Friedel-crafts reactions of vinylaziridine linked to an ester group

Article abstract of DOI:10.3987/COM-10-12115

Intermolecular Friedel-Crafts reactions of vinylaziridines 11, 12, 15, 16 and 20 linked to an ester with various benzene derivatives occurred at the C4 position selectively to afford 5-amino-4-aryl-2-hexenoate derivatives in good yields. The Japan Institute of Heterocyclic Chemistry.

Full text of DOI:10.3987/COM-10-12115

HETEROCYCLES, Vol. 83, No. 3, 2011
555
HETEROCYCLES, Vol. 83, No. 3, 2011, pp. 555 - 570. © The Japan Institute of Heterocyclic Chemistry
Received, 1st December, 2010, Accepted, 18th January, 2011, Published online, 26th January, 2011
DOI: 10.3987/COM-10-12115
FRIEDEL-CRAFTS REACTIONS OF VINYLAZIRIDINE LINKED TO AN
ESTER GROUP
Hisashi Takada,a Eiko Yasui,a Yui Sahara,a Yūki Chinen,a Hirotoshi
Tanaka,a Yusuke Morita,a Chihiro Kobiki,a Daiki Narisawa,a Megumi
Mizukami,b Masaaki Miyashita,a and Shinji Nagumoa*
a) Department of Applied Chemistry, Kogakuin University, Nakano 2665-1,
Hachioji, Tokyo 192-0015, Japan
b) Hokkaido Pharmaceutical University, School of Pharmacy, Katsuraoka 7-1,
Otaru 047-0264, Japan
Abstract – Intermolecular Friedel-Crafts reactions of vinylaziridines 11, 12, 15,
16 and 20 linked to an ester with various benzene derivatives occurred at the C4
position selectively to afford 5-amino-4-aryl-2-hexenoate derivatives in good
yields.
INTRODUCTION
Aziridine undergoes several types of reactions as well as epoxide due to its high ring strain. The
ring-opening reaction, in particular, is an important transformation1 and has widely been applied to
manifold natural product syntheses.2 Its synthetic value depends on the level of regiochemical selection
related to both electrophilic carbons in an aziridine moiety. The issue can often be solved by using
aziridines that are directly coupled with a -electron system. Ring-opening reactions of arylaziridine with
various nucleophiles such as organometal reagents and electron-rich arenes tend to proceed selectively at
a benzylic position.3 Ring-opening reactions of vinylaziridine with various organometal reagents and
sulfur-stabilized carbanion have also recently been reported. However, this type of reaction involves
another critical issue; that is, an SN2’-like ring-opening occurs competitively with an SN2-like one. The
coupling of sulfur-stabilized carbanion with vinylaziridine 1 resulted in the SN2 like ring-opening with
perfect regioselectivity.4 In contrast, most organometal reagents have been reported to react with
vinylaziridines 3 and 5 in an SN2’ fashion rather than in an SN2 fasion.5 Unlike arylaziridines, there are
few reports on regioselective Friedel-Crafts reaction of vinylaziridines. Akita et al. reported BF3・
Et2O-promoted intermolecular Friedel-Crafts reaction of vinylepoxides 7 linked to an ester group with

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HETEROCYCLES, Vol. 83, No. 3, 2011
activated arenes.6,7 Most arenes attacked 7 in an SN2 fashion with high regioselectivity. We thus report
herein regioselective Friedel-Crafts coupling of the corresponding vinylaziridines linked to an ester group
with various arenes.
Ts
CH2Ts
N
TsMe, BuLi
THF, -20 oC
74%
NHTs
MeO
MeO
2
1
BuMgBr, CuCN
TsN
TsHN
Bu
THF, -78 oC
99%
4
3
Me
MeCuCNLi
TsN
CO2Me
THF-Et2O (5 : 1), -78 oC
92%
CO2Me
NHTs
6
5
OMe
OMe
CO2Me
BF3 Et2O
CH2Cl2, -78 oC
O
CO2Me
OH
7
8
77%
Scheme 1
RESULTS AND DISCUSSION
Vinylaziridines 11, 12, 15, 16 and 20 were prepared as shown in Scheme 2. Staudinger reaction8 of
azidealcohol 9 with PPh3 in MeCN at 90 oC provided aziridine 10, which was converted into N-protected
N3
a
b or c
CO2Me
CO2Me
CO2Me
NH
NP
OH
9
10
11 (P = Boc, 78% from 9)
12 (P = CbZ, 71% from 9)
OBn
OBn
OBn
d (85%)
a (27%)
b or c
CO2Me
CO2Me
CO2Me
NH
14
NP
O
O
15 (P = Boc, 86%)
16 (P = CbZ, 84%)
13
OTBS
OTBS
OTBS
e
d (86%)
a (63%)
OH
CO2Me
CO2Me
NP
O
62%
17
18
19 (P = H)
20 (P = Boc)
b (98%)
Scheme 2. (a) PPh3, MeCN, 90 °C; (b) Boc2O, Et3N, THF; (c) CbZ-Cl, Et3N, CH2Cl2, 0 °C to rt; (d)
NaN3, NH4Cl, EtOH, 80 °C (e) Dess-Martin Periodinane, CH2Cl2, 0 °C then Ph3P=CHCO2Me, rt.

HETEROCYCLES, Vol. 83, No. 3, 2011
557
aziridine 11 and 12 by protection with Boc and CbZ groups. Dess-Martin oxidation9 of 17 followed by
Wittig reaction afforded vinylepoxide 18 in 62% yield. Treatment of 13 and 18 with NaN3/NH4Cl in
EtOH at 80 °C followed by Staudinger reaction gave 14 and 19, respectively, which were also converted
into 15, 16 and 20 by protection with Boc and CbZ groups.
Table 1. Friedel-Crafts Reactions of Simple Vinylaziridines
R1
R2
R1
R1
R2
R2
R3
R4
R3
4
2
21-26
1
R4
R3
R4
+
CO2Me
CO2Me
NP
CO2Me
BF3 Et2O
CH2Cl2
-78oC
NHP
NHP
31b (P = Boc)
37b (P = CbZ)
11 (P = Boc)
12 (P = CbZ)
27a-32a (P = Boc)
33a-38a (P = CbZ)
Entry
Ar
R1
R2
R3
R4
Aziridines
11
Products
Yields
Ratio (a : b)
OMe
H
H
H
H
H
OMe
H
1
21
22
23
24
25
26
21
22
23
24
25
26
27a
24%
17%
83%
76%
76%
64%
71%
79%
85%
81%
73%
99%
Me
2
11
11
11
11
11
12
12
12
12
12
12
28a
OMe OMe
H
3
29a
OMe
H
H
OMe
H
OMe
H
H
4
30a
5
OMe
31a + 31b
32a
ca. 2 : 1
OMe
OMe
H
OMe OMe
6
H
H
H
H
OMe
H
7
33a
Me
8
34a
OMe OMe
H
9
35a
OMe
H
H
OMe
H
OMe
H
H
10
11
12
36a
OMe
37a + 37b
38a
ca. 1.5 : 1
OMe
OMe OMe
Intermolecular Friedel-Crafts reactions of vinylaziridine 11 and 12 with various kinds of arenes (21-26)
o
was conducted in the presence of BF3·Et2O in CH2Cl2 for 30 min at -78 C under an argon atmosphere
(Table 1). As expected, the coupling of N-Boc vinylaziridine 11 with monomethoxybenzenes 21-22
occurred selectively at the C4 position to give 27a (24%) and 28a (17%), although their yields were
low.10 The yield increased when dimethoxybenzenes or trimethoxybenzene were used. The reactions with
1,2-dimethoxybenzene (23), 1,3-dimethoxybenzene (24) and 1,3,5-trimethoxybenzene (26) proceeded
smoothly to afford 5-amino-4-aryl-2-hexenoate 29a (83%), 30a (76%) and 32a (64%), respectively. On
the other hand, the reaction of 1,4-dimethoxybenzene (25) resulted in the formation of both SN2-type
product 31a and SN2’-type product 31b as an unseparable mixture (ca. 2 : 1). The yield in the reaction
with monomethoxybenzenes was drastically improved by using N-CbZ vinylaziridine 12 (Entries 7 and 8).
Other results for the reaction of 12 are all similar to those of the reaction of 11 (Entries 9-12). These
results indicate that the vinyl group exerts a strong directing effect on the regiochemical recognition of

