Regio- And Stereoselective Carboindation of Internal Alkynyl Ethers with Organosilicon or -stannane Nucleophiles

Article abstract of DOI:10.1021/acs.joc.9b01505

We achieved regio- and stereoselective carboindation of terminal and internal alkynyl ethers using InI₃ and organosilicon or -stannane nucleophiles to synthesize (Z)-β-alkoxyalkenylindiums. The carbometalation regio- and stereoselectively proce

Full text of DOI:10.1021/acs.joc.9b01505

Subscriber access provided by Nottingham Trent University
Article
Regio- and Stereoselective Carboindation of Internal Alkynyl
Ethers with Organosilicon or -stannane Nucleophiles
Kyoungmin Kang, Yoshihiro Nishimoto, and Makoto Yasuda
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 29 Aug 2019
Downloaded from pubs.acs.org on August 29, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 29
The Journal of Organic Chemistry
1
2
3
4
Regio- and Stereoselective Carboindation of Internal Alkynyl Ethers with Organosilicon or -
stannane Nucleophiles
5
6
Kyoungmin Kang†, Yoshihiro Nishimoto*‡, and Makoto Yasuda*†
7
8
9
†Department of Applied Chemistry and ‡Frontier Research Base for Global Young Researchers
Center for Open Innovation Research and Education (COiRE), Graduate School of Engineering,
Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Supporting Information Placeholder
-
R2
R2
C
R2
I2In
R1O
=
I3In
Nu Si
or
Nu Sn
+
InI3
+
C
Nu
Nu
OR1
R1O
+

COOR
Nu
CN
Ph Ph
CN
Highly regioselective
anti-Carboindation
In
Nu
Synthesis of tetra-
substituted enol ethers
O
LUMO of
InI3-alkyne complex
Ph
ABSTRACT: We achieved regio- and stereoselective carboindation of terminal and internal alkynyl
ethers using InI3 and organosilicon or -stannane nucleophiles to synthesize (Z)-β-
alkoxyalkenylindiums. The carbometalation regio- and stereoselectively proceeded in anti-addition
fashion, which was confirmed by X-ray diffraction analysis of (Z)-β-alkoxyalkenylindium products.
Theoretical calculation on the carboindation of alkynyl ethers to elucidate the effect of an alkoxy
group were conducted in parallel with calculations on a carbon analogue of the alkynyl ether. Reaction
profiles and computational data of carboindation suggest that the alkoxy group enhances the
interaction between InI3 and an alkyne moiety and reduces the activation energy. Many types of
carbon nucleophiles such as silyl ketene acetals, silyl ketene imines, a silyl cyanide, an alkynyl
stannane, and an allylic stannane were applicable to the present reaction system to give highly
functionalized metalated enol ethers (β-alkoxyalkenylindiums). The prepared β-
alkoxyalkenylindiums were transformed to various functionalized tetra-substituted enol ethers by
iodination followed by Suzuki coupling. The synthesis of a 7-membered ring compound containing
a phenol ether moiety was accomplished using a sequential process that included the present
stereoselective carboindation.
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 29
1
2
3
4
5
6
7
8
9
Recently, we reported a regioselective anti-
■ INTRODUCTION
carbozincation of terminal alkynyl ethers8 using
ZnBr2 and silyl ketene acetals to give β-
alkoxyalkenylzincs bearing an ester moiety, and
also established a selective synthetic method for
tri-substituted enol ethers (Scheme 1, D,
previous work). By continuing the investigation
to establish a more versatile carbometalation, we
discovered that an indium trihalide was effective
in the carbometalation of both terminal and
internal alkynyl ethers. Herein, we describe a
method for the synthesis of tetra-substituted enol
ethers by carbometalation of internal alkynyl
ethers via the use of InI3 and organosilicon or -
stannane nucleophiles (Scheme 1D, this work).
Multi-substituted enol ethers are an important
class of building blocks in organic synthesis due
to an electron-rich π-bond and its various
reactivities.1 Actually, valuable synthetic
transformations of enol ethers, such as the Diels-
Alder reaction2 and Claisen rearrangement,3 are
well established. There are two general
approaches for the synthesis of highly
substituted enol ethers. One is O-alkylation of
ketones under acidic or basic conditions,4 and
another is the transformation of metalated enol
ethers prepared via the carbometalation of
internal alkynyl ethers. The former method often
exhibits less stereoselectivity to give E/Z
mixtures due to an inability to control isomers.
(Scheme 1, A1). In contrast, the latter is a
promising strategy to exclusively synthesize one
isomer from among several possible isomers.
However, this strategy has not been well
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Syntheses of tetra-substituted enol
ethers
established,
because
the
regio-
and
stereoselective carbometalation of internal
alkynyl ethers is a difficult process (Scheme 1,
A2). For syn-carbometalations, Marek reported
a syn-carbocupration of internal alkynyl ethers
in the preparation of individual α-syn or β-syn
alkoxyalkenylcoppers.5 By changing an OR
group from cyclohexyloxy (-OCy) to 2-
tetrahydropyranyloxy
(-OTHP),
the
regioselectivity of alkoxyalkenylcoppers was
converted from β-syn to α-syn (Scheme 1, B). In
contrast, the anti-carbometalation of internal
alkynyl ethers remains a challenge. Only
intramolecular anti-carbolithiations of an
internal alkynyl ether for α-anti and β-anti
alkoxyalkenyllithiums has been reported
(Scheme 1, C). In the case of α-anti, however,
the substrate scope was narrow and only 5-
membered ring compounds were obtained.6 A
carbolithiation for the production of β-anti was
also established by using organolithium species
derived from an alkyl sulfone.7 In this case, the
produced alkenyllithium was not useful for
further transformations because it was quenched
by the acidic protons in the starting material. In
addition,
the
regioselectivity
of
the
alkenyllithium was low.
2
ACS Paragon Plus Environment

Page 3 of 29
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
A. General approach of tetra-substituted enol ethers
quenching with MeOH only a 10% yield of 3aa
1. O-Alkylation of ketones
was obtained (Table 1, entry 1). ZnBr2 was
ineffective in the carbometalation of internal
alkynyl ethers in contrast to that of terminal
versions.8 We recently reported that BiBr3,9a
AlBr3,9b GaBr3,9c and InBr39d are effective in the
carbometalation of simple alkynes. When these
metal salts were examined, InBr3 gave (E)-3aa
as a single isomer in 66% yield and the others
resulted in lower yields or in no reaction (Table
1, entries 2-6). Finally, InI3 gave the highest
yield (Table 1, entry 7). The reason that In salts
exhibit more efficient reactivity than Al, Zn, or
Ga salts would be that the large lobe of LUMO
on an indium atom effectively interacts with the
π-orbital of an internal alkyne. Typical Lewis
acids such as BF3‧OEt2, SnBr4, and FeBr3 were
not suitable to this carbometalation (See
supporting information (SI), Table S1).
Chloroform, diethyl ether, and toluene as
solvents gave the desired product 3aa in 68, 66,
and 58% yields, respectively (Table 1, entries 8,
9, and 10). A non-polar solvent such as hexane
(Table 1, entry 11) and a highly coordinative
solvent such as THF (Table 1, entry 12) did not
give the product. Therefore, the reaction
conditions of entry 7 proved to be optimal.
R2
R3
R1
MeC(OR)3 + acid
R2
R1
or
+ base
(RO)2SO2
OR
R3
O
(E/Z)-mixture
2. Transformation of metalated enol ethers via carbometalation
ketone
R1
OR

Mt Mt
R1

OR
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
R2
R2
syn
syn
-
-
(ref 5)
R1
R3
R2
Mt-R2
R3-X
(ref 5)
R1
OR
R1 R2


R1
Mt
OR

Mt

OR
alkynyl ethers
enol ethers
(This work)
R2
OR
anti
-
(This work)
anti
(ref 6)
-
B. syn-Carbocupration of alkynyl ethers (ref 5)
Et2Zn
CuBr•2LiBr
EtMgBr
CuI
Bu
Cu
O
Bu
Et
O
OR

O


THF, -30 °C
THF, RT

Bu
Et
Cu
syn
-
syn
-
C. Intramolecular anti-carbolithiation of alkynyl ethers (ref 6a, 7)
E+
Li
E
R' = H

ref 6a

OR
anti
OR

OR
-
Li

Li
Li

R'
+
R' = Ts
ref 7
OR
OR
Ts
Ts
anti
anti
-
(75 : 25)
-
Narrow substrate range
Limited application for tetra-substituted enol ethers
D. Intermolecular anti-Carboindation of alkynyl ether
Previous work (ref 8)
Table 1. Optimization for the carbometalation
of internal alkynyl ether 1aa
H
Nu
H
Nu-Si
+
+

ZnBr2

OR
Zn
OR
anti
-
Limited to terminal alkynes
This work
R'
R'
Nu
Mt
Me
H
Me
Me
+

MeOH
InI3
Nu-Si
+
OMe

MtXn
+
+
OR
In
OR
PhO
PhO
solvent
0 °C, 1 h
anti
-
OSiMe3
COOMe
COOMe
OPh
powerful synthetic method of tetra-substituted enol ethers
1a
2a
3aa
entry
solvent
yieldb of 3aa (%)
MtXn
ZnBr2
BiBr3
AlBr3
GaBr3
InCl3
InBr3
InI3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
1
2
3
4
5
6
7
10
0
■ RESULTS AND DISCUSSION
Optimization of the Reaction Conditions
0
37
15
66
73
8
InI3
InI3
InI3
InI3
InI3
CHCl3
Et2O
68
66
Based on our previous work for the
carbozincation of terminal alkynyl ethers using
ZnBr2,8 we investigated the carbometalation of
internal alkynyl ether 1a with silyl ketene acetal
2a (Table 1). ZnBr2, 1a, and 2a were mixed in
CH2Cl2 at 0 °C and then stirred for 1 h. After
9
toluene
hexane
THF
10
11
12
58
trace
0c
aReaction conditions: MtXn (0.5 mmol), 1a (0.5 mmol), 2a (1.5
mmol), CH2Cl2 (1 mL), 0 °C, and 1 h. bYields were determined
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 29
1
2
3
4
by 1H-NMR using Cl2CHCHCl2 as an internal standard.
cStarting materials were recovered.
hexane,
and
extraction
with
Et2O,
recrystallization of the obtained solid from
CH2Cl2/hexane gave a single crystal. X-ray
analysis revealed the structure of alkenylindium
coordinated by 3,5-dibromopyridine 4aa·3,5-
Br2Py (Scheme 2).10 The trans geometry
between an InI2 group and a substituent derived
from silyl ketene acetal 2a in the phenoxyalkene
moiety supported an anti-addition mechanism.
The length of the C-In bond (2.152(5) Å) is
similar to that of a typical In-C(sp2) bond.11 The
geometry around an indium atom is a distorted
trigonal bipyramid. An alkenyl group and two
iodine atoms occupy equatorial positions, and
two 3,5-dibromopyridines occupy axial
positions.
5
6
7
8
Isolation
and
Characterization
of
Alkenylindium 4
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The produced alkenylindiums in carboindation
were characterized by NMR spectroscopy and
X-ray diffraction analysis. After the
carboindation of alkynyl ether 1a using InI3 and
silyl ketene acetal 2a in CDCl3 at 0 °C for 1 h,
the in situ 1H NMR showed a full conversion of
1a and production of alkenylindium 4aa. The
addition of 3,5-dibromopyridine to the reaction
mixture generated a white precipitate. After
removal of the volatiles in vacuo, washing with
Scheme 2. Isolation and ORTEP drawing of 4aa·3,5-Br2Py produced by carboindation
°
Br
In-C = 2.152(5) A
Br
Br
Br
Br
OPh
Br
N
N
N
OPh
I
I
I
(3 eq.)
1a
2a
InI3
(1 eq)
I2In
O
In
+
+
CDCl3
O
C
I
(1 eq) (3 eq)
In
Me COOMe
Br
0 °C, 1 h
N
Me COOMe
N
4aa
O
Br
Br
Br
4aa
•3,5-Br2Py 52%
ORTEP drawing
Scheme 3. Reaction mechanism
R2
R2
SiMe3
R2
R2
I2In
R2
OSiMe3
I3In
I3In
O
OSiMe3
OMe
O
R3
InI3 +
I3In
+
OR5
OMe
R4
OSiMe3
OR5
R1O
R1O
OMe
-Me3SiI
R4

R1O
A-1
R3
OR1
R1O
2
R3 R4
R3 R4
R3
R4
1
TS-1
B-1
4
2
nucleophilic attack of silyl ketene acetal 2 to the
α-carbon atom occurs at the opposite side of InI3
to give zwitterionic alkenyl indium B-1 through
transition state TS-1.13 Then, elimination of
Me3SiI from B-1 affords alkenyl indium 4.
Simple internal alkyne 1b, 1-phenylbut-2-yne
(carbon analogue of 1a), was not applicable to
this transformation in contrast to 1a (Scheme 4).
Elucidation of the Reaction Mechanism
Using Theoretical Calculation
A plausible mechanism for the carboindation
of alkynyl ether 1 using InI3 and silyl ketene
acetal 2 is shown in Scheme 3. First, a carbon-
carbon triple bond of alkyne 1 coordinates to
InI3 to increase the positive charge at an α-
carbon of the OR1 group (A-1).12 The
4
ACS Paragon Plus Environment

Page 5 of 29
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
(B3LYP/DGDZVP(for In and I) and 6-
Scheme 4. Carboindation of internal alkyne 1b
31+g**(for others)). Reaction profiles for
alkynyl ether 1a (red line) and simple alkyne 1b
(blue line) are shown in Figure 1. In the reaction
of alkynyl ether 1a, the smaller activation
energy (G‡ = 17.9 kcal/mol) is estimated for
TS-1a,14 whereas the activation energy in the
reaction of 1b is very high (G‡ = 36.1 kcal/mol).
Me
H
Me
recovery
1b
MeOH
OMe
InI3
+
+
+
of
(46%)
CH2Cl2
0 °C, 1 h
OTMS
Ph COOMe
Ph
1b
(1 eq)
3ba
2a
(3 eq)
not observed
(1 eq)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The role of an alkoxy group in the reaction
mechanism was investigated by DFT calculation
Reaction profiles
SiMe3
Me
B3LYP/DGDZVP(for In and I) and
6-31+g**(for others)
O
I3In
SiMe3
OMe
Me
Me
O
PhH2C
OMe
I3In
Me SiMe3
O
46.8
TS-1b
CH2Ph
1b
OPh
1a
PhH2C
OMe
2a
I3In
I2In
Me
32.5
Me
Activation energy
36.1 kcal/mol
COOMe
+ Me3SiI
14.9
B-1b
PhH2C
19.2
2a
+
PhH2C
InI3
1a or 1b
TS-1a
Activation energy
17.9 kcal/mol
10.7
A-1b
1.3
+
+
4ba
8.0
2a
I2In
Me
B-1a
0.0
A-1a
I3In
Me SiMe3
SiMe3
Me
COOMe
+ Me3SiI
-19.7
O
PhO
Me
O
I3In
I3In
OMe
PhO
OMe
PhO
4aa
PhO
2a
+
Optimized structures of A-1a,TS-1a, B-1a, A-1b,TS-1b and B-1b
2.518
2.352
2.244
I
I
I
I
(a)
(b)
(c)
I
(d)
(e)
(f)
2.798
2.377
2.260
I
I
I
I
In
I I
O
I
O
Si
Si
In
I
In
O
Si
O
O
In
In
99.1°
In
O
O
O
I
73.8°
O
I
I
I
2.336
I
2.361
Si
O
O
A-1a
TS-1a
B-1a
A-1b
TS-1b
B-1b
Figure 1. Reaction profiles and optimized structures of A-1, TS-1, and B-1
We considered geometrical parameters,
enthalpies, and the NBO charges of 1a, 1b, A-
1a, A-1b, TS-1a, and TS-1b to reveal the details
of an activation mode of alkynes (1a and 1b) by
InI3 (Table 2).9b In the complexation between
InI3 and 1a (A-1a), coordination of 1a to InI3
considerably changes the length of the carbon-
carbon triple bond (D) from 1.209 to 1.236 Å,
the oxygen-carbon bond (C1-O) from 1.314 to
1.276 Å, and the angle of Me-C2-C1 (θ1) from
180.0° to 150.4°. The angle of In-C2-C1(θ2) in
A-1a is an obtuse angle, 99.1°, and the length of
In-C2 is 2.518 Å shorter than that of In-C1 (see
Figure 1, (a)). These geometrical changes
suggest that the indium atom effectively
interacted with the C2-atom rather than with the
C1-atom to withdraw π-electrons from a triple
bond. On the other hand, in case of the
coordination of simple internal alkyne 1b to InI3
(A-1b), the changes of D and θ1 are smaller than
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 29
1
2
3
those to 1a, the angle of In-C2-C1(θ2) is acute
Me
Me
Me
C2
I3In
I3In
C2
C1

C2
(see Figure 1, (d)), and the indium atom
interacted with both C1- and C2 atoms. Although
there are two distinguishable activation modes
of alkynes (A-1a and A-1b), the two optimized
transition states (TS-1a and TS-1b) are
relatively similar (see Figure 1, (b) and (e)).
Because the changes in geometrical parameters
such as θ1, θ2, D, and In-C2 in a path from A-1a
to TS-1a are smaller than the corresponding
changes in a path from A-1b to TS-1b, the
activation energy in the carboindation of 1a was
smaller than that in 1b. It is noteworthy that the
small change in the In-C2 bond represented an
effective interaction between the indium and C2
atoms in A-1a due to a conjugative electron
donation from the OPh group (The changes of
the In-C2 bond length from A-1a to TS-1a and
from A-1b to TS-1b amount to 0.166 Å and
0.421 Å, respectively.). The changes in the NBO
charges on C1- and C2-atoms were helpful in
evaluating the degree of the indium-alkyne
interaction. The coordination of 1a to InI3 (A-
1a) resulted in an increase of positive charge on
the C1-atom (from 0.299 to 0.448). The
considerable changes in the charges of A-1a
reduced the stabilization, but the strong bond-
forming interaction of In with C2 atoms
compensated for the disadvantage. The positive
charge on the C1-atom that is required by the
nucleophilic attack of 2a is sufficiently
increased in A-1a. The actual change is slight in
the charge of the C1-atom between A-1a and TS-
1a (from 0.448 to 0.436). On the other hand, the
large change in the NBO charge of the C1-atom
between A-1b and TS-1b (from -0.041 to 0.151)
led to a higher level of activation energy.
Therefore, the conjugative donation of an
alkoxy group accelerates the interaction of an
indium atom with the C2-atom to assist the
regioselective carboindation.

