenes with a water-soluble radical initiator in aqueous media: Facile synthesis of γ-lactones

Article abstract of DOI:10.1246/bcsj.74.1963

Radical reactions in water or aqueous ethanol using a water-soluble radical initiator are described. Heating a mixture of 2-iodoacetamide and 5-hexen-1-ol in water at 75 °C in the presence of a water-soluble radical initiator, 4,4′-azobis 4-cyanopentanoic acid), afforded 5-(4-hydroxybutyl)dihydrofuran-2(3H)-one in 95% yield. The use of 2-iodoacetic acid in place of 2-iodoacetamide also gave the same γ-lactone in 93% yield. The reaction of 2-iodoacetamide with 1-octene in aqueous ethanol was initiated by 2,2′-azobis(2-methylpropanamidine) dihydrochloride to provide γ-decanolactone. Employing water as a solvent is crucial to obtain lactone in satisfactory yield.

Full text of DOI:10.1246/bcsj.74.1963

em. Soc.
n.
© 2001 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 74, 1963–1970 (2001) 1963
e Chemical
ciety of Ja-
n
e Chemical
ciety of Ja-
n
Radical Addition of 2-Iodoalkanamide or 2-Iodoalkanoic Acid to
Alkenes with a Water-Soluble Radical Initiator in Aqueous Media:
Facile Synthesis of γ-Lactones
Radical Reaction in Aqueous Media
H. Yorimitsu et al.
Hideki Yorimitsu, Katsuyu Wakabayashi, Hiroshi Shinokubo, and Koichiro Oshima*
01
63
70
SJA8
09-2673
148
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Yoshida, Sakyo-ku, Kyoto 606-8501
(Received May 1, 2001)
Radical reactions in water or aqueous ethanol using a water-soluble radical initiator are described. Heating a mix-
ture of 2-iodoacetamide and 5-hexen-1-ol in water at 75 °C in the presence of a water-soluble radical initiator, 4,4ꢀ-azo-
bis(4-cyanopentanoic acid), afforded 5-(4-hydroxybutyl)dihydrofuran-2(3H)-one in 95% yield. The use of 2-iodoacetic
acid in place of 2-iodoacetamide also gave the same γ-lactone in 93% yield. The reaction of 2-iodoacetamide with 1-
octene in aqueous ethanol was initiated by 2,2ꢀ-azobis(2-methylpropanamidine) dihydrochloride to provide γ-decanolac-
tone. Employing water as a solvent is crucial to obtain lactone in satisfactory yield.
00
01
0
3.1
Recently, processes using a less toxic solvent or no solvent
have been required in the design of new synthetic methods
from the ecological point of view. Water might be the best
among many kinds of solvents. In the last decade, there has
been increasing recognition that organic reactions carried out
in aqueous media may offer advantages over those occurring in
organic solvents.1 For example, pericyclic reactions, such as
the Diels–Alder reaction,2 were carried out in water, and rate
enhancement was observed. Indium-mediated allylation of al-
dehyde is also a well-known reaction in water.3 However,
methods for carbon–carbon bond formation based on a radical
process in aqueous media have been limited.4 We have studied
radical reactions in aqueous media,5 and more recently have
focused on the reaction with water-soluble radical initiators.
Here we chose the following two commercially available initi-
good yield. Particularly, (3) provides a much less toxic and
safer synthesis of γ-lactone. Kharasch’s addition of α-bro-
moacetate to alkene employed highly explosive peracetic ac-
id.8 Radical addition of tributylstannyl iodoacetate to alkene
also provided γ-lactone.9,10 In this case, the stannyl ester
should be prepared in advance, and the toxic residual tin com-
pounds might be troublesome to handle.
Radical Addition of Benzenethiol to Carbon–Carbon Mul-
tiple Bonds and Radical Cyclization of N-Allyl-2-iodoal-
kanamide in Water
We first examined radical addition of benzenethiol to alk-
enes or alkynes (Scheme 1).11 Heating a mixture of N,N-dial-
ators (Fig. 1),6 4,4ꢀ-azobis(4-cyanopentanoic acid) (1a, t1/2
=
10 h, 69 °C in H2O) and 2,2ꢀ-azobis(2-methylpropanamidine)
dihydrochloride (1b, t1/2 = 10 h, 56 °C in H2O). We describe
in this paper7 that (1) the addition of PhSH to alkene or alkyne
proceeds smoothly to give the corresponding adducts, (2) atom
transfer cyclization of N,N-diallyl-2-iodoacetamide affords γ-
lactams in excellent yields, and (3) the addition of 2-iodoaceta-
mide to alkene followed by ionic cyclization gives γ-lactone in
Fig. 1. Water-soluble radical initiators.
Scheme 1.

1964 Bull. Chem. Soc. Jpn., 74, No. 10 (2001)
Radical Reaction in Aqueous Media
Table 1.
γ-Lactone Synthesis by Tandem Radical-Ionic
Reaction between 2-Iodoacetamide or 2-Iodoacetic Acid
and Alkenola)
Scheme 2.
2-Iodocarbonyl
Compound
R2 in alkenol
Product/%
lylacetamide (2, 1.0 mmol), benzenethiol (1.5 mmol), and 1b
(0.30 mmol) in water (10 mL) at 60 °C for 2 h provided N-
acetylpyrrolidine derivative 3 in 96% yield. In similar fashion,
treatment of diallylic ether 4 with benzenethiol in the presence
of 1a at 75 °C gave tetrahydrofuran derivative 5 in 75% yield.
The reaction of 3-butyn-1-ol (6) with PhSH at 60 °C in the
presence of 1b afforded 4-(phenylthio)-3-buten-1-ol (7) in
80% yield, in addition to 3,4-bis(phenylthio)-1-butanol (8,
8%).
12a: (CH2)4OH
12b: (CH2)3OH
12c: (CH2)2OH
13a: 95
13b: 85
13c: 91b)
13d: 88b)
13e: 84
13f: 94c)
13g: 84
(54/46)
12d: CH2OH
12e: CH2O(CH2)2Oi-Pr
12f: (CH2)2COOH
12g: CH(CH3)OH
These radical initiators were highly effective for the atom
transfer radical cyclization of 2-iodo amide 9 in water
(Scheme 2).12 Stirring a mixture of N,N-diallyl-2-iodoacet-
amide 9a (1.0 mmol) and 1a or 1b (0.30 mmol) at 75 °C or 60
°C in water (30 mL) for 1 h provided γ-lactam 10a in 80% or
99% yield, respectively. 2-Iodopropanamide 9b also under-
went cyclization in the presence of 1a or 1b to afford the corre-
sponding lactam 10b in 95% or 85% yield, respectively.13 The
effectiveness of 1a and 1b as an initiator in water was con-
firmed by these experiments.
