Synthetic studies on thiostrepton family of peptide antibiotics: Synthesis of the cyclic core portion containing the dehydropiperidine, dihydroquinoline, L-valine, and masked dehydroalanine segments

Article abstract of DOI:10.1016/j.tetlet.2005.07.122

The cyclic core portion containing the dehydropiperidine, dihydroquinoline, L-valine, and masked dehydroalanine (i.e., β-phenylselenoalanine) segments of the thiostrepton family of peptide antibiotics was synthesized via the consecutive coupling of these four segments followed by cyclization at the amide bond between the dehydropiperidine and masked dehydroalanine segments.

Full text of DOI:10.1016/j.tetlet.2005.07.122

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6423–6427
Synthetic studies on thiostrepton family of peptide
antibiotics: synthesis of the cyclic core portion containing the
dehydropiperidine, dihydroquinoline, L-valine, and masked
dehydroalanine segments
Tomonori Mori, Hiraku Tohmiya, Yukiko Satouchi, Shuhei Higashibayashi,ꢀ
Kimiko Hashimoto*,ꢁ and Masaya Nakata*
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku,
Yokohama 223-8522, Japan
Received 5 July 2005; revised 21 July 2005; accepted 25 July 2005
Abstract—The cyclic core portion containing the dehydropiperidine, dihydroquinoline, L-valine, and masked dehydroalanine (i.e.,
b-phenylselenoalanine) segments of the thiostrepton family of peptide antibiotics was synthesized via the consecutive coupling of
these four segments followed by cyclization at the amide bond between the dehydropiperidine and masked dehydroalanine segments.
ꢀ 2005 Elsevier Ltd. All rights reserved.
In the preceding letter1 we reported the synthesis of the
dihydroquinoline segment 1 of the thiostrepton family
of peptide antibiotics (e.g., thiostrepton, siomycins A
and C, and thiopeptin A1b, Fig. 1).2 In addition, we have
already reported the synthesis of the dehydropiperi-
dine,3 another dihydroquinoline,4 and pentapeptide5
segments.6,7 In this letter, we report the synthesis of
the siomycin cyclic core portion 2 containing the dehyd-
ropiperidine, dihydroquinoline 1, L-valine, and masked
dehydroalanine (i.e., b-phenyl- selenoalanine) segments.
The b-phenylselenoalanine portions in 2 would be trans-
formed into the dehydroalanine portions during the final
step of the total synthesis by the oxidative syn-elimina-
tion of the phenylseleno groups.8
We anticipated that the cyclic core portion 2 or its de-
hydroalanine derivative could be obtained by cyclization
of 3 which has several types of the masked dehydroala-
nine substructures (e.g., the L- and/or D-b-phenylseleno-
alanine substructures) or the two dehydroalanine
substructure via an intramolecular epoxide-opening
reaction (Fig. 2). However, all efforts under a variety
of reaction conditions resulted in the decomposition of
3 or no reaction.
Therefore, we investigated the intermolecular epoxide-
opening reaction between the model quinoline epoxide
49 (racemate) and L-valine benzyl ester 5 in the presence
of several types of Lewis acids as an epoxide activator.
The relevant experimental data are shown in Table 1.
By our reported procedure4 using LiClO4,10 a 1:1 mix-
ture of the coupling product 6 (40% isolated yield as a
1:1 diastereomeric mixture) and 8-hydroxyquinoline (7)
were obtained (entry 1). Other Lewis acids such as
Ti(i-PrO)4,11 Zn(OTf)2,10 Cu(OTf)2,12 and CeCl3Æ
7H2O13 were not effective for this coupling (entries 2–
5). In the case of Yb(OTf)3, which had been used as a
catalyst for the epoxide-opening with amines by Crotti
and co-workers14a and Yamamoto and co-workers,14b
the success depended on the solvent used. In CH2Cl2,14
the reaction resulted in a decomposition (entry 6). In
THF,14b compounds 4, 6, and 7 were obtained in a
Keywords: Thiostrepton; Dehydropiperidine; Dihydroquinoline; Dehy-
droalanine; Ytterbium triflate.