InI3
2a
D
4
5
6
7
8
9
C1
X
B-1
C1
X
X
O
OMe
SiMe3
TS-1
1
A-1
Db
(A)
In-C2
(A)
C1-X
(A)


NBO charge
°
°
°
C1
C2
(°)
(°)
1a
A-1a
TS-1a 1.282 2.352 1.298
1.209
-
1.314
180.0
-
+0.299
+0.448
+0.436
-0.134
-0.305
-0.411
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1.236 2.518 1.276
150.4
99.1
134.5 113.3
1b
1.212
-
1.469
180.0
-
-0.047
-0.041
+0.151
-0.002
-0.009
-0.331
A-1b
1.224 2.798 1.475
172.0
73.8
TS-1b 1.275 2.377 1.478
137.8 113.7
aOptimized by B3LYP/6-31+G(d,p) for H, C, O and DGDZVP
for In, I, at 298.15 K. bD is bond length of C1-C2.
The stereochemistry of carboindation to lead to
an anti-addition fashion is explained by the
LUMO of A-1a including the π* orbital of the
alkyne moiety (Figure 2). The π* orbital
fragment is localized at the C1 atom. In addition,
the lobe located on the opposite side to InI3
(indicated by arrows) is larger. In contrast,
another lobe on the C1 atom, which is located on
the same side of InI3, is smaller and is sterically
blocked by InI3. Therefore, the nucleophilic
attack of silyl ketene acetal 2a should occur
from the opposite side to InI3 to achieve the anti-
carboindation.
O
C1
I
C2 In
I
Me
I
A-1a
Figure 2. Explanation of the stereochemistry of carboindation
by the LUMO of A-1a
Scope and Limitations of Organosilicon
Nucleophiles
With the optimized reaction conditions in hand
(Table 1, entry 7), the scope of silyl ketene
acetals 2 was investigated (Table 3). To
synthesize tetra-substituted enol ethers, the
alkenylindium 4aa prepared from 1a, InI3, and
Table 2. Geometrical parametersa and the NBO
charges of 1a, 1b, A-1a, A-1b, TS-1a, and TS-
1b
6
ACS Paragon Plus Environment

Page 7 of 29
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
R1
Me
I2In
Me
R1
R2
I
Me
R1
R2
2a was treated with I2 to give the iodinated enol
I2
OMe
R2
InI3
+
+
ether 5aa in a 76% yield with retention of the
stereochemistry of 4aa. Various types of silyl
ketene acetals 2 were applicable to the
carboindation/iodination process. Monoalkyl-
and monoaryl-substituted silyl ketene acetals
were suitable substrates to give the desired
products (5aa-d) (Table 3, entries 1-4). Allyl-
substituted silyl ketene acetal 2e proved to be a
feasible nucleophile (Table 3, entry 5). The
chloride moiety tolerated the reaction conditions
(Table 3, entry 6). Carboindation using 2-
thienyl-substituted silyl ketene acetal 2g
afforded 5ag in a yield of 20% (Table 3, entry
7), because 2g would be decomposed in the
presence of a stoichiometric amount of InI3.
Dialkylsilyl ketene acetals (2h and 2i) gave the
corresponding enol ethers in medium to high
yields (5ah and 5ai) (Table 3, entries 8 and 9).
On the other hand, non-substituted silyl ketene
acetal 2j resulted in a complicated mixture
(Table 3, entry 10).
PhO
PhO
CH2Cl2
0 °C, 1 h
THF
OSiMe3
OPh
1a
COOMe
COOMe
2
4
5
yieldb
2
5
entry
substrate
product
Me
I
H
5aa
R = Me
76%
64%
69%
72%
2a
2b
2c
2d
1
2
3
4
R = Me
OMe
n
n
5ab
5ac
5ad
Bu
Bn
Ph
Bu
Bn
Ph
R
R
PhO
9
OSiMe3
COOMe
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
I
Me
H
OMe
69%
5
6
PhO
OSiMe3
COOMe
5ae
2e
H
I
Me
Cl
OMe
86%
20%
PhO
OSiMe3
COOMe
5af
Cl
2f
I
Me
S
S
PhO
7
OMe
H
COOMe
5ag
2g OSiMe3
I
Me
OMe
54%
80%
0%
8
9
PhO
OSiMe3
COOMe
5ah
2h
I
Me
OMe
Table 3. Scope and limitations of silyl ketene
acetals 2a
PhO
OSiMe3
COOMe
5ai
2i
I
Me
OiPr
PhO
10
OSitBuMe2
COOiPr
2j
5aj
aReaction conditions: InI3 (0.5 mmol), 1a (0.5 mmol), 2 (1.5
b
mmol), I2 (1.5 mmol), CH2Cl2 (1 mL), 0 °C, and 1 h. Isoated
yields.
The scope of silyl ketene imines 6 was shown
in Table 4. The iodinated products 7 were
obtained when the reaction mixture was treated
with PhI(OAc)2 instead of I2 for iodination of the
alkenylindiums.15 Carboindation of 1a with
various
α-alkyl-α-phenyl-substituted
silyl
ketene imines (6a, 6b, and 6c) followed by
iodination smoothly gave iodinated enol ethers
(7aa, 7ab, and 7ac) bearing a CN group (Table
4, entries 1-3). A diphenylcyanomethyl group
was successfully installed using 6d (Table 4,
entry 4). Silyl ketene imines bearing either an
electron donating group (6e) or an electron
withdrawing group (6f) gave the corresponding
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 29
1
2
3
4
5
6
7
8
9
compounds 7ae and 7af in moderate yields,
Scheme 5. anti-Carboindation using Me3SiCN 8
respectively (Table 4, entries 5 and 6). Thienyl-
substituted silyl ketene imine 6g was applicable,
although the yield was low (Table 4, entry 7).
Oxidative iodination gave iodinated (Z)-alkenes
selectively from (Z)-alkenylindium with the
retention of the stereochemistry of the alkene
moiety in all cases.
I
Me
CN
PhI(OAc)2
(2.2 eq.)
I2In
Me
CN
InI3
+
1a + Me3SiCN
CH2Cl2
0 °C, 1 h
0 °C, 1 h
PhO
8
(1.3 eq) (1 eq)
(5 eq)
PhO
9
57%
(32%)a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
aUsing InI3 (1 eq) and Me3SiCN (4 eq).
We attempted to use other types of
organosilicon nucleophiles such as an
alkynylsilane and an allylsilane, but these were
not applicable to the present carboindation (see
SI, Table S3).
Table 4. Scope of silyl ketene imines 6
I
Me
R1
R2
CN
R1 R2
Me
I2In
Me
R1
R2
CN
PhI(OAc)2
InI3
+
+
C
PhO
CH2Cl2
0 °C, 1 h
PhO
NTBS
OPh
1a
6
7
entry
substrate
product
yieldb
Organostannane
Carboindation
Nucleophiles
for
6
7
I
Me
R
Ph
1
2
3
R = Me 6a
Et 6b
R = Me 7aa
Et 7ab
90%
90%
41%
R
C
PhO
Ph
iPr
iPr
6c
7ac
To construct versatile carbon skeletons, instead
of organosilicon nucleophiles, we applied more
NTBS
CN
I
Me
Ph
Ph
Ph
Ph
nucleophilic
carboindation
organostannanes
system. The
to
use
the
of
4
5
89%
67%
C
PhO
NTBS
CN
6d
7ad
Me
Et
alkynylstannane 10 in the carboindation of 1a
gave the iodinated enol ether 12 in a 67% yield
with the treatment of PhI(OAc)2 (Scheme 6a).
The Z-form structure of 12 was determined by
X-ray diffraction analysis.
OMe
I
Et
PhO
OMe
C
CN
7ae
Me
Et
NTBS
6e
Cl
I
Et
6
7
76%
27%
PhO
Cl
C
NTBS
Scheme 6. Carboindation using organostannane
CN
7af
6f
S
I
Me
Me
Me
S
nucleophiles
PhO
C
CN
7ag
NTBS
6g
(a)
SnBu3
PhI(OAc)2
(2 eq)
I2In
Me
I
Me
InI3 + 1a
+
aReaction conditions: InI3 (0.5 mmol), 1a (0.5 mmol), 6 (1.0
mmol), PhI(OAc)2 (1.0 mmol), CH2Cl2 (1 mL), 0 °C, and 1 h.
bIsoated yields. TBS = tert-butyldimethylsilyl.
CH2Cl2
0 °C, 1 h
0 °C, 1 h
PhO
PhO
(1 eq) (1 eq)
Ph
10
Ph
Ph
11
12
15
67%
Me
(2.5 eq)
SnBu3
(b)
PhI(OAc)2
(2 eq)
I2In
PhO
Me
I
InI3 + 1a
+
CH2Cl2
0 °C, 1 h
0 °C, 1 h
Me3SiCN 8 also worked as a nucleophile to
afford the corresponding product 9. anti-
Carboindation of 1a using 1 equivalent of InI3
and 4 equivalents of Me3SiCN followed by
iodination by PhI(OAc)2 afforded product 9 in a
32% yield. Increasing the amount of InI3 and
Me3SiCN improved the yield of 9 to 57%
(Scheme 5).
PhO
(1 eq) (1 eq)
13
(3 eq)
14
81%
The complex between alkenylindium 11 and
3,5-dibromo pyridine was successfully analyzed
by X-ray crystallography, which revealed that
an anti-addition mechanism led to a trans-
8
ACS Paragon Plus Environment

Page 9 of 29
The Journal of Organic Chemistry
1
2
3
4
orientation between the indium and alkynyl
groups (Figure 3).
bond at a carbon-bearing ethoxy group, although
the yield of 3ka was low (Table 5, entry 10).
5
6
7
8
9
Table 5. Scope and limitations of internal
alkynyl ethers 1a
Br
Br
In
Br
N
°
N
In-C = 2.142 A
Br
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
I
O
O
In
N
I
Br
I2In
R
H
R
N
R
I
I
MeOH
Br
OMe
InI3
+
+
R'O
R'O
CH2Cl2
0 °C, 1 h
OTMS
Br
Br
COOMe
COOMe
yieldb
OR'
1
2a
4
3
11
•3,5-Br2Py
ORTEP drawing
1
3
product
entry
substrate
O
Figure 3. ORTEP drawing of 11·3,5-Br2Py
R
H
O
Me
3aa
3ca
1
2
3
R = H
72%
73%
Cl
Allylstannane 13 was also applicable to the
anti-carboindation of 1a to afford iodinated
compound 15 in an 81% yield (Scheme 6b). The
reaction of alkynes with an allylstannane in the
presence of Lewis acids such as EtAlCl2 or
ZrCl4 are known to give alkenylstannanes as
products via an anti-addition/transmetalation
mechanism.16 Furthermore, in a previous
experience with the carboindation of simple
alkynes, we found that organostannane
nucleophiles were inapplicable. It is noted that
enhancing the reactivity of a carbon-carbon
multiple-bond in carboindation by an alkoxy
group extends the scope of suitable nucleophiles.
Me
3da
OMe
80%
R
COOMe
Ph
1a, 1c, 1d
H
4
45%
Ph
PhO
PhO
COOMe
3ea
1e
H
3fa
R = Cl
5
6
7
R
68%
56%
57%
R
3ga
3ha
OMe
Ph
PhO
PhO
1f-1h
COOMe
H
Me
O
8
9
85%
0%
Me
O
COOMe
Me
1i
O
3ia
H
O
Me
COOMe
1j
3ja
Ph
H
Ph
Scope and Limitations of Alkynes
10
25%
EtO
EtO
COOMe
3ka
1k
As shown in Table 5, various types of alkynyl
ethers 1 were applied to the present
carboindation system. Aryl alkynyl ethers
bearing an electron-withdrawing group 1b or an
electron donating group 1c on an aryl ring gave
the corresponding products 3ca and 3da in high
yields, respectively (Table 5, entries 2 and 3).
Chloro (3fa), methoxy (3ga), and phenyl groups
(3ea and 3ja) endured these conditions (Table 5,
entries 4-7). 1-Naphtyl alkynyl ether 1h was
successfully transformed to product 3ha in an 85%
yield (Table 5, entry 8). However, bulky aryl
alkynyl ether 1j did not give the desired product
(Table 5, entry 9). The carboindation of phenyl
acetylene bearing an ethoxy group (1k)
exclusively formed the desired carbon-carbon
aReaction conditions: InI3 (0.5 mmol), 1a (0.5 mmol), 2a (1.5
b
mmol), I2 (1.5 mmol), CH2Cl2 (1 mL), 0 °C, and 1 h. Isoated
yields.
Application of Synthesized Iodinated Enol
Ethers to Suzuki Cross-Coupling Reactions
Cross-coupling reactions were conducted using
iodinated enol ethers prepared by the
carboindation/iodination process (Table 6).17
Iodinated compound 5a underwent Suzuki
coupling with p-tolylboronic acid to give tetra-
substituted enol ether 16 in a 76% yield with no
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 29
1
2
3
4
5
6
7
8
9
loss of stereochemistry in the alkene moiety of
Me
CN
Me
NH2
LiAlH4, AlCl3
Et2O, 0 °C
5a. Other iodinated compounds such as 9, 12,
and 15 also gave corresponding products in
moderate to high yields. Generally, the stereo-
and regioselective synthesis of tetra-substituted
enol ethers is a difficult process.18 This approach
could be one of the most reliable tools for the
selective synthesis of multi-substituted enol
ethers.
PhO
PhO
17
20 41%
Applications
of
Synthesized
Multi-
substituted Enol Ethers to the Construction
of a 7-Membered Ring Compound
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The developed carboindation was applied to
the synthesis of a 7-membered ring compound,
which is an important carbon framework in
natural compounds such as cyanthiwigin,21a
pseudolaric acid A,21b and sphenolobane-type
diterpenoids.21c The anti-carboindation of 1l
using InI3 and 2e gave triene compound 3le in a
60% yield with no stereoisomers. Triene
compound 3le underwent intramolecular olefin
metathesis21b by Grubbs catalyst to produce 7-
membered ring compound 21 (Scheme 8). The
perfect stereoselective synthesis of enol ether
3le led to an easy and efficient access to cyclic
compounds.
Table 6. Synthesis of tetra-substituted enol
ethers by Suzuki reactiona
Pd(PPh3)4
I
Me
R
(10 mol%)
K2CO3 (3 eq)
Me
R
+
B(OH)2
(2 eq)
Dioxane
90 °C, 8 h
PhO
PhO
R-I
(1 eq)
R-I
Me
R-I
entry
productb
Me
entry
productb
I
Ar
I
Me
Ar
Me
1
3
PhO
PhO
PhO
PhO
Ph
COOMe
COOMe
Ph
5a
16
12
18 78%
76%
Scheme 8. Construction of a 7-memberd ring
I
Me
CN
Ar
Me
I
Me
Ar
Me
2
4
PhO
PhO
17
CN
75%
PhO
PhO
19
using a Grubbs catalyst
9
15
42%
aReaction conditions: R-I (1 eq), p-tolylboronic acid (2 eq),
K2CO3 (3 eq), Pd(PPh3)4 (10 mol%). Solvent, temperature, and
reaction time are given in the table. bIsoated yields. Ar = p-Me-
C6H4
H
1.InI3
2.MeOH
cat. Grubbs II
+
OMe
PhO
PhO
21
benzene
70 ºC
OTMS
OPh
COOMe
3le
(60%)
COOMe
(58%)
1l
2e
N
N
Dipp
Dipp
Ph
Grubbs II
=
Cl
Cl
Rh
PCy3
Further transformation of 17 to amine 20 was
performed by reduction19 using lithium
aluminum hydride and aluminum chloride in a
41% yield (Scheme 7). Compound 20 is a
precursor of α-amino ketone, which is
commonly found in biological molecules,
natural products, and active pharmaceutical
ingredients.20
■ CONCLUSION
In conclusion, we achieved regio- and
stereoselective carboindation of alkynyl ethers
using organometallic nucleophiles and InI3 to
synthesize
β-alkoxyalkenylindiums.
An
efficient synthetic method for tetra-substituted
enol ethers was established via a sequential
process including the present carboindation. The
reaction proceeded in an anti-addition fashion,
which was confirmed by X-ray diffraction
Scheme 7. Further reduction to amine 20
10
ACS Paragon Plus Environment

