A new synthesis of amides and γ-lactones based on the conjugate addition of lithium enolate of amides to 1-chlorovinyl p-tolyl sulfoxides

Article abstract of DOI:10.1016/j.tet.2004.09.113

Reaction of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from chloromethyl p-tolyl sulfoxide and ketones or aldehydes, with lithium enolate of N,N-dimethylacetamide gave the adducts in good to quantitative yields. The adducts were converted to

Full text of DOI:10.1016/j.tet.2004.09.113

Tetrahedron 60 (2004) 11805–11812
A new synthesis of amides and g-lactones based on the conjugate
addition of lithium enolate of amides
to 1-chlorovinyl p-tolyl sulfoxides
*
Tsuyoshi Satoh, Yuhki Kamide and Shimpei Sugiyama
Department of Chemistry, Faculty of Science, Tokyo University of Science; Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Received 25 August 2004; accepted 29 September 2004
Available online 19 October 2004
Abstract—Reaction of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from chloromethyl p-tolyl sulfoxide and ketones or
aldehydes, with lithium enolate of N,N-dimethylacetamide gave the adducts in good to quantitative yields. The adducts were converted to
several kinds of amides in high overall yields. Treatment of the adducts with trifluoroacetic anhydride in the presence of NaI resulted in the
formation of g-tolylsulfanylated g-lactones in high yields. The scope and limitations of this method and the mechanism of the reactions
are also discussed. These procedures offer a new and effective method for the synthesis of amides and g-lactones having substituents on the
b-carbon from N,N-dimethylacetamide with carbon elongation.
q 2004 Elsevier Ltd. All rights reserved.
Carboxylic acids, esters, amides, and their derivatives are
among the most important compounds in organic chemistry1
including bioorganic2,3 and synthetic organic chemistry. In
view of their importance, development of new synthetic
methods for these compounds has still been actively
investigated in many laboratories worldwide.
1. Results and discussion
1.1. The addition reaction of the lithium enolate of N,N-
dimethylacetamide to 1-chlorovinyl p-tolyl sulfoxides
In previous studies, we have found that lithium ester
enolates added to 1-chlorovinyl p-tolyl sulfoxides in high
yields.4 Based on this experience, we investigated the
addition reaction of the vinylsulfoxides with the lithium
enolate of N,N-dimethylacetamide (Scheme 1).
One method for obtaining the desired carboxylic acid
derivatives is considered to be the elongation of carbons
from simple acetates or acetamides. Recently, we reported a
method for a synthesis of functionalized esters and lactones
from acetates and their homologues with 1-chlorovinyl
p-tolyl sulfoxides.4 In continuation of our interest in the
development of new synthetic methods by using 1-chloro-
vinyl p-tolyl sulfoxides,5,6 we turned our attention to the
reaction of 1-chlorovinyl p-tolyl sulfoxides with lithium
enolate of N,N-dimethylacetamide and its homologues, and
quite interesting results were obtained.
Thus, a THF solution of 1-chlorovinyl p-tolyl sulfoxide 2a,
derived from ketone 1 in three steps,7 was added dropwise to
a solution of 5 equiv of lithium enolate of N,N-dimethyl-
acetamide (generated from N,N-dimethylacetamide with
LDA) at K78 8C. An instantaneous reaction took place and
the adduct 3a was obtained as about a 5:3 mixture of two
diastereomers in a quantitative yield. Encouraged by this
Scheme 1.
Keywords: Amide; Amide enolate; Conjugate addition; g-Lactone; Sulfoxide.
* Corresponding author. Tel.: C81 3 5228 8272; fax: C81 3 3235 2214; e-mail: tsatoh@ch.kagu.tus.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.09.113

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T. Satoh et al. / Tetrahedron 60 (2004) 11805–11812
Table 1. Addition of lithium enolate of N,N-dimethylacetamide to 1-chlorovinyl p-tolyl sulfoxides 2
Entry
1
2
Conditionsa
Adduct 3
Yield (%)
97b
3b
2b
K78 8C, 1.5 h
99c
2c
3c
2
K78 8C, 3 h
2d
3d
3
4
5
6
K78wK10 8C, 2 h
K78wK10 8C, 2 h
K78wK10 8C, 2 h
K78 8C, 30 min
40d
2e-Z
86d
3e-a
2e-E
22d,e
3e-b
2ff
96g
3f
2gf
99h
3g
7
K78 8C, 30 min
a Five equivalents of lithum enolate of N,N-dimethylacetamide was reacted with 1-chlorovinyl p-tolyl sulfoxides 2.
b About 5:1 mixture of two diastereomers.
c About 10:1 mixture of two diastereomers.
d Single diastereomer.
e Starting material 75% was recovered.
f
A mixture of two geometrical isomers was used in this reaction.
g A mixture of four diastereomers.
h About 3:1 mixture of two diastereomers.
result, the addition reaction of lithium enolate of N,N-di-
methylacetamide with 1-chlorovinyl p-tolyl sulfoxides (2b–
2g) derived from ketones and aldehydes was investigated
and the results are summarized in Table 1.
Difference in reactivity between the geometrical isomers
2e-Z and 2e-E was observed (entries 4 and 5). The reason for
this result is obscure at present. The addition reaction with
the 1-chlorovinyl p-tolyl sulfoxides derived from alkyl
aldehyde 2f and aryl aldehyde 2g is shown in entries 6 and 7.
Both vinyl sulfoxides reacted with the lithium enolate at
K78 8C within 30 min without any problem to give the
adducts 3f and 3g in quantitative yields (entries 6 and 7).
The adducts were usually a mixture of diastereomers;
however, in the cases of the reaction with 2d and 2e,
a single diastereomer was obtained (entries 3–5). The
stereochemistry of both adducts has not yet been
determined.
