Selective reaction of benzyl alcohols with HI gas: Iodination, reduction, and indane ring formations

Article abstract of DOI:10.1016/j.tet.2017.11.009

Reactions of benzyl alcohols with HI in solvent-free conditions were examined. Three types of reactions (iodination, reduction, and ring formation) occurred depending on the degree of crowding around the benzyl position and the benzylic stabilization of substrates. Results also showed that the ring formation to give indanes proceeded efficiently when HI was used, and that compounds with electron-rich aromatic rings gave indane derivatives in good yields.

Full text of DOI:10.1016/j.tet.2017.11.009

Accepted Manuscript
Selective reaction of benzyl alcohols with HI gas: Iodination, reduction, and indane
ring formations
Shoji Matsumoto, Masafumi Naito, Takehisa Oseki, Motohiro Akazome, Yasuhiko
Otani
PII:
S0040-4020(17)31145-6
10.1016/j.tet.2017.11.009
TET 29089
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 29 August 2017
Revised Date: 31 October 2017
Accepted Date: 3 November 2017
Please cite this article as: Matsumoto S, Naito M, Oseki T, Akazome M, Otani Y, Selective reaction of
benzyl alcohols with HI gas: Iodination, reduction, and indane ring formations, Tetrahedron (2017), doi:
10.1016/j.tet.2017.11.009.
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Selective reaction of benzyl alcohols with HI
gas: Iodination, reduction, and indane ring
formations
Leave this area blank for abstract info.
Shoji Matsumotoa, , Masafumi Naito a , Takehisa Oseki a , Motohiro Akazome a , and Yasuhiko Otanib
a Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33
Yayoicho, Inageku, Chiba 263-8522, Japan
b GODO SHIGEN CO., LTD., 1365 Nanaido, Chosei-mura, Chosei-gun, Chiba 299-4333, Japan

ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Selective reaction of benzyl alcohols with HI gas: Iodination, reduction, and indane
ring formations
Shoji Matsumotoa, , Masafumi Naito a , Takehisa Oseki a , Motohiro Akazome a , and Yasuhiko Otanib
a Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33 Yayoicho, Inageku, Chiba 263-8522, Japan
b GODO SHIGEN CO., LTD., 1365 Nanaido, Chosei-mura, Chosei-gun, Chiba 299-4333, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Reactions of benzyl alcohols with HI in solvent-free conditions were examined. Three types of
reactions (iodination, reduction, and ring formation) occurred depending on the degree of
crowding around the benzyl position and the benzylic stabilization of substrates. Results also
showed that the ring formation to give indanes proceeded efficiently when HI was used, and that
compounds with electron-rich aromatic rings gave indane derivatives in good yields.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Hydrogen iodide
Iodination
Reduction
Ring formation
Solvent-free reaction
1. Introduction
Hydrogen iodide (HI) is commercially available as a 55–57
wt% aqueous solution for use as a synthetic reagent, and is used
as an acid,1 a reducing agent,2 a nucleophile,3 and so on.4
Recently, we explored the utilization of HI gas in reaction with
acetophenones to form α-alkylated acetophenones under solvent-
free conditions.5 Related to that reaction mechanism, we were
interested in the reactivity of benzyl alcohols toward HI. In this
manuscript, we described the reaction of benzyl alcohols with HI
gas; three types of reactions, i.e., iodination, reduction, and ring
formation, occurred at ambient temperature under solvent-free
conditions (Scheme 1). The formation of indane rings due to the
reaction of styrene derivatives with Brønsted acids has been
reported, although oligomerization occured in some cases as a
side reaction.6 Selective formations of indanes have been
achieved with styrene by using Lewis acids,7 transition metals,8
and ionic liquids.9 Benzyl alcohols can produce indanes through
dimerization.10 Stavber and co-workers reported that the reaction
of 2-phenyl-2-propanol in the presence of I2 at 70 °C gave indane
products under solvent-free conditions.11 Hence, we also
investigated the scope and limitations of indane ring formation
under ambient conditions.
Scheme 1. Three types of reactions of benzyl alcohols with
HI.