12a: (CH2)4OH
12c: (CH2)2OH
12d: CH2OH
13a: 93
13c: 95
13d: 76
13f: 100c)
12f: (CH2)2COOH
12a: (CH2)4OH
13h: 86
(55/45)
a) 2-Iodoacetamide or 2-iodoacetic acid (1.0 mmol), alk-
enol (1.5 mmol), and 1a (0.50 mmol) were employed
unless otherwise noted. b) Three molar amounts of alkenol
were employed. c) The product was isolated as allyl ester
after treatment with allyl bromide in the presence of
K2CO3 in acetone.
Radical Addition of 2-Iodoalkanamide or 2-Iodoalkanoic
Acid to Alkenes in Aqueous Media to Yield γ-Lactones
The success of intramolecular radical cyclization of 2-io-
doalkanamide encouraged us to investigate an intermolecular
radical addition reaction. Thus, we turned our attention to the
reaction of 2-iodoacetamide with alkenol. The addition of 2-
iodoacetamide to alkenol in water afforded γ-substituted γ-lac-
tone in high yields. For instance, the reaction of 2-iodoacet-
amide (11a) with 5-hexen-1-ol (12a) in the presence of 1a at
75 °C for 16 h provided 5-(4-hydroxybutyl)dihydrofuran-
2(3H)-one (13a) in an isolated yield of 95% (Scheme 3). The
reaction would proceed as follows: Radical 14 derived from
11a adds readily to the alkenyl terminal carbon of alkenol 12a
to provide 15. The iodine atom transfer reaction between the
radical 15 and 11a affords 8-hydroxy-4-iodooctanamide (16)
and regenerates 14. The compound 16 cyclizes to γ-lactone
13a via 17 under the reaction conditions14 due to the well-
known ionic lactonization15,16 of 4-iodoalkanamide. Typical
examples are shown in Table 1.17,18 Alcohol, having a terminal
alkene moiety, as well as 4-pentenoic acid (12f) was converted
into the corresponding lactone in excellent yield. However, the
addition to alkenol containing an internal double bond such as
2-buten-1-ol did not take place. 1-Octene did not give lactone
under the same reaction conditions because of the insolubility
of 1-octene in water, whereas hydrophilic allyl ether 12e gave
13e.
Not only 2-iodoacetamide but 2-iodoacetic acid (11b) pro-
vided γ-lactones in the reaction with alkenol in water at 75 °C
in the presence of 1a. Some representative results are also
summarized in Table 1. Interestingly, 11b was added to 4-
penten-1-ol (12b) to give tetrahydrofuran derivative 19 in 40%
yield in addition to the expected γ-lactone 13b (54%) (Scheme
4). The former compound 19 was obtained by an intramolecu-
lar etherification of the iodine transfer product 18.
Scheme 3.
The formation of 19 prompted us to examine the reaction of

H. Yorimitsu et al.
Bull. Chem. Soc. Jpn., 74, No. 10 (2001) 1965
Scheme 4.
Scheme 7.
Scheme 5.
Scheme 8.
iodoacetonitrile (20) with 4-penten-1-ol (Scheme 5). A mix-
ture of 20 and 12b was treated under the standard reaction con-
ditions. The anticipated tetrahydrofuran derivative 21 was ob-
tained in 66% yield. The addition of α-iodo-γ-butyrolactone
(23) or N,N-diethyl-2-iodoacetamide (25) to 4-penten-1-ol
yielded the corresponding product 24 or 26 in excellent yield,
respectively (Scheme 6). The addition of 20 to 4-pentenoic
acid provided γ-lactone 27 in high yield. Furthermore, 5-hex-
en-1-ol reacted with 20 to give tetrahydropyran 28 in 40%
yield, along with unsaturated ω-hydroxy nitriles. However,
synthesis of pyrrolidine using the radical addition-ionic cy-
clization methodology seems difficult (Scheme 7). Treatment
of N-(4-pentenyl)aniline (29) with 20 or 23 gave the corre-
sponding pyrrolidine 30 or 31 in 22% or 41% yield, respective-
ly.
Iodide was liberated in the transformation of 16 into 13.
Thus, it was anticipated that, by adding a catalytic amount of
sodium iodide, the use of 2-chloroacetamide instead of the
iodo amide 11a would provide 13. We have indeed found that
the radical-ionic tandem reaction of 2-chloroacetamide with 5-
hexen-1-ol in the presence of a substoichiometric amount of
NaI proceeds smoothly, as shown in Scheme 8. Heating a mix-
ture of 2-chloroacetamide (1.0 mmol), 5-hexen-1-ol (1.5
mmol), and NaI (0.50 mmol)19 in water (10 mL) at 75 °C for
16 h in the presence of 1a (0.50 mmol) provided 13a in 82%
yield.
We have been interested in radical reactions in aqueous me-
dia and have disclosed the attractive solvent effect of water.5a–5c
Accordingly, the solvent effect on the present reaction was ex-
amined (Scheme 9). The reaction of N-ethyl-2-iodoacetamide
(11d) with 5-hexen-1-ol in water afforded 13a in 75% yield.
On the other hand, very interestingly, the reaction did not pro-
ceed at all in refluxing benzene, and 11d was almost complete-
ly recovered. The results of further investigations are summa-
rized in Table 2. Benzene, THF, CH2Cl2, and acetonitrile were
completely ineffective for the synthesis of lactones.20 In each
case, 11d was recovered, that is, the radical addition step itself
did not take place. Employing protic solvents, such as ethanol
and methanol, led to some conversion to give γ-decanolactone
(13i) in 14 % and 26% yields, respectively. Water is the best
for this reaction.
Scheme 6.

1966 Bull. Chem. Soc. Jpn., 74, No. 10 (2001)
Radical Reaction in Aqueous Media
Scheme 11.
Scheme 9.
Water could enhance the reactivity of radical 33 and/or activate
the carbon-iodine bond in 11. Other factors may work in this
reaction. The exact role of water is not clear at present.22
Whereas hydrophilic olefins could be used in the present re-
action, hydrophobic compounds such as 1-octene were not
suitable. To extend the scope of this reaction, radical reaction
in aqueous ethanol was studied. Radical addition-lactonization
reaction proceeded less effectively in ethanol than in water in
the presence of 1a, as shown in Table 2. Thus, we tested 1b as
an initiator for the reaction in aqueous ethanol. A mixture of
iodoacetamide (2.0 mmol) and 1-octene (10 mmol)23 was heat-
ed in EtOH/H2O (6 mL/1 mL) at reflux in the presence of 1b
(0.20 mmol) for 30 min. Usual workup followed by silica gel
column purification provided 13i in 80% yield in addition to
ethyl 4-hydroxydecanoate (13iꢀ, 6%), derived from solvolysis
of the lactone. Hydroxy ester 13iꢀ could be easily converted
into 13i. Heating a crude mixture of 13i and 13iꢀ in refluxing 1
M HCl for 20 min yielded 13i in 83% yield after silica gel col-
umn purification. The reaction in aqueous ethanol is summa-
rized in Table 3. Although excess of olefin was necessary,24
good results were obtained compared with the reaction in wa-
ter. Water as a cosolvent is essential to give a satisfactory re-
sult. For example, the yield of 13i decreased to 47% on em-
ploying anhydrous ethanol (7 mL). The initiator 1b proved to
Table 2. Reaction in Various Solvents
Time
/h
Yield of
13/%
Recovered
11d/%
Solvent
benzene1)
16
24
24
24
40
40
16
0
0
0
97
89
100
100
68
THF1)
CH2Cl2
1)
CH3CN
MeOH1)
EtOH
0
26
14
75
77
0
H2O2)
1) Reflux. 2) 5-Hexen-1-ol was used.