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HETEROCYCLES, Vol. 83, No. 3, 2011
aziridine ring-opening, which is due to selective weakening of the allylic C-N bond by C=C−*C−N
overlap. It was also noteworthy that SN2’ reaction occurred to furnish 5-amino-2-aryl-4-hexenoate 31b
and 37b only in the case of using 25 (Entries 5 and 11). This may be explained by considering the
sequential mechanistic route, although further argument will be allowed (Scheme 3). Compound 25,
which is distinct from other arenes, undergoes competitive ortho-attack and ipso-attack11 leading to two
different types of benzenium ion A and B. The intermediate A is transformed to SN2 adduct 31a or 37a by
a simple deprotonation. On the other hand, B may undergo an intramolecular conjugated addition to form
bicyclic cation C, which is converted into SN2’ adduct 31b or 37b in two steps: (1) isomerization
including disconnection of the C-C bond leading to D and (2) deprotonation. An electron-releasing effect
of the methoxy group should be essential for smooth disconnection of C-C bond in C.
OMe
OMe
OMe
ortho attack
MeO
CO2Me
+
MeO
LA
N
H
LA
P
CO2Me
31a or 37a
CO2Me
MeO
ipso attack
11 or 12
25
NHP
NP
A
OMe
OMe
OMe
OMe
H
MeO
MeO
MeO
H
MeO
CO2Me
CO2Me
CO2Me
CO2Me
NP
NP
NHP
31b or 37b
NP
LA
LA
LA
B
C
D
Scheme 3
Table 2. Friedel-Crafts Reactions of Vinylaziridines Having an Oxygen Group at the C6 Position
R1
R1
R2
R2
R3
22-26
BF3
R4
R3
R4
P1O
CO2Me
+
NP2
Et2O
P1O
CO2Me
P1O
CO2Me
15 (P1 = Bn, P2 = Boc)
16 (P1 = Bn, P2 = CbZ)
20 (P1 = TBS, P2 = Boc)
CH2Cl2
-78oC
NHP2
NHP2
39a-46a
45b
Entry
Aziridines
P1
P2
Ar
R1
R2
R3
R4
Products
Yields
Ratio (a : b)
1
2
3
4
5
6
7
8
15
16
16
20
20
20
20
20
Bn
Bn
Boc
CbZ
CbZ
Boc
Boc
Boc
Boc
Boc
23
23
24
22
23
24
25
26
OMe OMe
OMe OMe
H
H
H
H
39a
40a
41a
42a
43a
44a
79%
73%
46%
67%
91%
85%
73%
84%
Bn
H
OMe
H
H
OMe
H
TBS
TBS
TBS
TBS
TBS
Me
OMe
H
OMe OMe
H
OMe
H
H
OMe
H
OMe
H
H
OMe
45a + 45b
3 : 1
OMe
OMe OMe
46a

HETEROCYCLES, Vol. 83, No. 3, 2011
559
Next, we carried out Friedel-Crafts reactions of vinylaziridines 15, 16 and 20 possessing an oxygen group
at the C6 position because the resulting products were expected to be valuable synthetic intermediates of
unnatural amino acids and nitrogen-containing natural products. As a result, also vinylaziridine
possessing a benzyloxy or silyloxy group at the C6 position was found to react smoothly with activated
arenes 22-26 to afford the target compounds 39a-46a and 45b in moderate to good yields.
In summary, intermolecular Friedel-Crafts reactions of vinylaziridines with various arenes were
performed. Only in the case of using 1,4-dimethoxybenzene, SN2’ and SN2 reactions proceeded
competitively to give two types of product. In other cases, Friedel-Crafts coupling proceeded
regioselectively at the C4 position to give only SN2-type products in good yields. Synthetic
transformation of the products 39-46 into unnatural amino acids is now in progress in our laboratory.
EXPERIMENTAL
General
Melting points were determined on a Yanagimoto MP-S3 micro melting point apparatus and were
uncorrected. IR spectra were recorded on a JASCO FT/IR-4100 as thin films using ATR (attenuated total
1
reflectance) or NaCl crystal. H and 13C NMR spectra were recorded on a JEOL JNN-ECX-400
spectrometer at 400 and 100 MHz, respectively. Chemical shifts were expressed in  parts per million
with tetramethylsilane as an internal standard ( = 0 ppm) for 1H NMR. Chemical shifts of carbon signals
were referenced to CDCl3 (C = 77.0 ppm). The following abbreviations are used: s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet, and br = broad. EI-mass spectra were recorded on a JEOL
JMS-GCmate II. FAB and ESI-mass spectra were recorded on a JEOL JMS-700. SI-mass spectra were
recorded on a Hitachi M-2000. Optical rotations were measured on a JASCO P-2200 polarimeter.
Column chromatography was carried out on Merck’s Silica gel 60 (70-230 mesh ASTM).
Tetrahydrofuran (THF) was distilled from sodium/benzophenone before use. Acetonitrile (MeCN) was
distilled from P2O5 immediately before use. All other reagents and solvents were purchased from
commercial sources and used without further purification.
(1’E,2RS,3RS)-2-(3’-Methoxy-3’-oxo-1’-propenyl)-3-methylaziridine-1-carboxylic acid tert-butyl
ester (11): To a solution of azide alcohol 9 (1.11 g, 6.00 mmol) in MeCN (25 mL) was added
triphenylphosphine (1.78 g, 6.79 mmol). The reaction mixture was stirred at 90 °C for 1 h, and after
cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The resulting
residue was dissolved in THF (20 mL) and cooled under an ice bath. After addition of Boc2O (2.84 mL,
12.4 mmol) and Et3N (0.92 mL, 6.60 mmol), the reaction mixture was stirred for 4 h, then quenched with

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HETEROCYCLES, Vol. 83, No. 3, 2011
brine, and extracted with AcOEt. The extract was dried over Na2SO4 and concentrated under reduced
pressure. The residue was purified by column chromatography on silica gel eluted with n-hexane/AcOEt
(10/1) to give Boc-aziridine 11 (1.12 g, 4.65 mmol, 78% in 2 steps) as a colorless oil. 1H-NMR (CDCl3)
: 6.50 (1H, dd, J = 15.6, 8.4 Hz), 6.14 (1H, d, J = 15.6 Hz), 3.74 (3H, s), 2.79 (1H, dd, J = 8.8, 2.8 Hz),
13
2.55 (1H, dq, J = 5.6, 2.8 Hz), 1.46 (9H, s), 1.34 (3H, d, J = 5.6 Hz); C-NMR (CDCl3) : 166.05 (s),
159.94 (s), 144.46 (d), 123.43 (d), 81.74 (s), 51.64 (q), 43.92 (d), 41.54 (d), 27.90 (3C, q), 16.11 (q); IR
(ATR) cm-1: 1712, 1655, 1137; SI-MS m/z 242 [M+H]+, 222, 204; HR-SIMS m/z calcd for C12H20NO4
242.1392 found 242.1371.
(1’E,2RS,3RS)-2-(3’-Methoxy-3’-oxo-1’-propenyl)-3-methylaziridine-1-carboxylic acid benzyl ester
(12): To a solution of azide alcohol 9 (0.964 g, 5.21 mmol) in MeCN (30 mL) was added
triphenylphosphine (1.50 g, 5.73 mmol). The reaction mixture was stirred at 90 °C for 1.5 h, and after
cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The resulting
residue was purified by column chromatography on silica gel eluted with n-hexane/AcOEt (1/1, finally
AcOEt only) to give aziridine 10 (2.99 g, containing Ph3P=O). To a mixture containing aziridine 10 in
CH2Cl2 (25 mL) was added CbZ-Cl (1.57 mL, 10.4 mmol) and Et3N (1.46 mL, 10.4 mmol). After being
stirred for 35 h at room temperature, the reaction mixture was quenched with brine and extracted with
AcOEt. The extract was dried over Na2SO4 and concentrated under reduced pressure. The resulting
residue was submitted to acetylation in order to remove benzyl alcohol. To a mixture containing
Cbz-aziridine 12 in CH2Cl2 (25 mL) was added acetic anhydride (3.0 mL) and pyridine (5.0 mL). After
being stirred for 21 h at room temperature, the reaction mixture was quenched with saturated aqueous
NaHCO3 and extracted with AcOEt. The extract was dried over Na2SO4 and concentrated under reduced
pressure. The residue was purified by column chromatography on silica gel eluted with n-hexane/AcOEt
(5/1) to give Cbz-aziridine 12 (1.02 g, 3.71 mmol, 71% in 2 steps) as a colorless oil. 1H-NMR (CDCl3) :
7.37-7.30 (5H, m), 6.51 (1H, dd, J = 15.6, 8.4 Hz), 6.14 (1H, d, J = 15.6 Hz), 5.17 (1H, d, J = 14.4 Hz),
5.14 (1H, d, J = 14.4 Hz), 3.73 (3H, s), 2.84 (1H, dd, J = 8.4, 2.8 Hz), 2.58 (1H, dq, J = 5.6, 2.8 Hz), 1.32
13
(3H, d, J = 5.6 Hz); C-NMR (CDCl3) : 165.93 (s), 160.83 (s), 143.83 (d), 135.54 (s), 128.53 (2C, d),
128.34 (3C, d), 123.80 (d), 68.30 (t), 51.68 (q), 44.08 (d), 41.90 (d), 16.11 (q); IR (film) cm-1: 1714, 1657,
1188; EI-MS m/z 275 [M]+, 232, 140; HR-MS m/z calcd for C15H17NO4 275.1158 found 275.1166.
(1’E,2RS,3SR)-2-Benzyloxymethyl-3-(3’-methoxy-3’-oxo-1’-propenyl)aziridine-1-carboxylic
acid
tert-butyl ester (15): To a solution of vinylepoxide 13 (408 mg, 1.64 mmol) in EtOH (30 mL) was added
sodium azide (314 mg, 4.83 mmol) and ammonium chloride (289 mg, 5.40 mmol). The reaction mixture
was stirred at 80 °C for 3 h, then quenched with H2O, and extracted with AcOEt. The extract was washed
with H2O, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by

