Synthesis, structure, and reaction of chiral 2-azidoimidazolinium salts: (7aS)-3-azido-5,6,7,7a-tetrahydro-2-[(1R)-1-phenylethyl]-1H-pyrrolo[1,2-c]imidazolium hexafluorophosphate and 2-azido-1,3-bis[(S)-1-phenylethyl]imidazolinium hexafluorophosphate

Article abstract of DOI:10.1016/j.tetlet.2016.03.036

Two chiral 2-azidoimidazolinium salts [(7aS)-3-azido-5,6,7,7a-tetrahydro-2-[(1R)-1-phenylethyl]-1H-pyrrolo[1,2-c]imidazolium hexafluorophosphate (2) and 2-azido-1,3-bis[(S)-1-phenylethyl]imidazolinium hexafluorophosphate (3)] were synthesized, and their structures were determined by X-ray single crystal structural analysis. Migratory amidation reaction of enol silyl ether with 3 proceeded, but good diastereoselectivity was not observed in the reaction.

Full text of DOI:10.1016/j.tetlet.2016.03.036

Tetrahedron Letters 57 (2016) 1794–1797
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis, structure, and reaction of chiral 2-azidoimidazolinium
salts: (7aS)-3-azido-5,6,7,7a-tetrahydro-2-[(1R)-1-phenylethyl]-1H-
pyrrolo[1,2-c]imidazolium hexafluorophosphate and 2-azido-1,3-bis
[(S)-1-phenylethyl]imidazolinium hexafluorophosphate
⇑
Mitsuru Kitamura , Akihiro Ishikawa, Tatsuo Okauchi
Department of Applied Chemistry, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu 804-8550, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Two chiral 2-azidoimidazolinium salts [(7aS)-3-azido-5,6,7,7a-tetrahydro-2-[(1R)-1-phenylethyl]-1H-
pyrrolo[1,2-c]imidazolium hexafluorophosphate (2) and 2-azido-1,3-bis[(S)-1-phenylethyl]imidazolin-
ium hexafluorophosphate (3)] were synthesized, and their structures were determined by X-ray single
crystal structural analysis. Migratory amidation reaction of enol silyl ether with 3 proceeded, but good
diastereoselectivity was not observed in the reaction.
Received 16 January 2016
Revised 8 March 2016
Accepted 11 March 2016
Available online 11 March 2016
Ó 2016 Published by Elsevier Ltd.
Keywords:
Chiral compounds
Azides
Imidazolinium salts
Migratory amidation
We have recently developed various synthetic methods using
2-azido-1,3-dimethylimidazolinium salts with nucleophilic com-
pounds. For example, 2-azido-1,3-dimethylimidazolinium chloride
(ADMC 1a) and its corresponding hexafluorophosphate (ADMP 1b)
were observed to be efficient diazo-transfer reagents (Fig. 1).1
ADMC 1a was prepared by the reaction of 2-chloro-1,3-
dimethylimidazolinium chloride (DMC) and sodium azide. ADMP
1b was isolated as a thermally stable crystal with a low explosibil-
ity.2b ADMC 1a and ADMP 1b reacted with 1,3-dicarbonyl
compounds under mild basic conditions to give 2-diazo-1,3-
dicarbonyl compounds in high yields; these products were easily
isolated because the reaction byproducts are highly soluble in
water.2 Naphthols reacted with ADMC 1a in the presence of Et3N
to give the corresponding diazonaphthoquinones in good to high
yields.3 Furthermore, ADMP 1b shows efficient diazo-transfer abil-
ity to primary amines even without the aid of a metal catalyst such
as Cu(II).4 2-Azidoimidazolinium salts 1 also show azide-transfer
ability to oxygen nucleophiles.5 In addition, migratory amidation
proceeded when ADMP 1b was treated with a benzyl aryl ketone
the azide group in the 2-azidoimidazolinium salt, the salt would
be a new asymmetric reagent for the introduction of a nitrogen
functional group. However, the synthesis of optically active chiral
2-azido-1,3-dialkylimidazolinium salts has not been previously
reported. Recently, Ishikawa developed efficient chiral cyclic
guanidine possessing an imidazoline structure.7,8 Inspired by the
results, we examined the synthesis of chiral 2-azido-1,3-dialkylim-
idazolinium salts and successfully prepared (7aS)-3-azido-5,6,7,7a-
tetrahydro-2-[(1R)-1-phenylethyl]-1H-pyrrolo[1,2-c]imidazolium
hexafluorophosphate (2) and 2-azido-1,3-bis[(S)-1-phenylethyl]
imidazolinium hexafluorophosphate (3) (Fig. 1). Although a fine
X-ray structure of 2-azido-1,3-dialkylimidazolinium salt has not
been reported,9 we determined the unambiguous structures of 2
and 3 by single-crystal X-ray diffraction, with good R factors. In this
Letter, we report the synthesis, structure, and reaction of optically
active chiral 2-azido-1,3-dialkylimidazolinium salts 2 and 3 in
detail.
