A novel synthesis, including asymmetric synthesis, of 2,4,4-trisubstituted 2-cyclopentenones based on the reaction of 1-chlorovinyl p-tolyl sulfoxides with acetonitrile and its homologues

Article abstract of DOI:10.1016/j.tet.2004.11.040

Reaction of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from chloromethyl p-tolyl sulfoxide and ketones in high overall yields, with cyanomethyllithium (lithium α-carbanion of acetonitrile) gave adducts in high to quantitative yields. The add

Full text of DOI:10.1016/j.tet.2004.11.040

Tetrahedron 61 (2005) 1245–1256
A novel synthesis, including asymmetric synthesis,
of 2,4,4-trisubstituted 2-cyclopentenones based on the reaction
of 1-chlorovinyl p-tolyl sulfoxides with acetonitrile
and its homologues
*
Daisuke Wakasugi and Tsuyoshi Satoh
Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Received 8 September 2004; accepted 11 November 2004
Available online 8 December 2004
Abstract—Reaction of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from chloromethyl p-tolyl sulfoxide and ketones in high
overall yields, with cyanomethyllithium (lithium a-carbanion of acetonitrile) gave adducts in high to quantitative yields. The adducts were
treated with LDA followed by lithium a-carbanion of the homologues of acetonitrile to give 3,5,5-trisubstituted enaminonitriles in good to
high yields. Hydrolysis of the enaminonitriles under acidic conditions gave 2,4,4-trisubstituted 2-cyclopentenones in good yields. By using
the optically active chloromethyl p-tolyl sulfoxide and unsymmetrical ketones, this procedure gave the optically pure 2,4,4-trisubstituted
2-cyclopentenones. 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 2,4,4-trisubstituted 2-cyclopentenones from four components, ketones, chloromethyl p-tolyl
sulfoxide, acetonitrile, and its homologues.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Recently, we reported a reaction of 1-chlorovinyl p-tolyl
sulfoxides 2, derived from ketones 1 and chloromethyl
p-tolyl sulfoxide in three steps, with cyanomethyllithium to
give 5,5-disubstituted enaminonitrile 3 in high to quanti-
tative yield.5 Acidic hydrolysis of 3 gave 4,4-disubstituted
2-cyclopentenones 4 in good yield (Scheme 1). Further,
when unsymmetrical ketones and optically active chloro-
methyl p-tolyl sulfoxide were used in this procedure, an
asymmetric synthesis of optically pure 4,4-disubstituted
2-cyclopentenones 4 was realized.6
The cyclopentane, including cyclopentanone and cyclo-
pentenone, ring system is among the most widely found
structures in natural compounds, especially in cyclopenta-
noid natural products.1 2-Cyclopentenones are undoubtedly
one of the most versatile intermediates in the synthesis of
cyclopentanes, because, the 3- and 5-positions of the
2-cyclopentenones are quite easily modified by a general
method, for example, 1,4-addition of the enone system and
aldol-type reaction, respectively. However, modification of
the 2-position of the 2-cyclopentenones has been recognized
to be relatively difficult.2 In view of the importance of
2-cyclopentenones in organic synthesis, several methods
such as the Nazarov cyclization3 and the Pauson–Khand
reaction4 have been reported.
Considering the usefulness of this procedure in the synthesis
of 4,4-disubstitued 2-cyclopentenones and the proposed
mechanism of the reaction from 2 to 3,5 we anticipated that
if we used several kinds of nitriles other than acetonitrile in
this reaction, highly substituted 2-cyclopentenones could be
Scheme 1.
Keywords: 2-Cyclopentenone; 2,4,4-Trisubstituted 2-cyclopentenone; Conjugate addition; Sulfoxide; Asymmetric synthesis.
* 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.2004.11.040

1246
D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
Scheme 2.
obtained. We investigated the reaction of 1-chlorovinyl
p-tolyl sulfoxides 2 with several lithium a-carbanion of
nitriles and found a quite versatile method for synthesis of
3,5,5-trisubstituted enaminonitriles 7 and 2,4,4-trisubsti-
tuted 2-cyclopentenones 8. The whole sequence is shown in
Scheme 2. Thus, the vinyl sulfoxides 2 was first treated with
cyanomethyllithium at K78 8C to give the adducts 5, which
were treated with LDA followed by the lithium a-carbanion
of the homologues of acetonitrile to afford 3,5,5-trisubsti-
tuted enaminonitriles 7. The enaminonitriles were hydro-
lyzed to give 2,4,4-trisubstituted 2-cyclopentenones 8 in
good to high yields. Herein we describe the details of this
investigation and the application of this procedure to an
asymmetric synthesis of optically active 2,4,4-trisubstituted
2-cyclopentenones.7
2c with lithium carbanion of propionitrile. We anticipated a
product like 9 if the expected reaction worked (Scheme 3).
Thus, 5 equiv of lithium a-carbanion of propionitrile was
generated from propionitrile and n-butyllithium in THF at
K78 8C. In this solution, a solution of 2c in THF was added
and the temperature of the reaction mixture was slowly
allowed to warm to room temperature. However, only a
complex mixture was obtained.
Next, to a solution of 3 equiv of lithium a-carbanion of
propionitrile was added a solution of 2c at K78 8C. The
reaction was quenched with water after 10 min to give the
adduct 10 in 91% yield.5b The adduct was treated with
3 equiv of LDA at K78 8C and to the solution was added a
solution of 4 equiv of cyanomethyllithium. The reaction
mixture was stirred and allowed to warm to room
temperature. We anticipated a product like 11 in this
treatment; however, we obtained a rather complex mixture
with 27% of the enaminonitrile 3a.
2. Results and discussion
2.1. The reaction of lithium a-carbanion of acetonitrile
and propionitrile with 1-chlorovinyl p-tolyl sulfoxides
This rather unexpected result was explained as follows.
Treatment of 10 with LDA afforded a-sulfinyl carbanion of
10, from which the lithium a-carbanion of propionitrile was
eliminated to give the vinyl sulfoxide 2c. The cyanomethyl-
lithium in the reaction mixture reacted with 2c to give the
enaminonitrile 3a.5
As the substrate used in this investigation we selected three
1-chlorovinyl p-tolyl sulfoxides 2a–c and synthesized them
from the corresponding ketones and chloromethyl p-tolyl
sulfoxide (see Table 1).5,6 First, we studied the reaction of
Table 1. Synthesis of 3,5,5-trisubstituted enaminoitriles 7 and 2,4,4-trisubstituted 2- cyclopentenones 8 from the vinyl sulfoxides 2 by the reaction with
acetonitrile followed by the homologues of acetonitrile
Entry
Vinyl sulfoxide 2
R2
Adduct 5
R3
Examinonitrile 7
2-Cyclopentenone 8
R1
Yield/%
Yield/%
Yield/%
1
2
3
5aa
5bb
97
99
CH3
7a
7b
7c
80
76
76
8a
8b
8cc
93
83
87
2a
CH3CH2
CH3
2b
4
5
6
CH3CH2
CH3
CH3CH2
7d
7e
7f
75
62
55
8dc
8e
89
74
72
2c Ph
Ph
5cd
93
8f
a The adduct 5a was 3:1 mixture of two diastereomers.
b The adduct 5b was a 7:3 mixture of two diastereomers.
c
d The adduct 5c was a 13:3 mixture of two diastereomers.

