Indium Catalyzed Hydrofunctionalization of Styrene Derivatives Bearing a Hydroxy Group with Organosilicon Nucleophiles

Article abstract of DOI:10.1021/acs.joc.7b02739

Hydrofunctionalization is one of the most important transformation reactions of alkenes. Herein, we describe the development of an indium-triiodide-catalyzed hydrofunctionalization of alkenes bearing a hydroxy group using various types of organosilicon nucleophiles. Indium triiodide was the most effective catalyst, whereas typical Lewis acids such as TiCl₄, AlCl₃, and BF₃·OEt₂ were ineffective. Many functional groups were successfully introduced, and these resulted in yields of 31-86%. Various styrene derivatives were also applicable to this reaction. Mechanistic investigation revealed that the present hydrofunctionalization proceeded through Br?nsted acid-catalyzed intramolecular hydroalkoxylation of alkenes followed by InI₃-catalyzed substitution reaction of cyclic ether intermediates.

Full text of DOI:10.1021/acs.joc.7b02739

Subscriber access provided by READING UNIV
Article
Indium Catalyzed Hydrofunctionalization of Styrene Derivatives
Bearing Hydroxy Group with Organosilicon Nucleophiles
Yuji Kita, Tetsuji Yata, Yoshihiro Nishimoto, and Makoto Yasuda
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02739 • Publication Date (Web): 11 Dec 2017
Downloaded from http://pubs.acs.org on December 11, 2017
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 free 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 accessible to all
readers and 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.
The Journal of Organic Chemistry 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 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Indium Catalyzed Hydrofunctionalization of Styrene Derivatives
Bearing Hydroxy Group with Organosilicon Nucleophiles
†
†
,‡
,†
Yuji Kita, Tetsuji Yata, Yoshihiro Nishimoto,* and Makoto Yasuda*
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
†
‡
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
Supporting Information Placeholder
ABSTRACT
Hydrofunctionalization is one of the most important transformation reactions of alkenes. Herein, we
described the development of an indium-triiodide-catalyzed hydrofunctionalization of alkenes
bearing a hydroxy group using various types of organosilicon nucleophiles. Indium triiodide was the
most effective catalyst, whereas typical Lewis acids such as TiCl
4
, AlCl
3
, BF
3
·OEt were ineffective.
2
Many functional groups were successfully introduced, and these resulted in yields of 31 to 86%.
Various styrene derivatives were also applicable to this reaction. Mechanistic investigation revealed
that the present hydrofunctionalization proceeded through Brønsted acid-catalyzed intramolecular
hydroalkoxylaiton of alkenes followed by InI
3
-catalyzed substitution reaction of cyclic ether
intermediates.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Main Text
INTRODUCTION
Alkenes are important fundamental materials in organic synthesis and industrial chemistry, and
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
many useful transformations of alkenes have been established. Therefore, the direct addition reaction
of alkenes with various reagents such as electrophilic, nucleophilic, and radical ones to give
functionalized alkanes with high selectivity and high step economy is highly desired even now. In
this context, many examples for hydrofunctionalization of alkenes through the addition of E-H (E =
2
C, O, N, P, and S) to alkenes have already been reported. One example involves the
hydrofunctionalization of Michael acceptors such as α,β-unsaturated carbonyl compounds or nitriles
3
with a variety of organosilicon nucleophiles, which is a well-developed method (Scheme 1-A).
However, the application of less-polar alkenes to the process of hydrofunctionalization has been
insufficiently developed, and available organosilicon nucleophiles are limited to silyl enolates, silyl
cyanides and silyl azides4 (Scheme 1-B). Our group also reported the regioselective
hydrofunctionalization of simple alkenes with silyl ketene acetals and a stoichiometric amount of
4
g
4f
indium or bismuth salts through carboindation or carbobismuthination, respectively. Herein, the
regioselective hydrofunctionalization of less-polar alkenes bearing a hydroxy group with
organosilicon nucleophiles was accomplished in the presence of catalytic amount of indium trihalide
(Scheme 1-C). The present reaction proceeded through a unique reaction mechanism including
Brønsted acid-catalyzed hydroalkoxylaiton of alkenes followed by InI -catalyzed substitution
3
reaction of cyclic ether intermediates, which is quite different from our previously reported method
ACS Paragon Plus Environment

Page 3 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
through carbometalation. In the present hydrofunctionalization, various organosilicon nucleophiles
as well as silyl ketene acetals were allowed to use. Moreover, not only mono-substituted alkenes but
also di- and tri-substituted alkenes, which often showed low reactivity for previously developed
hydrofunctionalization,4c,4f,4g,4j were applicable. It is noted that a wide range of functional groups
could be introduced into alkenes via a single synthetic operation.5
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 1. (A) Michael Addition; (B) Hydrofunctionalization by Organosilicon Nucleophiles
with Less-polarAlkenes; (C) This Work Allows the Introduction of Versatile Functional Groups
to Alkenes
RESULTS AND DISCUSSION
Optimization of Reaction Conditions. The reaction of styrene with silyl ketene acetal 2a was
attempted in the presence of a catalytic amount of indium tribromide, but instead of obtaining the
hydrofunctionalization product, the polymerization of styrene occurred (Scheme 2-A). Interestingly,
we found that o-(2-hydroxyethyl)styrene (1a) afforded the target product 3aa in a high yield (Scheme
2
-B).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Scheme 2. Investigation of Indium Bromide Catalyzed Reaction of Silyl Ketene Acetal with
Styrene (A) or Styrene Derivative 1a (B)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
That result prompted us to investigate the effect of acid catalysts on the hydrofunctionalization of
1
a with 2a (Table 1). As shown in Scheme 2-(B), InBr
3
gave 3aa in a 76% yield (entry 1). GaBr also
3
afforded 3aa in approximately the same yield (entry 2). On the other hand, the desired product 3aa
was not obtained, and starting alkene 1a and TMS-1a were recovered in the cases of the reaction
using InCl
3
, In(OTf)
3
or BiI
3
(entries 3-5). The reaction catalyzed by InI raised the yield of 3aa to
3
9
2% (entry 6). Without the addition of 2a, only cyclic ether 4 was produced in a high yield (entry 7).
Thus, the hydrofunctionalization product could be obtained via 4. Typical Lewis acids such as ZnCl ,
2
AlCl
3
, and TiCl were ineffective for the desired hydrofunctionalization and either gave the cyclic
4
ether 4 or recovered the starting material (entries 8-10). The reaction using BF
3
·OEt resulted in
2
complicated mixture (entry 11). Acationic gold catalyst, which is often used to functionalize alkenes,6
was ineffective (entry 12). The reaction catalyzed by HI aq. would not afford the product 3aa, but did
produce cyclic ether 4 in a high yield (entry 13).
ACS Paragon Plus Environment

