InBr3-catalyzed deoxygenation of carboxylic acids with a hydrosilane: Reductive conversion of aliphatic or aromatic carboxylic acids to primary alcohols or diphenylmethanes

Article abstract of DOI:10.1002/ejoc.201100161

A simple and practical procedure for the direct reduction of aliphatic carboxylic acids with a variety of functional groups to a primary alcohol using the mild reducing reagent tetramethyldisiloxane (TMDS), in the presence of a catalytic amount of InBr₃ has been developed. This simple reducing system, when used together with a hydrosilane, allows the preparation of the diphenylmethane derivative directly from an aromatic carboxylic acid and an aromatic compound. Copyright

Full text of DOI:10.1002/ejoc.201100161

FULL PAPER
DOI: 10.1002/ejoc.201100161
InBr3-Catalyzed Deoxygenation of Carboxylic Acids with a Hydrosilane:
Reductive Conversion of Aliphatic or Aromatic Carboxylic Acids to Primary
Alcohols or Diphenylmethanes
Norio Sakai,*[a] Keita Kawana,[a] Reiko Ikeda,[a] Yumi Nakaike,[a] and Takeo Konakahara[a]
Keywords: Carboxylic acids / Indium / Reduction / Silanes / Synthetic methods
A simple and practical procedure for the direct reduction of
aliphatic carboxylic acids with a variety of functional groups
to a primary alcohol using the mild reducing reagent tetra-
methyldisiloxane (TMDS), in the presence of a catalytic
amount of InBr3 has been developed. This simple reducing
system, when used together with a hydrosilane, allows the
preparation of the diphenylmethane derivative directly from
an aromatic carboxylic acid and an aromatic compound.
tional groups into its corresponding primary alcohol deriv-
ative. Another disclosure was that the application of a re-
ducing system consisting of InBr3 and PhSiH3 allows the
direct preparation of a diphenylmethane from an aromatic
carboxylic acid and a solvent. Herein, we report the results
of the reduction of a carboxylic acid with a hydrosilane in
the presence of InBr3.
Introduction
Selective reductive deoxygenation of a carboxylic acid
constitutes a central and important position in functional
group conversion.[1] Carboxylic acids are considered to be
relatively resistant to basic reducing reagents owing to the
elimination of the proton and subsequent formation of a
carboxylate ion as a conjugated base. To overcome this
problem, ingenious methods are used that consist of direct
hydrogenation with H2 gas,[2] use of strongly reducing alu-
minum hydrides such as LiAlH4,[3] AlH3,[4] Li(OMe)3-
AlH,[5] and DIBAL,[6] or effective borane reducing agents
such as Lewis acidic diborane (BH3)2,[7] its borane complex
BH3·SMe2,[8] 9-borabicyclo[3.3.1]nonane (9-BBN),[9] or a
NaBH4-additive system.[10] Recently, to selectively reduce a
carbonyl moiety in a reaction substrate, instead of these re-
ducing reagents, a novel reducing process with a milder and
easy-to-handle reducing agent, a hydrosilane, in the pres-
ence of a metal catalyst, has been demonstrated.[11,12] Our
group also found that an InBr3–Et3SiH reducing system ef-
fectively promotes the selective deoxygenation of carboxylic
acid derivatives and cleavage of a C–O bond of acetals to
afford the corresponding reductive products.[13] However,
with the exception of a few examples,[14] a systematic inves-
tigation into chemoselective reduction of a carboxylic acid
with a variety of functional groups using a hydrosilane has
not yet been undertaken. Continued research revealed that
a new reducing system that combines InBr3 with tet-
ramethyldisiloxane (TMDS) promotes the reductive trans-
formation of an aliphatic carboxylic acid with various func-
Results and Discussion
The model reduction of an aliphatic carboxylic acid, 4-
bromophenylacetic acid (1a), was initially conducted using
5 mol-% InBr3 and Et3SiH (4 equiv.), and deoxygenation
was completed within 3 h to produce mixtures of the ex-
pected primary alcohol 2a (50%) and an unexpected silyl
ether derivative 2aЈ (24%) (Table 1, entry 1). Changing the
solvent to 1,2-dichloroethane (DCE) improved the product
ratio of the products (entry 2), and the use of toluene deliv-
ered the same results as the use of chloroform (entry 3). On
the other hand, use of PhSiH3 was ineffective for this reac-
tion (entry 4). Interestingly, running this reaction with
4 equiv. (Si-H) of TMDS led to quantitative and selective
production of the primary alcohol 2a (entry 5).