HETEROCYCLES, Vol. 83, No. 3, 2011
561
column chromatography on silica gel eluted with n-hexane/AcOEt (4/1) to give azide alcohol (408 mg,
1.40 mmol, 85%) as a pale yellow oil. 1H-NMR (CDCl3) ; 7.39-7.28 (5H, m), 6.90 (1H, dd, J = 15.6, 7.2
Hz), 6.09 (1H, dd, J = 15.6, 1.6 Hz), 4.53 (2H, s), 4.21 (1H, m), 3.84 (1H, m), 3.75 (3H, s), 3.56 (1H, dd,
J = 9.6, 6.0 Hz), 3.51 (1H, dd, J = 9.6, 4.0 Hz), 2.91 (1H, m); 13C-NMR (CDCl3) : 165.87 (s), 141.35 (d),
137.28 (s), 128.42 (2C, d), 127.92 (d), 127.79 (2C, d), 124.42 (d), 73.47 (t), 71.79 (d), 70.06 (t), 63.73 (d),
51.74 (q); IR (ATR) cm-1: 3439, 2100, 1722, 1660; FAB (pos) m/z 292 [M+H]+, 264; HRMS (FAB-pos)
m/z calcd for C14H18N3O4 292.1297 found 292.1270. According to the conversion of 9 into 10, 14 (91.8
mg, 0.372 mmol, 27%) was obtained from the azide alcohol. Furthermore, 15 (362 mg, 1.04 mmol, 86%,
colorless oil) was obtained from 14 (300 mg, 1.22 mmol) according to the conversion of 10 into 11.
1H-NMR (CDCl3) : 7.37-7.27 (5H, m), 6.48 (1H, dd, J = 15.6, 8.8 Hz), 6.17 (1H, d, J = 15.6 Hz), 4.57
(1H, d, J = 11.8 Hz), 4.52 (1H, d, J = 11.8 Hz), 3.75 (1H, dd, J = 11.2, 4.0 Hz), 3.74 (3H, s), 3.64 (1H, dd,
13
J = 11.2, 4.0 Hz), 3.12 (1H, dd, J = 8.4, 2.8 Hz), 2.73 (1H, td, J = 4.0, 2.8 Hz), 1.43 (9H, s); C-NMR
(CDCl3) : 165.90 (s), 159.38 (s), 143.82 (d), 137.54 (s), 128.39 (2C, d), 127.76 (d), 127.61 (2C, d),
124.09 (d), 81.82 (s), 72.95 (t), 67.19 (t), 51.66 (q), 43.92 (d), 40.25 (d), 27.83 (3C, q); IR (ATR) cm-1:
1714, 1658; FAB (pos) m/z 348 [M+H]+, 292; HRMS (FAB-pos) m/z calcd for C19H26NO5 348.1811
found 348.1810.
(1’E,2RS,3SR)-2-Benzyloxymethyl-3-(3’-methoxy-3’-oxo-1’-propenyl)aziridine-1-carboxylic
acid
benzyl ester (16): Compound 16 (384 mg, 1.01 mmol, 84%, colorless oil) was obtained from 14 (297 mg,
1.20 mmol) according to the conversion of 10 into 12. 1H-NMR (CDCl3) : 7.41-7.23 (10H, m), 6.55 (1H,
dd, J = 15.6, 8.4 Hz), 6.16 (1H, d, J = 15.6 Hz), 5.10 (1H, d, J = 12.2 Hz), 5.06 (1H, d, J = 12.2 Hz), 4.42
(2H, s), 3.81 (1H, dd, J = 11.2, 3.2 Hz), 3.74 (1H, dd, J = 11.2, 3.2 Hz), 3.73 (3H, s), 3.27 (1H, dd, J = 8.0,
13
2.8 Hz), 2.72 (1H, q, J = 3.2 Hz); C-NMR (CDCl3) : 165.92 (s), 160.46 (s), 143.55 (d), 137.42 (s),
135.49 (s), 128.48 (2C, d), 128.41 (2C, d), 128.28 (3C, d), 127.78 (d), 127.51 (2C, d), 124.12 (d), 72.88
(t), 68.22 (t), 65.86 (t), 51.69 (q), 44.48 (d), 39.34 (d); IR (ATR) cm-1: 1716, 1659; FAB (pos) m/z 382
[M+H]+, 147; HRMS (FAB-pos) m/z calcd for C22H24NO5 382.1654 found 382.1659.
(2E,2’S,3’S)-3-[3’-(tert-Butyldimethylsilyloxymethyl)-oxiran-2’-yl]acrylic acid methyl ester (18): To
a solution of known alcohol 17 (1.46 g, 6.70 mmol) in CH2Cl2 (40 mL) was added Dess-Martin
Periodinane (8.53 g, 20.1 mmol) at 0 °C under Ar atmosphere for 30 min. After confirmation of
production of aldehyde by TLC, (carbomethoxymethylene)triphenylphosphorane (3.58 g, 10.1 mmol) was
added to the reaction mixture at room temperature. After being stirred for 17.5 h, the reaction mixture was
quenched with saturated aqueous Na2S2O3 (45 mL) and saturated aqueous NaHCO3 (45 mL) and filterd
through a celite pad. The resulting filtrate was extracted with AcOEt. The extract was washed with water
and brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by