D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
1247
Scheme 3.
2.2. Consecutive reaction of 1-chlorovinyl p-tolyl
sulfoxides with cyanomethyllithium and lithium
a-carbanion of the homologues of acetonitrile.7
in 93% yield (Table 1, entry 1). The same reaction of 5a
with butyronitrile was carried out. As shown in Table 1,
entry 2, the reaction of 5a with lithium a-carbanion of
butyronitrile gave 7b in 76% yield, which was hydrolyzed to
afford 8b in somewhat lower yield compared with the yield
in entry 1.
Finally, we tried the reaction shown in Table 1. 1-Chloro-
vinyl p-tolyl sulfoxide 2a, derived from cyclopentadeca-
none, was treated with 3 equiv of cyanomethyllithium at
K78 8C for 10 min to give the adduct 5a in 97% yield as a
3:1 mixture of two diastereomers (Table 1, entry 1). A
diastereomeric mixture of the adduct 5a was treated with
3 equiv of LDA followed by lithium a-carbanion of
propionitrile and the reaction mixture was stirred and
slowly allowed to warm to room temperature. Fortunately,
this reaction gave the desired 3,5,5-trisubstituted enamino-
nitrile 7a in 80% yield as colorless crystals.
To ascertain the generality of this procedure, we investi-
gated the reaction with other 1-chlorovinyl p-tolyl sulf-
oxides 2b and 2c with propionitrile and butyronitrile. The
results are summarized in Table 1, entries 3–6. The addition
reaction of 2b and 2c with cyanomethyllithium gave almost
quantitative yields of 5b and 5c, respectively. In the next
two steps, similar results were obtained with the adduct 5b
(entries 3 and 4). However, the reactions starting from the
adduct 5c (entries 5 and 6) showed somewhat lower yields
of the enaminonitrile (7e and 7f) and the 2-substituted
2-cyclopentenone (8e and 8f). In any event, generality of
this procedure was confirmed from the results described
above.
The presumed mechanism of this reaction is as follows
(Scheme 4). Treatment of the adduct 5a with 3 equiv of
LDA afforded the lithium a-sulfinyl carbanion 12. Upon
warming the reaction mixture, a-elimination of LiCl took
place to give a-sulfinyl carbenoid 13. Addition of lithium
a-carbanion of propionitrile to the electrophilic carbon of
the carbenoid 13 resulted in the formation of the dinitrile 14.
Finally, the Thorpe–Ziegler reaction8 of the dinitrile 14 with
concomitant elimination of the p-tolylsulfinyl group took
place to afford the enaminonitrile 7a.
2.3. Investigation of the scope and limitation of the
nitriles (R3CH2CN) used in this procedure
As described above, this procedure is quite a good way
for the synthesis of 2,4,4-trisubstituted 2-cyclopentenones. It
is interesting to investigate what kind of substituents could be
introduced at the 2-position. We studied this procedure with
heptanenitrile, isovaleronitrile, 3,3,3-triphenylpropionitrile,9
The enaminonitrile 7a was heated under reflux in acetic acid
containing H3PO4 and a small amount of water for 30 h to
afford the desired 2,4,4-trisubstituted 2-cyclopentenone 8a
Scheme 4.

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D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
Table 2. Synthesis of 3,5,5-trisubstituted enaminonitriles 7 and 2,4,4-trisubstituted 2-cyclopentenones 8 from the adducts 5 and the homologues of acetonitrile
Entry
Adduct 5 R3CH3CN
Enaminonitrile 7
2,4,4-Trisubstituted 2-cyclopentenone 8
Yield/%
Yield/%
1
5a
C6H13CN
7g
72
8g
87
2
3
5a
5a
(CH3)2CHCH2CN
7h
7i
79
46
8h
8i
91
51
Ph3CCH2CN
4
5
5a
5a
CH3CH]CHCH2CN
7j
76
64
8j
33
93
7k
8k
6
7
5b
5b
Ph3CCH2CN
7l
78
90
8l
89
99
7m
8m
8
9
5c
5c
Ph3CCH2CN
Complex mixture
—
CH3CH]CHCH2CN
7n
81
8n
8o
61
62
10
5c
7o
91
trans-3-pentenenitrile, and (4-methoxyphenyl)acetonitrile
and the results are summarized in Table 2.
rather complex reaction mixture and only 33% of the
2-cyclopentenone 8j could be obtained. Acetonitrile having
an aromatic group could be used in this reaction and the
2-cyclopentenone directly combined with the aromatic ring
at the 2-position 8k could be obtained in good overall yield
(entry 5).
As shown in Table 2, entries 1–5, the reaction of the adduct
5a with the five nitriles mentioned above gave the desired
enaminonitriles 7g–k in variable yields (46–79%). The
acidic hydrolysis of 7g–k gave the enones 8g–k,
respectively, in good to high yields except 8j. Long-chain
and branched-chain hydrocarbons were placed on the
2-position in good overall yields (entries 1 and 2).
2-Cyclopentenone having a quite bulky substituent (tri-
phenylmethyl group) 8i was also synthesized by this
procedure though the overall yield was not satisfactory
(entry 3). The enaminonitrile having an unsaturated carbon
chain on the 2-position, 7j, could be synthesized without
problem (entry 4); however, the acidic hydrolysis gave a
Entries 6 and 7 show the results of the reaction of 5b with
3,3,3-triphenylpropionitrile and (4-methoxyphenyl)aceto-
nitrile. The desired enones 8l and 8m were obtained in
high overall yields. Entries 8–10 show the results of the
reaction of 5c with 3,3,3-triphenylpropionitrile, trans-3-
pentenenitrile, and (4-methoxyphenyl)acetonitrile. Interest-
ingly, the reaction of 5c with 3,3,3-triphenylpropionitrile
only gave a complex mixture (entry 8). Two other reactions
gave the desired enones 8n and 8o in moderate overall yields.

D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
1249
2.4. Synthesis of 2-(3-hydroxypropyl)-4,4-dimethyl-2-
cyclopentenone from acetone by this procedure
2.5. Asymmetric synthesis of optically active 3,5,5-
trisubstituted enaminonitriles and 2,4,4-trisubstituted
2-cyclopentenones
Many cyclopentanoid natural products have geminal methyl
groups on the cyclopentane ring.1 As an application of our
method described above, we planned to synthesize 2-(3-
hydroxypropyl)-4,4-dimethyl-2-cyclopentenone 8q, which
was reported to be an intermediate in the total synthesis of
alliacolide,10 from acetone (Scheme 5).
We previously reported an asymmetric synthesis of 4,4-
disubstituted 2-pentenones 4 from the optically active
1-chlorovinyl p-tolyl sulfoxides 2 via the optically active
enaminonitriles 3 (Scheme 1).6 As an extension of our new
synthetic method described above, we investigated the
feasibility for the asymmetric synthesis of the 2,4,4-
trisubstituted 2-cyclopentenones (Scheme 6).
1-Chlorovinyl p-tolyl sulfoxide 2d was synthesized from
acetone in high overall yield.5b The vinyl sulfoxide 2d was
treated with cyanomethyllithium to give the adduct 5d in
quantitative yield as a 17:4 mixture of two diastereomers.
First, 5d was treated with 3 equiv of LDA followed by the
dianion of 5-hydroxypentanenitrile under the conditions
described above. The desired enaminonitrile bearing a
3-hydroxypropyl group at the 3-position 7p was obtained;
however, the yield was not satisfactory. The presence of the
free hydroxyl group in the reaction was thought to be the
reason for the lowered yield.
Optically pure E-1-chloro-1-hexenyl p-tolyl sulfoxide 15a
and its Z-isomer 15b were synthesized from 2-hexanone and
(R)-chloromethyl p-tolyl sulfoxide11 as reported before.6b
First, 15a was treated with cyanomethyllithium at K78 8C
for 10 min to afford the adduct 16a as a 17:4 mixture of two
diastereomers. These diastereomers could be separated by
column chromatography and from the 1H NMR spectrum of
each diastereomers, they were found to be diastereomeri-
cally pure. The diastereomers are thought to be based on the
two chiral carbons. This meant that the diastereomeric
excess of these isomers was over 99%.
Next, O-protected 5-hydroxypentanenitrile was reacted with
5d under the same conditions described above. As expected,
the desired enaminonitrile 7q was obtained in quantitative
yield. Finally, 7q was heated under reflux in acetic acid
containing H3PO4 and water. We obtained the desired 2-(3-
hydroxypropyl)-4,4-dimethyl-2-cyclopentenone 8q; how-
ever, the main product was found to be the acetate 8p.
The acetate 8p was transformed, in the usual manner, to
give the alcohol 8q in a quantitative yield. As a whole, the
desired 8q10 was obtained from 7q in 77% yield.
Next, a mixture of the adduct 16a was treated with 3 equiv
of LDA at K78 8C followed by lithium a-carbanion of
propionitrile in a similar manner described above. This
reaction gave optically active 17a as an oil in 72% yield. We
measured the optical purity of the product using HPLC with
CHIRALCEL OD and found that it was over 99%. As the
stereochemistry of the asymmetric induction of the reaction
of the vinyl sulfoxides 15 and cyanomethyllithium was
Scheme 5.