Page 5 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Table 1. The Effect of Acid Catalysts on the Hydrofunctionalization of Styrene Derivative 1a
with Organosilicon Nucleophile 2aa
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
yield (%)b
recovery of 1a (%)
entry
1
catalyst
time (h)
24
3aa
4
TMS-1a
InBr
3
76
0
0
0
0
15
5
0
0
0
8
0
0
0
0
0
2
GaBr
3
24
72
0
0
3
InCl
3
96
0
16
40
0
33
3
4
In(OTf)
3
24
0
5
BiI
3
72
0
91
0
6
InI
InI
3
24
92 (71)c
0
7 d
8
24
0
0
1
0
0
0
0
90
0
0
3
ZnCl
2
96
45
0
9
AlCl
3
24
56
57
0
10
11
12
TiCl
4
48
0
BF
3
·OEt
2
24
0
AuCl
3
/AgOTf
24
52
77
0
13
HI aq.
24
0
a
1st step: 1a (0.5 mmol), catalyst (0.05 mmol), ClCH
2
CH Cl (1 mL), 80 ˚C, 24 h. 2nd step: 2a (0.75 mmol),
2
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
b
1
rt, 2 h. The reaction was quenched with Bu
4
NF (1 M in THF). Yields were determined by H NMR using internal
c
d
standards (bromoform). Isolated yield. The 2nd step was not carried out.
Substrate Scope of Organosilicon Nucleophiles. Reactions of 1a with various organosilicon
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
nucleophiles 2 catalyzed by InI were carried out (Table 2). The bulky silyl ketene acetal 2b was
3
suitable for this reaction system to provide the cyclohexane derivative 3ab in high yield (entry 1).
The silyl enol ether 2c afforded the target product 3ac (entry 2). Hydrofunctionalization with the silyl
4
b
cyanide 2d occurred (entry 3), but the reported method that uses a Brønsted acid for hydrocyanation
of styrene gave only cyclic ether 4 (see Scheme S1 in Supporting Information for detail).
Methallylsilane 2e also provided the hydrofunctionalization product in moderate yield (entry 4).7
Reactions using allylsilane 2f, alkenylsilane 2g, alkynylsilane 2h, and propargylsilane 2i proceeded
efficiently in the presence of a catalytic amount of InI
3
/Me SiBr (entries 5-8). The addition of
3
Me
3
SiBr was necessary for the reactions using nucleophiles 2f-2i, which have a relatively low level
with Me
SiX showed high Lewis acidity.8
of nucleophilicity. In these cases, the combination of InX
3
3
To the best of our knowledge, the reaction using 2i is the first example of an intermolecular
9
Markovnikov hydroallenylation toward less-polar alkenes. Heteroatom nucleophiles such as silyl
sulfide 2j and silyl azide 2k were applicable to this reaction system (entries 9 and 10).10
ACS Paragon Plus Environment

Page 7 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Table 2. Scope of Hydrofunctionalization Using Various Organosilicon Nucleophilesa
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
entry
Nu-SiMe
3
Me
3
SiBr
yield of 3 (%)b
(x equiv)
(y mol %)
none
1c
3ab 74
2
2
b (3.0 equiv)
c (3.0 equiv)
2
none
none
none
3
3
ac 69
ad 31
3d
3
Me SiCN
2
d (5.0 equiv)
4
3
ae 55
2e (1.5 equiv)
2f (1.5 equiv)
2g (3.0 equiv)
2h (3.0 equiv)
5
6
7
10
20
20
3af 86
3ag 59
3
ah 54
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
8e
20
3ai 68
3aj 59
2i (3.0 equiv)
9
Me
j (3.0 equiv)
Me SiN
3
SiSPh
none
none
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
1
0f
3
3
3
ak 54
2
k (3.0 equiv)
a
1
st step: 1a (0.5 mmol), InI
3
(0.05 mmol), ClCH
2
CH Cl (1 mL), 80 ˚C, 24 h. 2nd step: 2 (0.75-2.5 mmol),
2
Me SiBr (0-0.1 mmol), rt, 2-14 h (See Experimental Section for detail). The reaction was quenched with
3
b
c
d
e
Bu
4
NF (1 M in THF). Isolated yield. InI
3
(20 mol %). InI (20 mol %), 70 ˚C at the 2nd step. 35 ˚C at the
3
f
2
nd step. 50 ˚C at the 2nd step.
Substrate Scope and Limitation of Styrene Derivatives. The scope of styrene derivatives with a
hydroxy moiety is shown in Table 3. In all cases, the nucleophilic attack of 2a took place at a benzylic
position exclusively and other regioisomers were not formed. The β-methylstyrene derivative 1b gave
the product 3ba, and the reaction of the α-methylstyrene derivative 1c formed vicinal quaternary
carbon atoms efficiently (entries 1 and 2). The reaction using the alkene 1d, which is not a styrene
derivative, provided no hydrofunctionalized product 3da and complicated mixture was obtained
(
entry 3). The result suggested that the present reaction system was limited to styrene derivatives. The
styrene derivatives 1e-1l, which have different carbon frameworks, were also suitable to this reaction
system. The reaction of β-(hydroxyalkyl)-substituted styrenes 1e and 1f afforded the target products
in modest yields (entries 4 and 5) while α-(hydroxyalkyl)-substituted substrates 1g and 1h gave higher
yields (entries 6 and 7). A variety of α-(hydroxyalkyl)-substituted styrenes were applicable to this
ACS Paragon Plus Environment