To get deeper insight into the solvent effect, the reaction was
performed in benzene at room temperature in the presence of
triethylborane21 in place of 1a (Scheme 10). A mixture of 11d
and 1-octene was treated with triethylborane in benzene at 25
°C. After 3 h, concentration of the reaction mixture yielded a
complex mixture containing 13i and the adduct 32. The start-
ing iodide 11d was completely consumed. An ethyl radical,
derived from triethylborane by the action of a trace of oxygen,
is reactive enough to abstract iodine from iodo amide.5e There-
fore, the reaction was initiated by triethylborane, and the prod-
ucts generated by the radical addition were obtained. Thus, the
reason for the recovery or the poor conversion of 11d in organ-
ic solvents in the presence of azo initiator 1a is that the radical
33, which is generated from 1a and is stabilized by a cyano
group, could not abstract iodine from iodo amide 11 (Scheme
11). The solvent effect of water works in the initiation step.
Table 3. Synthesis of Lactones in Aqueous Ethanol
R
13/%
12i: n-C6H13
13i: 83 (0)
12j: (CH2)8OH
13j: 83 (31)
12k: (CH2)3
13k: 79 (0)
12l: CH2CH2COCH3
13l: 72 (85)
The yields of 13 under the reaction conditions
Scheme 10.
in Table 1 are in parentheses.

H. Yorimitsu et al.
Bull. Chem. Soc. Jpn., 74, No. 10 (2001) 1967
diastereomer.): Bp 240 °C/0.1 torr. IR (neat) 3432, 2920, 1657,
1464, 1359, 1205, 1088, 1025, 740, 691 cm−1; 1H NMR (CDCl3)
δ 1.00 (d, J = 6.6 Hz, 3H × 0.32), 1.02 (d, J = 6.6 Hz, 3H ×
0.32), 1.06 (d, J = 6.6 Hz, 3H × 0.18), 1.07 (d, J = 6.6 Hz, 3H ×
0.18), 1.93–2.53 (m, 2H), 2.01 (s, 3H × 0.64), 2.02 (s, 3H ×
0.32), 2.71–2.89 (m, 1H), 2.92–3.11 (m, 1H), 3.14–3.40 (m, 2H),
3.48–3.60 (m, 1H), 3.62–3.93 (m, 1H), 7.18–7.38 (m, 5H); 13C
NMR (CDCl3) δ 12.92, 12.94, 15.96, 16.00, 21.83 (2C), 21.88,
21.92, 32.51, 32.60, 33.88, 35.01, 35.58, 35.75, 37.05, 38.38,
39.70, 41.50, 43.77, 45.55, 48.48, 50.30, 50.53, 51.97, 52.24,
52.32, 54.22, 54.25, 126.23, 126.25, 126.37, 126.39, 128.90 (4C),
128.99 (4C), 129.41 (2C), 129.51 (4C), 129.56 (2C), 135.56,
135.70, 135.74, 135.93, 168.95, 166.03, 169.32, 169.38. Found:
C, 67.19; H, 7.75%. Calcd for C14H19NOS: C, 67.43; H, 7.68%.
2-[4-(Phenylsulfanylmethyl)tetrahydrofuran-3-yl]ethanol
(5, 60/40 mixture of diastereomers): IR (neat) 3364, 2928,
be more effective than 1a, for which we assume the reason to
be as follows. The radical, derived from 1b, is stabilized with
the amide group resulting from hydrolysis of the amidine
group. The amide-stabilized radical would be less stable than
the radicals produced from AIBN and 1a, which the cyano
groups stabilize,25 and would be more reactive in iodine ab-
straction.
In summary, we have developed atom-transfer radical reac-
tions in aqueous media, using a water-soluble azo initiator.
Synthesis of γ-substituted γ-lactones has been accomplished by
a radical addition-lactonization sequence in a nontoxic solvent.
The reaction procedure is simple and safe, and no special tech-
nique is necessary. Similar to our previous reports, water as a
solvent or a cosolvent accelerates the reaction.
Experimental
1
2864, 1730, 1584, 1481, 1439, 1055, 898, 739, 690 cm−1; H
1H NMR (300 MHz) and 13C NMR (75.3 MHz) spectra were
taken on a Varian GEMINI 300 spectrometer in CDCl3 as a sol-
vent, and chemical shifts are given in δ value with tetramethylsi-
lane as an internal standard. IR spectra were determined on a
JASCO IR-810 spectrometer. Mass spectra were recorded on a
JEOL JMS-700 spectrometer. TLC analyses were performed on
commercial glass plates bearing 0.25-mm layer of Merck Silica
gel 60F254. Silica gel (Wakogel 200 mesh) was used for column
chromatography. The analyses were carried out at the Elemental
Analysis Center of Kyoto University. Unless otherwise noted,
materials obtained from commercial suppliers were used without
further purification. Dichloromethane and acetonitrile were dried
with molecular sieves 4A and 3A, respectively. Benzene was
dried over slices of sodium. THF was freshly distilled from sodi-
um benzophenone ketyl before use. Initiators 1a and 1b were pur-
chased from Fluka. Et3B was purchased from Aldrich Chemicals
and was diluted to prepare a 1.0 M hexane solution, which was
stored strictly under argon.
NMR (CDCl3) δ 1.50–1.63 (m, 1H), 1.69–1.84 (m, 1H), 1.86–2.19
(m, 2H), 2.36–2.52 (m, 1H), 2.79 (dd, J = 12.6, 9.6 Hz, 0.6H),
2.92 (dd, J = 12.9, 8.1 Hz, 0.4H), 3.06–3.13 (m, 1H), 3.44 (dd, J
= 8.4, 5.4 Hz, 0.4H), 3.54–3.74 (m, 3H), 3.79 (dd, J = 8.7, 4.8
Hz, 0.6H), 3.89–3.98 (m, 1.6H), 4.04 (dd, J = 8.7, 6.9 Hz, 0.4H),
7.17–7.37 (m, 5H); 13C NMR (CDCl3) For major isomer: δ 29.98,
32.42, 38.77, 41.08, 61.40, 71.94, 71.97, 126.27, 128.98 (2C),
129.49 (2C), 135.96, for minor isomer, δ 35.77, 37.20, 41.80,
44.51, 61.02, 72.62, 73.53, 126.24, 129.00 (2C), 129.28 (2C),
135.93. Found: C, 65.23; H, 7.43%. Calcd for C13H18O2S: C,
65.51; H, 7.61%.
