π-face-selective 1,3-dipolar cycloadditions of 3,4-Di-tert- butylthiophene 1-oxide with 1,3-dipoles

Article abstract of DOI:10.1080/10426500902856297

3,4-Di-tert-butylthiophene 1-oxide underwent 1,3-dipolar cycloadditions with 1,3-dipoles such as nitrile oxide, diazomethane, nitrile imide, nitrone, and azomethine ylide at its syn-π-face with respect to the S=O bond. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500902856297

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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π-Face-Selective 1,3-Dipolar
Cycloadditions of 3,4-Di-tert-
butylthiophene 1-Oxide with
1,3-Dipoles
Juzo Nakayama a , Tomohiro Furuya a , Yasuko Suzuki
a , Suguru Hiraiwa a & Yoshiaki Sugihara a
a Department of Chemistry, School of Science and
Engineering , Saitama University , Saitama, Japan
Published online: 28 Apr 2009.
To cite this article: Juzo Nakayama , Tomohiro Furuya , Yasuko Suzuki , Suguru
Hiraiwa & Yoshiaki Sugihara (2009) π-Face-Selective 1,3-Dipolar Cycloadditions of 3,4-
Di-tert-butylthiophene 1-Oxide with 1,3-Dipoles, Phosphorus, Sulfur, and Silicon and
the Related Elements, 184:5, 1175-1183, DOI: 10.1080/10426500902856297
To link to this article: http://dx.doi.org/10.1080/10426500902856297
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Phosphorus, Sulfur, and Silicon, 184:1175–1183, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902856297
π-Face-Selective 1,3-Dipolar Cycloadditions of
3,4-Di-tert-butylthiophene 1-Oxide with 1,3-Dipoles
Juzo Nakayama, Tomohiro Furuya, Yasuko Suzuki,
Suguru Hiraiwa, and Yoshiaki Sugihara
Department of Chemistry, School of Science and Engineering, Saitama
University, Saitama, Japan
3,4-Di-tert-butylthiophene 1-oxide underwent 1,3-dipolar cycloadditions with 1,3-
dipoles such as nitrile oxide, diazomethane, nitrile imide, nitrone, and azomethine
ylide at its syn-π-face with respect to the S O bond.
Keywords 1,3-Dipolar cycloaddition; π-face selectivity; heterocycles; stereochemistry;
thiophene 1-oxide
INTRODUCTION
π-Facial selectivity (diastereofacial selectivity) in Diels–Alder reactions
has been attracting considerable attention. It has been investigated
most extensively by using 5-substituted cyclopentadienes as the diene.1
Thiophene 1-oxides, which have the general structure shown in Figure
1, are no longer aromatic and hence highly reactive. They serve as a
type of cyclic diene that possesses two π-faces, i.e., syn- and anti-faces,
for Diels–Alder reactions, with respect to the S O bond. We have re-
ported that 3,4-di-tert-butylthiophene 1-oxide (1) undergoes syn-π-face-
selective Diels–Alder reactions with a wide range of dienophiles.2–4
Recently, we also reported that the S2O, formed by retro-Diels–Alder
reaction of bicyclic compound 2, disproportionates to S3 (triatomic sul-
fur) and SO2, and the resulting S3 undergoes a syn-π-face-selective
1,3-dipolar cycloaddition to 1, the counterpart of the S2O formation, to
give the final product 3; the stereochemistry of 3 was determined by X-
ray diffraction analysis (Scheme 1).5 We have now examined 1,3-dipolar
Received 27 December 2007; accepted 29 February 2008.
Dedicated to Professor Marian Mikolꢀajczyk, CBMiM PAN in Lꢀ o´dz´, Poland, on the
occasion of his 70th birthday.