Page 11 of 29
1
The Journal of Organic Chemistry
2
3
4
5
6
7
8
9
analysis of β-alkoxyalkenylindiums. We
oven temperature and pressure indicated. X-ray
diffraction analysis was carried out using
Rigaku XtaLAB Synergy with Hypix-6000HE.
discovered that an oxygen atom bonding at an
alkyne moiety boosted carboindation by
increasing the interaction of InI3 and the alkyne
moiety and stabilizing its transition state. The
scope of nucleophiles was considerably wide,
and silyl ketene acetals, silyl ketene imines, an
alkynyl stannane, and an allyl stannane were
Material Dehydrated solvents, CH2Cl2, CHCl3,
DMF, Et2O, toluene, hexane, benzene, 1,4-
dioxane, and THF, were purchased from Wako
Pure Chemical Industries and used as obtained.
Alkynyl ethers 1a22a and 1d22a were prepared by
modified reported methods22a, and these
compounds were reported. Alkynyl ether 1k22b
was prepared by reported methods22b. The
preparation and characterization of alkynyl
ethers 1c, 1e-1j, and 1l are described below.
Internal alkyne 1b22c was synthesized using a
procedure reported in the literature. Silyl ketene
acetals 2a,23a 2b,23b 2c,23c 2d,23b 2e,23d 2f,8 2g,8
2i,23b and 2j23e were prepared by known methods
and these compounds were reported. Silyl
ketene imines 6a,24a 6b,24a 6c,24b 6d,24c 6e,24a
6f,9b and 6g24d were prepared by known methods
and these compounds were reported. InI3
(indium iodide, 99.99%) was purchased from
Kojundo Chemical Laboratory Co., Ltd.. All
other reagents were commercially available.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
applicable.
The
prepared
β-
alkoxyalkenylindiums
were successfully
transformed to functionalized tetra-substituted
enol ethers through various organic reactions
such as halogenation and halogenation/Suzuki
coupling.
■ EXPERIMENTAL SECTION
General Information NMR spectra were
1
recorded on JEOL JNM-400 (400 MHz for H
NMR and 100 MHz for 13C NMR) spectrometer.
Chemical shifts were reported in ppm on the δ
1
scale relative to tetramethylsilane (δ = 0 for H
NMR) and residual CDCl3 (δ = 77.0 for 13C
NMR) as an internal reference. All new
compounds were characterized by 1H, 13C{1H},
13C off-resonance techniques, DEPT, COSY,
HMQC, and HMBC. Infrared (IR) spectra were
recorded on a JASCO FT/IR-6200 Fourier
transform infrared spectrophotometer. Positive
EI and CI High-resolution mass spectra were
recorded on a magnetic sector type mass
spectrometer (JEOL JMS-700). Column
chromatographies were performed with silica
gel or alumina. Purification by recycled HPLC
or GPC was performed using a SHIMADZU
recycling HPLC system (SPD-20A, RID-10A,
DGU-20A, LC-6AD, and FCV-20H2) from the
Japan Analytical Industry Co. (NEXT recycling
preparative GPC). Reactions were carried out in
dried solvents under a nitrogen atmosphere,
unless otherwise stated. An oil bath was used for
reactions requiring heating. Reagents were
purchased from Aldrich or Tokyo Chemical
Industry Co., Ltd. (TCI), Wako Pure Chemical
Industries, Ltd., and used either after
purification by distillation or without
purification for solid substrates. Bulb-to-Bulb
distillation (Kugelrohr) was accomplished at the
Phenyl prop-1-ynyl ether (1a)22a
A solution of n-BuLi (1.6 M hexane solution, 160 mmol,
100 mL) was added dropwise to a solution of 1,2-
dichloro-1-phenoxyethene (79.8 mmol, 15.1 g) in Et2O
(200 mL) at -78 °C. Then, the mixture was warmed to -20
°C and stirred for 2 h. MeI (100 mmol, 15.2 g) and HMPA
(160 mmol, 26.4 g) were added to the reaction mixture at
-20 °C and stirred at 50 °C for 8 h. The mixture was
poured into hexane (200 mL) and sat. NH4Cl aq (100 mL)
and then extracted with hexane (50 x 3 mL). The collected
organic layer was dried over MgSO4. The solvent was
evaporated and the residue was purified by short alumina
column chromatography and then by distillation (bp.
60 °C, 12 torr) to give the desired product as a yellow oil
(7.90 g, 75%). This is a known compound, and the
spectroscopic data were identical to that found in the
literature.22a
4-Chlorophenyl prop-1-ynyl ether (1c)
A solution of n-BuLi (1.6 M hexane solution, 50 mmol,
32 mL) was added dropwise to a solution of 1,2-dichloro-
1-(4-chlorophenoxy)ethene (20 mmol, 4.4 g) in Et2O (40
mL) at -78 °C. Then, the mixture was warmed to -20 °C
and stirred for 2 h. MeI (43 mmol, 6.5 g) and N,N'-
dimethylpropyleneurea (DMPU) (49 mmol, 6.3 g) were
added to the reaction mixture at -20 °C, and stirred at
50 °C for 8 h. The mixture was poured into hexane (100
mL) and sat. NH4Cl aq (50 mL) and then extracted with
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 29
1
2
hexane (20 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
over MgSO4. The solvent was evaporated and the residue
was purified by alumina column chromatography to give
the desired product as a yellow oil (2.20 g, 66%).; IR:
was purified by short alumina column chromatography,
and then by distillation (bp. 130 °C, 0.71 torr) to give the
desired product as a colorless oil (0.803 g, 45%).; IR:
3
4
5
6
7
8
9
1
1
(neat) 2288 (C≡C) cm-1; H NMR: (400 MHz, CDCl3)
(neat) 2279 (C≡C) cm-1; H NMR: (400 MHz, CDCl3)
7.29 (d, J = 9.2 Hz, 2H), 7.19 (d, J = 9.2 Hz, 2H), 1.88 (s,
3H, 3-H3); 13C NMR: (100 MHz, CDCl3) 154.9 (C), 129.4
(CH), 128.9 (C), 116.2 (CH), 81.8 (C), 40.6 (C), 1.7
(CH3); HRMS: (EI, 70 eV) Calculated: (C9H7ClO)
166.0815 (M+) Found: 166.0813.
7.35 (t, J = 8.0 Hz, 2H, m), 7.24 (d, J = 8.0 Hz, 2H, o),
7.13 (t, J = 8.0 Hz, 1H, p), 3.70 (t, J = 6.8 Hz, 2H, 5-H2),
2.48 (t, J = 6.8 Hz, 2H, 3-H2), 2.00 (quint, J = 6.8 Hz, 2H,
4-H2); 13C NMR: (100 MHz, CDCl3) 156.1 (s), 129.6 (d),
124.1 (d), 114.8 (d), 83.9 (s), 43.8 (t), 42.6 (s), 31.9 (t),
14.7 (t); HRMS: (EI, 70 eV) Calculated: (C11H11ClO)
194.0498 (M+) Found: 194.0499.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4-Methoxyphenyl prop-1-ynyl ether (1d)22a
A solution of n-BuLi (1.6 M hexane solution, 6 mmol,
3.8 mL) was added dropwise to a solution of ethynyl 4-
methoxyphenyl ether8 (6.1 mmol, 0.90 g) in THF (10 mL)
at -78 °C. Then, the mixture was warmed to -20 °C and
stirred for 2 h. MeI (9.2 mmol, 1.3 g) and N,N'-
dimethylpropyleneurea (DMPU) (4.2 mmol, 0.53 g) were
added to the reaction mixture at -20 °C, and stirred at
25 °C for 1 h. The mixture was poured into hexane (20
mL) and sat. NH4Cl aq (10 mL) and then extracted with
hexane (10 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by alumina column chromatography to give
the desired product as a yellow oil (0.53 g, 54%). This is
a known compound, and the spectroscopic data were
identical to that reported in the literature.22a
Phenyl 5-methoxypent-1-ynyl ether (1g)
A solution of n-BuLi (1.6 M hexane solution, 11 mmol,
6.8 mL) was added dropwise to a solution of ethynyl
phenyl ether (10.0 mmol, 1.18 g) in THF (20 mL) at -
78 °C. Then, the mixture was stirred for 1 h at -78 °C. 1-
Iodo-3-methoxypropane (8.23 mmol, 1.71 g) and N,N'-
dimethylpropyleneurea (DMPU) (9.53 mmol, 1.22 g)
were added to the reaction mixture at -78 °C, and stirred
at 50 °C for 8 h. The mixture was poured into hexane (50
mL) and sat. NH4Cl aq (10 mL) and then extracted with
hexane (10 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by short alumina column chromatography,
and then by distillation (bp. 110 °C, 0.14 torr) to give the
desired product as a yellow oil (0.775 g, 50%).; IR: (neat)
2278 (C≡C) cm-1; 1H NMR: (400 MHz, CDCl3) 7.34 (t, J
= 7.8 Hz, 2H, m), 7.25 (d, J = 7.8 Hz, 2H, o), 7.11 (t, J =
7.8 Hz, 1H, p), 3.50 (t, J = 7.1 Hz, 2H, 5-H2), 3.35 (s, 3H,
OMe), 2.37 (t, J = 7.1 Hz, 2H, 3-H2), 1.82 (quint, J = 7.1
Hz, 2H, 4-H2); 13C NMR: (100 MHz, CDCl3) 156.3 (s),
129.5 (d), 123.9 (d), 114.7 (d), 83.4 (s), 71.3 (t), 58.7 (q),
43.9 (s), 29.3 (t), 14.0 (t).; HRMS: (EI, 70 eV) Calculated:
(C12H14O2) 190.0994 (M+) Found: 190.0992.
Phenyl 3-phenylprop-1-ynyl ether (1e)
A solution of n-BuLi (1.6 M hexane solution, 11 mmol,
6.8 mL) was added dropwise to a solution of ethynyl
phenyl ether8 (10.0 mmol, 1.18 g) in THF (20 mL) at -
78 °C. Then, the mixture was stirred for 1 h at -78 °C.
Benzyl bromide (10.0 mmol, 1.71 g) and N,N'-
dimethylpropyleneurea (DMPU) (10.0 mmol, 1.29 g)
were added to the reaction mixture at -78 °C and stirred at
50 °C for 8 h. The mixture was poured into hexane (50
mL) and sat. NH4Cl aq (10 mL) and then extracted with
hexane (10 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by short alumina column chromatography,
and then by distillation (bp. 160 °C, 0.35 torr) to give the
desired product as a yellow oil (0.533 g, 26%).; IR: (neat)
2280 (C≡C) cm-1; 1H NMR: (400 MHz, CDCl3) 7.42-7.10
(m, 10H, OPh and 3-Ph), 3.71 (s, 2H, 3-H2); 13C NMR:
(100 MHz, CDCl3) 156.2 (s), 137.6 (s), 129.6 (d), 128.4
(d), 127.8 (d), 126.5 (d), 124.0 (d), 114.8 (d), 85.1 (s), 42.5
(s), 23.6 (t); HRMS: (EI, 70 eV) Calculated: (C15H12O)
208.0887 (M+) Found: 208.0891.
Phenyl 5-phenylpent-1-ynyl ether (1h)
A solution of n-BuLi (1.6 M hexane solution, 10 mmol,
6.3 mL) was added dropwise to a solution of ethynyl
phenyl ether (9.43 mmol, 1.11 g) in THF (20 mL) at -
78 °C. Then, the mixture was stirred for 1 h at -78 °C. (3-
Bromopropyl)benzene (8.83 mmol, 2.03 g) and N,N'-
dimethylpropyleneurea (DMPU) (10.5 mmol, 1.35 g)
were added to the reaction mixture at -78 °C, and stirred
at 50 °C for 8 h. The mixture was poured into hexane (50
mL) and sat. NH4Cl aq (10 mL) and then extracted with
hexane (10 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by short alumina column chromatography,
and then by distillation (bp. 200 °C, 0.71 torr) to give the
desired product as a colorless oil (0.800 g, 34%).; IR:
Phenyl 5-chloropent-1-ynyl ether (1f)
A solution of n-BuLi (1.6 M hexane solution, 10 mmol,
6.3 mL) was added dropwise to a solution of ethynyl
phenyl ether (9.22 mmol, 1.09 g) in THF (20 mL) at -
78 °C. Then, the mixture was stirred for 1 h at -78 °C. 1-
Bromo-3-chloropropane (9.81 mmol, 1.60 g) and N,N'-
dimethylpropyleneurea (DMPU) (10.4 mmol, 1.34 g)
were added to the reaction mixture at -78 °C, and stirred
at 50 °C for 8 h. The mixture was poured into hexane (50
mL) and sat. NH4Cl aq (10 mL) and then extracted with
hexane (10 x 3 mL). The collected organic layer was dried
1
(neat) 2277 (C≡C) cm-1; H NMR: (400 MHz, CDCl3)
7.38-7.11 (m, 10H, OPh and 5-Ph), 2.77 (t, J = 7.2 Hz, 2H,
5-H2), 2.30 (t, J = 7.2 Hz, 2H, 3-H2), 1.88 (quint, J = 7.2
Hz, 2H, 4-H2); 13C NMR: (100 MHz, CDCl3) 156.3 (s),
141.8 (s), 129.5 (d), 128.5 (d), 128.3 (d), 125.8 (d), 123.9
(d), 114.8 (d), 83.7 (s), 44.2 (s), 34.9 (t), 31.0 (t), 16.8 (t).;
HRMS: (EI, 70 eV) Calculated: (C17H16O) 236.1201(M+)
Found: 236.1199.
12
ACS Paragon Plus Environment

Page 13 of 29
1
The Journal of Organic Chemistry
1-Naphthyl prop-1-ynyl ether (1i)
7.11 (t, J = 7.7 Hz, 1H, p), 5.07 (s, 1H, 5-HA), 4.85 (s, 1H,
2
3
4
5
6
7
8
9
A solution of n-BuLi (1.6 M hexane solution, 20 mmol,
13 mL) was added dropwise to a solution of 1,2-dichloro-
1-(1-naphthoxy)ethene25 (9.95 mmol, 2.38 g) in Et2O (20
mL) at -78 °C. Then, the mixture was stirred for 1 h at -78
°C. MeI (20.6 mmol, 2.93 g) and N,N'-
dimethylpropyleneurea (DMPU) (13.5 mmol, 1.73 g)
were added to the reaction mixture at -78 °C, and stirred
at 50 °C for 8 h. The mixture was poured into hexane (50
mL) and sat. NH4Cl aq (10 mL) and then extracted with
hexane (10 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by alumina column chromatography to give
the desired product as a yellow oil (0.544 g, 30%).; IR:
5-HB), 2.99 (s, 2H, 3-H2), 1.83 (s, 3H, 4-Me); 13C NMR:
(100 MHz, CDCl3) 156.2 (s), 141.4 (s), 129.5 (d), 124.0
(d), 114.8 (d), 111.2 (t), 85.2 (s), 41.8 (s), 26.1 (t), 22.1
(q); HRMS: (EI, 70 eV) Calculated: 172.0888 (M+)
(C12H12O) Found: 172.0890.
General procedure for the carboindation of alkynyl
ether 1 using InI3 and a silyl ketene acetal 2 to give
enol ether 3 (Table 6)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Alkynyl ether 1 (0.50 mmol) was added to a solution of
InI3 (0.50 mmol) and a silyl ketene acetal 2 (1.50 mmol)
in dichloromethane (1 mL). The mixture was stirred at
0 °C for 1 h. The mixture was poured into ethyl acetate
(20 mL) and sat. NaHCO3 aq (10 mL), and then extracted
with ethyl acetate (10 x 3 mL). The collected organic layer
was dried over MgSO4. The solvent was evaporated and
the residue was purified by column chromatography.
(neat) 2295 (C≡C) cm-1; H NMR: (400 MHz, CDCl3)
1
8.20-8.17 (m, 1H), 7.86-7.84 (m, 1H), 7.61 (d, J = 8.0 Hz,
2H), 7.54-7.52 (m, 2H), 7.45 (t, J = 8.0 Hz, 1H), 1.98 (s,
3H, 13-H3); 13C NMR: (100 MHz, CDCl3) 152.2 (s), 134.3
(s), 127.5 (d), 126.7 (d), 126.1 (d), 125.3 (d), 123.7 (s),
123.6 (d), 120.8 (d), 108.1 (d), 82.0 (s), 41.2 (s), 1.8 (q);
HRMS: (EI, 70 eV) Calculated: (C13H10O) 182.0732 (M+)
Found: 182.0734.
Methyl (E)-2-methyl-3-phenoxypent-3-enoate (3aa)
m
p
o
i
O
3
O
2
4
5
1
2,6-Dimethylphenyl prop-1-ynyl ether (1j)
OMe
A solution of n-BuLi (1.6 M hexane solution, 20 mmol,
13 ml) was added dropwise to a solution of 1,2-dichloro-
1-(2,6-dimethylphenoxy)ethene26 (9.87 mmol, 2.15 g) in
Et2O (20 mL) at -78 °C. Then, the mixture was stirred for
1 h at -78 °C. MeI (20.6 mmol, 2.93 g) and N,N'-
dimethylpropyleneurea (DMPU) (13.1 mmol, 1.70 g)
were added to the reaction mixture at -78 °C, and stirred
at 50 °C for 8 h. The mixture was poured into hexane (50
mL) and sat. NH4Cl aq (10 mL) and then extracted with
hexane (10 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by alumina column chromatography to give
the desired product as a yellow oil (0.269 g, 17%).; IR:
Phenyl prop-1-ynyl ether 1a (0.442 mmol, 0.0584 g) was
added to a solution of InI3 (0.514 mmol, 0.255 g) and
methylketene methyl trimethylsilyl acetal 2a (1.64 mmol,
0.263 g) in dichloromethane (1 mL) at 0 °C. The mixture
was stirred for 1 h at 0 °C. The mixture was poured into
ethyl acetate (20 mL) and sat. NaHCO3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a colorless oil (0.074 g, 76%).;
IR: (neat) 1745 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.29 (t, J = 7.7 Hz, 2H, m), 7.05 (t, J = 7.7 Hz, 1H, p), 7.00
(d, J = 7.7 Hz, 2H, o), 4.72 (q, J = 7.1 Hz, 1H, 4-H), 3.72
(s, 3H, OMe), 3.69 (q, J = 7.3 Hz, 1H, 2-H), 1.63 (d, J =
7.1 Hz, 3H, 5-H3), 1.43 (d, J = 7.3 Hz, 3H, 2-Me).; 13C
NMR: (100 MHz, CDCl3) 173.3 (C, C-1), 156.2 (C, i),
154.1 (C, C-3), 129.4 (CH, m), 123.2 (CH, p), 119.9 (CH,
o), 103.4 (CH, C-4), 52.1 (CH3, OMe), 39.6 (CH, C-2),
14.3 (CH3, 2-Me), 11.4 (CH3, C-5).; HRMS: (EI, 70 eV)
Calculated: (C13H16O3) 220.1099 (M+) Found: 220.1103.
Methyl (E)-3-(4-chlorophenoxy)-2-methylpent-3-enoate
(3ca)
(neat) 2282 (C≡C) cm-1; H NMR: (400 MHz, CDCl3)
1
7.01 (m, 3H, 3-H x 2, 4-H), 2.37 (s, 6H, 2-Me x 2), 1.72
(s, 3H, 3'-H3); 13C NMR: (100 MHz, CDCl3) 153.8 (s),
129.4 (s), 129.0 (d), 125.6 (d), 86.1 (s), 32.0 (q), 15.9 (s),
1.5 (q); HRMS: (EI, 70 eV) Calculated: (C11H12O)
160.0888 (M+) Found: 160.0889.
Phenyl 4-methylpent-4-en-1-ynyl ether (1l)
A solution of n-BuLi (1.6 M hexane solution, 11 mmol,
7.0 mL) was added dropwise to a solution of ethynyl
phenyl ether (9.75 mmol, 1.15 g) in THF (20 mL) at -
78 °C. Then, the mixture was stirred for 1 h at -78 °C. 3-
Bromo-2-methylprop-1-ene (9.18 mmol, 1.71 g) and N,N'-
dimethylpropyleneurea (DMPU) (9.53 mmol, 1.22 g)
were added to the reaction mixture at -78 °C, and stirred
at 50 °C for 8 h. The mixture was poured into hexane (50
mL) and sat. NH4Cl aq (10 mL) and then extracted with
hexane (10 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by short alumina column chromatography to
give the desired product as a yellow oil (0.937 g, 50%).;
IR: (neat) 2281 (C≡C) cm-1; 1H NMR: (400 MHz, CDCl3)
7.34 (t, J = 7.7 Hz, 2H, m), 7.26 (d, J = 7.7 Hz, 2H, o),
3'
Cl
2'
4'
1'
O
3
O
2
4
5
1
OMe
A solution of 4-chlorophenyl prop-1-ynyl ether 1c (0.505
mmol, 0.0842 g) was added to a solution of InI3 (0.545
mmol, 0.270 g) and methylketene methyl trimethylsilyl
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 29
1
2
3
4
5
6
7
8
m
acetal 2a (1.58 mmol, 0.253 g) in dichloromethane (1 mL)
p
o
at 0 °C. The mixture was stirred for 1 h at 0 °C. The
mixture was poured into ethyl acetate (20 mL) and sat.
NaHCO3 aq (10 mL), and then extracted with ethyl acetate
(10 x 3 mL). The collected organic layer was dried over
MgSO4. The solvent was evaporated and the residue was
purified by silica gel column chromatography
(hexane/ethyl acetate = 88:12, column length 11 cm and
diameter 2.7 cm) and GPC to give the product as a
colorless oil (0.093 g, 73%). The structure of 3ca was
determined by 1H-NOE experiment and 2D spectra of the
i
O
3
O
2
4
5
1
OMe
2'
1'
3'
4'
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Phenyl 3-phenylprop-1-ynyl ether 1e (0.522 mmol,
0.109 g) was added to a solution of InI3 (0.547 mmol,
0.269 g) and methylketene methyl trimethylsilyl acetal 2a
(1.60 mmol, 0.256 g) in dichloromethane (1 mL) at 0 °C.
The mixture was stirred for 1 h at 0 °C. The mixture was
poured into ethyl acetate (20 mL) and sat. NaHCO3 aq (10
mL), and then extracted with ethyl acetate (10 x 3 mL).
The collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a colorless oil (0.064 g, 43%).;
IR: (neat) 1739 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.29-7.27 (m, 4H, m and 3'-H x 2), 7.19-7.17 (m, 3H, 2'-
H x 2 and 4'-H), 7.06-7.03 (m, 3H, p and o), 4.83 (t, J =
8.0 Hz, 1H, 4-H), 3.80 (q, J = 7.1 Hz, 1H, 2-H), 3.73 (s,
3H, OMe), 3.43 (dd, J = 16.0, 8.0 Hz, 2H, 5-HH), 3.37 (dd,
J = 16.0, 8.0 Hz, 2H, 5-HH), 1.49 (d, J = 7.1 Hz, 3H, 2-
Me); 13C NMR: (100 MHz, CDCl3) 173.1 (C, C-1), 155.8
(C, i), 155.0 (C, C-3), 140.4 (C, C-1'), 129.5 (CH, m),
128.4 (CH), 128.1 (CH), 126.1 (CH), 123.6 (CH, p), 120.3
(CH, o), 106.7 (CH, C-4), 52.1 (CH3, OMe), 39.9 (CH, C-
2), 32.5 (CH2, C-5), 14.6 (CH3, 2-Me); HRMS: (EI, 70
eV) Calculated: (C19H20O3) 296.1412 (M+) Found:
296.1413.
1
compound.; IR: (neat) 1743 (C=O) cm-1; H NMR: (400
MHz, CDCl3) 7.18 (d, J = 8.7 Hz, 2H, 3'-H x 2), 6.88 (d,
J = 8.7 Hz, 2H, 2'-H x 2), 4.67 (q, J = 7.2 Hz, 1H, 4-H),
3.64 (s, 3H, OMe), 3.62 (q, J = 7.2 Hz, 1H, 2-H), 1.56 (d,
J = 7.2 Hz, 3H, 2-Me), 1.35 (d, J = 7.2 Hz, 3H, 5-H3); 13C
NMR: (100 MHz, CDCl3) 173.0 (s, C-1), 154.8 (s, C-1'),
153.8 (s, C-3), 129.4 (d, C-2'), 128.1 (s, C-3'), 121.0 (d, C-
2'), 104.2 (d, C-4), 52.1 (q, OMe), 39.5 (s, C-2), 14.2 (q,
2-Me), 11.4 (q, C-5); HRMS: (EI, 70 eV) Calculated:
(C13H15ClO3) 254.0710 (M+) Found: 254.0711.
Methyl (E)-3-(4-methoxyphenoxy)-2-methylpent-3-
enoate (3da)
3'
MeO
2'
4'
1'
O
3
O
2
4
5
1
OMe
A solution of (4-methoxyphenyl)(prop-1-ynyl)ether 1d
(0.524 mmol, 0.0850 g) was added to a solution of InI3
(0.551 mmol, 0.273 g) and methylketene methyl
trimethylsilyl acetal 2a (1.76 mmol, 0.282 g) in
dichloromethane (1 mL) at 0 °C. The mixture was stirred
for 1 h at 0 °C. The mixture was poured into ethyl acetate
(20 mL) and sat. NaHCO3 aq (10 mL), and then extracted
with ethyl acetate (10 x 3 mL). The collected organic layer
was dried over MgSO4. The solvent was evaporated and
the residue was purified by silica gel column
chromatography (hexane/ethyl acetate = 88:12, column
length 11 cm and diameter 2.7 cm) and GPC to give the
product as a colorless oil (0.105 g, 80%).; IR: (neat) 1743
(C=O) cm-1; 1H NMR: (400 MHz, CDCl3) 6.92 (d, J = 9.2
Hz, 2H, 2'-H x 2), 6.83 (d, J = 9.2 Hz, 2H, 3'-H x 2), 4.54
(q, J = 7.2 Hz, 1H, 4-H), 3.78 (s, 3H, 4'-OMe), 3.74 (s,
3H, 1-OMe), 3.68 (q, J = 7.2 Hz, 1H, 2-H), 1.59 (d, J =
7.2 Hz, 3H, 5-H3), 1.44 (d, J = 7.2 Hz, 3H, 2-Me); 13C
NMR: (100 MHz, CDCl3) 173.3 (s, C-1), 155.7 (s, C-4'),
155.3 (s, C-3), 149.1 (s, C-1'), 121.6 (d, C-2'), 114.4 (d, C-
3'), 100.6 (d, C-4), 55.5 (q, 4'-OMe), 52.0 (q, 1-COOMe),
39.5 (d, C-2), 14.3 (q, 2-Me), 11.3 (q, C-5); HRMS: (EI,
70 eV) Calculated: (C14H18O4) 250.1205 (M+) Found:
250.1209.
Methyl (E)-7-chloro-2-methyl-3-phenoxyhept-3-enoate
(3fa)
m
p
o
i
O
3
O
2
4
5
1
OMe
6
7
Cl
Phenyl 5-chloropent-1-ynyl ether 1f (0.532 mmol, 0.104
g) was added to a solution of InI3 (0.529 mmol, 0.262 g)
and methylketene methyl trimethylsilyl acetal 2a (1.59
mmol, 0.254 g) in dichloromethane (1 mL) at 0 °C. The
mixture was stirred for 1 h at 0 °C. The mixture was
poured into ethyl acetate (20 mL) and sat. NaHCO3 aq (10
mL), and then extracted with ethyl acetate (10 x 3 mL).
The collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a transparent oil (0.097 g,
64%).; IR: (neat) 1741 (C=O) cm-1; 1H NMR: (400 MHz,
Methyl (E)-2-methyl-3-phenoxy-5-phenylpent-3-enoate
(3ea)
14
ACS Paragon Plus Environment