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D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
Scheme 6.
Table 3. Synthesis of optically 3,5,5-trisubstituted cyclopentadienyl enaminonitriles 17 from the optically active adduct 16 with lithium a-carbanion of
heptanenitrile and isovaleronitrile
Entry
Adduct 16
Nitrile
Enaminonitrile 17
Yield/%
Enantiomeric
excess/% eea
1
16a
C6H13CN
17c
17d
88
98
99
2
3
16b
16a
C6H13CN
81
83
(CH3)2CHCH2CN
17e
O99
O99
4
16b
(CH3)2CHCH2CN
17f
89
a The enantiomeric excess was measured by using HPLC with CHIRALCEL OD (hexane/2-propanolZ20:1).

D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
1251
already established by our previous work,6b the absolute
configuration of 17a is R. Finally, the optically active 17a
was treated in the acidic media to give optically pure (S)-4-
butyl-2,4-dimethyl-2-cyclopentenone 18a in 81% yield
([a]3D0ZK46.7).
17.1 Hz), 4.56 (1H, s), 7.35, 7.74 (each 2H, d, JZ8.3 Hz).
MS m/z (%) 435 (MC, 1.4), 419 (1.8), 385 (4), 296 (4), 260
(7), 248 (5), 141 (9), 140 (100), 139 (10). Calcd for
C25H38ClNOS: M, 435.2363. Found: m/z 435.2376.
Compound 5a-P. IR (neat) 2929, 2858, 2242 (CN), 1461,
1
In a similar way, the addition reaction of 15b with
cyanomethyllithium gave the adduct 16b as a 7:2 mixture
of two diastereomers with 99% diastereomeric excess. From
16b the enaminonitrile 17b and the optically pure (R)-4-
butyl-2,4-dimethyl-2-cyclopentenone 18b (the enantiomer
of 18a) were synthesized in similar chemical yields. The
specific rotation of 18b showed C43.4.
1089, 1060 (SO), 811, 756 cmK1; H NMR d 1.31–1.59
(24H, m), 1.76–1.79 (2H, m), 1.88–1.98 (2H, m), 2.44 (3H,
s), 2.80, 2.85 (each 1H, d, JZ17.1 Hz), 4.26 (1H, s), 7.36,
7.48 (each 2H, d, JZ8.3 Hz). MS m/z (%) 435 (MC, 1.5),
419 (2.2), 385 (7), 296 (4), 260 (7), 248 (4), 221 (4), 140
(100), 139 (10). Calcd for C25H38ClNOS: M, 435.2363.
Found: m/z 435.2372.
Table 3 shows the results for the asymmetric synthesis of
optically active enaminonitriles 17c–f from 16a and 16b
with hexanenitrile and isovaleronitrile. As shown in the
table, both enantiomers of the enaminonitriles were
obtained in 81–89% yield with over 98% enantiomeric
excess. These results show that the procedure described
above is a quite versatile and reliable method for the
preparation of optically active 2,4,4-trisubstituted
2-cyclopentenones.
3.1.2. {8-[Chloro(p-tolylsulfinyl)methyl]-1,4-dioxaspiro-
[4.5]dec-8-yl}acetonitrile (5b). Compound 5b-L. Colorless
crystals, mp 110–111 8C (AcOEt–hexane); IR (KBr) 2948,
2881, 2243 (CN), 1454, 1107, 1082, 1053 (SO), 813,
1
503 cmK1; H NMR d 1.61–1.79 (4H, m), 1.85–1.88 (1H,
m), 2.01–2.05 (1H, m), 2.25–2.31 (1H, m), 2.36–2.41 (1H,
m), 2.44 (3H, s), 2.90, 3.46 (each 1H, d, JZ17.1 Hz), 3.96
(4H, s), 4.69 (1H, s), 7.35, 7.75 (each 2H, d, JZ8.3 Hz). MS
m/z (%) 367 (MC, 11), 230 (32), 228 (100), 200 (16), 192
(49), 184 (40), 148 (26), 140 (66), 139 (35), 120 (16). Anal.
Calcd for C18H22ClNO3S: C, 58.77; H, 6.03; Cl, 9.64; N,
3.81; S, 8.72%. Found: C, 58.80; H, 5.78; Cl, 9.55; N, 3.74;
S, 8.70%.
3. Experimental
3.1. General
Compound 5b-P. Colorless crystals, mp 166–167 8C
(AcOEt–hexane); IR (KBr) 2940, 2897, 2239 (CN), 1114,
1
All melting points are uncorrected. H NMR spectra were
1
1085, 1053 (SO), 820, 515 cmK1; H NMR d 1.67–2.20
measured in a CDCl3 solution with JEOL JNM-LA 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, diisopropylamine was 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 and chloromethyl p-tolyl sulfoxide
as reported before.5,6
(6H, m), 2.32–2.42 (2H, m), 2.44 (3H, s), 2.90, 2.99 (each
1H, d, JZ17.4 Hz), 3.97 (4H, s), 4.48 (1H, s), 7.36, 7.48
(each 2H, d, JZ8.2 Hz). MS m/z (%) 367 (MC, 15), 230
(32), 228 (100), 192 (61), 184 (38), 148 (30), 140 (68), 139
(34), 120 (16). Anal. Calcd for C18H22ClNO3S: C, 58.77; H,
6.03; Cl, 9.64; N, 3.81; S, 8.72%. Found: C, 58.77; H, 5.91;
Cl, 9.55; N, 3.73; S, 8.72%.
3.1.3. 4-Chloro-3,3-diphenyl-4-(p-tolylsulfinyl)butyro-
nitrile (5c). Compound 5c-L. Colorless crystals, mp 198–
199 8C (AcOEt–hexane); IR (KBr) 2950, 2926, 2247 (CN),
1595, 1494, 1443, 1083, 1051 (SO), 705 cmK1; 1H NMR d
2.44 (3H, s), 3.54, 4.34 (each 1H, d, JZ16.2 Hz), 5.31 (1H,
s), 7.22 (2H, d, JZ6.7 Hz), 7.29–7.35 (5H, m), 7.49 (3H,
m), 7.60–7.63 (2H, m), 7.72 (2H, d, JZ8.0 Hz). MS m/z (%)
393 (MC, trace), 254 (73), 214 (54), 179 (66), 178 (65), 140
(100), 139 (26). Anal. Calcd for C23H20ClNOS: C, 70.13; H,
5.12; Cl, 9.00; N, 3.56; S, 8.14%. Found: C, 70.01; H, 4.94;
Cl, 8.93; N, 3.57; S, 8.16%.
2a, 2b, 2c, 2d, 3a, 10, 15a, and 15b are known compounds.5,6
3.1.1. {1-[Chloro(p-tolylsulfinyl)methyl]cyclopenta-
decyl}acetonitrile (5a). Acetonitrile (0.096 ml;
1.80 mmol) was added to
a solution of n-BuLi
(1.80 mmol) in 10 ml of dry THF at K78 8C with stirring.
The solution was stirred for 10 min and a solution of 2a
(237.0 mg; 0.60 mmol) in 2 ml of dry THF was added. The
reaction mixture was stirred for 10 min and the reaction was
quenched by adding satd aq. NH4Cl. The whole was
extracted with CHCl3. The products (less polar product
5a-L and more polar product 5a-P) were isolated by silica
gel column chromatography to give 5a-L (190.8 mg; 73%)
and 5a-P (61.9 mg; 23%) as a colorless oil.
Compound 5c-P. Colorless crystals, mp 68–69 8C (AcOEt–
hexane); IR (KBr) 2926, 2852, 2241 (CN), 1632, 1495,
1447, 1087, 1058 (SO), 700 cmK1; 1H NMR d 2.41 (3H, s),
3.57, 3.85 (each 1H, d, JZ17.1 Hz), 5.01 (1H, s), 7.26–7.48
(14H, m). MS m/z (%) 393 (MC, trace), 256 (31), 254 (95),
218 (40), 214 (69), 179 (78), 178 (77), 140 (100), 139 (30).
Anal. Calcd for C23H20ClNOS: C, 70.13; H, 5.12; Cl, 9.00;
N, 3.56; S, 8.14%. Found: C, 69.94; H, 5.25; Cl, 8.94; N,
3.58; S, 7.76%.
Compound 5a-L. IR (neat) 2930, 2858, 2243 (CN), 1461,
1
1083, 1054 (SO), 812, 756 cmK1; H NMR d 1.31–1.44
(24H, m), 1.73 (2H, br t, JZ11.6 Hz), 1.99 (2H, br quintet,
JZ14.3 Hz), 2.44 (3H, s), 2.65, 3.24 (each 1H, d, JZ
3.1.4. 2-Amino-3-methylspiro[4.14]nonadeca-1,3-diene-
1-carbonitrile (7a). To a solution of LDA (0.23 mmol) in