Interestingly, the addition reaction of the lithium enolate
with the 1-chlorovinyl p-tolyl sulfoxides derived from
cyclodecanone and cyclopentadecanone (2b and 2c) was
found to be sluggish compared to the reaction with 2a;
however, on prolonging the reaction time to 3 h, the desired
adducts 3b and 3c were obtained in quantitative yields
(entries 1 and 2).
The reaction with the 1-chlorovinyl p-tolyl sulfoxides 2d
and 2e, derived from benzophenone and acetophenone, was
found to be very sluggish, and warming the reaction mixture
from K78 to K10 8C was required (entries 3–5). It is
interesting to note that, in a previous study,4 the addition
reaction of lithium enolate of tert-butylacetate to 2d
and 2e did not proceed at all and the starting sulfoxides
were recovered. Conjugation of the phenyl group to the
1-chlorovinyl p-tolyl sulfoxides was thought to be the
reason for these results.
Next, the addition reaction of the dianions of acetamide,
N-methylacetamide, and N-(4-methoxyphenyl)acetamide to
1-chlorovinyl p-tolyl sulfoxides 2a and 2c was examined
(Scheme 2). The reaction of 5 equiv of these dianions with
the vinyl sulfoxides 2a or 2c at K78 8C did not proceed at
all. When the temperature of the reaction mixture was
slowly allowed to warm to K10 8C, we observed decompo-
sition of the vinyl sulfoxides and obtained only a complex
mixture with no desired adduct.

T. Satoh et al. / Tetrahedron 60 (2004) 11805–11812
11807
benzene.8 The desired reduction cleanly took place to
afford the sulfoxide 4a in 90% yield.
The sulfinyl group in 4a was cleanly reduced with Raney
nickel9 in refluxing ethanol for 1 h to give 5a in 93% yield.
The other adducts 3b and 3c were converted to the reduced
compounds having a methyl group at the b-position (5b and
5c) in high overall yields. By these reactions, a new method
for a synthesis of amides having a quaternary carbon at the
b-position was realized starting from N,N-dimethylaceta-
mide with carbon elongation.
Scheme 2.
The higher basicity of the dianions, compared with the
lithium enolate of N,N-dimethylacetamide, was thought to
be the reason for these results, because we have already
observed that the reaction of the 1-chlorovinyl p-tolyl
sulfoxides 2 with a highly basic reagent, such as lithium
diisopropylamide, resulted in their decomposition.
1.3. Trial to a synthesis of g-lactams
Kita et al. reported a synthesis of b-lactams from b-amido
sulfoxides via intramolecular Pummerer-type cyclization.10
We attempted to synthesize g-lactams from the adducts,
g-amido sulfoxides, by using a similar cyclization.
1.2. Transformation of the carbon bearing a chlorine
atom and a sulfinyl group in the adduct to a methyl
group
In order to transform the adducts to simple amides,
reduction of the chlorine and sulfinyl groups was investi-
gated (Scheme 3). First, 3a was treated with Bu3SnH in the
presence of a catalytic amount of AIBN in refluxing
As already mentioned, the addition reaction of the dianions
of N-mono-substituted acetamide and acetamide with
1-chlorovinyl p-tolyl sulfoxides failed (see Scheme 2). We
synthesized N-benzyl-N-(4-methoxyphenyl)acetamide 6
Scheme 3.
Scheme 4.

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T. Satoh et al. / Tetrahedron 60 (2004) 11805–11812
Scheme 5.
from N-benzyl p-anisidine, and the lithium enolate of amide
7, derived from 6, was reacted with 2c. The addition
reaction worked excellently to afford the adduct 8 in 92%
yield (Scheme 4).
the oxygen of the amide group to give an ether having
iminium ion 14. The trifluoroacetoxy anion then attacks
the carbon of the iminium ion to afford 15, which was
hydrolyzed in the work-up process to give the g-lactone 11.
The 4-methoxyphenyl group in 8 was eliminated with ceric
ammonium nitrate (CAN)11 to afford the desired g-amido
sulfoxide 9, though the yield was low. The amide 9 was
treated with excess trifluoroacetic anhydride (TFAA) in
the presence of NaI in acetone at K50 8C.12 We obtained
not the expected g-lactam 10 but spiro-lactone having a
p-tolylsulfanyl group at the g-position 11 in 22% yield as
a main product.
1.4. Synthesis of lactones from the adducts 3
As mentioned above, the Pummerer-type cyclization of
g-amido sulfoxide 9 was found to give g-lactone 11. From
the presumed mechanism shown in Scheme 5, we expected
that the treatment of the adducts 3 derived from N,N-
dimethylacetamide with TFAA also gave lactones. In fact,
treatment of the adduct 3a with TFAA in the presence of
NaI in acetone at K50 8C gave g-lactone having a
p-tolylsulfanyl group at the g-position 16a in 49% yield
(Table 2, entry 1). The results of this reaction with the
adducts 3c–3g are summarized in Table 2.
The presumed mechanism of this interesting reaction is
shown in Scheme 5. First, the reaction of the sulfoxide 9
with TFAA gives an acyloxysulfonium ion 12.13 The iodide
anion attacks the chlorine atom to afford thionium ion 13.
The anticipated reaction, attack of the nitrogen lone pair to
the thionium ion, did not take place and no desired g-lactam
10 was obtained. Instead, the thionium ion was attacked by
As shown in Table 2, about 70–90% of g-lactones 11, 16a,
and 16d–16g were obtained by this reaction. In some cases,
aldehydes 17c, 17f, and 17g were obtained as by-products.