Page 9 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
reaction system. The reaction of styrene derivatives bearing electron donating groups 1i and 1j, as
well as electron withdrawing groups 1k and 1l, proceeded smoothly to give target products 3ia-3la
in moderate to high yields (entries 8-11). The trisubstituted alkene 1m was suitable for this reaction
system (entry 12). The intermolecular addition of silyl enolates to trisubstituted alkenes without
electron-withdrawing group has not been reported and the use of disubstituted alkenes usually
resulted in low yields due to their steric hindrance.4f,4g Therefore, it is advantage of this work that
trisubstituted substrate was applicable and disubstituted alkenes gave moderate to high yield.
Table 3. Scope of Hydrofunctionalization Using Various Styrene Derivativesa,b
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
entry
1
3
temp.
(˚C)
80
yieldc
(%)
52
1d
2
3
4
5
80
80
80
80
53
0
28
30
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
6d
rt
rt
rt
rt
rt
rt
70
59
66
70
57
45
77
56
7
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
8
9
10
1
1
12e
a1st step: 1 (0.5 mmol), InI
3
2 2
(0.05 mmol), ClCH CH Cl (1 mL), rt-80 ˚C, 1-120 h (See Experimental Section for detail). 2nd step:
2
a (0.75 mmol), rt, 2 h. The reaction was quenched with Bu
4
NF (1 M in THF). bCorresponding cyclic ethers were obtained
c
d
e
without addition of 2a (see Table S1 in Supporting Information for detail). Isolated yield. 2a (3 equiv). 2a (4 equiv).
Mechanistic Investigation. Hydrofunctionalization with styrene derivative 1n, including a
methoxyalkyl group, was attempted, but gave neither the target product 5 nor the cyclic ether 4
(
Scheme 3-A). Moreover, the hydroalkoxylation of styrene with methanol as an external alcohol in
the presence of a catalytic amount of InI afforded no benzyl ether 6 (Scheme 3-B). These control
3
experiments suggested that the intramolecular hydroxy group is necessary for this type of
hydrofunctionalization. Taking into account the result of entry 13 in Table 1, the hydroalkoxylation
of 1a can be catalyzed by a Brønsted acid, which can be generated via the alcoholysis of InI with 1a
3
ACS Paragon Plus Environment

Page 11 of 56
The Journal of Organic Chemistry
1
2
11
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
in situ. Thus, control experiments were carried out as shown in Scheme 4 to identify the active
catalyst species for hydroalkoxylation. InI or HI aq. efficiently catalyzed the hydroalkoxylation
3
1
2
while the addition of K
2
CO , or 2,6-di(tert-butyl)-4-methylpyridine as a proton scavenger, entirely
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
prevented the InI -catalyzed hydroalkoxylation of 1a. Therefore, these results indicated that in situ-
3
generated Brønsted acid promoted the formation of the cyclic ether 4.
Scheme 3. Investigation of Styrene Derivatives without OH Group.
Scheme 4. Hydroalkoxylation in the Presence of a Proton Scavenger
Proposed Mechanism. A proposed mechanism for the InI -catalyzed hydrofunctionalization of 1a
3
with an organosilicon nucleophile (Me
3
SiNu) is shown in Scheme 5. Atrace amount of InI undergoes
3
alcoholysis with 1a to give HI. The alkene moiety of 1a is protonated and then alkoxylation occurs
to afford cyclic ether 4. The interaction between InI and the ethereal oxygen of 4 cleaves the oxygen-
3
carbon bond to generate carbocation 9. A nucleophilic attack of the organosilicon compound to 9
occurs to produce the hydrofunctionalization product 10. Transmetalation of the alkoxyindium moiety
of 10 with Me
3
SiI regenerates the InI catalyst. The indium trihalide catalyzed substitution reaction
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
of ethers by an organosilicon nucleophile (Me
3
SiNu) has been previously reported by our group.13
Target alcohol product 3 is obtained after quenching by Bu
NF. In our previous reports4f,4g, an
1
4
4
indium trihalide coordinated to a carbon-carbon double bond and acted as a π Lewis acid to activate
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
alkenes. Contrastively, in the present reaction, InI mainly contributes to the generation of a Brønsted
3
acid to transform an alkene into a cyclic ether intermediate and the substitution reaction of the
intermediate with nucleophiles.
Scheme 5. Proposed Mechanism
Selective Functionalization of Alkenes. We demonstrated the selective functionalization of
1
5
substrate 1o with two types of alkene moieties (Scheme 6). When 1o underwent our developed
hydrofunctionalization using silyl ketene acetal 2a, hydroalkylation took place selectively at the
alkene moiety with a hydroxyalkyl group to afford product 12oa (Scheme 6-A). By contrast, when
4
f
utilizing the BiBr -mediated hydrofunctionalization conditions, polymerization of 1o just occurred.
3
Moreover, the selective hydroazidation proceeded in the InI -mediated reaction of 1o with silyl azide
3
1
6
2
k to give 12-N (Scheme 6-B). On the other hand, the reported iron-mediated hydroazidation using
3
NaN
3
occurred at both alkene moieties of 1o to give product 13-N . The other reported system using
3
ACS Paragon Plus Environment

Page 13 of 56
The Journal of Organic Chemistry
1
2
1
7
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Brønsted acid catalyst and Me
3
SiN
3
as an azide source was employed to afford no hydroazidation
product but a hydroalkoxylation intermediate and starting material 1o. The selective hydrocyanation
of 1o with silyl cyanide 2d was also observed under InI -catalyzed conditions to give 12od
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
b
exclusively, while the reported method resulted in polymerization of 1o (Scheme 6-C). These results
showed the advantage of the InI
3
-catalyzed system for selective functionalization of the complex
molecules.
Scheme 6. Selective Hydrofunctionalization of the Substrate 1o with Two Types of Alkene
Moieties.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
a
b
1) 1o (0.5 mmol), InI
3
(10 mol %), ClCH
2
CH
2
Cl (10 mL), 5 ˚C, 17 h. 2) 2a (1.5 mmol), rt, 12 h. 1o (0.2
c
mmol), BiBr
3
(0.3 mmol), 2a (0.3 mmol) and CH
2
Cl
2
(0.2 mL), rt, 8 h. 1) 1o (0.5 mmol), InI
3
(10 mol %),
d
ClCH
2
CH
2
Cl (10 mL), 5 ˚C, 5 h. 2) Me
3
SiN
3
(2k, 1.5 mmol), rt, 17 h. 1o (0.5 mmol), NaN
3
(4.0 mmol),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
e
Fe
2
(ox)
3
·6H
2
O (2.5 mmol), NaBH
4
(3.2 mmol), THF (20 mL) and H
2
O (20 mL), 0 ˚C, 0.5 h. 1o (0.5
f
mmol), TfOH (25 mol %), Me
3
SiN
3
(2k, 1.5 mmol), SiO
2
(1.25 g), CH
2
Cl
2
(2.5 mL), rt, 1 h. 1) 1o (0.5
g
mmol), InI
3
(10 mol %), ClCH
2 2
CH Cl (10 mL), 5 ˚C, 19 h. 2) Me
3
SiCN (2d, 2.5 mmol), rt, 35 h. 1o (0.5
mmol), TfOH (2.2 mmol), Me
3
SiCN (2d, 2.1 mmol), PhCF (4.5 mL), -5 ˚C, 1 h.
3
CONCLUSION
We have developed an InI catalyzed hydrofunctionalization of alkenes with a hydroxyalkyl group
3
using organosilicon nucleophiles such as silyl enolate, allylsilane, alkenylsilane, alkynylsilane,
propargylsilane, silyl cyanide, silyl sulfide and silyl azide. Many functional groups that would be
used for further elaboration were added to the alkene moiety in a single step. Various styrene
derivatives were suitable for this reaction. It is noted that addition reaction of silyl enolate proceeded
efficiently for not only monosubstituted alkenes but also multi-substituted ones compared with
previously reported hydrofunctionalization. The selective functionalization of styrene derivatives
with two alkene moieties was accomplished to show the preference of an alkene moiety with a
hydroxyalkyl group. Mechanistic investigation showed that this hydrofunctionalization is composed
of two steps: the hydroalkoxylation of an alkene catalyzed by a Brønsted acid and a sequential
ACS Paragon Plus Environment