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HETEROCYCLES, Vol. 83, No. 3, 2011
column chromatography on silica gel eluted with n-hexane/AcOEt (19/1) to give vinylepoxide 18 (1.13 g,
4.15 mmol, 62%) as a colorless oil. 1H-NMR (CDCl3) : 6.72 (1H, dd, J = 15.8, 7.2 Hz), 6.16 (1H, d, J =
15.8 Hz), 3.89 (1H, dd, J = 12.4, 3.2 Hz), 3.78 (1H, dd, J = 12.4, 4.0 Hz), 3.75 (3H, s), 3.44 (1H, dd, J =
13
7.2, 2.0 Hz), 3.06 (1H, m), 0.90 (9H, s), 0.084 (3H, s), 0.075 (3H, s); C-NMR (CDCl3) : 166.03 (s),
144.44 (d), 123.47 (d), 62.15 (t), 61.06 (d), 53.50 (d), 51.72 (q), 25.78 (3C, q), 18.30 (s), -5.39 (q), -5.41
(q); IR (film) cm-1: 1729, 1660; FAB (pos) m/z 273 [M+H]+, 215, 147; HRMS (FAB-pos) m/z calcd for
C13H25O4Si 273.1522 found 273.1519; []D23 −16.17 (CDCl3, c 1.14).
(1’E,2S,3R)-2-(tert-Butyldimethylsilyloxymethyl)-3-(3’-methoxy-3’-oxo-1’-propenyl)aziridine-1-car-
boxylic acid tert-butyl ester (20): To a solution of vinylepoxide 18 (50.0 mg, 0.184 mmol) in EtOH (1
mL) was added sodium azide (36.5 mg, 0.551 mmol) and ammonium chloride (29.8 mg, 0.551 mmol).
The reaction mixture was stirred at 80 °C for 4 h and then quenched with water (4.5 mL) at room
temperature. The mixture was extracted with AcOEt. The extract was washed with water, dried over
Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography
on silica gel eluted with n-hexane/AcOEt (14/1) to give azide alcohol (50.0 mg, 0.159 mmol, 86%) as a
pale yellow oil. 1H-NMR (CDCl3) ; 6.96 (1H, dd, J = 15.6, 6.8 Hz), 6.12 (1H, dd, J = 15.6, 1.2 Hz), 4.19
(1H, m), 3.77 (3H, s), 3.74-3.64 (3H, m), 2.63 (1H, m), 0.91 (9H, s), 0.10 (3H, s), 0.09 (3H, s); 13C-NMR
(CDCl3) : 165.93 (s), 141.71 (d), 124.38 (d), 72.90 (d), 63.58 (d), 62.97 (t), 51.80 (q), 25.78 (3C, q),
18.20 (s), -5.48 (q), -5.50 (q); IR (film) cm-1: 3460, 2106, 1730, 1662, 1257, 1118; ESI-MS (pos) m/z 338
26
[M+Na]+, 296; HRMS (ESI-pos) m/z calcd for C13H25N3O4SiNa 338.1512 found 338.1489; []D −5.69
(CDCl3, c 1.06). To a solution of azide alcohol (0.114 g, 0.361 mmol) in MeCN (2 mL) was added
triphenylphosphine (0.107 g, 0.397 mmol). The reaction mixture was stirred at 90 °C for 1 h and then
concentrated under reduced pressure. The residue was purified by column chromatography on silica gel
eluted with n-hexane/AcOEt (9/1) to give aziridine 19 (61.9 mg, 0.228 mmol, 63%) as a pale yellow oil.
To a solution of aziridine 19 (0.180 g, 0.663 mmol) in THF (4 mL) was added Boc2O (0.298 g, 1.33
mmol) and Et3N (0.102 mL, 0.730 mmol) at 0 °C. After being stirred at room temperature for 22 h, the
reaction mixture was quenched with water and extracted with AcOEt. The extract was washed with water
and brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel eluted with benzene to give Boc-aziridine 20 (0.241 g, 0.650, 98%)
1
as a colorless oil. H-NMR (CDCl3) : 6.50 (1H, dd, J = 15.6, 8.8 Hz), 6.17 (1H, d, J = 15.6 Hz), 3.93
(1H, dd, J = 11.6, 3.6 Hz), 3.76 (1H, dd, J = 12.6, 4.8 Hz), 3.75 (3H, s), 3.07 (1H, dd, J = 8.8, 2.8 Hz),
2.66 (1H, q, J = 3.6 Hz), 1.45 (9H, s), 0.89 (9H, s), 0.07 (3H, s), 0.06 (3H, s); 13C-NMR (CDCl3) :
166.01 (s), 159.43 (s), 144.17 (d), 123.82 (d), 81.69 (s), 60.93 (t), 51.68 (q), 45.87 (d), 40.23 (d), 27.93
(3C, q), 25.87 (3C, q), 18.35 (s), -5.29 (q), -5.34 (q); IR (ATR) cm-1: 1719, 1658, 1139; SI-MS m/z: 372

HETEROCYCLES, Vol. 83, No. 3, 2011
563
[M+H]+, 316, 277; HR-MS m/z: calcd for C18H34NO5Si 372.2206 found 372.2199; []D26 +2.36 (CDCl3, c
1.04).
General procedure for Friedel-Crafts reactions of vinylaziridines 11, 12, 15, 16, 20 and various
kinds of benzene derivatives
To a solution of vinylaziridines 11, 12, 15, 16, 20 (0.4 mmol) and benzene derivatives 21-26 (0.6 mmol)
in CH2Cl2 (3 mL) was added BF3・Et2O (0.2 mmol) at -78 oC under Ar atmosphere. The reaction mixture
was stirred for 30 min, then quenched with saturated aqueous NaHCO3, and extracted with Et2O. The
extract was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel eluted with n-hexane/AcOEt (9/1) to give coupling compounds
27-46.
(2E,4RS,5RS)-5-tert-Butoxycarbonylamino-4-(4’-methoxyphenyl)hex-2-enoic acid methyl ester
(27a): White powder; Mp 82-83 °C (CHCl3/ Et2O/ Hex); 1H-NMR (CDCl3) : 7.17 (1H, dd, J = 15.6, 8.8
Hz), 7.11 (2H, d, J = 8.6 Hz), 6.87 (2H, d, J = 8.6 Hz), 5.82 (1H, dd, J = 15.6, 0.8 Hz), 4.37 (1H, br), 4.03
(1H, br), 3.80 (3H, s), 3.69 (3H, s), 3.35 (1H, t, J = 8.4 Hz), 1.43 (9H, s), 1.01 (3H, d, J = 6.4 Hz);
13C-NMR (CDCl3) : 166.72 (s), 158.72 (s), 155.16 (s), 149.08 (d), 131.28 (s), 129.32 (2C, d), 122.02 (d),
114.21 (2C, d), 79.45 (s), 55.25 (q), 54.79 (d), 51.45 (q), 50.07 (d), 28.30 (3C, q), 18.73 (q); IR (ATR)
cm-1: 3340, 1713, 1678 ; EI-MS m/z: 349 [M]+; HR-MS m/z: calcd for C19H28NO5 [M+1]+ 350.1967
found 350.1970.
(2E,4RS,5RS)-5-tert-Butoxycarbonylamino-4-(2’-methoxy-5’-methylphenyl)hex-2-enoic acid methyl
1
ester (28a): White powder; Mp 94-96 °C (CHCl3/ Et2O/ Hex); H-NMR (CDCl3) : 7.21 (1H, dd, J =
15.6, 9.2 Hz), 7.03-6.93 (2H, m), 6.76 (1H, d, J = 8.4Hz), 5.82 (1H, dd, J = 15.6, 1.6Hz), 4.46 (1H, br),
4.17 (1H, br), 3.79 (3H, s), 3.75 (1H, t, J = 8.4Hz), 3.68 (3H, s), 2.26 (3H, s), 1.42 (9H, s), 0.99 (3H, d, J
13
= 6.4Hz); C-NMR (CDCl3) : 166.89 (s), 155.30 (s), 154.84 (s), 149.13 (d), 130.01 (s), 129.50 (d),
128.37 (d), 127.69 (s), 121.98 (d), 110.89 (d), 79.19 (s), 55.69 (q), 51.35 (q), 49.35 (d), 49.09 (d), 28.27
(3C, q), 20.49 (q), 19.30 (q); IR (ATR) cm-1: 3367, 1717, 1682; EI-MS m/z: 363 [M]+; HR-MS m/z: calcd
for C20H29NO5 363.2046 found 363.2017.
(2E,4RS,5RS)-5-tert-Butoxycarbonylamino-4-(3’,4’-dimethoxyphenyl)hex-2-enoic acid methyl ester
(29a): White powder; Mp 106-107 °C (benzene/ Hex); Anal. Calcd for C20H29NO6: C, 63.31; H, 7.70; N,
3.69. Found: C, 63.60; H, 7.80; N, 3.65; 1H-NMR (CDCl3) : 7.18 (1H, dd, J = 15.6, 8.8 Hz), 6.83 (1H, d,
J = 8.0 Hz), 6.75 (1H, dd, J = 8.0, 1.8 Hz), 6.71 (1H, br s), 5.84 (1H, dd, J = 15.6, 0.8 Hz), 4.56 (1H, br s),
4.05 (1H, m), 3.88 (3H, s), 3.86 (3H, s), 3.70 (3H, s), 3.32 (1H, t, J = 8.8 Hz),1.43 (9H, s), 1.03 (3H, d, J
13
= 8.8 Hz); C-NMR (CDCl3) : 166.68 (s), 155.18 (s), 149.15 (s), 148.89 (d), 148.19 (s), 131.81 (s),
122.12 (d), 120.49 (d), 111.38 (d), 111.09 (d), 79.49 (s), 55.90 (q), 55.88 (q), 55.37 (d), 51.46 (q), 50.04

