Enantioselective desymmetrization of meso-N-(heteroarenesulfonyl)aziridines with TMSN3 catalyzed by chiral Lewis acids

Article abstract of DOI:10.1016/j.tetlet.2010.05.065

A catalytic enantioselective desymmetrization of meso-N- (heteroarenesulfonyl)aziridines with TMSN3 using chiral Lewis acids afforded products with high enantioselectivity. As proof of the utility of this procedure, the precursor of selective κ-opioid agonist (1S,2S)-(-)-U-50,488 was synthesized.

Full text of DOI:10.1016/j.tetlet.2010.05.065

Tetrahedron Letters 51 (2010) 3820–3823
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Tetrahedron Letters
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Enantioselective desymmetrization of meso-N-(heteroarenesulfonyl)aziridines
with TMSN3 catalyzed by chiral Lewis acids
*
Shuichi Nakamura , Masashi Hayashi, Yasutoshi Kamada, Ryosuke Sasaki, Yuichi Hiramatsu,
Norio Shibata, Takeshi Toru
Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A catalytic enantioselective desymmetrization of meso-N-(heteroarenesulfonyl)aziridines with TMSN3
Received 27 March 2010
Revised 13 May 2010
Accepted 17 May 2010
Available online 21 May 2010
using chiral Lewis acids afforded products with high enantioselectivity. As proof of the utility of this
procedure, the precursor of selective
j-opioid agonist (1S,2S)-(ꢀ)-U-50,488 was synthesized.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric catalysis
Heteroarenesulfonyl groups
Chiral Lewis acids
Chiral diamines
Stereocontroller
Optically active vicinal diamines are very important compounds
for the synthesis of natural compounds and stereoselective cata-
lysts. Furthermore, vicinal diamine compounds have demonstrated
a range of bioactivity that includes antiparasitic [e.g., (R)-praziquan-
tel, oxamniquine],1 anticancer [(ꢀ)-quinocarcin],2 and protease
inhibitory activity.3,4 Therefore, the stereoselective synthesis of chi-
ral vicinal diamine compounds has received considerable atten-
tion.5 One of the most efficient methods for the synthesis of chiral
vicinal diamine precursors is the catalytic enantioselective desym-
metrization of meso-aziridines with azide compounds. This type of
reaction affords chiral b-aminoazides, which can be easily con-
verted to chiral vicinal diamines. Although there are many reports
on the enantioselective desymmetrization of meso-aziridines with
various nucleophiles,6 this type of reaction with azide compounds
is still rare.7 Jacobsen and co-workers pioneered the highly enantio-
selective desymmetrization of aziridines with TMSN3 by using a
chiral chromium catalyst (up to 94% ee).7a Recently, Shibasaki7b
and Parquett7d,e reported that the ring-opening reaction of N-(4-
nitrobenzoyl)aziridines with TMSN3 using different chiral yttrium
catalysts gave products with high enantioselectivity. Antilla and
co-workers demonstrated that chiral phosphoric acids could be
used for the ring-opening reaction of aziridines.7c Despite the
impressive progress achieved in this reaction, expanding the scope
of catalytic enantioselective desymmetrization of aziridines with
respect to both the chiral catalyst and the substrate would be highly
desirable. Although the N-sulfonyl group certainly enhances the
reactivity of the ring-opening reaction of aziridines to attack an
azide, to our knowledge, there are no reports on the enantioselective
desymmetrization of N-(arenesulfonyl)aziridines with an azide.
Recently, we8 and others9 have developed novel bifunctional coor-
dinative heteroarenesulfonyl groups whose conformations and
reactivities can be controlled by chelation with chiral Lewis acids
or organocatalysts. Herein, we report the catalytic enantioselective
desymmetrization of meso-aziridines having a heteroarenesulfonyl
group with TMSN3 using chiral Lewis acids prepared from commer-
cially available bis(oxazoline) ligands (Fig. 1).