Page 15 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
substitution reaction of cyclic ether catalyzed by InI
3
. This transformation of alkene to ether allowed
us to synthesize alkenes with many types of functional groups, which cannot be introduced into
alkenes in our previous works. Therefore, this work provides a novel method for functionalization of
alkenes.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
EXPERIMENTAL SECTION
General Information. New compounds were characterized by H, 13C, 13C off-resonance
1
1
13
techniques, COSY, HMQC, HMBC, IR, MS, HRMS. H (400 MHz) and C NMR (100 MHz) spectra
were obtained with TMS as internal standard. IR spectra were recorded as thin films. Bulb-to-bulb
distillation (Kugelrohr) was accomplished at the oven temperature and pressure indicated. High-
resolution mass spectra were obtained by magnetic sector type mass spectrometer. All reactions were
carried out under nitrogen. All products were obtained as racemic mixtures.
Material. Dehydrated ClCH
2
CH Cl was purchased and used without further purification.
2
Organosilicon nucleophiles 2a, 2d, 2e, 2f, 2h and 2k are commercially available. Styrene derivatives
a, 1d, 1e, 1f, 1g, 1h, 1l and organosilicon nucleophiles 2b, 2c, 2g, 2i and 2j were synthesized by
literature procedures and spectral data of these compounds were shown below. Styrene derivatives
b, 1c, 1i, 1j, 1k, 1m, 1n and 1o are new compounds, and synthetic method and spectral data of these
1
1
compounds were shown below. All metal salt and Me SiBr are commercially available.
3
(1a) 2-(2-vinylphenyl)ethan-1-ol18
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
To a three necked flask, THF (56 mL) and 1-bromo-2-vinylbenzene (4.15 g, 20 mmol) were added.
This solution was cooled at -78 °C and n-BuLi (1.6 M hexane solution, 14 mL, 22 mmol) was dropped
over 15 minutes. After stirring for 1.5 h at -78 °C, to the reaction mixture was dropped ethylene oxide
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(1.1 M in THF, 25 mL, 30 mmol) and the reaction mixture was stirred for 0.5 h at -78 °C. The mixture
was warm to room temperature and quenched by sat. NH Cl aq. (25 mL). This solution was extracted
4
with diethyl ether (20 mL x 3) and the collected organic layer was dried (MgSO ). The solvent was
4
evaporated and the residue was purified by column chromatography (hexane/ethyl acetate = 80:20,
column length 11 cm, diameter 26 mm, spherical silica gel) to give the product (1.36 g, 45%). This
is known compound and spectroscopic data were identical with those from literature.
(1b) 2-(2-(prop-1-en-1-yl)phenyl)ethan-1-ol
To a three necked flask, THF (56 mL) and 1-bromo-2-(prop-1-en-1-yl)benzene (4.15 g, 20 mmol)
were added. This solution was cooled at -78 °C and n-BuLi (1.6 M hexane solution, 14 mL, 22 mmol)
was dropped over 15 minutes. After stirring for 1.5 h at -78 °C, to the reaction mixture was dropped
ethylene oxide (1.1 M in THF, 25 mL, 30 mmol) and the reaction mixture was stirred for 0.5 h at -
7
8 °C. The mixture was warm to room temperature and quenched by sat. NH Cl aq. (25 mL). This
4
solution was extracted with diethyl ether (20 mL x 3) and the collected organic layer was dried
ACS Paragon Plus Environment