Having found the optimal conditions shown in Table 1,
entry 5, a variety of aliphatic carboxylic acids were used to
establish the generality of this reduction (Table 2). Most of
the reductive deoxygenation reactions were cleanly com-
pleted within one hour, and the corresponding primary
alcohol derivatives were produced in moderate to good
yields. In particular, the reducing system was tolerant of the
presence of a terminal or internal olefin moiety on the fatty
acid, and the alcohols 2e and 2f were afforded in good
yields. Because neither the bromine nor the iodide substitu-
ents on the benzene ring nor the double bond moiety were
affected by the present reducing system, it was anticipated
that the reaction may proceed through an ionic pathway
[a] Department of Pure and Applied Chemistry, Faculty of Science
and Technology, Tokyo University of Science (RIKADAI),
Noda, Chiba 278-8510, Japan
Fax: +81-4-7123-9890
E-mail: sakachem@rs.noda.tus.ac.jp
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100161.
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InBr3-Catalyzed Deoxygenation of Carboxylic Acids
Table 1. Examination of reaction conditions.
Table 2. Synthesis of primary alcohols 2 from aliphatic carboxylic
acids.[a]
Entry
Silane
(Si-H equiv.)
Solvent
Time
[h]
Yield 2a[a,b]
[%]
1
2
3
4
5
Et3SiH (4)
Et3SiH (4)
Et3SiH (4)
PhSiH3 (4)
TMDS (4)
CHCl3
DCE
toluene
CHCl3
CHCl3
3
3
3
1
1
50 (24)
67 (6)
50 (23)
36 (n.d.)[c]
99 (trace)
[a] NMR yield. [b] Yield of the corresponding silyl ether derivative
are given in parentheses. [c] n.d. = not detected.
rather than a radical path. To further understand the reac-
tion mechanism, the use of substrate 1g, with a cyclopro-
pane ring, was examined. Unfortunately, the reduction re-
sulted in the generation of a complex product mixture.
Furthermore, when the substrate contained a nitro group
on the benzene ring, although the above optimal conditions
were entirely ineffective, the addition of Me3SiCl success-
fully enabled the reduction to produce the corresponding
alcohol 2j in a 75% yield. This result implied that addition
of a silyl halide promoted the reduction. When the substrate
contained a hydroxyl group on the benzene ring, a polymer-
like product was obtained rather than the reduced product.
When the reaction was conducted with an aliphatic carb-
oxyl acid containing either a thioether moiety, a naphthyl,
or a fluorenyl ring, the expected aliphatic alcohols 2l–n were
obtained in good yields. Moreover, use of an aliphatic carb-
[a] Isolated yield. [b] Me3SiCl (1 equiv.) was added to the reaction
mixture. [c] InBr3 (10 mol-%).
alyst to 1 mol-% resulted in a slightly reduced product yield
(entry 5). Running this reaction with InCl3 and In(OTf)3,
instead of either with InBr3 or without the catalyst, ren-
dered the reduction entirely inactive.
oxylic acid with a thiophene ring gave the product 2o in a Table 3. Further examination of reaction conditions.
good yield when 10 mol-% indium catalyst was used. Un-
fortunately, when substrates with a nitrogen-containing
functional group, such as a nitro or an amino group, were
reacted under the standard conditions, the expected re-
Entry
Silane
(Si-H equiv.)
Solvent Time Yield 4a[a]
Ratio[b]
ortho/para
duction did not proceed and only starting materials were
recovered (see below Table 4, entry 6). This catalytic reduc-
ing system simultaneously converted an aldehyde or an es-
ter moiety into the corresponding alcohol or ether, respec-
tively.[13b,13d]
However, the reducing system using InBr3 and Et3SiH in
CHCl3 could not be applied to the reduction of benzoic
acid and its related derivatives (Table 3, entry 1). When the
reducing agent was changed to TMDS, contrary to expecta-
tions, the benzyl alcohol derivative was also not produced
(entry 2). Surprisingly, when the solvent was changed to tol-
[h]
[%]
1
2
3
Et3SiH (4)
TMDS (4)
TMDS (4)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
CHCl3
CHCl3
toluene
toluene
toluene
toluene
3
3
1
Ͻ1
3
5
n.r.
n.r.
84
94
78
–
–
39:61
39:61
38:62
–
4
5[c]
6[d]
n.r.
[a] NMR yield. [b] The ratio of ortho and para was determined by
NMR spectroscopy. [c] InBr3 [1 mol-%]. [d] Without InBr3.