or enol silyl ether of an aryl ketone, giving
a-aryl amide
(Scheme 1).6 These reactions were initiated by the attack of a
nucleophile at an azide moiety in 1. We hypothesized that if an
efficient asymmetric environment could be constructed around
⇑
Corresponding author. Tel./fax: +81 93 884 3304.
E-mail address: kita@che.kyutech.ac.jp (M. Kitamura).
Figure 1. 2-Azido-1,3-dialkylimidazolinium salts 1–3.
http://dx.doi.org/10.1016/j.tetlet.2016.03.036
0040-4039/Ó 2016 Published by Elsevier Ltd.

M. Kitamura et al. / Tetrahedron Letters 57 (2016) 1794–1797
1795
Scheme 1. Migratory amidation with ADMP 1b.
Figure 2. ORTEP of 2. Thermal ellipsoids set at 50%. Crystal data of 2: C14H18F6N5P,
M = 401.29, orthorhombic, a = 8.457 (2), b = 10.074 (3), c = 20.740 (6) Å, V = 1766.9
(8) Å3, T = 123 K, space group P212121, Z = 4, 19,639 reflections measured, 3201
unique (Rint = 0.045), which were used in all calculations. R[F2 > 2
r
(F2)] = 0.045, wR
(F2) = 0.115.
Scheme 2. Synthesis of chiral bicyclic 2-azido-1,3-dialkylimidazolinium salt 2. (a)
DCC (1.1 equiv), DMAP (1.1 equiv), CH2Cl2, rt, 26 h (93%); (b) 3 M HCl aq., MeOH,
50 °C, 8 h (83%); (c) LiAlH4 (4.5 equiv), THF, 60 °C, 7 h; (d) thiocarbonyl imidazole
(1.1 equiv), o-dichlorobenzene, reflux, 6 h (2 steps, 62%); (e) (COCl)2 (1.4 equiv),
toluene, 70 °C, 5 h; (f) KPF6 (1.3 equiv), CH3CN, rt, 0.5 h (2 steps, 75%); (g) NaN3
(2.0 equiv), CH3CN, 0 °C, 1 h (52%).
Bicyclic 2-azido-1,3-dialkylimidazolinium salt 2 was synthe-
sized as shown in Scheme 2. First, bicyclic thiourea 8 was synthe-
sized from N-Boc-L-proline 5 and (R)-1-phenylethylamine (6) in
four steps using
a procedure similar to that of Ishikawa
(Scheme 2).8b Thiourea 810 was converted into chloroimidazolin-
ium chloride 9 by treatment with oxalyl chloride, and 9 was subse-
quently transformed to azidoimidazolinium salt
2 by anion
exchange with KPF6 and successive azide introduction with sodium
azide.11
Figure 3. ORTEP of 3. Thermal ellipsoids set at 50%. Crystal data of 3: C19H22F6N5P,
M = 465.38, monoclinic, a = 6.961 (3), b = 21.148 (7), c = 14.194 (6) Å, V = 2087.4
(13) Å3, T = 123 K, space group P21, Z = 4, 26,019 reflections measured, 7397 unique
Moreover, C2-symmetric azidoimidazolinium salt 3 was synthe-
sized via known chloroimidazolinium chloride 128b prepared from
(S)-1-phenylethylamine (6) and oxalaldehyde 11 (Scheme 3).12
Single crystals of 2 and 3 were obtained by recrystallization
from a mixed solvent of hexane and ethyl acetate, and we success-
fully determined their X-ray structures (Figs. 2 and 3, Table 1).13
In Table 2, bond lengths and bond angles of azide moieties in
several azides are shown as a reference.14 The N(1)–N(2) and
(Rint = 0.060), which were used in all calculations. R[F2 > 2 (F2)] = 0.054, wR(F2)
r
= 0.107.