Table 2. Synthesis of g-lactones 16 and N,N-dimethylamides having a formyl group at the b-position 17 from the adducts 3
Entry
1
3
16 Yield
16aa 49
17 Yield
R1
R2
b
—
3a
2
3
4
5
6
3c
3d
3e-a
3f
–(CH2)14
–
11a 85
16d 75
16ec 91
16fa 81
16gd 68
17c 13
—
—
17f 15
17g 21
b
Ph
Ph
Ph
CH3
H
b
PhCH2CH2
Ph
3g
H
a See lit. 4.
b No aldehyde was obtained.
c About 3:1 inseparable mixture of diastereomers.
d About 5:1 inseparable mixture of diastereomers.

T. Satoh et al. / Tetrahedron 60 (2004) 11805–11812
11809
These aldehydes were thought to be produced form the
competitive addition of the trifluoroacetoxy anion to the
corresponding thionium ione 13 (see Scheme 5). Finally,
the p-tolylsulfanyl group was reduced with Bu3SnH in the
presence of AIBN14 to give g-lactones 18 in high yields
(Scheme 6).
diastereomers); IR (neat) 2938, 1637 (CO), 1494, 1454,
1400, 1262, 1143, 1109, 1051 (SO), 895, 812, 787,
1
714 cmK1; H NMR d 1.65–1.75 (4H, m), 2.03–2.37 (4H,
m), 2.41 (3H, s), 2.79–3.35 (2H, m), 2.96, 3.09 (each 1.12H,
s, NCH3), 2.98, 3.08 (each 1.88H, s, NCH3), 3.95 (4H, s),
5.51 (0.38H, s), 5.80 (0.62H, s), 7.29 (2H, t, JZ8.1 Hz),
7.49 (0.8H, d, JZ8.1 Hz), 7.68 (1.2H, d, JZ8.1 Hz). MS
m/z (%) 413 (MC, 0.4), 360 (7), 334 (2), 329 (2), 274 (100),
238 (68), 211 (72), 182 (12), 149 (23), 99 (52), 72 (64).
Calcd for C20H28ClNO4S: M, 413.1427. Found: m/z
413.1425.
2.1.2. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclodecyl}-
N,N-dimethylacetamide (3b). Main product: colorless
oil; IR (neat) 2926, 1638 (CO), 1484, 1445, 1263, 1216,
1
1148, 1125, 1048 (SO), 1017, 811, 755 cmK1; H NMR d
1.59–2.27 (18H, m), 2.41 (3H, s), 2.49 (1H, d, JZ16.8 Hz),
2.96 (3H, s), 3.04 (3H, s), 3.22 (1H, d, JZ16.8 Hz), 5.90
(1H, s), 7.29, 7.70 (each 2H, d, JZ8.0 Hz). Minor product:
colorless oil; IR (neat) 2924, 1639 (CO), 1482, 1399, 1260,
Scheme 6. Reduction of the p-tolylsulfanyl group of 16 with Bu3SnH.
1
1088, 1060 (SO), 810, 754 cmK1; H NMR d 1.62–2.22
In conclusion, we have developed a novel and versatile
procedure for a synthesis of N,N-dimethylamides having
a tertiary or a quaternary carbon at the b-position from
1-chlorovinyl p-tolyl sulfoxides and N,N-dimethylaceta-
mide with carbon elongation. Pummerer-type cyclization
of the adducts 3, g-amido sulfoxides, was found to give
g-lactones and by this reaction a novel synthesis of
g-lactones having a tertiary and a quaternary carbon at the
b-position was realized.
(18H, m), 2.40 (3H, s), 2.70, 2.76 (each 1H, d, JZ16.8 Hz),
2.95 (3H, s), 3.08 (3H, s), 5.55 (1H, s), 7.31 (2H, d, JZ
8.0 Hz), 7.53 (2H, d, JZ8.0 Hz).
2.1.3. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclopenta-
decyl}-N,N-dimethylacetamide (3c). Main product: color-
less oil; IR (neat) 2927, 2856, 1644 (CO), 1494, 1461, 1398,
1
1265, 1141, 1084, 1052 (SO), 810, 787 cmK1; H NMR d
1.25–1.87 (28H, m), 2.41 (3H, s), 2.53 (1H, d, JZ16.8 Hz),
2.96 (3H, s), 3.05 (3H, s), 3.21 (1H, d, JZ16.8 Hz), 5.81
(1H, s), 7.29, 7.69 (each 2H, d, JZ8.3 Hz). MS m/z (%) 481
(MC, 0.3), 427 (4), 395 (2), 323 (100), 295 (100), 294 (100),
246 (42), 238 (18). Calcd for C27H44ClNO2S: M, 481.2781.
Found: m/z 481.2768. Minor product: colorless oil; IR (neat)
2928, 2857, 1640 (CO), 1494, 1460, 1399, 1263, 1141,
2. Experimental
2.1. General
All melting points are uncorrected. IR spectra were
measured with Perkin–Elmer Spectrum One FT-IR spec-
trometer. 1H NMR spectra were measured in a CDCl3
solution with JEOL JNM-LA 300 and 500 spectrometer.
Electron-impact mass spectra (MS) were obtained at 70 eV
by direct insertion. Silica gel 60 (Merck) containing 0.5%
fluorescence reagent 254 and a quartz column were used for
column chromatography and the products having UV
absorption were detected by UV irradiation. In experiments
requiring a dry reagent and solvent, N,N-diisopropylamine
and benzene were distilled from CaH2 and THF was
distilled from diphenylketyl. Acetone was dried over CaSO4
and distilled before use. 1-Chlorovinyl p-tolyl sulfoxides 2
used in this study were synthesized from the corresponding
ketones or aldehydes and chloromethyl p-tolyl sulfoxide as
reported before.4,5a
1
1089, 1061 (SO), 810, 754 cmK1; H NMR d 1.26–1.98
(28H m), 2.40 (3H, s), 2.69, 2.73 (each 1H, d, JZ17.1 Hz),
2.94 (3H, s), 3.07 (3H, s), 5.49 (1H, s), 7.31 (2H, d, JZ
8.0 Hz), 7.52 (2H, d, JZ8.0 Hz). MS m/z (%) 481 (MC,
0.15), 342 (100), 306 (61), 294 (12), 139 (8), 72 (64). Calcd
for C27H44ClNO2S: M, 481.2781. Found: m/z 481.2782.