We examined the enantioselective desymmetrization of
meso-N-(heteroarenesulfonyl)aziridines 1a–g10 by using a catalytic
amount of chiral Lewis acids prepared from various bis(oxazoline)s
Lewis acid
R
bis(oxazoline)
O2S
N
M
L
SO2Py
*
N
R
ML2
N
*
L
*
R
R
R
NHSO2Py
NH2
TMSN3
R
R
*
*
R
*
R
*
N3
NH2
* Corresponding author.
Figure 1. Catalytic enantioselective ring-opening reaction of meso-N-(2-pyr-
E-mail address: snakamur@nitech.ac.jp (S. Nakamura).
idinesulfonyl)aziridines with TMSN3.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.065

S. Nakamura et al. / Tetrahedron Letters 51 (2010) 3820–3823
3821
Table 1
1) Mg(NTf2)2
bis(oxazoline) 3
2) TMSN3
O2
NHSO2Ar
Enantioselective desymmetrization of N-(heteroarenesulfonyl)aziridines 1a–g with
S
N
TMSN3 in the presence of various chiral Lewis acidsa
N
N3
CHCl3, rt
1) Mg(NTf2)2
bis(oxazoline)
2) TMSN3
a:
b:
c:
d:
e:
f:
R = p-TolylSO2
1h
R = 2-PyridylSO2
R = 8-QuinolylSO2
R = 6-Me-2-PyridylSO2
R = 2-ThienylSO2
R = 2-PyridylCO
R = 2-PyridylCH2
2h: 64%, 64% ee
NHR
N3
N
R
1) Mg(NTf2)2
bis(oxazoline) 3
2) TMSN3
O2
S
CHCl3, rt
NHSO2Ar
N
1a-g
2a-g
N
g:
toluene, 40 ºC
N3
1i
2i: 51%, 65% ee
O
N
O
O
O
O
O
1) Mg(NTf2)2
bis(oxazoline) 3
2) TMSN3
N
N
O2
N
N
NHSO2Ar
S
N
N
N
N
R2
R2
N
Ph
Ph
N3
3: R2 = Ph
CHCl3, rt
4: R2 = t-Bu
5
2j: no reaction
1j
6
Run
1
Ligand
2
Yield (%)
Eeb (%)
1) Mg(NTf2)2
bis(oxazoline) 3
2) TMSN3
O2S
N
NHSO22-Py
N3
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1d
1d
1d
3
3
3
3
3
3
3
4
5
6
2a
2b
2c
2d
2e
2f
2g
2d
2d
2d
Trace
98
—
Ph
70(S)
Ph
67
63
60
CHCl3, rt
Ph
Ph
1k
85(S) (99)c
2k 91%, 80% ee
Trace
99
Trace
12
—
11
—
0
39
—
Scheme 1. Enantioselective ring-opening reaction of 1h–k.
52
10
Trace
a
H
N
1) PPh3
2) H2O
Mg(NTf2)2 (0.1 equiv), bis(oxazoline) (0.2 equiv), and TMSN3 (3.0 equiv) were
used.
H
N
S
N
S
N
b
O2
Ee was determined by HPLC analysis using chiral columns.
Ee obtained after single recrystallization from toluene is shown in parenthesis.
O2
CH3CN
c
N3
NH2
2d: 99% ee
7: 99%
Boc
N
H
N
Br-(CH2)4-Br
Boc2O
S
N
S
N
3–6 and Mg(NTf2)2. The results are shown in Table 1. The reaction
of N-(p-toluenesulfonyl)aziridine 1a with TMSN3 using Mg(NTf2)2/
Box-Ph 3 as a chiral Lewis acid catalyst did not afford product 2a,
whereas N-(2-pyridinesulfonyl)- and N-(8-quinolinesulfonyl)aziri-
dines 1b, c afforded products 2b, c with good enantioselectivity
(entries 1–3). Interestingly, N-(6-methyl-2-pyridinesulfonyl)aziri-
dine 1d showed higher enantioselectivity than 1b (entry 4). The
reaction of N-(2-thiophenesulfonyl)aziridine 1e did not afford
product 2e in good yield (entry 5). The reaction of N-picolyl- and
N-pyridylmethyl-substituted aziridine 1f, g did not afford good
results (entries 6 and 7). After optimization of chiral Lewis acids
derived from other Box ligands such as Box-tBu 4, indaBox 5, and
Pybox 6, we found Mg(NTf2)2/3 to be an efficient chiral Lewis
acid for asymmetric desymmetrization of 1d (entries 8–10).11,12
Recrystallization of (S)-2d (85% ee) from toluene afforded enantio-
merically pure (S)-2d (entry 4).