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D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
2 ml of dry THF was added a solution 5a (33.1 mg;
0.076 mmol) in 1 ml of dry THF at K78 8C and the reaction
mixture was stirred for 30 min. To the reaction mixture was
added lithium a-carbanion of propionitrile (0.30 mmol),
which was generated from propionitrile and n-BuLi at
K78 8C, through a cannula and the temperature of the
reaction mixture was slowly allowed to warm to room
temperature for 2.5 h. The reaction mixture was quenched
by satd aq. NH4Cl. The whole was extracted with CHCl3.
The product was isolated by silica gel column chromato-
graphy to give 19.0 mg (80%) of 7a as colorless crystals; mp
162–164 8C (AcOEt–hexane); IR (KBr) 3424 (NH), 3346
(NH), 2930, 2854, 2168 (CN), 1648, 1623, 1565, 1451,
3.1.9. 2-Amino-3-ethyl-5,5-diphenylcyclopenta-1,3-
diene-1-carbonitrile (7f). Colorless crystals; mp 164–
165 8C (AcOEt–hexane); IR (KBr) 3352 (NH), 3232
(NH), 2969, 2175 (CN), 1651, 1562, 1490, 1445, 758,
699 cmK1; 1H NMR d 1.24 (3H, t, JZ7.3 Hz), 2.26 (2H, q,
JZ7.3 Hz), 4.69 (2H, br s, NH), 6.58 (1H, s), 7.22–7.29
(10H, m). MS m/z (%) 287 (25), 286 (MC, 95), 271 (62),
256 (34), 257 (100). Anal. Calcd for C20H18N2: C, 83.88; H,
6.34; N, 9.78%. Found: C, 83.63; H, 6.09; N, 9.75%.
3.1.10. 3-Methylspiro[4.14]nonadec-3-en-2-one (8a). To a
solution 7a (97.2 mg; 0.31 mmol) in 21 ml acetic acid was
added phosphoric acid (85%, 9 ml) and water (2 ml). The
reaction mixture was stirred and heated under reflux for
32 h. The reaction mixture was neutralized with 10% aq.
NaOH and the whole was extracted with CHCl3. The
product was isolated by silica gel column chromatography
to give 83.3 mg (93%) of 8a as a colorless oil; IR (neat)
1
1421 cmK1; H NMR d 1.34–1.59 (28H, m), 1.85 (3H, d,
JZ1.3 Hz), 4.42 (2H, br s, NH), 6.20 (1H, q, JZ1.3 Hz).
MS m/z (%) 315 (25), 314 (MC, 100), 147 (20), 134 (24),
133 (38), 132 (17). Anal. Calcd for C21H34N2: C, 80.20; H,
10.90; N, 8.91%. Found: C, 80.18; H, 10.94; N, 8.91%.
1
2929, 2857, 1709 (CO), 1639, 1459, 1330, 756 cmK1; H
3.1.5. 2-Amino-3-ethylspiro[4.14]nonadeca-1,3-diene-1-
carbonitrile (7b). Colorless crystals; mp 132–134 8C
(AcOEt–hexane); IR (KBr) 3427 (NH), 3347 (NH), 2932,
NMR d 1.31–1.44 (28H, m), 1.73 (3H, d, JZ1.3 Hz), 2.19
(2H, s), 7.23 (1H, q, JZ1.3 Hz). MS m/z (%) 291 (16), 290
(MC, 69), 262 (28), 123 (27), 110 (39), 109 (100), 108 (35).
Calcd for C20H34O: M, 290.2608. Found: m/z 290.2625.
1
2855, 2166 (CN), 1646, 1563, 1459, 1423, 842 cmK1; H
NMR d 1.16 (3H, t, JZ7.3 Hz), 1.26–1.54 (28H, m), 2.16
(2H, q, JZ7.3 Hz), 4.40 (2H, br s, NH), 6.18 (1H, s). MS
m/z (%) 329 (26), 328 (MC, 100), 161 (18), 159 (15), 148
(24), 147 (43), 146 (22). Anal. Calcd for C22H36N2: C,
80.43; H, 11.04; N, 8.53%. Found: C, 80.30; H, 11.10; N,
8.43%.
3.1.11. 3-Ethylspiro[4.14]nonadec-3-en-2-one (8b).
Colorless oil; IR (neat) 2930, 2857, 1709 (CO), 1460 cmK1
;
1H NMR d 1.07 (3H, t, JZ7.5 Hz), 1.33–1.44 (28H, m), 2.15
(2H, dq, JZ7.5, 1.1 Hz), 2.21 (2H, s), 7.19 (1H, t, JZ1.1 Hz).
MS m/z (%) 305 (25), 304 (MC, 100), 137 (24), 124 (53), 123
(80), 122 (24). Calcd for C21H36O: M, 304.2764. Found: m/z
304.2774.
3.1.6. 10-Amino-11-methyl-1,4-dioxa-dispiro[4.2.4.2]-
tetradeca-9,11-diene-9-carbonitrile (7c). Colorless crys-
tals; mp 243–244 8C (CHCl3–hexane); IR (KBr) 3405 (NH),
3356 (NH), 3245, 2929, 2165 (CN), 1663, 1560, 1452,
3.1.12. 3-Methylspiro[4.5]dec-3-ene-2,8-dione (8c).
Colorless crystals; mp 84–85 8C (AcOEt–hexane); IR
(KBr) 2963, 2946, 2868, 1712 (CO), 1701 (CO), 1637,
1069, 977 cmK1; 1H NMR d 1.80 (3H, d, JZ1.2 Hz), 1.82–
1.86 (2H, m), 1.94–2.00 (2H, m), 2.44–2.51 (4H, m), 2.49
(2H, s), 7.21 (1H, q, JZ1.2 Hz). MS m/z (%) 179 (14), 178
(MC, 100), 122 (42), 121 (31), 108 (92). Anal. Calcd for
C11H14O2: C, 74.13; H, 7.92%. Found: C, 73.90; H, 7.80%.
1
1092 cmK1; H NMR d 1.45 (2H, br d, JZ12.8 Hz), 1.73
(2H, dt, JZ12.8, 4.1 Hz), 1.89 (3H, s), 1.92 (2H, m), 2.02
(2H, br t, JZ12.4 Hz), 3.97 (4H, s), 4.46 (2H, br s, NH),
6.49 (1H, s). MS m/z (%) 246 (MC, 32), 218 (26), 145 (15),
133 (15), 132 (100), 131 (14). Anal. Calcd for C14H18N2O2:
C, 68.27; H, 7.37; N, 11.37%. Found: C, 67.88; H, 7.32; N,
11.30%.
3.1.13. 3-Ethylspiro[4.5]dec-3-ene-2,8-dione (8d). Color-
less crystals; mp 58–59 8C (AcOEt–hexane); IR (KBr)
3.1.7. 10-Amino-11-ethyl-1,4-dioxa-dispiro[4.2.4.2]tetra-
deca-9,11-diene-9-carbonitrile (7d). Colorless crystals;
mp 195–196 8C (AcOEt–hexane); IR (KBr) 3410 (NH),
3354 (NH), 3245, 2964, 2162 (CN), 1661, 1557, 1436,
1090 cmK1; 1H NMR d 1.18 (3H, t, JZ7.3 Hz), 1.45 (2H, br
d, JZ12.9 Hz), 1.75 (2H, dt, JZ12.9, 4.2 Hz), 1.92 (2H, br
d, JZ13.2 Hz), 2.03 (2H, br t, JZ10.4 Hz), 2.19 (2H, dt,
JZ7.3, 1.8 Hz), 3.97 (4H, s), 4.48 (2H, br s, NH), 6.46 (1H,
br s). MS m/z (%) 261 (9), 260 (MC, 40), 232 (27), 147 (20),
146 (100), 131 (15). Calcd for C15H20N2O2: M, 260.1524.
Found: m/z 260.1525.
1
2970, 2933, 1698 (CO), 1337, 970 cmK1; H NMR d 1.11
(3H, t, JZ7.5 Hz), 1.81–1.85 (2H, m), 1.94–2.00 (2H, m),
2.21 (2H, q, JZ7.5 Hz), 2.44–2.48 (4H, m), 2.50 (2H, s),
7.15 (1H, s). MS m/z (%) 193 (10), 192 (MC, 100), 164 (32),
136 (73), 135 (45), 123 (18), 122 (74), 121 (20), 107 (23).
Anal. Calcd for C12H16O2: C, 74.97; H, 8.39%. Found: C,
74.92; H, 8.30%.
3.1.14. 2-Methyl-4,4-diphenyl-2-cyclopentenone (8e).
Colorless crystals; mp 91–92 8C (hexane); IR (KBr) 1697
(CO), 1493, 1445, 752, 704 cmK1; 1H NMR d 1.88 (3H, d,
JZ1.2 Hz), 3.17 (2H, s), 7.14–7.33 (10H, m), 7.63 (1H, d,
JZ1.2 Hz). MS m/z (%) 249 (22), 248 (MC, 100), 220 (39),
205 (93), 171 (35), 129 (21), 128 (35), 115 (25). Anal. Calcd
for C18H16O: C, 87.06; H, 6.49%. Found: C, 86.83; H,
6.26%.
3.1.8. 2-Amino-3-methyl-5,5-diphenylcyclopenta-1,3-
diene-1-carbonitrile (7e). Colorless crystals; mp 171–
172 8C (AcOEt–hexane); IR (KBr) 3456 (NH), 3366
(NH), 3232, 2166 (CN), 1654, 1624, 1563, 1445,
1
698 cmK1; H NMR d 1.96 (3H, d, JZ1.5 Hz), 4.69 (2H,
br s, NH), 6.62 (1H, q, JZ1.5 Hz), 7.21–7.29 (10H, m). MS
m/z (%) 273 (23), 272 (MC, 100), 258 (21), 257 (52), 195
(15). Anal. Calcd for C19H16N2: C, 83.79; H, 5.92; N,
10.29%. Found: C, 83.38; H, 5.76; N, 10.19%.
3.1.15. 2-Ethyl-4,4-diphenyl-2-cyclopentenone (8f).
Colorless oil; IR (neat) 3059, 3026, 2969, 2935, 1709
(CO), 1634, 1597, 1493, 1446, 761, 700 cmK1; 1H NMR d