4-(Phenylsulfanyl)-3-buten-1-ol (7, 50/50 mixture of diastere-
omers): IR (neat) 3335, 2930, 1583, 1479, 1439, 1047 cm−1; 1H
NMR (CDCl3) δ 1.61 (broad s, 1H), 2.43 (dt, J = 7.2, 7.2 Hz, 1H),
2.54 (dt, J = 7.2, 7.2 Hz, 1H), 3.65–3.80 (m, 2H), 5.85 (dt, J =
9.3, 7.2 Hz, 0.5H), 5.91 (dt, J = 15.3, 7.2 Hz, 0.5H), 6.28 (d, J =
15.3 Hz, 0.5H), 6.36 (d, J = 9.3 Hz, 0.5H), 7.17–7.38 (m, 5H);
13C NMR (CDCl3) δ 32.34, 36.08, 61.38 (2C), 124.03, 125.43,
126.27 (2C), 128.67, 128.78 (2C), 128.84 (2C), 128.92 (4C),
131.70, 135.69, 135.82. HRMS Found: 180.0609. Calcd for
C10H12OS: 180.0609.
Typical Procedure for Synthesis of γ-Lactone in Water.
A
water-soluble radical initiator 1a (0.14 g, 0.50 mmol) was added
to a solution of 2-iodoacetamide (11a, 0.19 g, 1.0 mmol) and 5-
hexen-1-ol (12a, 0.15 g, 1.5 mmol) in water (10 mL). After being
flushed with argon, the mixture was heated at 75 °C for 16 h, and
then cooled to 25 °C. Saturated NaHCO3 (5 mL) was added, and
the product was extracted with ethyl acetate (20 mL × 2). The
combined organic layer was washed with water, dried over anhy-
drous sodium sulfate, and concentrated in vacuo. The residue was
purified by silica gel column chromatography (hexane : ethyl ace-
tate = 1 : 2) to give 0.15 g of γ-lactone 13a in 95% yield.
3,4-Bis(phenylsulfanyl)-1-butanol (8): IR (neat) 3346, 2930,
1
1583, 1479, 1439, 1049, 741, 692 cm−1; H NMR (CDCl3) δ
1.68–1.83 (m, 2H), 2.21–2.33 (m, 1H), 2.91 (dd, J = 14.4, 10.5
Hz, 1H), 3.25–3.35 (m, 2H), 3.87 (dt, J = 6.0, 5.4 Hz, 2H), 7.14–
7.37 (m, 10H); 13C NMR (CDCl3) δ 35.23, 39.48, 45.17, 60.34,
126.38, 127.49, 128.98 (2C), 129.05 (2C), 129.83 (2C), 132.67
(2C), 133.58, 135.47. Found: C, 66.42; H, 6.39%. Calcd for
C16H18OS2: C, 66.16; H, 6.25%.
Synthesis of γ-Lactone in Aqueous Ethanol.
Iodoacet-
N,N-Diallyl-2-iodopropanamide (9b) was prepared as fol-
lows. Chloroacetyl chloride (16 mmol) was added dropwise to a
dichloromethane solution (15 mL) of diallylamine (15 mmol) and
pyridine (16 mmol) at −78 °C. The resulting mixture was
warmed to room temperature and was stirred for 1 h. Usual work-
up gave a crude oil, which was dissolved in acetone (30 mL). So-
dium iodide (30 mmol) was added to the solution at 25 °C. The
mixture was stirred for 3 h. Extractive workup followed by silica
gel column purification provided 9b in 83% overall yield. IR
amide (2.0 mmol) was placed in a round-bottomed flask, and etha-
nol (6 mL) and water (1 mL) were added to dissolve iodoaceto-
amide. 1-Octene (10 mmol) and 1b (0.40 mmol) were added, and
the whole mixture was heated at reflux (bath temp. 90 °C) for 30
min under argon. The product was extracted with ethyl acetate
(20 mL × 2). The combined organic layer was dried and concen-
trated. 1 M HCl was added to the crude oil, and the mixture was
heated at reflux for 20 min. Extraction and concentration fol-
lowed by silica gel column purification provided 0.29 g (1.7
mmol) of γ-decanolactone in 83% yield.
1
(neat) 2976, 2914, 1655, 1459, 1224, 991, 923 cm−1; H NMR
(CDCl3) δ 1.96 (d, J = 6.6 Hz, 3H), 3.61 (dddd, J = 15.3, 6.3, 1.2,
1.2 Hz, 1H), 3.78 (dddd, J = 18.0, 4.5, 1.8, 1.8 Hz, 1H), 4.09
(dddd, J = 18.0, 4.8, 3.0, 1.8 Hz, 1H), 4.38 (dddd, J = 15.3, 4.8,
3.0, 1.8 Hz, 1H), 4.52 (q, J = 15.3 Hz, 1H), 5.10–5.26 (m, 4H),
5.74–5.92 (m, 2H); 13C NMR (CDCl3) δ 13.40, 23.49, 48.16,
49.59, 116.12, 117.00, 132.04, 132.76, 170.85. Found: C, 38.89;
Characterization Data. Compounds 2,26 4,27 9a,12h and
10a12h are found in the literature. Lactone 13i is commercially
available.
1-Acetyl-3-methyl-4-(phenylsulfanylmethyl)-1-pyrrolidine
(3, 64/36 mixture of diastereomers. Two rotamers exist for each

1968 Bull. Chem. Soc. Jpn., 74, No. 10 (2001)
Radical Reaction in Aqueous Media
1
H, 5.05%. Calcd for C9H14INO: C, 38.73; H, 5.06%.
(neat) 3380, 2938, 1749, 1183 cm−1; H NMR (CDCl3) δ 1.60–
1-Allyl-4-iodomethyl-3-methylpyrrolidin-2-one (10b): For
trans isomer (faster moving band, Rf = 0.40, hexane/ethyl acetate
= 1/1) IR (Nujol) 2960, 2924, 1689, 1442, 1270, 1241, 1188, 920
cm−1; 1H NMR (CDCl3) δ 1.25 (d, J = 6.9 Hz, 3H), 2.08–2.27 (m,
2H), 3.00 (dd, J = 10.2, 7.8 Hz, 1H), 3.17 (dd, J = 10.2, 8.4 Hz,
1H), 3.41 (dd, J = 10.2, 4.5 Hz, 1H), 3.44 (dd, J = 10.2, 7.8 Hz,
1H), 3.57–3.99 (m, 2H), 5.16–5.24 (m, 2H), 5.66–5.80 (m,1H);
13C NMR (CDCl3) δ 8.01, 14.63, 42.56, 43.74, 45.02, 51.59,
118.09, 132.12, 175.47. Found: C, 38.88; H, 5.09%. Calcd for
C9H14INO: C, 38.73; H, 5.06%. For cis isomer (slower moving
band Rf = 0.34, hexane/ethyl acetate = 1/1) IR (Nujol) 2966,
2.05 (m, 6H), 2.36 (sextet, J ꢁ 7 Hz, 1H), 2.55 (dd, J = 9.3, 6.9
Hz, 2H), 3.70 (t, J = 6.3 Hz, 3H), 4.55 (m, 1H); 13C NMR
(CDCl3) δ 27.70, 28.10, 28.59, 31.72, 61.69, 80.91, 177.66.