2.1.4. 4-Chloro-N,N-dimethyl-3,3-diphenyl-4-(p-tolylsul-
finyl)butanamide (3d). Colorless crystals; mp 182–183 8C
(AcOEt–hexane); IR (KBr) 2924, 1626 (CO), 1493, 1444,
1
1058 (SO), 814, 707 cmK1; H NMR d 2.39 (3H, s), 2.41
(3H, s), 2.68 (3H, s), 3.30 (1H, d, JZ13.4 Hz), 4.61 (1H, br
d), 7.04 (1H, s), 7.21–7.24 (5H, m), 7.30 (2H, d, JZ8.3 Hz),
7.44–7.47 (3H, m), 7.66–7.68 (2H, m), 7.84 (2H, d, JZ
8.0 Hz). MS m/z (%) 439 (MC, 0.1), 422 (3) 353 (8), 300
(50), 264 (75), 253 (40), 234 (10), 191 (28), 178 (30), 139
(23), 115 (16), 91 (30), 72 (100). Calcd for C25H26ClNO2S:
M, 439.1373. Found: m/z 439.1369. Anal. Calcd for
C25H26ClNO2S: C, 68.24; H, 5.96; Cl, 8.06; N, 3.18; S,
7.29. Found: C, 67.92; H, 5.85; Cl, 7.97; N, 3.27; S, 7.24.
2.1.1. 2-{8-[Chloro(p-tolylsulfinyl)methyl]-1,4-dioxaspiro-
[4.5]dec-8-yl}-N,N-dimethylacetamide (3a). N,N-Di-
methylacetamide (0.39 ml; 4.0 mmol) was added to a
solution of LDA (4.0 mmol) in 4 ml of dry THF at
K78 8C with stirring. The solution was stirred for 10 min,
then a solution of 2a (262 mg; 0.8 mmol) in THF (4 ml) was
added. The solution was stirred for 5 min, then the reaction
was quenched by adding sat. aq. NH4Cl. The whole was
extracted with AcOEt–hexane (1:1). The product was
purified by silica gel column chromatography to afford 3a
(318 mg, 96%). Colorless oil (about 5:3 mixture of two
2.1.5. 4-Chloro-3,N,N-trimethyl-3-phenyl-4-(p-tolylsulfi-
nyl)butanamide (3e-a). Colorless crystals; mp 127–128 8C
(AcOEt–hexane); IR (KBr) 2923, 1619 (CO), 1495, 1399,
1088, 1054 (SO), 815, 707, 628 cmK1; 1H NMR d 2.04 (3H,
s), 2.41 (3H, s), 2.78 (3H, s), 2.85 (3H, s), 3.19, 3.23 (each
1H, d, JZ15.9 Hz), 5.80 (1H, s), 7.27–7.36 (5H, m), 7.51

11810
T. Satoh et al. / Tetrahedron 60 (2004) 11805–11812
(2H, d, JZ7.7 Hz), 7.77 (2H, d, JZ7.9 Hz). MS m/z (%)
377 (MC, 1), 360 (1.6), 341 (3), 324 (10), 291 (3), 279 (3),
238 (43), 218 (5), 202 (80), 190 (28), 139 (10), 129 (20), 91
(30), 72 (100). Calcd for C20H24ClNO2S: M, 377.1216.
Found: m/z 377.1208. Anal. Calcd for C20H24ClNO2S: C,
63.56; H, 6.40; Cl, 9.38; N, 3.71; S, 8.48. Found: C, 63.55;
H, 6.29; Cl, 9.31; N, 3.71; S, 8.39.
s), 2.64, 2.69 (each 1H, d, JZ16.5 Hz), 2.96 (3H, s), 3.04
(1H, d, JZ13.7 Hz), 3.08 (3H, s), 3.21 (1H, d, JZ13.5 Hz),
7.29, 7.57 (each 2H, d, JZ8.0 Hz). MS m/z (%) 377 (MC,
0.6), 360 (9), 291 (9), 274 (26), 238 (100), 139 (7), 109 (5),
87 (25), 72 (50). Calcd for C22H35NO2S: M, 377.2386.
Found: m/z 377.2378.
2.1.11. N,N-Dimethyl-2-{1-[(p-tolylsulfinyl)methyl]cyclo-
pentadecyl}acetamide (4c). Colorless oil; IR (neat) 2929,
2857, 1644 (CO), 1494, 1460, 1042 (SO), 812, 787,
2.1.6. 4-Chloro-3,N,N-trimethyl-3-phenyl-4-(p-tolylsulfi-
nyl)butanamide (3e-b). Colorless oil; IR (neat) 2925, 1639
(CO), 1495, 1399, 1084, 1051 (SO) cmK1; 1H NMR d 1.80
(3H, s), 2.40 (3H, s), 2.93 (1H, d, JZ16.2 Hz), 2.98 (6H, s),
3.95 (1H, d, JZ16.2 Hz), 7.27–7.37 (3H, m), 7.44 (2H, t,
JZ7.6 Hz), 7.67–7.74 (4H, m). MS m/z (%) 377 (MC, 0.3),
362 (0.4), 291 (4), 238 (22), 202 (30), 191 (15), 158 (5), 129
(18), 124 (17), 91 (40), 72 (100). Calcd for C20H24ClNO2S:
M, 377.1216. Found: m/z 377.1218.