D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
1253
1.17 (3H, t, JZ7.4 Hz), 2.30 (2H, dq, JZ7.4, 1.2 Hz), 3.18
(2H, s), 7.13–7.33 (10H, m), 7.58 (1H, br t, JZ1.2 Hz). MS
m/z (%) 263 (22), 262 (MC, 100), 261 (53), 233 (39), 205
(68), 185 (18), 157 (39), 129 (18), 115 (26). Calcd for
C19H18O: M, 262.1356. Found: m/z 262.1342.
(2H, br s, NH), 3.92–3.98 (4H, m), 6.43 (1H, s), 7.14–7.32
(15H, m). MS m/z (%) 475 (37), 474 (MC, 100), 360 (17),
242 (15), 243 (57), 165 (17). Calcd for C32H30N2O2: M,
474.2305. Found: m/z 474.2299.
3.1.22. 10-Amino-11-(4-methoxyphenyl)-1,4-dioxa-di-
spiro[4.2.4.2]tetradeca-9,11-diene-9-carbonitrile (7m).
Colorless crystals; mp 223 8C (AcOEt–hexane); IR (KBr)
3462 (NH), 3353 (NH), 2937, 2893, 2169 (CN), 1647, 1509,
1247, 1106, 1031, 837 cmK1; 1H NMR d 1.55–1.62 (2H, m),
1.79 (2H, dt, JZ12.7, 3.7 Hz), 1.96 (2H, br d, JZ13.1 Hz),
2.12 (2H, br t, JZ11.3 Hz), 3.84 (3H, s), 3.98 (4H, s), 4.61
(2H, br s, NH), 6.71 (1H, s), 6.96, 7.29 (each 2H, d, JZ
8.9 Hz). MS m/z (%) 339 (24), 338 (MC, 100), 294 (28), 293
(22), 276 (28), 237 (35), 246 (66). Anal. Calcd for
C20H22N2O3: C, 70.99; H, 6.55; N, 8.28%. Found: C,
71.04; H, 6.59; N, 8.14%.
3.1.16. 2-Amino-3-pentylspiro[4.14]nonadeca-1,3-diene-
1-carbonitrile (7g). Colorless crystals; mp 109–110 8C
(hexane); IR (KBr) 3424 (NH), 3359 (NH), 2929, 2857,
2165 (CN), 1673, 1648, 1557 cmK1; 1H NMR d 0.91 (3H, t,
JZ6.9 Hz), 1.33–1.57 (34H, m), 2.12 (2H, dt, JZ7.7,
1.4 Hz), 4.39 (2H, br s, NH), 6.17 (1H, t, JZ1.4 Hz). MS
m/z (%) 371 (29), 370 (MC, 100), 313 (32), 189 (18), 145
(10), 132 (12). Anal. Calcd for C25H42N2: C, 81.02; H,
11.42; N, 7.56%. Found: C, 81.12; H, 11.63; N, 7.48%.
3.1.17. 2-Amino-3-isopropylspiro[4.14]nonadeca-1,3-
diene-1-carbonitrile (7h). Colorless crystals; mp 113–
115 8C (AcOEt–hexane); IR (KBr) 3434 (NH), 3349 (NH),
3.1.23. (E)-2-Amino-5,5-diphenyl-3-propenylcyclopenta-
1,3-diene-1-carbonitrile (7n). Colorless crystals; mp 146–
147 8C (AcOEt–hexane); IR (KBr) 3474 (NH), 3421 (NH),
3330 (NH), 3230 (NH), 3026, 2183 (CN), 1657, 1557, 761,
701 cmK1; 1H NMR d 1.86 (3H, d, JZ6.4 Hz), 4.77 (2H, br
s, NH), 6.03 (1H, d, JZ15.9 Hz), 6.17 (1H, dq, JZ15.9,
6.4 Hz), 6.75 (1H, s), 7.22–7.30 (10H, m). MS m/z (%) 299
(25), 298 (MC, 100), 297 (38), 283 (26), 205 (13). Calcd for
C21H18N2: M, 298.1468. Found: m/z 298.1462.
1
2932, 2852, 2165 (CN), 1643, 1559, 1459, 1420 cmK1; H
NMR d 1.14 (6H, d, JZ6.7 Hz), 1.34–1.55 (28H, m), 2.41
(1H, septet, JZ6.7 Hz), 4.44 (2H, br s, NH), 6.17 (1H, s).
MS m/z (%) 343 (28), 342 (MC, 100), 327 (28), 299 (22),
161 (24). Anal. Calcd for C23H38N2: C, 80.64; H, 11.18; N,
8.18%. Found: C, 80.77; H, 11.41; N, 8.08%.
3.1.18. 2-Amino-3-(triphenylmethyl)spiro[4.14]non-
adeca-1,3-diene-1-carbonitrile (7i). Colorless crystals;
mp 202–203 8C (AcOEt–hexane); IR (KBr) 3483 (NH),
3.1.24. 2-Amino-3-(4-methoxyphenyl)-5,5-diphenyl-
cyclopenta-1,3-diene-1-carbonitrile (7o). Colorless crys-
tals; mp 171–173 8C (AcOEt–hexane); IR (KBr) 3465 (NH),
3344 (NH), 3058, 2179 (CN), 1650, 1621, 1604, 1508, 1242,
1027, 831, 701 cmK1; 1H NMR d 3.84 (3H, s), 4.84 (2H, br