Address correspondence to Juzo Nakayama, Department of Chemistry, School of
Science and Engineering, Saitama University, Sakura-ku, Saitama, Saitama 338-8570,
Japan. E-mail: nakayama@mail.saitama-u.ac.jp
1175

1176
J. Nakayama et al.
Anti-π-face to the S=O bond
R
S
R
R
O
R
Syn-π-face to the S=O bond
FIGURE 1 General structure and two π-faces of thiophene 1-oxides.
cycloadditions of 1 with a series of 1,3-dipoles to know more about the
stereochemical course of the reaction. To our knowledge, π-facial se-
lectivity in 1,3-dipolar cycloadditions has been far less investigated.6–9
O
S
tBu
SO
S
tBu
2
retro-Diels-Alder reaction
O
O
S
O
S
S
+
S
S
+
S
dispropor-
tionation
tBu
S
tBu
tBu
O
tBu
S
O
1,3-dipolar
cycloaddition
S
S
3
1
S
SCHEME 1 Syn-π-face-selective 1,3-dipolar cycloaddition of S3 to thiophene
1-oxdide 1.
Initially, 1,3-dipolar cycloadditions of 1 with propargyl-allenyl type
1,3-dipoles were examined. The reaction of 1 with acetonitrile oxide,
generated in situ by reaction of nitroethane with phenyl isocyanate
in the presence of Et3N in CH2Cl2 at room temperature,10 furnished
the single 1,3-dipolar cycloadduct 4a11 in 80% yield (Scheme 2). On
the other hand, the reaction of 1 with benzonitrile oxide in CH2Cl2,
generated by treatment of α-chlorobenzaldehyde oxime (PhCCl NOH)
with Et3N,12 afforded a 10:1 mixture of the two diastereomers 4b and
4bꢀ,11 which were isolated in 80% and 7% yields, respectively. The ratio
4b:4bꢀ showed solvent dependency; it was 23:1 and 24:1 in benzene and
toluene, respectively.
The regiochemistry of the addition in the formation of 4a was de-
termined by observation of the coupling (1.1 Hz) between Ha and the

1,3-Dipolar Cycloaddition
1177
H
b S
Ha
tBu
tBu
tBu
tBu
–
S
+
RT
O
+
–
Me
N O
O
CH2Cl2
80%
O
Me
1
N
4a
tBu
H
b S
N
tBu
Ph
Hb
O
O
tBu
Ha
+
+
+
tBu
Ph
N O
1
S
O
Ph
Ha
CH2Cl2
N
4b
80%
O
4b'
7%
SCHEME 2 1,3-Diploar cycloaddition of 1 with nitrile oxides.
oxazole methyl protons. The configuration of the sulfinyl group was de-
termined on the basis of aromatic solvent-induced shift (ASIS) and
Eu(thd)3-induced shift [Eu(thd)3; europium tris(2,2,6,6-tetramethyl-
3,5-heptanedionate)]. It is well documented that benzene coordinates to
the sulfur atom of the sulfinyl group,13−17 whereas the europium atom
of Eu(thd)3 coordinates to the oxygen atom. Thus, for the adduct 4a,
the 1H NMR spectrum in C6D6 would result in the high field shift of Ha
and Hb, while the oxazole methyl signal remains virtually unchanged.
On the other hand, Eu(thd)3 would bring about the low field shift of
Ha, Hb, and the methyl protons. Indeed, the spectrum in C6D6 resulted
in the high field shift of Ha and Hb by 0.60 and 0.43 ppm, respectively,
keeping the methyl signal virtually unchanged. Meanwhile, Eu(thd)3
(0.2 molar amount) brought about the low field shift of Ha, Hb, and
methyl signals by 0.52, 0.45, and 0.56 ppm, respectively. The ASIS and
Eu(thd)3-induced shift for 4b were similar to those described above.
Meanwhile, Ha of 4b’ remote from the coordinated benzene showed a
negligibly small ASIS (0.03 ppm low field shift), whereas Hb moved to a
high field by 0.59 ppm. The above methods were also used for the deter-
mination of the stereochemistry of the other 1,3-dipolar cycloadducts
described below.
The reaction of 1 with an equimolar amount of diazomethane at 0 ◦C
produced the single adduct 4c11 in 93% yield (Scheme 3). In the 1H NMR
of 4c, Ha appeared as a d/d (J = 9.5/8.0 Hz) due to the coupling with
the methylene protons in agreement with the assigned regiochemistry.