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(d), 28.29 (3C, q), 18.89 (q); IR (ATR) cm-1: 3365, 1710, 1683; EI-MS m/z: 379 [M]+; HR-MS m/z: calcd
for C20H29NO6 379.1995 found 379.1979.
(2E,4RS,5RS)-5-tert-Butoxycarbonylamino-4-(2’,4’-dimethoxyphenyl)hex-2-enoic acid methyl ester
1
(30a): White powder; Mp 93-94 °C (Et2O/ Hex); H-NMR (CDCl3) : 7.20 (1H, dd, J = 15.6, 8.8 Hz),
7.06 (1H, d, J = 8.0 Hz), 6.47-6.43 (2H, m), 5.80 (1H, dd, J = 15.6, 0.8 Hz), 4.45 (1H, br), 4.14 (1H, m),
3.793 (3H, s), 3.789 (3H, s), 3.71 (1H, t, J = 8.8 Hz), 3.68 (3H, s), 1.42 (9H, s), 0.99 (3H, d, J = 6.8 Hz);
13C-NMR (CDCl3) : 166.90 (s), 159.76 (s), 157.94 (s), 155.26 (s), 149.24 (d), 129.37 (d), 121.69 (d),
120.28 (s), 104.45 (d), 98.80 (d), 79.12 (s), 55.39 (q), 55.27 (q), 51.30 (q), 49.23 (d), 48.61 (d), 28.26 (3C,
q), 19.16 (q); IR (ATR) cm-1: 3390, 1714, 1693; EI-MS m/z: 379 [M]+; HR-MS m/z: calcd for C20H29NO6
379.1995 found 379.1979.
(2E,4RS,5RS)-5-tert-Butoxycarbonylamino-4-(2’,5’-dimethoxyphenyl)hex-2-enoic acid methyl ester
(31a) & (2SR,3E,5RS)-5-tert-Butoxycarbonylamino-2-(2’,5’-dimethoxyphenyl)hex-3-enoic acid
methyl ester (31b): Compound 31a and 31b were obtained as a mixture in the ratio of 2 : 1. White
1
powder; Mp 78-80 °C (for 31a, CHCl3/ Et2O/ Hex); H-NMR (C6D6): 7.58 (1H for 31a, dd, J = 15.2,
8.8 Hz), 6.81 (1H for 31a, d, J = 2.8 Hz), 6.66 (1H for 31b, dd, J = 8.8, 3.2 Hz), 6.62 (1H for 31a, dd, J =
8.8, 3.2 Hz), 6.48 (1H for 31b, d, J = 9.2 Hz), 6.42 (1H for 31a, d, J = 8.8 Hz), 6.23 (1H for 31b, s), 6.10
(1H for 31b, ddd, J = 15.2, 8.0, 1.2 Hz), 5.98 (1H for 31a, d, J = 15.2 Hz), 5.47 (1H for 31b, dd, J = 15.2,
8.0 Hz), 4.81 (1H for 31b, d, J = 8.4 Hz), 4.43 (1H for 31a, m), 4.32 (1H for 31b, br), 4.20-4.01 (1H for
31a and 1H for 31b), 3.56 (1H for 31a, t, J = 9.2 Hz), 3.40 (3H for 31b, s), 3.36 (3H for 31a, s), 3.332
(3H for 31b, s), 3.329 (3H for 31b, s), 3.29 (3H for 31a, s), 3.26 (3H for 31a, s), 1.45 (9H for 31a, s),
1.42 (9H for 31b, s), 0.83 (3H for 31a and 3H for 31b, d, J = 6.4 Hz); 13C-NMR (CDCl3) : 173.18 (s),
166.77 (s), 155.24 (s), 153.66 (s), 153.59 (s), 151.23 (s), 150.85 (s), 155.01 (s), 148.68 (d), 135.10 (d),
129.05 (s), 128.12 (s), 126.13 (d), 122.18 (d), 115.26 (d), 114.91 (d), 112.51 (d), 112.37 (d), 111.98 (d),
111.87 (d), 79.18 (s), 56.19 (q), 56.03 (q), 55.62 (q), 52.08 (q), 51.33 (q), 49.19 (d), 47.99 (d), 28.31 (3C,
q), 28.23 (3C, q), 20.80 (q), 19.27 (q); IR (ATR) cm-1: 3376, 1718, 1680; EI-MS m/z: 379 [M]+; HR-MS
m/z: calcd for C20H29NO6 379.1995 found 379.1979.
(2E,4RS,5RS)-5-tert-Butoxycarbonylamino-4-(2’,4’,6’-trimethoxyphenyl)hex-2-enoic acid methyl
ester (32a): White powder; Mp 124-126 °C (Et2O/ Hex); Anal. Calcd for C21H31NO7: C21H31NO7: C,
1
61.60; H, 7.63; N, 3.42. Found: C, 61.97; H, 7.91; N, 3.42; H-NMR (CDCl3) : 7.38 (1H, dd, J = 15.6,
8.8 Hz), 6.10 (2H, s), 5.75 (1H, dd, J = 15.6, 0.8 Hz), 4.51-4.30 (2H, m), 3.85 (1H, t, J = 8.8 Hz), 3.794
13
(3H, s), 3.787 (6H, s), 3.67 (3H, s), 1.43 (9H, s), 0.92 (3H, d, J = 6.4 Hz); C-NMR (CDCl3) : 167.25
(s), 160.26 (s), 158.78 (2C, s), 155.46 (s), 149.85 (d), 121.05 (d), 108.65 (s), 90.86 (2C, d), 78.90 (s),
55.65 (2C, q), 55.24 (q), 51.19 (q), 47.68 (d), 45.59 (d), 28.31 (3C, q), 19.59 (q); IR (ATR) cm-1: 3381,