K2CO3
DMAP
O2
O2
N
N
CH3CN
CH3CN
8: 87%, 99% ee
9: 66%, 99% ee
H
O
Cl
N
Boc
Mg
N
Cl
N
MeOH
N
10: 99%
(1S,2S)-(−)-U-50,488
Scheme 2. Synthesis of (1S,2S)-U-50,488.
diamine 7, which was successfully alkylated by 1,4-dibromobutane
to give the pyrrolidine derivative 8 in high yield (Scheme 2).16
The sulfonamide group of 8 was protected by Boc2O, after which
the 6-methyl-2-pyridinesulfonyl group was removed by magne-
sium in MeOH17 to give the N-Boc amide 10 in high yield. The
N-Boc amide 10 would be transformed to enantiomerically pure
U-50,488.15a
With these optimized condition, the ring-opening reaction of
1h, i afforded the products 2h, i in good yield with moderate
enantioselectivity, although the reaction of 1j did not afford the
product 2j (Scheme 1). Furthermore, acyclic aziridine 1k using
Mg(NTf2)2/3 afforded product 2k in high yield with good enanti-
oselectivity .
To assess the synthetic potential of this stereoselective prepara-
tion of chiral vicinal diamines, we tried to prepare U-50,488, which
The enantioselective desymmetrization of N-(2-pyridinesulfo-
nyl)aziridines 1b, d with TMSN3 gave products 2b, d in good yield
with good enantioselectivity, whereas the reaction of N-(p-tolu-
enesulfonyl)aziridine 1a did not afford the product. This result
shows that the 2-pyridinesulfonyl group acts as an efficient
has been reported to be a highly selective
j-opioid agonist free
from the adverse side effects of
l
-opioid agonists like morphine.13
The pharmacological activities of U-50,488 are related to the con-
figuration of its stereogenic centers. (1S,2S)-(ꢀ)-U-50,488 exhibits
activating group. Assuming that Mg(II) forms a tetrahedral
greater
j
agonist activity than its enantiomer and cis diastereo-
bidentate-coordinating complex with the substrate,18 the pre-
sumed structure of most reactive complex 1d-Mg(II)/3 is shown
in Figure 2, where two Box nitrogens, one pyridyl nitrogen, and
aziridine nitrogen coordinate to Mg(II). In this structure, the pyri-
dyl group in 1d plays an important role in stabilizing the chelation
structure. Thus, TMSN3 approaches aziridine avoiding steric repul-
mers.14 Therefore, the stereoselective synthesis of (1S,2S)-U-
50,488 is important. However, to our knowledge, there is no report
on the enantioselective synthesis of U-50,488 through the catalytic
enantioselective ring-opening reactions of aziridines.15 Reduction
of azide group of 2d by triphenylphosphine yielded N-sulfonylated

3822
S. Nakamura et al. / Tetrahedron Letters 51 (2010) 3820–3823
Nakashima, H.; Shibata, N.; Toru, T. Synlett 2009, 1639–1642; For
enantioselective reaction using organocatalysts having a heteroarenesulfonyl
group, see: (h) Nakamura, S.; Hara, N.; Nakashima, H.; Kubo, K.; Shibata, N.;
Toru, T. Chem. Eur. J. 2008, 14, 8079–8081; (i) Hara, N.; Nakamura, S.; Shibata,
N.; Toru, T. Chem. Eur. J. 2009, 15, 6790–6793.