s, NH), 6.84 (1H, s), 6.96 (2H, d, JZ8.6 Hz), 7.25–7.32
(10H, m), 7.34 (2H, d, JZ8.6 Hz). MS m/z (%) 365 (28),
364 (MC, 100), 349 (8), 287 (11). Anal. Calcd for
C25H20N2O: C, 82.39; H, 5.53; N, 7.69%. Found: C,
82.35; H, 5.47; N, 7.63%.
2930, 2856, 2182 (CN), 1637, 1552, 1492, 1445, 702 cmK1
;
1H NMR d 1.26–1.66 (28H, m), 3.87 (2H, br s, NH), 6.18
(1H, s), 7.16 (6H, m), 7.24–7.34 (9H, m). MS m/z (%) 543
(43), 542 (MC, 100), 456 (16), 243 (37), 165 (11). Anal.
Calcd for C39H46N2: C, 86.30; H, 8.54; N, 5.16%. Found: C,
85.83; H, 8.50; N, 5.00%.
3.1.19. (E)-2-Amino-3-propenylspiro[4.14]nonadeca-1,3-
diene-1-carbonitrile (7j). Colorless crystals; mp 92–93 8C
(hexane); IR (KBr) 3484 (NH), 3342 (NH), 2930, 2856,
2177 (CN), 1662, 1557, 1423, 961 cmK1; 1H NMR d 1.34–
1.54 (28H, m), 1.84 (3H, d, JZ6.4 Hz), 4.50 (2H, br s, NH),
5.97 (1H, d, JZ15.9 Hz), 6.06 (1H, dq, JZ15.9, 6.4 Hz),
6.37 (1H, s). MS m/z (%) 341 (26), 340 (MC, 100), 173 (16),
160 (18), 159 (18), 111 (13). Anal. Calcd for C23H36N2: C,
81.12; H, 10.66; N, 8.23%. Found: C, 81.20; H, 10.89; N,
8.07%.
3.1.25. 3-Pentylspiro[4.14]nonadec-3-en-2-one (8g).
Colorless oil; IR (neat) 2929, 2857, 1709 (CO), 1460 cmK1
;
1H NMR d 0.89 (3H, t, JZ7.0 Hz), 1.24–1.49 (34H, m), 2.11
(2H, dt, JZ15.4, 1.3 Hz), 2.20(2H, s), 7.19(1H, t, JZ1.3 Hz).
MS m/z (%) 347 (28), 346 (MC, 100), 166 (13), 165 (32), 163
(12), 151 (12), 109 (10). Calcd for C24H42O: M, 346.3233.
Found: m/z 346.3226.
3.1.20. 2-Amino-3-(4-methoxyphenyl)spiro[4.14]non-
adeca-1,3-diene-1-carbonitrile (7k). Colorless crystals;
mp 164–165 8C (AcOEt–hexane); IR (KBr) 3459 (NH),
3.1.26. 3-Isopropylspiro[4.14]nonadec-3-en-2-one (8h).
Colorless oil; IR (neat) 2930, 2858, 1708 (CO), 1460,
1369, 1002 cmK1 1H NMR d 1.07 (6H, d, JZ6.7 Hz),
;
2930, 2855, 2173 (CN), 1645, 1603, 1509, 1247, 832 cmK1
;
1.33–1.44 (28H, m), 2.20 (2H, s), 2.59 (1H, double septet,
JZ6.7, 1.0 Hz), 7.15 (1H, d, JZ1.0 Hz). MS m/z (%) 319
(26), 318 (MC, 100), 276 (20), 275 (15), 138 (32), 137 (40).
Calcd for C22H38O: M, 318.2920. Found: m/z 318.2913.
1H NMR d 1.27–1.70 (28H, m), 3.84 (3H, s), 4.55 (2H, br s,
NH), 6.44 (1H, s), 6.94, 7.28 (each 2H, d, JZ8.6 Hz). MS
m/z (%) 407 (29), 406 (MC, 100), 304 (7), 225 (12), 224 (5),
146 (6). Anal. Calcd for C27H38N2O: C, 79.76; H, 9.42; N,
6.89%. Found: C, 79.79; H, 9.47; N, 6.74%.
3.1.27. 3-(Triphenylmethyl)spiro[4.14]nonadec-3-en-2-
one (8i). Colorless crystals; mp 144–145 8C (AcOEt–
hexane); IR (KBr) 3056, 3029, 2928, 2855, 1715 (CO),
1492, 1446, 746, 699 cmK1; 1H NMR d 1.27–1.50 (28H, m),
2.30 (2H, s), 7.12–7.26 (15H, m), 7.32 (1H, s). MS m/z (%)
519 (40), 518 (MC, 100), 441 (8), 296 (30), 268 (9), 243
(11), 215 (7), 165 (10). Anal. Calcd for C38H46O: C, 87.98;
H, 8.94%. Found: C, 88.06; H, 8.97%.
3.1.21. 10-Amino-11-(triphenylmethyl)-1,4-dioxa-di-
spiro[4.2.4.2]tetradeca-9,11-diene-9-carbonitrile (7l).
Colorless crystals; mpO300 8C (AcOEt–hexane); IR
(KBr) 3478 (NH), 3336 (NH), 2941, 2893, 2180 (CN),
1
1653, 1556, 1491, 1099, 750, 703 cmK1; H NMR d 1.57–
1.67 (4H, m), 1.90–1.93 (2H, m), 2.05–2.10 (2H, m), 3.91