*
Corresponding authors. Tel.: +81 45 566 1577; fax: +81 45 566 1551
(M.N.); tel.: +81 75 595 4673; fax: +81 75 595 4763 (K.H.); e-mail
addresses: kimikoh@mb.kyoto-phu.ac.jp; msynktxa@applc.keio.
ac.jp
ꢀ Present address: Research Center for Molecular-Scale Nanoscience,
Institute for Molecular Science, Okazaki 444-8787, Japan.
ꢁ Present address: Kyoto Pharmaceutical University, 1 Shichono-cho,
Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.07.122

6424
T. Mori et al. / Tetrahedron Letters 46 (2005) 6423–6427
O
O
H
N
N
R6
S
H
O
O
N
O
O
R3
R2
N
H
H
S
OTMSE
SePh
N
N
S
N
N
O
O
H
H
H
H
H
O
HN
O
H
H
H
R1
H
O
N
N
N
S
N
N
SePh
N
OH
O
OH
H
H
H
H
NH
H
O
HN
OTBS
O
H
S
H
N
NH
H
O
N
H
O
N
O
O
H
H
H
R5
N
NH
O
OTMSE
S
N
N
NH
HN
O
S
t-BuO
O
R4
H
H
H
HO
NHBoc
H
N
N
S
2
H
TBSO
1
TBSO
H
H
H
O
HO
H
OH
Thiostrepton: R1 = CH2CH3, R2 = CH3, R3 = H, R4 = CH3, R5 = O, R6 = NH2
Siomycin A: R1 = CH3, R2 = R3 = CH2 (dehydroalanine), R4 = CH3, R5 = O, R6 = NH2
Siomycin C: R1 = CH3, R2 = R3 = CH2 (dehydroalanine), R4 = CH3, R5 = O, R6 = OMe
Siomycin D1: R1 = CH3, R2 = R3 = CH2 (dehydroalanine), R4 = H, R5 = O, R6 = NH2
Thiopeptin A1b: R1 = CH3, R2 = CH3, R3 = H, R4 = CH3, R5 = S, R6 = OMe
Figure 1.
O
4:3:3 ratio (entry 7). The best result so far obtained was
when a 1:10 CH2Cl2–H2O was used as the biphasic sol-
vent, affording 6 in 73% isolated yield together with an
ca. 10% yield of the starting material 4 (entry 8). The
presence of water seems to be crucial to this epoxide-
opening reaction.15
S
OTMSE
R4 R3
N
N
O
O
R2
R1
H
H
N
N
S
N
H
O
H
HN
O
H
O
N
H
N
O
These results prompted us to investigate the reaction of
4 with tripeptide 8a16 (L-valine–L-alanine–L-alanine sub-
structure) and 8b16 (L-valine–L-b-phenylselenoalanine–
L-b-phenylselenoalanine substructure) (Scheme 1).
Quinoline epoxide 4 (1.0 equiv) was treated with 8a
(1.1 equiv) in 1:10 CH2Cl2–H2O in the presence of a cat-
alytic amount (0.2 equiv) of Yb(OTf)3 at rt for 48 h, giv-
ing a 15:76:9 mixture of 4, 9a, and 7. In contrast, the
coupling of 4 with 8b under the same conditions affor-
ded a 44:56 mixture of 4 and 7; unfortunately, no 9b
OTMSE
H
S
O
NH2
N
O
H
NHBoc
TBSO
3
H
R1, R2 = H, CH2SePh: R3, R4 = H, CH2SePh
and
R1 = R2 = CH2 (dehydroalanine): R3 = R4 = CH2 (dehydroalanine)
Figure 2.