N(2)–N(3) bond lengths of sulfonylazides are 1.24–1.28 Å,
1.11–1.13 Å, respectively (Runs 1–5). The difference between N
(1)–N(2) and N(2)–N(3) bond lengths is 0.12–0.17 Å. In contrast,
the difference between N(1)–N(2) and N(2)–N(3) bond lengths of
alkyl azides is smaller (0.05–0.08 Å) than those of sulfonylazides.
Compound 2 crystallized in the orthorhombic space group
P212121.13 The azide group of 2 is bent, with an N(1)–N(2)–N(3)
angle of 171.7(3)°. The N(1)–N(2) and N(2)–N(3) bond lengths of
2 are 1.267(3) and 1.116(4) Å, respectively, and the difference of
between N(1)–N(2) and N(2)–N(3) bond lengths was 0.15 Å. These
data are more similar to those of sulfonyl azides than to those of
alkyl azides. The dihedral N(2)–N(1)–C(1)–N(4) angle is 19.9(4)°,
indicating that the azide group is less twisted with reference to
the imidazoline ring plane (<30°) than that of ADMP, in which
the corresponding dihedral angle is À39.85° (computational
calculation; B3LYP/6-31G⁄⁄).4b The chiral 1-phenylethyl group
(–CH(CH3)Ph) in 2 is opposite to the azide group, and the
Scheme 3. Synthesis of C2-symmetric chiral 2-azido-1,3-dialkylimidazolinium salt
3. (a) Cat. AcOH, CH2Cl2, rt, 24 h (76%); (b) NaBH4 (5.0 equiv), MeOH, rt, 27 h (88%);
(c) CSCl2 (1.5 equiv), Et3N (2.0 equiv), CH2Cl2, rt, 5 h (47%); (d) (COCl)2 (1.8 equiv),
toluene, 70 °C, 26 h (92%); (e) KPF6 (1.8 equiv), CH3CN, rt, 1 h (97%); (f) NaN3
(1.7 equiv), CH3CN, 0 °C, 1 h (84%).