5-[3-(t-Butyldimethylsiloxy)propyl]dihydrofuran-2(3H)-one
(13bꢀ): IR (neat) 2926, 1768, 1463, 1255, 1181, 1097, 834, 774
1
cm−1; H NMR (CDCl3) δ 0.04 (s, 6H), 0.88 (s, 9H), 1.53–1.92
(m, 5H), 2.33 (sextet, J ꢁ 7 Hz, 1H), 2.53 (dd, J = 9.3, 6.3 Hz,
2H), 3.62–3.67 (m, 2H), 4.52 (quintet, J ꢁ 7 Hz, 1H); 13C NMR
(CDCl3) δ −5.58 (2C), 18.08, 25.73 (3C), 27.83, 28.27, 28.67,
31.98, 62.33, 80.80, 177.28. Found: C, 60.15; H, 10.10%. Calcd
for C13H26O3Si: C, 60.42; H, 10.14%.
1
2926, 1689, 1439, 1266, 1192, 930 cm−1; H NMR (CDCl3) δ
5-(2-Hydroxyethyl)dihydrofuran-2(3H)-one (13c):
IR
1
1.13 (d, J = 7.8 Hz, 3H), 2.62 (dq, J = 7.8, 7.8 Hz, 1H), 2.73–
2.86 (m, 1H), 3.08 (dd, J = 9.9, 9.9 Hz, 1H), 3.11 (dd, J = 10.2,
6.6 Hz, 1H), 3.27 (dd, J = 9.9, 5.7 Hz, 1H), 3.46 (dd, J = 10.2,
7.2 Hz, 1H), 3.89 (ddd, J = 6.0, 1.5, 1.5 Hz, 2H), 5.20 (ddt, J =
18.3, 1.5, 1.5 Hz, 1H), 5.21 (ddt, J = 9.6, 1.5, 1.5 Hz, 1H), 3.89
(ddt, J = 18.3, 9.6, 1.5 Hz, 1H); 13C NMR (CDCl3) δ 4.22, 10.00,
39.15, 40.99, 45.09, 51.25, 118.29, 132.24, 176.09. Found: C,
38.89; H, 5.11%. Calcd for C9H14INO: C, 38.73; H, 5.06%.
(neat) 3184, 2926, 1753, 1180, 1045 cm−1; H NMR (CDCl3) δ
1.78–1.86 (broad, 1H), 1.87–2.00 (m, 3H), 2.39 (sextet, J ꢁ 7 Hz,
1H), 2.56 (dd, J = 9.3, 6.6 Hz, 2H), 3.83 (t, J = 6.0 Hz, 2H), 4.71
(quintet, J ꢁ 7 Hz, 1H); 13C NMR (CDCl3) δ 28.06, 28.57, 38.06,
59.12, 78.50, 177.30.
5-[2-(t-Butyldimethylsiloxy)ethyl]dihydrofuran-2(3H)-one
(13cꢀ): IR (neat) 2928, 1774, 1458, 1255, 1179, 1092, 836, 775
1
cm−1; H NMR (CDCl3) δ 0.05 (s, 6H), 0.88 (s, 9H), 1.76–1.99
1-Allyloxy-2-isopropoxyethane (12e)
was prepared from
(m, 3H), 2.35 (sextet, J ꢁ 7 Hz, 1H), 2.53 (dd, J = 9.3, 6.9 Hz,
2H), 3.75 (t, J = 6.0 Hz, 2H), 4.67 (quintet, J ꢁ 7 Hz, 1H); 13C
NMR (CDCl3) δ −5.67 (2C), 18.06, 25.72 (3C), 27.98, 28.63,
38.43, 59.05, 78.06, 177.30. Found: C, 58.74; H, 9.98%. Calcd
for C12H24O3Si: C, 58.97; H, 9.90%.
5-(6-Methyl-2,5-dioxaheptyl)dihydrofuran-2(3H)-one (13e):
Bp 155 °C/0.1 torr. IR (neat) 2968, 2868, 1778, 1369, 1128, 1087
cm−1; 1H NMR (CDCl3) δ 1.16 (d, J = 6.0 Hz, 6H), 2.08–2.79 (m,
4H), 3.54–3.75 (m, 7H), 4.62–4.70 (m, 1H); 13C NMR (CDCl3) δ
21.86 (2C), 23.90, 28.22, 67.30, 71.35, 71.86, 72.67, 79.08,
177.52. HRMS Found: m/z 187.0966. Calcd for C10H18O4−CH3:
187.0970.
commercially available 2-isopropoxyethanol and allyl bromide by
the action of stoichiometric sodium hydride in refluxing THF. Bp
125 °C/50 torr. IR (neat) 2966, 2852, 1648, 1468, 1368, 1080,
995, 920 cm−1; 1H NMR (CDCl3) δ 1.17 (d, J = 6.0 Hz, 6H), 3.59
(s, 4H), 3.62 (septet, J = 6.0 Hz, 1H), 4.04 (ddd, J = 6.0 , 1.5, 1.5,
Hz, 2H), 5.18 (ddt, J = 10.5, 1.8, 1.5 Hz, 1H), 5.28 (ddt, J = 17.1,
1.8, 1.5 Hz, 1H), 5.93 (ddt, J = 17.1, 10.5, 6.0 Hz, 1H); 13C NMR
(CDCl3) δ 21.83 (2C), 67.30, 69.62, 71.77, 72.11, 116.86, 134.87.
HRMS Found: m/z 129.0911. Calcd for C8H16O2 − CH3:
129.0916.
N-(4-Pentenyl)phthalimide (12k) was synthesized by treat-
ment of 1-bromo-4-pentene with an equimolar amount of potassi-
um phthalimide in DMF at 90 °C overnight. IR (neat) 2939, 1771,
Lactone 13f was quantitatively converted into allyl ester by
treatment with allyl bromide (1.5 eq.) and K2CO3 (1.5 eq.) in re-
fluxing acetone for 3 h.
1
1713, 1641, 1396, 1371, 1188, 1072, 993, 719 cm−1; H NMR
(CDCl3) δ 1.79 (tt, J = 7.2, 7.2 Hz, 2H), 2.13 (dt, J = 7.2, 7.2 Hz,
2H), 3.71 (t, J = 7.2 Hz, 2H), 4.99 (dd, J = 9.9, 1.2 Hz, 1H), 5.06
(dd, J = 17.1, 1.2 Hz, 1H), 5.82 (ddt, J = 17.1, 9.9, 7.2 Hz, 1H),
7.69–7.74 (m, 2H), 7.82–7.88 (m, 2H); 13C NMR (CDCl3) δ
27.43, 30.78, 37.37, 115.25, 123.12 (2C), 132.13, 133.85 (2C),
137.30 (2C), 168.42 (2C). Found: C, 72.60; H, 6.07%. Calcd for
C13H13NO2: C, 72.54; H, 6.09%.