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565
1710, 1177; EI-MS m/z: 409 [M]+; HR-MS m/z: calcd for C21H32NO7 [M+1]+ 410.2179 found 410.2158.
(2E,4RS,5RS)-5-Benzyloxycarbonylamino-4-(4’-methoxyphenyl)hex-2-enoic acid methyl ester (33a):
White powder; Mp 81-83 °C (CHCl3/ Et2O/ Hex); Anal. Calcd for C22H25NO5: C, 68.91; H, 6.57; N, 3.65.
1
Found: C, 68.94; H, 6.55; N, 3.60; H-NMR (CDCl3) : 7.39-7.30 (5H, m), 7.15 (1H, dd, J = 15.8, 8.8
Hz), 7.08 (2H, d, J = 8.8Hz), 6.85 (2H, d, J = 8.8Hz), 5.83 (1H, dd, J = 15.8, 1.2Hz), 5.09 (2H, s), 4.60
(1H, br d, J = 8.8Hz), 4.10 (1H, br), 3.79 (3H, s), 3.70 (3H, s), 3.44 (1H, br t, J = 7.6Hz), 1.04 (3H, d, J =
6.8Hz); 13C-NMR (CDCl3) : 166.64 (s), 158.79 (s), 155.59 (s), 148.56 (d), 136.46 (s), 130.77 (s), 129.42
(2C, d), 128.52 (2C, d), 128.11 (d), 128.04 (2C, d), 122.39 (d), 114.23 (2C, d), 66.67 (t), 55.24 (q), 53.78
(d), 51.53 (q), 50.60 (d), 18.66 (q); IR (ATR) cm-1: 3339, 1712, 1689; FAB-MS (pos) m/z: 384[M+1]+,
308, 206; HRMS (FAB-pos) m/z calcd for C22H26NO5 384.1811 found 384.1821.
(2E,4RS,5RS)-5-Benzyloxycarbonylamino-4-(2’-methoxy-5’-methylphenyl)hex-2-enoic acid methyl
1
ester (34a): Colorless oil; H-NMR (CDCl3) : 7.38-7.29 (5H, m), 7.20 (1H, dd, J = 15.6, 8.4 Hz), 7.01
(1H, dd, J = 8.4, 2.0Hz), 6.95 (1H, br) 6.76 (1H, d, J = 8.0Hz), 5.84 (1H, dd, J = 15.6, 0.8Hz), 5.08 (2H,
s), 4.71 (1H, br d, J = 8.8Hz), 4.23 (1H, br q, J = 7.2Hz), 3.84 (1H, br t, J = 8.8Hz), 3.77 (3H, s), 3.69
13
(3H, s), 2.26 (3H, s), 1.03 (3H, d, J = 6.4Hz); C-NMR (CDCl3) : 166.82 (s), 155.75 (s), 154.82 (s),
148.67 (d), 136.58 (s), 130.02 (s), 129.68 (d), 128.54 (d), 128.49 (2C, d), 128.02 (d), 127.98 (2C, d),
127.26 (s), 122.27 (d), 110.92 (d), 66.55 (t), 55.52 (q), 51.46 (q), 49.92 (d), 48.26 (d), 20.50 (q), 19.20
(q); IR (film) cm-1: 3334, 1722, 1689; EI-MS m/z: 397[M]+; HR-MS m/z: calcd for C23H27NO5 397.1889
found 397.1916.
(2E,4RS,5RS)-5-Benzyloxycarbonylamino-4-(3’,4’-dimethoxyphenyl)hex-2-enoic acid methyl ester
(35a): White powder; Mp 83-85 °C (CHCl3/ Et2O/ Hex); Anal. Calcd for C23H27NO6: C, 66.81; H, 6.58;
1
N, 3.39. Found: C, 66.58; H, 6.67; N, 3.39; H-NMR (CDCl3) : 7.39-7.29 (5H, m), 7.16 (1H, dd, J =
15.6, 8.4 Hz), 6.81 (1H, d, J = 8.4 Hz), 6.72 (1H, d, J = 8.4 Hz), 6.67 (1H, s), 5.85 (1H, dd, J = 15.6, 1.2
Hz), 5.12 (1H, d, J = 12.0 Hz), 5.07 (1H, d, J = 12.0 Hz), 4.59 (1H, br d, J = 8.4 Hz), 4.11 (1H, m), 3.86
(3H, s), 3.84 (3H, s), 3.71 (3H, s), 3.41 (1H, t, J = 8.0 Hz), 1.06 (3H, d, J = 6.4 Hz); 13C-NMR (CDCl3) :
166.57 (s), 155.61 (s), 149.10 (d), 148.39 (s), 148.20 (s), 136.40 (s), 131.37 (s), 128.47 (2C, d), 128.07 (d),
127.98 (2C, d), 122.41 (d), 120.50 (d), 111.33 (d), 111.16 (d), 66.63 (t), 55.83 (q), 55.81 (q), 54.35 (d),
51.49 (q), 50.52 (d), 18.80 (q); IR (ATR) cm-1: 3362, 1705, 1689; EI-MS m/z: 413[M]+; HR-MS m/z:
calcd for C23H27NO6 413.1838 found 413.1823.
(2E,4RS,5RS)-5-Benzyloxycarbonylamino-4-(2’,4’-dimethoxyphenyl)hex-2-enoic acid methyl ester
(36a): White powder; Mp 84-86 °C (Et2O/ Hex); Anal. Calcd for C23H27NO6: C, 66.81; H, 6.58; N, 3.39.
1
Found: C, 66.65; H, 6.60; N, 3.42; H-NMR (CDCl3) : 7.38-7.31 (5H, m), 7.18 (1H, dd, J = 15.8, 8.8
Hz), 7.03 (1H, d, J = 8.0 Hz), 6.47-6.41 (2H, m), 5.82 (1H, dd, J = 15.8, 0.8 Hz), 5.08 (2H, s), 4.67 (1H,

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br d, J = 7.2 Hz), 4.26-4.15 (1H, m), 3.84-3.74 (7H, m), 3.69 (3H, s), 1.03 (3H, d, J = 6.8 Hz); 13C-NMR
(CDCl3) : 166.86 (s), 159.90 (s), 157.96 (s), 155.74 (s), 148.77 (d), 136.59 (s), 129.58 (d), 128.49 (2C,
d), 128.02 (d), 127.99 (2C, d), 122.07 (d), 119.87 (s), 104.46 (d), 98.84 (d), 66.55 (t), 55.39 (q), 55.33 (q),
51.46 (q), 49.90 (d), 47.66 (d), 19.10 (q); IR (ATR) cm-1: 3343, 1713, 1696; EI-MS m/z: 413[M]+;
HR-MS m/z: calcd for C23H28NO6 [M+1]+ 414.1917 found 414.1894.
(2E,4RS,5RS)-5-Benzyloxycarbonylamino-4-(2’,5’-dimethoxyphenyl)hex-2-enoic acid methyl ester
(37a)
&
(2SR,3E,5RS)-5-Benzyloxycarbonylamino-2-(2’,5’-dimethoxyphenyl)hex-3-enoic acid
methyl ester (37b): Compound 37a and 37b were obtained as a mixture in the ratio of ca. 1.5 : 1 as a
1
colorless oil. H-NMR (CDCl3) : 7.40-7.28 (5H for 37a and 5H for 37b, m), 7.19 (1H for 37a, dd, J =
15.6, 8.8 Hz), 6.82-6.70 (3H for 37a and 3H for 37b, m), 5.95 (1H for 37b, ddd, J = 15.6, 7.6, 1.4 Hz),
5.85 (1H for 37a, dd, J =15.6, 0.8 Hz), 5.55 (1H for 37b, dd, J = 15.6, 5.0 Hz), 5.08 (2H for 37a and 2H
for 37b, s), 4.73 (1H for 37a and 1H for 37b, m), 4.57 (1H for 37b, d, J = 8.0 Hz), 4.33 (1H for 37b, br),
4.23 (1H for 37a, m), 3.87 (1H for 37a, m), 3.75 (6H for 37a, s), 3.74 (6H for 37b, s), 3.69 (3H for 37a,
s), 3.67 (3H for 37b, s), 1.24 (3H for 37b, J = 6.8 Hz), 1.04 (3H for 37a, J = 6.4 Hz); 13C-NMR (CDCl3)
: 173.07 (s), 166.68 (s), 155.71 (s), 155.40 (s), 153.60 (s), 153.57 (s), 151.19 (s), 150.83 (s), 148.23 (d),
136.53 (s), 136.48 (s), 134.55 (d), 128.65 (s), 128.45 (5C, d), 127.97 (3C, d), 127.93 (3C, d), 126.65 (d),
122.49 (d), 115.28 (d), 115.22 (d), 112.57 (d), 112.37 (d), 111.94 (d), 111.90 (d), 66.52 (2C, t), 56.17 (q),
55.96 (q), 55.63 (q), 55.60 (q), 52.11 (q), 51.43 (q), 49.81 (d), 48.30 (d), 47.97 (d), 47.80 (d), 20.78 (q),
19.17 (q); IR (ATR) cm-1: 3334, 1716, 1652, 1498; EI-MS m/z: 413 [M]+; HR-MS m/z: calcd for
C23H27NO6 [M]+ 413.1838 found 413.1847.
(2E,4RS,5RS)-5-Benzyloxycarbonylamino-4-(2’,4’,6’-trimethoxyphenyl)hex-2-enoic acid methyl
1
ester (38a): Colorless oil; H-NMR (CDCl3) : 7.41-7.28 (6H, m), 6.10 (2H, s), 5.77 (1H, dd, J = 15.6,
0.8 Hz), 5.09 (2H, s), 4.73 (1H, br d, J = 8.4 Hz), 4.47 (1H, m), 3.93 (1H, t, J = 9.2 Hz), 3.79 (6H, s), 3.78
(3H, s), 3.67 (3H, s), 0.97 (3H, d, J = 6.4 Hz); 13C-NMR (CDCl3) : 167.13 (s), 160.31 (s), 158.71 (2C, s),
155.82 (s), 149.49 (d), 136.72 (s), 128.40 (2C, d), 127.88 (3C, d), 121.30 (d), 108.45 (s), 90.84 (2C, d),
66.34 (t), 55.61 (q), 55.21 (2C, q), 51.25 (q), 48.47 (d), 44.68 (d), 19.61 (q); IR (film) cm-1: 3345, 1716,
1650; EI-MS m/z: 443 [M]+; HR-MS m/z: calcd for C24H29NO7 [M+1]+ 444.2022 found 444.2040.
(2E,4RS,5SR)-6-Benzyloxy-5-tert-butoxycarbonylamino-4-(3’,4’-dimethoxyphenyl)hex-2-enoic acid
methyl ester (39a): Colorless oil; 1H-NMR (CDCl3) : 7.37-7.25 (5H, m), 7.20 (1H, dd, J = 15.6, 9.2 Hz),
6.83-6.70 (3H, m), 5.81 (1H, d, J = 15.6 Hz), 5.09 (1H, d, J = 10.4 Hz), 4.43 (1H, d, J = 12.0 Hz), 4.32
(1H, d, J = 12.0 Hz), 4.08 (1H, m), 3.85 (3H, s), 3.82 (3H, s), 3.67 (3H, s), 3.65 (1H, t, J = 10.0 Hz), 3.39
13
(1H, dd, J = 9.2, 2.4 Hz), 3.23 (1H, dd, J = 9.2, 2.4 Hz), 1.43 (9H, s); C-NMR (CDCl3) : 166.48 (s),
155.44 (s), 149.08 (s), 148.93 (d), 147.97 (s), 137.68 (s), 131.89 (s), 128.26 (2C, d), 127.65 (d), 127.48