Table 1. Coupling reaction between 4 and 5
H
OH
OH
O
OBn
H
N
N
HN
N
OBn
+
+
O
H2N
O
5 (1.1 equiv)
4 (1.0 equiv)
6
7
Entry
Lewis acid (equiv)
Solvent
Temperature (ꢁC)
Time (h)
Ratioa of 4:6:7
1
2
3
4
5
6
7
8
LiClO4 (5.0)
CH3CN
THF
CH3CN
CH3CN
9:1 CH3CN–H2O
CH2Cl2
THF
70
Reflux
rt
70
rt
rt
Reflux
rt
15
25
22
22
22
21
30
24
0:49:51b
90:10:0
Decomposition
21:0:79
No reaction
Decomposition
40:30:30
9:91:0b
Ti(i-PrO)4 (2.0)
Zn(OTf)2 (1.0)
Cu(OTf)2 (0.1)
CeCl3Æ7H2O (0.5)
Yb(OTf)3 (0.5)
Yb(OTf)3 (0.1)
Yb(OTf)3 (0.2)
1:10 CH2Cl2–H2O
a The ratio of 4:6:7 was based on 1H NMR analysis of the crude products.
b Isolated yield of 6 after silica gel column chromatography was 40% (entry 1) and 73% (entry 8).

T. Mori et al. / Tetrahedron Letters 46 (2005) 6423–6427
R1 R2
6425
O
O
H
H
H
N
OR3
R
S
OEt
S
+
H2N
N
N
H
H
N
N
O
O
O
H
H
8a: R1 = R2 = R3 = Me
NH2
NH
NH2
NH
4 (1.0 equiv)
S
S
8b: R1 = R2 = CH2SePh, R3 = Fm
a,b
H
N
H
N
EtO
N
N
Yb(OTf)3 (0.2 equiv),
1:10 CH2Cl2-H2O, rt, 48 h
R
H
H
O
S
S
O
O
O
O
H
H
R1
R2
HN
BocN
H
H
H
OH
OH
OR3
N
HN
N
N
N
14
15
H
H
+
O
O
O
(R = CO2TMSE)
c
9a: R1 = R2 = R3 = Me
9b: R1 = R2 = CH2SePh, R3 = Fm
7
R
R
S
S
N
N
N
Scheme 1. Coupling reaction between 4 and 8.
H
O
O
H
N
H
N
NHBpoc
d,e
NHBpoc
S
S
NH
H
H
was obtained. Therefore, we selected the stepwise elon-
gation of the L-valine and masked dehydroalanine
(i.e., b-phenylselenoalanine) segments into the real dihy-
droquinoline segment 1.
H
N
H
N
N
R
R
N
H
H
S
S
OH
O
H
H
NHBoc
BocN
O
Along this line, dihydroquinoline 11 (75% ee, 1.0 equiv)
was coupled with L-valine 9-fluorenylmethyl (Fm) ester
1017 (2.0 equiv) in the presence of a catalytic amount
(0.2 equiv) of Yb(OTf)3 in 1:2 CH2Cl2–H2O at rt to give
11 in 48% yield together with a 7% yield of the diastereo-
mer of 11 arising from the enantiomer of 1, a 6% yield of
the regioisomer of 11, and a 13% yield of the recovered 1
(Scheme 2). After silylation (96% yield) of 11, the t-butyl
ester of the resulting 12 was deprotected with B-bromo-
catecholborane18 to give 13 in 79% yield.
17
16
Scheme 3. Synthesis of dehydropiperidine 17. Reagents and condi-
tions: (a) Ti(i-PrO)4 (1.0 equiv), trimethylsilylethanol, 100 ꢁC, 6 h; (b)
Boc2O (1.1 equiv), DMAP (0.2 equiv), Et3N (1.1 equiv), THF, 0 ꢁC,
1 h, 66%; (c) Bpoc-Ala-OH (2.0 equiv), CIP (2.0 equiv), HOAt (2.0
equiv), i-Pr2NEt (5.0 equiv), CH2Cl2, rt, 1.5 h, 83%; (d) Cs2CO3 (1.0
equiv), trimethylsilylethanol, rt, 10 h; (e) t-BuOCl (1.1 equiv), THF,
ꢀ78 ꢁC, 1 h, then DMAP (0.2 equiv), Et3N (10 equiv), rt, 3 h, 61%.