Page 17 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(MgSO
4
). The solvent was evaporated and the residue was purified by column chromatography
(hexane/ethyl acetate = 80:20, column length 11 cm, diameter 26 mm, spherical silica gel) to give the
-1 1
product (E/Z = 99: 1, 1.67 g, 51%). IR: (neat) 3359 (OH) cm ; H NMR: (400 MHz, CDCl ) 7.43 (d,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
J = 5.5 Hz, 1H, 5-H), 7.23-7.11 (m, 3H, 6-H, 7-H and 8-H), 6.65 (dq, J = 15.6, 1.4 Hz, 1H, 9-H), 6.11
(dq, J = 15.6, 6.9 Hz, 1H, 10-H), 3.80 (t, J = 6.9 Hz, 2H, 1-H
2
), 2.94 (t, J = 6.9 Hz, 2H, 2-H ), 1.90
2
1
3
(dd, J = 6.9, 1.4 Hz, 3H, 11-H
3
), 1.41 (s, 1H, OH); C NMR: (100 MHz, CDCl ) 137.3 (s, C-3), 134.9
3
(s, C-4), 130.2 (d, C-8), 128.3 (d, C-9), 127.9 (d, C-10), 126.9 (d), 126.8 (d), 126.2 (d, C-5), 63.1 (t,
+
C-1), 36.4 (t, C-2), 18.9 (q, C-11); MS: (CI, 70 eV) m/z 163 ([M + 1] , 43); HRMS: (EI, 70 eV);
Calculated (C11H14O) 162.1045 (M); Found: 162.1046.
(1c) 2-(2-(prop-1-en-2-yl)phenyl)ethan-1-ol
To a three necked flask, THF (56 mL) and 1-bromo-2-(prop-1-en-2-yl)benzene (3,49 g, 20 mmol)
were added. This solution was cooled at -78 °C and n-BuLi (1.6 M hexane solution, 14 mL, 22 mmol)
was dropped over 15 minutes. After stirring for 1.5 h at -78 °C, to the reaction mixture was dropped
ethylene oxide (1.1 M in THF, 25 mL, 30 mmol) and the mixture was stirred for 0.5 h at -78 °C. The
reaction mixture was warm to room temperature and quenched by sat. NH Cl aq. (25 mL). This
4
solution was extracted with diethyl ether (20 mL x 3) and the collected organic layer was dried
(MgSO
4
). The solvent was evaporated and the residue was purified by column chromatography
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(hexane/ethyl acetate = 80:20, column length 11 cm, diameter 26 mm, spherical silica gel) to give the
-
1
-1 1
product (1.53 g, 47%). IR: (neat) 3359 (OH) cm , 1639 (C=C) cm ; H NMR: (400 MHz, CDCl )
3
A
B
7.29-7.15 (m, 3H), 7.15-7.09 (m, 1H, 7-H), 5.23-5.17 (m, 1H, 10-H ), 4.89-4.82 (m, 1H, 10-H ), 3.81
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
(t, J = 7.2 Hz, 2H, 1-H
2
), 2.92 (t, J = 7.2 Hz, 2H, 2-H
2
), 2.05 (s, 3H, 11-H ), 1.39 (s, 1H, OH); C
3
NMR: (100 MHz, CDCl ) 145.4 (s, C-9), 144.3 (s, C-8), 134.6 (s, C-3), 129.6 (d, C-4), 128.4 (d, C-
3
7), 126.9 (d), 126.3 (d), 115.2 (t, C-10), 63.7 (t, C-1), 36.1 (t, C-2), 25.3 (q, C-11); MS: (CI, 70 eV)
+
m/z 163 ([M + 1] , 100); HRMS: (EI, 70 eV) Calculated (C11
H14O) 162.1045 (M) Found: 162.1043.
(1d) (2-allylphenyl)methanol19
To a three necked flask, (2-bromophenyl)methanol (9.45 g, 50 mmol), hexane (50 mL), Et2O (5
mL), 3,4-dihydro-2H-pyran (5.12 g, 60 mmol) and Amberlyst15 (6.3 g) were added. After stirring for
4
5 minutes, the reaction mixture was purified by column chromatography (hexane, column length 11
cm, diameter 26 mm, silica 75 g and Amberlyst15 6.2 g) to give 2-((2-bromobenzyl)oxy)tetrahydro-
2
H-pyran (7.2 g, 53%).
To a three necked flask, magnesium turning (0.73 g, 30 mmol) and THF (10 mL) were added. Three
drops of a solution of 2-((2-bromobenzyl)oxy)tetrahydro-2H-pyran (7.2 g, 27 mmol) in THF (12 mL)
was dropped into the vessel, and then ten drops of 1,2-dibromoethane was added to the reaction
mixture. The reminding THF solution of 2-((2-bromobenzyl)oxy)tetrahydro-2H-pyran was dropped
into the reaction mixture over 10 minutes. After stirring for 15 minutes, the mixture was refluxed for
ACS Paragon Plus Environment

Page 19 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1 hour, and then cooled at 30 °C. A solution of allyl bromide (4.4 g, 36 mmol) in THF (10 mL) was
dropped over 5 minutes. After stirring for 17 hours, the reaction mixture was quenched by sat. NH Cl
4
aq. (30 mL) under ice bath. The solution was extracted by ethyl acetate (30 mL x 4). The collected
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
organic layer was dried (MgSO ) and the solvent was evaporated to give 2-((2-
4
allylbenzyl)oxy)tetrahydro-2H-pyran (6.35 g, 100%).
To a three necked flask, 2-((2-allylbenzyl)oxy)tetrahydro-2H-pyran (6.27 g, 27 mmol), MeOH (38
mL) and 1N HCl aq. (38 mL) were added. After stirring for 20 hours at 50 °C, the reaction mixture
was quenched by Et
2
O (100 mL). The mixture was extracted by Et O (50 mL x 3) and the collected
2
organic layer was dried (MgSO ). The solvent was evaporated and the residue was purified by column
4
chromatography (hexane/ethyl acetate = 60:40, column length 11 cm, diameter 26 mm, spherical
silica gel) to give (2-allylphenyl)methanol as the target product (4.0 g, 100%). This is known
compound and spectroscopic data were identical with those from literature.
(1e) (E)-5-phenylpent-4-en-1-ol20
To a three necked flask, THF (250 mL) and LiAlH (5.1 g, 130 mmol) were added. This solution
4
was cooled at 0 °C and 5-phenylpent-4-yn-1-ol (4.28 g, 26 mmol) was added to the mixture and the
reaction mixture was stirred for 1 h at 0 °C. After refluxing for 2 day, to the reaction mixture was
dropped sat. potassium sodium tartrate aq. (100 mL) at 0 °C. This solution was extracted with diethyl
ether (100 mLx 3) and the collected organic layer was washed by sat. NaCl aq. (100 mL). The organic
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
layer was dried (MgSO ) and the solvent was evaporated and the residue was purified by column
4
chromatography (hexane/ethyl acetate = 80:20, column length 11 cm, diameter 26 mm, spherical
silica gel) to give the product (3,24 g, 77%). This is known compound and spectroscopic data were
identical with those from literature.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(1f) (E)-4-phenylbut-3-en-1-ol 21
To a three necked flask, THF (21 mL) and LiAlH (1.78 g, 47 mmol) were added. This solution was
4
cooled at 0 °C and 4-phenylbut-3-yn-1-ol (2.34 g, 16 mmol) in THF (21 mL) was dropped to the
mixture over 10 minutes. After refluxing for 15 h, the reaction mixture was quenched by
Na
2
SO
4
·10H
2
O at 0 °C. This mixture was filtered and the filtrate was dried (MgSO ). The solvent
4
was evaporated and the residue was purified by column chromatography (hexane/ethyl acetate =
0:20, column length 11 cm, diameter 26 mm, spherical silica gel) to give the product (2.21 g, 93%).
This is known compound and spectroscopic data were identical with those from literature.
8
(
1g) 5-phenylhex-5-en-1-ol22
To a two necked flask, Pd(PPh
3
4
) (0.695 g, 0.6 mmol), 1,4-dioxane (40 mL), phenyl boronic acid
(3.05 g, 24 mmol), 5-hexyne-1-ol (2.10 g, 20 mmol) and acetic acid (0.13 g, 2.0 mmol) were added.
After stirring for 10 minutes at rt, the reaction mixture was stirred for 16 h at 80 °C. The reaction
ACS Paragon Plus Environment