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567
(2C, d), 121.95 (d), 120.23 (d), 111.32 (d), 110.59 (d), 79.42 (s), 73.16 (t), 69.38 (t), 55.72 (2C, q), 53.93
(d), 51.22 (q), 50.90 (d), 28.10 (3C, q); IR (ATR) cm-1: 3366, 1707, 1653; FAB-MS (pos) m/z: 486
[M+1]+, 430, 386; HRMS (FAB-pos) m/z calcd for C27H36NO7 486.2492 found 486.2517.
(2E,4RS,5SR)-6-Benzyloxy-5-benzyloxycarbonylamino-4-(3’,4’-dimethoxyphenyl)hex-2-enoic acid
1
methyl ester (40a): Colorless oil; H-NMR (CDCl3) : 7.39-7.22 (10H, m), 7.18 (1H, dd, J = 15.6, 8.8
Hz), 6.79 (1H, d, J = 8.4 Hz), 6.74 (1H, d, J = 8.4 Hz), 6.71 (1H, s), 5.82 (1H, d, J = 15.6 Hz), 5.26 (1H, d,
J = 9.6 Hz), 5.14 (1H, d, J = 12.4 Hz), 5.08 (1H, d, J = 12.4 Hz), 4.40 (1H, d, J = 11.8 Hz), 4.31 (1H, d, J
= 11.8 Hz), 4.16 (1H, m), 3.86 (3H, s), 3.82 (3H, s), 3.69 (1H, t, J = 9.6 Hz), 3.68 (3H, s), 3.40 (1H, dd, J
13
= 9.6, 3.2 Hz), 3.23 (1H, dd, J = 9.6, 2.8 Hz); C-NMR (CDCl3) : 166.53 (s), 156.01 (s), 149.15 (s),
148.56 (d), 148.10 (s), 137.63 (s), 136.37 (s), 131.71 (s), 128.46 (2C, d), 128.34 (2C, d), 128.03 (d),
127.92 (2C, d), 127.74 (d), 127.54 (2C, d), 122.35 (d), 120.30 (d), 111.36 (d), 110.78 (d), 73.22 (t), 69.34
(t), 66.75 (t), 55.80 (2C, q), 54.51 (d), 51.43 (q), 50.35 (d); IR (ATR) cm-1: 3342, 1718, 1654; FAB-MS
(pos) m/z: 520 [M+1]+, 476; HRMS (FAB-pos) m/z calcd for C30H34NO7 520.2335 found 520.2341.
(2E,4RS,5SR)-6-Benzyloxy-5-benzyloxycarbonylamino-4-(2’,4’-dimethoxyphenyl)hex-2-enoic acid
methyl ester (41a): Colorless oil; 1H-NMR (CDCl3) : 7.42-7.20 (11H, m), 7.04 (1H, d, J = 8.0 Hz), 6.43
(1H, s), 6.42 (1H, d, J = 7.6 Hz), 5.78 (1H, d, J = 15.6 Hz), 5.22 (1H, d, J = 9.6 Hz), 5.12 (1H, d, J = 12.4
Hz), 5.07 (1H, d, J = 12.4 Hz), 4.43 (1H, m), 4.37 (1H, d, J = 11.8 Hz), 4.28 (1H, d, J = 11.8 Hz), 3.98
(1H, t, J = 9.6 Hz), 3.78 (3H, s), 3.77 (3H, s), 3.66 (3H, s), 3.42 (1H, dd, J = 9.6, 3.2 Hz), 3.24 (1H, dd, J
= 9.6, 2.4 Hz); 13C-NMR (CDCl3) : 166.82 (s), 160.01 (s), 158.01 (s), 156.04 (s), 148.78 (d), 137.92 (s),
136.55 (s), 130.12 (d), 128.42 (3C, d), 128.24 (2C, d), 127.93 (d), 127.87 (d), 127.54 (d), 127.46 (2C, d),
121.92 (d), 119.73 (s), 104.47 (d), 98.85 (d), 73.12 (t), 69.82 (t), 66.58 (t), 55.26 (2C, q), 52.98 (d), 51.30
(q), 45.70 (d); IR (ATR) cm-1: 3342, 1718, 1654; FAB-MS (pos) m/z: 520 [M+1]+, 476, 444; HRMS
(FAB-pos) m/z calcd for C30H34NO7 520.2335 found 520.2314.
(2E,4R,5S)-5-tert-Butoxycarbonylamino-6-tert-butyldimethylsilyloxy-4-(2’-methoxy-5’-methylphenyl)-
hex-2-enoic acid methyl ester (42a): Colorless oil; 1H-NMR (CDCl3) : 7.25 (1H, dd, J = 15.6, 9.2 Hz),
7.05-6.96 (2H, m), 6.74 (1H, d, J = 8.4 Hz), 5.77 (1H, d, J = 15.6 Hz), 4.89 (1H, d, J = 9.6 Hz), 4.27 (1H,
br t, J = 10.0 Hz), 3.93 (1H, t, J = 9.6 Hz), 3.77 (3H, s), 3.66 (3H, s), 3.51 (1H, dd, J = 10.0, 3.2 Hz), 3.32
(1H, dd, J = 10.0, 2.0 Hz), 2.24 (3H, s), 1.42 (9H, s), 0.88 (9H, s), -0.06 (3H, s), -0.10 (3H, s); 13C-NMR
(CDCl3) : 166.94 (s), 155.63 (s), 155.02 (s), 149.40 (d), 130.40 (d), 129.90 (s), 128.51 (d), 127.25 (s),
121.77 (d), 110.76 (d), 79.26 (s), 62.66 (t), 55.34 (q), 53.56 (d), 51.24 (q), 45.87 (d), 28.29 (3C, q), 25.78
(3C, q), 20.38 (q), 18.22 (s), -5.79 (q), -5.84 (q); IR (film) cm-1: 3451, 3370, 1723, 1651; EI-MS m/z: 493
27
[M]+; HR-MS m/z: calcd for C26H44NO6Si [M+1]+ 494.2938 found 444.2918; []D −47.53 (CDCl3, c
1.04).