2. Results and discussion
First, we examined the reactivities of primary, secondary, and
tertiary benzyl alcohols with HI gas; their substituents were fixed
with methyl and phenyl groups (Table 1). Unique selectivity was
observed. Compounds with less crowding around the benzyl
position, such as 1a and 1b gave iodination products 2a and 2b
(entries 1–3). The use of more than one equivalent of HI led to
the efficient generation of 2a. Even with one equivalent of HI, 2b
was obtained in good yield (80%) from secondary alcohol 1b,
whose benzyl cation would be stabilized efficiently. When
tertiary alcohol 1c was treated with HI gas, a cyclized product,
indane 4c, was obtained in 62% yield (entry 4). With secondary
alcohol 1d, which contains a second phenyl ring, a complex
mixture was obtained. However, we were able to find reduction
product 3d, which was produced in 14% yield (entry 5). In the
case of tertiary alcohol 1e, a mixture of reduction product 3e and
indane 4e was obtained; iodination product 2e was not found
(entry 6). When this reaction was conducted with
———
Corresponding author. Tel.: +0-000-000-0000; fax: +0-000-000-0000; e-mail: author@university.edu

2
Tetrahedron
ACCEPTED MANUSCRIPT
Table 1. Reaction of various benzyl alcohols with HI gas
% yielda
3 [reduction]
entry
compound
R1
H
R2
H
equiv. of HI
2 [iodination]
4 [ring formation]b
1
2
3
4
5
6
7
8
1a
1
1.5
1
1
1
1
1
2
42
77
80
0
0
0
0
0
0
–
–
0
62
–
53
–
1b
1c
1d
1e
1f
Me
Me
Ph
Ph
Ph
H
Me
H
Me
Ph
0
14
46
24
64
0
0
–
a Yield was determined by integration of 1H NMR peaks using p-chlorobenzaldehyde as an internal standard.
b Yield was estimated as the formation of one molecule of 4 from two molecules of 1.
triphenylmethanol (1f), reduction product 3f was obtained (entry
7). The yield of 3f was increased when two equivalents of HI
were used (entry 8). The reduction of triphenylmethanol
derivatives with aqueous HI has been reported in the literature12
and required refluxing conditions. When HI gas is used, the
reaction can proceed at ambient temperatures.
Under those conditions, the formation of ethers as side
products is plausible. However, the corresponding ethers could
1
not be found in crude H NMR spectra. This may because the
products can be formed from the ethers under the reaction
conditions. To test this hypothesis, we examined the reaction of
the ethers under the same conditions (Scheme 2). The results
showed that the corresponding products could be obtained from
the ethers. The reaction of dibenzyl ether (5a), the ethereal form
of 1a, gave iodination product 2a in 91% yield, along with the
leaving alcohol (80%). Ether 5b gave iodination product 2b in
50% yield with 13% of the corresponding alcohol. Unfortunately,
we could not prepare the corresponding ethers of 1c and 1f.
Hence, we attempted to the reactions of their methyl ethers (6a
and 6b, respectively). These reactions also produced 4c and 3f.
Therefore, the ethers are also possible reaction intermediates.
Scheme 2. Reaction of ethers with HI gas.
According to those results, the preferred reaction can be
predicted based on the stabilization of the intermediate and the
crowding at the benzyl position. The proposed reaction
mechanism is depicted in Scheme 3. First, alcohol 1 is protonated
by HI to generate an oxonium ion. After elimination of H2O,
benzyl cation A is formed. Intermediate A can produce ether B
by reacting with 1. However, ether B can generate A under acidic
conditions. With less crowded benzyl cations such as those of 1a
and 1b, iodide counter ion can attach easily to the cation to give
iodination product 2. When an additional substituent is attached
to the benzyl cation, there are two possible paths. One path is the
formation of reduction product 3. The additional phenyl group at
the benzyl position in 1d, 1e, and 1f weakens the C–I bond even
though the C–I bond was formed because of the static interaction.
The C–I bond (2.285 Å) of triphenylmethyl iodide (CCDC
Refcode: TEWWEX)13 is longer than the typical C–I bond
distance (2.162 Å).14 Therefore, iodide can be removed by HI to
form a benzyl anion (C). Furthermore, reduction product 3 is
obtained via the protonation of C. The formation of 3 in greater
than 50% yield in the presence of two equivalents of HI is
reasonable (Table 1, entry 8). The formation of reduction product
3 through homolytic cleavage of the C–I bond in the iodinated
compound is also plausible. However, Kahr and co-workers
reported that triphenylmethyl iodide is stable under these
conditions (reacted at 25 °C). The other path from cation A is
taken when the temperature is below 80 °C.13 Consequently, the
radical path via homolytic cleavage can be excluded from our
reaction when there is an additional substituent, since the
cyclization reaction occurs. When there is a β-hydrogen at the
cationic carbon as with 1c and 1e, an elimination reaction occurs
to give styrene derivative D. Carbon–carbon bond formation
occurs between intermediate D and cation A to give tertiary
cation E. Intramolecular nucleophilic attack by the phenyl ring
and elimination of HI produce cyclization product 4.