With the optimal conditions shown in Table 3 estab-
uene, the diphenylmethane derivative 4a was produced lished, the generality of this reductive substitution was ex-
through the deoxygenation and substitution reaction with amined using several aromatic carboxylic acids 3 (Table 4).
the solvent in 84% yield (entry 3).[15] This direct prepara- For example, when the benzoic acid was substituted on the
tion of a diphenylmethane derivative from a carboxylic acid benzene ring with an electron-donating group, such as a
and an aromatic compound has not been extensively methyl or a methoxy group, the reaction proceeded
studied,[16] thus, our focus turned to the development of a smoothly to afford the corresponding bisarylmethane deriv-
facile preparation of the derivative and a re-examination of atives 4a and 4b in good yields (entries 1 and 2). However,
the reaction conditions. Finally, 5 mol-% InBr3 and 6 equiv. for benzene derivatives with an electron-withdrawing group,
(Si-H) of PhSiH3 in toluene at 60 °C emerged as the optimal such as a halogen or CN substituent, the yield of the prod-
conditions (entry 4). Decreasing the amount of indium cat- uct 4 was remarkably decreased (entries 5 and 6). In short,
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N. Sakai et al.
FULL PAPER
the decrease in the yield depends entirely on the nucleophi-
licity of the type of substituent on the benzene ring and was
almost proportional to the electron-withdrawing strength of
the substituent.[17] In particular, use of the cyano group,
which is one of the strongest electron-withdrawing substitu-
ents, gave no product, and only starting carboxylic acid was
recovered (entry 6). In contrast, the type of substituent on
the carboxylic acid had no effect on the yield of the di-
phenylmethane derivative 4 (entries 8–10).
Table 4. Synthesis of diphenylmethanes 4.
Scheme 2. Plausible reaction pathway for the reduction of an ali-
phatic carboxylic acid.
Entry
Ar
Ph-R
Time Product
[h]
Yield[a]
[%]
1
2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph-Me
Ph-OMe
Ph-H
Ph-Ph
Ph-Br
Ph-CN
p-xylene
p-xylene
1
1
1
1
1
6
2
2
2
2
4a
4b
4c
4d
4e
4f
83 (39:61)[c]
When the reaction of benzyl alcohol (5) was examined
in the presence of 5 mol-% InBr3 in anisole, contrary to
expectations, the substitution did not occur (Scheme 3). In
contrast, use of the benzyl silyl ether 6 under the same con-
ditions gave the corresponding diphenylmethane derivative
4b in 98% yield. Thus, a plausible mechanism for the for-
mation of the diphenylmethane derivative may proceed
through substitution of the silyl ether derivative generated
in situ, which is activated by InBr3 with a solvent mole-
cule.[19]
85 (39:61)[c]
3
72
4[b]
5
59 (50:50)[c]
38 (34:66)[c]
6
7
8
9
n.r.
91
85
82
77
4g
4h
4i
p-tolyl
4-Cl-C6H4 p-xylene
2-Cl-C6H4 p-xylene
10
4j
[a] Isolated yield. [b] CHCl3 was used as a solvent. [c] The ratio
ortho/para given in parenthesis was determined by NMR spec-
troscopy.
To better understand the reaction pathway, several con-
trol experiments shown in Scheme 1 were conducted. For
example, when the reaction with 3-phenylpropionic acid
(1b) was carried out with 5 mol-% InCl3 and 4 equiv. (Si-
H) of TMDS in CHCl3 in the presence of Me3SiCl, surpris-
ingly, the corresponding primary alcohol 2b was obtained
in quantitative yield. Without Me3SiCl, the desired product
was not formed (Scheme 1). These results strongly support
the idea that the silyl halide functions as a promoter to
move the reduction forward (see footnote [b] in Table 2).
On the basis of the control experiments, a plausible mecha-
nism for the reduction of an aliphatic carboxylic acid is
shown in Scheme 2: (i) first, hydroindation of a starting car-
boxylic acid with HInBr2 and an exchange reaction of the
formed intermediate with silyl bromide generated in situ,
consecutively occurs to give an acetal intermediate with a
silyl group;[14c] (ii) the acetal undergoes re-reduction to-
gether with InBr3-promoted desiloxylation, finally leading
to the corresponding primary alcohol with hydrolysis and
regeneration of InBr3.[18]
Scheme 3. Formation of a diphenylmethane derivative.