1796
M. Kitamura et al. / Tetrahedron Letters 57 (2016) 1794–1797
Table 1
Selected geometric parameters for 2 and 3 (distances in Å, angles in degrees)
2
3-A
3-B
N(1)–N(2) 1.267(3)
N(1)–N(2) 1,265(5)
N(6)–N(7) 1.248(5)
N(2)–N(3) 1.116(4)
N(2)–N(3) 1.121(5)
N(7)–N(8) 1.116(5)
C(1)–N(1) 1.372(4)
C(1)–N(1) 1.385(5)
C(20)–N(6) 1.369(5)
C(1)–N(4) 1.327(4)
C(1)–N(4) 1.317(5)
C(20)–N(9) 1.325(5)
C(1)–N(5) 1.319(4)
C(1)–N(5) 1.328(5)
C(20)–N(10) 1.322(5)
N(1)–N(2)–N(3) 171.7(3)
N(2)–N(1)–C(1)–N(4) 19.9(4)
N(2)–N(1)–C(1)–N(5) À160.7(2)
C(1)–N(5)–C(7)–C(9) 95.6(3)
N(1)–N(2)–N(3) 168.6(4)
N(2)–N(1)–C(1)–N(4) 14.0(6)
N(2)–N(1)–C(1)–N(5) À167.0(3)
C(1)–N(5)–C(12)–C(14) À128.7(4)
C(1)–N(4)–C(4)–C(6) À85.7(4)
N(6)–N(7)–N(8) 168.9(4)
N(7)–N(6)–C(20)–N(9) À4.6(6)
N(7)–N(6)–C(20)–N(10) 177.4(3)
C(20)–N(10)–C(31)–C(33) À148.3(3)
C(20)–N(9)–C(23)–C(25) À85.0
Table 2
Bond lengths of azide moieties in several azides, as determined by X-ray analysis and
computational methods (distances in Å, angles in degrees)
Run
Azide
Methoda
N(1)–N(2)
N(2)–N(3)
N(1)–N(2)–N(3)
1
2
3
4
5
6
7
8
14b
14b
15c
16d
17e
17e
18f
X-ray
X-ray
X-ray
X-ray
X-ray
X-ray
Calc
1.244(3)
1.251(3)
1.2781(16)
1.273(3)
1.258(3)
1.178(3)
1.237
1.125(3)
1.129(3)
1.1103(16)
1.121(3)
1.116(4)
1.133(3)
1.156
173.8(2)
173.5(3)
172.43(13)
174.2(3)
173.0(3)
172.8(3)
172.7
1bg,h
Calc
1.251
1.129
168.86
a
X-ray: X-ray single crystal structure. Calc: computational calculation.
Data are quoted from Ref. 14b Two crystallographically independent molecules
b
Scheme 4. Reaction of enol silyl ether 4 with chiral azidoimidazolinium salts 2 and
3.
are observed in the unit, as shown in Runs 1 and 2.
c
The data are quoted from Ref. 14f.
The data are quoted from Ref. 14c.
d
e
The data are quoted from Ref. 14d Data for the sulfonyl azide component of 14
located nearly in the imidazoline ring plane. With respect to the
conformation of chiral 1-phenylethylgroups (–CH(CH3)Ph) in 3,
the most bulky phenyl groups are located almost perpendicular
to the imidazoline ring, and the next-bulkiest groups (i.e., methyl
groups) are located opposite to the azide group. The smallest
groups (i.e., hydrogens) are located near the azide group. The ten-
dencies of the lengths of the C–N bonds connecting the azide and
imidazoline ring (C(1)–N(1) 1.385(5) Å and C(20)–N(6) 1.369
(5) Å) and the C–N bonds in the imidazoline ring (C(1)–N(4)
1.317(5) Å, C(1)–N(5) 1.328(5) Å, C(20)–N(9) 1.325(5) Å, and
C(20)–N(10) 1.322(5) Å) are similar to the corresponding tenden-
cies observed in 2, which suggests that the structure of 3 is not like
the guanidinodiazonium resonance form II but is rather like the
azidoimidazolinium resonance form I in the solid state.
To examine the efficiency of 2 and 3 as chiral reagents, we
attempted migratory amidation reactions with enol silyl ether 4.
In the reaction of bicyclic 2, the desired migratory amidation pro-
duct 19 was not obtained; the formation of bicyclic formation urea
20 was observed after quenching with water (Scheme 4). The reac-
tion of C2-symmetric 3 and 4 proceeded to give desired product 21
and the alkyl azide component of 14 are shown in Run 5 and Run 6, respectively.
f
Optimized by calculation (MP2/6-311G). The data are quoted from Ref. 15.
g
Optimized by calculation (B3LYP/6-31G⁄⁄). The data are quoted from Ref. 4b.
h
Dihedral angles N(4)–C–N(1)–N(2) and N(5)–C–N(1)–N(2) are À39.85° and
149.60°, respectively.