Page 15 of 29
1
The Journal of Organic Chemistry
m
CDCl3) 7.31 (t, J = 7.7 Hz, 2H, m), 7.08 (t, J = 7.7 Hz, 1H,
p), 7.00 (d, J = 7.7 Hz, 2H, o), 4.56 (t, J = 7.3 Hz, 1H, 4-
2
3
p
o
H), 3.75-3.72 (m, 4H, OMe and 2-H), 3.54-3.53 (m, 2H,
7-H2), 2.21 (q, J = 7.3 Hz, 2H, 5-H2), 1.79 (quint, J = 7.3
Hz, 2H, 6-H2), 1.46 (d, J = 7.0 Hz, 3H, 2-Me); 13C NMR:
(100 MHz, CDCl3) 173.0 (C, C-1), 155.8 (C, i), 155.3 (C,
C-3), 129.5 (CH, m), 123.5 (CH, p), 120.2 (CH, o), 106.3
(CH, C-4), 52.1 (CH3, OMe), 44.1 (CH2, C-7), 39.9 (CH,
C-2), 32.5 (CH2, C-6), 23.4 (CH2, C-5), 14.6 (CH3, 2-Me);
HRMS: (EI, 70 eV) Calculated: (C15H19ClO3) 282.1023
(M+) Found: 282.1025.
4
5
6
7
8
9
i
O
O
3
2
4
5
1
OMe
6
7
2'
1'
3'
4'
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Phenyl 5-phenylpent-1-ynyl ether 1h (0.494 mmol,
0.116 g) was added to a solution of InI3 (0.515 mmol,
0.255 g) and methylketene methyl trimethylsilyl acetal 2a
(1.53 mmol, 0.245 g) in dichloromethane (1 mL) at 0 °C.
The mixture was stirred for 1 h at 0 °C. The mixture was
poured into ethyl acetate (20 mL) and sat. NaHCO3 aq (10
mL), and then extracted with ethyl acetate (10 x 3 mL).
The collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a colorless oil (0.093 g, 57%).;
IR: (neat) 1743 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.30-7.27 (m, 4H, Ar), 7.19-7.15 (m, 3H, Ar), 7.06 (t, J =
7.7 Hz, 1H, p), 7.01 (d, J = 7.7 Hz, 2H, o), 4.70 (t, J = 7.7
Hz, 1H, 4-H), 3.71 (s, 3H, OMe), 3.64 (q, J = 7.7 Hz, 1H,
2-H), 2.60 (t, J = 7.7 Hz, 2H, 7-H2), 2.10-2.04 (m, 2H, 5-
H2), 1.72-1.62 (m, 2H, 6-H2), 1.43 (d, J = 7.7 Hz, 3H, 2-
Me); 13C NMR: (100 MHz, CDCl3) 173.2 (s, C-1), 156.2
(s, i), 153.9 (s, C-3), 142.1 (s, C-1'), 129.4 (d), 128.34 (d),
128.29 (d), 125.7 (d), 123.2 (d, p), 119.9 (d, o), 108.8 (d,
C-4), 52.1 (q, OMe), 39.9 (d, C-2), 35.3 (t, C-7), 31.7 (t,
C-6), 26.0 (t, C-5), 14.6 (q, 2-Me); HRMS: (EI, 70 eV)
Calculated: (C21H24O3) 324.1725 (M+) Found: 324.1721.
Methyl (E)-2-methyl-3-(naphthalen-1-yloxy)pent-3-
Methyl (E)-7-methoxy-2-methyl-3-phenoxyhept-3-
enoate (3ga)
m
p
o
i
O
3
O
2
4
5
1
OMe
6
7
MeO
Phenyl 5-methoxypent-1-ynyl ether 1g (0.532 mmol,
0.101 g) was added to a solution of InI3 (0.541 mmol,
0.268 g) and methylketene methyl trimethylsilyl acetal 2a
(1.61 mmol, 0.258 g) in dichloromethane (1 mL) at 0 °C.
The mixture was stirred for 1 h at 0 °C. The mixture was
poured into ethyl acetate (20 mL) and sat. NaHCO3 aq (10
mL), and then extracted with ethyl acetate (10 x 3 mL).
The collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a colorless oil (0.079 g, 53%).;
IR: (neat) 1745 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.29 (t, J = 7.7 Hz, 2H, m), 7.06 (t, J = 7.7 Hz, 1H, p), 7.01
(d, J = 7.7 Hz, 2H, o), 4.66 (t, J = 7.5 Hz, 1H, 4-H), 3.74-
3.69 (m, 4H, 2-H and COOMe), 3.35 (t, J = 6.2 Hz, 2H,
7-H2), 3.31 (s, 3H, 7-OMe), 2.11 (q, J = 7.5 Hz, 2H, 5-H2),
1.63-1.56 (m, 2H, 6-H2), 1.44 (d, J = 6.9 Hz, 3H, 2-Me);
13C NMR: (100 MHz, CDCl3) 173.1 (C, C-1), 156.1 (C,
i), 154.2 (C, C-3), 129.4 (CH, m), 123.2 (CH, p), 119.9
(CH, o), 108.2 (CH, C-4), 71.6 (CH2, C-7), 58.5 (CH3, 7-
OMe), 52.0 (CH3, 1-OMe), 39.8 (CH, C-2), 29.7 (CH2, C-
6), 22.9 (CH2, C-5), 14.6 (CH3, 2-Me); HRMS: (EI, 70
eV) Calculated: (C16H22O4) 278.1518 (M+) Found:
278.1517.
enoate (3ia)
7'
6'
5'
8'
9'
4'
3'
10'
1'
O
3
O
2'
2
4
1
OMe
5
A solution of 1-naphthyl prop-1-ynyl ether 1i (0.500
mmol, 0.0912 g) was added to a solution of InI3 (0.547
mmol, 0.269 g) and methylketene methyl trimethylsilyl
acetal 2a (1.60 mmol, 0.256 g) in dichloromethane (1 mL)
at 0 °C. The mixture was stirred for 1 h at 0 °C. The
mixture was poured into ethyl acetate (20 mL) and sat.
NaHCO3 aq (10 mL), and then extracted with ethyl acetate
(10 x 3 mL). The collected organic layer was dried over
MgSO4. The solvent was evaporated and the residue was
purified by silica gel column chromatography
(hexane/ethyl acetate = 88:12, column length 11 cm and
diameter 2.7 cm) and GPC to give the product as a
colorless oil (0.116 g, 82%).; IR: (neat) 1743 (C=O) cm-1;
Methyl (E)-2-methyl-3-phenoxy-7-phenylhept-3-enoate
(3ha)
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 29
1
2
1H NMR: (400 MHz, CDCl3) 8.06-8.05 (m, 1H), 7.83-
m
o
i
p
7.81 (m, 1H), 7.58 (d, J = 8.0 Hz, 1H, 4'-H), 7.47-7.46 (m,
2H), 7.39 (t, J = 8.0 Hz, 1H, 3'-H), 7.10 (d, J = 8.0 Hz, 1H,
2'-H), 4.58 (q, J = 7.2 Hz, 1H, 4-H), 3.82-3.75 (m, 4H,
OMe and 2-H), 1.60 (d, J = 7.2 Hz, 3H, 5-H3), 1.56 (d, J
= 7.2 Hz, 3H, 2-Me); 13C NMR: (100 MHz, CDCl3) 173.4
(s, C-1), 154.3 (s, C-3), 151.5 (s, C-1'), 134.8 (s, C-5'),
127.7 (d), 127.4 (s, C-10'), 126.3 (d), 125.8 (d), 125.7 (d),
123.6 (d, C-4'), 122.1 (s), 115.2 (d, C-2'), 102.0 (d, C-4),
52.1 (q, OMe), 39.8 (d, C-2), 14.6 (q, 2-Me), 11.4 (q, C-
5); HRMS: (EI, 70 eV) Calculated: (C17H18O3) 270.1256
(M+) Found: 270.1257.
3
4
5
6
7
8
9
O
O
2
4
5
1
3
OMe
1'
6
2'
3'
7
HA HB
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Phenyl(4-methylpent-4-en-1-ynyl)ether 1l (0.500 mmol,
0.086 g) was added to a solution of InI3 (0.533 mmol,
0.264 g) and allylketene methyl trimethylsilyl acetal 2e
(1.55 mmol, 0.289 g) in dichloromethane (1 mL) at 0 °C.
The mixture was stirred for 1 h at 0 °C. The mixture was
poured into ethyl acetate (20 mL) and sat. NaHCO3 aq (10
mL), and then extracted with ethyl acetate (10 x 3 mL).
The collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as colorless oil (0.085 g, 60%).;
IR: (neat) 1742 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.31 (t, J = 7.7 Hz, 2H, m), 7.08 (t, J = 7.7 Hz, 1H, o), 7.02
(d, J = 7.7 Hz, 2H, p), 5.85 (ddt, J = 17.1, 10.1 and 7.0 Hz,
1H, 2'-H), 5.17 (dd, J = 17.1 and 1.7 Hz, 1H, 3'-HA), 5.07
(dd, J = 10.1, 1.7 Hz, 1H, 3'-HB), 4.69-4.68 (m, 3H, 4-H,
7-H x 2), 3.72 (s, 3H, OMe), 3.63 (dd, J = 8.8 and 6.4 Hz,
1H, 2-H), 2.79-2.64 (m, 2H, 1'-H2), 2.70 (d, J = 8.0 Hz,
2H, 5-H2), 1.69 (s, 3H, 6-Me); 13C NMR: (100 MHz,
CDCl3) 172.1 (s, C-1), 155.5 (s, i), 153.1 (s, C-3), 144.3
(s, C-6), 135.4 (d, C-2'), 129.5 (d, m), 123.7 (d, p), 120.6
(d, q), 116.9 (t, C-3'), 110.6 (t, C-7), 106.4 (d, C-4), 52.1
(q, OMe), 45.3 (d, C-2), 34.6 (t, C-5), 33.1 (t, C-1'), 22.5
(q, 6-Me); HRMS: (EI, 70 eV) Calculated: (C18H22O3)
286.1569 (M+) Found: 286.1570.
Methyl (E)-3-ethoxy-2-methyl-4-phenylbut-3-enoate
(3ka)
O
3
O
2
4
1
OMe
1'
2'
3'
4'
Ethyl phenylethynyl ether 1k (0.517 mmol, 0.0756 g)
was added to a solution of InI3 (0.555 mmol, 0.275 g) and
methylketene methyl trimethylsilyl acetal 2a (1.79 mmol,
0.287 g) in dichloromethane (1 mL) at 0 °C. The mixture
was stirred for 1 h at 0 °C. The mixture was poured into
ethyl acetate (20 mL) and sat. NaHCO3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a colorless oil (0.0301 g, 25%).
The structure of 3ka was determined by 1H-NOE
experiment and 2D spectra of the compound.; IR: (neat)
1744 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3) 7.31 (t, J
= 7.5 Hz, 2H, 7-H x 2), 7.24 (d, J = 7.5 Hz, 2H, 6-H x 2),
7.18 (t, J = 7.5 Hz, 1H, 8-H), 5.68 (s, 1H, 4-H), 3.87-3.85
(m, 2H, OCH2CH3), 3.78 (q, J = 7.2 Hz, 1H, 2-H), 3.70 (s,
3H, OMe), 1.33 (d, J = 7.2 Hz, 3H, 2-Me), 1.31 (t, J = 6.9
Hz, 3H, OCH2CH3); 13C NMR: (100 MHz, CDCl3) 173.5
(s, C-1), 156.7 (s, C-3), 137.0 (s, C-5), 128.8 (d, C-6),
128.3 (d, C-7), 125.7 (d, C-8), 100.9 (d, C-4), 62.9 (t,
OCH2CH3), 52.0 (q, OMe), 40.5 (d, C-2), 14.9 (q, 2-Me),
14.3 (q, OCH2CH3); HRMS: (EI, 70 eV) Calculated:
234.1256 (M+) (C14H18O3) Found: 234.1260.
(Z)-(5-Methoxy-4-methyl-5-oxo-3-phenoxypent-2-en-2-
yl)indium diiodide bis-3,5-dibromopyridine complex
(4aa·3,5-Br2Py)
m
p
o
i
Br
Br
O
N
I
COOMe
3
5
In
2
4
I
1'
1
Me
N
2'
Br
Br
3'
Methyl (E)-2-allyl-6-methyl-3-phenoxyhepta-3,6-
dienoate (3le)
All preparations and manipulations were carried out
under an anhydrous N2 atmosphere using standard glove
box techniques. Phenyl prop-1-ynyl ether 1a (1.02 mmol,
0.135 g) was added to a solution of InI3 (1.02 mmol, 0.505
g) and methylketene methyl trimethylsilyl acetal 2a (3.70
mmol, 0.594 g) in CDCl3 (2 mL) at 0 °C. The mixture was
stirred for 1 h at 0 °C. To obtain a suitable crystal to X-ray
crystallography analysis, 3,5-dibromopyridine (2.62
mmol, 0.621 g) was added to the reaction mixture at room
temperature to give an immediately suspended solution.
16
ACS Paragon Plus Environment