Conclusions
An efficient reduction procedure that is capable of di-
rectly converting a variety of carboxylic acids into primary
alcohols using an InBr3–(Me2SiH)2O reducing system has
been developed. This simple catalytic system appears to be
remarkably tolerant of several functional groups including
a C=C bond, a halogen on the benzene ring, a nitro group,
a thioether moiety, and a heterocyclic ring. Furthermore,
diphenylmethane derivatives were produced directly from
the corresponding aromatic carboxylic acid and an aro-
matic compound using this InBr3-PhSiH3 reducing system.
Experimental Section
General Methods: Column chromatography was performed using
silica gel. Chloroform and 1,2-dichloroethane were distilled from
P2O5 and kept dry with molecular sieves (4 Å). Benzene, toluene,
p-xylene, and THF were dried and distilled prior to use. Other or-
ganic solvents, indium(III) salts, and hydrosilanes were commer-
cially available, and were used without further purification. All re-
actions were carried out under a N2 atmosphere, unless otherwise
Scheme 1. Examination of an additive effect of Me3SiCl.
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Eur. J. Org. Chem. 2011, 3178–3183

InBr3-Catalyzed Deoxygenation of Carboxylic Acids
noted. 1H NMR spectra were measured at 500 (or 300) MHz using
tetramethylsilane (TMS) as internal standard. 13C NMR spectra
were measured at 125 (or 75) MHz using TMS or the center peak
of chloroform (δ = 77.0 ppm) as internal standard. High-resolution
mass spectra (FAB or ESI) were measured using a matrix. Benzyl
alcohol (5) and carboxylic acids 1 and 3 were commercially avail-
able and used without a further purification.
29.4, 29.1, 28.9, 25.7 ppm. MS (EI): m/z = 170 (100) [M+]. HRMS
(FAB): calcd. for C11H22O 170.1671; found 170.1669.
Oleyl Alcohol (2f): 154 mg (96%); colorless oil. 1H NMR
(300 MHz, CDCl3): δ = 5.35 (t, J = 5.4 Hz, 2 H, CH), 3.64 (t, J =
6.6 Hz, 2 H, CH2OH), 2.01 (q, J = 5.4 Hz, 4 H, CH=CHCH2),
1.52–1.61 (m, 2 H, CH2CH2OH), 1.19–1.45 (m, 22 H), 0.88 (t, J =
5.4 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 129.9,
129.8, 99.9, 63.0, 32.8, 31.9, 29.74, 29.72, 29.5, 29.50, 29.48, 29.38,
29.30, 29.21, 27.19, 27.17, 25.7, 22.7, 14.1 ppm. MS (EI): m/z =
268 [M+], 82 (100). HRMS (FAB): calcd. for C18H36O 268.2766;
found 268.2760.
2-(2-Iodophenyl)ethanol (2h): 101 mg (68%); colorless oil. 1H NMR
(300 MHz, CDCl3): δ = 7.84 (d, 1 H, ArH), 7.24–7.32 (m, 2 H,
ArH), 6.90–6.95 (m, 1 H, ArH), 3.86 (q, J = 6.3 Hz, 2 H, CH2OH),
3.02 (d, J = 6.3 Hz, 2 H, ArCH2), 1.59 (br. s, 1 H, OH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 141.0, 139.7, 130.3, 128.38, 128.33,
100.7, 62.2, 43.6 ppm. MS (FAB): m/z = 248 [M+]. HRMS (FAB):
calcd. for C8H9IO 247.9698; found 247.9692.
2-(2-Methylphenyl)ethanol (2i): 64 mg (79%); colorless oil. 1H
NMR (500 MHz, CDCl3): δ = 7.13–7.24 (m, 4 H, ArH), 3.82 (t, J
= 6.9 Hz, 2 H, CH2OH), 2.89 (t, J = 6.9 Hz, 2 H, ArCH2), 2.33 (s,
3 H, ArCH3), 1.59 (br. s, 1 H, OH) ppm. 13C NMR (125 MHz,
CDCl3): δ = 136.5, 136.4, 130.4, 129.6, 126.6, 126.0, 62.6, 36.3,
19.4 ppm. MS (EI): m/z = 136 [M+], 105 (100). HRMS (FAB):
calcd. for C9H12O 136.0888; found 136.0881.
General Procedure for the Synthesis of Primary Alcohols from Ali-
phatic Carboxylic Acids: To freshly distilled CHCl3 (0.6 mL) was
successively added 1 (0.6 mmol), InBr3 (10.6 mg, 0.0300 mmol),
and TMDS (212 μL, 1.20 mmol) under a nitrogen atmosphere. The
resulting solution was stirred at 60 °C (bath temperature). The reac-
tion was quenched with H2O (2 mL) and the organic layer was
dried with anhydrous Na2SO4 and evaporated under reduced pres-
sure. The crude product was purified by silica gel column
chromatography (hexane/AcOEt) to afford the corresponding
alcohol.
