Stereoselective preparation of (1Z)- and (1E)-N-Boc-1-amino-1,3-dienes by stereospecific base-promoted 1,4-elimination

Article abstract of DOI:10.1016/j.tet.2014.12.039

The base-promoted 1,4-elimination reaction of N-Boc-1-amino-4-methoxy-2-alkene 1 is shown to proceed with perfect stereoselectivity to afford the corresponding N-Boc-1-amino-1,3-diene 2 in good yields. The reaction is highly stereospecific. The substrate

Full text of DOI:10.1016/j.tet.2014.12.039

Accepted Manuscript
Stereoselective preparation of (1Z)- and (1E)-N-Boc-1-amino-1,3-dienes by
stereospecific base-promoted 1,4-elimination
Eiji Tayama, Yuka Toma
PII:
S0040-4020(14)01736-0
10.1016/j.tet.2014.12.039
TET 26260
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 30 October 2014
Revised Date: 10 December 2014
Accepted Date: 11 December 2014
Please cite this article as: Tayama E, Toma Y, Stereoselective preparation of (1Z)- and (1E)-N-Boc-1-
amino-1,3-dienes by stereospecific base-promoted 1,4-elimination, Tetrahedron (2015), doi: 10.1016/
j.tet.2014.12.039.
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Stereoselective preparation of (1Z)- and
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stereospecific base-promoted 1,4-elimination
Eiji Tayama, Yuka Toma
Department of Chemistry, Faculty of Science, Niigata University, Niigata 950-2181, Japan

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Tetrahedron
journal homepage: www.elsevier.com
Stereoselective preparation of (1Z)- and (1E)-N-Boc-1-amino-1,3-dienes by
stereospecific base-promoted 1,4-elimination
Eiji Tayama , Yuka Toma
Department of Chemistry, Faculty of Science, Niigata University, Niigata 950-2181, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The base-promoted 1,4-elimination reaction of N-Boc-1-amino-4-methoxy-2-alkene 1 is shown
to proceed with perfect stereoselectivity to afford the corresponding N-Boc-1-amino-1,3-diene 2
in good yields. The reaction is highly stereospecific. The substrate E-1 gave 1Z-2 by the “Syn-
Effect” and Z-1 gave 1E-2 via formation of a chelated intermediate. Our method is widely
applicable to the preparation of various types of N-Boc-1-amino-1,3-dienes 2.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Elimination
1-Amino-1,3-diene
1,3-Dienamide
Stereoselective
Stereospecific
1. Introduction
concerted 1,4-elimination via formation of a chelate intermediate
complex of sodium bis(trimethylsilyl)amide (NaHMDS) A,
eventually leading to the 1E,3E-isomer. In that paper, we gave
one example of a reaction starting from the E-isomer (E-1) in
support the proposed intermediate A (eq 2). The reaction
proceeded via an open-chain intermediate B, affording a mixture
of 1Z,3E- and 1Z,3Z-isomers of 2. A reasonable explanation for
the 1Z-selectivity could not be advanced at that time. Recently,
Inomata and Ukaji reported a “Syn-Effect” evident in the 1,4-
elimination reactions of (E)-4-alkoxy-2-butenyl benzoates with
potassium hydroxide, in the presence of a palladium(II) catalyst
1-Amino-1,3-dienes are useful building blocks in organic
synthesis that function as reactive diene components in Diels–
Alder reactions enabling the construction of nitrogen-containing
fused-ring compounds.1
Though N-acyl-1-amino-1,3-dienes
(1,3-dienamides) are less reactive than the other 1-amino-1,3-
dienes, they are sufficiently stable towards air and moisture and
are easily handled in laboratory experiments.
Traditional
methods for the preparation of N-acyl-1-amino-1,3-dienes
include N-acylation of conjugated imines followed by
isomerization of the resulting N-acyliminium ions,2 and Curtius
affording sterically unfavourable Z-dienes.19,20
This work
rearrangements of 2,4-dienoic acids.3
In natural product
suggested that the 1Z-selectivity in our base-promoted 1,4-
elimination reaction of E-1 might also be explained by the “Syn-
Effect” at work in the open-chain intermediate B. Therefore, we
decided to further investigate the scope and limitations of our
base-promoted 1,4-elimination of N-Boc-4-methoxy-2-butenes
(1). Described herein is a stereoselective and stereospecific
method for the synthesis of various N-Boc-1-amino-1,3-dienes
(2) by 1,4-elimination reactions.
synthesis, copper catalyzed coupling of amides with dienyl
iodides4 (Buchwald protocol5) or palladium catalyzed cross-
couplings of alkenyl stannanes with alkenyl iodides6 have been
used to construct N-acyl-1-amino-1,3-diene components. To
date, a number of synthetic methods have been developed;7–16
however, stereoselective and E/Z-stereo-controlled synthetic
protocols are still limited.
In considering new methods for the preparation of N-acyl-1-
amino-1,3-dienes, we have studied base-promoted 1,4-
elimination reactions,17 which enable the construction of various
1,3-dienes components18 and have been used for the
stereoselective preparation of N-Boc-1-amino-1,3-diene (1E,3E-
2) through the 1,4-elimination of (Z)-N-Boc-4-substituted-4-
2. Results and discussion
We first selected (Z)-tert-butyl (4-methoxybut-2-en-1-
yl)(phenyl)carbamate (Z-1a) as a substrate for the synthesis of
tert-butyl buta-1,3-dien-1-yl(phenyl)carbamate (E-2a) by a base-
promoted 1,4-elimination proceeding though the chelated
intermediate A, as depicted in Scheme 1 (Table 1). The reactions
were carried out under the various conditions to clarify the
methoxy-2-butene (Z-1)17d (Scheme 1, eq 1).
The
stereoselectivity may be rationalized as resulting from
a
———
Corresponding author. Tel.: +81-25-262-7740; fax: +81-25-262-7740; e-mail: tayama@chem.sc.niigata-u.ac.jp

ACCEPTED MANUSCRIPT
2
Tetrahedron
effects of base and solvent. Treatment of Z-1a with 1.5
however, the reaction in Et2O afforded Z-2a in 79% yield with
excellent Z-selectivity (entry 10).
equivalents of n-butyllithium (n-BuLi) in THF at 0 °C for 3 h
afforded the desired 1,4-eliminated product (2) in 82% yield with
excellent stereoselectivity (entry 1). The C1–C2 stereochemistry
was assigned as E based on the 1H NMR coupling constant (J1-H,2-
Table 1. Base-promoted 1,4-elimination of Z-1a
= 14 Hz). When the reaction was carried out in diethyl ether
H
(Et2O), the yield was diminished (entry 2). Use of lithium
diisopropylamide (LDA) in THF improved the yield to 94% with
the same level of E-selectivity (entry 3). Reactions employing
lithium bis(trimethylsilyl)amide (LiHMDS) were unsuccessful,
resulting in the recovery of Z-1a at temperatures from 0 °C to
room temperature (entries 4, 5). When the reactions were carried
out with NaHMDS, 2a was obtained in moderate yields (entries
6, 7), though the formation of undesirable side products at room
temperature resulted in none of the substrate Z-1a being
recovered (entry 7). When Et2O was employed as the solvent, in
hopes of minimizing side reactions (entry 8), the yield was
improved to 79%, but the E-selectivity decreased (E/Z = 85/15).
The use of potassium bis(trimethylsilyl)amide (KHMDS) gave
2a in lowest E-selectivities (entries 9, 10). It seems that the
greater Lewis acidity of Li+, as compared to Na+ or K+, stabilizes
the chelated intermediate A, and thereby improve the E-
selectivity.
Entry
Base
Solvent Temp. (°C)
2a (%)a
82
E/Zb
>98/2
>98/2
>98/2
>98/2
90/10
95/5
1
n-BuLi
THF
Et2O
THF
THF
THF
THF
THF
Et2Of
THF
Et2O
0
0
0
0
rt
0
rt
rt
0
0
2
n-BuLi
64
3
LDAc
94
4
LiHMDSd
LiHMDSd
NaHMDSd
NaHMDSd
NaHMDSd
KHMDSe
KHMDSe
4g,h
25g,i
58j
5
6
7
57g,k
95/5
8
79
85/15
81/19
80/20
9
31
10
79
a Isolated yield unless otherwise noted. b Determined by 1H NMR assay of the
isolated product. c 1.0 M THF/hexanes solution (Aldrich). d 1.0 M THF
solution (Aldrich). e 0.5 M toluene solution (TCI). f The resulting solvent is
Et2O/THF = 4/1. g Determined by 1H NMR of the crude product using
mesitylene as an internal standard. h 96% recovery of Z-1a. i 67% recovery
of Z-1a. j 22% recovery of Z-1a. k 0% recovery of Z-1a
Table 2. Base-promoted 1,4-elimination of E-1a
Entry
Base
Solvent Temp. (°C)
2a (%)a
65
E/Zb
30/70
30/70
16/84
9/91
1
n-BuLi
THF
Et2O
THF
Et2O
THF
THF
THF
Et2Og
THF
Et2O
0
0
0
0
0
0
rt
rt
0
0
2
n-BuLi
52
3
LDAc
56
4
LDAd
89
5
LiHMDSe
NaHMDSe
NaHMDSe
NaHMDSe
KHMDSf
KHMDSf
4
3/97
6
71
2/>98
9/91
Scheme 1. Stereospecific formation of N-Boc-1-amino-1,3-
dienes 2 by base-promoted 1,4-elimination of Z- or E-1
7
45
8
69
2/>98
–
9
messy
79
Next, we investigated the reaction of E-1a under similar
conditions, which gave Z-2a by the “Syn-Effect” present in the
open-chain intermediate B, as depicted in Scheme 1 (Table 2).
The reaction of E-1a with n-BuLi at 0 °C afforded 2a as a 30:70
mixture of E- and Z-2a (entries 1, 2). Use of LDA improved the
Z-selectivity (entries 3, 4). The reaction with LiHMDS in THF
did not proceed (entry 5); therefore, we attempted the reaction
with the more-reactive NaHMDS, which resulted in the highly
stereoselective formation of the desired 2a in 71% yield (entry
6). The C1–C2 stereochemistry of 2a was assigned as Z based on
the 1H NMR coupling constant (J1-H,2-H = 9 Hz). When the
reaction was carried out at room temperature, both the yield and
Z-selectivity decreased and the formation of undesirable side
products was observed (entry 7). The side reactions were
minimized by using Et2O as the primary solvent (entry 8),
enabling the isolation of Z-2a in the yield and Z-selectivity
comparable to entry 6. Similar results were obtained in the
reaction with KHMDS. A complicated mixture was obtained in
THF due to the extensive formation of side products (entry 9);
10
2/>98
a Isolated yield. b Determined by 1H NMR assay of the isolated product. c 1.0
M THF/hexanes solution (Aldrich). d Prepared from n-BuLi and
diisopropylamine in Et2O at 0 °C. e 1.0 M THF solution (Aldrich). f 0.5 M
toluene solution (TCI). g The resulting solvent is Et2O/THF = 4/1.
To define the scope and limitations of the Z-stereoselective
preparation of N-Boc-1,3-dienamides Z-2 by 1,4-elimination, we
prepared a series of E-1 and used them in reactions with
NaHMDS in Et2O–THF at room temperature (Table 3). The
reactions of the N-(4-methoxyphenyl) and N-[(S)-1-phenylethyl]
derivatives (E-1b and E-1c) proceeded with the same levels of
yield and Z-selectivity (entries 1, 2). Racemization of Z-2c was
not observed by HPLC analysis using a chiral column, indicating
that a methine proton in the N-[(S)-1-phenylethyl] substituent
was not deprotonated. However, when the reaction of N-methyl
derivative E-1d was carried out under the same conditions, the
yield was lower (entry 3, 48%). The undesirable deprotonation
of the N-methyl protons might proceed because of the decreased
steric repulsion. Next, we attempted the reactions of 4,4-