We also investigated indane ring formation, which involves
selective carbon–carbon bond formation. The results are
presented in Table 2. According to the reaction mechanism in
Scheme 3, a catalytic amount of HI is sufficient to advance the
reaction. However, the use of one molar equivalent of HI gave
indane 4c efficiently in 62% yield (entries 1–3). It is reasonable
that H2O generated as a side product would decrease the acidity
of HI. This reaction could be conducted in CHCl3 (entry 4).
However, the formation of 4c was inhibited strongly when

R1 = R2 = H (
)
I
OH
R2
R1
1a
ACCEPTED MANUSCRIPT
R1 = Me, R2 = H (
)
R2
R1
1b
less crowding
1
2
R1 = Ph, R2 = H (
R1 = Ph, R2 = Me (
1f
)
HI
1d
H
I
weakened
I
H
1e
)
R2
R2
I
OH2
R2
R1
R1 = R2 = Ph (
)
H
– I2
R2
crowding and
additional phenyl group
3
C
– H2O
R2
stabilized benzyl anion
Me
I
Me
R1
R1
1H
I
R1 = Me, R2 = Me (
)
Me
R1
R1
1c
Me
R1 = Ph, R2 = Me (
)
I
R1
I
– HI
A
1e
R1
R1
crowding and
A
existence of ꢀhydrogen
D
R
E
R1
OH
4
R2
1
R1
– HI
R2
R2
O
R1 R1
B
Scheme 3. Plausible reaction mechanism and requirements of 2, 3, and 4 formation.
aqueous HI was used (entry 5). The results suggest that it is
important to conduct the reaction under anhydrous conditions.
The use of other acids such as HCl and MeSO3H gave
unsatisfactory results (entries 6 and 7). Therefore, efficient
indane formation requires the HI. The presence of a methyl
group, which is an electron-donating substituent, on the phenyl
ring increased the yield (entries 8–10). In contrast, lower yields
were obtained with compounds with chloro- and trifluoromethyl
groups, which are electron-withdrawing substituents (entries 11
and 12), which destabilize benzyl cation intermediate A in
Scheme 1. Substrates with naphthyl groups reacted efficiently to
give the corresponding indanes (entries 13 and 14). In paticular,
Table 2. Indane ring formation by reaction of 1 with HI gasa
the 2-naphthyl substrate gave a single isomer 4m in 79% yield
(entry 14) although reactions also occurred at the 1 and 3
positions of the naphthalene ring. The use of heteroaromatics
gave no indane product and led to either a complex mixture (Ar =
2-thienyl group) or no reaction (Ar = pyridyl group). Substrates
with longer alkyl groups gave undesirable results. For example, a
complex mixture was obtained in the reaction of 3-phenylpentan-
3-ol. Furthermore, an elimination reaction occurred and no
indane ring was formed when diisopropylphenylmethanol was
treated with HI (eq. 1). We also examined the reaction of a
styrene with HI because the styrene is formed in the proposed
reaction mechanism. When α-methylstyrene
equiv.
of HI
1
2
0.5
1
entry
compound
Ar
Ph
% yield
1
2
3
1c
62
44
33
64
4b
5c
6
1
complex mixture
d
–
0
trace
was treated with HI gas, corresponding indane
4c was obtained. However, the yield was not
as high as that of the reaction with alcohol 1c
(eq. 2). We were unable to explain the
e
7
8
9
10
11
12
13
14
–
1g
1h
1i
1j
1k
1l
4-MeC6H4
3-MeC6H4
2-MeC6H4
4-ClC6H4
4-CF3C6H4
1-naphthyl
2-naphthyl
1
1
1
1
1
1
1
84
64f
64
49
differences between those reactions, but the
gradual production of styrene derivatives
prevent polymerization.
complex mixture
4m
78
1m
79g
In conclusion, three types of reaction occurred between benzyl
alcohols and HI. The product selectivity depended on the degree
of crowding and the benzylic stabilization. These reactions were
conducted under solvent-free conditions at ambient temperature.
Furthermore, the indane ring formation, which involves a
reaction between two molecules, proceeded efficiently even
under solvent-free conditions.
a
Reaction conditions: substrate (1.0 mmol), 25 °C, 1 d. Yield was
determined by integration of H NMR peaks using p-chlorobenzaldehyde
as an internal standard.