Hydroxy lactones 13 were silylated with t-butyldimethylsilyl
chloride in the presence of imidazole in DMF in more than 90%
yield to afford analytically pure material.
5-[2-(Allyloxycarbonyl)ethyl]dihydrofuran-2(3H)-one
(13fꢀ): IR (neat) 2942, 1774, 1739, 1650, 1439, 1376, 1345,
1264, 1141, 1044, 990, 926 cm−1; 1H NMR (CDCl3) δ 1.81–2.10
(m, 3H), 2.37 (sextet, J ꢁ 7 Hz, 1H), 2.45–2.63 (m, 4H), 4.50–
4.61 (m, 3H), 5.25 (ddt, J = 10.5, 1.2, 1.2 Hz, 1H), 5.32 (ddt, J ꢁ
17.4, 1.2, 1.2 Hz, 1H), 5.92 (ddt, J = 17.4, 10.5, 5.7 Hz, 1H); 13
C
NMR (CDCl3) δ 27.62, 28.44, 29.85, 30.44, 65.13, 79.46, 118.32,
131.97, 172.29, 176.79. Found: C, 60.61; H, 7.12%. Calcd for
C10H14O4: C, 60.59; H, 7.12%.
5-(4-Hydroxybutyl)-3-methyldihydrofuran-2(3H)-one (13h,
1/1 mixture of diastereomers): IR (neat) 3347, 2925, 1755, 1180
cm−1; 1H NMR (CDCl3) δ 1.25 (d, J = 6.9 Hz, 1.5H), 1.28 (d, J =
7.2 Hz, 1.5H), 1.42–1.84 (m, 6.5H), 1.96–2.18 (m, 1H), 2.50 (ddd,
J = 12.6, 8.4, 5.4 Hz, 0.5H), 2.61–2.90 (m, 2H), 3.67 (t, J = 5.7
Hz, 2H), 4.30–4.40 (m, 0.5H), 4.48–4.57 (m, 0.5H); 13C NMR
(CDCl3) δ 14.75, 15.50, 21.35, 21.40, 31.82, 31.87, 33.80, 34.84,
34.92, 35.07, 35.66, 36.96, 62.05 (2C), 78.41, 78.62, 179.99,
180.50.
5-(4-Hydroxybutyl)dihydrofuran-2(3H)-one (13a):
IR
(neat) 3346, 2922, 1752, 1180 cm−1; H NMR (CDCl3) δ 1.40–
1.94 (m, 9H), 2.34 (sextet, J ꢁ 7 Hz, 1H), 2.54 (dd, J = 9.3, 6.9
Hz, 2H), 3.67 (t, J = 6.0 Hz, 2H), 4.51 (quintet, J ꢁ 7 Hz, 1H);
13C NMR (CDCl3) δ 21.25, 27.55, 28.52, 31.84, 34.93, 61.87,
80.92, 177.65; MS m/z (rel intensity) 157 (M−1, 1), 140 (3), 128
(25), 110 (22), 85 (100).
1
5-[4-(t-Butyldimethylsiloxy)butyl]dihydrofuran-2(3H)-one
(13aꢀ): IR (neat) 2926, 1777, 1460, 1255, 1180, 1098, 836, 775
5-[4-(t-Butyldimethylsiloxy)butyl]-3-methyldihydrofuran-
2(3H)-one (13hꢀ, 1/1 mixture of diastereomers): IR (neat) 2928,
1
cm−1; H NMR (CDCl3) δ 0.04 (s, 6H), 0.88 (s, 9H), 1.41–1.67
(m, 5H), 1.70–1.91 (m, 2H), 2.31 (sextet, J ꢁ 7 Hz, 1H), 2.52 (dd,
J = 9.3, 6.9 Hz, 2H), 3.61 (t, J = 6.0 Hz, 2H), 4.48 (quintet, J ꢁ 7
Hz, 1H); 13C NMR (CDCl3) δ −5.58 (2C), 18.09, 21.45, 25.74
(3C), 27.76, 28.62, 32.21, 35.15, 62.63, 80.83, 177.26. Found: C,
62.01; H, 10.44%. Calcd for C14H28O3Si: C, 61.72; H, 10.36%.
2856, 1775, 1460, 1250, 1188, 1166, 1097, 1002, 835, 773 cm−1
;
1H NMR (CDCl3) δ 0.05 (s, 6H), 0.89 (s, 9H), 1.27 (d, J = 6.9 Hz,
1.5H), 1.28 (d, J = 7.2 Hz, 1.5H), 1.39–1.84 (m, 6.5H), 1.95–2.18
(m, 1H), 2.48 (ddd, J = 12.3, 9.0, 5.4 Hz, 0.5H), 2.59–2.73 (m,
1H), 3.62 (t, J = 6.0 Hz, 2H), 4.29–4.39 (m, 0.5H), 4.46–4.55 (m,
0.5H); 13C NMR (CDCl3) δ −5.55 (4C), 14.92, 15.69, 18.12,
5-(3-Hydroxypropyl)dihydrofuran-2(3H)-one (13b):
IR

H. Yorimitsu et al.
Bull. Chem. Soc. Jpn., 74, No. 10 (2001) 1969
21.53, 21.60, 25.76 (7C), 32.21, 32.27, 33.84, 35.03, 35.13, 35.25,
35.74, 37.16, 62.68 (2C), 78.28, 78.52, 179.64, 180.12. Found: C,
62.84; H, 10.48%. Calcd for C15H30O3Si: C, 62.89; H, 10.55%.
5-(1-Hydroxyethyl)dihydrofuran-2(3H)-one (13g, 54/46 mix-
ture of diastereomers): IR (neat) 3342, 2974, 1753, 1191, 1139,
1021, 986, 918 cm−1; 1H NMR (CDCl3) δ 1.19 (d, J = 6.3 Hz, 3H
× 0.46), 1.27 (d, J = 6.3 Hz, 3H × 0.54), 2.00–2.69 (m, 5H), 3.79
(dq, J = 6.3, 6.3 Hz, 0.5H), 4.08–4.17 (m, 0.5H), 4.32–4.45 (m,
1H); 13C NMR (CDCl3) δ 17.58, 18.28, 20.79, 23.82, 28.44,
28.52, 67.23, 69.60, 83.65, 84.23, 177.71, 178.05.
1H), 2.46 (dd, J = 7.5, 3.6 Hz, 1H), 2.48 (dd, J = 7.8, 2.7 Hz,
1H), 3.74 (dt, J = 8.4, 6.9 Hz, 1H), 3.82–3.96 (m, 2H); 13C NMR
(CDCl3) δ 14.11, 25.54, 30.95, 31.18, 67.80, 76.98, 119.77.