1
756 cmK1; H NMR d 1.21–1.71 (28H, m), 2.40 (3H, s),
2.66, 2.72 (each 1H, d, JZ16.5 Hz) 2.96 (3H, s), 3.08 (3H,
s), 3.10, 3.21 (each 1H, d, JZ13.7 Hz), 7.29, 7.56 (each 2H,
d, JZ8.0 Hz). MS m/z (%) 447 (MC, 1), 430 (10), 344 (30),
308 (100), 306 (8), 137 (5), 124 (5), 87 (15), 72 (30). Calcd
for C27H45NO2S: M, 447.3171. Found: m/z 447.3168.
2.1.12. N,N-Dimethyl-2-(8-methyl-1,4-dioxaspiro[4.5]-
dec-8-yl)acetamide (5a). A solution of 4a (100 mg;
0.27 mmol) and excess of Raney Ni in EtOH was stirred
and refluxed for 1 h. The Raney Ni was filtered off, and the
filtrate was evaporated to give a residue, which was purified
by silica gel column chromatography to afford 5a (60.6 mg;
93%) as a colorless oil; IR (neat) 2931, 1638 (CO), 1509,
1397, 1246, 1101, 1036, 942 cmK1; 1H NMR d 1.09 (3H, s),
1.46–1.71 (8H, m), 2.30 (2H, s), 2.94 (3H, s), 3.04 (3H, s),
3.93 (4H, s). MS m/z (%) 241 (MC, 7), 226 (3), 196 (8), 179
(7), 154 (100), 139 (10), 99 (52), 87 (90), 72 (26). Calcd for
C13H23NO3: M, 241.1676. Found: m/z 241.1670.
2.1.7. 3-[Chloro(p-tolylsulfinyl)methyl]-N,N-dimethyl-5-
phenylpentanamide (3f). One of the four diastereomers
was isolated: colorless oil; IR (neat) 2927, 1645 (CO), 1495,
1
1455, 1400, 1052 (SO), 812, 753, 701 cmK1; H NMR d
1.71–1.79 (1H, m), 2.23–2.30 (1H, m), 2.42 (3H, s), 2.51
(1H, dd, JZ16.2, 9.8 Hz), 2.62 (1H, dd, JZ16.2, 5.2 Hz),
2.74–2.84 (2H, m), 2.92 (3H, s), 2.96 (3H, s), 3.20–3.22
(1H, m), 4.91 (1H, d, JZ2.2 Hz), 7.19–7.32 (7H, m), 7.70
(2H, d, JZ8.3 Hz). MS m/z (%) 391 (MC, 6), 374 (3), 337
(10), 305 (5), 252 (100), 215 (42), 129 (37), 91 (90), 72 (95),
65 (13). Calcd for C21H26ClNO2S: M, 391.1373. Found: m/z
391.1375.
2.1.13. N,N-Dimethyl-2-(1-methylcyclodecyl)acetamide
(5b). Colorless oil; IR (neat) 2928, 1644 (CO), 1483,
2.1.8. 4-Chloro-N,N-dimethyl-3-phenyl-4-(p-tolylsulfi-
nyl)butanamide (3g). Colorless oil (about 3:1 diastereo-
meric mixture); IR (neat) 2927, 1643 (CO), 1495, 1455,
1400, 1244, 1142, 1084, 1048 (SO), 1016, 813, 755,
1
1445, 1393, 1262, 1141 cmK1; H NMR d 0.99 (3H, s),
1.37–1.55 (18H, m), 2.21 (2H, s), 2.94 (3H, s), 3.04 (3H, s).
MS m/z (%) 239 (MC, 0.5), 224 (10), 88 (7), 87 (100), 72
(15), 45 (12). Calcd for C15H29NO: M, 239.2249. Found:
m/z 239.2252.
1
702 cmK1; H NMR d 2.41 (3H, s), 2.87 (0.75H, s), 2.90
(2.25H, s), 2.92–3.33 (3H, m), 3.04 (3H, s), 4.75 (0.75H, d,
JZ3.4 Hz), 5.30 (0.25H, d, JZ7.1 Hz), 7.28–7.63 (9H, m).
MS m/z (%) 363 (MC, trace), 224 (32), 188 (7), 160 (5), 140
(15), 115 (30), 91 (26), 72 (82). Calcd for C19H22ClNO2S.
M, 363.1060. Found: m/z 363.1057.
2.1.14. N,N-Dimethyl-2-(1-methylcyclopentadecyl)aceta-
mide (5c). Colorless oil; IR (neat) 2929, 2856, 1645 (CO),
1
1462, 1393, 1260, 1126, 806, 754 cmK1; H NMR d 1.0
(3H, s), 1.21–1.59 (28H, m), 2.22 (2H, s), 2.94 (3H, s), 3.03
(3H, s). MS m/z (%) 309 (MC, 3), 87 (100), 72 (12), 55 (6),
45 (6). Calcd for C20H39NO: M, 309.3032. Found: m/z
309.3026.
2.1.9. N,N-Dimethyl-2-{8-[(p-tolylsulfinyl)methyl]-1,4-
dioxaspiro[4.5]dec-8-yl}acetamide (4a). AIBN (37 mg;
0.23 mmol) was added to a solution of 3a (315 mg;
0.76 mmol) and Bu3SnH (0.31 ml; 1.14 mmol) in 15 ml of
benzene. The atmosphere in the flask was replaced with Ar,
and the reaction mixture was stirred and refluxed for 30 min.
The benzene was evaporated and the residue was purified by
silica gel column chromatography to give 4a (259 mg; 90%)
as a colorless oil; IR (neat) 2933, 1639 (CO), 1494, 1451,
2.1.15. N-Benzyl-2-{1-[chloro(p-tolylsulfinyl)methyl]-
cyclopentadecyl}-N-(4-methoxyphenyl)acetamide (8).