Page 21 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
mixture was filtered and the solvent was evaporated and the residue was purified by column
chromatography (hexane/ethyl acetate = 80:20, column length 11 cm, diameter 26 mm, spherical
silica gel) to give the product (3.17 g, 90%). This is known compound and spectroscopic data were
identical with those from literature.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(1h) 4-phenylpent-4-en-1-ol22
To a two necked flask, Pd(PPh
3
4
) (0.692 g, 0.6 mmol), 1,4-dioxane (60 mL), phenyl boronic acid
(3.04 g, 24 mmol), 4-pentyne-1-ol (1.65 g, 20 mmol) and acetic acid (0.22 mL, 4.0 mmol) were added.
The reaction mixture was stirred for 16 h at 80 °C. The mixture was filtered and the solvent was
evaporated and the residue was purified by column chromatography (hexane/ethyl acetate = 80:20,
column length 11 cm, diameter 26 mm, spherical silica gel) to give the product (2.60 g, 80%). This is
known compound and spectroscopic data were identical with those from literature.
(1i) 5-(p-tolyl)hex-5-en-1-ol
To a two necked flask, Pd(PPh
3
4
) (0.343 g, 0.297 mmol), 1,4-dioxane (20 mL), p-tolyl boronic acid
(1.70 g, 12.5 mmol), 5-hexyn-1-ol (0.981 g, 0.999 mmol) and acetic acid (0.101 g, 1.68 mmol) were
added. After stirring for 24 h at 80 ℃, the reaction mixture was filtered through a short pad of celite
and the filtrate was evaporated. The residue was purified by column chromatography (hexane/ethyl
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
acetate = 80:20, column length 11 cm, diameter 26 mm, spherical silica gel) to give the product (1.17
-1
-1 1
g, 61%). IR: (neat) 3444 (OH) cm , 1624 (C=C) cm ; H NMR: (400 MHz, CDCl ) 7.29 (d, J = 8.2
3
A
Hz, 2H, o), 7.13 (d, J = 8.2 Hz, 2H, m), 5.24 (d, J = 1.4 Hz, 1H, 6-H ), 5.01 (d, J = 1.4 Hz, 1H, 6-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
B
H ), 3.62 (t, J = 6.3 Hz, 2H, 1-H
2
), 2.51 (t, J = 7.7 Hz, 2H, 4-H
2
), 2.34 (s, 3H, 7-H ), 1.67-1.54 (m,
3
1
3
2H, 2-H
2
), 1.54-1.41 (m, 2H, 3-H
2
), 1.67-1.41 (br, 1H, OH); C NMR: (100 MHz, CDCl ) 148.0 (s,
3
C-5), 138.1 (s, p), 137.0 (s, i), 128.9 (d, m), 125.9 (d, o), 111.6 (t, C-6), 62.7 (t, C-1), 35.0 (t, C-4),
32.3 (t, C-2), 24.3 (t, C-3), 21.0 (q, C-7); MS: (EI, 70 eV) m/z 190 (M, 28); HRMS: (EI, 70 eV)
Calculated (C13H18O) 190.1358 (M) Found: 190.1355.
(1j) 5-(4-methoxyphenyl)hex-5-en-1-ol
To a two necked flask, Pd(PPh
3
4
) (0.352 g, 0.305 mmol), 1,4-dioxane (20 mL), p-methoxy phenyl
boronic acid (1.85 g, 12.2 mmol), 5-hexyn-1-ol (0.977 g, 9.95 mmol) and acetic acid (0.117 g, 1.95
mmol) were added. After stirring for 24 h at 80 ℃, the reaction mixture was filtered through a short
pad of celite and the filtrate was evaporated. The residue was purified by column chromatography
(hexane/ethyl acetate = 80:20, column length 11 cm, diameter 26 mm, spherical silica gel) to give the
-1
-1 1
product (0.993 g, 48%). IR: (neat) 3400 (OH) cm , 1608 (C=C) cm ; H NMR: (400 MHz, CDCl )
3
A
B
7.35 (d, J = 8.9 Hz, 2H, o), 6.86 (d, J = 8.9 Hz, 2H, m), 5.21 (s, 1H, 6-H ), 4.98 (s, 1H, 6-H ), 3.81
(s, 3H, OMe), 3.65 (t, J = 6.0 Hz, 2H, 1-H
2
), 2.51 (t, J = 7.5 Hz, 2H, 4-H
2
), 1.66-1.46 (m, 4H, 2-H
2
ACS Paragon Plus Environment