TMSE = trimethylsilylethyl,
Boc = t-butoxycarbonyl,
DMAP =
4-dimethylaminopyridine, Bpoc = 1-methyl-1-(4-biphenylyl)ethoxy-
carbonyl, CIP = 2-chloro-1,3-dimethylimidazolidium hexafluorophos-
phate, HOAt = 1-hydroxy-7-azabenzotriazole.
The coupling partner, the dehydropiperidine segment
17, was prepared from 14 (Scheme 3), which was a syn-
thetic intermediate of our former dehydropiperidine seg-
ment.3 Since it seems apparent that the ethyl esters
cannot be hydrolyzed after the construction of the cyclic
peptide which contains the lactone function, these ethyl
esters were changed to the trimethylsilylethyl (TMSE)
protecting groups. The treatment of 14 with trimethylsil-
ylethanol in the presence of Ti(i-PrO)419 followed by the
Boc protection of the oxazolidinone amine gave 15 in
66% yield. Condensation of 15 (1.0 equiv) with Bpoc-
Ala-OH20 (2.0 equiv) using CIP,21 HOAt, and i-Pr2NEt
afforded 16 in 83% yield. The selective deprotection of
the oxazolidinone in the presence of the TMSE esters
O
O
N
H
a
t-BuO
22
+
OFm
was realized by Cs2CO3 in trimethylsilylethanol and
H2N
the successive chlorination with t-BuOCl23 and dehydro-
chlorination with triethylamine and DMAP gave the
dehydropiperidine segment 17 in 61% yield.
O
10
TBSO
O
H
1
OR
8
O
OTBS
H
The preparation of the b-phenylselenoalanine dipeptide
22, the masked precursor to the labile dehydroalanine
portion, started with the known Boc-L-serine b-lactone
1824 (Scheme 4). Phenylselenylation of 18 by the proce-
dure reported by us5 (PhSeH, DMF, rt, 2 h) gave 19,25
which was treated with 9-fluorenylmethanol,26 and
DCC in the presence of a catalytic amount of DMAP
to give fluorenylmethyl (Fm) ester 20 in 82% yield from
18. The acidic treatment of 20 followed by condensation
with 19 using CIP, HOAt, and i-Pr2NEt in CH2Cl2
afforded 21 in 88% yield. The treatment of 21 with
TFA provided dipeptide 22, which was used without
purification for the next step.
H
H
H
N
H
N
H
t-BuO
OFm HO
c
N
H
N
H
R
O
TBSO
TBSO
H
H
R = CO2Fm
11: R = H
12: R = TBS
13
b
Scheme 2. Synthesis of dihydroquinoline carboxylic acid 13. Reagents
and conditions: (a) 1 (1.0 equiv), 10 (2.0 equiv), Yb(OTf)3 (0.2 equiv),
1:2 CH2Cl2–H2O, rt, 5 d, 48%; (b) TBSOTf (3.0 equiv), 2,6-lutidine
(10 equiv), CH2Cl2, 0 ꢁC, 15 min, 96%; (c) B-bromocatecholborane
(2.0 equiv), CH2Cl2, rt, 1 d, 79%. Tf = trifluoromethanesulfonyl,
TBS = t-butyldimethylsilyl.

6426
T. Mori et al. / Tetrahedron Letters 46 (2005) 6423–6427
SePh
coupled with the third segment 22 (1.2 equiv) with CIP,
O
H
a
HOAt, and i-Pr2NEt in CH2Cl2 to give 24 in 94% yield
from 23. Deprotection of the Bpoc group in 24 with
OH
O
BocHN
O
BocHN
27
Mg(ClO4)2 in acetonitrile followed by deprotection of
18
19
the Fm group afforded the cyclization precursor 25 in
67% yield. Final cyclization was carried out under a vari-
ety of condensation conditions including EDC–HOAt–
NMM, PyBOP–i-Pr2NEt,28 DPPA–i-Pr2NEt,29 and
HATU–base.30 Among them, the best conditions were
HATU (5.0 equiv) and NMM (5.0 equiv) in CH2Cl2
(1 mM for 25) at rt for 1 d, affording 231 in 79% yield.