Page 17 of 29
1
The Journal of Organic Chemistry
After the volatiles were removed in vacuo, the residue was
1742 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3) 7.27 (t, J
2
washed with hexane (2 mL x 5) and extracted using
diethyl ether (2 mL x 5). The volatiles were removed to
give alkenylindiums 3,5-dibromopyridine complex as a
white solid (0.567 g, 52%). The solid was recrystallized in
hexane/dichloromethane solvent to give a crystal suitable
for X-ray crystallography analysis. The structure of
4aa·3,5-Br2Py was confirmed by X-ray crystallography
analysis (CCDC 1908815).; 1H NMR: (400 MHz, CDCl3)
8.75 (d, J = 1.9 Hz, 4H, 1'-H x 4), 8.11 (t, J = 1.9 Hz, 2H,
3'-H x 2), 7.17 (t, J = 7.7 Hz, 2H, m), 6.95 (t, J = 7.7 Hz,
1H, p), 6.80 (d, J = 7.7 Hz, 2H, o), 3.64 (s, 3H, OMe), 3.52
(q, J = 7.2 Hz, 1H, 4-H), 1.97 (s, 3H, 1-H3), 1.31 (d, J =
7.2 Hz, 3H, 4-Me); 13C NMR: (100 MHz, CDCl3) 172.6
(s, C-5), 155.5 (s, i), 152.9 (s, C-3), 148.1 (d, C-1'), 143.6
(d, C-3'), 132.0 (s, C-2), 129.4 (d, m), 123.0 (d, p), 121.4
(s, C-2'), 116.9 (d, o), 52.2 (q, OMe), 40.7 (s, C-4), 16.8
(q, C-1), 15.0 (q, 4-Me).
= 7.8 Hz, 2H, m), 7.01-6.97 (m, 3H, o and p), 3.76 (q, J =
7.2 Hz, 1H, 2-H), 3.55 (s, 3H, OMe), 2.60 (s, 3H, 5-H3),
1.32 (d, J = 7.0 Hz, 3H, 2-Me); 13C NMR: (100 MHz,
CDCl3) 171.8 (C, C-1), 155.1 (C, i), 149.6 (C, C-3), 129.3
(CH, m), 122.3 (CH, p), 116.1 (CH, o), 88.5 (C, C-4), 52.1
(CH3, OMe), 40.2 (CH, C-2), 27.3 (CH3, C-5), 14.4 (CH3,
2-Me); HRMS: (EI, 70 eV) Calculated: 346.0066 (M+)
(C13H15IO3) Found: 346.0064.
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Methyl (Z)-2-(2-iodo-1-phenoxyprop-1-en-1-
yl)hexanoate (5ab)
m
p
o
i
O
1'
O
1
I
OMe
2
2'
3'
3
6
5
4
General procedure for the carboindation of alkynyl
ether 1 using InI3 and a silyl ketene acetal 2 to give an
iodinated enol ether 5 (Table 3)
Phenyl prop-1-ynyl ether 1a (0.481 mmol, 0.0636 g) was
added to a solution of InI3 (0.535 mmol, 0.265 g) and
butylketene methyl trimethylsilyl acetal 2b (1.45 mmol,
0.295 g) in dichloromethane (1 mL) at 0 °C. The mixture
was stirred for 1 h at 0 °C. Then, 0.45 M of I2 in a
tetrahydrofuran solution (4 mL) was added to the reaction
mixture at 0 °C, and the resultant mixture was stirred at
room temperature for 1 h. The mixture was poured into
ethyl acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a colorless oil (0.120 g, 64%).;
IR: (neat) 1743 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.27 (t, J = 8.0 Hz, 2H, m), 7.00 (t, J = 7.7 Hz, 1H, p), 6.95
(d, J = 7.7 Hz, 2H, o), 3.63 (t, J = 7.5 Hz, 1H, 2-H), 3.48
(s, 3H, OMe), 2.63 (s, 3H, 3'-H3), 1.89-1.70 (m, 2H, 3-H2),
1.32-1.27 (m, 4H, 4-H2 and 5-H2), 0.89 (t, J = 7.0 Hz, 3H,
6-H3); 13C NMR: (100 MHz, CDCl3) 171.3 (C, C-1), 155.1
(C, i), 148.8 (C, C-1'), 129.3 (CH, m), 122.3 (CH, p), 116.1
(CH, o), 89.4 (C, C-2'), 51.9 (CH, OMe), 45.9 (CH3, C-2),
29.3 (CH2), 28.7 (CH2, C-3), 27.5 (CH2, C-3'), 22.5 (CH2),
13.9 (CH3, C-6); HRMS: (EI, 70 eV) Calculated:
388.0535 (M+) (C16H21IO3) Found: 388.0531.
Alkynyl ether 1 (0.50 mmol) was added to a solution of
InI3 (0.50 mmol) and a silyl ketene acetal 2 (1.5 mmol) in
dichloromethane (1 mL). The mixture was stirred at 0 °C
for 1 h. And then, 4.5 M of I2 in tetrahydrofuran solution
(1.8 mmol/ 4 mL) was added, and then the resultant
mixture was stirred at room temperature for 1 h. The
mixture was quenched using 10 wt% Na2S2O3 aq (10 mL)
and was extracted with ethyl acetate (3 x 10 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
column chromatography.
Methyl (Z)-4-iodo-2-methyl-3-phenoxypent-3-enoate
(5aa)
m
p
o
i
O
O
I
2
1
OMe
3
4
5
Phenyl prop-1-ynyl ether 1a (0.469 mmol, 0.0620 g) was
added to a solution of InI3 (0.521 mmol, 0.258 g) and
methylketene methyl trimethylsilyl acetal 2a (1.55 mmol,
0.249 g) in dichloromethane (1 mL) at 0 °C. The mixture
was stirred for 1 h at 0 °C. Then, 0.45 M of I2 in
tetrahydrofuran solution (4 mL) was added to the reaction
mixture at 0 °C, and the resultant mixture was stirred at
room temperature for 1 h. The mixture was poured into
ethyl acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a colorless liquid (0.123 g,
Methyl (Z)-2-benzyl-4-iodo-3-phenoxypent-3-enoate
(5ac)
m
o
i
p
O
O
I
2
1
3
OMe
4
5
3'
1'
2'
4'
5'
Phenyl prop-1-ynyl ether 1a (0.548 mmol, 0.0724 g) was
added to a solution of InI3 (0.521 mmol, 0.258 g) and
benzylketene methyl trimethylsilyl acetal 2c (1.54 mmol,
1
76%). The structure of 5aa was determined by H-NOE
experiment and 2D spectra of the compound.; IR: (neat)
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 29
1
2
3
4
5
6
7
8
0.363 g) in dichloromethane (1 mL) at 0 °C. The mixture
eV) Calculated: 408.0222 (M+) (C18H17IO3) Found:
408.0225.
Methyl (Z)-2-allyl-4-iodo-3-phenoxypent-3-enoate (5ae)
was stirred for 1 h at 0 °C. Then, 0.45 M of I2 in
tetrahydrofuran solution (4 mL) was added to the reaction
mixture at 0 °C, and the resultant mixture was stirred at
room temperature for 1 h. The mixture was poured into
ethyl acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a colorless oil (0.152 g, 69%).;
IR: (neat) 1743 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.27-7.21 (m, 7H, 1'-Ph and m), 7.03-6.96 (m, 3H, o and
p), 3.89 (dd, J = 8.5, 6.5 Hz, 1H, 2-H), 3.39 (s, 3H, OMe),
3.15 (dd, J = 13.3, 6.5 Hz, 1H, 1'-HH), 3.08 (dd, J = 14.0,
8.7 Hz, 1H, 1'-HH), 2.29 (s, 3H, 5-H3); 13C NMR: (100
MHz, CDCl3) 170.6 (s, C-1), 155.0 (s, i), 147.4 (s, C-3),
138.3 (s, C-2'), 129.3 (d), 129.1 (d), 128.3 (d), 126.6 (d),
122.3 (d, p), 116.1 (s, o), 90.7 (s, C-4), 51.9 (q, OMe),
48.0 (d, C-2), 35.0 (t, C-1'), 27.2 (q, C-5'); HRMS: (EI, 70
eV) Calculated: 422.0379 (M+) (C19H19IO3) Found:
422.0380.
m
o
i
p
O
O
I
2
9
1
3
OMe
4
5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1'
2'
3'
HA HB
Phenyl prop-1-ynyl ether 1a (0.545 mmol, 0.0720 g) was
added to a solution of InI3 (0.517 mmol, 0.256 g) and
allylketene methyl trimethylsilyl acetal 2e (1.79 mmol,
0.335 g) in dichloromethane (1 mL) at 0 °C. The mixture
was stirred for 1 h at 0 °C. Then, 0.45 M of I2 in a
tetrahydrofuran solution (4 mL) was added to the reaction
mixture at 0 °C, and the resultant mixture was stirred at
room temperature for 1 h. The mixture was poured into
ethyl acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a brown oil (0.133 g, 69%).;
IR: (neat) 1741 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.27 (t, J = 8.0 Hz, 2H, m), 7.00 (t, J = 8.0 Hz, 1H, p), 6.95
(d, J = 8.0 Hz, 2H, o), 5.76 (ddt, J = 16.9, 10.3, 6.6 Hz,
1H, 2'-H), 5.11 (dd, J = 16.9, 1.5 Hz, 1H, 3'-HA), 5.06 (dd,
J = 10.3, 1.5 Hz, 1H, 3'-HB), 3.73 (t, J = 6.6 Hz, 1H, 4-H),
3.48 (s, 3H, OMe), 2.62 (s, 3H, 5-H3), 2.57-2.47 (m, 2H,
1'-H2); 13C NMR: (100 MHz, CDCl3) 170.6 (s, C-1), 155.1
(s, i), 148.0 (s, C-3), 134.6 (d, C-2'), 129.3 (d, m), 122.3
(d, p), 117.4 (t, C-3'), 116.1 (d, o), 89.8 (s, C-4), 52.0 (q,
OMe), 46.0 (d, C-2), 33.1 (t, C-1'), 27.6 (q, C-5); HRMS:
(EI, 70 eV) ;Calculated: 372.0222 (M+) (C15H17O3I)
Found: 372.0216.
Methyl (Z)-4-iodo-3-phenoxy-2-phenylpent-3-enoate
(5ad)
m
o
i
O
O
I
2
1
OMe
3
4
5
1'
4'
2'
3'
Phenyl prop-1-ynyl ether 1a (0.479 mmol, 0.0633 g) was
added to a solution of InI3 (0.520 mmol, 0.258 g) and
phenylketene methyl trimethylsilyl acetal 2d (1.52 mmol,
0.337 g) in dichloromethane (1 mL) at 0 °C. The mixture
was stirred for 1 h at 0 °C. Then, 0.45 M of I2 in a
tetrahydrofuran solution (4 mL) was added to the reaction
mixture at 0 °C, and the resultant mixture was stirred at
room temperature for 1 h. The mixture was poured into
ethyl acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a colorless oil (0.140 g, 68%).;
IR: (neat) 1743 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.33-7.21 (m, 7H, 2-Ph and m), 6.97 (t, J = 7.7 Hz, 1H, p),
6.91 (d, J = 7.7 Hz, 2H, o), 4.93 (s, 1H, 2-H), 3.53 (s, 3H,
OMe), 2.60 (s, 3H, 5-H3); 13C NMR: (100 MHz, CDCl3)
170.0 (C, C-1), 155.0 (C, i), 147.9 (C, C-3), 134.6 (C, C-
1’), 129.2 (CH), 129.1 (CH), 128.4 (CH), 127.7 (CH),
122.1 (CH, p), 116.0 (CH, o), 89.8 (C, C-4), 52.4 (C,
OMe), 51.8 (CH3, C-2), 27.7 (CH3, C-5); HRMS: (EI, 70
Methyl (Z)-2-(3-chloropropyl)-4-iodo-3-phenoxypent-3-
enoate (5af)
m
p
o
i
O
O
1
I
2
OMe
3'
3
4
5
1'
2'
Cl
Phenyl prop-1-ynyl ether 1a (1.05 mmol, 0.139 g) was
added to a solution of InI3 (1.07 mmol, 0.530 g) and 3-
chloropropylketene methyl trimethylsilyl acetal 2f (3.08
mmol, 0.687 g) in dichloromethane (2 mL)at 0 °C. The
mixture was stirred for 1 h at 0 °C. Then, 0.45 M of I2 in
a tetrahydrofuran solution (8 mL) was added to the
reaction mixture at 0 °C, and the resultant mixture was
stirred at room temperature for 1 h. The mixture was
poured into ethyl acetate (25 mL) and sat. Na2S2O3 aq (10
18
ACS Paragon Plus Environment

Page 19 of 29
1
The Journal of Organic Chemistry
m
mL), and then extracted with ethyl acetate (10 x 3 mL).
The collected organic layer was dried over MgSO4. The
2
3
p
o
i
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a yellow oil (0.367 g, 86%).;
IR: (neat) 1742 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.27 (t, J = 7.7 Hz, 2H, m), 7.01 (t, J = 7.7 Hz, 1H, p), 6.95
(d, J = 7.7 Hz, 2H, o), 3.66 (t, J = 8.9 Hz, 1H, 2-H), 3.53
(t, J = 6.5 Hz, 2H, 3'-H2), 3.49 (s, 3H, OMe), 2.63 (s, 3H,
5-H3), 2.04-1.73 (m, 4H, 1'-H2 and 2'-H2); 13C NMR: (100
MHz, CDCl3) 170.7 (s, C-1), 154.8 (s, i), 148.2 (s, C-3),
129.3 (d, m), 122.5 (d, p), 116.1 (d, o), 89.8 (d, C-4), 52.0
(q, OMe), 45.0 (d, C-2), 44.4 (t, C-3'), 30.0 (t, C-2'), 27.5
(q, C-5), 26.2 (t, C-1'); HRMS: (EI, 70 eV) Calculated:
407.9989 (M+) (C15H18ClO3I) Found: 407.9991.
4
5
6
7
8
9
O
O
I
2
1
OMe
3
4
5
Phenyl prop-1-ynyl ether 1a (0.480 mmol, 0.0635 g) was
added to a solution of InI3 (0.518 mmol, 0.257 g) and
dimethylketene methyl trimethylsilyl acetal 2h (1.43
mmol, 0.250 g) in dichloromethane (1 mL) at 0 °C. The
mixture was stirred for 1 h at 0 °C. Then, 0.45 M of I2 in
a tetrahydrofuran solution (4 mL) was added to the
reaction mixture at 0 °C, and the resultant mixture was
stirred at room temperature for 1 h. The mixture was
poured into ethyl acetate (20 mL) and sat. Na2S2O3 aq (10
mL), and then extracted with ethyl acetate (10 x 3 mL).
The collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a white solid (0.093 g, 54%).
The solid was recrystallized in dichloromethane solvent to
give a crystal suitable for X-ray crystallography analysis.
The structure of 5ah was confirmed by X-ray
crystallography analysis (CCDC 1908814).; mp: 52-
53 °C; IR: (KBr) 1742 (C=O) cm-1; 1H NMR: (400 MHz,
CDCl3) 7.31 (t, J = 7.7 Hz, 2H, m), 7.08 (d, J = 7.7 Hz,
2H, o), 7.01 (t, J = 7.7 Hz, 1H, p), 3.79 (s, 3H, OMe), 2.44
(s, 3H, 5-H3), 1.41 (s, 6H, 2-Me x 2); 13C NMR: (100 MHz,
CDCl3) 176.2 (C, C-1), 156.3 (C, i), 152.8 (C, C-3), 129.5
(CH, m), 121.7 (CH, p), 115.3 (CH, o), 89.2 (C, C-4), 52.6
(CH3, OMe), 47.7 (C, C-2), 27.3 (CH3, C-5), 25.6 (CH3,
2-Me); HRMS: (EI, 70 eV) Calculated: 360.0222 (M+)
(C14H17IO3) Found: 360.0222.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ethyl (Z)-4-iodo-3-phenoxy-2-(thien-2-yl)pent-3-
enoate(5ag)
m
p
o
i
O
O
I
2
1
OEt
3
2'
4
5
1'
S
3'
4'
Phenyl prop-1-ynyl ether 1a (0.468 mmol, 0.0619 g) was
added to a solution of InI3 (0.531 mmol, 0.263 g) and
thien-2-ylketene methyl trimethylsilyl acetal 2g (1.79
mmol, 0.409 g) in dichloromethane (1 mL) at 0 °C. The
mixture was stirred for 1 h at 0 °C. Then, 0.45 M of I2 in
a tetrahydrofuran solution (4 mL) was added to the
reaction mixture at 0 °C, and the resultant mixture was
stirred at room temperature for 1 h. The mixture was
poured into ethyl acetate (20 mL) and sat. Na2S2O3 aq (10
mL), and then extracted with ethyl acetate (10 x 3 mL).
The collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a yellow oil (0.161 g, 20%).;
IR: (neat) 1741 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.22-7.26 (m, 3H, 4'-H and m), 7.01-6.89 (m, 5H, 2'-H, 3'-
H, o and p), 5.14 (s, 1H, 2-H), 4.05-3.98 (m, 2H,
OCH2CH3), 2.64 (s, 3H, 5-H3), 1.18 (t, J = 7.2 Hz, 3H,
OCH2CH3); 13C NMR: (100 MHz, CDCl3) 168.7 (s, C-1),
155.0 (s, i), 147.9 (s, C-3), 136.2 (s, C-1'), 129.3 (d, m),
127.2 (d, C-2'), 126.3 (d, C-3'), 125.8 (d, C-4'), 122.4 (d,
p), 116.2 (d, o), 90.0 (s, C-4), 62.0 (t, OCH2CH3), 47.1 (d,
C-2), 27.8 (q, C-5), 13.9 (q, OCH2CH3); HRMS: (EI, 70
eV) Calculated: 427.9943 (M+) (C17H17SIO3) Found:
427.9938.
Methyl (Z)-1-(2-iodo-1-phenoxyprop-1-en-1-
yl)cyclohexane-1-carboxylate (5ai)
m
o
i
p
O
O
1'
I
2'
3'
OMe
1
4
2
3
Phenyl prop-1-ynyl ether 1a (0.535 mmol, 0.0707 g) was
added to a solution of InI3 (0.503 mmol, 0.249 g) and
(methoxytrimethylsiloxymethylene)cyclohexane 2i (1.62
mmol, 0.348 g) in dichloromethane (1 mL) at 0 °C. The
mixture was stirred for 1 h at 0 °C. Then, 0.45 M of I2 in
a tetrahydrofuran solution (4 mL) was added to the
reaction mixture at 0 °C, and the resultant mixture was
stirred at room temperature for 1 h. The mixture was
poured into ethyl acetate (20 mL) and sat. Na2S2O3 aq (10
mL), and then extracted with ethyl acetate (10 x 3 mL).
The collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
Methyl (Z)-4-iodo-2-methyl-3-phenoxypent-3-enoate
(5ah)
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 29
1
2
3
4
5
6
7
8
88:12, column length 11 cm and diameter 2.7 cm) and
29.4 (CH3, C-5), 28.4 (CH3, 2-Me); HRMS: (EI, 70 eV)
GPC to give the product as a yellow solid (0.161 g, 80%).;
mp: 65-69 °C; IR: (KBr) 1730 (C=O) cm-1; 1H NMR: (400
MHz, CDCl3) 7.30 (t, J = 8.0 Hz, 2H, m), 7.07 (d, J = 8.0
Hz, 2H, o), 7.00 (t, J = 8.0 Hz, 1H, p), 3.77 (s, 3H, OMe),
Calculated: 389.0277 (M+) (C18H16NOI) Found: 389.0280.
(Z)-4-Iodo-2-ethyl-3-phenoxy-2-phenylpent-3-enenitrile
(7ab)
m
p
o
2.53 (s, 3H, 3'-H3), 2.07 (m, 2H), 1.80-1.28 (m, 8H); 13
C
NMR: (100 MHz, CDCl3) 175.0 (C, 1-COOMe), 156.3 (C,
i), 152.9 (C, C-1'), 129.4 (CH, m), 121.6 (CH, p), 115.3
(CH, o), 90.6 (C, C-2'), 52.6 (C, C-1), 52.2 (CH3, OMe),
33.7 (CH2), 27.3 (CH3, C-3'), 25.1 (CH2), 22.6 (CH2);
HRMS: (CI, 70 eV) Calculated: 401.0614 ([M + H]+)
(C17H22IO3) Found: 401.0613.
General procedure for the carboindation of alkynyl
ether 1 using InI3 and a silyl ketene imine 6 to give an
iodinated enol ether 7 (Table 4)
Alkynyl ether 1 (0.50 mmol) was added to a solution of
InI3 (0.50 mmol) and silyl ketene imine 6 (1.0 mmol) in
dichloromethane (1 mL). The mixture was stirred at 0 °C
for 1 h. And then, iodobenzene diacetate (1.0 mmol) was
added, and the resultant mixture was stirred at room
temperature for 1 h. The mixture was quenched using 10
wt% Na2S2O3 aq (10 mL) and was extracted with ethyl
acetate (3 x 10 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by column chromatography.
i
O
3
1
9
I
CN
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4
5
1'
2'
Et
3'
4'
Phenyl prop-1-ynyl ether 1a (0.539 mmol, 0.0712 g) was
added to a solution of InI3 (0.572 mmol, 0.283 g) and tert-
butyldimethylsilyl ethylphenylketene imine 6b (1.15
mmol, 0.298 g) in dichloromethane (1 mL) at 0 °C. The
mixture was stirred for 1 h at 0 °C. Then, iodobenzene
diacetate (0.944 mmol, 0.304 g) was added to the reaction
mixture at 0 °C, and the resultant mixture was stirred at
room temperature for 1 h. The mixture was poured into
ethyl acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a yellow solid (0.196 g, 90%).
The solid was recrystallized in dichloromethane solvent to
give a crystal suitable for X-ray crystallography analysis.
The structure of 7ab was confirmed by X-ray
crystallography analysis (CCDC 1908816).; mp: 121-
124 °C; IR: (KBr) 2235 (C≡N) cm-1; 1H NMR: (400 MHz,
CDCl3) 7.48 (d, J = 8.2 Hz, 2H, 2'-H x 2), 7.40-7.34 (m,
5H, 3'-H x 2, 4'-H and m), 7.08 (m, 3H, o and p), 2.34 (s,
3H, 5-H3), 2.16-2.01 (m, 2H, 2-CH2CH3), 0.68 (t, J = 7.2
Hz, 3H, 2-CH2CH3); 13C NMR: (100 MHz, CDCl3) 156.0
(s, i), 148.9 (s, C-3), 138.3 (s, C-1'), 130.1 (d, m), 128.9
(d), 128.0 (d), 126.1 (d, C-2'), 122.4 (d, p), 119.4 (s, C-1),
114.9 (d, o), 94.9 (s, C-4), 50.8 (s, C-2), 32.8 (t, 2-
CH2CH3), 28.3 (q, C-5), 8.9 (q, 2-CH2CH3).; HRMS: (EI,
70 eV) Calculated: 403.0433 (M+) (C19H18NOI) Found:
403.0428.
(Z)-4-Iodo-2-methyl-3-phenoxy-2-phenylpent-3-
enenitrile (7aa)
m
p
o
i
O
3
1
I
CN
2
4
5
1'
2'
3'
4'
Phenyl prop-1-ynyl ether 1a (0.536 mmol, 0.0708 g) was
added to a solution of InI3 (0.548 mmol, 0.272 g) and tert-
butyldimethylsilyl methylphenylketene imine 6a (1.03
mmol, 0.253 g) in dichloromethane (1 mL) at 0 °C. The
mixture was stirred for 1 h at 0 °C. Then, iodobenzene
diacetate (1.07 mmol, 0.344 g) was added to the reaction
mixture at 0 °C, and the resultant mixture was stirred at
room temperature for 1 h. The mixture was poured into
ethyl acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a colorless oil (0.187 g, 90%).;
IR: (neat) 2236 (C≡N) cm-1; 1H NMR: (400 MHz, CDCl3)
7.53 (d, J = 7.6 Hz, 2H, 2'-H x 2), 7.42-7.36 (m, 5H, m, 3'-
H x 2 and 4'-H), 7.10-7.08 (m, 3H, p, o), 2.35 (s, 3H, 2-
Me), 1.70 (s, 3H, 5-H3); 13C NMR: (100 MHz, CDCl3)
155.8 (C, i), 148.0 (C, C-3), 140.9 (C, C-1'), 130.1 (CH,
m), 129.3 (CH), 128.0 (CH), 125.1 (CH, C-2'), 122.5 (CH),
120.6 (C, C-1), 114.9 (CH), 94.5 (C, C-4), 45.2 (C, C-2),
(Z)-4-Iodo-2-isopropyl-3-phenoxy-2-phenylpent-3-
enenitrile (7ac)
m
p
o
i
O
3
I
2
4
5
1
1'
2'
NC
3'
4'
Phenyl prop-1-ynyl ether 1a (0.495 mmol, 0.0655 g) was
added to a solution of InI3 (0.561 mmol, 0.278 g) and tert-
butyldimethylsilyl isopropylphenylketene imine 6c (1.02
mmol, 0.280 g) in dichloromethane (1 mL) at 0 °C. The
20
ACS Paragon Plus Environment