C(7)–C(9) bond between the phenyl group and chiral center C(7)
places almost perpendicular to the imidazoline ring plane (95.6
(3)° for the dihedral C(1)–N(5)–C(7)–C(9) angle). The bond length
of C(1)–N(1) (1.372(4) Å) is the longest among the C–N
bond connected to C(1) (1.327(4) Å for C(1)–N(4), 1.319(4) Å for
C(1)–N(5)). These data suggest that the structure of 2 is similar
to azidoimidazolinium I (Ia and Ib), not to guanidinodiazonium II
(Fig. 4).
Compound 3 crystallized in the monoclinic space group P21,
with two crystallographically independent molecules 3-A and 3-
B in the unit.13 The bending angles of N(1)–N(2)–N(3) and
N(6)–N(7)–N(8) are 168.6(4)° and 168.9(4)°, respectively, which
are slightly smaller than that of 2 and those of various sulfonyl
azides. The difference in the bond lengths between two kinds of
N–N bonds in the azide group (N(terminal)–N(center) and N(cen-
ter)–N(inside)) are similar to that of 2 and the azide group in sul-
fonyl azides (1.265(5) Å for N(1)–N(2), 1.121(5) Å for N(2)–N(3),
1.248(5) Å for N(6)–N(7), and 1.116(5) Å for N(7)–N(8)). The dihe-
dral angles for N(2)–N(1)–C(1)–N(4) and N(7)–N(6)–C(20)–N(9)
are 14.0(6)°, and À4.6(6)°, respectively, and the azide groups are
in 78% yield, which was converted to a-aryl amide 22 in 92% yield.
However, diastereoselectivity was not observed in the reaction of 3
and 4 (ca. 1:1 by 1H NMR) and the enantiomer ratio of 22 was
54:46, as determined by chiral HPLC analysis.16 As previously men-
tioned, the X-ray analysis of 3 shows that the smallest substituent,
hydrogen, on the chiral center is placed near the azide group in the
solid state, which suggests that the asymmetric environment
around the azide group in 3 is not well constructed, which would
explain why the reaction of
diastereoselectivity.
3
and
4
afforded low
In conclusion, we synthesized the chiral 2-azidoimidazolinium
salts 2 and 3 and characterized their structure by X-ray single-
crystal structural analysis. The X-ray analysis results suggested
that the structures of 2 and 3 are not like the resonance form of
guanidinodiazonium but rather like azidoimidazolinium resonance
form in the solid state. We are continuing to develop a new chiral
Figure 4. Resonance structure of 2-azido-1,3-dialkylimidazolinium salt.

M. Kitamura et al. / Tetrahedron Letters 57 (2016) 1794–1797
1797
18.8 mmol) was added at 0 °C. After stirring the mixture for 5 h at 70 °C,
volatile materials were removed in vacuo to give crude 9. The crude 9 was
diluted with MeCN (50 mL), and potassium hexafluorophosphate (3.12 g,
17.0 mmol) was added to the solution. After stirring the mixture for 30 min at
room temperature, the mixture was passed through Celite pad. The filtrate was
concentrated in vacuo to afford crude compound, which was purified by
recrystallization (hexane/EtOAc) to give the pure 10 (3.97 g, 10.1 mmol) in 75%
yield (2 steps). Spectral data for 10: 1H NMR (500 MHz, CDCl3) d 7.45–7.40 (m,
3H), 7.39–7.30 (m, 2H), 5.31 (q, 1H, J = 7.0 Hz), 4.41–4.39 (m, 1H), 4.13–4.11
(m, 1H), 3.94–3.89 (m, 2H), 3.58–3.53 (m. 1H), 2.42–2.35 (m, 1H), 2.30–2.22
(m, 1H), 2.19–2.02 (m, 2H), 1.76 (dd, 3H, J = 7.0, 2.1 Hz); 13C NMR (125.7 MHz,
CDCl3) d 156.0, 136.8, 129.6, 129.4, 126.6, 62.7, 57.8, 50.2, 47.2, 30.1, 25.4, 16.2;
IR (KBr): 3462, 1653, 1559, 1497, 1457, 1276, 1111, 834, 703, 557; HRMS
azidoimidazolinium salt with a shielded azide group for the enan-
tioselective introduction of nitrogen functional groups.