Found: C, 66.99; H, 9.00%. Calcd for C7H11NO: C, 67.17; H,
8.86%.
3-(Tetrahydrofuran-2-ylmethyl)dihydrofuran-2(3H)-one
(24, 1/1 mixture of diastereomers): IR (neat) 2941, 1767, 1715,
1398, 1373, 1180, 1047, 721 cm−1; 1H NMR (CDCl3) δ 1.43–1.70
(m, 2H), 1.80–2.15 (m, 5H), 2.44–2.54 (m, 1H), 2.58–2.69 (m,
0.5H), 2.75–2.87 (m, 0.5H), 3.68–3.78 (m, 1H), 3.81–3.96 (m,
1.5H), 3.98–4.08 (m, 0.5H), 4.14–4.24 (m, 1H), 4.32–4.41 (m,
1H); 13C NMR (CDCl3) δ 25.25, 25.39, 28.58, 29.27, 31.33,
31.43, 35.86, 36.03, 36.65, 37.60, 66.48, 66.53, 67.52, 67.54,
76.20, 77.56, 179.57, 179.72. Found: C, 63.52; H, 8.47%. Calcd
for C9H14O3: C, 63.51; H, 8.29%.
Acetylation of 13g (acetic anhydride, pyridine, overnight, 95%
yield) provided analytically pure sample 13gꢀ.
5-[1-(Acetoxy)ethyl]dihydrofuran-2(3H)-one (13gꢀ, 50/50
mixture of diastereomers): IR (neat) 2940, 1780, 1739, 1374,
1242, 1180, 1137, 1074, 1048, 981, 941 cm−1; 1H NMR (CDCl3)
δ 1.28 (d, J = 6.6 Hz, 1.5H), 1.31 (d, J = 6.6 Hz, 1.5H), 1.92–
2.20 (m, 1H), 2.06 (s, 1.5H), 2.08 (s, 1.5H), 2.24–2.36 (m, 1H),
2.46–2.64 (m, 2H), 4.51 (septet, J ꢁ 4 Hz, 1H), 4.96–5.04 (m,
0.5H), 5.04–5.13 (m, 0.5H); 13C NMR (CDCl3) δ 15.02, 15.72,
20.84 (2C), 22.46, 23.78, 27.81, 28.00, 70.44, 71.13, 80.67, 80.92,
170.09, 170.24, 176.66 (2C). Found: C, 55.79; H, 6.94%. Calcd
for C8H12O4: C, 55.81; H, 7.02%.
N,N-Diethyl-3-(tetrahydrofuran-2-yl)propanamide
(26):
IR (neat) 2966, 2928, 1640, 1629, 1459, 1380, 1096, 1066, 1020
1
cm−1; H NMR (CDCl3) δ 1.11 (t, J = 4.2 Hz, 3H), 1.17 (t, J =
4.2 Hz, 3H), 1.44–1.56 (m, 1H), 1.70–2.07 (m, 5H), 2.32–2.54 (m,
2H), 3.33 (q, J = 4.2 Hz, 2H), 3.37 (q, J = 4.2 Hz, 2H), 3.72 (q, J
ꢁ 7 Hz, 1H), 3.80–3.89 (m, 2H); 13C NMR (CDCl3) δ 12.96,
14.20, 25.59, 29.82, 31.17, 31.33, 40.01, 41.83, 67.61, 78.68,
172.04. Found: C, 66.25; H, 10.67%. Calcd for C11H21NO2: C,
66.29; H, 10.62%.
5-(8-Hydroxyoctyl)dihydrofuran-2(3H)-one (13j): Mp 57–
59 °C. IR (Nujol) 3402, 3335, 2856, 1747, 1198, 1182, 970 cm−1
;
1H NMR (CDCl3) δ 1.26–1.66 (m, 14H), 1.68–1.92 (m, 2H), 2.33
(sextet, J ꢁ 7 Hz, 1H), 2.54 (dd, J = 9.6, 6.6 Hz, 2H), 3.64 (t, J =
6.6 Hz, 2H), 4.49 (quintet, J ꢁ 7 Hz, 1H); 13C NMR (CDCl3) δ
24.93, 25.42, 27.72, 28.61, 28.96, 29.00, 29.11, 32.43, 35.27,
62.57, 80.99, 177.54. Found: C, 66.99; H, 10.61%. Calcd for
C12H22O3: C, 67.26; H, 10.35%.
3-(5-Oxotetrahydrofuran-2-yl)propionitrile (27): IR (neat)
1
2939, 2247, 1771, 1423, 1157 cm−1; H NMR (CDCl3) δ 1.83–
2.09 (m, 3H), 2.36–2.48 (m, 1H), 2.53–2.62 (m, 4H), 4.54–4.64
(m, 1H); 13C NMR (CDCl3) δ 13.85, 27.42, 28.33, 31.23, 78.09,
118.62, 176.24. Found: C, 60.27; H, 6.67%. Calcd for C7H9NO2:
C, 60.42; H, 6.52%.
5-(3-Phthalimidopropyl)dihydrofuran-2(3H)-one
(13k):
3-(Tetrahydropyran-2-yl)propionitrile (28): IR(neat) 2936,
1
Mp 76–79 °C. IR (Nujol) 2941, 1767, 1715, 1398, 1180, 1047,
721 cm−1; 1H NMR (CDCl3) δ 1.61–1.98 (m, 5H), 2.34 (sextet, J
ꢁ 7 Hz, 1H), 2.54 (dd, J = 9.3, 7.2 Hz, 2H), 3.75 (t, J ꢁ 6 Hz,
2H), 4.55 (quintet, J ꢁ 7 Hz, 1H), 7.70–7.67 (m, 2H), 7.81–7.88
(m, 2H); 13C NMR (CDCl3) δ 24.30, 27.53, 28.35, 32.41, 36.96,
79.87, 122.98 (2C), 131.74 (2C), 133.84 (2C), 168.14 (2C),
176.86. Found: C, 65.87; H, 5.53%. Calcd for C15H15NO4: C,
65.92; H, 5.53%.
2849, 2245, 1443, 1090, 1049, 880 cm−1; H NMR (CDCl3) δ
1.22–1.35 (m, 1H), 1.42–1.64 (m, 4H), 1.71–1.88 (m, 3H), 2.44–
2.51 (m, 2H), 3.31–3.47 (m, 2H), 3.94–4.00 (m, 1H); 13C NMR
(CDCl3) δ 13.32, 23.11, 25.79, 31.48, 31.86, 68.44, 75.32, 119.98.
Found: C, 68.78; H, 9.15%. Calcd for C8H13NO: C, 69.03; H,
9.41%.
N-(4-Pentenyl)aniline (29) was prepared by treating a mix-
ture of aniline (20 mmol) and 1-bromo-4-pentene (10 mmol) with
potassium carbonate (20 mmol) in acetone at reflux (32% yield).