TMSN3
9. Enantioselective conjugate addition: (a) Esquivias, J.; Arrayás, R. G.;
Carretero, J. C. J. Org. Chem. 2005, 70, 7451–7454; Aza Diels–Alder
reaction: (b) Esquivias, J.; Arrayás, R. G.; Carretero, J. C. J. Am. Chem. Soc.
2007, 129, 1480–1481; (c) Esquivias, J.; Alonso, I.; Arrayás, R. G.; Carretero, J.
C. Synthesis 2009, 113–126; Mannich-type reaction: (d) González, A. S.;
Arrayás, R. G.; Carretero, J. C. Org. Lett. 2006, 8, 2977–2980; (e) Hernández-
Toribio, J.; Arrayás, R. G.; Carretero, J. C. J. Am. Chem. Soc. 2008, 130, 16150–
16151; (f) Hernández-Toribio, J.; Arrayás, R. G.; Carretero, J. C. Chem. Eur. J.
2010, 16, 1153–1157; (g) Morimoto, H.; Lu, G.; Aoyama, N.; Matsunaga, S.;
Shibasaki, M. J. Am. Chem. Soc. 2007, 129, 9588–9589; (h) Lu, G.; Morimoto,
H.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2008, 47, 6847–6850;
(i) González, A. S.; Arrayás, R. G.; Rivero, M. R.; Carretero, J. C. Org. Lett. 2008,
10, 4335–4337.
N
S
O
(S)-2d
Mg
O
Py
10. N-(Heteroarenesulfonyl)aziridines were prepared by reported procedures, see:
(a) Wright, S. W.; Hallstrom, K. N. J. Org. Chem. 2006, 71, 1080–1084; (b)
Mordini, A.; Russo, F.; Valacchi, M.; Zani, L.; Degl’Innocenti, A.; Reginato, G.
Tetrahedron 2002, 58, 7153–7163.
11. Other chiral Lewis acids derived from Mg(OTf)2, CuOTf, Cu(OTf)2, and Zn(OTf)2
with 3 afforded product 2d with lower enantioselectivity than that using
Mg(NTf2)2/3.
Figure 2. Presumed reaction model of 1d-Mg(II)/3.
12. We also examined the reaction in CH2Cl2, ClCH2CH2Cl, toluene, Et2O, and
CH3CN, giving the product 2d with lower enantioselectivity than that in CHCl3.
13. (a) Szmuszkovicz, J. Prog. Drug Res. 1999, 53, 1–51; (b) Bachand, B.; Tarazi, M.;
St-Denis, Y.; Edmunds, J. J.; Winocour, P. D.; Leblond, L.; Siddiqui, M. A. Bioorg.
Med. Chem. Lett. 2001, 11, 287–290; (c) St-Denis, Y.; Levesque, S.; Bachand, B.;
Edmunds, J. J.; Leblond, L.; Preville, P.; Tarazi, M.; Winocour, P. D.; Siddiqui, M.
A. Bioorg. Med. Chem. Lett. 2002, 12, 1181–1184; (d) Bursavich, M. G.; Rich, D. H.
J. Med. Chem. 2002, 45, 541–558.
14. (a) De Costa, B. R.; Bowen, W. D.; Hellewell, S. B.; George, C.; Rothman, R. B.;
Reid, A. A.; Walker, J. M.; Jacobson, A. E.; Rice, K. C. J. Med. Chem. 1989, 32,
1996–2002; (b) De Costa, B. R.; Bowen, W. D.; Thurkauf, A.; Finn, D. T.; Vazirani,
S.; Rothman, R. B.; Band, L.; Contreras, P. C.; Gray, N. M. J. Med. Chem. 1990, 33,
3100–3110.
sion with the phenyl group in Box-Ph 3, therefore (1S,2S)-2d is
preferably formed.
