Hydrosilanes are not always a reducing reagent: A ruthenium-catalyzed introduction of primary alkyl groups to electron-rich aromatic rings using esters as a source of the alkyl groups

Article abstract of DOI:10.1016/j.tet.2011.08.033

A triruthenium cluster, (μ₃, η², η³, η⁵-acenaphthylene)Ru₃(CO) ₇ effectively catalyzes primary-alkylation reaction of electron-rich aromatic rings using a combination of hydrosilane and est

Full text of DOI:10.1016/j.tet.2011.08.033

Tetrahedron 67 (2011) 7667e7672
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Hydrosilanes are not always a reducing reagent: a ruthenium-catalyzed
introduction of primary alkyl groups to electron-rich aromatic rings using esters
as a source of the alkyl groups
,
b
,
b
a
a
a,b
Hideo Nagashima a , Yuichi Kubo , Mitsunobu Kawamura , Takashi Nishikata , Yukihiro Motoyama
*
a Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga, Fukuoka 816-8580, Japan
b Graduate School of Engineering Sciences, Kyushu University, Kasuga, Fukuoka 816-8580, Japan
a r t i c l e i n f o
a b s t r a c t
A triruthenium cluster, (m3, , , h
h2 h3 5-acenaphthylene)Ru3(CO)7 effectively catalyzes primary-alkylation
Article history:
Received 5 July 2011
Received in revised form 10 August 2011
Accepted 13 August 2011
Available online 18 August 2011
reaction of electron-rich aromatic rings using a combination of hydrosilane and ester as a source of
the primary-alkyl group. The reaction involves electrophilic substitution of arenes by carbocationic
species stabilized by a neighboring alkoxy or siloxy group generated during the reduction of esters giving
alkylated arenes after reductive removal of the alkoxy or siloxy group at the benzylic position.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Ruthenium cluster
Reduction
Alkylation
Ester
Hydrosilane
1. Introduction
The ionic mechanism explains the reduction of aralkyl ketone to
aralkanes by combination of Et3SiH and CF3CO2H. The aralkyl ke-
Hydrosilanes are important precursor of various organosilanes
via catalytic hydrosilylation of alkenes and alkynes.1 Hydrosilanes
are also useful for reducing reagents of ketones, aldehydes, and
imines.2 Since they are less reactive than alumino- and borohy-
drides, a promoter, such as Brønsted acids,2 Lewis acids,3 fluoride
anion,4 and transition metal catalysts5 is necessary to carry out the
hydride reduction. The reduction proceeds through cationic in-
termediates; in the acidic media, the carbonyl function of ketones
or aldehydes is activated by a proton or a Lewis acid; this places
a positive charge on oxygen and makes the carbonyl group more
electrophilic. Subsequent nucleophilic addition of a hydride from
the hydrosilane to form the corresponding alcohols (Scheme 1).
tone is first converted to the benzylic alcohols, which is followed by
benzyl cation formation and subsequent hydride reduction to give
the aralkanes.2,3 As a closely related reaction, alkyl halides, alco-
hols, and ethers are reduced by Et3SiH to alkanes by hydrosilanes
via a carbocationic intermediate in the presence of a strong Lewis
acid, e.g., B(C6F5)3.6 Interestingly, the ionic mechanism suggests
that the carbocationic intermediate is not only trapped by the hy-
dride but also carbonucleophiles.7 This possibility is realized in
special cases where stable carbocationic intermediates are formed
or highly reactive nucleophiles are used.
Recent progress of InX3 chemistry showed that FreideleCrafts
benzylation or reductive allylation with allyl trimethylsilanes were
possible by the reaction of ketones with Me2ClSiH in the presence
of InX3.7,8 Very recently, Sakai and co-workers extends the protocol
to the reaction of benzoic acids with hydrosilanes in the presence of
arenes led to FriedeleCrafts benzylation.8b In the InX3-promoted
reactions, various arenes can be used for the FreideleCrafts re-
action, but only the reactions through benzyl cations are possible.
In contrast, Augustine and co-workers reported that various alde-
hydes behave as alkylating reagents for electron-rich aromatic rings
by treatment with hydrosilanes in CF3CO2H.9
H-Si
H
R
R
H
R
R
R
R
O
H
H
Si
+
C
O
C
O
C
Scheme 1. The ionic mechanism for acid-catalyzed hydrosilane reduction of ketones.
Transition metal-catalyzed hydrosilylation of carbonyl com-
pounds is generally explained by oxidative addition of a SieH bond
of the hydrosilane to a transition metal species, which is followed
* Corresponding author. E-mail address: nagasima@cm.kyushu-u.ac.jp (H.
Nagashima).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.033