1
b Reacted in CHCl3 (3.3 M).
c 55 wt% aqueous HI was used instead of HI gas.
d Conc. HCl (1 equiv.) was used as the acid.
e MeSO3H (1 equiv.) was used as the acid.
f Obtained as regioisomers (68 : 32, determend from 1H NMR analysis).
g Obtained as a single isomer (4m).

4
Tetrahedron
2-(4-Chlorophenyl)propan-2-ol (1j): The titled compound
ACCEPTED MANUSCRIPT
was prepared in 65% yield (1.116 g, 6.54 mmol) according to the
3. Experimental section
similar procedure mentioned in 2-(4-tolyl)propan-2-ol with Mg
(0.254 g, 10.5 atom), MeI (2.080 g, 14.7 mmol), and 4-
chloroacetophenone (1.557 g, 10.1 mmol) as colorless solid: mp
General: Melting points were determined with Yanaco MP-J3
and values were uncorrected. H and 13C NMR measurements
were performed on a Varian MURCURY plus (300 MHz)
spectrometer and a Bruker AVANCE III-400M (400 MHz)
1
43-45 ºC [lit.:18 43.3 ºC]; H NMR (CDCl3, 300 MHz) δ 1.57 (s,
1
6H), 1.74 (s, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.42 (d, J = 8.8 Hz,
1
2H).19
spectrometer. Chemical shifts (δ) of H NMR were expressed in
parts per million downfield from tetramethylsilane in CDCl3 (δ =
0) as an internal standard. Multiplicities are indicated as s
(singlet), d (doublet), t (triplet), sept (septet), m (multiplet), and
coupling constants (J) are reported in hertz units. Chemical shifts
(δ) of 13C NMR are expressed in parts per million downfield or
upfield from CDCl3 (δ = 77.0) as an internal standard. Infrared
spectra (IR) spectra were recorded on a JASCO FT/IR-460 plus
spectrometer. Mass spectra were carried out on a THERMO
Scientific Exactive in Center for Analytical Instrumentation,
Chiba University. Analytical thin-layer chromatography (TLC)
was performed on glass plates that had been pre-coated with
silica gel (0.25 mm layer thickness). Column chromatography
was performed on 70–230 mesh silica gel. Anhydrous THF was
distilled from sodium benzophenone ketyl immediately prior to
use. Anhydrous CHCl3 was distilled from CaCl2 after washing
with aq. NaOH, and was stored with MS 4Å. Other chemical
materials were used as obtained commercially.
2-(4-(Trifluoromethyl)phenyl)propan-2-ol (1k): The titled
compound was prepared in 41% yield (1.04 g, 4.92 mmol)
according to the similar procedure mentioned in 2-(2-
tolyl)propan-2-ol with Mg (0.291 g, 12.0 atom), 4-
(trifluoromethyl)bromobenzene (2.755 g, 12.2 mmol), and
acetone (1.0 mL, 13.6 mmol) as pale yellow solid: 37-38 ºC
[lit.:20 40.5-41.5 ºC]; 1H NMR (CDCl3, 300 MHz) δ 1.60 (s, 6H),
1.78 (s, 1H), 7.60 (s, 4H); 13C NMR (CDCl3, 75 MHz) δ 31.8,
72.5, 124.2 (q, JC-F = 270.1 Hz), 124.8, 125.2 (q, JC-C-C-F = 3.9
Hz), 128.9 (q, JC-C-F = 31.9 Hz), 153.0.21
2-(Naphthalen-1-yl)propan-2-ol (1l): The titled compound
was prepared in 39% yield (0.732 g, 3.93 mmol) according to the
similar procedure mentioned in 2-(4-tolyl)propan-2-ol with Mg
(0.265 g, 10.9 atom), MeI (1.553 g, 10.9 mmol), and 1-
acetylnaphthalene (1.730 g, 10.2 mmol) as colorless solid: mp 78
ºC; 1H NMR (CDCl3, 300 MHz) δ 1.85 (s, 6H), 1.99 (s, 1H), 7.39
(t, J = 7.5 Hz, 1H), 7.45 (dt, J = 1.5 and 6.8 Hz, 1H), 7.50 (dt, J =
1.8 and 6.8 Hz, 1H), 7.57 (dd, J = 1.1 and 7.3 Hz, 1H), 7.76 (d, J
= 8.1 Hz, 1H), 7.85 (dd, J = 2.2 and 9.6 Hz, 1H), 8.81 (d, J = 8.4
Hz, 1H).22
3.1 Preparation of the Reactant
2-(4-Tolyl)propan-2-ol (1g): To
a suspension of Mg
(turnings) (0.293 g, 12.1 atom) in anhydrous Et2O (17.5 mL) was
dropwise added MeI (1.90 g, 13.4 mmol) at 0 ºC. The suspension
was stirred for 1.5 h at room temperature until Mg was
disappeared. To the solution was dropwise added 4-
methylacetophenone (1.36 g, 10.1 mmol) at 0 ºC, and the mixture
was stirred for 12 h at room temperature. To the reaction mixture
was added H2O (25 mL) and saturated aqueous NH4Cl (25 mL).