2-(4-Bromophenyl)ethanol (2a): 119 mg (99%); colorless oil. 1H
NMR (500 MHz, CDCl3): δ = 7.43 (d, J = 8.5 Hz, 2 H, ArH), 7.11
(d, J = 8.5 Hz, 2 H, ArH), 3.84 (t, J = 6.5 Hz, 2 H, CH2OH), 2.82
(t, J = 6.5 Hz, 2 H, Ar-CH2), 1.47 (br. s, 1 H, OH) ppm. 13C NMR
(125 MHz, CDCl3): δ = 137.5, 131.6, 130.7, 120.3, 63.4, 38.5 ppm.
MS (FA): m/z (%) = 202 [M+ + H], 171 (100). HRMS (FAB): calcd.
for C8H9BrO 199.9837; found 199.9830.
Triethyl[2-(4-Bromophenyl)ethoxy]silane (2aЈ): 49 mg (24%); color-
less oil. 1H NMR (500 MHz, CDCl3): δ = 7.39 (d, J = 8.2 Hz, 2
H, ArH), 7.08 (d, J = 8.2 Hz, 2 H, ArH), 3.77 (t, J = 7.0 Hz, 2 H,
CH2O), 2.78 (t, J = 7.0 Hz, 2 H, Ar-CH2), 0.92 (t, J = 7.9 Hz, 9
H, SiCH2CH3), 0.55 (q, J = 7.9 Hz, 6 H, SiCH2) ppm. 13C NMR
(125 MHz, CDCl3): δ = 138.2, 131.2, 130.8, 119.9, 63.7, 38.9, 6.6,
4.3 ppm. MS (ESI): m/z = 337 [M+ + Na]. HRMS (ESI): calcd. for
C14H23BrNaOSi 337.0599; found 337.0591.
1
2-(4-Nitrophenyl)ethanol (2j): 76 mg (75%); white solid. H NMR
(300 MHz, CDCl3): δ = 8.16 (d, J = 8.8 Hz, 2 H, ArH), 7.41 (d, J
= 8.8 Hz, 2 H, ArH), 3.93 (t, J = 6.4 Hz, 2 H, CH2OH), 2.98 (t, J
= 6.4 Hz, 2 H, ArCH2), 1.82 (br. s, 1 H, OH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 146.7, 146.6, 129.8, 123.7, 62.8, 38.8 ppm.
MS (FAB): m/z = 168 [M+ + H]. HRMS (FAB): calcd. for
C8H10NO3 168.0661; found 168.0651.
2-(Phenylthio)ethanol (2l): 51 mg (55%); colorless oil. 1H NMR
(300 MHz, CDCl3): δ = 7.19–7.40 (m, 5 H, ArH), 3.74 (q, J =
6.0 Hz, 2 H, CH2OH), 3.11 (t, J = 6.0 Hz, 2 H, SCH2), 2.22 (br. s,
1 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 134.8, 130.1,
129.0, 126.6, 60.2, 37.2 ppm. MS (FAB): m/z = 154 [M+]. HRMS
(FAB): calcd. for C8H10OS 154.0452; found 154.0448.
2-(1-Naphthyl)ethanol (2m): 65 mg (63%); white solid. 1H NMR
(300 MHz, CDCl3): δ = 7.23–8.04 (m, 7 H, ArH), 3.95 (q, J =
6.7 Hz, 2 H, CH2OH), 3.32 (t, J = 6.7 Hz, 2 H, ArCH2), 1.63 (br.
s, 1 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 134.3, 133.9,
132.0, 128.8, 127.3, 127.1, 126.0, 125.6, 125.5, 123.6, 62.9,
36.1 ppm. MS (EI): m/z (%) = 172 (100) [M+]. HRMS (FAB):
calcd. for C12H12O 172.0888; found 172.0880.
9-Fluorenylmethanol (2n): 60 mg (51%); white solid. 1H NMR
(300 MHz, CDCl3): δ = 7.76 (d, J = 7.5 Hz, 2 H, ArH), 7.59 (d, J
= 7.5 Hz, 2 H, ArH), 7.28–7.41 (m, 4 H, ArH), 4.09 (t, J = 6.0 Hz,
1 H, CH), 4.01 (d, J = 6.0 Hz, 2 H, CH2OH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 144.3, 141.4, 127.6, 127.0, 124.7, 120.0, 65.1,
50.3 ppm. MS (FAB): m/z = 196 [M+]. HRMS (FAB): calcd. for
C14H12O 196.0888; found 196.0890.