Incidentally, diphenyldiazomethane, trimethylsilyl azide, and phenyl
azide failed to react with 1.

1178
J. Nakayama et al.
H
b S
Ha
tBu
tBu
O
tBu
tBu
S
+
0 °C/Et2O
93%
+
H2C N N
O
N
CH2
N
1
4c
SCHEME 3 1,3-Diploar cycloaddition of 1 with diazomethane.
Benzonitrile N-phenylimide (6), generated from 5,18 added to 1 to
furnish 4d11 in about 50% yield (Scheme 4).19 The structure of 4d was
determined by X-ray diffraction analysis (Figure 2).20 Interestingly,
methyl protons and methyl carbons of thetert-butyl group attached to
the sp3 carbon appeared as a broad singlet both in the 1H and 13C NMR
spectra, probably because of the restricted rotation.
H
tBu
tBu
Et3N
–HCl
b S
O
Ph
Cl
1
+
Ha
–
N
H
Ph
N N Ph
N
PhH
60 °C
~50%
N Ph
Ph
Ph
6
N
4d
5
SCHEME 4 1,3-Diploar cycloaddition of 1 with nitirile imine 6.
Next, reactions with allyl type 1,3-dipoles were investigated. Heating
equimolar amounts of 1 and nitrone 7 in refluxing toluene provided the
sole adduct 4e11 in 61% yield (Scheme 5). Similarly, the reaction with
nitrone 8 gave the adduct 4f11 in 73% yield.
The reaction of 1 with azomethine ylide 9,21 generated from three
molar amounts of amine 10, gave a 10:1 diastereomeric mixture of 4g
and 4gꢀ11 in good combined yield; only 4g was isolated in pure form in
73% yield (Scheme 6).
For the attempted reaction with carbonyl ylide 11, its precursor
tetracyanoethylene oxide 12 reduced 1 to give thiophene 13 and car-
bonyl cyanide14, as was reported by us.22 The reaction with ozone pro-
ceeded smoothly, but gave a complex mixture after treatment with Zn
in acetic acid, from which a crystalline product, the structure of which
could not be determined unambiguously, was isolated in low yield.
tBu
But
+
NC
NC
CN
O
NC
NC
O
NC
NC
CN
CN
O
–
CN
S
12
11
13
14

1,3-Dipolar Cycloaddition
1179
H
b S
Ha
tBu
tBu
PhMe
reflux
Ph
H
O–
+
Me
O
tBu
tBu
S
+
N
Ph
Hc
O
+
O
61%
N
1
7
Me
4e
H
b S
tBu
tBu
O
PhMe
reflux
Ha
Hc
N O–
+
1
O
73%
N
8
4f
SCHEME 5 1,3-Diploar cycloaddition of 1 with nitrones 7 and 8.
H
CH2Ph
N
b S
Ha
tBu
tBu
tBu
CH2Ph
N
O
Hb
–
1
+
+
+
CH2
CH2
N
tBu
S
9
Ha
CH2Ph
O
4g'
4g: 73%
CF3CO2H
4g:4g' = 10:1
CH2Ph
N
Me3SiH2C
CH2OMe
10
SCHEME 6 1,3-Diploar cycloaddition of 1 with azomethine imide 9.
A Mulliken population analysis (B3LYP/6-31G* level23) of 1 pre-
dicted that the positive charges are located at the 3- and 4-positions,
while the negative charges are located at the 2- and 5-positions (Fig-
ure 3). Thus, the observed regioselectivity is in agreement with the
electronic demand, where the positive end of 1,3-dipoles adds to the 2-
position, and the negative end adds to the 3-position. The observed re-
gioselectivity is also in harmony with the steric demand that is brought
about by bulky tert-butyl group. Only in the case of diazomethane, the
steric demand governs the regiochemistry, where the less bulky nega-
tive end (diazo nitrogen) added to the congested 3-position, while the
bulkier negative end (CH2) added to the less congested 2-position.