After being extracted with EtOAc (30 mL × 3), the organic layer
was dried with MgSO4. After the concentration, 2-(4-tolyl)proan-
2-ol (1.44 g, 9.55 mmol) was obtained in 94% yield as colorless
oil: 1H NMR (CDCl3, 300 MHz) δ 1.57 (s, 6H), 1.72 (s, 1H), 2.34
(s, 3H), 7.15 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H).15
2-(Naphthalen-2-yl)propan-2-ol (1m): The titled compound
was prepared in 64% yield (1.227 g, 6.59 mmol) according to the
similar procedure mentioned in 2-(4-tolyl)propan-2-ol with Mg
(0.278 g, 11.4 atom), MeI (1.716 g, 12.1 mmol), and 2-
acetylnaphthalene (1.744 g, 10.3 mmol) as colorless solid: mp
55-56 ºC; 1H NMR (CDCl3, 300 MHz) δ 1.68 (s, 6H), 1.87 (s,
1H), 7.42-7.49 (m, 2H), 7.60 (dd, J = 1.9 and 8.7 Hz, 1H), 7.81-
7.85 (m, 3H), 7.93 (d, J = 1.8 Hz, 1H).23
Bis(1-phenylethyl) ether (5b):24 To
a solution of 1-
phenylethanol (1b) (0.362 g, 2.97 mmol) in MeNO2 (3 mL) was
added TfOH (14 ꢀL, 016 mmol) at room temperature, and the
mixture was stirred for 2 h at that temperature. After removal of
MeNO2 in vacuo, to the reaction mixture was added saturated
aqueous NaHCO3 (5 mL). After being extracted with hexane (10
mL × 3), the organic layer was dried with MgSO4. After the
concentration, the residue was subject to column chromatography
on SiO2 (hexane : EtOAc = 5 : 1) to give bis(1-phenylethyl) ether
(diastereomer ratio = 73 : 27) (0.2425 g, 1.07 mmol, 72%) as
2-(3-Tolyl)propan-2-ol (1h): The titled compound was
prepared in 80% yield (1.251 g, 8.32 mmol) according to the
similar procedure mentioned in 2-(4-tolyl)propan-2-ol with Mg
(0.254 g, 10.4 atom), MeI (1.651 g, 11.6 mmol), and 3-
1
methylacetophenone (1.451 g, 10.8 mmol) as yellowish oil: H
NMR (CDCl3, 300 MHz) δ 1.57 (s, 6H), 1.79 (s, 1H), 2.37 (s,
3H), 7.06 (d, J = 7.0 Hz, 1H), 7.20-7.32 (m, 3H); 13C NMR
(CDCl3, 75 MHz) δ 21.6, 31.7, 72.5, 121.4, 125.1, 127.4, 128.1,
137.8, 149.0. HRMS (ESI): Calcd. for C10H14NaO ([M+Na]+)
173.0937, found 173.0936.
1
colorless oil: H NMR (CDCl3, 300 MHz) δ 1.38 (d, J = 6.6 Hz,
4.38H), 1.47 (d, J = 6.4 Hz, 1.62H), 4.25 (q, J = 6.5 Hz, 1.46H),
4.53 (q, J = 6.4 Hz, 0.54H), 7.26-7.39 (m, 10H).