Page 23 of 56
The Journal of Organic Chemistry
1
2
1
3
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
and 3-H
2
), 1.39 (s, 1H, OH); C NMR: (100 MHz, CDCl ) 158.9 (s, p), 147.5 (s, C-5), 133.5 (s, i),
3
127.1 (d, o), 113.6 (d, m), 110.9 (t, C-6), 62.8 (t, C-1), 55.2 (q, OMe), 35.0 (t, C-4), 32.3 (t, C-3), 24.3
(t, C-2); MS: (EI, 70 eV) m/z 206 (M, 24); HRMS: (EI, 70 eV) Calculated (C13
Found: 206.1308.
H
18
2
O ) 206.1307 (M)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(1k) 4-(4-chlorophenyl)pent-4-en-1-ol
To a two necked flask, Pd(PPh
3
4
) (0.352 g, 0.305 mmol), 1,4-dioxane (20 mL), p-chloro phenyl
boronic acid (1.81 g, 11.6 mmol), 4-pentyn-1-ol (0.811 g, 9.64 mmol) and acetic acid (0.125 g, 2.08
mmol) were added. After stirring for 24 h at 80 ℃, the reaction mixture was filtered through a short
pad of celite and the filtrate was evaporated. The residue was purified by column chromatography
(hexane/ethyl acetate = 80:20, column length 11 cm, diameter 26 mm, spherical silica gel) to give the
-1
-1 1
product (0.715 g, 36%). IR: (neat) 3433 (OH) cm , 1716 (C=C) cm ; H NMR: (400 MHz, CDCl )
3
A
7.34 (d, J = 8.9 Hz, 2H), 7.29 (d, J = 8.9 Hz, 2H), 5.28 (d, J = 0.92 Hz, 1H, 5-H ), 5.10 (d, J = 0.92
B
Hz, 1H, 5-H ), 3.65 (t, J = 6.4 Hz, 2H, 1-H
2
), 2.57 (t, J = 7.8 Hz, 2H, 3-H ), 1.70 (tt, J = 7.8, 6.4 Hz,
2
1
3
2H, 2-H
2
), 1.29 (s, 1H, OH); C NMR: (100 MHz, CDCl ) 146.8 (s, C-4), 139.4 (s, i), 133.2 (s, p),
3
128.4 (d), 127.4 (d), 113.0 (t, C-5), 62.2 (t, C-1), 31.4 (t, C-3), 30.9 (t, C-2); MS: (EI, 70 eV) m/z 196
(M, 2); HRMS: (EI, 70 eV) Calculated (C11H13ClO) 196.0655 (M) Found: 196.0654.
(1l) 4-(4-fluorophenyl)pent-4-en-1-ol22
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
To a two necked flask, Pd(PPh
3
) (0.328 g, 0.3 mmol), 1,4-dioxane (20 mL), p-fluorophenyl boronic
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
acid (1.69 g, 12 mmol), 4-pentyne-1-ol (0.839 g, 10 mmol) and acetic acid (0.13 g, 2.0 mmol) were
added. The reaction mixture was stirred for 24 h at 80 °C. The mixture was filtered and the solvent
was evaporated and the residue was purified by column chromatography (hexane/ethyl acetate =
8
0:20, column length 11 cm, diameter 26 mm, spherical silica gel) to give the product (0.341 g, 19%).
This is known compound and spectroscopic data were identical with those from literature.
(
1m) 2-(2-(but-2-en-2-yl)phenyl)ethan-1-ol
To a three necked flask, THF (35 mL) and 1-bromo-2-(but-2-en-2-yl)benzene (2.55 g, 12 mmol)
were added. This solution was cooled at -78 °C and n-BuLi (1.6 M hexane solution, 9 mL, 13 mmol)
was dropped over 15 minutes. After stirring for 1.5 h at -78 °C, to the reaction mixture was dropped
ethylene oxide (1.1 M in THF, 16 mL,18 mmol) and the mixture was stirred for 0.5 h at -78 °C. The
reaction mixture was warm to room temperature and quenched by sat. NH Cl aq. (15 mL). This
4
solution was extracted with diethyl ether (20 mL x 3) and the collected organic layer was dried
(
MgSO
4
). The solvent was evaporated and the residue was purified by column chromatography
(
hexane/ethyl acetate = 80:20, column length 11 cm, diameter 26 mm, spherical silica gel) to give the
-1 1
product (0.368 g, 17%, ratio of stereoisomer = 85:15). IR: (neat) 3352 (OH) cm ; H NMR: (400
ACS Paragon Plus Environment

Page 25 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
MHz, CDCl
3
) major stereoisomer 7.30-7.19 (m, 3H, 4-H, 5-H and 6-H), 7.03 (dd, J = 5.6, 3.6 Hz, 1H,
7-H), 5.58 (qq, J = 6.5, 1.7 Hz, 1H, 10-H), 3.80 (dd, J = 7.0, 12.8 Hz, 2H, 1-H ), 2.91-2.76 (m, 2H,
2
1
3
2-H
2
), 1.96 (m, 3H, 11-H
3
), 1.41-1.33 (br, 1H, OH), 1.37 (d, J = 6.5 Hz, 3H, 12-H ); C NMR: (100
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
MHz, CDCl ) major stereoisomer 142.3 (s, C-8), 136.7 (s, C-9), 135.3 (s, C-3), 129.5 (d, C-4), 128.8
3
(d, C-7), 126.8 (d), 126.6 (d), 122.4 (d, C-10), 63.4 (t, C-1), 36.1 (t, C-2), 26.0 (q, C-11), 14.8 (q, C-
12); MS: (CI, 70 eV) m/z 176 (M, 5); HRMS: (EI, 70 eV) Calculated (C12H16O) 176.1201 (M) Found:
176.1205.
(1n) 1-(2-methoxyethyl)-2-vinylbenzene
To a branched reactor vessel, NaOH aq. (50 wt%, 1g), benzene (2 mL), 2-(2-vinylphenyl)ethan-1-
ol (0.737 g, 5 mmol), tributylamine (0.0492 g, 0.27 mmol) and dimethyl sulfate (0.962 g, 8 mmol)
were added. After stirring for 3 h at 40 °C, the reaction mixture was quenched by diethyl ether (4 mL)
and H
2
O (4 mL). This solution was extracted with diethyl ether (5 mL x 3), and washed by H O (4
2
mL) and sat. NaCl aq. (5 mL). The collected organic layer was dried (MgSO ). The solvent was
4
evaporated and the residue was purified by column chromatography (hexane) column length 11 cm,
diameter 26 mm, spherical silica gel) to give the product (0.649 g, 81%). IR: (neat) 1115 (OMe) cm-
1; 1H NMR: (400 MHz, CDCl
) 7.49 (dd, J = 3.6, 5.3 Hz, 1H), 7.24-7.15 (m, 3H), 7.01 (dd, J = 17.4,
3
A
B
11.1 Hz, 1H, 9-H), 5.64 (dd, J = 17.4, 1.4 Hz, 1H, 10-H ), 5.30 (dd, J = 11.1, 1.4 Hz, 1H, 10-H ),
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
3.53 (t, J = 7.7 Hz, 2H, 1-H
2
), 3.34 (s, 3H, 11-H
3
), 2.97 (t, J = 7.7 Hz, 2H, 2-H ); C NMR: (100
2
MHz, CDCl ) 136.9 (s, C-8), 135.9 (s, C-3), 134.4 (d, C-9), 130.0 (d, C-4), 127.7 (d), 126.7 (d), 125.8
3
(d), 115.7 (t, C-10), 73.0 (t, C-1), 58.6 (q, C-11), 33.5 (t, C-2); MS: (CI, 70 eV) m/z 163 ([M + 1]+,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
100), 131 (52); HRMS: (EI, 70 eV) Calculated (C11
H
14O) 162.1045 (M ) Found: 162.1046; Analysis:
11
C H14O (162.10) Calculated: C, 81.44; H, 8.70 Found: C, 81.16; H, 8.52.
(1o) 2-(2-(prop-1-en-2-yl)phenyl)ethan-1-ol
To a two necked flask, Pd(PPh
3
) (0.420 g, 0.363 mmol), 1,4-dioxane (20 mL), p-vinyl boronic acid
4
(
2.20 g, 14.9 mmol), 4-pentyn-1-ol (1.05 g, 12.5 mmol) and acetic acid (0.13 mL, 2.40 mmol) were
added. After stirring for 29 h at 80 ℃, the reaction mixture was filtered through a short pad of celite
and the filtrate was evaporated. The residue was purified by column chromatography (hexane/ethyl
acetate = 80:20, column length 11 cm, diameter 26 mm, spherical silica gel) to give the product (1.77
-1
-1 1
g, 75%). IR: (neat) 3359 (OH) cm , 1628 (C=C) cm ; H NMR: (400 MHz, CDCl
3
) 7.42-7.36 (m,
A
A
4
H), 6.71 (dd, J = 18.4, 10.6 Hz, 1H, 6-H), 5.76 (d, J = 18.4 Hz, 1H, 7-H ), 5.33 (s, 1H, 5-H ), 5.25
B
B
(
d, J = 10.6 Hz, 1H, 7-H ), 5.10 (s, 1H, 5-H ), 3.66 (t, J = 6.3 Hz, 2H, 1-H ), 2.61 (t, J = 7.7 Hz, 2H,
2
13
3
-H
2
), 1.73 (tt, J = 6.3, 7.7 Hz, 2H, 2-H
2
), 1.51 (br, 1H, OH); C NMR: (100 MHz, CDCl ) 147.4 (s,
3
C-4), 140.2 (s, i), 136.7 (s, p), 136.3 (d, C-6), 126.2 (d), 126.1 (d), 113.7 (t, C-7), 112.5 (t, C-5), 62.4
+
(
t, C-1), 31.4 (t, C-3), 31.1 (t, C-2); MS: (CI, 70 eV) m/z 189 ([M + 1] , 100); HRMS: (EI, 70 eV)
ACS Paragon Plus Environment