3-Phenyl-1-propanol (2b): 69 mg (84%); colorless oil. 1H NMR
(300 MHz, CDCl3): δ = 7.26–7.31 (m, 2 H, ArH), 7.26–7.21 (m, 3
H, ArH), 3.66 (t, J = 6.5 Hz, 2 H, PhCH2), 2.70 (t, J = 7.7 Hz, 2
H, CH2OH), 1.89 (m, 2 H, PhCH2CH2) ppm. 13C NMR (75 MHz,
CDCl3): δ = 141.8, 128.38, 128.35, 125.8, 62.2, 34.2, 32.0 ppm. MS
(EI): m/z = 136 [M+], 118 (100). HRMS (FAB): calcd. for C9H12O
136.0888; found 136.0890.
2-Phenyl-1-propanol (2c): 72 mg (88%); colorless oil. 1H NMR
(500 MHz, CDCl3): δ = 7.32–7.38 (m, 2 H, ArH), 7.21–7.23 (m, 3
H, ArH), 3.68 (d, J = 6.9 Hz, 2 H, CH2OH), 2.90–2.97 (m, 1 H,
CH), 1.60 (br. s, 1 H, OH), 1.27 (d, J = 7.1 Hz, 2 H, CH3) ppm.
13C NMR (125 MHz, CDCl3): δ = 143.7, 128.6, 127.4, 126.6, 68.6,
42.4, 17.5 ppm. MS (EI): m/z (%) = 136 [M+], 105 (100). HRMS
(FAB): calcd. for C9H12O 136.0888; found 136.0889.
1-Dodecanol (2d): 106 mg (95%); colorless oil. 1H NMR (500 MHz,
CDCl3): δ = 3.64 (t, J = 6.6 Hz, 2 H, CH2OH), 1.57 (m, 2 H,
CH2CH2OH), 1.22–1.39 (br. s, 18 H), 0.88 (t, J = 6.9 Hz, 3 H,
CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 63.0, 32.8, 31.9,
29.64, 29.61, 29.60, 29.58, 29.4, 29.3, 25.7, 22.7, 14.1 ppm. MS (EI):
m/z = 185 [M+ – H], 169 (100). HRMS (FAB): calcd. for C12H26O
186.1984; found 186.1982.
2-Thiopheneethanol (2o): 56% (73%); colorless oil. 1H NMR
(300 MHz, CDCl3): δ = 7.16–7.18 (m, 1 H, ArH), 6.94–6.97 (m, 1
H, ArH), 6.87–6.88 (m, 1 H, ArH), 3.86 (q, J = 6.1 Hz, 2 H,
CH2OH), 3.08 (t, J = 6.1 Hz, 2 H, ArCH2), 1.69 (br. s, 1 H,
OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 140.7, 127.0, 125.6,
124.0, 63.5, 33.3 ppm. MS (EI): m/z (%) = 128 [M+], 97 (100).
HRMS (FAB): calcd. for C6H8OS 128.0296; found 128.0311.
10-Undecen-1-ol (2e): 94 mg (92%); colorless oil. 1H NMR
(500 MHz, CDCl3):
δ = 5.81 (ddt, J = 17, 11 Hz, 1 H,
CH2=CHCH2), 4.99 (dd, J = 17, 1.5 Hz, 1 H, CH2=CHCH2), 4.93
(dd, J = 11, 1.5 Hz, 1 H, CH2=CHCH2), 3.63 (t, J = 6.6 Hz, 2 H,
CH2OH), 2.01–2.06 (m, 2 H, CH2=CHCH2), 1.59 (br. s, 1 H, OH),
1.53–1.59 (m, 2 H, CH2CH2OH), 1.28–1.38 (m, 14 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 139.2, 114.1, 63.0, 33.7, 32.7, 29.5,
General Procedure for the Synthesis of Diphenylmethane from an
Aromatic Carboxylic Acid: To the benzene derivative solution
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N. Sakai et al.
FULL PAPER
(0.6 mL) was successively added 1 (0.6 mmol), InBr3 (10.6 mg,
0.0300 mmol) and PhSiH3 (148 μL, 1.20 mmol) under a nitrogen
atmosphere. The resulting solution was stirred at 60 °C (bath tem-
perature). The reaction was quenched with H2O (2 mL) and the
combined organic layer was dried with anhydrous Na2SO4 and
evaporated under reduced pressure. The crude product was purified
by silica gel column chromatography (hexane/AcOEt, 99.5:0.5) to
afford the corresponding diphenylmethane derivative.