2-(2-Tolyl)propan-2-ol (1i): To Mg (turnings) (0.271 g, 11.2
atom) was dropwise added a solution of 2-bromotoluene (1.773
g, 10.4 mmol) in anhydrous THF (25 mL) at 0 ºC. The
suspension was stirred for 3 h at refluxing conditions. To the
solution was dropwise added acetone (2.0 mL, 27.3 mmol) at 0
ºC, and the mixture was stirred for 12 h at 40 ºC. To the reaction
mixture was added H2O (25 mL) and saturated aqueous NH4Cl
(25 mL). After being extracted with EtOAc (30 mL × 3), the
organic layer was dried with MgSO4. After the concentration, the
residue was subject to column chromatography on SiO2 (hexane :
CHCl3 = 5 : 1) to give 2-(2-tolyl)propan-2-ol (0.826 g, 5.50
mmol, 53%) as colorless cubic crystals: mp 36-38 ºC [lit.:16 38-
39 ºC]; 1H NMR (CDCl3, 300 MHz) δ 1.66 (s, 6H), 1.70 (s, 1H),
2.60 (s, 3H), 7.13-7.16 (m, 3H), 7.45 (m, 1H).17
2-Phenyl-2-methoxypropane (6a): To a solution of 2-
phenyl-2-propanol (1c) (1.413 g, 10.4 mmol) in THF (20 mL)
was added NaH (60 wt% oil dispersion) (1.422 g, 35.6 mmol)
and MeI (4.755 g, 33.5 mmol) at room temperature, and the
mixture was stirred for 15 h at that temperature. To the reaction
mixture was added H2O (30 mL). After being extracted with
EtOAc (30 mL × 3), the organic layer was dried with MgSO4.
After the concentration, the residue was subject to column
chromatography on SiO2 (hexane : EtOAc = 9 : 1) to give 2-
phenyl-2-methoxypropane (0.850 g, 5.66 mmol, 54%) as
colorless oil: 1H NMR (CDCl3, 300 MHz) δ 1.53 (s, 6H), 3.07 (s,
3H), 7.25 (t, J = 7.1 Hz, 1H), 7.35 (t, J = 7.8 Hz, 2H), 7.42 (d, J =
8.2 Hz, 2H).25

Triphenylmethyl methyl ether (6b): The titled compound
25 ºC for 2 d. After reducing pressure to release HI gas, to the
reaction mixture was added saturated Na2S2O3 (20 mL) and brine
(15 mL). After being extracted with CHCl3 or Et2O (15 mL × 3),
the organic layer was dried with MgSO4. After the concentration,
ca. 10.0 mg of the residue was combined with p-
chlorobenzaldehyde (ca. 10.0 mg) as an internal standard. And
ACCEPTED MANUSCRIPT
was prepared in 71% yield (0.589 g, 2.15 mmol) according to the
similar procedure mentioned in 2-phenyl-2-methoxypropane with
triphenylmethanol (0.786 g, 3.01 mmol), NaH (60 wt% oil
dispersion) (0.147 g, 3.67 mmol) and MeI (0.28 mL, 4.50 mmol)
1
as colorless solid: mp = 78-79 ºC [lit.:26 82.6-82.9 ºC]: H NMR
1
(CDCl3, 400 MHz) δ 3.06 (s, 3H), 7.23 (t, J = 7.3 Hz, 3H), 7.30
the mixture was measured with H NMR to determine the yield
(t, J = 7.7 Hz, 6H), 7.44 (d, J = 7.1 Hz, 6H).27
by the integration of methyl, methylene or methine peak of the
product and formyl peak of p-chlorobenzaldehyde (9.98 ppm).
Furthermore, the reaction mixture included in p-
chlorobenzaldehyde was subject to column chromatography on
SiO2 to give the product.
2,4-Dimethyl-3-phenylpentan-3-ol:28 To a suspension of Mg
(turnings) (0.4862 g, 0.02 atom) in THF (2.5 mL) was dropwise
added a solution of 2-bromopropane (2.540 g, 20.7 mmol) in
anhydrous THF (25 mL) at 0 ºC. After being stirred for 3 h,
ZnCl2 (0.147 g, 1.08 mmol) was added to the solution at 0 ºC,
and the solution was stirred for 40 min at that temperature. To the
mixture was dropwise added a solution of isobutylophenone
(1.487 g, 10.0 mmol) in THF (10 mL) at 0 ºC, and the mixture
was stirred for 16 h at room temperature. To the reaction mixture
was added saturated aqueous NH4Cl (25 mL). After being
extracted with EtOAc (30 mL × 3), the organic layer was dried
with MgSO4. After the concentration, the residue was subjected
to column chromatography on SiO2 (n-hexane : EtOAc = 20 : 1)
to give 2,4-dimethyl-3-phenylpentan-3-ol (0.330 g, 1.72 mmol)
in 17% yield as colorless oil: 1H NMR (CDCl3, 300 MHz) δ 0.77
(d, J = 6.8 Hz, 6H), 0.85 (d, J = 6.8 Hz, 6H), 1.49 (s, 1H), 2.31
(sept, J = 6.8 Hz, 1H), 7.22 (tt, J = 2.5 and 7.0 Hz, 1H), 7.31
(diffused t, J = 7.9 Hz, 2H), 7.38 (diffused d, J = 7.2 Hz, 2H).