To a solution of acetyl chloride (1.27 mmol) in 13 ml of
CH2Cl2 was added a solution of N-benzyl p-anisidine
(213 mg; 1 mmol) in 1 ml of CH2Cl2 followed by Et3N
(2 mmol) and the solution was stirred at room temperature
for 1 h. The reaction was quenched by adding sat. aq. NH4Cl
and the whole was extracted with CH2Cl2. The product was
purified by silica gel column chromatography to afford 6
(255 mg; 99%). The amide 6 (646 mg; 2.5 mmol) in THF
(6.5 ml) was added to a solution of LDA (2.5 mmol) in
3.5 ml of dry THF at K78 8C with stirring. The solution was
stirred for 10 min, then a solution of 2c (198 mg; 0.5 mmol)
in THF (4 ml) was added. The solution was stirred for
15 min and the reaction was quenched by adding sat. aq.
NH4Cl. The whole was extracted with AcOEt. The product
was purified by silica gel column chromatography to afford
1398, 1275, 1104, 1037 (SO), 1016, 938, 906, 788 cmK1
;
1H NMR d 1.61–2.10 (8H, m), 2.40 (3H, s), 2.73, 2.79 (each
1H, d, JZ16.5 Hz), 2.96 (3H, s), 3.08 (3H, s), 3.21 (2H, s),
3.93 (4H, s), 7.30 (2H, d, JZ8.0 Hz), 7.54 (2H, d, JZ
8.0 Hz). MS m/z (%) 379 (MC, 0.6), 362 (20), 276 (8), 240
(97), 196 (12), 178 (3), 153 (12), 139 (5), 99 (10). Calcd for
C20H29NO4S: M, 379.1815. Found: m/z 379.1809.
2.1.10. N,N-Dimethyl-2-{1-[(p-tolylsulfinyl)methyl]cyclo-
decyl}acetamide (4b). Colorless oil; IR (neat) 2925, 2869,
1640 (CO), 1494, 1483, 1398, 1261, 1141, 1086, 1041 (SO),
1
812, 753 cmK1; H NMR d 1.25–1.85 (18H, m), 2.40 (3H,

T. Satoh et al. / Tetrahedron 60 (2004) 11805–11812
11811
8 (299 mg; 92%) as colorless crystals; mp 112–113 8C
(AcOEt–CH3CN); IR (KBr) 2928, 2855, 1651 (CO), 1511,
(35), 152 (15), 105 (40). Calcd for C23H20O2S: M,
360.1184. Found: m/z 360.1181.
1
1401, 1249, 1049 (SO), 837 cmK1; H NMR d 1.13–1.96
(28H, m), 2.24, 3.08 (each 1H, d, JZ17.1 Hz), 2.43 (3H, s),
3.80 (3H, s), 4.84 (2H, s), 6.02 (1H, s), 6.83, 6.94 (each 2H,
d, JZ8.3 Hz), 7.23–7.27 (5H, m), 7.30, 7.74 (each 2H, d,
JZ8.3 Hz). MS m/z (%) 650 ([MCH]C, 10), 510 (60), 474
(15), 437 (17), 255 (10), 213 (20), 212 (10), 122 (10), 91
(100). Calcd for C39H53ClNO3S: MCH, 650.3434. Found:
m/z 650.3436. Anal. Calcd for C39H52ClNO3S: C, 72.03; H,
8.06; Cl, 5.45; N, 2.15; S, 4.93. Found: C, 71.70; H, 8.14; Cl,
5.36; N, 2.16; S, 4.94.
2.1.19. 4-Methyl-4-phenyl-5-(p-tolylsulfanyl)dihydro-
furan-2-one (16e). Colorless oil (about 3:1 diastereomeric
mixture); IR (neat) 2925, 1790 (CO), 1495, 1445, 1195, 970,
1
700 cmK1; H NMR d 1.63 (2.3H, s), 1.64 (0.7H, s), 2.32
(0.7H, s), 2.33 (2.3H, s), 2.65, 3.19 (each 0.25H, d, JZ
16.8 Hz), 2.79, 3.05 (each 0.75H, d, JZ16.8 Hz), 5.78
(0.75H, s), 5.79 (0.25H, s), 7.10–7.49 (9H, m). MS m/z (%)
298 (MC, 50), 175 (100), 147 (8), 131 (67), 105 (57), 91
(45), 77 (20). Calcd for C18H18O2S: M, 298.1028. Found:
m/z 298.1030.
2.1.16. N-Benzyl-2-{1-[chloro(p-tolylsulfinyl)methyl]-
cyclopentadecyl}acetamide (9). A solution of CAN
(118 mg; 0.22 mmol) in 0.5 ml of water was added to a
solution of 8 (70 mg; 0.11 mmol) in 1.35 ml CH3CH2CN at
room temperature and the reaction mixture was stirred for
five days at room temperature. The reaction was quenched
by adding sat. aq. NaHCO3 at 0 8C follwed by Na2SO3
(41 mg; 0.33 mmol). The suspension was filtered through a
celite pad. The whole was extracted with AcOEt. The
product was purified by silica gel column chromatography
to afford 9 (8.1 mg; 14%) as an orange oil; IR (neat) 3326
(NH), 2928, 2856, 1651 (CO), 1542, 1458, 1041 (SO),
2.1.20. N,N-Dimethyl-3-formyl-5-phenylpentanamide
(17f). Colorless oil; IR (neat) 2926, 2855, 1718 (CHO),
1638 (CO), 1509, 1455, 1400, 1243, 1145, 749, 701 cmK1
;
1H NMR d 1.76–1.83 (1H, m), 2.05–2.13 (1H, m), 2.44 (1H,
dd, JZ16.5, 4.9 Hz), 2.65–2.72 (2H, m), 2.78 (1H, dd, JZ
16.5, 8.3 Hz), 2.93 (3H, s), 3.01 (3H, s), 7.18–7.21 (3H, m),
7.27–7.30 (2H, m), 9.81 (1H, s). MS m/z (%) 233 (MC, 3),
205 (8), 204 (8), 165 (18), 129 (100), 114 (38), 91 (58), 72
(78), 65 (10). Calcd for C14H19NO2: M, 233.1418, Found:
m/z 233.1407.