20.97, 20.96, 19.2 ppm. MS (EI): m/z (%) = 210 [M+], 195 (100).
HRMS (FAB): calcd. for C6H18 210.1409; found 210.1428.
2-[(4-Chlorophenyl)methyl]-1,4-dimethylbenzene (4i): 113 mg (82%);
colorless oil. 1H NMR (500 MHz, CDCl3): δ = 7.22 (d, J = 8.5 Hz,
2 H, ArH), 7.04 (m, 3 H, ArH), 6.97 (d, J = 8.0 Hz, 1 H, ArH),
6.89 (s, 1 H, ArH), 3.89 (s, 2 H, CH2), 2.28 (s, 3 H, CH3), 2.16 (s,
3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 139.0, 138.1,
135.5, 133.3, 131.6, 130.7, 130.3, 130.0, 128.4, 127.3, 38.8, 20.9,
19.1 ppm. MS (EI): m/z (%) = 230 (100) [M+]. HRMS (FAB):
1
2- and 4-Benzyltoluene (4a): 90 mg (83%); colorless oil. H NMR
(500 MHz, CDCl3): δ = 7.06–7.28 (m, 9 H, o- and p-ArH), 3.98 (s, calcd. for C15H15Cl 230.0862; found 230.0862.
2 H, o-CH2), 3.93 (s, 2 H, p-CH2), 2.30 (s, 3 H, p-CH3), 2.23 (s, 3
2-[(2-Chlorophenyl)methyl]-1,4-dimethylbenzene (4j): 106 mg (77%);
H, o-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 141.4, 140.4,
138.9, 138.1, 136.6, 135.5, 130.3, 129.9, 129.1, 128.90, 128.85,
128.80, 128.7, 128.4, 128.4, 126.4, 126.0, 125.9, 41.5, 39.4, 21.0,
19.6 ppm. MS (FAB): m/z = 181 [M+ – H]. HRMS (FAB): calcd.
for C14H13 181.1017; found 181.1033.
colorless oil. 1H NMR (500 MHz, CDCl3): δ = 7.38 (d, J = 7.8 Hz,
1 H, ArH), 7.08–7.15 (m, 2 H, ArH), 7.07 (d, J = 7.6 Hz, 1 H,
ArH), 6.98 (d, J = 7.6 Hz, 1 H, ArH), 6.87 (d, J = 7.1 Hz, 1 H,
ArH), 6.82 (s, 1 H, ArH), 4.02 (s, 2 H, CH2), 2.27 (s, 3 H, CH3),
2.18 (s, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 138.2,
137.2, 135.5, 134.2, 133.6, 130.5, 130.2, 129.3, 128.9, 127.35,
1
2- and 4-Benzylanisole (4b): 101 mg (85%); colorless oil. H NMR
(500 MHz, CDCl3): δ = 7.05–7.28 (m, 7 H, o- and p-ArH), 6.81– 127.28, 126.7, 36.6, 20.1, 19.0 ppm. MS (FAB): m/z = 230 [M+].
6.86 (m, 2 H, o- and p-ArH), 3.97 (s, 2 H, o-CH2), 3.92 (s, 2 H, p-
CH2), 3.80 (s, 3 H, o-CH3), 3.76 (s, 3 H, p-CH3) ppm. 13C NMR
(125 MHz, CDCl3): δ = 158.0, 157.3, 141.6, 141.0, 133.2, 130.3,
129.8, 129.4, 128.9, 128.8, 128.4, 128.2, 127.4, 125.9, 125.7, 120.4,
113.9, 110.4, 55.3, 55.2, 41.0, 35.8 ppm. MS (FAB): m/z = 198 [M+].
HRMS (FAB): calcd. for C14H14O 198.1045; found 198.1040.
HRMS (FAB): calcd. for C15H15Cl 230.0862; found 230.0869.
Preparation of (Benzyloxy)trietylsilane (6): To freshly distilled THF
(10 mL) were successively added benzyl alcohol (1.0 mL, 10 mmol),
triethylamine (1.4 mL, 10 mmol), and bromotriethylsilane
(10 mmol) under a nitrogen atmosphere. The reaction mixture was
stirred at room temperature overnight, then evaporated under re-
duced pressure. The residue was purified by silica gel column
chromatography (hexane/AcOEt) to afford (benzyloxy)triethylsi-
lane (6).