Acknowledgments
This work was supported by JSPS KAKENHI Grant Number
26410054.
Supplementary data
35
23
(FAB+) Found; m/z, 249.1164. Calcd for C14
H
ClN2: (MÀPF6)+ 249.1159; [
a]
D
18
Supplementary data (experimental procedure and physical data
for 20, 21, and 22. 1H and 13C NMR spectra of 2, 3, 8, 10, 13, 20, 21,
and 22) associated with this article can be found, in the online ver-
sion, at http://dx.doi.org/10.1016/j.tetlet.2016.03.036.
À97.0 (c 1.02, MeOH); mp 124–126 °C; white solid. To a solution of 10 (2.64 g,
6.70 mmol) in MeCN (20 mL), sodium azido (516 mg, 7.94 mmol) was added.
After stirring the mixture for 1 h at 0 °C, the mixture was passed through Cerite
pad. The filtrate was concentrated in vacuo to afford crude compounds, which
were purified by recrystallization (hexane/EtOAc) to give 2 (1.41 g, 3.51 mmol)
in 52% yield. Spectral data for 2: 1H NMR (500 MHz, CDCl3) d 7.45–7.36 (m, 3H),
7.32–7.30 (m, 2H), 5.31 (q, 1H, J = 7.1 Hz), 4.44–4.40 (m, 1H), 4.11 (q, 1H,
J = 7.1 Hz), 3.94–387 (m, 2H), 3.57–3.53 (m, 1H), 2.40–2.37 (m, 1H), 2.29–2.27
(m, 1H), 2.14–2.09 (m, 2H), 1.63 (d, 3H, J = 7.1 Hz); 13C NMR (125.7 MHz,
References and notes
1. For a review, see: (a) Kitamura, M. J. Synth. Org. Chem. Jpn. 2014, 72, 14;
Preparation of ADMP, see: (b) Kitamura, M.; Murakami, K. Org. Synth. 2015, 92,
171.
2. (a) Kitamura, M.; Tashiro, N.; Okauchi, T. Synlett 2009, 2943; (b) Kitamura, M.;
Tashiro, N.; Miyagawa, S.; Okauchi, T. Synthesis 2011, 1037.
3. (a) Kitamura, M.; Tashiro, N.; Sakata, R.; Okauchi, T. Synlett 2010, 2503; (b)
Kitamura, M.; Sakata, R.; Tashiro, N.; Ikegami, A.; Okauchi, T. Bull. Chem. Soc.
Jpn. 2015, 88, 824.
4. (a) Kitamura, M.; Yano, M.; Tashiro, N.; Miyagawa, S.; Sando, M.; Okauchi, T.
Eur. J. Org. Chem. 2011, 458; (b) Kitamura, M.; Kato, S.; Yano, M.; Tashiro, N.;
Shiratake, Y.; Sando, M.; Okauchi, T. Org. Biomol. Chem. 2014, 12, 4397.
5. (a) Kitamura, M.; Tashiro, N.; Takamoto, Y.; Okauchi, T. Chem. Lett. 2010, 39,
732; (b) Kitamura, M.; Koga, T.; Yano, M.; Okauchi, T. Synlett 2012, 1335.
6. (a) Kitamura, M.; Miyagawa, S.; Okauchi, T. Tetrahedron Lett. 2011, 52, 3158; (b)
Kitamura, M.; Murakami, K.; Shiratake, Y.; Okauchi, T. Chem. Lett. 2013, 42, 691.
7. (a) Ishikawa, T.; Isobe, T. J. Synth. Org. Chem. Jpn. 2003, 61, 58; (b) Ishikawa, T.
Arkivoc 2006, vii, 148; For reviews, see: (c) Ishikawa, T. Chem. Pharm. Bull. 2010,
58, 1555.
8. (a) Isobe, T.; Fukuda, K.; Ishikawa, T. Tetrahedron: Asymmetry 1998, 9, 1729; (b)
Isobe, T.; Fukuda, K.; Ishikawa, T. J. Org. Chem. 2000, 65, 7770; (c) Isobe, T.;
Fukuda, K.; Tokunaga, T.; Seki, H.; Yamaguchi, K.; Ishikawa, T. J. Org. Chem.