As described above, the 1,3-dipolar cycloadditions of 1 took place
preferentially at the syn-π-face to the S O bond. This would best be
explained as follows. The 1-oxide 1 has a bent structure at C1 and C4
with a tilt angle of 9.3◦ (Figure 4). Thus, for the syn-π-face addition,
the transition state can be easily reached with a smaller conformational

1180
J. Nakayama et al.
FIGURE 2 ORTEP plot of molecular structure of 4d in the crystal. Ellipsoids
are drawn at 50% probability level.
tBu
0.149
But
0.139
–0.436
–0.430
0.777
S
–0.592
O
1
FIGURE 3 Mulliken population analysis of 1 (B3LYP/6-31G* level).
tBu
tBu
°
Greater conformational
B
C
change of 1
A
S
Anti-face addition
O
S
tBu C2
C1
(4)
O
(3)
9.3°
°
Syn-face addition
tBu
S
O
tBu
Smaller conformational
A
C
change of 1
B
FIGURE 4 Conformational changes required at the transition states.

1,3-Dipolar Cycloaddition
1181
change of 1, whereas, for the anti-face addition, a larger conformational
change is required to reach the transition state, where the inversion
at C1 and C4 is required.2–4 Accordingly, the activation energy of the
reaction would be smaller for the syn-π-face addition than for the anti-
π-face addition, thus making the former process more favorable.
REFERENCES
[1] W. Oppolozer, In: Comprehensive Organic Synthesis, L. A. Paquette (Ed.) (Pergamon
Press, Oxford, 1991), Vol. 5, Chapter 4.1.
[2] T. Otani, J. Takayama, Y. Sugihara, A. Ishii, and J. Nakayama, J. Am. Chem. Soc.,
125, 8255 (2003).
[3] J. Takayama, S. Fukuda, Y. Sugihara, A. Ishii, and J. Nakayama, Tetrahedron Lett.,
44, 5159 (2003).
[4] J. Takayama, Y. Sugihara, T. Takayanagi, and J. Nakayama, Tetrahedron Lett., 46,
4165 (2005).
[5] J. Nakayama, S. Aoki, J. Takayama, A. Sakamoto, Y. Sugihara, and A. Ishii, J. Am.
Chem. Soc., 126, 9085 (2004).
[6] M. Burdisso, R. Gandolfi, P. Pevarello, A. L. Poppi, and A. Rastelli, Tetrahedron
Lett., 26, 4653 (1985).
[7] H. Landen, B. Margraf, and H.-D. Martin, Tetrahedron Lett., 29, 6593 (1988).
[8] H. Landen, B. Margraf, H.-D. Martin, and A. Steigel, Tetrahedron Lett., 29, 6597
(1988).
[9] H. Hake, H. Landen, H.-D. Martin, B. Mayer, A. Steigel, G. Distefano, and A.
Modelli, Tetrahedron Lett., 29, 6601 (1988).
[10] T. Mukaiyama and T. Hoshino, J. Am. Chem. Soc., 82, 5339 (1960).