Page 21 of 29
1
The Journal of Organic Chemistry
mixture was stirred for 1 h at 0 °C. Then, iodobenzene
(Z)-2-Ethyl-4-iodo-2-(4-methoxyphenyl)-3-
2
3
4
5
6
7
8
9
diacetate (1.01 mmol, 0.304 g) was added to the reaction
mixture at 0 °C, and the resultant mixture was stirred at
room temperature for 1 h. The mixture was poured into
ethyl acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a yellow solid (0.0862 g,
phenoxypent-3-enenitrile (7ae)
m
p
o
i
O
3
1
I
CN
2
4
5
1'
2'
Et
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3'
4'
41%).; mp: 101-111 °C; IR: (KBr) 2234 (C≡N) cm-1; H
1
OMe
Phenyl prop-1-ynyl ether 1a (0.536 mmol, 0.0709 g) was
NMR: (400 MHz, CDCl3); 7.44-7.26 (m, 7H, 2-Ph and m),
7.04 (t, J = 7.7 Hz, 1H, p), 6.97 (d, J = 7.7 Hz, 2H, o),
2.62-2.52 (m, 1H, 2-CH(CH3)2), 2.43 (s, 3H, 5-H3), 1.06
(d, J = 6.5 Hz, 3H, 2-CH(CH3)(CH3)), 0.83 (d, J = 6.5 Hz,
3H, 2-CH(CH3) (CH3)); 13C NMR: (100 MHz, CDCl3)
155.6 (s, i), 148.4 (s, C-3), 135.2 (s, C-1'), 129.7 (d, m),
128.4 (d), 128.0 (s), 127.7 (s), 122.3 (s, p), 119.8 (s, C-1),
115.3 (s, o), 95.0 (s, C-4), 55.1 (s, C-2), 34.7 (d, 2-
CH(CH3)2), 29.2 (q, C-5), 19.4 (q, 2-CH(CH3)(CH3)),
18.8 (q, 2-CH(CH3)(CH3)); HRMS: (EI, 70 eV)
Calculated: 417.0590 (M+) (C20H20NOI) Found: 417.0585.
(Z)-4-Iodo-3-phenoxy-2,2-diphenylpent-3-enenitrile
added to a solution of InI3 (0.567 mmol, 0.281 g) and tert-
butyldimethylsilyl ethyl(4-methoxyphenyl)ketene imine
6e (0.984 mmol, 0.280 g) in dichloromethane (1 mL) at
0 °C. The mixture was stirred for 1 h at 0 °C. Then,
iodobenzene diacetate (0.998 mmol, 0.321 g) was added
to the reaction mixture at 0 °C, and the resultant mixture
was stirred at room temperature for 1 h. The mixture was
poured into ethyl acetate (20 mL) and sat. Na2S2O3 aq (10
mL), and then extracted with ethyl acetate (10 x 3 mL).
The collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a white solid (0.156 g, 67%).;
(7ad)
m
p
o
mp: 130-138 °C;IR: (KBr) 2235 (C≡N) cm-1; H NMR:
1
i
O
(400 MHz, CDCl3) 7.40-7.35 (m, 4H, m and 2'-H x 2),
7.08-7.06 (m, 3H, o and p), 6.91 (d, J = 8.9 Hz, 2H, 3'-H
x 2), 3.83 (s, 3H, OMe), 2.37 (s, 3H, 5-H3), 2.08-2.02 (m,
3
I
2
4
5
1
1'
2'
2H, 2-CH2CH3), 0.69 (t, J = 7.3 Hz, 3H, 2-CH2CH3); 13
C
NC
3'
NMR: (100 MHz, CDCl3) 159.0 (s, C-4'), 156.0 (s, i),
149.1 (s, C-3), 130.2 (s, C-1'), 130.0 (d, m), 127.3 (d, C-
2'), 122.4 (d, p), 119.6 (s, C-1), 114.8 (d, o), 114.1 (d, C-
3'), 94.8 (s, C-4), 55.3 (q, OMe), 50.1 (s, C-2), 32.8 (t, 2-
CH2CH3), 28.3 (q, C-5), 8.9 (q, 2-CH2CH3); HRMS: (EI,
70 eV) Calculated: 433.0539 (M+) (C20H20NO2I) Found:
433.0536.
4'
Phenyl prop-1-ynyl ether 1a (0.532 mmol, 0.0703 g) was
added to a solution of InI3 (0.551 mmol, 0.273 g) and tert-
butyldimethylsilyl diphenylketene imine 6d (1.00 mmol,
0.308 g) in dichloromethane (1 mL) at 0 °C. The mixture
was stirred for 1 h at 0 °C. Then iodobenzene diacetate
(0.995 mmol, 0.321 g) was added to the reaction mixture
at 0 °C, and the resultant mixture was stirred at room
temperature for 1 h. The mixture was poured into ethyl
acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and then
extracted with ethyl acetate (10 x 3 mL). The collected
organic layer was dried over MgSO4. The solvent was
evaporated and the residue was purified by silica gel
column chromatography (hexane/ethyl acetate = 88:12,
column length 11 cm and diameter 2.7 cm) and GPC to
give the product as a yellow solid (0.202 g, 84%).; mp:
107-114 °C; IR: (KBr) 2239 (C≡N) cm-1; 1H NMR: (400
MHz, CDCl3) 7.35-7.18 (m, 10H, 2-Ph x 2), 7.06 (t, J =
7.9 Hz, 2H, m), 6.86 (t, J = 7.9 Hz, 1H, p), 6.60 (d, J = 7.9
Hz, 2H, o), 2.53 (s, 3H, 5-H3); 13C NMR: (100 MHz,
CDCl3) 154.1 (C, i), 146.3 (C, C-3), 137.4 (C, C-1'), 129.1
(CH), 128.4 (CH, m), 128.1 (CH), 127.9 (CH), 122.1 (CH,
p), 120.2 (C, C-1), 115.0 (CH, o), 95.3 (C, C-4), 54.8 (C,
C-2), 29.6 (CH3, C-5); HRMS: (EI, 70 eV) Calculated:
451.0433 (M+) (C23H18NOI) Found: 451.0430.
(Z)-2-(4-Chlorophenyl)-2-ethyl-4-iodo-3-phenoxypent-
3-enenitrile (7af)
m
p
o
i
O
3
1
I
CN
2
4
5
1'
Et
2'
3'
4'
Cl
Phenyl prop-1-ynyl ether 1a (0.527 mmol, 0.0696 g) was
added to a solution of InI3 (0.547 mmol, 0.271 g) and tert-
butyldimethylsilyl ethyl(4-chlorophenyl)ketene imine 6f
(1.08 mmol, 0.316 g) in dichloromethane (1 mL) at 0 °C.
The mixture was stirred for 1 h at 0 °C. Then, iodobenzene
diacetate (1.02 mmol, 0.329 g) was added to the reaction
mixture at 0 °C, and the resultant mixture was stirred at
21
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 29
1
2
3
4
5
6
7
8
m
room temperature for 1 h. The mixture was poured into
p
o
ethyl acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a white solid (0.175 g, 76%).;
i
O
I
2
CN
3
4
1
Phenyl prop-1-ynyl ether 1a (1.19 mmol, 0.157 g) was
added to a solution of InI3 (1.52 mmol, 0.756 g) and
trimethylsilyl cyanide (5.90 mmol, 0.586 g) in
dichloromethane (3 mL) at 0 °C. The mixture was stirred
for 1 h at 0 °C. Then, iodobenzene diacetate (2.63 mmol,
0.847 g) was added to the reaction mixture at 0 °C, and
the resultant mixture was stirred at room temperature for
1 h. The mixture was poured into ethyl acetate (20 mL)
and sat. Na2S2O3 aq (20 mL), and then extracted with ethyl
acetate (20 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by silica gel column chromatography
(hexane/ethyl acetate = 88:12, column length 11 cm and
diameter 2.7 cm) to give the product as a yellow oil (0.194
9
1
mp: 120-134 °C; IR: (KBr) 2236 (C≡N) cm-1; H NMR:
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(400 MHz, CDCl3) 7.41-7.39 (m, 6H, m, 2'-H x 2 and 3'-
H x 2), 7.09 (t, J = 7.7 Hz, 1H, p), 7.05 (d, J = 7.7 Hz, 2H,
o), 2.36 (s, 3H, 5-H3), 2.07 (q, J = 7.3 Hz, 2H, CH2CH3),
0.69 (t, J = 7.3 Hz, 3H, CH2CH3); 13C NMR: (100 MHz,
CDCl3) 155.9 (s, i), 148.5 (s, C-3), 136.9 (s), 134.0 (s),
130.1 (d, m), 129.1 (d), 127.5 (d), 122.6 (d, p), 119.0 (s,
C-1), 114.8 (d, o), 95.0 (s, C-4), 50.3 (s, C-2), 32.7 (t,
CH2CH3), 28.3 (q, C-5), 8.9 (q, CH2CH3); HRMS: (EI, 70
eV) Calculated: 437.0043 (M+) (C19H17ClNOI) Found:
437.0043.
(Z)-4-Iodo-2-methyl-3-phenoxy-2-(thien-2-yl)pent-3-
enenitrile (7ag)
m
1
g, 57%).; IR: (neat) 2215 (C≡N) cm-1; H NMR: (400
p
o
MHz, CDCl3) 7.37 (t, J = 7.7 Hz, 2H, m), 7.17 (t, J = 7.7
Hz, 1H, p), 7.03 (d, J = 7.7 Hz, 2H, o), 2.83 (s, 3H, 4-H3);
13C NMR: (100 MHz, CDCl3) 154.3 (s, i), 129.9 (s, m),
128.1 (s, C-1), 124.6 (s, p), 116.9 (s, o), 110.8 (s, C-2),
104.5 (s, C-3), 27.9 (q, C-4); HRMS: (EI, 70 eV)
Calculated: 284.9651 (M+) (C10H8NOI) Found: 284.9653.
(Z)-(3-Phenoxy-5-phenylpent-2-en-4-yn-2-yl)indium
diiodide bis-3,5-dibromopyridine complex (11·3,5-
i
O
3
1
I
CN
2
4
5
1'
S
2'
4'
3'
Phenyl prop-1-ynyl ether 1a (0.534 mmol, 0.0706 g) was
added to a solution of InI3 (0.554 mmol, 0.274 g) and tert-
butyldimethylsilyl methyl(thien-2-yl)ketene imine 6g
(1.04 mmol, 0.261 g) in dichloromethane (1 mL) at 0 °C.
The mixture was stirred for 1 h at 0 °C. Then, iodobenzene
diacetate (1.02 mmol, 0.329 g) was added to the reaction
mixture at 0 °C, and the resultant mixture was stirred at
room temperature for 1 h. The mixture was poured into
ethyl acetate (20 mL) and sat. Na2S2O3 aq (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as a yellow oil (0.058 g, 27%).;
IR: (neat) 2237 (C≡N) cm-1; 1H NMR: (400 MHz, CDCl3)
7.36 (t, J = 7.7 Hz, 2H, m), 7.29 (dd, J = 5.2, 1.2 Hz, 1H,
2'-H), 7.18 (dd, J = 3.7, 1.2 Hz, 1H, 4'-H), 7.07 (t, J = 7.7
Hz, 1H, p), 7.03 (d, J = 7.7 Hz, 2H, o), 6.96 (dd, J = 5.2,
3.7 Hz, 1H, 3'-H), 2.57 (s, 3H, 5-H3), 1.84 (s, 3H, 2-Me);
13C NMR: (100 MHz, CDCl3) 155.6 (C, i), 147.4 (C, C-
3), 143.9 (C, C-1'), 130.0 (CH, m), 126.8 (CH, C-3'), 125.9
(CH, C-2'), 125.3 (CH, C-4'), 122.6 (CH, p), 120.1 (C, C-
1), 114.9 (CH, o), 95.8 (C, C-4), 41.5 (C, C-2), 29.9 (CH3,
2-Me), 28.7 (CH3, C-5); HRMS: (EI, 70 eV) Calculated:
394.9841 (M+) (C16H14NOIS) Found: 394.9844.
Br2Py)
m
p
o
i
Br
Br
O
N
I
3
In
2
4
I
1'
5
1
Me
N
2'
Br
Br
3'
All preparations and manipulations were carried out
under an anhydrous N2 atmosphere using standard glove
box techniques. Phenyl prop-1-ynyl ether 1a (1.02 mmol,
0.135 g) was added to a solution of InI3 (0.496 mmol,
0.246 g) and tributyl(phenylethynyl)stannane 10 (1.44
mmol, 0.563 g) in CH2Cl2 (2 mL) at 0 °C. The mixture
was stirred for 1 h at 0 °C. To obtain a suitable crystal for
X-ray crystallography analysis, 3,5-dibromopyridine
(1.91 mmol, 0.451 g) was added to the reaction mixture at
room temperature to give an immediately suspended
solution. After the volatiles were removed in vacuo, the
residue was washed with hexane (2 mL x 5), extracted by
diethyl ether (2 mL x 5), and then the volatiles were
removed in vacuo to give a pale brown solid. This solid
was washed with hexane (2 mL x 5) and then the volatiles
were removed in vacuo to give a crude product that
included a small amount of Bu3SnX. The crude product
(Z)-3-Iodo-2-phenoxybut-2-enenitrile (9)
22
ACS Paragon Plus Environment