ACCEPTED MANUSCRIPT
3
disubstituted derivatives (E-1e–1g). The 4,4-dimethyl-N-(4-
methoxyphenyl) derivative (E-2e) was obtained in moderate
yield (entry 4, 62%); however, the N-[(S)-1-phenylethyl]
derivative (E-2f) was not (entry 5, 23%). As the reactions of the
4,4-dimethyl derivatives proceeded rapidly, we performed the
reactions with E-1f and E-1g at reflux, affording the desired
products Z-2f and Z-2g in moderate yields (entries 6, 7). A slight
decrease of Z-selectivity was observed in the case of the N-
methyl derivative (E-2g, entry 7, E/Z = 7/93).
Table 3. Effects of 4- and N-substituents in base-promoted
1,4-elimination of E-1
Entry R1
R2
H
Temp. (°C)
2 (%)a
82
E/Zb
Scheme 2. 1,4-Elimination of N-allyl derivatives 1h
1
2
3
4
5
6
7
p-MeO-Ph
b
c
d
e
f
rt
2/>98
2/>98
2/>98
2/>98
2/>98
2/>98
7/93
(S)-CHMePh
Me
H
rt
82
H
rt
48
p-MeO-Ph
(S)-CHMePh
(S)-CHMePh
Me
Me
Me
Me
Me
rt
62
rt
23
f
Reflux
Reflux
65
g
55
a Isolated yield. b Determined by 1H NMR assay of the isolated product.
Figure 1. “Syn-Effect” in the base-promoted 1,4-elimination
of E-1
To demonstrate further synthetic transformations, we prepared
the N-allyl derivatives 1h as substrates and examined their
reactions with 2.0 equivalents of NaHMDS in Et2O–THF
(Scheme 2). The 1,4-elimination of E-1h was initiated at
approximately 0 °C, yielding Z-2h with isomerization of the N-
allyl substituent into the Z-enamide as a result of deprotonation
of allylic methylene proton (eq 1).
The elimination–
isomerization product 1Z,1’Z-3h was obtained in moderate yields
at room temperature or above. None of the previously described
reactions occurred at –20 °C. In contrast, the 1,4-elimination of
Z-1h proceeded in good yield (80%) even at –20 °C (eq 2). At
reflux, the elimination–isomerization product 1E,1’Z-3h was
obtained as the major product. Though the reason is unclear at
present, it is safe to say that E-1 is less reactive than Z-1 in the
base-promoted 1,4-elimination because of the inaccessibility of
the chelated intermediate A (Scheme 1), which enhances the rate
of 1,4-elimination.
Scheme 3. Study on C3–C4 stereoselectivity in the base-
promoted 1,4-elimination of 4-substituted E-1
In summary, we have demonstrated a stereoselective and
stereospecific base-promoted 1,4-elimination reaction of N-Boc-
1-amino-4-methoxy-2-alkenes 1 to afford the corresponding N-
Boc-1-amino-1,3-dienes 2.21 The reaction of Z-1 affords 1E-2
via formation of the chelated intermediate A. In contrast, the
reaction of E-1 affords 1Z-2 by the “Syn-Effect” of the open-
chain intermediate B. Both reactions proceed with perfect levels
of E- or Z-selectivities. Our method is widely applicable to the
preparation of various types of N-Boc-1-amino-1,3-dienes 2
which can act as useful building blocks in organic synthesis.22
The high 1Z-stereoselectivity of E-1 to Z-2 in this 1,4-
elimination can be explained by “Syn-Effect”, as proposed by
Inomata and Ukaji19 (Figure 1). Interactions between the σ-
orbital(s) of the allylic C–H σ-bond(s) and the antibonding (π*)
orbital of the C=C double bond affords s-cis conformation in the
transition state B*, which leads to 1Z-alkenes by 1,4-elimination.
3. Experimental
3.1. General
Finally, we prepared 4-butyl- and 4-phenyl-substituted
derivatives E-1i, E-1j and used them in reactions to investigate
the C3–C4 stereoselectivity of the 1,4-elimination (Scheme 3).
The corresponding eliminated products (2i or 2j) were obtained
as a mixture of two isomers (~ 9/1) in similar yields. The
stereochemistries of 2 were determined by their 1H NMR
coupling constants. The C1–C2 stereochemistries of both isomers
were determined to be 1Z (J1-H,2-H = 9–10 Hz). The C3–C4
stereochemistry was determined to be 3E for the major isomer
(J3-H,4-H = 15–16 Hz) and 3Z for the minor isomer (J3-H,4-H = 12
Hz). The “Syn-Effect” did not control the C3–C4 stereochemistry,
where the sterically favored trans-alkene was formed preferably.
Infrared spectra were recorded on a Perkin Elmer Spectrum
GX FT-IR spectrometer. 1H and 13C NMR spectra were
measured on a Varian 400 MHz spectrometer (1H: 400 MHz, 13C:
100 MHz) and a 700 MHz spectrometer (1H: 700 MHz, 13C: 175
MHz). The splitting patterns are denoted as follows: s, singlet; d,
doublet; t, triplet; q, quartet; m, multiplet; and br, broad peak.
Specific rotations were recorded on a JASCO Polarimeter P–
1010. High-resolution mass spectra were measured on a Thermo