2000, 65, 7774; (d) Isobe, T.; Fukuda, K.; Yamaguchi, K.; Seki, H.; Tokunaga, T.;
Ishikawa, T. J. Org. Chem. 2000, 65, 7779; (e) Oda, Y.; Hada, K.; Miyata, M.;
Takahata, C.; Hayashi, Y.; Takahashi, M.; Yajima, N.; Fujinami, M.; Ishikawa, T.
Synthesis 2014, 46, 2201.
CDCl3) d 156.1, 136.8, 129.6, 129.4, 126.6, 62.8, 57.8, 50.2, 47.2, 30.2, 25.4, 16.3;
23
mp 171–173 °C; [
a]
D
À78.3 (c 0.996, MeOH); Anal. Calcd for C14H18F6N5P: C,
41.90; H, 4.52; N, 17.45. Found: C, 42.00; H; 4.49, N; 17.35; white solid.
12. Preparation of 3. To a solution 128b (3.13 g, 8.99 mmol) in MeCN (50 mL),
potassium hexafluorophosphate (2.53 g, 13.6 mmol) was added at room
temperature under argon. After stirring the mixture for 1 h, the mixture was
passed through Celite pad. The filtrate was concentrated in vacuo to afford
crude compounds, which were purified by recrystallization (EtOAc/acetone) to
give 13 (3.88 g, 8.46 mmol) in 97% yield. Spectral data for 13: 1H NMR
(500 MHz, CDCl3)
d 7.45–7.44 (m, 8H), 7.40–7.38 (m, 2H), 5.34 (q, 2H,
J = 7.1 Hz), 4.39–4.34 (m, 2H), 4.01–3.96 (m, 2H), 1.80 (d, 6H, J = 7.0 Hz); 13C
NMR (125.7 MHz, CDCl3) d 153.5, 136.2, 129.5, 129.3, 127.2, 57.5, 45.2, 17.7; IR
(KBr) 2982, 2084, 1653, 1455, 1359, 1294, 1204, 1138, 1028, 839, 709, 557;
HRMS (FAB+) Found; m/z, 313.1461. Calcd for C19
H
ClN2: (MÀPF6)+ 313.1472;
35
22
23
mp 210–214 °C; [
a]
D
À13.6 (c 0.987, acetone). To a solution of 13 (1.10 g,
2.41 mmol) in MeCN (12 mL), sodium azide (236 mg, 3.63 mmol) was added at
0 °C under argon. After stirring the mixture for 1 h, the mixture was passed
through Celite pad. The filtrate was concentrated in vacuo to afford crude
compounds, which were purified by recrystallization (hexane/EtOAc) to give 3
(809 mg, 2.02 mmol) in 84% yield. Spectral data for 3: 1H NMR (500 MHz,
CDCl3) d 7.47–7.43 (m, 4H), 7.40–7.35 (m, 6H), 5.25 (q, 2H, J = 5.4 Hz), 3.86–
3.81 (m, 2H), 3.62–3.58 (m, 2H), 1.70 (d, 6H, J = 7.0 Hz); 13C NMR (125.7 MHz,
CDCl3) d 153.7, 137.0, 129.5, 129.2, 126.6, 55.5, 43.2, 18.0; IR (KBr) d 2906,
2345, 2166, 1538, 835, 556 cmÀ1; Anal. Calcd for C19H22F6N5P: C, 49.04; H,
4.76; N, 15.05. Found: C, 49.11; H; 4.72, N; 14.95; HRMS (FAB+) Found; m/z,
9. Although we previously showed single-crystal X-ray structure of ADMP 1b, the
19H22N5: (MÀPF6)+ 320.1875; mp 171–173 °C;
[a]
D
23
R factor was large for discussing the structure.4b
320.1867. Calcd for
À7.44 (c 1.07, acetone), yellow crystal.