Iodinated products, (iodomethyl)benzene (2a),29 (1-
iodoethyl)benzene
diphenylmethane
(2b),30
(3d),31
and
reduction
products,
1,1-diphenylethane
(3e),32
triphenylmethane (3f),33 were assigned by the corresponding
proton peaks at benzylic positions compared with the chemical
shift reported in the literatures.
1,1,3-Trimethyl-3-phenyl-2,3-dihydro-1H-indene
(4c):
Colorless oil; 1H NMR (CDCl3, 300 MHz) δ 1.04 (s, 3H), 1.35 (s,
3H), 1.69 (s, 3H), 2.19 (d, J = 13.0 Hz, 1H) 2.42 (d, J = 13.0 Hz,
1H), 7.11-7.29 (m, 9H).34
1-Methyl-1,3,3-triphenyl-2,3-dihydro-1H-indene
(4e):
1
colorless solid; H NMR (CDCl3, 300 MHz) δ 1.54 (s, 3H), 3.09
(d, J = 13.5 Hz, 1H), 3.39 (d, J = 13.5 Hz, 1H), 7.00-7.29 (m,
19H).34
3.2 Handling the apparatus for HI collection
1,1,3,5-Tetramethyl-3-(4-tolyl)-2,3-dihydro-1H-indene
(4g): Colorless oil; H NMR (CDCl3, 300 MHz) δ 1.04 (s, 3H),
1.32 (s, 3H), 1.66 (s, 3H), 2.16 (d, J = 13.0 Hz, 1H), 2.30 (s, 3H),
2.35 (s, 3H), 2.37 (d, J = 13.0 Hz, 1H), 6.90 (s, 1H), 7.03-7.09
(m, 6H).34
[Caution!: HI is corrosive in the case to contact with
moisture. The experiment should be conducted into fume
hood.] To pick up anhydrous HI, the stainless tube of the
apparatus for HI collection was dehydrated by heating with
heating gun in vacuo with vacuum pump. The apparatus was
filled with argon gas and was made depression. This cycle was
repeated in several times. After filled with argon gas, the vacuum
pump was exchanged to the line for HI collection. Argon gas was
flowed through the apparatus for 10 min (the flow was controlled
by the control valve for argon). And the following operation was
done at the same time: closing the control valve of argon and
opening the valve of HI cylinder. After 5 min to flow HI gas (the
flow was controlled by the control valve for HI gas), it was
picked up through rubber septum with a syringe attached with
disposable needle. The apparatus was worked off as follows. The
valve of HI cylinder was closed and the control valve of argon
was opened. After continuing argon flow until the neutralization
of the evolved gas (checked by pH paper), the valve of argon
cylinder was closed. The line for HI collection was exchanged to
the vacuum pump, and the apparatus was made depression for 30
min. During the reduced pressure, the stainless tube was heated
with heating gun. The vacuum pump was stopped, and the
apparatus was filled with argon with an application of pressure
(4~5 MPa). The depression and the filling of argon was repeated
in three times to completely exclude HI gas.
1
1,3,3,5-Tetramethyl-1-(3-tolyl)-2,3-dihydro-1H-indene and
1,1,3,4-Tetramethyl-3-(3-tolyl)-2,3-dihydro-1H-indene (4h):
Colorless oil; 1H NMR (CDCl3, 300 MHz) δ 1.03 (s, 0.96H), 1.20
(s, 2.04H), 1.33 (s, 0.96H), 1.34 (s, 2.04H), 1.65 (s, 0.96H), 1.76
(s, 2.04H), 1.89 (s, 2.04H), 2.15 (d, J = 13.3 Hz, 0.68H), 2.16 (d,
J = 13.0 Hz, 0.32H), 2.28 (d, J = 13.3 Hz, 0.68H), 2.30 (s,
2.04H+0.96H), 2.39 (s, 0.96H), 2.40 (d, J = 12.9 Hz, 0.32H),
6.91-7.22 (m, 7H); 13C NMR (CDCl3, 75 MHz) δ 19.2, 21.5,
21.7, 27.5, 29.7, 30.4, 30.6, 31.1, 31.2, 31.6, 42.6, 42.7, 50.3,
51.3, 59.4, 61.3, 120.2, 123.1, 123.5, 123.8, 124.8, 126.1, 126.2,
127.0, 127.3, 127.4, 127.5, 127.8, 127.9, 129.4, 134.7, 136.7,
137.4, 137.5, 146.0, 147.0, 150.7, 151.1, 152.3, 152.7. HRMS
(ESI): Calcd. for C20H23 ([M-H]-) 263.1794, found 263.1796.