ACCEPTED MANUSCRIPT
4
Tetrahedron
Fisher Scientific LC/FT-MS spectrometer. HPLC analyses
were performed using a JASCO HPLC pump PU-2080 and a
UV/VIS detector UV-2075. Reactions involving air- or
7.39-7.32 (2H, m, Ph), 7.28-7.20 (3H, m, Ph), 6.56 (1H, d, J =
9.2 Hz, 1-H), 5.57 (1H, ddd, J = 16.8, 11.6, 10.0 Hz, 3-H), 5.40
(1H, dd, J = 11.6, 9.2 Hz, 2-H), 4.98 (1H, dd, J = 16.8, 2.0 Hz, 4-
H), 4.72 (1H, d, J = 10.0 Hz, 4-H), 1.45 (9H, s, t-Bu); 13C NMR
(100 MHz, CDCl3) δ 153.1, 141.6, 130.6, 128.9, 127.2, 127.0,
126.4, 116.9, 115.6, 81.6, 28.1; HRMS–ESI (m/z): [M+Na]+
calcd for C15H19NO2Na: 268.1308. Found: 268.1311 (aq.
HCO2Na was added to improve sensitivity).
moisture-sensitive compounds were conducted in appropriate
round-bottomed flasks with a magnetic stirring bar under an
argon atmosphere. Lithium bis(trimethylsilyl)amide solution
(LiHMDS: 1.0 M in THF), sodium bis(trimethylsilyl)amide
solution (NaHMDS: 1.0
M
in THF), and lithium
diisopropylamide solution (LDA: 1.0 M in THF/hexanes) were
purchased from Aldrich. Potassium bis(trimethylsilyl)amide
solution (KHMDS: 0.5 M in toluene) was purchased from Tokyo
Chemical Industry (TCI) Co., Ltd. Tetrahydrofuran (THF) and
diethyl ether (Et2O) were purchased from KANTO Chemical Co.,
3.3.2. (Z)-tert-Butyl buta-1,3-dien-1-yl(4-
methoxyphenyl)carbamate (Z-2b)
Colorless crystals. IR (KBr) 3087, 3046, 3000, 2973, 2937,
2842, 1692, 1642, 1605, 1586, 1512, 1477, 1457, 1432, 1393,
1370, 1322, 1300, 1249, 1162, 1113, 1044, 1033, 1024, 1007,
Inc., Japan as an anhydrous solvent.
For thin layer
991, 917, 904, 851, 841, 823, 798, 765, 755, 735 cm-1; H NMR
1
chromatography (TLC) analysis throughout this work, Merck
TLC plates (silica gel 60 F254) were used. The products were
purified by preparative column chromatography on silica gel
(silica gel 60N, spherical neutral, KANTO Chemical Co., Inc.,
Japan).
(400 MHz, CDCl3) δ 7.15 (2H, ddd, J = 8.8, 2.8, 2.8 Hz, ArH),
6.89 (2H, ddd, J = 8.8, 2.8, 2.8 Hz, ArH), 6.59 (1H, d, J = 9.4 Hz,
1-H), 5.56 (1H, ddd, J = 16.5, 11.2, 10.4 Hz, 3-H), 5.33 (1H, dd,
J = 11.2, 9.4 Hz, 2-H), 4.96 (1H, dd, J = 16.5, 2.2 Hz, 4-H), 4.71
(1H, d, J = 10.4 Hz, 4-H), 3.82 (3H, s, OCH3), 1.45 (9H, s, t-Bu);
13C NMR (100 MHz, CDCl3) δ 158.0, 153.4, 134.3, 130.7, 128.5,
127.0, 116.5, 114.2, 81.5, 55.4, 28.1; HRMS–ESI (m/z): [M+H]+
calcd for C16H22NO3: 276.1594. Found: 276.1588.
3.2. Preparation of E-2a by 1,4-Elimination of Z-1a
A solution of Z-1a (145 mg, 0.523 mmol) in THF (3.1 mL)
was treated with a LDA solution (1.0 M in THF/hexanes, 0.79
mL, 0.79 mmol) at 0 °C under an argon atmosphere and the
mixture was stirred for 3 h at the same temperature. The
resulting mixture was quenched with saturated aqueous
ammonium chloride and extracted with ethyl acetate. The
combined extracts were washed with brine, dried over sodium
3.3.3. (S,Z)-tert-Butyl buta-1,3-dien-1-yl(1-
phenylethyl)carbamate (Z-2c)
Colorless oil. [α]22
–6.7 (c 1.00, EtOH); 99% ee
589
[determined by HPLC analysis: Daicel Chiralpak AD–H column,
n-hexane/2-propanol = 99/1 as the eluent, flow rate = 0.50
mL/min, tR = 8.9 min for (R)-Z-2c and 12.3 min for (S)-Z-2c]; IR
(film) 3085, 3028, 2976, 2932, 1688, 1646, 1493, 1475, 1451,
1392, 1366, 1304, 1250, 1164, 1085, 1041, 1026, 985, 908, 862,
796, 783, 766, 699 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.34-7.21
(5H, m, Ph), 6.32 (1H, dddd, J = 17.2, 10.9, 10.2, 0.8 Hz, 3-H),
5.86 (1H, dddd, J = 10.9, 8.0, 0.8, 0.8 Hz, 2-H), 5.58-5.45 (2H, m,
1-H and NCHCH3), 5.20 (1H, dddd, J = 17.2, 1.9, 0.8, 0.8 Hz, 4-
H), 5.09 (1H, dddd, J = 10.2, 1.9, 1.9, 0.8 Hz, 4-H), 1.52 (3H, d,
J = 7.2 Hz, NCHCH3), 1.42 (9H, s, t-Bu); 13C NMR (100 MHz,
CDCl3) δ 154.1, 141.2, 131.8, 128.2, 127.7, 127.1, 127.0, 124.3,
117.9, 80.3, 54.4, 28.2, 17.4; HRMS–ESI (m/z): [M+Na]+ calcd
for C17H23NO2Na: 296.1621. Found: 296.1619 (aq. HCO2Na was
added to improve sensitivity).
sulfate, and concentrated.
The residue was purified by
chromatography on silica gel (n-hexane/ethyl acetate = 20/1 as
the eluent) to give E-2a (120.1 mg, 94% yield) as a yellow oil.
3.2.1. (E)-tert-Butyl buta-1,3-dien-1-
yl(phenyl)carbamate (E-2a)
Yellow oil. IR (KBr) 3064, 3001, 2973, 2936, 1703, 1644,
1594, 1495, 1477, 1454, 1425, 1391, 1368, 1347, 1320, 1284,
1251, 1155, 1071, 1049, 1031, 1017, 1000, 930, 896, 863, 764,
1
704 cm-1; H NMR (400 MHz, CDCl3) δ 7.45-7.39 (2H, m, Ph),
7.35 (1H, d, J = 14.2 Hz, 1-H), 7.34 (1H, tt, J = 7.6, 1.4 Hz, Ph),
7.15 (2H, ddd, J = 7.6, 1.4, 1.4 Hz, Ph), 6.31 (1H, ddd, J = 16.8,
10.8, 10.4 Hz, 3-H), 5.05 (1H, dd, J = 14.2, 10.8 Hz, 2-H), 4.83
(1H, dd, J = 16.8, 1.6 Hz, 4-H), 4.81 (1H, dd, J = 10.4, 1.6 Hz, 4-
H), 1.42 (9H, s, t-Bu); 13C NMR (100 MHz, CDCl3) δ 152.3,
138.5, 135.0, 133.0, 129.2, 128.6, 127.7, 113.0, 112.3, 81.7, 28.1;
HRMS–ESI (m/z): [M+Na]+ calcd for C15H19NO2Na: 268.1308.
Found: 268.1307 (aq. HCO2Na was added to improve sensitivity).
3.3.4. (Z)-tert-Butyl buta-1,3-dien-1-
yl(methyl)carbamate (Z-2d)
Colorless oil. IR (film) 3087, 2977, 2928, 2855, 1708, 1644,
1592, 1477, 1455, 1432, 1420, 1392, 1367, 1329, 1255, 1152,
1
1045, 1027, 995, 928, 895, 865, 839, 778 cm-1; H NMR (400
3.3. Representative procedure for preparation of Z-2a by 1,4-
Elimination of E-1a
MHz, CDCl3) δ 6.62 (1H, dddd, J = 16.8, 11.4, 10.1, 0.8 Hz, 3-
H), 6.35 (1H, br, 1-H), 5.39 (1H, dd, J = 11.4, 10.2 Hz, 2-H),
5.15 (1H, dddd, J = 16.8, 2.0, 0.8, 0.8 Hz, 4-H), 5.06 (1H, ddd, J
= 10.1, 2.0, 2.0 Hz, 4-H), 3.17 (3H, s, NCH3), 1.48 (9H, s, t-Bu);
13C NMR (100 MHz, CDCl3) δ 154.0, 131.4, 128.5, 116.7, 114.7,
80.9, 36.4, 28.2; HRMS–ESI (m/z): [M+Na]+ calcd for
C10H17NO2Na: 206.1152. Found: 206.1149 (aq. HCO2Na was
added to improve sensitivity).
A solution of E-1a (140 mg, 0.505 mmol) in Et2O (3.0 mL)
was treated with a NaHMDS solution (1.0 M in THF, 0.76 mL,
0.76 mmol) at room temperature under an argon atmosphere and
the mixture was stirred for 3 h. The resulting mixture was
quenched with saturated aqueous ammonium chloride and
extracted with ethyl acetate. The combined extracts were washed
with brine, dried over sodium sulfate, and concentrated. The
residue was purified by chromatography on silica gel (n-
hexane/ethyl acetate = 20/1 to 10/1 as the eluent) to give Z-2a
(85.4 mg, 69% yield) as pale yellow crystals.
3.3.5. (Z)-tert-Butyl (4-methoxyphenyl)(4-
methylpenta-1,3-dien-1-yl)carbamate (Z-2e)
Yellow solid. IR (KBr) 3050, 2970, 2932, 2908, 2837, 1692,
1604, 1509, 1455, 1388, 1370, 1325, 1292, 1248, 1160, 1143,
1095, 1054, 1030, 1001, 982, 957, 854, 824, 791, 777, 766, 738
3.3.1. (Z)-tert-Butyl buta-1,3-dien-1-
yl(phenyl)carbamate (Z-2a)
1
cm-1; H NMR (400 MHz, CDCl3) δ 7.15 (2H, d, J = 8.8 Hz,
ArH), 6.86 (2H, ddd, J = 8.8, 2.8, 2.8 Hz, ArH), 6.35 (1H, d, J =
9.0 Hz, 1-H), 5.61 (1H, dd, J = 11.4, 9.0 Hz, 2-H), 5.26 (1H, d, J
= 11.4 Hz, 3-H), 3.80 (3H, s, OCH3), 1.65 (3H, s, 4-CH3), 1.54
(3H, s, 4-CH3), 1.45 (9H, s, t-Bu); 13C NMR (100 MHz, CDCl3) δ
Pale yellow crystals. IR (KBr) 3085, 3009, 2981, 2969, 2932,
1700, 1644, 1592, 1496, 1454, 1434, 1393, 1369, 1333, 1304,
1283, 1254, 1165, 1113, 1073, 1044, 1019, 993, 905, 858, 823,
1
793, 768, 756, 733, 695 cm-1; H NMR (400 MHz, CDCl3) δ