1
810 cmK1; H NMR d 1.20–1.99 (28H, m), 2.40 (3H, s),
2.1.21. 4-Phenyl-5-(p-tolylsulfanyl)dihydrofuran-2-one
(16g). Colorless oil (about 5:1 diastereomeric mixture); IR
(neat) 2922, 1774 (CO), 1490, 1456, 1410, 1288, 1245,
2.43 (1H, d, JZ5.2 Hz), 2.50, 3.09 (each 1H, d, JZ
13.8 Hz), 4.45 (1H, dd, JZ14.7, 5.8 Hz), 4.52 (1H, dd, JZ
14.7, 5.8 Hz), 4.91 (1H, s), 7.18–7.38 (7H, m), 7.43 (2H, d,
JZ8.0 Hz). MS m/z (%) 543 (MC, trace), 385 (36), 368
(23), 136 (12), 91 (100). Calcd for C32H46ClNO2S: M,
543.2938. Found: m/z 543.2941.
1
1177, 1149, 947, 921, 830, 698 cmK1; H NMR d 2.32
(0.5H, s), 2.35 (2.5H, s), 2.72 (1H, dd, JZ17.7, 7.9 Hz),
2.89 (1H, dd, JZ17.7, 9.3 Hz), 3.58 (0.83H, m), 4.09
(0.17H, m), 5.63 (0.83H, d, JZ6.8 Hz), 6.03 (0.17H, JZ
6.7 Hz), 7.10–7.43 (9H, m). MS m/z (%) 284 (MC, 41), 161
(100), 160 (7), 124 (47), 105 (62), 91 (58), 77 (30), 65 (10).
Calcd for C17H16O2S: M, 284.0872. Found: m/z 284.0862.
2.1.17. 2-(1-Formylcyclopentadecyl)-N,N-dimethylaceta-
mide (17c). A solution of NaI (110 mg; 0.73 mmol) in
7.5 ml of dry acetone was stirred for 15 min at K55 8C.
TFAA (0.103 ml; 0.73 mmol) was added dropwise to a
solution of NaI with stirring at K55 8C and the solution was
stirred for 15 min. The adduct 3c (70 mg; 0.15 mmol) in
1.5 ml of dry acetone was added dropwise to the suspention
of NaI and TFAA at K55 8C dropwise with stirring and the
reaction mixture was stirred for 10 min. The reaction
mixture turned from light yellow to black green in color.
The reaction was quenched by adding sat. aq. NaHCO3
followed by sat. aq. Na2SO3. The whole was extracted with
ether–benzene. The organic layer was washed with sat. aq.
NaHCO3 and dried over MgSO4. The solvent was
evaporated and the residue was purified by silica gel
column chromatography to give 11 (50 mg; 85%) and the
aldehyde 17c (6.1 mg; 13%). 17c: colorless oil; IR (neat)
2930, 2858, 1722 (CHO), 1638 (CO), 1461, 1402, 1216,
2.1.22. N,N-Dimethyl-4-oxo-3-phenylbutanamide (17g).
Colorless oil; IR (neat) 2924, 1722 (CO), 1645, 1494, 1408,
1
1264, 1149, 879, 759 cmK1; H NMR d 2.54 (1H, dd, JZ
16.5, 4.9 Hz), 2.94 (3H, s), 3.01 (3H, s), 3.25 (1H, dd, JZ
16.5, 8.9 Hz), 4.36 (1H, dd, JZ8.9, 4.9 Hz), 7.22–7.38 (5H,
m), 9.79 (1H, s). MS m/z (%) 205 (MC, 7), 191 (35), 177
(100), 176 (7), 147 (12), 131 (11), 120 (10), 105 (58), 104
(36), 72 (90). Calcd for C12H15NO2: M, 205.1103. Found:
m/z 205.1099.
2.1.23. 4,4-Diphenyldihydrofuran-2-one (18d). AIBN
(16 mg; 0.1 mmol) was added to a solution of 16d (36 mg;
0.1 mmol) and Bu3SnH (0.11 ml; 0.4 mmol) in 10 ml of
benzene. The atmosphere in the flask was replaced with Ar
and the reaction mixture was stirred and refluxed for 2 h.
The benzene was evaporated and the residue was purified by
silica gel column chromatography to give 18d (23.6 mg;
99%) as colorless crystals; mp 105–106 8C (AcOEt–
hexane); IR (KBr) 2964, 1781 (CO), 1177, 1022,
1
757 cmK1; H NMR d 1.17–1.69 (28H, m), 2.61 (2H, s),
2.91 (3H, s), 3.01 (3H, s), 9.68 (1H, s). MS m/z (%) 323
(MC, 25), 294 (42), 279 (15), 252 (15), 238 (7), 224 (5), 196
(7), 168 (9), 140 (12), 127 (15), 95 (7), 87 (100), 72 (57).
Calcd for C20H37NO2: M, 323.2824. Found: m/z 323.2820.
1
700 cmK1; H NMR d 3.20 (2H, s), 4.84 (2H, s), 7.16–
7.36 (10H, m). MS m/z (%) 238 (MC, 28), 180 (100), 165
(40), 89 (15), 77 (10). Calcd for C16H14O2: M, 238.0992.
Found: m/z 238.0986. Anal. Calcd for C16H14O2: C, 80.65;
H, 5.92. Found: C, 80.43; H, 5.65.
2.1.18. 4,4-Diphenyl-5-(p-tolylsulfanyl)dihydrofuran-2-
one (16d). Colorless oil; IR (neat) 2924, 1790 (CO), 1494,
1447, 1171, 953, 699 cmK1; 1H NMR d 2.35 (3H, s), 3.12,
3.56 (each 1H, d, JZ16.8 Hz), 6.34 (1H, s), 7.13–7.16 (4H,
m), 7.28–7.37 (8H, m), 7.43 (2H, d, JZ8.2 Hz). MS m/z (%)
360 (MC, 25), 237 (100), 219 (30), 191 (10), 180 (50), 165
2.1.24. 4-Methyl-4-phenyldihydrofuran-2-one (18e).