In conclusion, the enantioselective desymmetrization of N-(2-
pyridinesulfonyl)aziridines in the presence of Mg(NTf2)2/3 afforded
chiral b-aminoazides with good enantioselectivity. The 2-pyr-
idinesulfonyl group works as an efficient activating group for the
ring-opening reaction of aziridines. To our knowledge, this result
is the first example for the enantioselective desymmetrization of
N-(arenesulfonyl)aziridines with an azide. As a proof of the
utility of this procedure, the precursor of enantiomerically pure
15. Previously, (1S,2S)-U-50,488 was synthesized through an enzymatic
resolution, see: (a) González-Sabín, J.; Gotor, V.; Rebolledo, F. Chem. Eur. J.
2004, 10, 5788–5794; For dynamic kinetic resolution using ruthenium-
catalyzed hydrogenation, see: (b) Liu, S.; Xie, J.-H.; Wang, L.-X.; Zhou, Q.-L.
Angew. Chem., Int. Ed. 2007, 46, 7506–7508.
(1S,2S)-(ꢀ)-U-50,488, which is a selective
j-opioid agonist, was
synthesized.
16. Typical procedure for the asymmetric desymmetrization of 1d using the
catalyst Mg(NTf2)2/3 (Table 1, entry 4). To a solution of Mg(NTf2)2 (4.6 mg,
Acknowledgments
7.9
0.079 mmol) in CHCl3 (0.2 mL) was added and stirred for 1 h. Then,
TMSN3 (31 l, 0.24 mmol) was added at room temperature. The reaction
lmol) and 3 (5.5 mg, 0.016 mmol) in CHCl3 (0.8 mL), 1d (20 mg,
l
This work was supported by Research for Promoting Technolog-
ical Seeds from JST and the Uehara Memorial Foundation.
mixture was stirred for 63 h. Water (1.0 mL) was added and the mixture
was stirred for 10 min at room temperature. The organic phase was
separated and the aqueous phase was extracted with CH2Cl2 (3 ꢁ 5 mL).
The combined organic phase was dried over Na2SO4 and concentrated. The
residue was purified by chromatography (benzene/ethyl acetate = 90:10) to
References and notes
afford 2d (14.7 mg, 63%, 85% ee) as a white solid; ½a D25
ꢂ
+56.0 (c 0.42, CHCl3,
99% ee); mp 106.5–107.0 °C; Rf = 0.15 (benzene/ethyl acetate = 90:10); 1H
NMR (CDCl3) d 1.20–1.50 (m, 4H), 1.50–1.80 (m, 2H), 2.00–2.20 (m, 2H),
2.63 (s, 3H, CH3), 3.00–3.20 (m, 2H, CH), 5.17–5.21 (br, 1H, NH), 7.29–7.35
(m, 1H, Py), 7.72–7.84 (m, 2H, Py); 13C NMR (CDCl3) d 23.5, 23.8, 24.3, 30.1,
31.2, 56.8, 63.7, 118.9, 126.5, 137.9, 157.1, 159.9; IR (KBr) 3253, 2941, 2858,
2099 (N3), 1451, 1332 (SO2) cmꢀ1; MS(APCI) m/z 268.1 [M+H–N2], 296.1
[M+H]; HPLC (CHIRALPAKÒ OD-H, hexane/i-PrOH = 90:10, 1.0 mL/min) tR
11.4 (minor), tS 19.1 (major) min.
1. (a) Andrews, P.; Thomas, H.; Pohlke, R.; Seubert, J. Med. Res. Rev. 1983, 3, 147–
200; (b) Fenwick, A.; Keiser, J.; Utzinger, J. Drugs Future 2006, 31, 413–425.
2. Scott, J. D.; Williams, R. M. Chem. Rev. 2002, 102, 1669–1730.
3. (a) Szmuszkovicz, J.; Von Voigtlander, P. F. J. Med. Chem. 1982, 25, 1125–1126;
(b) Clark, C. R.; Halfpenny, P. R.; Hill, R. G.; Horwell, D. C.; Hughes, J.; Jarvis, T.