ACCEPTED MANUSCRIPT
5
157.6, 153.6, 135.3, 134.8, 128.0, 124.9, 118.9, 113.9, 113.2,
81.1, 55.4, 28.1, 26.3, 17.8; HRMS–ESI (m/z): [M+H]+ calcd for
C18H26NO3: 304.1907. Found: 304.1900.
13C NMR (100 MHz, CDCl3) δ 153.2-152.1 (m), 135.5, 132.3,
131.0, 116.0, 112.4, 110.3, 81.6, 47.0-45.5 (m), 28.1; HRMS–
ESI (m/z): [M+Na]+ calcd for C12H19NO2Na: 232.1308. Found:
232.1307 (aq. HCO2Na was added to improve sensitivity).
3.3.6. (S,Z)-tert-Butyl (4-methylpenta-1,3-dien-1-
yl)(1-phenylethyl)carbamate (Z-2f)
3.3.10. tert-Butyl (E)-buta-1,3-dien-1-yl((Z)-prop-
1’-en-1’-yl)carbamate (1E,1’Z-3h)
Pale yellow oil. [α]22
+3.8 (c 1.00, EtOH); 98% ee
589
[determined by HPLC analysis: Daicel Chiralpak AD–H column,
n-hexane/2-propanol = 95/5 as the eluent, flow rate = 0.50
mL/min, tR = 7.4 min for (R)-Z-2f and 7.9 min for (S)-Z-2f]; IR
(film) 3032, 2976, 2929, 1686, 1608, 1494, 1477, 1451, 1389,
1365, 1304, 1250, 1207, 1164, 1085, 1042, 1025, 981, 930, 911,
Colorless oil. IR (film) 3085, 3039, 2978, 2931, 1712, 1663,
1643, 1603, 1478, 1455, 1434, 1421, 1398, 1368, 1314, 1302,
1
1253, 1157, 1080, 997, 937, 882, 854, 795, 768, 711 cm-1; H
NMR (400 MHz, CDCl3) δ 7.08 (1H, d, J = 14.2 Hz, 1-H), 6.34
(1H, dddd, J = 17.2, 10.4, 10.4, 0.4 Hz, 3-H), 5.82 (1H, dq, J =
8.0, 1.8 Hz, 1’-H), 5.62 (1H, dq, J = 8.0, 7.0 Hz, 2’-H), 5.55 (1H,
dddd, J = 14.2, 10.4, 0.8, 0.8 Hz, 2-H), 5.06-4.99 (1H, m, 4-H),
4.91-4.85 (1H, m, 4-H), 1.53 (3H, dd, J = 7.0, 1.8 Hz, 3’-H), 1.49
(9H, s, t-Bu); 13C NMR (100 MHz, CDCl3) δ 152.0, 135.2, 130.5,
125.9, 124.1, 112.9, 112.0, 81.5, 28.1, 12.5; HRMS–ESI (m/z):
[M+Na]+ calcd for C12H19NO2Na: 232.1308. Found: 232.1306.
1
862, 781, 763, 737, 699 cm-1; H NMR (400 MHz, CDCl3) δ
7.34-7.19 (5H, m, Ph), 6.03 (1H, dd, J = 11.3, 8.2 Hz, 2-H), 5.78
(1H, dq, J = 11.3, 1.2 Hz, 3-H), 5.60-5.30 (2H, br, 1-H and
NCHCH3), 1.77 (3H, s, 4-CH3), 1.72 (3H, d, J = 1.2 Hz, 4-CH3),
1.52 (3H, d, J = 7.2 Hz, NCHCH3), 1.41 (9H, s, t-Bu); 13C NMR
(100 MHz, CDCl3) δ 154.3, 141.4, 136.4, 128.1, 127.04, 126.98,
123.7, 121.5, 120.2, 79.9, 54.2, 28.2, 26.3, 18.3, 17.5; HRMS–
ESI (m/z): [M+H]+ calcd for C19H28NO2: 302.2115. Found:
302.2110.
3.3.11. tert-Butyl (1Z)-octa-1,3-dien-1-yl(phenyl)
carbamate (1Z-2i)
Yellow oil. 1Z,3E/1Z,3Z = 87/13; IR (film) 3040, 2957, 2928,
2871, 1713, 1650, 1610, 1596, 1495, 1455, 1411, 1392, 1367,
1318, 1301, 1254, 1161, 1077, 1071, 1033, 1009, 997, 973, 926,
859, 832, 733, 693 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.37-7.29
(2H, m, Ph), 7.29-7.12 (3H, m, Ph), 6.49 (0.13H, d, J = 9.2 Hz, 1-
H), 6.36 (0.87H, d, J = 8.6 Hz, 1-H), 5.70 (0.13H, ddd, J = 11.8,
9.2, 1.0 Hz, 2-H), 5.50 (0.87H, dt, J = 14.8, 6.6 Hz, 4-H), 5.43
(0.87H, dd, J = 11.2, 8.6 Hz, 2-H), 5.39-5.27 (1H, m, 3-H and 4-
H), 5.19-5.10 (0.13H, m, 3-H), 2.11-2.02 (0.26H, m, 5-H), 1.80
(1.74H, dt, J = 6.6, 6.6 Hz, 5-H), 1.46 (9H, s, t-Bu), 1.32-1.23
(0.52H, m, 6-H and 7-H), 1.21-1.08 (3.48H, m, 6-H and 7-H),
0.87 (0.39H, t, J = 7.2 Hz, 8-H), 0.80 (2.61H, t, J = 7.2H, 8-H);
13C NMR (100 MHz, CDCl3, assigned only 1Z,3E) δ 153.3, 141.8,
135.0, 128.7, 127.0, 126.0, 124.9, 124.0, 116.9, 81.3, 32.1, 30.8,
28.1, 21.9, 13.8; HRMS–ESI (m/z): [M+H]+ calcd for
C19H28NO2: 302.2115. Found: 302.2112.
3.3.7. (Z)-tert-Butyl methyl(4-methylpenta-1,3-dien-
1-yl)carbamate (Z-2g)
Colorless oil. 1Z/1E = 93/7; IR (film) 3049, 2976, 2926, 1706,
1654, 1610, 1477, 1452, 1436, 1366, 1341, 1276, 1255, 1148,
1
1103, 1048, 1020, 982, 935, 869, 768, 757, 729 cm-1; H NMR
(400 MHz, CDCl3) δ 7.22-6.92 (0.07H, br, 1-H), 6.16 (0.93H, br,
1-H), 5.99 (0.93H, dd, J = 11.4, 1.0 Hz, 3-H), 5.79 (0.07H, d, J =
10.4 Hz, 3-H), 5.58 (1H, dd, J = 11.4, 10.0 Hz, 2-H), 3.12 (2.79H,
s, NCH3), 3.06 (0.21H, s, NCH3), 1.81 (2.79H, s, 4-CH3), 1.78
(0.21H, d, J = 4.0 Hz, 4-CH3), 1.74 (3H, s, 4-CH3), 1.50 (0.63H,
s, t-Bu), 1.47 (8.37H, s, t-Bu); 13C NMR (100 MHz, CDCl3,
assigned only 1Z) δ 154.5, 135.4, 126.6, 119.4, 113.0, 80.4, 36.5,
28.3, 26.4, 18.1; HRMS–ESI (m/z): [M+Na]+ calcd for
C12H21NO2Na: 234.1465. Found: 234.1462.
3.3.8. tert-Butyl (Z)-buta-1,3-dien-1-yl((Z)-prop-1’-
en-1’-yl)carbamate (1Z,1’Z-3h)
3.3.12. tert-Butyl phenyl((1Z)-4-phenylbuta-1,3-
dien-1-yl)carbamate (1Z-2j)
Colorless oil. IR (film) 3086, 3037, 2978, 2931, 2867, 1714,
1663, 1643, 1593, 1478, 1439, 1401, 1368, 1307, 1252, 1166,
1074, 1033, 994, 944, 901, 857, 811, 785, 761, 729 cm-1; 1H
NMR (400 MHz, CDCl3) δ 6.62 (1H, dddd, J = 17.2, 11.0, 10.6,
0.8 Hz, 3-H), 6.25 (1H, broad d, J = 8.8 Hz, 1-H), 6.15 (1H, dq, J
= 8.3, 1.6 Hz, 1’-H), 5.50 (1H, dddd, J = 11.0, 8.8, 0.8, 0.8 Hz, 2-
H), 5.26 (1H, dq, J = 8.3, 7.0 Hz, 2’-H), 5.15-5.07 (1H, m, 4-H),
5.04-4.98 (1H, m, 4-H), 1.53 (3H, dd, J = 7.0, 1.6 Hz, 3’-H), 1.49
(9H, s, t-Bu); 13C NMR (100 MHz, CDCl3) δ 152.7, 131.2, 127.7,
126.1, 118.9, 116.6, 81.4, 28.1, 13.0; HRMS–ESI (m/z): [M+H]+
calcd for C12H20NO2: 210.1489. Found: 210.1487.
Yellow solid. 1Z,3E/1Z,3Z = 90/10; IR (KBr) 3059, 2979,
2931, 1706, 1636, 1594, 1492, 1454, 1391, 1367, 1324, 1305,
1285, 1254, 1161, 1090, 1073, 1012, 973, 937, 859, 846, 758,
1
741, 696 cm-1; H NMR (400 MHz, CDCl3) δ 7.47-7.20 (5H, m,
ArH), 7.17 (2H, dddd, J = 7.2, 7.2, 1.4, 1.4 Hz, ArH), 7.11 (1H, tt,
J = 7.2, 1.4 Hz, ArH), 6.94-6.88 (2H, m, ArH), 6.69 (0.9H, d, J =
9.2 Hz, 1-H), 6.64 (0.1H, d, J = 9.6 Hz, 1-H), 6.24 (0.9H, d, J =
15.5 Hz, 4-H), 6.09 (0.1H, d, J = 11.8 Hz, 4-H), 5.95-5.82 (0.1H,
m, 3-H), 5.88 (0.9H, dd, J = 15.5, 11.8 Hz, 3-H), 5.56 (0.1H, dd,
J = 11.8, 11.8 Hz, 2-H), 5.50 (0.9H, dd, J = 11.8, 9.2 Hz, 2-H),
1.47 (9H, s, t-Bu); 13C NMR (100 MHz, CDCl3, assigned only
1Z,3E) δ 153.0, 141.5, 137.4, 131.1, 129.2, 128.3, 127.6, 127.04,
127.03, 126.8, 126.1, 123.0, 81.8, 28.1; HRMS–ESI (m/z):
[M+Na]+ calcd for C21H23NO2Na: 344.1621. Found: 344.1616.
3.3.9. (E)-tert-Butyl allyl(buta-1,3-dien-1-
yl)carbamate (E-2h)
Colorless oil. IR (film) 3086, 3043, 2978, 2931, 1710, 1642,
1604, 1535, 1476, 1448, 1426, 1372, 1329, 1293, 1253, 1232,
1
1218, 1159, 1056, 996, 967, 930, 879, 857, 767, 721 cm-1; H
Acknowledgments
NMR (400 MHz, CDCl3) δ 7.32-6.92 (1H, br, 1-H), 6.30 (1H,
ddd, J = 16.6, 10.4, 10.4 Hz, 3-H), 5.78 (1H, ddt, J = 17.0, 10.6,
5.2 Hz, CH2CH=CH2), 5.53 (1H, dd, J = 14.0, 10.4 Hz, 2-H),
5.15 (1H, d, J = 10.6 Hz, CH2CH=CH2), 5.12 (1H, d, J = 17.0 Hz,
CH2CH=CH2), 5.02 (1H, d, J = 16.6 Hz, 4-H), 4.87 (1H, d, J =
10.4 Hz, 4-H), 4.13 (2H, br, CH2CH=CH2), 1.50 (9H, s, t-Bu);
This work was supported by the JGC-S Scholarship
Foundation (No.1307).
References and notes
1. For reviews: (a) Oppolzer, W. In Comprehensive Organic
Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford,

ACCEPTED MANUSCRIPT
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Tetrahedron
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Supplementary Material
Supplementary data associated with this article can be found,
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ACCEPTED MANUSCRIPT
Stereoselective preparation of
(1Z)- and (1E)-N-Boc-1-amino-1,3-dienes by
stereospecific base-promoted 1,4-elimination
Eiji Tayama* and Yuka Toma
Department of Chemistry, Faculty of Science, Niigata University 950–2181, Japan
E-mail: tayama@chem.sc.niigata-u.ac.jp
Supplementary data
Contents:
Preparation of substrates 1
S2–12
Copies of NMR spectra of 2 and 3
S13–25
S1