Page 23 of 29
1
The Journal of Organic Chemistry
was
purified
by
recrystallization
of
a
allyltributylstannane 13 (1.65 mmol, 0.548 g) in
dichloromethane (1 mL) at 0 °C. The mixture was stirred
for 1 h at 0 °C. Then, iodobenzene diacetate (1.00 mmol,
0.323 g) was added to the reaction mixture at 0 °C, and
the resultant mixture was stirred at room temperature for
1 h. The mixture was poured into ethyl acetate (20 mL)
and sat. Na2S2O3 aq (10 mL), and then extracted with ethyl
acetate (10 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by silica gel column chromatography
(hexane/ethyl acetate = 95:5, column length 11 cm and
diameter 2.7 cm) and GPC to give the product as a yellow
oil (0.130 g, 81%). The structure of 15 was determined by
1H-NOE experiment and 2D spectra of the compound.; IR:
2
3
4
5
6
7
8
9
hexane/dichloromethane solution to yield the desired
complex as a white solid (31%, 0.171 g). The structure of
11·3,5-Br2Py was confirmed by X-ray crystallography
analysis (CCDC 1908821). 1H NMR: (400 MHz, CDCl3)
8.70 (d, J = 1.9 Hz, 4H, 1'-H x 4), 8.06 (t, J = 1.9 Hz, 2H,
3'-H x 2), 7.29-7.23 (m, 7H, 5-Ph and m), 7.00 (t, J = 7.7
Hz, 1H, p), 6.85 (d, J = 7.7 Hz, 2H, o), 2.23 (s, 3H, 1-
H3);13C NMR: (100 MHz, CDCl3) 155.2 (s, i), 148.4 (d,
C-1'), 143.0 (d, C-3' ), 140.8 (br, C-2), 138.0 (s, C-3),
131.6 (d), 129.1 (d, m), 128.9 (d), 128.3 (d), 123.1 (d, p),
121.9 (s, C-6), 121.4 (s, C-2'), 117.1 (d, o), 96.5 (s, C-5),
80.9 (s, C-4), 18.6 (q, C-1).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(Z)-4-Iodo-3-phenoxy-1-phenyl-pent-3-en-1-yne (12)
(neat) 1593 (C=C) cm-1; H NMR: (400 MHz, CDCl3)
1
m
p
o
7.30 (t, J = 7.7 Hz, 2H, m), 7.04 (t, J = 7.7 Hz, 1H, p), 6.92
(d, J = 7.7 Hz, 2H, o), 5.74 (ddt, J = 16.2, 10.9, 6.3 Hz,
1H, 2-H), 5.05 (d, J = 10.9 Hz, 1H, 1-HA), 5.04 (d, J =
16.2 Hz, 1H, 1-HB), 3.06 (d, J = 6.3 Hz, 2H, 3-H2), 2.54
(s, 3H, 6-H3); 13C NMR: (100 MHz, CDCl3) 154.9 (s, i),
150.1 (s, C-4), 132.5 (d, C-2), 129.6 (d, m), 122.5 (d, p),
117.0 (t, C-1), 116.8 (d, o), 84.6 (s, C-5), 32.5 (t, C-3),
26.8 (q, C-6); HRMS: (EI, 70 eV) Calculated: 300.0011
(M+) (C12H13OI) Found: 300.0012.
i
O
I
3
4
5
2
1
1'
Phenyl prop-1-ynyl ether 1a (0.537 mmol, 0.0710 g) was
added to a solution of InI3 (0.560 mmol, 0.278 g) and
tributyl(phenylethynyl)stannane 10 (1.27 mmol, 0.497 g)
in dichloromethane (1 mL) at 0 °C. The mixture was
stirred for 1 h at 0 °C. Then, iodobenzene diacetate (1.09
mmol, 0.354 g) was added to the reaction mixture at 0 °C,
and the resultant mixture was stirred at room temperature
for 1 h. The mixture was poured into ethyl acetate (20 mL)
and sat. Na2S2O3 aq (10 mL), and then extracted with ethyl
acetate (10 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by silica gel column chromatography
(hexane/ethyl acetate = 95:5, column length 11 cm and
diameter 2.7 cm) and GPC to give the product as a white
solid (0.130 g, 67%). The solid was recrystallized in
dichloromethane solvent to give a crystal suitable for X-
ray crystallography analysis. The structure of 12 was
confirmed by X-ray crystallography analysis (CCDC
Methyl (Z)-2-methyl-3-phenoxy-4-(p-tolyl)pent-3-
enoate (16)
m
p
o
i
O
O
4'
3'
2
1'
1
3
OMe
2'
4
Pd(PPh3)4 (0.019 mmol, 0.0220 g) was added to a
solution of methyl (Z)-4-iodo-2-methyl-3-phenoxypent-3-
enoate 5aa (0.194 mmol, 0.0671 g), p-tolylboronic acid
(0.388 mmol, 0.0527 g), and K2CO3 (0.581 mmol, 0.0803
g) in 1,4-dioxane (1 mL) at room temperature. The
mixture was stirred at 90 °C for 8 h. Then, the mixture was
poured into ethyl acetate (20 mL) and brine (10 mL) and
extracted with ethyl acetate (10 x 3 mL). The collected
organic layer was dried over MgSO4. The solvent was
evaporated and the residue was purified by silica gel
column chromatography (hexane/ethyl acetate = 88:12,
column length 11 cm and diameter 2.7 cm) and GPC to
give the product as a brown oil. (0.0459 g, 76%).; IR:
1908819).; mp: 109 °C; IR: (KBr) 2204 (C≡C) cm-1; H
1
NMR: (400 MHz, CDCl3) 7.35-7.26 (m, 7H, 1-Ph and m),
7.10-7.08 (m, 3H, o and p), 2.79 (s, 3H, 5-H3); 13C NMR:
(100 MHz, CDCl3) 155.4 (s, i), 136.3 (s, C-3), 131.4 (d),
129.3 (d, m), 129.0 (d), 128.3 (d), 123.1 (d, p), 121.7 (s,
C-1'), 117.5 (d, o), 96.7 (s, C-1), 92.9 (s, C-4), 79.9 (s, C-
2), 28.1 (q, C-5); HRMS: (EI, 70 eV) Calculated:
360.0013 (M+) (C17H13OI) Found: 360.0007.
(neat) 1742 (C=O) cm-1; H NMR: (400 MHz, CDCl3)
1
7.19 (d, J = 8.2 Hz, 2H, 2'-H x 2), 7.09 (t, J = 7.9 Hz, 2H,
m), 6.97 (d, J = 8.2 Hz, 2H, 3'-H x 2), 6.84-6.78 (m, 3H, p
and o), 3.76 (q, J = 7.3 Hz, 1H, 2-H), 3.60 (s, 3H, OMe),
2.21 (s, 3H, 4'-Me), 2.11 (s, 3H, 4-Me), 1.39 (d, J = 7.3
Hz, 3H, 2-Me); 13C NMR: (100 MHz, CDCl3) 173.3 (s, C-
1), 156.8 (s, i), 144.3 (s, C-3), 136.9 (s, C-1'), 136.2 (s, C-
4'), 128.9 (s, m), 128.5 (s, C-3'), 127.8 (s, C-2'), 124.8 (s,
C-4), 121.2 (s, p), 116.0 (s, o), 51.9 (s, OMe), 41.6 (s, C-
2), 21.1 (s, 4'-Me), 18.9 (s, 4-Me), 14.5 (s, 2-Me); HRMS:
(EI, 70 eV) Calculated: 310.1569 (M+) (C20H22O3) Found:
310.1565.
(Z)-5-Iodo-4-phenoxy-hex-4-en-1-ene (15)
m
p
o
i
O
2
I
3
4
1
5
6
Phenyl prop-1-ynyl ether 1a (0.531 mmol, 0.0702 g) was
added to a solution of InI3 (0.539 mmol, 0.267 g) and
23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 29
1
2
3
4
5
6
7
8
(Z)-2-Phenoxy-3-(p-tolyl)but-2-enenitrile (17)
solid was recrystallized in dichloromethane solvent to
m
p
give a crystal suitable for X-ray crystallography analysis.
The structure of 18 was confirmed by X-ray
crystallography analysis (CCDC 1908822).; mp: 130-
136 °C; IR: (KBr) 2200 (C≡C) cm-1; 1H NMR: (400 MHz,
CDCl3) 7.38 (d, J = 8.2 Hz, 2H, 2'-H x 2), 7.30-7.27 (m,
7H, 1-Ph and m), 7.10-7.07 (m, 4H, 3'-H x 2 and o), 7.02
(t, J = 7.3 Hz, 1H, p), 2.41 (s, 3H, 5-H3), 2.31 (s, 3H, 4'-
Me); 13C NMR: (100 MHz, CDCl3) 156.6 (C, i), 137.3 (C,
C-4'), 135.1 (C, C-1'), 131.3 (CH), 130.7 (C, C-4), 129.9
(C, C-3), 129.2 (CH, m), 128.7 (CH, C-3'), 128.5 (CH),
128.2 (CH), 127.8 (CH, C-2'), 122.5 (C, C-1''), 122.3 (CH,
p), 117.3 (CH, o), 95.4 (C, C-1), 84.3 (C, C-2), 21.2 (CH3,
4'-Me), 20.1 (CH3, C-5); HRMS: (EI, 70 eV) Calculated:
324.1514 (M+) (C24H20O) Found: 324.1515.
o
i
O
2
4'
3'
1
3
1'
CN
2'
9
4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Pd(PPh3)4 (0.0346 mmol, 0.0403 g) was added to a
solution of methyl (Z)-3-iodo-2-phenoxybut-2-enenitrile
8 (0.485 mmol, 0.138 g), p-tolylboronic acid (1.10 mmol,
0.150 g) and K2CO3 (1.47 mmol, 0.204 g) in 1,4-dioxane
(5 mL) at room temperature. The mixture was stirred at 90
°C for 8 h. Then, the mixture was poured into ethyl acetate
(20 mL) and brine (10 mL) and extracted with ethyl
acetate (10 x 3 mL). The collected organic layer was dried
over MgSO4. The solvent was evaporated and the residue
was purified by silica gel column chromatography
(hexane/ethyl acetate = 88:12, column length 11 cm and
diameter 2.7 cm) and GPC to give the product as a white
solid (0.0901 g, 75%). The solid was recrystallized in
dichloromethane solvent to give a crystal suitable for X-
ray crystallography analysis. The structure of 17 was
confirmed by X-ray crystallography analysis (CCDC
1908823).; mp: 60-68 °C; IR: (KBr) 2213 (C≡N) cm-1; 1H
NMR: (400 MHz, CDCl3) 7.37-7.33 (m, 4H, 6'-H x 2 and
m), 7.15 (d, J = 8.2 Hz, 2H, 3'-H x 2), 7.11 (t, J = 7.6 Hz,
1H, p), 7.02 (d, J = 7.6 Hz, 2H, o), 2.44 (s, 3H, 8-Me),
2.33 (s, 3H, 4-H3); 13C NMR: (100 MHz, CDCl3) 155.5 (C,
i), 140.0 (C, C-2), 139.5 (C, C-4'), 132.4 (C, C-1'), 129.8
(CH, m), 129.1 (CH, C-2'), 127.8 (CH, C-3'), 123.8 (CH,
p), 121.5 (C, C-1), 116.6 (CH, o), 114.7 (C, C-2), 21.3
(CH3, 4'-Me), 19.9 (CH3, C-4); HRMS: (EI, 70 eV)
Calculated: 249.1154 (M+) (C17H15NO) Found: 249.1157.
(Z)-3-Phenoxy-1-phenyl-4-(p-tolyl)pent-3-en-1-yne (18)
(Z)-4-Phenoxy-5-(p-tolyl)hex-4-en-1-ene (19)
m
p
o
i
O
4'
3'
4
1'
2
5
6
2'
3
1
Pd(PPh3)4 (0.0101 mmol, 0.0117 g) was added to a
solution of methyl (Z)-5-iodo-4-phenoxy-hex-4-en-1-ene
15 (0.104 mmol, 0.0313 g), p-tolylboronic acid (0.226
mmol, 0.0307 g) and K2CO3 (0.408 mmol, 0.0564 g) in
1,4-dioxane (0.5 mL) at room temperature. The mixture
was stirred at 90 °C for 8 h. Then, the mixture was poured
into ethyl acetate (20 mL) and brine (10 mL) and extracted
with ethyl acetate (10 x 3 mL). The collected organic layer
was dried over MgSO4. The solvent was evaporated and
the residue was purified by silica gel column
chromatography (hexane/ethyl acetate = 88:12, column
length 11 cm and diameter 2.7 cm) and GPC to give the
product as colorless oil (0.0099 g, 36%). The structure of
19 was determined by 1H-NOE experiment and 2D spectra
of the compound.; IR: (neat) 1595 (C=C) cm-1; 1H NMR:
(400 MHz, CDCl3) 7.23-7.21 (m, 4H, 2'-H x 2 and m),
7.03 (d, J = 7.9 Hz, 2H, 3'-H x 2), 6.94 (t, J = 7.3 Hz, 1H,
p), 6.88 (d, J = 7.6 Hz, 2H, o), 5.85 (ddt, J = 16.8, 10.2,
6.4 Hz, 1H, 2-H), 5.10 (ddt, J = 16.8, 1.6, 1.6 Hz, 1H, 1-
HA), 5.06 (ddt, J = 10.2, 1.6, 1.6 Hz, 1H, 1-HB), 3.09 (dd,
J = 6.4, 1.6 Hz, 2H, 3-H2), 2.26 (s, 3H, 4'-Me), 2.09 (s,
3H, 6-H3); 13C NMR: (100 MHz, CDCl3) 156.6 (C, i),
143.9 (C, C-4), 137.1 (C, C-1'), 136.0 (C, C-4'), 133.7 (CH,
C-2), 129.3 (CH, m), 128.5 (CH, C-3'), 127.6 (CH, C-2'),
123.0 (C, C-5), 121.5 (CH, p), 116.8 (CH, o), 116.1 (CH2,
C-1), 33.9 (CH2, C-3), 21.1 (CH3, 4'-Me), 18.6 (CH3, C-
6); HRMS: (EI, 70 eV) Calculated: 264.1514 (M+)
(C19H20O) Found: 264.1513.
m
p
o
i
O
4'
3'
1'
3
2'
4
5
2
1''
1
Pd(PPh3)4 (0.0261 mmol, 0.0301 g) was added to a
solution of methyl (Z)-4-iodo-3-phenoxy-1-phenyl-pent-
3-en-1-yne 12 (0.229 mmol, 0.0825 g), p-tolylboronic
acid (0.482 mmol, 0.0656 g) and K2CO3 (0.785 mmol,
0.108 g) in 1,4-dioxane (1 mL) at room temperature. The
mixture was stirred at 90 °C for 8 h. Then, the mixture was
poured into ethyl acetate (20 mL) and brine (10 mL) and
extracted with ethyl acetate (10 x 3 mL). The collected
organic layer was dried over MgSO4. The solvent was
evaporated and the residue was purified by silica gel
column chromatography (hexane/ethyl acetate = 92:8,
column length 11 cm and diameter 2.7 cm) and GPC to
give the product as a white solid (0.0577 g, 78%). The
(Z)-2-Phenoxy-3-(p-tolyl)but-2-en-1-ylamine (20)19
24
ACS Paragon Plus Environment

Page 25 of 29
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
H), 3.71 (s, 3H, OMe), 3.46 (m, 1H, 7-H), 2.79 (dd, J =
p
18.1, 5.8 Hz, 1H, 6-HH), 2.69-2.62 (m, 2H, 6-HH and 3-
HH), 2.51-2.48 (m, 1H, 3-HH), 1.75 (s, 3H, 4-Me); 13C
NMR: (100 MHz, CDCl3) 172.8 (C, 7-COOMe), 156.0 (C,
i), 153.0 (C, C-1), 140.8 (C, C-4), 129.5 (CH, m), 123.0
(CH, p), 121.0 (CH, C-5), 119.4 (CH, o), 108.8 (CH, C-
2), 52.1 (CH3, OMe), 46.8 (CH, C-7), 29.1 (CH2, C-3),
27.5 (CH2, C-6), 25.3 (CH3, 4-Me); HRMS: (EI, 70 eV)
Calculated: 258.1256 (M+) (C16H18O3) Found: 258.1254.
m
i
O
2
4'
3'
o
3
1'
1
2'
4
NH2
A solution of (Z)-2-phenoxy-3-(p-tolyl)but-2-enenitrile
17 (0.095 mmol, 0.024 g) was added to a suspension of
LiAlH4 (0.47 mmol, 0.018 g) and AlCl3 (0.15 mmol, 0.020
g) in diethyl ether (0.25 mL) at 0 °C. The reaction mixture
was stirred for 18 h and then, the reaction mixture was
quenched with an aqueous solution of NaOH (20 wt%) at
0 °C. The organic phase was separated off, and the
aqueous phase was extracted three times with portions of
diethyl ether. The collected organic layer was dried over
MgSO4. The solvent was evaporated and the residue was
purified by silica gel column chromatography
(hexane/ethyl acetate = 70:30, column length 11 cm and
diameter 2.7 cm) to give the product as a yellow liquid
(0.0098 g, 41%).; IR: (neat) 3373 (N-H,br) cm-1, 1594
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
■ COMPUTATIONAL DETAILS
Quantum chemical calculations of the
mechanism of reaction between an indium-
alkyne complex A-1 and silyl ketene acetal 2a
were performed under vacuum at 298 K and 1
bar. All calculations and geometry optimizations
were performed using the B3LYP/6-31+G(d,p)
for H, C and O, and DGDZVP for In and I level
of theory. Stationary points, minima, and
transition states on the potential energy surface
were identified by vibrational analysis.
Transition state structures were verified by the
presence of one negative eigenvalue reaction
path, which was followed by intrinsic reaction
coordinate (IRC) analysis and an inspection of
the displacement along the vibrational mode
corresponding to the imaginary frequency.
Gibbs free energies were calculated as a sum of
the single-point electronic energy and thermal
correction to the Gibbs free energy. All quantum
chemical computations were performed using
the Gaussian09 rev.C.01.
(C=C) cm-1; H NMR: (400 MHz, CDCl3) 7.24-7.22 (m,
1
4H, Ar), 7.04 (d, J = 7.7 Hz, 2H, Ar), 6.95 (t, J = 7.7 Hz,
1H, p), 6.89 (d, J = 7.7 Hz, 2H, o), 3.57 (s, 2H, 1-H2), 2.27
(s, 3H, 4'-Me), 2.15 (s, 3H, 4-H3); 13C NMR: (100 MHz,
CDCl3) 156.5 (s, i), 146.6 (s, C-3), 136.8 (s, C-1'), 136.3
(s, C-4'), 129.5 (d), 128.6 (d), 127.5 (d), 123.1 (s, C-2),
121.6 (d, p), 116.4 (d, o), 39.7 (t, C-1), 21.1 (q, 4'-Me),
18.5 (q, C-4); HRMS: (EI, 70 eV) Calculated: 253.1467
(M+) (C17H19NO) Found: 253.1464.
7-methoxycarbonyl-4-methyl-1-phenoxycyclohepta-1,4-
diene (21)
m
p
o
i
O
O
1
2
7
3
OMe
6
4
5
■ ASSOCIATED CONTENT
A
solution of methyl (E)-2-allyl-6-methyl-3-
phenoxyhepta-3,6-dienoate 3le(0.467 mmol, 0.134 g) and
(1,3-bis(2,4,6-trimethylphenyl)-2-
Supporting Information
The Supporting Information is available free of
charge on the ACS Publications website.
Optimization of Reaction Conditions (Table S1
and Table S2)
Scope of organosilicon nucleophile (Table S3)
X-ray crystallographic data (Figure S1-7 and
Table 4-10)
midazolidinylidene)dichloro(phenylmethylene)(tricycloh
exylphosphine)ruthenium
[Grubbs
catalyst
2nd
Generation] (0.020 mmol, 0.017 g) in benzene (1 mL) was
stirred for 2 h at 70 °C. The reaction was monitored H-
1
NMR. After the reaction was completed, the mixture was
poured into ethyl acetate (20 mL) and brine (10 mL), and
then extracted with ethyl acetate (10 x 3 mL). The
collected organic layer was dried over MgSO4. The
solvent was evaporated and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate =
88:12, column length 11 cm and diameter 2.7 cm) and
GPC to give the product as colorless oil (0.049 g, 41%).;
IR: (neat) 1740 (C=O) cm-1; 1H NMR: (400 MHz, CDCl3)
7.30 (t, J = 7.7 Hz, 2H, m), 7.06-7.02 (m, 3H, p and o),
5.53 (t, J = 6.6 Hz, 1H, 5-H), 5.13 (t, J = 5.8 Hz, 1H, 2-
NOE experiments
Calculated data (Figure S8 and Table S11-12)
Cartesian coordinates of the compounds
Copies of 1H and 13C NMR spectra of materials
and products
CIF files of X-ray crystal analysis
25
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 29
1
2
3
4
5
6
7
8
14470-14475. (e) Nishimoto, Y.; Kita, Y.; Ueda,
■ AUTHOR INFORMATION
H.; Imaoka, H.; Chiba, K.; Yasuda, M.; Baba, A.
Coupling Reaction of Enol Derivatives with
Silyl ketene acetals Catalyzed by Gallium
Trihalides. Chem. Eur. J. 2016, 22, 11837-
11845.
Corresponding Authors
*E-mail: yasuda@chem.eng.osaka-u.ac.jp
*E-mail: nishimoto@chem.eng.osaka-u.ac.jp
9
(2) For recent reviews and examples: (a) Hall,
D. G.; Rybak, T.; Verdelet, T. Multicomponent
ORCID
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Kang Kyoungmin: 0000-0002-1146-2505
Nishimoto Yoshihiro: 0000-0002-7182-0503
Yasuda Makoto: 0000-0002-6618-2893
Hetero-[4+2]
Cycloaddition/Allylboration
Reaction: From Natural Product Synthesis to
Drug Discovery. Acc. Chem. Res. 2016, 49,
2489−2500. (b) Jørgensen K. A. Hetero-Diels-
Alder Reactions of Ketones - A Challenge for
Chemists. Eur. J. Org. Chem. 2004, 2004, 2093-
2102. (c) Manchand, P. S. (2001). Ethyl Vinyl
Ether. In Encyclopedia of Reagents for Organic
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENTS
This work was supported by JSPS KAKENHI
Grants Number JP15H05848, in Middle
Molecular Strategy, JP16K05719, JP18K19079,
JP18H01977, and JP19K05455. Y. N.
acknowledges support from the Frontier
Research Base for Global Young Researchers,
Osaka University, of the MEXT program and
from Mitsui Chemicals Award in Synthetic
Organic Chemistry and Shorai Foundation for
Science and Technology. K.K. acknowledges
financial support from the “Program for Leading
Graduate Schools: Interactive Materials Science
Cadet Program” of Osaka University.
Synthesis,
(Ed.).
doi:10.1002/047084289X.re125 (d) Ciufolini,
M. A.; Bishop, M. J. Studies Towards
Streptonigrinoids:Formal
Synthesis
of
Lavendamycin Methyl Ester. J. Chem. Soc.,
Chem. Commun. 1993, 1463−1464.
(3) (a) Claisen L. Über Umlagerung von Phenol-
allyläthern in C-Allyl-phenole. Ber. Dtsch.
Chem. Ges. 1912, 45, 3157-3166. (b) Burns, J.
M.; Krenske, E. H.; McGeary, R. P. Claisen
Rearrangements of Benzyl Vinyl Ethers and
Heterobenzyl Vinyl Ethers. Synthesis 2018, 50,
1750-1772. (c) Tellam, J. P.; Carbery D. R.
Development
of
the
Ireland-Claisen
Rearrangement of Alkoxy- and Aryloxy-
Substituted Allyl Glycinates. J. Org. Chem.
2010, 75, 7809-7821. (d) Tejedor, D.; Mndez-
Abt, G.; Garcia-Tellado, F. A Convenient
Domino Access to Substituted Alkyl 1,2-
Dihydropyridine-3-carboxylates from Propargyl
Enol Ethers and Primary Amines. Chem. Eur. J.
2010, 16, 428-431.
(4) Acid conditions: (a) LaMattina, J. L.; Muse,
D. E. Synthesis and Reactions of p-Nitrophenyl
2,2-Diethoxypropionate and p-Nitrophenyl 2-
Ethoxypropenoate. J. Org. Chem. 1987, 52,
3479-3481. (b) Holsworth, D. D.; Stier, M.;
Edmunds, J. J. He, W.; Place, S.; Maiti S. An
Expeditious Synthesis of 6-Alkyl-5-(4’-
aminophenyl)-pyrimidine-2,4-diamines.
■ REFERENCES
(1) For recent reviews and recent advances: (a)
Winternheimer, D. J.; Shade, R. E.; Merlic, C.
A. Methods for Vinyl Ether Synthesis.
Synthesis 2010, 2010, 2497-2511. (b) Patel, H.
H.; Prater, M. B.; Squire, S. O. Jr.; Sigman, M.
S. Formation of Chiral Allylic Ethers via an
Enantioselective
Palladium
Catalyzed
Alkenylation of Acyclic Enol Ethers. J. Am.
Chem. Soc. 2018, 140, 5895-5898. (c) Chulsky
K.; Dobrovetsky R. Metal-Free Catalytic
Reductive Cleavage of Enol Ethers. Org. Lett.
2018, 20, 6804-6807. (d) Liu, J.; Krajangsri, S.;
Singh, T.; Seriis, G. D.; Chumnanvej, N.; Wu,
H.; Andersson P. G. Regioselective Iridium-
Catalyzed Asymmetric Monohydrogenation of
1,4-Dienes. J. Am. Chem. Soc. 2017, 139,
Synthetic Communications 2003, 33, 3467-
3475. (c) Roush, W. R.; Coffey D. S. Synthesis
26
ACS Paragon Plus Environment