Page 27 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Calculated (C13H16O) 188.1201 (M) Found: 188.1199.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(2b) (cyclohexylidene(methoxy)methoxy)trimethylsilane4g
To a solution of diisopropylamine (11.5 g, 110 mmol) in THF (80 mL) was added n-BuLi (63 mL,
1
.6 M in hexane) at 0 ºC. The resulted solution was stirred for 10 min at room temperature. Then, a
solution of methyl cyclohexanecarboxyrate (11.4 g, 80 mmol) in THF (30 mL) was slowly added to
the LDA solution at -78 ºC. After the solution was stirred for 2h at -78 ºC, trimethylsilylchloride (10.8
g, 100 mmol) was added to the reaction mixture, and the reaction mixture was stirred for 20 h at room
temperature. The reaction mixture was poured into ice water and hexane, which was extracted with
hexane. The organic phase was washed with brine, dried (MgSO ) and concentrated. The obtained
4
crude oil was purified by distillation (bp. 100-102 ºC, 20 mmHg) to give the desired product (14.3 g,
3%). This is known compound and spectroscopic data were identical with those from literature.
8
(
2c) 3-trimetylsilyloxy-2-pentene23
To a solution of diisopropylamine (10.1 g, 100 mmol) in THF (100 mL) was added n-BuLi (1.6 M
in hexane, 63 mL, 100 mmol) at 0 °C. After stirring at 0 °C for 15 min, then to reaction mixture was
added 3-pentanone (6.89 g, 80 mmol) dropwise at -78 °C. After stirred for 30 min at -78 °C, Me SiCl
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 56
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(10.9 g, 100 mmol) was added dropwise at -78 °C. The reaction mixture was allowed to reach room
temperature and stirred for 30 min. Then, sat. NaHCO aq. (50 mL) was added and the solution was
3
extracted with pentane (50 mL x 3). The organic layer was dried (MgSO ). The solvent was
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
evaporated and the residue was purified by distillation under reduced pressure (76 °C, 85 mmHg) to
give the product (12.0 g, 76% yield, E/Z = 5:1). This is known compound and spectroscopic data
were identical with those from literature.
(2g) (E)-trimethyl(styryl)silane24,25
To a three necked flask, trimethyl(phenylethynyl)silane (3.63 g, 20.8 mmol) and dry hexane (5 mL)
were added. To the reaction mixture was dropped DIBAL-H (1.0 M in hexane, 24 mL, 24 mmol).
After stirring for 13 h at rt, the reaction mixture was quenched by 4 N HCl aq. (17 mL) at 0 °C. The
mixture was extracted by Et O (20 mLx 3) and the collected organic layer was washed with sat. NaCl
2
aq. (60 mL x 3). The organic layer was dried (MgSO ) and the solvent was evaporated and the residue
4
was purified by distillation under reduced pressure (112 °C, 23 mmHg) to give the product (2.23 g,
60%). This is known compound and spectroscopic data were identical with those from literature.
(2i) trimethyl(prop-2-yn-1-yl)silane26
To a three necked flask, Mg (1.82 g, 75 mmol), Et
2
O (16 mL) and HgCl (0.255 g, 0.94 mmol) were
2
ACS Paragon Plus Environment

Page 29 of 56
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
added. After vigolously stirring for 30 minutes at rt, propargyl bromide (1.1 M in Et
2
O, 2 mL, 2.2
mmol) was dropped to the mixture. The reaction mixture was cooled into 0 °C and propargyl bromide
(1.1 M in Et O, 31 mL, 34.1 mmol) was dropped to the reaction mixture. After stirring for 30 minutes
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
at rt, the reaction mixture was cooled into 0 °C and Me SiCl (3.34 g, 30.7 mmol) was dropped to the
3
reaction mixture. After vigolously stirring for 9 h at rt, the reaction mixture was filtered through a
celite pad and the filtrate was purified by column chromatography (Et O, column length 11 cm,
2
diameter 26 mm, spherical silica gel) to give the product (51wt% in Et O, 2.91 g, 36%). This is known
2
compound and spectroscopic data were identical with those from literature.
(2j) trimethyl(phenylthio)silane27,28
To a three necked flask, Et O (32 mL) and benzenethiol (3.60 g, 33 mmol) were added. This solution
2
was cooled at -78 °C and n-BuLi (1.6 M hexane solution, 52 mL, 82.5 mmol) was dropped to the
mixture over 15 minutes, followed by Me SiCl was dropped over 4 minutes. After stirring for 2 hours,
3
the reaction mixture was quenched by dry hexane (18 mL). The solvent was evaporated and the
residue was filtered and the residue was washed by hexane. The solvent was evaporated and the
residue was purified by distillation under reduced pressure (110 °C, 20 mmHg) to give the product
(4.82 g, 81%). This is known compound and spectroscopic data were identical with those from
literature.
ACS Paragon Plus Environment