ACCEPTED MANUSCRIPT
Preparation of substrates 1
(Z)-tert-Butyl (4-methoxybut-2-en-1-yl)(phenyl)carbamate (Z-1a)
(Step 1-1) Sodium hydride (60 wt.% in oil, 0.26 g, 6.5 mmol) was added to a solution of (Z)-2-buten-1,4-diol
(1.7 mL, 21 mmol) in THF (20 mL) at 0 °C under an argon atmosphere. The mixture was stirred for 30 min
at room temperature and cooled to 0 °C. The resulting mixture was treated with iodomethane (0.31 mL, 5.0
mmol) and stirred for 10 min at the same temperature. After stirring for 17 h at room temperature, the
resulting mixture was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate.
The combined extracts were dried over sodium sulfate and concentrated. The residue was purified by
chromatography on silica gel (hexane/ethyl acetate = 1/2 as the eluent) to give (Z)-4-methoxybut-2-en-1-ol (4)
(378 mg, 74% yield) as a pale yellow oil. (Step 1-2) A solution of 4 (378 mg, 3.70 mmol) in diethyl ether
(6.3 mL) was treated with phosphorus tribromide (0.36 mL, 3.8 mmol) at room temperature. After stirring
for 1 h at the same temperature, the resulting mixture was diluted with water at 0 °C and extracted with ethyl
acetate. The combined extracts were washed with saturated aqueous sodium hydrogen carbonate and water.
The organic layer was dried over sodium sulfate and concentrated to give (Z)-1-bromo-4-methoxybut-2-ene
(5) (426 mg, 70% yield) as a pale yellow oil. (Step 2-1) A solution of aniline (0.911 mL, 10.0 mmol) and di-
tert-butyl dicarbonate (2.34 mL, 10.2 mmol) in THF (5.0 mL) was stirred for 1 h at room temperature. The
resulting mixture was concentrated to obtain crude tert-butyl phenylcarbamate (6) (2.11 g, quant.) as colorless
crystals. (Step 2-2) A solution of 6 (742 mg, 3.84 mmol) and 5 (547 mg, 3.31 mmol) in DMF (10.9 mL) was
treated with sodium hydride (60 wt.% in oil, 0.20 g, 5.0 mmol) at 0 °C under an argon atmosphere. The
resulting mixture was stirred for 1 h at 50 °C and quenched with saturated aqueous ammonium chloride at 0 °C.
Extractive workup and purification of the residue by chromatography on silica gel (hexane/ethyl acetate = 5/1
as the eluent) afforded Z-1a (822 mg, 90% yield) as a yellow oil; IR (film) 3063, 2977, 2929, 2817, 1698, 1597,
1496, 1475, 1455, 1384, 1333, 1296, 1279, 1254, 1221, 1169, 1144, 1115, 1041, 1015, 953, 911, 864, 806, 759,
719, 697 cm-1; 1H NMR (400 MHz, CDCl3)  7.35-7.24 (2H, m, Ph), 7.22-7.07 (3H, m, Ph), 5.76-5.57 (2H, m,
CH=CH), 4.29 (2H, d, J = 6.4 Hz, CH2), 3.87 (2H, d, J = 6.0 Hz, CH2), 3.21 (3H, s, OCH3), 1.43 (9H, s, t-Bu);
13C NMR (100 MHz, CDCl3)  154.4, 142.4, 129.1, 128.6, 128.5, 126.7, 125.9, 80.3, 67.8, 57.8, 47.2, 28.2;
HRMS–ESI (m/z): [M+Na]+ calcd for C16H23NO3Na: 300.1570. Found: 300.1563 (aq. HCO2Na was added to
improve sensitivity).
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ACCEPTED MANUSCRIPT
(E)-tert-Butyl (4-methoxybut-2-en-1-yl)(phenyl)carbamate (E-1a)
(Step 1) A solution of 6 (1.08 g, 5.59 mmol) in THF (28 mL) was treated with sodium hydride (60 wt.% in oil,
0.29 g, 7.3 mmol) at 0 °C and stirred for 10 min under an argon atmosphere. 3-Bromo-1-propyne (0.51 mL,
6.8 mmol) was added to the mixture at the same temperature and the mixture was stirred for 12 h at room
temperature. The resulting mixture was quenched with saturated aqueous ammonium chloride at 0 °C and
extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, and
concentrated. Purification of the residue by chromatography on silica gel (hexane/ethyl acetate = 20/1 to 10/1
as the eluent) gave N-tert-butoxycarbonyl-N-(prop-2-ynyl)aniline (7) (1.09 g, 84% yield) as a yellow oil.
(Step 2) A solution of 7 (933 mg, 4.03 mmol) in THF (19 mL) was treated with a 1.64 M n-butyllithium hexane
solution (2.57 mL, 4.21 mmol) at –78 °C under an argon atmosphere and stirred for 10 min at the same
temperature. Paraformaldehyde (270 mg, 9.0 mmol) was added to the solution and the mixture was stirred
for 15 min at –78 °C and for 2 h at room temperature. The resulting mixture was quenched with saturated
aqueous ammonium chloride and extracted with ethyl acetate. The combined extracts were washed with
brine, dried over sodium sulfate, and concentrated. The residue was purified by chromatography on silica
gel (hexane/ethyl acetate = 2/1 to 1/1 as the eluent) to obtain tert-butyl (4-hydroxybut-2-yn-1-
yl)(phenyl)carbamate (8) (918 mg, 87% yield) as a yellow oil. (Step 3) A 1.0 M sodium bis(2-
methoxyethoxy)aluminum hydride toluene solution (4.3 mL, 4.3 mmol) was added to a solution of 8 (913 mg,
3.49 mmol) in toluene (17 mL) at 0 °C under an argon atmosphere and the mixture was stirred for 1 h at the
same temperature. The resulting mixture was quenched with water at 0 °C and treated with a 1 M aqueous
potassium hydrogen sulfate to dissolve inorganic salts. The mixture was extracted with ethyl acetate and the
combined extracts were washed with saturated aqueous sodium hydrogen carbonate and brine. The organic
layer was dried over sodium sulfate and concentrated to obtain (E)-tert-butyl (4-hydroxybut-2-en-1-
yl)(phenyl)carbamate (9) (1.14 g) as a yellow viscous oil.
(Step 4) A mixture of 9 (587 mg),
tetrabutylammonium iodide (166 mg, 0.45 mmol), and 50 wt.% aqueous sodium hydroxide solution (2.3 mL)
in benzene (24 mL) was treated with dimethyl sulfate (0.25 mL, 2.6 mmol) and stirred for 46 h at room
temperature. The resulting mixture was quenched with saturated aqueous ammonium chloride and extracted
with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, and
concentrated. Purification of the residue by chromatography on silica gel (hexane/ethyl acetate = 6/1 to 4/1
as the eluent) gave E-1a (454 mg, 91% yield from 8) as a pale yellow oil; IR (film) 3063, 2977, 2929, 2822,
1697, 1597, 1496, 1473, 1455, 1384, 1366, 1301, 1278, 1252, 1168, 1124, 1092, 1049, 1011, 972, 945, 909,
864, 760, 697 cm-1; 1H NMR (400 MHz, CDCl3)  7.34-7.27 (2H, m, Ph), 7.20 (2H, broad d, J = 7.6 Hz, Ph),
S3

ACCEPTED MANUSCRIPT
7.16 (1H, tt, J = 7.6, 1.2 Hz, Ph), 5.80 (1H, dtt, J = 15.4, 5.8, 1.2 Hz, CH=CH), 5.64 (1H, dtt, J = 15.4, 5.8, 1.2
Hz, CH=CH), 4.23 (2H, ddt, J = 5.8, 1.2, 1.2 Hz, CH2), 3.89 (2H, ddt, J = 5.8, 1.2, 1.2 Hz, CH2), 3.27 (3H, s,
OCH3), 1.44 (9H, s, t-Bu); 13C NMR (100 MHz, CDCl3)  154.4, 142.7, 129.2, 128.7, 128.5, 126.4, 125.7,
80.3, 72.3, 57.7, 51.7, 28.3; HRMS–ESI (m/z): [M+Na]+ calcd for C16H23NO3Na: 300.1570. Found: 300.1566
(aq. HCO2Na was added to improve sensitivity).
(E)-tert-Butyl (4-methoxybut-2-en-1-yl)(4-methoxyphenyl)carbamate (E-1b)
(Step 1-1) A solution of methyl propargyl ether (1.69 mL, 20.0 mmol) in THF (60 mL) was treated with a 1.64
M n-butyllithium hexane solution (12.8 mL, 21.0 mmol) at 0 °C under an argon atmosphere and the mixture
was stirred for 30 min at the same temperature. Paraformaldehyde (0.90 g, 30 mmol) was added to the
solution in one portion at 0 °C and the mixture was stirred for 12 h at room temperature. The resulting mixture
was diluted with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic
solution was dried over sodium sulfate and concentrated. The residue was dissolved in diethyl ether (75 mL)
and treated with sodium bis(2-methoxyethoxy)aluminum hydride toluene solution (65 wt.%, 9.0 mL, 30 mmol)
at 0 °C under an argon atmosphere. The mixture was stirred for 1 h at 0 °C and 1 h at room temperature.
The resulting mixture was quenched with saturated aqueous potassium sodium tartrate at 0 °C and stirred for
1 h at room temperature. The mixture was extracted with ethyl acetate and the combined extracts were dried
over sodium sulfate. Evaporation of the solvent and purification of the residue by bulb to bulb distillation
under vacuum (2 hPa, 80 to 90 °C) afforded (E)-4-methoxybut-2-en-1-ol (10) (1.48 g, 72% yield) as a colorless
oil. (Step 1-2) Asolution of 10 (802 mg, 7.85 mmol) in ether (16 mL) was treated with phosphorus tribromide
(0.74 mL, 7.9 mmol) at 0 °C. After stirring for 30 min at the same temperature, the resulting mixture was
diluted with water at 0 °C and extracted with ethyl acetate. The combined extracts were washed with
saturated aqueous sodium hydrogen carbonate and water. The organic layer was dried over sodium sulfate
and concentrated to give (E)-1-bromo-4-methoxybut-2-ene (11) (776 mg, 60% yield) as a pale yellow oil.
(Step 2-1) A solution of p-anisidine (1.27 g, 10.3 mmol) and di-tert-butyl dicarbonate (2.34 mL, 10.2 mmol)
in THF (5.0 mL) was stirred for 40 h at room temperature. The resulting mixture was concentrated to obtain
crude tert-butyl (4-methoxyphenyl)carbamate (12) (2.33 g, quant.) as colorless crystals. (Step 2-2) Asolution
of 12 (216 mg, 0.967 mmol) and 11 (156 mg, 0.95 mmol) in DMF (5 mL) was treated with sodium hydride
S4