C.; Rees, D. C.; Schofield, D. J. Med. Chem. 1988, 31, 831–836; (c) Costello, G. F.;
James, R.; Shaw, J. S.; Slater, A. M.; Stutchbury, N. C. J. J. Med. Chem. 1991, 34,
181–189; (d) Barlow, J. J.; Blackburn, T. P.; Costello, G. F.; James, R.; Le Count, D.
J.; Main, B. G.; Pearce, R. J.; Russell, K.; Shaw, J. S. J. Med. Chem. 1991, 34, 3149–
3158.
Compound 7: ½ ꢂ +16.7 (c 0.41, MeOH, 99% ee); mp 145.0–147.0 °C;
a 2D5
Rf = 0.11 (CH2Cl2/MeOH = 90:10); 1H NMR (CDCl3) d 1.05–1.40 (m, 4H), 1.55–
1.75 (m, 2H), 1.80–2.10 (m, 2H), 2.10–2.60 (br, 2H, NH2), 2.39–2.49 (m, 1H,
CH), 2.62 (s, 3H, CH3), 2.80–2.95 (m, 1H, CH), 7.30–7.33 (m, 1H, Py), 7.72–
7.84 (m, 2H, Py); 13C NMR (CDCl3) d 24.2, 24.7, 25.0, 32.9, 34.8, 55.0, 61.1,
119.0, 126.4, 137.9, 157.5, 159.6; IR (KBr) 3354, 3035, 2936, 2861, 1591,
1452, 1314 (SO2) cmꢀ1; MS(ESI) m/z 270.1 [M+H].
4. For biologically active chiral vicinal diamines, see: Kotti, S. R. S. S.; Timmons, C.;
Li, G. Chem. Biol. Drug Des. 2006, 67, 101–114.
5. For reviews, see: (a) Lucet, D.; Gall, T. L.; Mioskowski, C. Angew. Chem., Int. Ed.
1998, 37, 2580–2627; (b) Kizirian, J.-C. Chem. Rev. 2008, 108, 140–205.
6. For reviews, see: (a) Pineschi, M. Eur. J. Org. Chem. 2006, 4979–4988; (b) Hu, X.
E. Tetrahedron 2004, 60, 2701–2743; (c) Schneider, C. Angew. Chem., Int. Ed.
2009, 48, 2082–2084.
Compound 8: ½ ꢂ +54.6 (c 0.43, MeOH, 99% ee); mp 153.0–155.5 °C;
a 2D5
Rf = 0.20 (CH2Cl2/MeOH = 90:10); 1H NMR (CDCl3) d 1.00–1.40 (m, 4H), 1.60–
1.80 (m, 7H), 2.25–2.60 (m, 7H), 2.62 (s, 3H, CH3), 2.70–2.90 (m, 1H), 7.29–
7.33 (m, 1H, Py), 7.72–7.86 (m, 2H, Py); 13C NMR (CDCl3) d 21.5, 23.4, 24.0,
24.1, 24.7, 32.4, 46.4, 55.1, 61.5, 119.6, 126.3, 137.6, 156.2, 159.6; IR (KBr)
3207, 2931, 2860, 2810, 1591, 1452, 1343 (SO2) cmꢀ1; MS(ESI) m/z 324.2
[M+H]; HPLC (CHIRALPAKÒ OD-H, hexane/i-PrOH = 90:10, 0.5 mL/min) tR
15.1 (minor), tS 16.3 (major) min.
7. (a) Li, Z.; Fernandez, M.; Jacobsen, E. N. Org. Lett. 1999, 1, 1611–1613; (b)
Furuta, Y.; Mita, T.; Fukada, N.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2006,
128, 6312–6313; (c) Rowland, E. B.; Rowland, G. B.; Rivera-Otero, E.; Antilla, J.
C. J. Am. Chem. Soc. 2007, 129, 12084–12085; (d) Wu, B.; Gallucci, J. C.;
Parquette, J. R.; RajanBabu, T. V. Angew. Chem., Int. Ed. 2008, 47, 1126–1129; (e)
Wu, B.; Parquette, J. R.; RajanBabu, T. V. Science 2009, 326, 1662–1663.