The structure of 2 was confirmed by the mass spectrum
and the 1H and 13C NMR spectra, including H–H
COSY, HMQC, and HMBC.
b
SePh
OFm
SePh
O
H
H
H
c,d
N
RHN
OFm
SePh
BocHN
H
O
O
20
21: R = Boc
22: R = H
e
Scheme 4. Synthesis of b-phenylselenoalanine dipeptide 22. Reagents
and conditions: (a) PhSeH (1.2 equiv), DMF, rt, 2 h; (b) 9-fluorenyl-
methanol (1.2 equiv), DCC (1.2 equiv), DMAP (0.2 equiv), CH2Cl2, rt,
4 h, 82% (two steps); (c) 1:1 TFA–CH2Cl2, rt, 1 h, aq NaHCO3 work-
up; (d) 19 (1.1 equv), CIP (1.1 equiv), HOAt (1.1 equiv), i-Pr2NEt
(2.5 equiv), CH2Cl2, rt, 1 h, 88% (two steps); (e) 1:1 TFA–CH2Cl2, rt,
0.5 h, aq NaHCO3 work-up. DCC = 1,3-dicyclohexylcarbodiimide,
TFA = trifluoroacetic acid.
In summary, we have synthesized the siomycin cyclic
core portion 2 containing the dehydropiperidine, dihy-
droquinoline, L-valine, and masked dehydroalanine seg-
ments via the consecutive coupling of these four
segments, followed by cyclization at the amide bond be-
tween the dehydropiperidine and masked dehydroala-
nine segments. Synthetic studies for the total synthesis
of the thiostrepton family of peptide antibiotics are
now in progress.
With all the segments in hand, we next focused on their
coupling and cyclization (Scheme 5). Condensation of
dehydropiperidine 17 (1.2 equiv) and dihydroquinoline
13 (1.0 equiv) was realized with CIP, DMAP, and
i-Pr2NEt in CH2Cl2 to give 23 in 67% yield. After depro-
tection of the Fm ester in 23 with 1:1 diethylamine–
CH2Cl2,26 the resulting carboxylic acid (1.0 equiv) was
Acknowledgements
We thank Professor Shuichi Matsumura (Keio Univer-
sity) for the measurement of the mass spectrum of 2.
This research was partially supported by a Grant-in-
O
O
O
OTBS
H
H
N
H
S
OTMSE
S
OTMSE
HO
N
CO2Fm
N
O
N
O
H
H
N
H
N
NHBpoc
NHBpoc
13
S
S
N
N
TBSO
H
H
H
FmO
OTBS
O
H
H
TMSEO
N
TMSEO
N
H
a
N
N
O
H
H
H
O
O
S
S
N
NH
OH
O
H
H
H
NHBoc
NHBoc
17
23
TBSO
O
H
SePh
O
H
H
NH2
FmO
b,c
N
H
SePh
O
O
22
S
OTMSE
S
OTMSE
SePh
SePh
N
O
N
O
O
O
H
H
H
H
H
H
H
N
N
N
R1
O
R2
N
SePh
O
H
S
S
N
N
H
SePh
N
H
H
H
O
HN
O
H
HN
OTBS
H
H
f
TMSEO
N
TMSEO
N
N
H
N
O
OTBS
H
H
H
O
O
S
S
N
NH
H
N
NH
H
O
O
H
H
NHBoc
NHBoc
2
24: R1 = NHBpoc, R2 = CO2Fm
25: R1 = NH2, R2 = CO2H
d,e
TBSO
TBSO
H
H
Scheme 5. Synthesis of the cyclic core portion 2. Reagents and conditions: (a) 17 (1.2 equiv), 13 (1.0 equiv), CIP (1.2 equiv), DMAP (0.5 equiv),
i-Pr2NEt (2.5 equiv), CH2Cl2, rt, 10 min, 67%; (b) 1:1 Et2NH–CH2Cl2, rt, 1 h; (c) 22 (1.2 equiv), CIP (1.2 equiv), HOAt (1.2 equiv), i-Pr2NEt
(2.5 equiv), CH2Cl2, 0 ꢁC, 0.5 h, 94% (two steps); (d) Mg(ClO4)2 (5.0 equiv), acetonitrile, 40 ꢁC, 5.5 h; (e) 10% Et2NH–CH2Cl2, rt, 2.5 h, 67% (two
steps); (f) HATU (5.0 equiv), NMM (5.0 equiv), CH2Cl2 (1 mM for 25), rt, 1 d, 79%. HATU = O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluro-
nium hexafluorophosphate, NMM = N-methylmorpholine.