ACCEPTED MANUSCRIPT
(60 wt.% in oil, 57 mg, 1.4 mmol) at 0 °C under an argon atmosphere. The mixture was stirred for 1 h at
50 °C and quenched with saturated aqueous ammonium chloride at 0 °C. Extractive workup and purification
of the residue by chromatography on silica gel (hexane/ethyl acetate = 5/1 as the eluent) afforded E-1b (209
mg, 72% yield) as a yellow oil; IR (film) 2976, 2931, 2836, 1702, 1692, 1610, 1585, 1512, 1452, 1443, 1390,
1366, 1313, 1293, 1248, 1168, 1145, 1124, 1106, 1036, 1004, 973, 945, 910, 864, 834, 768, 731 cm-1; 1H NMR
(400 MHz, CDCl3)  7.09 (2H, br, ArH), 6.83 (2H, ddd, J = 9.2, 2.8, 2.8 Hz, ArH), 5.78 (1H, dtt, J = 16.0, 5.8,
1.2 Hz, CH=CH), 5.62 (1H, dt, J = 16.0, 5.8 Hz, CH=CH), 4.17 (2H, dd, J = 5.8, 1.2 Hz, CH2), 3.89 (2H, dd,
J = 5.8, 1.2 Hz, CH2), 3.79 (3H, s, ArOCH3), 3.28 (3H, s, 4-OCH3), 1.42 (9H, s, t-Bu); 13C NMR (100 MHz,
CDCl3)  157.5, 154.8, 135.6, 129.3, 128.8, 127.9, 113.8, 80.1, 72.4, 57.7, 55.3, 52.0, 28.3; HRMS–ESI (m/z):
[M+Na]+ calcd for C17H25NO4Na: 330.1676. Found: 330.1660 (aq. HCO2Na was added to improve sensitivity).
(S,E)-tert-Butyl (4-methoxybut-2-en-1-yl)(1-phenylethyl)carbamate (E-1c)
(Step 1) A mixture of (S)-1-phenylethylamine (0.90 g, 7.4 mmol), 3-bromo-1-propyne (0.53 mL, 7.0 mmol),
and potassium carbonate (1.21 g, 8.75 mmol) in acetonitrile (14 mL) was stirred for 17 h at room temperature.
The resulting mixture was filtered through a pad of Celite and the filtrate was concentrated. The residue was
purified by chromatography on silica gel (dichloromethane/methanol = 25/1 to 10/1 as the eluent) to obtain
(S)-N-(1-phenylethyl)-N-(prop-2-yn-1-yl)amine (13) (0.67 g, 60% yield) as a pale yellow oil. (Step 2) A
mixture of 13 (0.67 g, 4.2 mmol) and di-tert-butyl dicarbonate (0.98 mL, 4.3 mmol) was stirred for 15 h at
room temperature. The volatiles were removed under reduced pressure to obtain crude (S)-N-tert-
butoxycarbonyl-N-(1-phenylethyl)-N-(prop-2-yn-1-yl)amine (14) (1.22 g, quant.) as a colorless oil. (Step 3)
A solution of 14 (1.27 g, 4.90 mmol) in THF (30 mL) was treated with a 1.64 M n-butyllithium hexane solution
(3.81 mL, 6.25 mmol) at –78 °C under an argon atmosphere and stirred for 10 min at the same temperature.
Paraformaldehyde (357 mg, 11.9 mmol) was added to the solution and the mixture was stirred for 15 min at –
78 °C and for 22 h at room temperature. The resulting mixture was quenched with saturated aqueous
ammonium chloride and extracted with ethyl acetate. The combined extracts were washed with brine, dried
over sodium sulfate, and concentrated. The residue was purified by chromatography on silica gel
(hexane/ethyl acetate = 2/1 to 1/1 as the eluent) to obtain (S)-tert-butyl (4-hydroxybut-2-yn-1-yl)(1-
phenylethyl)carbamate (15) (846 mg, 60% yield) as a yellow oil. (Step 4) A 1.0 M sodium bis(2-
S5

ACCEPTED MANUSCRIPT
methoxyethoxy)aluminum hydride toluene solution (3.4 mL, 3.4 mmol) was added to a solution of 15 (806
mg, 2.79 mmol) in toluene (14 mL) at 0 °C under an argon atmosphere and the mixture was stirred for 1 h at
the same temperature. The resulting mixture was quenched with water at 0 °C and treated with a 1 M aqueous
potassium hydrogen sulfate to dissolve inorganic salts. The mixture was extracted with ethyl acetate and the
combined extracts were washed with saturated aqueous sodium hydrogen carbonate and brine. The organic
layer was dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica
gel (hexane/ethyl acetate = 2/1 to 1/1 as the eluent) to obtain (S,E)-tert-butyl (4-hydroxybut-2-en-1-yl)(1-
phenylethyl)carbamate (16) (765 mg, 94% yield) as a yellow viscous oil. (Step 5) A mixture of 16 (760 mg,
2.61 mmol), tetrabutylammonium iodide (48 mg, 0.13 mmol), and 50 wt.% aqueous sodium hydroxide solution
(2.7 mL) in benzene (13 mL) was treated with dimethyl sulfate (0.30 mL, 3.2 mmol) and stirred for 15 h at
room temperature. The resulting mixture was quenched with saturated aqueous ammonium chloride and
extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, and
concentrated. Purification of the residue by chromatography on silica gel (hexane/ethyl acetate = 5/1 as the
eluent) gave E-1c (688 mg, 86% yield) as a pale yellow oil; []22589 –82.8 (c 1.00, EtOH); IR (film) 3061, 3029,
2976, 2930, 2821, 1689, 1495, 1450, 1402, 1365, 1327, 1294, 1275, 1252, 1167, 1135, 1042, 1026, 973, 911,
865, 771, 735, 700 cm-1; 1H NMR (400 MHz, CDCl3)  7.33-7.19 (5H, m, Ph), 5.70-5.20 (3H, br, CH=CH and
NCHCH3), 3.81 (2H, d, J = 5.6 Hz, CH2), 3.72 (1H, br, CH2), 3.45 (1H, br, CH2), 3.26 (3H, s, OCH3), 1.51
(3H, d, J = 6.8 Hz, NCHCH3), 1.44 (9H, s, t-Bu); 13C NMR (100 MHz, CDCl3)  155.6, 141.9, 131.0, 128.2,
127.8, 127.0, 79.7, 72.5, 57.7, 53.4, 44.8, 28.4, 17.7; HRMS–ESI (m/z): [M+Na]+ calcd for C18H27NO3Na:
328.1883. Found: 328.1876 (aq. HCO2Na was added to improve sensitivity).
(E)-tert-Butyl (4-methoxybut-2-en-1-yl)(methyl)carbamate (E-1d)
(Step 1) A solution of 40 wt.% methylamine methanol solution (2.0 mL, 20 mmol) was diluted with THF (3
mL) and treated with di-tert-butyl dicarbonate (2.3 mL, 10 mmol) at 0 °C. The solution was stirred for 3 h
at room temperature and concentrated to obtain crude tert-butyl methylcarbamate (17) (0.77 g, 59% yield) as
a colorless oil. (Step 2) Asolution of 17 (0.77 g, 5.9 mmol) in DMF (13 mL) was treated with sodium hydride
(60 wt.% in oil, 0.29 g, 7.3 mmol) at 0 °C under an argon atmosphere. After stirring for 15 min at room
temperature, 3-bromo-1-propyne (0.65 mL, 8.6 mmol) was added to the mixture at 0 °C. The mixture was
S6