8. (a) Nakamura, S.; Sato, N.; Sugimoto, M.; Toru, T. Tetrahedron: Asymmetry 2004,
15, 1513–1516; (b) Sugimoto, H.; Nakamura, S.; Hattori, M.; Ozeki, S.; Shibata,
N.; Toru, T. Tetrahedron Lett. 2005, 46, 8941–8944; (c) Nakamura, S.;
Nakashima, H.; Sugimoto, H.; Shibata, N.; Toru, T. Tetrahedron Lett. 2006, 47,
7599–7602; (d) Nakamura, S.; Sano, H.; Nakashima, H.; Kubo, K.; Shibata, N.;
Toru, T. Tetrahedron Lett. 2007, 48, 5565–5568; (e) Nakamura, S.; Nakashima,
H.; Sugimoto, H.; Sano, H.; Hattori, M.; Shibata, N.; Toru, T. Chem. Eur. J. 2008,
14, 2145–2152; (f) Nakamura, S.; Nakashima, H.; Yamamura, A.; Shibata, N.;
Toru, T. Adv. Synth. Catal. 2008, 350, 1209–1212; (g) Nakamura, S.; Sakurai, Y.;
Compound 9: ½a 2D5
+57.2 (c 0.47, MeOH, 99% ee); mp 88.0–91.0 °C; Rf = 0.30
ꢂ
(AcOEt); 1H NMR (CDCl3) d 1.20–1.40 (m, 4H), 1.26 (s, 9H, CH3), 1.60–1.70
(m, 4H), 1.70–1.85 (m, 2H), 1.90–2.40 (m, 4H), 2.59 (s, 3H, CH3), 2.70–2.90
(m, 2H), 3.45–4.60 (m, 1H, CH),4.20–4.34 (m, 1H, CH), 7.27–7.31 (m, 1H, Py),
7.68–7.76 (m, 1H, Py), 7.99–8.02 (m, 1H, Py); 13C NMR (CDCl3) d 13.9, 23.6,
24.0, 25.1, 25.3, 27.5, 31.0, 46.9, 57.9, 61.4, 119.8, 126.1, 137.2, 150.5, 157.4,
158.9; IR (KBr) 2932, 2855, 2791, 1733, 1591, 1456, 1342 (SO2) cmꢀ1
;
MS(ESI) m/z 424.3 [M+H]; HPLC (CHIRALPAKÒ OD-H, hexane/i-PrOH = 90:10,
1.0 mL/min) tS 5.3 (major), tR 6.0 (minor) min.

S. Nakamura et al. / Tetrahedron Letters 51 (2010) 3820–3823
3823
Compound 10:
½
a 2D5
ꢂ
+33.1 (c 0.21, MeOH, 99% ee); Rf = 0.10 (CH2Cl2/
1.10–1.50 (m, 4H), 1.45 (s, 9H, CH3),
18. A tetrahedral Mg(II) complex has been proposed, see: (a) Corey, E. J.; Ishihara,
K. Tetrahedron Lett. 1992, 33, 6807–6810; (b) Sibi, M. P.; Sausker, J. B. J. Am.
Chem. Soc. 2002, 124, 984–991; An octahedral structure has been also
proposed: (c) Sibi, M. P.; Petrovic, G.; Zimmerman, J. J. Am. Chem. Soc. 2005,
127, 2390–2391; (d) Gothelf, K. V.; Hazell, R. G.; Jorgensen, K. A. J. Org. Chem.
1998, 63, 5483–5488.
MeOH = 90:10); 1H NMR (CDCl3)
d
1.55–1.85 (m, 8H), 2.30–1.70 (m, 5H), 3.20–3.40 (m, 1H, CH), 5.25 (br, 1H,
NH); MS(ESI) m/z 269.3 [M+H].
17. (a) Goulaouic-Dubois, C.; Guggisberg, A.; Hesse, M. J. Org. Chem. 1995, 60,
5969–5972; (b) Pak, C. S.; Lim, D. S. Synth. Commun. 2001, 31, 2209–2214.