[11] Supporting information of cycloadducts 4a–4g (satisfactory elemental analyses
were obtained except 4d whose analysis sample could not be supplied19). 4a: color-
less crystals; mp 193–194◦C; IR (KBr) ν 1048 cm−1 (S O); 1H NMR (CDCl3) δ1.05
(s, 9H), 1.35 (s, 9H), 2.18 (d, 3H, J = 1.1 Hz), 4.86 (d, 1H, J = 1.1 Hz, Ha), 6.61 (s,
1H, Hb); 1H NMR (C6D6) δ1.74 (s, 9H), 1.11 (s, 9H), 2.14 (d, 3H, J = 1.5 Hz), 4.26
(d, 1H, J = 1.5 Hz, Ha), 6.18 (s, 1H, Hb); 1H NMR (CDCl3/0.2 mol eq. Eu(thd)3)
δ1.19 (s, 9H), 1.47 (s, 9H), 2.73 (broad s, 3H), 5.38 (broad s, 1H, Ha), 7.06 (broad s,
1H, Hb); 13C NMR (CDCl3) δ 13.9, 27.9, 32.6, 36.1, 36.6, 74.9, 108.4, 134.4, 153.2,
163.1. 4b: colorless crystals; mp 167–168 ◦C; IR (KBr) ν 1048 cm−1 (S O); 1H NMR
(CDCl3) δ 1.14 (s, 9H), 1.41 (s, 9H), 5.54 (s, 1H, Ha), 6.61 (s, 1H, Hb), 7.35–7.40 (m,
3H), 7.68–7.75 (m, 2H); 1H NMR (C6D6) δ 0.80 (s, 9H), 1.12 (s, 9H), 5.14 (s, 1H,
Ha), 6.14 (s, 1H, Hb), 7.02–7.12 (m, 3H), 7.80 (d, 2H, J = 1.1); 1H NMR (CDCl3/0.2
mol eq. Eu(thd)3) δ 1.29 (s, 9H), 1.53 (s, 9H), 6.04 (broad s, 1H, Ha), 7.10 (broad s,
1H, Hb), 7.32–7.35 (m, 3H), 8.32 (br, 2H); 13C NMR (CDCl3) δ 27.6, 32.5, 36.2, 37.6,
73.4, 111.0, 127.1, 128.3, 128.7, 130.0, 134.4, 153.0, 163.5. 4bꢀ: colorless crystals;
mp 169–170◦C; IR (KBr) ν 1039 cm−1 (S O); 1H NMR (CDCl3) δ 1.25 (s, 9H), 1.41
(s, 9H), 4.80 (s, 1H, Ha), 6.63 (s, 1H, Hb), 7.44–7.50 (m, 3H), 7.79–7.86 (m, 2H); 1
H
NMR (C6D6) δ 1.06 (s, 9H), 1.08 (s, 9H), 4.83 (s, 1H, Ha), 6.04 (s, 1H, Hb), 7.01–7.04
(m, 3H), 7.90–7.93 (m, 2H); 1H NMR (CDCl3/0.2 mol eq. Eu(thd)3) δ 1.39 (s, 9H),
1.46 (s, 9H), 5.25 (s, 1H, Ha), 6.81 (s, 1H, Hb), 7.43–7.47 (m, 3H), 7.90–7.95 (m, 2H);
13C NMR (CDCl3) δ 27.2, 32.5, 36.7, 37.3, 79.8, 111.0, 126.9, 127.8, 129.1, 130.3,
130.7, 151.8, 166.8. 4c: colorless crystals; mp 153–154 ◦C; IR (KBr) ν 1031 cm−1
(S O); 1H NMR (CDCl3) δ 1.12 (s, 9H), 1.34 (s, 9H), 3.83 (dd, 1H, J = 8.0, 9.5 Hz,

1182
J. Nakayama et al.
Ha), 4.78 (dd, 1H, J = 8.0, 18.7 Hz), 4.81 (dd, 1H, J = 9.5, 18.7 Hz), 6.35 (s, 1H, Hb);
1H NMR (C6D6) δ 0.74 (s, 9H), 1.03 (s, 9H), 2.99 (dd, 1H, J = 8.3, 9.8 Hz, Ha), 4.43
(dd, 1H, J = 9.8, 19.0 Hz), 4.93 (dd, 1H, J = 8.1, 18.8 Hz), 5.87 (s, 1H, Hb); 1H NMR
(CDCl3/0.2 mol eq. Eu(thd)3) δ 1.16 (s, 9H), 1.49 (s, 9H), 4.35 (t, 1H, J = 9.0 Hz,
Ha), 5.30 (dd, 1H, J = 9.5, 18.8 Hz), 5.92 (br, 1H), 6.98 (broad s, 1H, Hb); 13C NMR