ACCEPTED MANUSCRIPT
stirred for 2.5 h at room temperature and quenched with saturated aqueous ammonium chloride at 0 °C.
Extractive workup and purification of the residue by chromatography on silica gel (hexane/ethyl acetate = 10/1
as the eluent) afforded tert-butyl methyl(prop-2-yn-1-yl)carbamate (18) (0.56 g, 56% yield) as a yellow oil.
(Step 3) A solution of 18 (0.56 g, 3.3 mmol) in THF (17 mL) was treated with a 1.64 M n-butyllithium hexane
solution (2.00 mL, 3.30 mmol) at –78 °C under an argon atmosphere and stirred for 10 min at the same
temperature. Paraformaldehyde (0.20 g, 6.7 mmol) was added to the solution and the mixture was stirred for
15 min at –78 °C and for 2 h at room temperature. The resulting mixture was quenched with saturated
aqueous ammonium chloride and extracted with ethyl acetate. The combined extracts were washed with
brine, dried over sodium sulfate, and concentrated. The residue was purified by chromatography on silica
gel (hexane/ethyl acetate = 2/1 as the eluent) to obtain tert-butyl (4-hydroxybut-2-yn-1-yl)(methyl)carbamate
(19) (0.58 g, 88% yield) as a brown oil. (Step 4) A 1.0 M sodium bis(2-methoxyethoxy)aluminum hydride
toluene solution (3.5 mL, 3.5 mmol) was added to a solution of 19 (0.58 g, 2.9 mmol) in toluene (15 mL) at
0 °C under an argon atmosphere and the mixture was stirred for 1 h at the same temperature. The resulting
mixture was quenched with water at 0 °C and treated with a 1 M aqueous potassium hydrogen sulfate to
dissolve inorganic salts. The mixture was extracted with ethyl acetate and the combined extracts were washed
with brine. The organic layer was dried over sodium sulfate and concentrated to obtain (E)-tert-butyl (4-
hydroxybut-2-en-1-yl)(methyl)carbamate (20) (346 mg, 59% yield) as a brown oil. (Step 5) A mixture of 20
(346 mg, 1.72 mmol), tetrabutylammonium iodide (32 mg, 0.087 mmol), and 50 wt.% aqueous sodium
hydroxide solution (1.8 mL) in benzene (8.6 mL) was treated with dimethyl sulfate (0.20 mL, 2.1 mmol) and
stirred for 13 h at room temperature. The resulting mixture was quenched with saturated aqueous ammonium
chloride and extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium
sulfate, and concentrated. Purification of the residue by chromatography on silica gel (hexane/ethyl acetate
= 5/1 as the eluent) gave E-1d (342 mg, 92% yield) as a colorless oil; IR (film) 2977, 2929, 2823, 1693, 1480,
1454, 1421, 1392, 1366, 1301, 1247, 1176, 1150, 1121, 1044, 975, 912, 878, 771 cm-1; 1H NMR (400 MHz,
CD3OD)  5.73-5.60 (2H, m, CH=CH), 3.95-3.91 (2H, m, CH2), 3.85-3.81 (2H, m, CH2), 3.32 (3H, s, OCH3),
2.83 (3H, s, NCH3), 1.46 (9H, s, t-Bu); 13C NMR (100 MHz, CD3OD)  157.6, 130.4-129.8 (m), 129.6, 81.2,
73.5, 58.4-58.0 (m), 51.8-50.5 (m), 34.4, 28.8; HRMS–ESI (m/z): [M+Na]+ calcd for C11H21NO3Na: 238.1414.
Found: 238.1407.
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ACCEPTED MANUSCRIPT
(E)-tert-Butyl (4-methoxy-4-methylpent-2-en-1-yl)(4-methoxyphenyl)carbamate (E-1e)
(Step 1) A solution of 12 (1.13 g, 5.06 mmol) in DMF (25 mL) was treated with sodium hydride (60 wt.% in
oil, 0.24 g, 6.0 mmol) at 0 °C under an argon atmosphere and stirred for 30 min. 3-Bromo-1-propyne (0.52
mL, 6.9 mmol) was added to the mixture at the same temperature and the mixture was stirred for 1 h at 50 °C.
The resulting mixture was quenched with saturated aqueous ammonium chloride at 0 °C and extracted with
ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, and concentrated.
Purification of the residue by chromatography on silica gel (hexane/ethyl acetate = 5/1 as the eluent) gave tert-
butyl (4-methoxyphenyl)(prop-2-yn-1-yl)carbamate (21) (1.22 g, 92% yield) as a yellow oil. (Step 2) A
solution of 21 (1.13 g, 4.32 mmol) in THF (22 mL) was treated with a 1.64 M n-butyllithium hexane solution
(2.64 mL, 4.33 mmol) at –78 °C under an argon atmosphere and stirred for 10 min at the same temperature.
Acetone (0.64 mL, 8.7 mmol) was added to the solution and the mixture was stirred for 15 min at –78 °C and
for 2 h at room temperature. The resulting mixture was quenched with saturated aqueous ammonium chloride
and extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate,
and concentrated. The residue was purified by chromatography on silica gel (hexane/ethyl acetate = 2/1 to
1/1 as the eluent) to obtain tert-butyl (4-hydroxy-4-methylpent-2-yn-1-yl)(4-methoxyphenyl)carbamate (22)
(971 mg, 70% yield) as a yellow oil. (Step 3) A 1.0 M sodium bis(2-methoxyethoxy)aluminum hydride
toluene solution (3.7 mL, 3.7 mmol) was added to a solution of 22 (971 mg, 3.04 mmol) in toluene (15 mL) at
0 °C under an argon atmosphere and the mixture was stirred for 1 h at the same temperature. The resulting
mixture was quenched with water at 0 °C and treated with a 1 M aqueous potassium hydrogen sulfate to
dissolve inorganic salts. The mixture was extracted with ethyl acetate and the combined extracts were washed
with saturated aqueous sodium hydrogen carbonate and brine. The organic layer was dried over sodium
sulfate and concentrated. The residue was purified by chromatography on silica gel (hexane/ethyl acetate =
2/1 to 1/1 as the eluent) to obtain (E)-tert-butyl (4-hydroxy-4-methylpent-2-en-1-yl)(4-
methoxyphenyl)carbamate (23) (858 mg, 88% yield) as a yellow viscous oil. (Step 4) A solution of 23 (852
mg, 2.65 mmol) in THF (13 mL) was treated with sodium hydride (60 wt.% in oil, 0.16 g, 4.0 mmol) at 0 °C
under an argon atmosphere and stirred for 10 min. The mixture was treated with iodomethane (0.25 mL, 4.0
mmol) at the same temperature and refluxed for 2 h. The resulting mixture was quenched with saturated
aqueous ammonium chloride at 0 °C and extracted with ethyl acetate. The combined extracts were washed
with brine, dried over sodium sulfate, and concentrated. Purification of the residue by chromatography on
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ACCEPTED MANUSCRIPT
silica gel (hexane/ethyl acetate = 5/1 as the eluent) gave E-1e (741 mg, 83% yield) as a yellow oil; IR (film)
2975, 2933, 2835, 2824, 1702, 1610, 1585, 1513, 1455, 1443, 1390, 1365, 1294, 1248, 1171, 1106, 1073, 1036,
1005, 975, 935, 869, 834, 767, 730 cm-1; 1H NMR (400 MHz, CDCl3)  7.08 (2H, br, ArH), 6.82 (2H, ddd, J
= 8.8, 2.8, 2.8 Hz, ArH), 5.62 (1H, dt, J = 15.8, 6.0 Hz, CH=CH), 5.48 (1H, d, J = 15.8 Hz, CH=CH), 4.18
(2H, dd, J = 6.0, 1.2 Hz, CH2), 3.78 (3H, s, ArOCH3), 3.05 (3H, s, 4-OCH3), 1.43 (9H, s, t-Bu), 1.22 (6H, s, 4-
CH3); 13C NMR (100 MHz, CDCl3)  157.5, 154.7, 138.1, 135.4, 128.0, 125.6, 113.8, 80.0, 74.5, 55.3, 52.0,
50.2, 28.3, 25.7; HRMS–ESI (m/z): [M+Na]+ calcd for C19H29NO4Na: 358.1989. Found: 358.1983 (aq.
HCO2Na was added to improve sensitivity).
(S,E)-tert-Butyl (4-methoxybut-2-en-1-yl)(1-phenylethyl)carbamate (E-1f)
(Step 1) A solution of 14 (1.13 mg, 4.36 mmol) in THF (27 mL) was treated with a 1.64 M n-butyllithium
hexane solution (3.41 mL, 5.59 mmol) at –78 °C under an argon atmosphere and stirred for 10 min at the same
temperature. Acetone (0.78 mL, 10.6 mmol) was added to the solution and the mixture was stirred for 15
min at –78 °C and for 4 h at room temperature. The resulting mixture was quenched with saturated aqueous
ammonium chloride and extracted with ethyl acetate. The combined extracts were washed with brine, dried
over sodium sulfate, and concentrated. The residue was purified by chromatography on silica gel
(hexane/ethyl acetate = 2/1 to 1/1 as the eluent) to obtain (S)-tert-butyl (4-hydroxy-4-methylpent-2-yn-1-yl)(1-
phenylethyl)carbamate (24) (1.03 g, 74% yield) as a yellow oil. (Step 2) A 1.0 M sodium bis(2-
methoxyethoxy)aluminum hydride toluene solution (3.9 mL, 3.9 mmol) was added to a solution of 24 (1.03 g,
3.24 mmol) in toluene (16 mL) at 0 °C under an argon atmosphere and the mixture was stirred for 1 h at the
same temperature. The resulting mixture was quenched with water at 0 °C and treated with a 1 M aqueous
potassium hydrogen sulfate to dissolve inorganic salts. The mixture was extracted with ethyl acetate and the
combined extracts were washed with saturated aqueous sodium hydrogen carbonate and brine. The organic
layer was dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica
gel (hexane/ethyl acetate = 2/1 to 1/1 as the eluent) to obtain (S,E)-tert-butyl (4-hydroxy-4-methylpent-2-en-
1-yl)(1-phenylethyl)carbamate (25) (986 mg, 95% yield) as a yellow viscous oil. (Step 3) A solution of 25
(986 mg, 3.09 mmol) in THF (16 mL) was treated with sodium hydride (60 wt.% in oil, 0.19 g, 4.8 mmol) at
0 °C under an argon atmosphere and stirred for 30 min. The mixture was treated with iodomethane (0.29 mL,
4.7 mmol) at the same temperature and stirred for 5 h at room temperature. The resulting mixture was
quenched with saturated aqueous ammonium chloride at 0 °C and extracted with ethyl acetate. The combined
extracts were washed with brine, dried over sodium sulfate, and concentrated. Purification of the residue by
chromatography on silica gel (hexane/ethyl acetate = 20/1 to 10/1 as the eluent) gave E-1f (918 mg, 89% yield)
S9