C
10. Thomasset, A.; Bouchardy, L.; Bournaud, C.; Guillot, R.; Toffano, M.; Vo-Thanh,
G. Synthesis 2014, 46, 242.
13. Crystallographic data for the structures in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplementary publication nos.
CCDC. Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-336033 or e-
mail: deposit@ccdc.cam.ac.Uk). CCDC 1416637 contains the supplementary
crystallographic data for 2. CCDC 1416639 contains the supplementary
crystallographic data for 3.
11. Preparation of 2. To a solution of amide 710 (6.10 g, 28.0 mmol) in THF (140 mL),
LiAlH4 (4.82 g, 127 mmol) was added at 0 °C. After stirring the mixture for 7 h
at 60 °C, the reaction was quenched by adding water at 0 °C and the resulting
mixture was passed through Celite pad. The filtrate extracted with CH2Cl2
three times, and washed with brine, and then dried over anhydrous Na2SO4.
The solvent was removed in vacuo to afford crude diamine (6.05 g). The crude
compound was dissolved in o-dichlorobenzene (140 mL), and thiocarbonyl
imidazole (5.60 g, 31.5 mmol) was added. After stirring the mixture for 6 h at
reflux (185 °C), the solvent was removed in vacuo to afford crude compounds,
which were purified by column chromatography (SiO2; hexane/EtOAc = 4:1),
and then recrystallization (hexane/EtOAc) to give pure 8 (4.25 g, 17.3 mmol) in
62% yield (2 steps). Spectral data for 8: 1H NMR (500 MHz, CDCl3) d 7.35–7.26
(m, 5H), 6.10 (q, 1H, J = 7.1 Hz), 4.19–4.09 (m, 1H), 3.82–3.75 (m, 1H), 3.42–
14. (a) Besenyei, G.; Párkányi, L.; Foch, I.; Simándi, L. I.; Kálmán, A. J. Chem. Soc.,
Perkin Trans.
Crystallogr., Sect.
2
2000, 1798; (b) Vicarel, M. L.; Norris, P.; Zeller, M. Acta
2006, 62, o1751; (c) Katritzky, A. R.; El Khatib, M.;
E
Bol’shakov, O.; Khelashvili, L.; Steel, P. J. J. Org. Chem. 2010, 75, 6532; (d)
Basanagouda, M.; Nayak, S. K.; Row, T. N. G.; Kulkarni, M. V. Acta Crystallogr.,
Sect. E 2010, 66, o2780; (e) Laus, G.; Admer, V.; Hummel, M.; Kahlenberg, V.;
Wurst, K.; Nerdinger, S.; Schottenberger, H. Crystals 2012, 2, 118; (f) Fischer, N.;
Goddard-Borger, E. D.; Greiner, R.; Klapötke, T. M.; Skelton, B. W.; Stierstorfer, J.
J. Org. Chem. 2012, 77, 1760.
3.24 (m, 3H), 2.07–1.82 (m, 3H), 1.56 (d, 3H, J = 7.1 Hz), 1.42–1.24 (m, 1H); 13
C
NMR (125.7 MHz, CDCl3, (d = 77.0) d 185.3, 139.6, 128.6, 127.6, 127.1, 59.4,
15. Bräse, S.; Banert, K. Organic Azides; Wiley: Wiltshire, 2010; p 373.
16. The enantiomeric ratio was determined by HPLC analysis using a chiral column
(DAICEL CHIRALCEL OD-H, hexane/i-PrOH = 9:1).
53.6, 48.1, 46.6, 30.9, 24.7, 15.3; IR (KBr): 2972, 1653, 1490, 1436, 1385, 1293,
701; HRMS (FAB+) Found; m/z, 247.1274. Calcd for C14H19N2S: (M+H)+
23
247.1269; mp 120–122 °C; [
a
]
+52.3 (c 0.992, CHCl3); colorless crystal. To
D
a solution of 8 (3.31 g, 13.5 mmol) in toluene (60 mL), oxalyl chloride (1.6 mL,