(CDCl3) δ 28.4, 33.4, 36.4, 37.6, 60.1, 74.1, 119.4, 134.7, 161.7. 4d: colorless crystals;
1H NMR (CDCl3) δ 0.84 (s, 9H), 1.25 (broad s, 9H), 4.87 (s, 1H, Ha), 6.84 (s, 1H, Hb),
7.28–7.31 (m, 4H), 7.33–7.38 (m, 2H), 7.59–7.61 (m, 2H, J = 7.6 Hz), 7.80–7.82 (m,
2H, J = 7.8 Hz); 13C NMR (CDCl3) δ 28.1 (broad s), 33.7, 37.2, 40.1, 74.6, 97.0, 125.7,
128.2, 128.66, 128.72, 128.9, 131.2, 131.8, 135.4, 143.5, 146.9, 168.6. 4e: colorless
crystals; mp 127–128 ◦C; IR (KBr) ν 1038 cm−1 (S O); 1H NMR (CDCl3): δ 1.09 (s,
9H), 1.40 (s, 9H), 2.61 (s, 3H), 4.33 (d, 1H, J = 7.6 Hz, Hc), 4.61 (d, 1H, J = 7.6 Hz,
Ha), 6.41 (s, 1H, Hb), 7.20–7.37 (m, 3H), 7.42–7.48 (m, 2H);1H NMR (C6D6) δ 0.87 (s,
9H), 1.20 (s, 9H), 2.46 (s, 3H), 4.35 (d, 1H, J = 8.3 Hz, Ha), 4.57 (d, 1H, J = 8.8 Hz,
Hc), 6.04 (s, 1H, Hb), 7.07–7.22 (m, 3H), 7.67 (d, 2H, J = 6.8 Hz); 1H NMR (CDCl3,
0.2 mol eq. Eu(fod)3,fod = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate)
δ 1.27 (s, 9H), 1.55 (s, 9H), 2.91 (s, 3H), 4.34 (broad s, 1H, Hc), 5.37 (m, 1H, Ha),
7.02 (broad s, 1H, Hb), 7.32–7.46 (m, 3H), 8.27 (broad s, 2H);13C NMR (CDCl3) δ
28.0, 33.1, 35.9, 37.7, 43.1, 70.8, 78.0, 104.0, 128.0, 128.5, 128.7, 132.8, 137.1, 165.1.
4f: colorless crystals; mp 193.5–194.5 ◦C; IR (KBr) ν 1040 cm−1 (S O); 1H NMR
(CDCl3) δ 1.02 (s, 9H), 1.34 (s, 9H), 1.68–1.83 (m, 2H), 1.95–2.14 (m, 2H), 2.77–2.89
(m, 1H, J = 13.6 Hz), 3.38–3.48 (m, 1H, J = 13.6 Hz), 4.04 (d, 1H, J = 3.3 Hz, Ha),
4.18–4.26 (m, 1H, J = 4.2 Hz, Hc), 6.39 (s, 1H, Hb); 1H NMR (C6D6) δ 0.79 (s, 9H),
1.26 (s, 9H), 1.52–1.84 (m, 4H), 2.39–2.54 (m, 1H, J = 13.6 Hz), 3.15–3.25 (m, 1H,
J = 13.6 Hz), 3.60 (d, 1H,J = 3.4 Hz, Ha), 4.45–4.54 (m, 1H, J = 4.2 Hz, Hc), 6.14 (s,
1H, Hb); 1H NMR (CDCl3/0.2 mol eq. Eu(thd)3) δ 1.08 (s, 9H), 1.39 (s, 9H), 1.69–1.84
(m, 2H), 2.00–2.19 (m, 2H), 2.84–2.95 (m, 1H), 3.44–3.53 (m, 1H), 4.24 (broad s, 1H,
Ha), 4.58–4.69 (m, 1H, Hc), 6.61 (s, 1H, Hb); 13C NMR (CDCl3) δ 25.0, 28.1, 32.3,
32.4, 35.90, 35.91, 57.0, 62.4, 78.4, 104.0, 133.5, 166.0. 4g: colorless crystals; mp
128–129 ◦C; IR (KBr) ν 1044 cm−1 (S O); 1H NMR (CDCl3) δ 1.00 (s, 9H), 1.27 (s,
9H), 2.66 (d, 1H, J = 9.9 Hz), 2.84–3.03 (m, 3H), 3.61 (s, 2H), 4.12 (t, 1H, J = 8.3
Hz, Ha), 6.35 (s, 1H, Hb), 7.23–7.31 (m, 5H); 1H NMR (C6D6) δ 0.71 (s, 9H), 0.96
(s, 9H), 2.50 (d, 1H, J = 9.6 Hz), 2.65–2.72 (m, 2H), 3.24–3.41 (m, 3H), 3.66 (t, 1H,
J = 8.1 Hz, Ha), 6.07 (s, 1H, Hb), 7.23–7.31 (m, 5H); 1H NMR (CDCl3/0.2 mol eq.