1,3,3,4-Tetramethyl-1-(2-tolyl)-2,3-dihydro-1H-indene (4i):
1
Colorless thin plate crystals; mp 64-65 ºC; H NMR (CDCl3, 300
MHz) δ 1.22 (s, 3H), 1.48 (s, 3H), 1.74 (s, 3H), 2.11 (d, J = 13.2
Hz, 1H) ,2.17 (s, 3H), 2.43 (s, 3H), 2.53 (d, J = 13.2 Hz, 1H),
6.83 (d, J = 7.5 Hz, 1H), 7.00-7.11 (m, 6H).35
5-Chloro-3-(4-chlorophenyl)-1,1,3-trimethyl-2,3-dihydro-
1H-indene (4j):34 Colorless solid; mp 69-71 ºC; 1H NMR
(CDCl3, 300 MHz) δ 1.03 (s, 3H), 1.32 (s, 3H), 1.65 (s, 3H), 2.19
(d, J = 13.2 Hz, 1H), 2.36 (d, J = 13.2 Hz, 1H), 7.03 (d, J = 2.0
Hz, 1H), 7.07-7.13 (m, 3H), 7.19-7.27 (m, 3H).
3.3 Procedure for the Reaction of Benzyl Alcohols with HI
gas
In a round bottom flask fitted with three-way cock with
septum was placed benzyl alcohol analogue (1.0-1.5 mmol). The
flask was filled with nitrogen after reducing pressure. After slight
decompression to ease to the gas introduction, HI gas (0.5-2.0
equiv.) was brought in the vessel with syringe through the
septum (the weight of HI gas was calculated the change of the
weight of the equipment before and after the introduction of HI
gas). And nitrogen gas was introduced into vessel to release
deference of pressure against atmosphere. The mixture stood at
1,1,3-Trimethyl-3-(naphthalen-2-yl)-2,3-dihydro-1H-
cyclopenta[a]naphthalene (4l):36 Colorless solid; mp 193-194
ºC; 1H NMR (CDCl3, 300 MHz) δ 1.50 (s, 3H), 1.62 (s, 3H), 1.94
(d, J = 14.8 Hz, 1H), 2.01 (s, 3H), 3.04 (d, J = 14.6 Hz, 1H),
6.80-6.89 (m, 2H), 7.13-7.26 (m, 3H), 7.52-7.88 (m, 10H).
1,3,3-Trimethyl-1-(naphthalen-2-yl)-2,3-dihydro-1H-
cyclopenta[a]naphthalene (4m): Colorless solid; mp 116-117

6
Tetrahedron
ACCEPTED MANUSCRIPT
1
ºC [lit.:37 118-120 ºC, 122-124 ºC (after recyrst.)]; H NMR
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4652−4660.
(CDCl3, 300 MHz) δ 1.40 (s, 3H), 1.45 (s, 3H), 2.08 (s, 3H), 2.36
(d, J = 13.5 Hz, 1H), 2.47 (d, J = 13.5 Hz, 1H), 7.09 (t, J = 7.0
Hz, 1H), 7.21 (dd, J = 1.9 and 8.6 Hz, 1H), 7.29 (t, J = 7.0 Hz,
1H), 7.35-7.48 (m, 4H), 7.65 (d, J = 8.7 Hz, 1H), 7.75-7.85 (m,
5H).35
(2,4-Dimethylpent-2-en-3-yl)benzene: 1H NMR (CDCl3, 300
MHz) δ 0.87 (d, J = 6.9 Hz, 6H), 1.36 (s, 3H), 1.81 (s, 3H), 3.05
(sept, J = 6.9 Hz, 1H), 6.97 (diffused d, J = 8.2 Hz, 2H), 7.21-
7.32 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ 19.3, 21.6, 22.4,
29.9, 125.6, 125.9, 127.5, 130.0, 140.8, 141.4. HRMS (ESI):
Calcd. for C13H22N ([M+NH4]+) 192.1747, found 192.1751.
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Acknowledgments
This work was supported by a Leading Research Promotion
Program “Soft Molecular Activation” from Chiba University,
Japan.
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Supplementary data
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Supplementary data associated with this article can be found
in the online version at
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