Colorless oil; IR (neat) 2965, 1778 (CO), 1170, 1022,

11812
T. Satoh et al. / Tetrahedron 60 (2004) 11805–11812
1
766, 702 cmK1; H NMR d 1.53 (3H, s), 2.68, 2.92 (each
1H, d, JZ16.8 Hz), 4.42, 4.43 (each 1H, d, JZ8.9 Hz),
7.18–7.40 (5H, m). MS m/z (%) 176 (MC, 20), 118 (100),
103 (13), 91 (11), 78 (9), 51 (7). Calcd for C11H12O2: M,
176.0837. Found: m/z 176.0837.
1997. (d) Davies, S. G.; Ichihara, O. J. Syn. Org. Chem. Jpn
1997, 55, 26. (e) Palomo, C.; Aizpurua, J. M.; Ganboa, I.;
Oiarbide, M. Synlett 2001, 1813. (f) Liu, M.; Sibi, M. P.
Tetrahedron 2002, 58, 7991.
4. Satoh, T.; Sugiyama, S.; Kamide, Y.; Ota, H. Tetrahedron
2003, 59, 4327.
2.1.25. 4-Phenyldihydrofuran-2-one (18g). Colorless
crystals; mp 40–41 8C (AcOEt–hexane); IR (KBr) 2904,
5. Some recent papers for the new synthetic methods by using
1-chlorovinyl p-tolyl sulfoxides: (a) Satoh, T.; Ota, H.
Tetrahedron 2000, 56, 5113. (b) Satoh, T.; Yoshida, M.;
Ota, H. Tetrahedron Lett. 2001, 42, 9241. (c) Satoh, T.;
Sakamoto, T.; Watanabe, M. Tetrahedron Lett. 2002, 43, 2043.
(d) Satoh, T.; Sugiyama, S.; Ota, H. Tetrahedron Lett. 2002,
43, 3033. (e) Satoh, T.; Yoshida, M.; Takahashi, Y.; Ota, H.
Tetrahedron: Asymmetry 2003, 14, 281. (f) Satoh, T.;
Wakasugi, D. Tetrahedron Lett. 2003, 44, 7517. (g) Ota, H.;
Chyouma, T.; Iso, S.; Satoh, T. Tetrahedron Lett. 2004, 45,
3903. (h) Satoh, T.; Ogino, Y.; Nakamura, M. Tetrahedron
Lett. 2004, 45, 5785.
1
1764 (CO), 1457, 1355, 1164, 1011, 761, 703 cmK1; H
NMR d 2.68 (1H, dd, JZ17.4, 9.2 Hz), 2.93 (1H, dd, JZ
17.4, 8.8 Hz), 3.79 (1H, m), 4.27, 4.67 (each 1H, t, JZ
8.9 Hz), 7.23–7.39 (5H, m). MS m/z (%) 162 (MC, 27), 104
(100), 91 (7), 78 (12), 51 (10), 28 (32). Calcd for C10H10O2:
M, 162.0680. Found: m/z 162.0681. Anal. Calcd for
C10H10O2: C, 74.06; H, 6.21. Found: C, 73.75; H, 6.20.
Acknowledgements
6. An account for the new synthetic method by using 1-chloro-
vinyl aryl sulfoxides: Satoh, T. Chem. Record 2004, 3, 329.
7. (a) Satoh, T.; Takano, K.; Ota, H.; Someya, H.; Matsuda, K.;
Koyama, M. Tetrahedron 1998, 54, 5557. (b) Satoh, T.;
Kawashima, T.; Takahashi, S.; Sakai, K. Tetrahedron 2003,
59, 9599.
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan, which is gratefully
acknowledged.
8. (a) Ramaiah, M. Tetrahedron 1987, 43, 3541. (b) Satoh, T.;
Sato, T.; Oohara, T.; Yamakawa, K. J. Org. Chem. 1989, 54,
3973.
References and notes
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amides, lactones, and their derivatives: (a) Patai, S. The
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Tetrahedron 1999, 55, 3025. (c) Fustero, S.; Pina, B.; Garcia
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(e) Sano, S. Yakugaku Zasshi 2000, 120, 28. (f) Sano, S.;
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C.; Diaz-de-Villegas, M. D. Tetrahedron: Asymmetry 2000,
11, 645. (h) Beller, M.; Eckert, M. Angew. Chem., Int. Ed.
2000, 39, 1010.
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1 1989, 1201.
13. (a) Block, E. Reaction of Organosulfur Compounds;
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A.; Gunn, D. E.; Osterhout, M. H. Synthesis, 1353.
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14. (a) Gutierrez, C. G.; Stringham, R. A.; Nitasaka, T.;
Glasscock, K. G. J. Org. Chem. 1980, 45, 3393. (b) Gutierrez,
C. G.; Summerhays, L. R. J. Org. Chem. 1984, 49, 5206.
(c) Watanabe, Y.; Araki, T.; Ueno, Y.; Endo, T. Tetrahedron
Lett. 1986, 27, 5385. (d) Satoh, T.; Kubota, K. Tetrahedron
Lett. 2000, 41, 2121.
3. Recent monograph and reviews for the chemistry and
synthesis of b-amino acids: (a) Cole, D. C. Tetrahedron
1994, 50, 9517. (b) Juaristi, E.; Quintana, D.; Escalante, J.
Aldrichimica Acta 1994, 27, 3. (c) Enantioselective Synthesis
of b-Amino Acids; Juaristi, E., Ed.; Wiley-VCH: New York,