Diphenylmethane (4c): 73 mg (72%); colorless oil. 1H NMR
(500 MHz, CDCl3): δ = 7.17–7.29 (m, 10 H, ArH), 3.97 (s, 2 H,
CH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 141.1, 128.9, 128.4,
126.0, 41.9 ppm. MS (EI): m/z = 168 (100) [M+]. HRMS (FAB):
calcd. for C13H12 168.2344; found 168.2332.
(Benzyloxy)triethylsilane (6):[20] 2.0 g (92%); colorless oil. 1H NMR
(300 MHz, CDCl3): δ = 7.24–7.34 (m, 5 H, ArH), 4.74 (s, 2 H,
CH2), 0.98 (t, J = 7.9 Hz, 9 H, SiCH2CH3), 0.65 (q, J = 7.9 Hz, 6
2- and 4-Benzylbiphenyl (4d): 86 mg (59%); colorless solid. 1H
NMR (500 MHz, CDCl3): δ = 6.95–7.55 (m, 14 H, o- and p-ArH), H, SiCH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.3, 128.2,
3.99 (s, 2 H, p-CH2), 3.94 (s, 2 H, o-CH2) ppm. 13C NMR 126.9, 126.2, 64.7, 6.7, 4.5 ppm. MS (EI): m/z (%) = 222 [M+], 82
(125 MHz, CDCl3): δ = 142.3, 141.7, 141.4, 141.0, 140.2, 139.0, (100). HRMS (FAB): calcd. for C13H22OSi 222.1440; found
138.2, 130.3, 130.1, 129.30, 129.27, 128.9, 128.8, 128.7, 128.5, 222.1429.
128.2, 128.0, 127.4, 127.2, 127.1, 127.04, 126.97, 126.85, 126.13,
Supporting Information (see footnote on the first page of this arti-
126.12, 125.7, 41.6, 39.0 ppm. MS (FAB): m/z = 244 [M+]. HRMS
cle): NMR spectra for all prepared compounds are supplied.
(FAB): calcd. for C19H16 244.1252; found 244.1274.
2- and 4-Benzylbromobenzene (4e): 56 mg (38%); colorless oil. 1H
Acknowledgments
NMR (500 MHz, CDCl3): δ = 7.03–7.39 (m, 9 H, o- and p-ArH),
4.11 (s, 2 H, o-CH2), 3.92 (s, 2 H, p-CH2) ppm. 13C NMR
This work was partially supported by a grant from the Japan Pri-
vate School Promotion Foundation supported by the Ministry of
Education, Culture, Sports, Science and Technology (MEXT) and
by a grant from the Center for Colloid and Interface Science
(CCIS) program supported by MEXT. The authors thank Shin-
Etsu Chemical Co., Ltd. for a gift of silanes.
(125 MHz, CDCl3): δ = 140.42, 140.37, 140.1, 139.5, 132.8, 131.5,
131.1, 130.6, 129.0, 128.8, 128.6, 128.5, 127.9, 127.4, 126.3, 126.2,
124.9, 119.9, 41.7, 41.3 ppm. MS (FAB): m/z = 247 [M+ + H].
HRMS (FAB): calcd. for C13H12Br 247.0122; found 244.0104.
1,4-Dimethyl-2-(phenylmethyl)benzene (4g): 107 mg (91%); color-
less oil. 1H NMR (500 MHz, CDCl3): δ = 7.26 (t, J = 7.6 Hz, 2 H,
ArH), 7.17 (t, J = 7.6 Hz, 1 H, ArH), 7.12 (d, J = 7.6 Hz, 2 H,
ArH), 7.04 (d, J = 7.8 Hz, 1 H, ArH), 6.96 (d, J = 7.8 Hz, 1 H,
ArH), 6.93 (s, 1 H, ArH), 3.94 (s, 2 H, CH2), 2.28 (s, 3 H, CH3),
2.19 (s, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 140.5,
138.6, 135.3, 133.4, 130.8, 130.2, 128.7, 128.3, 127.1, 125.8, 39.4,
21.0, 19.2 ppm. MS (EI): m/z (%) = 196 [M+], 181 (100). HRMS
(FAB): calcd. for C15H16 196.1252; found 196.1260.
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1
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Eur. J. Org. Chem. 2011, 3178–3183

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Received: February 3, 2011
Published Online: May 2, 2011
Eur. J. Org. Chem. 2011, 3178–3183
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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