1254
D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
3.1.28. (E)-3-Propenylspiro[4.14]nonadec-3-en-2-one
(8j). Colorless oil; IR (neat) 2930, 2857, 1709 (CO),
1459, 971 cmK1; 1H NMR d 1.33–1.46 (28H, m), 1.78 (3H,
dd, JZ6.7, 1.5 Hz), 2.25 (2H, s), 6.04 (1H, dd, JZ15.3,
1.5 Hz), 6.62 (1H, dq, JZ15.3, 6.7 Hz), 7.26 (1H, s). MS
m/z (%) 317 (26), 316 (MC, 100), 149 (18), 136 (25), 121
(9), 105 (8). Calcd for C22H36O: M, 316.2765. Found: m/z
316.2772.
MS m/z (%) 269 (MC, 9), 140 (100), 139 (56), 92 (43), 91
(22). Anal. Calcd for C13H16ClNOS: C, 57.88; H, 5.98; Cl,
13.14; N, 5.19; S, 11.88%. Found: C, 57.84; H, 5.88; Cl,
13.08; N, 5.11; S, 11.74%.
Compound 5d-P. Colorless crystals, mp 136 8C (AcOEt–
hexane); IR (KBr) 2980, 2946, 2239 (CN), 1087, 1054 (SO),
811, 515 cmK1; 1H NMR d 1.48 (3H, s), 1.51 (3H, s), 2.44
(3H, s), 2.71, 2.76 (each 1H, d, JZ16.8 Hz), 4.24 (1H, s),
7.36, 7.49 (each 2H, d, JZ8.2 Hz). MS m/z (%) 269 (MC,
9), 140 (100), 139 (54), 92 (44), 91 (17). Anal. Calcd for
C13H16ClNOS: C, 57.88; H, 5.98; Cl, 13.14; N, 5.19; S,
11.88%. Found: C, 57.71; H, 5.85; Cl, 13.08; N, 5.05; S,
11.82%.
3.1.29. 3-(4-Methoxyphenyl)spiro[4.14]nonadec-3-en-2-
one (8k). Colorless crystals; mp 54–55 8C (hexane); IR
1
(KBr) 2928, 2854, 1698 (CO), 1600, 1509, 831 cmK1; H
NMR d 1.35–1.54 (28H, m), 2.38 (2H, s), 3.82 (3H, s), 6.90
(2H, d, JZ8.6 Hz), 7.64 (1H, s), 7.67 (2H, d, JZ8.6 Hz).
MS m/z (%) 383 (29), 382 (MC, 100), 354 (18), 201 (18),
159 (7), 121 (8). Anal. Calcd for C26H38O2: C, 81.62; H,
10.01%. Found: C, 81.74; H, 10.14%.
3.1.35. 2-Amino-3-(3-hydroxypropyl)-5,5-dimethylcyclo-
penta-1,3-diene-1-carbonitrile (7p). Colorless oil; IR
1
(neat) 3361 (OH), 2930, 2173 (CN), 1652, 1565 cmK1; H
NMR d 1.23 (6H, s), 1.77–1.82 (2H, m), 2.31 (2H, t, JZ
7.3 Hz), 2.42 (1H, t, JZ7.0 Hz), 3.69–3.73 (2H, m), 4.68
(2H, br s, NH), 6.12 (1H, s). MS m/z (%) 192 (MC, 61), 177
(41), 159 (23), 147 (100), 133 (54), 132 (31), 131 (22).
Calcd for C11H16N2O: M, 192.1262. Found: m/z 192.1261.
3.1.30. 3-(Triphenylmethyl)spiro[4.5]dec-3-ene-2,8-
dione (8l). Colorless crystals; mp 242–243 8C (AcOEt–
hexane); IR (KBr) 3050, 2933, 1712 (CO), 1490, 1444, 751,
1
702 cmK1; H NMR d 1.88 (2H, m), 1.96–2.04 (2H, m),
2.40–2.46 (4H, m), 2.60 (2H, s), 7.11–7.28 (16H, m). MS
m/z (%) 407 (33), 406 (MC, 100), 329 (28), 296 (68), 268
(30), 243 (24), 165 (31). Anal. Calcd for C29H26O2: C,
85.68; H, 6.45%. Found: C, 85.30; H, 6.51%.
3.1.36. 2-Amino-3-[3-(tert-butyldiphenylsilanyloxy)prop-
yl]-5,5-dimethylcyclopenta-1,3-diene-1-carbonitrile
(7q). Colorless oil; IR (neat) 3355 (NH), 3072, 2931, 2859,
1
3.1.31. 3-(4-Methoxyphenyl)spiro[4.5]dec-3-ene-2,8-
dione (8m). Colorless crystals; mp 106–107 8C (AcOEt–
hexane); IR (KBr) 2944, 2872, 1709 (CO), 1693 (CO),
2177 (CN), 1651, 1567, 1428, 1111 (OSi), 702 cmK1; H
NHR d 1.07 (9H, s), 1.20 (6H, s), 1.70–1.76 (2H, m), 2.29
(2H, t, JZ6.7 Hz), 3.70 (2H, t, JZ5.8 Hz), 4.59 (2H, br s,
NH), 6.03 (1H, s), 7.38–7.46 (6H, m), 7.64–7.66 (4H, m).
MS m/z (%) 430 (MC, 14), 374 (24), 373 (100), 295 (17),
199 (35). Calcd for C27H34N2OSi: M, 430.2441. Found: m/z
430.2434.
1
1612, 1599, 1510, 1256, 833 cmK1; H NMR d 1.91–1.95
(2H, m), 2.03–2.09 (2H, m), 2.45–2.56 (4H, m), 2.68 (2H,
s), 3.83 (3H, s), 6.93 (2H, d, JZ9.2 Hz), 7.59 (1H, s), 7.71
(2H, d, JZ9.2 Hz). MS m/z (%) 271 (19), 270 (MC, 100),
212 (63), 213 (88), 200 (28). Anal. Calcd for C17H18O3: C,
75.53; H, 6.71%. Found: C, 75.69; H, 6.73%.
3.1.37. 3-(3,3-Dimethyl-5-oxocyclopent-1-enyl)propyl
acetate (8p). Colorless oil; IR (neat) 2959, 2867, 1741
(CO), 1706 (CO), 1242 (COC), 1044, 756 cmK1; 1H NMR d
1.20 (6H, s), 1.69–1.75 (2H, m), 2.05 (3H, s), 2.22 (2H, dt,
JZ7.6, 1.3 Hz), 2.28 (2H, s,), 4.07 (2H, t, JZ6.6 Hz), 7.07
(1H, t, JZ1.3 Hz). MS m/z (%) 210 (MC, trace), 151 (16),
150 (100), 135 (95), 107 (44). Calcd for C12H18O3: M,
210.1256. Found: m/z 210.1259.
3.1.32. (E)-4,4-Diphenyl-2-propenyl-2-cyclopentenone
(8n). Colorless crystals; mp 59–60 8C (AcOEt–hexane);
IR (KBr) 3023, 2933, 1705 (CO), 1489, 1444, 976, 764,
1
701 cmK1; H NMR d 1.84 (3H, dd, JZ6.7, 1.5 Hz), 3.21
(2H, s), 6.15 (1H, dd, JZ15.9, 1.5 Hz), 6.75 (1H, dq, JZ
15.9, 6.7 Hz), 7.14–7.32 (10H, m), 7.62 (1H, s). MS m/z (%)
275 (25), 274 (MC, 100), 231 (72), 217 (48), 170 (45), 155
(38), 142 (32), 128 (38), 115 (37). Anal. Calcd for C20H18O:
C, 87.56; H, 6.61%. Found: C, 87.64; H, 6.46%.
3.1.38. 2-(3-Hydroxypropyl)-4,4-dimethyl-2-cyclopente-
none (8q). To a solution of 8p (12.9 mg; 0.061 mmol) in
MeOH (3 ml) was added aq. K2CO3 (0.5 M, 0.4 ml) at room
temperature and the reaction mixture was stirred for 40 min.
The whole was extracted with CHCl3. The product was
isolated by silica gel column chromatography to give 8q
(10.2 mg; 99%) as a colorless oil; IR (neat) 3419 (OH),
3.1.33. 2-(4-Methoxyphenyl)-4,4-diphenyl-2-cyclopente-
none (8o). Colorless crystals; mp 159–160 8C (AcOEt–
hexane); IR (KBr) 2835, 1702 (CO), 1605, 1509, 1254,
1
1035, 835, 758, 701 cmK1; H NMR d 3.34 (2H, s), 3.83
1
(3H, s), 6.93 (2H, d, JZ8.9 Hz), 7.21–7.27 (6H, m), 7.32–
7.35 (4H, m), 7.76 (2H, d, JZ8.9 Hz), 8.01 (1H, s). MS m/z
(%) 341 (28), 340 (MC, 100), 312 (15), 281 (16), 263 (16),
235 (21), 221 (25). Anal. Calcd for C24H20O2: C, 84.68; H,
5.92%. Found: C, 84.36; H, 5.88%.
2958, 2869, 1695 (CO), 1060 cmK1; H NMR d 1.21 (6H,
s), 1.80–1.85 (2H, m), 2.04 (1H, br s, OH), 2.26 (2H, t, JZ
7.3 Hz), 2.30 (2H, s), 3.59 (2H, br t, JZ5.3 Hz), 7.10 (1H,
s). MS m/z (%) 168 (MC, 8), 150 (90), 135 (100), 125 (15),
122 (24), 112 (30), 109 (67), 107 (62). Calcd for C10H16O2:
M, 168.1148. Found: m/z 168.1133.
3.1.34. 3-Chloro-2,2-dimethyl-3-(p-tolylsulfinyl)propio-
nitrile (5d). Compound 5d-L. Colorless crystals, mp
62 8C (AcOEt–hexane); IR (KBr) 2973, 2939, 2243 (CN),
3.1.39. (S)-(RS)-2-[Chloro(p-tolylsulfinyl)methyl]-2-
methylhexanenitrile (16a). 16a-L/16a-PZ17:4.
1
1082, 1046 (SO), 809, 501 cmK1; H NMR d 1.41 (3H, s),
1.52 (3H, s), 2.44 (3H, s), 2.76, 3.12 (each 1H, d, JZ
16.8 Hz), 4.44 (1H, s), 7.34, 7.73 (each 2H, d, JZ8.2 Hz).
Compound 16a-L. Colorless oil; IR (neat) 2959, 2872, 2243
(CN), 1462, 1055 (SO), 813 cmK1; 1H NMR d 0.96 (3H, t,