T. Mori et al. / Tetrahedron Letters 46 (2005) 6423–6427
6427
16. The synthesis of 8a and 8b will be reported elsewhere.
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Aid for the 21st Century COE program ꢂKEIO Life
Conjugate Chemistryꢃ from the Ministry of Education,
Culture, Sports, Science, and Technology, Japan, and
a Grant-in-Aid for Scientific Research on Priority Areas
(A) ꢂExploitation of Multi-Element Cyclic Moleculesꢃ
from the Ministry of Education, Culture, Sports, Sci-
ence, and Technology, Japan.
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K. C.; Safina, B. S.; Zak, M.; Estrada, A. A.; Lee, S. H.
Angew. Chem., Int. Ed. 2004, 43, 5087–5092; (f) Nicolaou,
K. C.; Zak, M.; Safina, B. S.; Lee, S. H.; Estrada, A. A.
Angew. Chem., Int. Ed. 2004, 43, 5092–5097.
29. DPPA = diphenylphosphoryl azide: Shioiri, T.; Nino-
miya, K.; Yamada, S. J. Am. Chem. Soc. 1972, 94,
6203–6205.
7. Recently, a total synthesis of thiostrepton has appeared;
see Refs. 6e,f.
30. Carpino, L. A. J. Am. Chem. Soc. 1993, 115, 4397–4398.
27
31. Data of 2: ½aꢁD ꢀ85.2 (c 1.00, CHCl3); IR (KBr): 2955,
8. The b-phenylselenoalanine strategy for synthetic studies
on thiostrepton family of peptide antibiotics, see: Higashi-
bayashi, S.; Mori, T.; Goto, T.; Shinko, K.; Kohno, M.;
Tohmiya, H.; Hashimoto, K.; Nakata, M. Tennen Yuki
Kagobutsu Toronkai Yoshishu 2002, 44, 521–526. See also
Refs. 5, 6d,f.
9. Agarwal, S. K.; Boyd, D. R.; Davies, R. J. H.; Hamilton,
L.; Jerina, D. M.; McCullough, J. J.; Porter, H. P. J.
Chem. Soc., Perkin Trans. 1 1990, 1969–1974.
10. Chini, M.; Crotti, P.; Macchia, F. Tetrahedron Lett. 1990,
31, 4661–4664.