ACCEPTED MANUSCRIPT
as a pale yellow oil; []23589 –80.3 (c 1.00, EtOH); IR (film) 3088, 3061, 3029, 2975, 2933, 2822, 1686, 1495,
1450, 1401, 1364, 1327, 1304, 1251, 1207, 1170, 1076, 1041, 1026, 976, 913, 864, 835, 773, 734, 700 cm-1;
1H NMR (400 MHz, CDCl3)  7.35-7.21 (5H, m, Ph), 5.75-5.05 (3H, br, CH=CH and NCHCH3), 3.73 (1H, br,
CH2), 3.51 (1H, br, CH2), 3.08 (3H, s, OCH3), 1.53 (3H, d, J = 7.2 Hz, NCHCH3), 1.46 (9H, s, t-Bu), 1.18 (3H,
s, 4-CH3), 1.17 (3H, s, 4-CH3); 13C NMR (100 MHz, CDCl3)  155.6, 141.9, 136.6, 128.2, 127.2, 127.1, 127.0,
79.6, 74.5, 53.0, 50.3, 44.9, 28.4, 25.8, 25.6, 17.5; HRMS–ESI (m/z): [M+Na]+ calcd for C20H31NO3Na:
356.2196. Found: 356.2190 (aq. HCO2Na was added to improve sensitivity).
(E)-tert-Butyl (4-methoxy-4-methylpent-2-en-1-yl)(methyl)carbamate (E-1g): prepared by the same
procudure with E-1f using 17 as a starting material (30% overall yield from 17);
colorless oil; IR (film) 2976, 2932, 2823, 1701, 1480, 1458, 1420, 1390, 1364, 1306,
1246, 1210, 1173, 1148, 1077, 977, 923, 880, 846, 813, 771 cm-1; 1H NMR (400 MHz,
CDCl3)  5.58-5.45 (2H, m, CH=CH), 3.82 (2H, br, CH2), 3.15 (3H, s, OCH3), 2.82
(3H, s, NCH3), 1.46 (9H, s, t-Bu), 1.27 (6H, s, 4-CH3); 13C NMR (100 MHz, CDCl3)  155.6, 138.1-137.3 (m),
125.4-124.6 (m), 79.3, 74.5, 50.7-49.5 (m), 50.2, 33.5, 28.3, 25.7; HRMS–ESI (m/z): [M+Na]+ calcd for
C13H25NO3Na: 266.1727. Found: 266.1714 (aq. HCO2Na was added to improve sensitivity).
(E)-tert-Butyl allyl(4-methoxybut-2-en-1-yl)carbamate (E-1h)
(Step 1) Di-tert-butyl dicarbonate (1.2 mL, 5.2 mmol) was added to a solution of allylamine (0.41 mL, 5.5
mmol) in THF (10 mL) at 0 °C. The solution was stirred for 2 h at room temperature and concentrated to
obtain crude tert-butyl allylcarbamate (26) (730 mg, 89% yield) as a colorless oil. (Step 2) A solution of 26
(730 mg, 4.64 mmol) in DMF (9.3 mL) was treated with sodium hydride (60 wt.% in oil, 0.22 g, 5.5 mmol) at
0 °C under an argon atmosphere. After stirring for 10 min at room temperature, 3-bromo-1-propyne (0.42
mL, 5.6 mmol) was added to the mixture at 0 °C. The mixture was stirred for 17 h at room temperature and
quenched with saturated aqueous ammonium chloride at 0 °C. Extractive workup and purification of the
residue by chromatography on silica gel (hexane/ethyl acetate = 10/1 as the eluent) afforded tert-butyl
allyl(prop-2-yn-1-yl)carbamate (27) (602 mg, 66% yield) as a yellow oil. (Step 3) A solution of 27 (561 mg,
2.87 mmol) in THF (9.6 mL) was treated with a 1.64 M n-butyllithium hexane solution (1.84 mL, 3.02 mmol)
at –78 °C under an argon atmosphere and stirred for 30 min at the same temperature. Paraformaldehyde (0.13
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g, 4.3 mmol) was added to the solution and the mixture was stirred for 15 min at –78 °C and for 2.5 h at room
temperature. The resulting mixture was quenched with saturated aqueous ammonium chloride and extracted
with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, and
concentrated. The residue was purified by chromatography on silica gel (hexane/ethyl acetate = 2/1 as the
eluent) to obtain tert-butyl allyl(4-hydroxybut-2-yn-1-yl)carbamate (28) (416 mg, 64% yield) as a brown oil.
(Step 4) A 1.0 M sodium bis(2-methoxyethoxy)aluminum hydride toluene solution (2.2 mL, 2.2 mmol) was
added to a solution of 28 (416 mg, 1.85 mmol) in toluene (9.3 mL) at 0 °C under an argon atmosphere and the
mixture was stirred for 1 h at the same temperature. The resulting mixture was quenched with saturated
aqueous potassium sodium tartrate and stirred for 1 h at room temperature. The mixture was extracted with
ethyl acetate and the combined extracts were washed with brine. The organic layer was dried over sodium
sulfate and concentrated to obtain (E)-tert-butyl allyl(4-hydroxybut-2-en-1-yl)carbamate (29) (251 mg, 60%
yield) as a brown oil. (Step 5) A mixture of 29 (251 mg, 1.10 mmol), tetrabutylammonium iodide (20 mg,
0.054 mmol), and 50 wt.% aqueous sodium hydroxide solution (1.1 mL) in benzene (5.5 mL) was treated with
dimethyl sulfate (0.12 mL, 1.3 mmol) and stirred for 22 h at room temperature. The resulting mixture was
quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The combined
extracts were washed with brine, dried over sodium sulfate, and concentrated. Purification of the residue by
chromatography on silica gel (hexane/ethyl acetate = 3/1 as the eluent) gave E-1h (255 mg, 96% yield) as a
colorless oil; IR (film) 3081, 2977, 2929, 2822, 1692, 1644, 1536, 1454, 1407, 1365, 1246, 1172, 1142, 1123,
1
1054, 975, 922, 875, 772, 703 cm-1; H NMR (400 MHz, CDCl3)  5.84-5.58 (3H, m, CH=CH and
CH2CH=CH2), 5.21-5.04 (2H, m, CH2CH=CH2), 3.91 (2H, dt, J = 4.4, 1.2 Hz, CH2), 3.80 (4H, br, CH2), 3.33
(3H, s, OCH3), 1.45 (9H, s, t-Bu); 13C NMR (100 MHz, CDCl3)  155.3, 133.9, 129.0, 128.6, 117.0-115.9 (m),
79.6, 72.4, 57.8, 48.6, 47.5, 28.3; HRMS–ESI (m/z): [M+Na]+ calcd for C13H23NO3Na: 264.1570. Found:
263.1566 (aq. HCO2Na was added to improve sensitivity).
(Z)-tert-Butyl allyl(4-methoxybut-2-en-1-yl)carbamate (Z-1h)
A solution of 26 (348 mg, 2.21 mmol) in THF was treated with a 1.64 M n-butyllithium hexane solution
(1.35 mL, 2.21 mmol) at 0 °C under an argon atmosphere. After stirring for 30 min at the same temperature,
the mixture was treated with 5 (276 mg, 1.67 mmol) and stirred for 23 h at room temperature. The resulting
mixture was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The
combined extracts were washed with brine, dried over sodium sulfate, and concentrated. Purification of the
residue by chromatography on silica gel (hexane/ethyl acetate = 15/1 to 10/1 as the eluent) gave Z-1h (162 mg,
40% yield) as a colorless oil; IR (film) 3080, 2977, 2929, 2817, 1698, 1644, 1541, 1456, 1405, 1365, 1345,
1325, 1289, 1248, 1171, 1145, 1114, 994, 954, 922, 874, 771, 713 cm-1; 1H NMR (400 MHz, CDCl3)  5.84-
5.48 (3H, m, CH=CH and CH2CH=CH2), 5.19-5.05 (2H, m, CH2CH=CH2), 3.98 (2H, d, J = 6.4 Hz, CH2),
3.95-3.70 (4H, br, CH2), 3.33 (3H, s, OCH3), 1.46 (9H, s, t-Bu); 13C NMR (100 MHz, CDCl3)  155.3, 134.0,
129.4-128.0 (m), 129.2, 117.0-116.0 (m), 79.7, 67.9, 58.1, 48.7, 43.5-42.5 (m), 28.4; HRMS–ESI (m/z):
[M+H]+ calcd for C13H24NO3: 242.1751. Found: 242.1746.
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(E)-tert-Butyl (4-methoxyoct-2-en-1-yl)(phenyl)carbamate (E-1i): prepared by the same procudure with E-
1f using 7 and valeraldehyde instead of 14 and acetone (51% overall yield from 7);
yellow oil; IR (film) 2957, 2931, 2860, 2819, 1702, 1597, 1497, 1455, 1386, 1366,
1
1341, 1298, 1278, 1253, 1170, 1096, 1046, 1010, 972, 866, 765, 757, 697 cm-1; H
NMR (400 MHz, CDCl3)  7.33-7.27 (2H, m, Ph), 7.23-7.13 (3H, m, Ph), 5.68 (1H,
dddd, J = 15.6, 6.0, 6.0, 0.8 Hz, CH=CH), 5.35 (1H, dd, J = 15.6, 7.8 Hz, CH=CH),
4.27 (1H, ddd, J = 15.6, 6.0, 0.8 Hz, 1-H), 4.22 (1H, ddd, J = 15.6, 6.0, 0.8 Hz, 1-H), 3.48 (1H, dt, J = 7.8, 6.8
Hz, 4-H), 3.16 (3H, s, OCH3), 1.62-1.49 (1H, m, CH2CH2CH2CH3), 1.49-1.11 (5H, m, CH2CH2CH2CH3), 1.44
(9H, s, t-Bu), 0.87 (3H, t, J = 7.0 Hz, CH2CH2CH2CH3); 13C NMR (100 MHz, CDCl3)  154.4, 142.5, 133.5,
128.8, 128.5, 126.6, 125.8, 81.9, 80.3, 55.9, 51.6, 35.1, 28.3, 27.4, 22.6, 14.0; HRMS–ESI (m/z): [M+Na]+
calcd for C20H31NO3Na: 356.2196. Found: 356.2189 (aq. HCO2Na was added to improve sensitivity).
(E)-tert-Butyl (4-methoxy-4-phenylbut-2-en-1-yl)(phenyl)carbamate (E-1j): prepared by the same
procudure with E-1a using benzaldehyde instead of paraformaldehyde (58% overall
yield from 7); yellow oil; IR (film) 3061, 3028, 2977, 2929, 2820, 1698, 1597, 1495,
1454, 1388, 1366, 1299, 1279, 1252, 1167, 1093, 1028, 1010, 970, 907, 861, 757, 698
1
cm-1; H NMR (400 MHz, CDCl3)  7.34-7.21 (7H, m, Ph), 7.19-7.12 (3H, m, Ph),
5.80 (1H, dtd, J = 15.7, 6.0, 1.2 Hz, CH=CH), 5.63 (1H, ddt, J = 15.7, 6.8, 1.2 Hz, CH=CH), 4.60 (1H, d, J =
6.8 Hz, 4-H), 4.29-4.17 (2H, m, 1-H), 3.26 (3H, s, OCH3), 1.38 (9H, s, t-Bu); 13C NMR (100 MHz, CDCl3) 
154.4, 142.5, 140.9, 133.3, 128.6, 128.3, 128.2, 127.5, 126.6, 126.5, 125.7, 83.5, 80.3, 56.2, 51.6, 28.2;
HRMS–ESI (m/z): [M+Na]+ calcd for C22H27NO3Na: 376.1883. Found: 376.1877 (aq. HCO2Na was added to
improve sensitivity).
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1H_E-2a.esp
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