D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
1255
JZ7.0 Hz), 1.32–1.47 (4H, m), 1.39 (3H, s), 1.85–1.91 (1H,
m), 1.97–2.03 (1H, m), 2.44 (3H, s), 2.64, 3.18 (each 1H, d,
JZ16.8 Hz), 4.55 (1H, s), 7.35, 7.74 (each 2H, d, JZ
8.0 Hz). MS m/z (%) 311 (MC, 4), 142 (5), 141 (9), 140
(100), 139 (18), 123 (5). Calcd for C16H22ClNOS: M,
311.1111. Found: m/z 311.1115.
1328 cmK1; 1H NMR d 0.89 (3H, t, JZ7.2 Hz), 1.16 (3H, s),
1.18–1.32 (4H, m), 1.38–1.50 (2H, m), 1.74 (3H, d, JZ
1.2 Hz), 2.14, 2.32 (each 1H, d, JZ18.6 Hz), 7.05 (1H, q, JZ
1.2 Hz). MS m/z (%) 166 (MC, 25), 123 (10), 110 (32), 109
(100). Calcdfor C11H18O: M, 166.1356. Found: m/z 166.1356.
Compound 18a. [a]3D0ZK46.7 (c 0.88, acetone).
Compound 18b. [a]3D0ZC43.4 (c 1.55, acetone).
Compound 16a-P. Colorless oil; IR (neat) 2933, 2864, 2238
(CN), 1089, 1060 (SO), 813, 514 cmK1; 1H NMR d 0.97 (3H,
t, JZ7.0 Hz), 1.32–1.44 (4H, m), 1.40 (3H, s), 1.82–1.88 (1H,
m), 1.92–1.98(1H,m), 2.44(3H, s), 2.79, 2.85(each1H,d,JZ
17.1 Hz), 4.35 (1H, s), 7.36, 7.48 (each 2H, d, JZ8.3 Hz).
3.1.43. (R)-2-Amino-5-butyl-5-methyl-3-pentylcyclo-
penta-1,3-dienecarbonitrile (17c) and (S)-2-amino-5-
butyl-5-methyl-3-pentyl-cyclopenta-1,3-dienecarbo-
nitrile (17d). Colorless oil; IR (neat) 3462 (NH), 3358
(NH), 3252 (NH), 2929, 2860, 2175 (CN), 1651, 1564,
1457, 1417, 1379 cmK1; 1H NMR d 0.85 (3H, t, JZ7.3 Hz),
0.90–0.92 (3H, m), 1.06–1.13 (2H, m), 1.21 (3H, s), 1.22–
1.26 (2H, m), 1.21–1.35 (6H, m), 1.51–1.55 (2H, m), 2.14
(2H, t, JZ7.6 Hz), 4.42 (2H, br s, NH), 6.04 (1H, s). MS m/z
(%) 246 (MC, 40), 203 (44), 190 (77), 189 (100), 165 (28),
133 (89), 132 (31). Calcd for C16H26N2: M, 246.2094.
Found: m/z 246.2097.
Racemic 16a-P. Colorless crystals; mp 67–68 8C (AcOEt–
hexane); IR (KBr) 2943, 2870, 2236 (CN), 1084, 1047 (SO),
816, 517 cmK1; Anal. Calcd for C16H22ClNOS: C, 61.62;
H, 7.11; Cl, 11.37; N, 4.49; S, 10.28%. Found: C, 61.63; H,
7.07; Cl, 11.24; N, 4.49; S, 10.09%.
3.1.40. (R)-(RS)-2-[Chloro(p-tolylsulfinyl)methyl]-2-
methylhexanenitrile (16b). 16b-L/16b-PZ7:2.
Compound 16b-L. Colorless oil; IR (neat) 2960, 2865, 2243
1
(CN), 1597, 1463, 1082, 1051 (SO), 813, 756 cmK1; H
Compound 17c. [a]2D7ZK64.2 (c 0.65, acetone).
NMR d 0.93 (3H, t, JZ6.9 Hz), 1.20–1.39 (4H, m), 1.48
(3H, s), 1.71–1.80 (2H, m), 2.44 (3H, s), 3.00, 3.05 (each
1H, d, JZ16.8 Hz), 4.42 (1H, s), 7.35, 7.73 (each 2H, d, JZ
8.0 Hz). MS m/z (%) 311 (MC, 4), 142 (5), 141 (9), 140
(100), 139 (18), 124 (5), 123 (5). Calcd for C16H22ClNOS:
M, 311.1110. Found: m/z 311.1120.
Compound 17d. [a]2D7ZC63.9 (c 1.14, acetone). Racemic
compound is colorless crystals, low melting solid; IR (KBr)
3451 (NH), 3355 (NH), 3250 (NH), 2929, 2860, 2170 (CN),
1651, 1567, 1467, 1419, 1379 cmK1
.
3.1.44. (R)-2-Amino-5-butyl-3-isopropyl-5-methylcyclo-
penta-1,3-dienecarbonitrile (17e) and (S)-2-amino-5-
butyl-3-isopropyl-5-methylcyclopenta-1,3-dienecarbo-
nitrile (17f). Colorless oil; IR (neat) 3445 (NH), 3359 (NH),
3249 (NH), 2962, 2929, 2175 (CN), 1652, 1615, 1558,
Compound 16b-P. Colorless crystals; mp 120–121 8C
(AcOEt–hexane); IR (KBr) 2940, 2872, 2240 (CN), 1463,
1
1087, 1050 (SO), 816, 518 cmK1; H NMR d 0.96 (3H, t,
JZ7.2 Hz), 1.27–1.34 (2H, m), 1.37–1.43 (2H, m), 1.47
(3H, s), 1.78–1.84 (1H, m), 1.88–1.95 (1H, m), 2.44 (3H, s),
2.68, 2.81 (each 1H, d, JZ17.1 Hz), 4.27 (1H, s), 7.36, 7.48
(each 2H, d, JZ8.2 Hz). Anal. Calcd for C16H22ClNOS: C,
61.62; H, 7.11; Cl, 11.37; N, 4.49; S, 10.28%. Found: C,
61.57; H, 7.03; Cl, 11.31; N, 4.47; S, 10.15%.
1
1417 cmK1; H NMR d 0.85 (3H, t, JZ7.3 Hz), 1.02–1.13
(2H, m), 1.15(6H, d, JZ7.0 Hz),1.19–1.26(2H, m), 1.20(3H,
s), 1.56–1.61 (2H, m), 2.42 (1H, septet, JZ7.0 Hz), 4.45 (2H,
br s, NH), 6.03 (1H, s). MS m/z (%) 219 (10), 218 (MC, 44),
203 (35), 175 (60), 162 (68), 161 (100), 147 (55), 146 (57).
Calcd for C14H22N2: M, 218.1781. Found: m/z 218.1778.
Racemic 16b-P. Colorless crystals; mp 94–95 8C (AcOEt–
hexane).
Compound 17e. [a]2D9ZK80.7 (c 0.91, acetone).
Compound 17f. [a]2D8ZC86.6 (c 1.48, acetone). Racemic
compound is colorless crystals; mp 66–67 8C (hexane); IR
(KBr) 3440 (NH), 3354 (NH), 3251 (NH), 2963, 2928, 2164
3.1.41. (R)-2-Amino-5-butyl-3,5-dimethylcyclopenta-1,3-
diene-1-carbonitrile (17a) and (S)-2-amino-5-butyl-3,5-
dimethylcyclopenta-1,3-diene-1-carbonitrile (17b).
Colorless oil; IR (neat) 3446 (NH), 3359 (NH), 3242
(NH), 2959, 2929, 2862, 2175 (CN), 1652, 1568, 1456,
(CN), 1671, 1648, 1560, 1419 cmK1
.
1
828 cmK1; H NMR d 0.85 (3H, t, JZ7.3 Hz), 1.07–1.12
(2H, m), 1.20 (3H, s), 1.22–1.28 (2H, m), 1.53–1.61 (2H,
m), 1.87 (3H, d, JZ1.6 Hz), 4.42 (2H, br s, NH), 6.07 (1H,
q, JZ1.6 Hz). MS m/z (%) 191 (5), 190 (MC, 29), 147 (45),
134 (60), 133 (100), 118 (22). Calcd for C12H18N2: M,
190.1469. Found: m/z 190.1469.
Acknowledgements
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.
Compound 17a. [a]2D7ZK122.1 (c 2.0, acetone).
Compound 17b. [a]2D7ZC119.4 (c 1.11, acetone).
References and notes
3.1.42. (S)-4-Butyl-2,4-dimethylcyclopent-2-enone (18a)
and (R)-4-butyl-2,4-dimethylcyclopent-2-enone (18b).
Colorless oil; IR (neat) 2958, 2928, 1713 (CO), 1640, 1456,
1. Some reviews and a monograph for the synthesis of

1256
D. Wakasugi, T. Satoh / Tetrahedron 61 (2005) 1245–1256
cyclopentanoid natural products: (a) Trost, B. M. Chem. Soc.
6. (a) Satoh, T.; Yoshida, M.; Ota, H. Tetrahedron Lett. 2001, 42,
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Tetrahedron: Asymmetry 2003, 14, 281.
Rev. 1982, 11, 141. (b) Paquette, L. A. Aldrichim. Acta 1984,
17, 43. (c) Ho, T.-L. Carbocyclic Construction in Terpene
Synthesis; VCH: Weinheim, 1988.
7. Preliminary results of this study were reported as
a
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