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HETEROCYCLES, Vol. 83, No. 3, 2011
(2E,4R,5S)-5-tert-Butoxycarbonylamino-6-tert-butyldimethylsilyloxy-4-(3’,4’-dimethoxyphenyl)hex-
2-enoic acid methyl ester (43a): Colorless oil; 1H-NMR (CDCl3) : 7.19 (1H, dd, J = 15.6, 9.2 Hz), 6.82
(1H, d, J = 8.4 Hz), 6.77 (1H, dd, J = 8.4, 1.6 Hz), 6.73 (1H, d, J = 1.6 Hz), 5.78 (1H, dd, J = 15.6, 1.2
Hz), 4.90 (1H, d, J = 9.6 Hz), 3.99 (1H, m), 3.87 (6H, s), 3.68 (3H, s), 3.59 (1H, t, J = 10.0 Hz), 3.51 (1H,
dd, J = 10.0, 3.2 Hz), 3.35 (1H, dd, J = 10.0, 2.4 Hz), 1.44 (9H, s), 0.91 (9H, s), -0.01 (3H, s), -0.03 (3H,
s); 13C-NMR (CDCl3) : 166.63 (s), 155.57 (s), 149.35 (s), 149.17 (s), 148.11 (d), 132.03 (s), 121.97 (d),
120.47 (d), 111.43 (d), 110.89 (d), 79.53 (s), 62.22 (t), 55.84 (q), 55.81 (q), 55.06 (d), 51.32 (q), 50.38 (d),
28.23 (3C, q), 25.83 (3C, q), 18.20 (s), -5.56 (q), -5.63 (q); IR (film) cm-1: 3451, 3370, 1722, 1653;
EI-MS m/z: 509 [M]+; HR-MS m/z: calcd for C26H43NO7Si [M]+ 509.2809 found 509.2822; []D29 −56.62
(CDCl3, c 1.03).
(2E,4R,5S)-5-tert-Butoxycarbonylamino-6-tert-butyldimethylsilyloxy-4-(2’,4’-dimethoxyphenyl)hex-
2-enoic acid methyl ester (44a): Colorless oil; 1H-NMR (CDCl3) : 7.22 (1H, dd, J = 15.6, 9.2 Hz), 7.07
(1H, d, J = 8.4 Hz), 6.47-6.41 (2H, m), 5.74 (1H, d, J = 15.6 Hz), 4.88 (1H, d, J = 10.0 Hz), 4.22 (1H, m),
3.91 (1H, t, J = 9.6 Hz), 3.79 (3H, s), 3.77 (3H, s), 3.66 (3H, s), 3.51 (1H, dd, J = 10.0, 3.2 Hz), 3.35 (1H,
dd, J = 10.0, 2.0 Hz), 1.43 (9H, s), 0.88 (9H, s), -0.06 (3H, s), -0.09 (3H, s); 13C-NMR (CDCl3) : 166.99
(s), 159.93 (s), 158.10 (s), 155.63 (s), 149.59 (d), 130.03 (d), 121.52 (d), 120.01 (s), 104.40 (d), 98.78 (d),
79.25 (s), 62.57 (t), 55.33 (q), 55.24 (q), 53.59 (d), 51.24 (q), 44.99 (d), 28.29 (3C, q), 25.80 (3C, q),
18.21 (s), -5.74 (2C, q); IR (ATR) cm-1: 1714; EI-MS m/z: 509 [M]+; HR-MS m/z: calcd for C26H43NO7Si
[M]+ 509.2809 found 509.2825; []D27 −43.73 (CDCl3, c 1.04).
(2E,4R,5S)-5-tert-Butoxycarbonylamino-6-tert-butyldimethylsilyloxy-4-(2’,5’-dimethoxyphenyl)hex-
2-enoic acid methyl ester (45a) & (2S,3E,5S)-5-tert-Butoxycarbonylamino-6-tert-butyldimethyl-
silyloxy-2-(2’,5’-dimethoxyphenyl)hex-3-enoic acid methyl ester (45b): Compound 45a and 45b were
obtained as a mixture in the ratio of 3 : 1 as a colorless oil. 1H-NMR (CDCl3) : 7.23 (1H for 45a, dd, J =
15.6, 8.8 Hz), 6.84-6.72 (3H for 45a and 3H for 45b, m), 5.99 (1H for 45b, ddd, J = 15.6, 8.0, 1.6 Hz),
5.77 (1H for 45a, d, J = 15.6 Hz), 5.56 (1H for 45b, dd, J = 15.6, 5.6 Hz), 4.89 (1H for 45a, d, J = 9.6 Hz),
4.80 (1H for 45b, br), 4.61 (1H for 45b, d, J = 7.6 Hz), 4.25 (1H for 45a, m), 4.20 (1H for 45b, br), 3.96
(1H for 45a, t, J = 9.2 Hz, 3.754 (3H for 45a and 3H for 45b, s), 3.750 (3H for 45a and 3H for 45b, s),
3.672 (3H for 45b, s), 3.665 (3H for 45a, s), 3.65-3.55 (2H for 45b, m), 3.52 (1H for 45a, dd, J = 10.0,
3.2 Hz), 3.36 (1H for 45a, dd, J = 10.0, 2.4 Hz), 1.44 (9H for 45b, s), 1.43 (9H for 45a, s), 0.87 (9H for
45a, s), 0.85 (9H for 45b, s), 0.01 (3H for 45b, s), 0.00 (3H for 45b, s), -0.06 (3H for 45a, s), -0.09 (3H
13
for 45a, s); C-NMR (CDCl3) : 173.12 (s), 166.88 (s), 155.59 (s), 155.26 (s), 153.65 (s), 153.27 (s),
151.39 (s), 150.87 (s), 149.02 (d), 131.54 (d), 128.56 (s), 128.08 (s), 127.67 (d), 121.98 (d), 115.50 (d),
115.32 (d), 112.74 (d), 112.62 (d), 111.84 (d), 79.31 (s), 65.24 (t), 62.67 (t), 56.19 (q), 55.79 (q), 55.68

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(q), 55.65 (q), 53.54 (d), 52.07 (q), 51.28 (q), 48.06 (d), 45.70 (d), 28.35 (3C, q), 28.28 (3C, q), 25.79 (3C,
q), 18.22 (s), -5.55 (2C, q), -5.78 (2C, q); IR (ATR) cm-1: 1714, 1498, 1222, 1167; EI-MS m/z: 509 [M]+,
26
396, 274; HR-MS m/z: calcd for C26H43NO7Si [M]+ 509.2809 found 509.2801; []D −32.91 (CDCl3, c
1.03).
(2E,4R,5S)-5-tert-Butoxycarbonylamino-6-tert-butyldimethylsilyloxy-4-(2’,4’,6’-trimethoxyphenyl)-
hex-2-enoic acid methyl ester (46a): Colorless oil; 1H-NMR (CDCl3)  7.30 (1H, dd, J = 15.6, 8.4 Hz),
6.08 (2H, s), 5.73 (1H, d, J = 15.6 Hz), 4.87 (1H, d, J = 10.0 Hz), 4.54 (1H, m), 4.19 (1H, t, J = 9.2 Hz),
3.80 (3H, s), 3.76 (6H, s), 3.65 (3H, s), 3.50 (1H, dd, J = 10.0, 2.8 Hz), 3.31 (1H, dd, J = 10.0, 2.0 Hz),
1.43 (9H, s), 0.85 (9H, s), -0.09 (3H, s), -0.14 (3H, s); 13C-NMR (CDCl3) : 167.32 (s), 160.29 (s), 158.96
(2C, s), 155.75 (s), 149.69 (d), 120.90 (d), 107.81 (s), 90.61 (d), 78.92 (s), 62.85 (t), 55.48 (2C, q), 55.26
(q), 52.29 (d), 51.14 (q), 40.45 (d), 28.32 (3C, q), 25.75 (3C, q), 18.20 (s), -5.83 (q), -5.89 (q); IR (film)
cm-1: 3450, 3379, 1720,1650; SI-MS m/z: 540 [M+H]+, 440, 265; HR-SIMS m/z: calcd for C26H46NO7Si
[M+1]+ 540.2993 found 540.2982; []D26 −41.89 (CDCl3, c 1.06).
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ion. However, a methyl group would be incapable of promoting the isomerization of the benzenium
ion C.