11. (a) Caron, M.; Sharpless, K. B. J. Org. Chem. 1985, 50,
1557–1560; (b) Canas, M.; Poch, M.; Verdaguer, X.;
2895, 2860, 2360, 1720, 1500, 1480, 1405, 1255, 1220, 1095,
1
840, 780, 695 cmꢀ1; H NMR (CD3OD, 300 MHz, 40 ꢁC)
8.28 (quinoline H-3, 1H, s), 8.26 (thiazole H-5, 1H, s), 7.94
(thiazole H-5, 1H, s), 7.53–7.40 (Ph, 4H, m), 7.30–7.12
(Ph, 6H, m), 7.27 (thiazole H-5, 1H, s), 6.89 (quinoline H-
5, 1H, d, J = 10.0 Hz), 6.40 (quinoline H-6, 1H, dd,
J = 5.4, 10.0 Hz), 5.85 (Thr-b, 1H, m), 5.52 (piperidine H-
6, 1H, br s), 5.31 (MeCH(OTBS), 1H, q, J = 6.2 Hz), 5.21
(Thr-a, 1H, m), 4.94 (quinoline H-8, 1H, br s), 4.74–4.60
(2 · PhSeAla-a, 2H, m), 4.52–4.33 (2 · Me3SiCH2CH2,
4H, m), 4.20 (Ala-a, 1H, q, J = 7.0 Hz), 3.52–2.68
(2 · PhSeAla-b, piperidine H-3 and H-4, Val-a, 9H, m),
3.38 (quinoline H-7, 1H, dd, J = 1.2, 5.4 Hz), 2.01 (Val-b,
1H, m), 1.40 (MeCH(OTBS), 3H, d, J = 6.2 Hz), 1.40
(Thr-c, 3H, d, J = 6.2 Hz), 1.33 (Boc, 9H, s), 1.30 (Ala-b,
3H, d, J = 7.0 Hz), 1.20–1.04 (2 · Me3SiCH2CH2, 4H, m),
0.98 (Val-c, 3H, d, J = 7.0 Hz), 0.95 (t-BuMe2Si, 9H, s),
0.81 (Val-c, 3H, d, J = 6.8 Hz), 0.69 (t-BuMe2Si, 9H, s),
0.10 and 0.08 (2 · Me3SiCH2CH2, 18H, each s, contam-
inated with 6H of 2 · t-BuMe2Si), ꢀ0.01 (t-BuMe2Si, 3H,
s), ꢀ0.30 (t-BuMe2Si, 3H, s); 13C NMR (CD3OD,
75 MHz, 40 ꢁC) : d 176.6, 176.3, 175.1, 172.4, 171.1,
170.8, 165.9, 164.5, 162.8, 156.9, 156.9, 153.8, 152.5, 149.0,
148.1, 146.6, 134.2, 133.9, 132.4, 132.0, 131.6, 130.3, 130.2,
128.9, 128.4, 128.2, 128.1, 123.7, 122.9, 121.0, 81.6, 74.0,
73.1, 68.5, 67.8, 67.7, 67.3, 64.7, 64.6, 61.5, 61.3, 55.0, 52.6,
32.8, 30.4, 28.9, 28.6, 28.2, 26.4, 26.2, 26.0, 19.8, 19.1, 18.9,
18.3, 18.2, 18.0, ꢀ1.4, ꢀ1.4, ꢀ4.0, ꢀ4.1, ꢀ4.6, ꢀ4.6;
LRMS (MALDI-TOF) Calcd for C84H121N11O14S3Se2-
Si4Na (M+Na)+: 1898.6. Found: 1898.5.
`
Moyano, A.; Pericas, M. A.; Riera, A. Tetrahedron Lett.
1991, 32, 6931–6934.
12. Sekar, G.; Singh, V. K. J. Org. Chem. 1999, 64, 287–289.
13. (a) Reddy, L. R.; Reddy, M. A.; Bhanumathi, N.; Rao, K.
R. Synthesis 2001, 831–832; (b) Sabitha, G.; Babu, R. S.;
Rajkumar, M.; Yadav, J. S. Org. Lett. 2002, 4, 343–345.
14. (a) Chini, M.; Crotti, P.; Favero, L.; Macchia, F.;
Pineschi, M. Tetrahedron Lett. 1994, 35, 433–436; (b)
Meguro, M.; Asao, N.; Yamamoto, Y. J. Chem. Soc.,
Perkin Trans. 1 1994, 2597–2601.
15. The precise role of water has not been clarified. The
reaction of epoxides with amines in the presence of
Yb(OTf)3 in an aqueous solution, see: Beaton, M.; Gani,
D. Tetrahedron Lett. 1998, 39, 8549–8552. The reaction of
an epoxide with NaN3 in the presence of Yb(OTf)3 in an
aqueous solution, see: Fringuelli, F.; Pizzo, F.; Vaccaro, L.
J. Org. Chem. 2001, 66, 3554–3558.