Page 27 of 29
1
The Journal of Organic Chemistry
2
3
4
5
6
7
8
9
of the Naphthoquinone Nucleus of Awamycin. J.
Enantioselective Cyclocarbolithiation. Org.
Lett. 2002, 4, 2193-2195.
Org. Chem. 1995, 60, 4412-4418. Base
conditions: (d) Zard, S. Z. The Xanthate Route
to Ketones: When the Radical Is Better than the
Enolate. Acc. Chem. Res. 2018, 51, 1722-1733.
(e) Bates, R. B.; Caldera, S. α-Alkoxyacrylic
Acids from α-Keto Acids J. Org. Chem. 1993,
58, 6920-6921. (f) Gonzalez-Liste, P. J.; Leon,
F.; Arribas, I.; Rubio, M.; García-Garrido, S. E.;
(7) anti-Carbometaltaion reported. Funk, R. L.;
Bolton, G. L.; Brummond, K. M.; Ellestad, K.
E.; Stallman, J. B. Facile Intramolecular
Carbolithiation Reactions of Alkylthio- and
Alkoxyacetylenes by Stabilized Carbanions. A
Novel Strategy for Synthesis of Fuctionalized
Carbocycles. J. Am. Chem. Soc. 1993, 115,
7023-7024.
(8) Our previous report: Nishimoto, Y.; Kang,
K.; Yasuda, M. Regio- and Stereoselective Anti-
Carbozincation of Alkynyl Ethers Using ZnBr2
toward (Z)-β-Zincated Enol Ether Synthesis.
Org. Lett. 2017, 19, 3927-3930.
(9) (a) Nishimoto, Y.; Takeuchi, M.; Yasuda,
M.; Baba, A. Regio- and Stereoselective
Carbobismuthination of Alkynes. Angew.
Chem., Int. Ed. 2012, 51, 1051-1054. (b)
Nishimoto, Y.; Hirase, R.; Yasuda M. Anti-
Carboalumination of Alkynes Using Aluminum
Trihalide and Silyl Ketene Imines: Stereo- and
Regioselective Synthesis of Alkenylaluminum
Compounds Bearing a Cyano Group. Org. Lett.
2018, 20, 3651−3655. (c) Nishimoto, Y.; Ueda,
H.; Yasuda, M.; Baba, A. Carbogallation of
Alkynes Using Gallium Tribromide and Silyl
ketene acetals and Synthetic Application to
Cross-Coupling with Aryl Iodides. Chem. - Eur.
J. 2011, 17, 11135-11138. (d) Nishimoto, Y.;
Moritoh, R.; Yasuda, M.; Baba, A. Regio- and
Stereoselective Generation of Alkenylindium
Compounds from Indium Tribromide, Alkynes,
and Silyl ketene acetals. Angew. Chem., Int. Ed.
2009, 48, 4577-4580. (e) Nishimoto, Y.; Yi, J.;
Takata, T.; Baba, A.; Yasuda, M. Regio- and
Stereoselective Allylindation of Alkynes Using
InBr3 and Allylic Silanes: Synthesis,
Characterization, and Application of 1,4-
Dienylindiums toward Skipped Dienes.
Molecules 2018, 23, 1884.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Cadierno,
V.;
Pizzano,
A.
Highly
Stereoselective Synthesis and Hydrogenation of
(Z)‑1-Alkyl-2-arylvinyl Acetates: a Wide Scope
Procedure for the Preparation of Chiral
Homobenzylic Esters. ACS Catal. 2016, 6,
3056-3060.
(5) (a) Basheer, A.; Marek, I. Recent Advances
in Carbocupration of α-Heterosubstituted
Alkynes. Beilstein J. Org. Chem. 2010, DOI:
10.3762/bjoc.6.77. (b) Levin, A.; Basheer, A.;
Marek, I. Regiodivergent Carbometalation
Reactions of Ynol Ether Derivatives. Synlett
2010, 2010, 329-332. (c) Alexakis, A.; Cahiez,
G.; Normant, J. F.; Villieras, J. Vinylic
Organocopper Compounds. VIII. Study of
the Regioselectivity of the Addition of
Organocopper Derivatives to Heterosubstituted
Alkynes.
Use of the Formed Vinylic
Organocopper Complexes in Synthesis. Bull.
Soc. Chim. Fr. 1977, 693-698. (d) Normant, J.
F.; Alexakis, A.; Commercon, A.; Cahiez, G.;
Villieras, J. Alkoxy- and Alkylthiovinyl
Organocuprous Compounds: Intermediates in
the
Synthesis
of
Stereospecific
Heterosubstituted Alkenes. C. R. Seances Acad.
Sci., Ser. C 1974, 279, 763-765.
(6) (a) Lhermet, R.; Ahmad, M.; Hauduc, C.;
Fressigne, C.; Durandetti, M.; Jacques
Maddaluno, J. Intramolecular Carbolithiation of
Heterosubstituted Alkynes: An Experimental
and Theoretical Study. Chem. Eur. J. 2015, 21,
8105-8111. (b) Hanna, R.; Daoust, B.
Intramolecular Regioselective Addition of
Radicals and Carbanions to Ynol ethers. A
Strategy for the Synthesis of Exocyclic Enol
Ethers. Tetrahedron 2011, 67, 92-99. (c) Gralla,
G.; Wibbeling, B.; Hoppe, D.; Synthesis of an
Ethynyl Carbamate and Application for
(10) When the volatiles was removed without
addition of pyridine, the reaction mixture was
complicated. In this case, the produced
alkenylindium might be protonated or
decomposed.
(11) Reported In-C bond distances in the crystal
of Ph3In were from 2.11(2) to 2.15(2)Å. Malone
27
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 29
1
2
3
4
5
6
7
8
9
J. F.; McDonald W. S. The Crystal Structures of
Triphenylgallium and Triphenylindium. J.
Chem. Soc. D, 1969, 591-592.
Buten-l-ols and 3-Butyn-l-ols: An Efficient
Synthesis of 7-Butyrolactones. J. Org. Chem.
1991, 56, 1099-1105. (c) Yoshikawa, T.; Shindo,
M. Stereoselective Synthesis of (E)-2-En-4-
ynoic Acids with Ynolates: Catalytic
Conversion to Tetronic Acids and 2-Pyrones.
Org. Lett. 2009, 11, 5378-5381.
(12) (a) Perez S., J.; Sarandeses, L. A.; Martinez,
M. M.; Alonso-Maranon, L. Indium(III) as π-
Acid Catalyst for the Electrophilic Activation of
Carbon–carbon Unsaturated Systems. Org.
Biomol. Chem., 2018, 16, 5733-5747. (b) Du,
G.; Wang, G.; Ma, W.; Yang, Q.; Bao, W.;
Liang, X.; Zhu, L.; Lee, C-S. Syntheses of
Diverse Natural Products via Dual-Mode Lewis
Acid Induced Cascade Cyclization Reactions.
Synlett 2017, 28, 1394-1406. (c) Baba, A.;
Yasuda, M.; Nishimoto, Y. Yuki Gosei Kagaku
Kyokaishi 2014, 72, 1360-1373.
(13) Zwitterion form was generated in
intramolecular oxyindation: Kita, Y.; Yata, T.;
Nishimoto, Y.; Chiba, K.; Yasuda, M. Selective
Oxymetalation of Terminal Alkynes via 6-Endo
Cyclization: Mechanistic Investigation and
Application to the Efficient Synthesis of 4-
Substituted Isocoumarins. Chem. Sci. 2018, 9,
6041-6052.
(14) InI3 showed the higher efficiency in this
carboindation than InBr3 and InCl3 because
large iodine atoms would stabilize the transition
state by delocalizing an increased negative
charge on an InI3 moiety. The similar situation
reported in our related paper (see ref.13).
(15) When I2 was used as reagent for iodination,
the yield of 6b was 20%.
(16) Matsukawa, Y.; Asao, N.; Kitahara, H.;
Yamamoto, Y. Lewis Acid Catalyzed
Allylstannylation of Unactivated Alkynes.
Tetrahedron 1999, 55, 3779-3790.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(19) Bunce, R. A.; Smith, C. L.; Lewis J. R.
Tetrahydro-1,5-benzoxazepines
Tetrahydro-1H-1,5-benzodiazepines
and
a
by
Tandem
Reduction-Reductive
Amination
Reaction. J. Heterocyclic Chem. 2004, 41, 963-
970.
(20) (a) Erdik, E. Electrophilic α-Amination of
Carbonyl Compounds. Tetrahedron 2004, 60,
8747−8782. (b) Ciganek, E. Electrophilic
Amination of Carbanions, Enolates, and Their
Surrogates. Organic Reactions (Hoboken, NJ,
United States) 2009, 72, 1−366.
(21) (a) Xu, T.; Li, C. -C.; Yang, Z. A Concise
Approach for the Total Synthesis of Pseudolaric
Acid A. Org. Lett. 2011, 13, 2630-2633. (b)
Chang, Y.; Shi, L.; Huang, J.; Shi, L.; Zhang, Z.;
Hao, H. -D.; Gong, J.; Yang, Z. Stereoselective
Total Synthesis of (±)-5-epi-Cyanthiwigin I via
an Intramolecular Pauson−Khand Reaction as
the Key Step. Org. Lett. 2018, 20, 2876-2829.
(c) Nakashima, K.; Inoue, K.; Sono, M.; Tori, T.
Total Synthesis and Absolute Configuration of
Liverwort Diterpenes, (-)-13(15)E,16E-3β,4β-
Epoxy-18-hydroxysphenoloba-13(15),16-diene
and
(-)-13(15)Z,16E-3β,4β-Epoxy-18-
hydroxysphenoloba-13(15),16-diene, by Use of
the Ring Closing Metathesis Reaction Applied
to Seven-Membered Carbocycles with a
Trisubstituted Double Bond. J. Org. Chem. 2002,
67, 6034-6040.
(22) (a) Zeiler, A.; Michael J. Ziegler, J. M.;
Rudolph, M.; Rominger, F.; Hashmi, A. S. K.
Scope and Limitations of the Intermolecular
Furan-Yne Cyclization. Adv. Synth. Catal. 2015,
357, 1507-1514. (b) Shen, W-. B.; Xiao, X-. Y.;
Sun, Q.; Zhou, B.; Zhu, X-. Q.; Yan, J-. Z.; Lu
X.; Ye, L- W. Highly Site Selective Formal
[5+2] and [4+2] Annulations of Isoxazoles with
Heterosubstituted Alkynes by Platinum
Catalysis: Rapid Access to Functionalized 1,3-
Oxazepines and 2,5-Dihydropyridines. Angew.
(17) We investigated direct coupling between
alkenylindiums and aryl iodides with Pd
catalysts, but the desired coupling did not occur.
Probably, the transmetallation between indium
species and Pd catalysts hardly occurs due to the
steric hindrance of the alkenylindium.
(18) Selected examples; (a) Kato, K.; Motodate,
S.; Mochida, T.; Kobayashi, T.; Akita, H
Intermolecular
Methoxycarbonylation
of
Terminal Alkynes Catalyzed by Palladium(II)
Bis(oxazoline) Complexes. Angew. Chem. Int.
Ed. 2009, 48, 3326-3328. (b) Tamaru, Y.
Palladium(II)-Catalyzed Carbonylation of 3-
28
ACS Paragon Plus Environment

Page 29 of 29
1
The Journal of Organic Chemistry
2
3
4
5
6
7
8
9
Chem. Int. Ed. 2017, 56, 605-609. (c) Tan, E. H.
(25) Trost, B. M.; Hung, C-I. H.; Koester, D. C.;
Miller,Y. Development of Non‑C2‑symmetric
ProPhenol Ligands. The Asymmetric Vinylation
of N‑Boc Imines. Org. Lett. 2015, 17, 3778-
3781.
(26) Hashmi, A. S. K.; Rudolph, M.; Huck, J.;
Frey, W.; Bats, J. W.; Hamzic, M. Gold
Catalysis: Switching the Pathway of the Furan-
Yne Cyclization. Angew. Chem. Int. Ed. 2009,
48, 5848-5852.
P; Lloyd-Jones, G. C.; Harvey, J. N.; Lennox, A.
J. J.; Mills, B. M. [(RCN)2PdCl2]-Catalyzed E/Z
Isomerization of Alkenes: A Non-Hydride
Binuclear Addition–Elimination Pathway.
Angew. Chem. Int. Ed. 2011, 50, 9602-9606.
(23) (a) Yoshihiro Nishimoto, Y.; Okita, A.;
Yasuda, M.; Baba, A. Indium Tribromide
Catalyzed Cross-Claisen Condensation between
Carboxylic Acids and Ketene Silyl Acetals
Using Alkoxyhydrosilanes. Angew. Chem. Int.
Ed. 2011, 50, 8623-8625. (b) Nishimoto, Y.;
Ueda, H.; Yasuda, M.; Baba, A. Gallium
Tribromide Catalyzed Coupling Reaction of
Alkenyl Ethers with Ketene Silyl Acetals.
Angew. Chem. Int. Ed. 2012, 51, 8073-8076. (c)
Ran, R.-Q.; He, J.; Xiu, S.-D.; Wang, K.-B.; Li,
C.-Y. Synthesis of 3-Pyrrolin-2-ones by
Rhodium-Catalyzed Transannulation of 1-
Sulfonyl-1,2,3-triazole with Ketene Silyl Acetal.
Org. Lett. 2014, 16, 3704-3707. (d) Toya, H,;
Okano, K.; Takasu, K.; Ihara, M.; Takahashi,
A.; Tanaka, H.; Tokuyama, H. Enantioselective
Total Synthesis of (-)- and (+)-Petrosin. Org.
Lett. 2010, 12, 5196-5199. (e) Peifer, M.; Berger,
R.; Shurtle, V. W.; Conrad, J. C.; MacMillan, D.
W. C. A General and Enantioselective Approach
to Pentoses: A Rapid Synthesis of PSI-6130, the
Nucleoside Core of Sofosbuvir. J. Am. Chem.
Soc. 2014, 136, 5900-5903.
(24) Mermerian, A. H.; Fu, G. C.
Nucleophile‐Catalyzed Asymmetric Acylations
of Silyl Ketene Imines: Application to the
Enantioselective Synthesis of Verapamil.
Angew. Chem. Int. Ed. 2005, 44, 949-952. (b)
Denmark, S. E.; Wilson, T. W.; Burk, M. T.;
Heemstra, J. R. Enantioselective Construction of
Quaternary Stereogenic Carbons by the Lewis
Base Catalyzed Additions of Silyl Ketene
Imines to Aldehydes. J. Am. Chem. Soc. 2007,
129, 14864-14865. (c) Freerksen, R. W.;
Selikson, S. J.; Wroble, R. R.; Kyler, S. K.; Watt,
D. S. Oxidative Decyanation of Secondary
Nitriles to Ketones. J. Org. Chem. 1983, 48,
4087-4096. (d) Guin, J.; Varseev, G.; List, B.
Catalytic Asymmetric Protonation of Silyl
Ketene Imines. J. Am. Chem. Soc. 2013, 135,
2100-2103.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
29
ACS Paragon Plus Environment