Eu(thd)3) δ 1.09 (s, 9H), 1.36 (s, 9H), 2.84 (m, 1H), 3.07–3.20 (m, 3H), 3.71 (s, 2H),
4.43 (broad s, 1H, Ha), 6.70 (broad s, 1H, Hb), 7.23–7.35 (m, 5H); 13C NMR (CDCl3)
δ 29.1, 33.5, 36.0, 36.5, 51.7, 60.1, 61.0, 66.4, 76.0, 127.0, 128.2, 128.5, 133.1, 138.4,
166.1. 4gꢀ: 1H NMR (CDCl3) δ 1.15 (s, 9H), 1.29 (s, 9H), 2.42 (dd, 1H, J = 7.4, 9.9
Hz), 2.53 (d, 1H, J = 9.9 Hz), 2.79 (d, 1H, J = 9.9 Hz), 3.11 (t, 1H, J = 9.2 Hz, Ha),
3.47–3.54 (m, 3H), 6.50 (s, 1H, Hb), 7.23–7.31 (m, 5H).
[12] G. W. Perold, A. P. Steyn, and F. V. K. von Reiche, J. Am. Chem. Soc., 79, 462 (1957).
[13] C. H. Green and D. G. Hellier, J. Chem. Soc., Perkin Trans. 2, 458 (1972).
[14] C. H. Green and D. G. Hellier, J. Chem. Soc., Perkin Trans. 2, 243 (1973).
[15] C. H. Green and D. G. Hellier, J. Chem. Soc., Perkin Trans. 2, 190 (1975).
[16] G. W. Buchanan and D. G. Hellier, Can. J. Chem., 54, 1428 (1976).
[17] J. G. Pritchard and P. C. Lauterbur, J. Am. Chem. Soc., 83, 2105 (1961).
[18] R. Huisgen, M. Seidel, G. Wallbillich, and H. Knupfer, Tetrahedron, 17, 3 (1962).
[19] Caution! The precursor compound 5 caused a severe skin eruption. Therefore, the
yield of 4d was not optimized.
[20] Crystal data for 4d: C25H30N2OS, M = 406.57, orthorhombic, space group Pbca; a =
3
˚
˚
16.6749(19), b = 10.7803(6), c = 24.0477(14) A; Z = 8; V = 4322.8(4) A ; Dc = 1.249

1,3-Dipolar Cycloaddition
1183
g/cm3, µ = 0.168 mm−1; measured reflections 30101, independent reflections 5199
[R(int) = 0.0863], R = 0.0788, Rw = 0.1523, GOF = 1.091. Crystallographic data
for the structural analysis have been deposited at the Cambridge Crystallographic
Data Center, CCDC No. 671816 for 4d. Copies of this information can be obtained
from The Director, DDCD, 12 Union Road, Cambridge CB2 1EZ, UK (Fax: +44-
1223-336033; e-mail: deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
[21] Y. Terao, H. Kotaki, N. Imai, and K. Achiwa, Chem. Pharm. Bull., 33, 2762 (1985).
[22] J. Nakayama, A. Tai, S. Iwasa, T. Furuya, and Y. Sugihara, Tetrahedron Lett., 46,
1395 (2005).
[23] Although a crystalline product was isolated in low yield, its structure could not be
determined unambiguously.
[24] M. J. Frisch et al., Gaussian, Inc., Pittsburgh, PA, 1998.