5-(3-Oxobutyl)dihydrofuran-2(3H)-one (13l):
IR (neat)
2936, 1771, 1715, 1423, 1358, 1180, 980, 916 cm−1; H NMR
(CDCl3) δ 1.76–1.93 (m, 2H), 1.96–2.08 (m, 1H), 2.18 (s, 3H),
2.37 (sextet, J ꢁ 7 Hz, 1H), 2.55 (dd, J = 9.6, 6.9 Hz, 2H), 2.67 (t,
J ꢁ 7 Hz, 2H), 4.52 (m, 1H); 13C NMR (CDCl3) δ 27.68, 28.40,
29.02, 29.71, 38.85, 79.64, 176.91, 207.46. Found: C, 61.58; H,
7.84%. Calcd for C8H12O3: C, 61.52; H, 7.74%.
IR (neat) 3410, 2932, 1603, 1506, 1321, 1259, 912, 748, 692 cm−1
;
1
1H NMR (CDCl3) δ 1.72 (tt, J = 7.5, 6.9 Hz, 2H), 2.17 (dt, J =
6.9, 6.6 Hz, 2H), 3.13 (t, J = 7.5 Hz, 2H), 3.50–3.80 (broad s,
1H), 4.97–5.10 (m, 2H), 5.84 (ddt, J = 16.8, 9.9, 6.6 Hz, 1H),
6.60 (dd, J = 8.7, 0.9 Hz, 2H), 6.69 (tt, J = 7.5, 0.9 Hz, 1H), 7.17
(dd, J = 8.7, 7.5 Hz, 2H); 13C NMR (CDCl3) δ 28.53, 31.19,
43.29, 112.73 (2C), 115.12, 117.19, 129.29 (2C), 138.13, 148.47.
Found: C, 81.88; H, 9.55%. Calcd for C11H15N: C, 81.94; H,
9.38%.
3-(Tetrahydrofuran-2-yl)propanoic acid (19) was isolated
as allyl ester after treatment with allyl bromide in the presence of
K2CO3 in refluxing acetone.
Allyl 3-(Tetrahydrofuran-2-yl)propanoate (19ꢀ): IR (neat)
3-(1-Phenyl-2-pyrrolidinyl)propanenitrile (30):
IR (neat)
1
2932, 2862, 1737, 1648, 1376, 1236, 1158, 1066, 988, 927 cm−1
;
2936, 2245, 1599, 1504, 1367, 1159 cm−1; H NMR (CDCl3) δ
1.63–1.76 (m, 1H), 1.79–1.86 (m, 1H), 1.95–2.12 (m, 4H), 2.28–
2.46 (m, 2H), 3.17 (dt, J = 8.7, 8.1 Hz, 1H), 3.44–3.51 (m, 1H),
3.79–3.87 (m, 1H), 6.60 (d, J = 8.1 Hz, 2H), 6.70 (t, J = 7.5 Hz,
1H), 7.21–7.28 (m, 2H); 13C NMR (CDCl3) δ 13.95, 23.26, 28.51,
29.93, 48.54, 56.86, 112.01 (2C), 116.26, 119.56, 129.42 (2C),
147.00. Found: C, 78.08; H, 8.33%. Calcd for C13H16N2: C,
77.96; H, 8.05%.
1H NMR (CDCl3) δ 1.48 (ddt, J = 10.5, 7.5, 7.5 Hz, 1H), 1.77–
2.05 (m, 5H), 2.36–2.56 (m, 2H), 3.71 (q, J ꢁ 7 Hz, 1H), 3.80–
3.90 (m, 2H), 4.58 (ddd, J = 5.7, 0.9, 0.9 Hz, 2H), 5.23 (ddt, J =
10.5, 1.5, 0.9 Hz, 1H), 5.31 (ddt, J = 16.5, 1.5, 0.9 Hz, 1H), 5.93
(ddt, J = 16.5, 10.5, 5.7 Hz, 1H); 13C NMR (CDCl3) δ 25.49,
30.48, 30.86, 30.98, 64.87, 67.54, 78.01, 117.99, 132.30, 173.24.
Found: C, 64.93; H, 8.94%. Calcd for C10H16O3: C, 65.19; H,
8.75%.
3-(1-Phenyl-2-pyrrolidinylmethyl)dihydrofuran-2(3H)-one
(31, 1/1 mixture of diastereomers): IR (neat) 2932, 1771, 1599,
3-(Tetrahydrofuran-2-yl)propanenitrile (21):
IR (neat)
1
1
2953, 2872, 2245, 1445, 1427, 1074, 1024, 910 cm−1; H NMR
1373, 1157, 1024 cm−1; H NMR (CDCl3) δ 1.74–2.26 (m, 7H),
(CDCl3) δ 1.44–1.57 (m, 1H), 1.72–1.97 (m, 4H), 2.00–2.11 (m,
2.36–2.47 (m, 0.5H), 2.48–2.60 (m, 1.5H), 3.13–3.24 (m, 1H),

1970 Bull. Chem. Soc. Jpn., 74, No. 10 (2001)
Radical Reaction in Aqueous Media
3.42-3.50 (m, 1H), 3.79–3.88 (m, 0.5H), 4.14–4.53 (m, 2.5H),
6.57 (d, J = 8.1 Hz, 1H), 6.64–6.70 (m, 2H), 7.19–7.26 (m, 2H);
13C NMR (CDCl3) δ 22.95, 23.26, 29.10, 29.71, 29.91, 30.08,
33.60, 33.78, 36.49, 37.14, 48.07, 48.40, 55.87, 56.43, 66.43,
66.51, 111.67 (2C), 112.09 (2C), 115.72 (2C), 129.27 (2C),
129.30 (2C), 147.17 (2C), 179.31, 179.50. HRMS Found: m/z
245.1414. Calcd for C15H18NO: 245.1416.
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12 Selected examples of atom transfer radical cyclization for
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This work was supported by Grants-in-Aid for Scientific
Research (Nos. 12305058 and 10208208) from the Ministry of
Education, Culture, Sports, Science and Technology. H. Y. ac-
knowledges JSPS for financial support. H. S. also thanks
Banyu Pharmaceutical Co., Ltd.
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a) T. Nakamura, H. Yorimitsu, H. Shinokubo, and K.
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mmol), 5-hexen-1-ol (1.5 mmol), and 1b (0.5 mmol) at 75 °C for 5
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18 Reaction in refluxing water lowered the yield of lactone
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19 Reducing the amount of NaI (0.20 mmol) resulted in for-
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6
Recent example using a water-soluble initiator: A. E.
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20 The use of AIBN, instead of 1a, also led to recovery of
iodo amide.
7
A part of this work was reported: H. Yorimitsu, K.
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23 When 4 mmol or 6 mmol of 1-octene was employed, the
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24 Non-volatile olefins could be recovered easily.
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