7668
H. Nagashima et al. / Tetrahedron 67 (2011) 7667e7672
by insertion of a C]O bond to either MeSi or MeH bond. Reductive
elimination of silyl ethers regenerates an active metal species for
activation of another hydrosilane molecule to establish the catalytic
cycle (Scheme 2).1 Various transition metal compounds are in-
vestigated as the catalyst, and mechanistic studies of the metal-
catalyzed hydrosilylation generally exclude the cationic in-
termediates except recent studies on the hydrosilylation of ketones
using cationic iridium or ruthenium catalysts.1,10
from esters is introduced to the aromatic ring by treatment with
hydrosilanes and a catalytic amount of 1.
2. Results and discussion
As reported earlier, treatment of esters, R1CO2R2, with hydro-
silanes in the presence of 1 mol % of 1 at rt gives the corresponding
alkyl or silyl ethers in good yields (Scheme 4, Eq. 1).11b,f The new
finding is that an aromatic compound,1,3,5-trimethoxybenzene (3),
added to the reaction mixture, is substituted by a primary-alkyl
group, R1CH2, on the aromatic ring as shown in Scheme 4, Eq. 2.
The reactions of ethyl dihydrocinnamate with several hydrosilanes
are summarized in Table 1. A mixture of 3 and ethyl dihy-
drocinnamate (1.2 equiv to 3) was treated with several hydrosilanes
(4.8 equiv to 3) in the presence of 1 (1 mol %) at rt. In the absence of
solvents, the reactions with EtMe2SiH,1,1,3,3-tetramethyldisiloxane
(TMDS), or PhMe2SiH were complete in a few hours to give the
corresponding alkylated product 4a in good yields (runs 1e3). The
reaction with sterically more crowded Et3SiH was slower (run 4).
The reactionwithout solvents is important for selective formation of
the monoalkylated product. In diluted tetrahydropyran solutions,
longer reaction time was required to obtain the product in moderate
to good yields, and concomitant formation of the dialkylated prod-
uct 5a was observed (runs 5 and 6).
R
M
R
C
O
Si-H
O
C
R
R
H
C
O
R
R
H
H
M
M
M
R
R
C
O
Si
Si
Si
R
R
O-Si
R
O-Si
C
C
H
R
H
Scheme 2. Catalytic cycles of transition metal-catalyzed hydrosilylation of ketones.
We have recently found that a triruthenium cluster 1 is a highly
efficient catalyst for hydrosilylation of carbonyl compounds.11
Utility of 1 is seen in successful reduction of carboxylic acids, es-
ters, and amides, which is hardly achieved with conventional cat-
alysts and trialkylsilanes. In the course of the studies, we were
aware that outcome of the reaction might suggest the involvement
of cationic intermediates as shown in Scheme 3, though there is no
compound having acidic or Lewis acidic property to activate SieH
bond.
Table 1
Alkylation of 1,3,5-trimethoxybenzene (3) by the reaction with ethyl dihy-
drocinnamate and hydrosilanes
MeO
R1
OMe
1
(1 mol %)
4a
OMe
+
R3SiH (4.8 equiv)
Ph
(1.2 equiv)
+
3
CO2Et
rt
MeO
R1
OMe
R1
(CO)2
Ru
5a
OMe
?
Si + H-["Ru"]
+ H-Si
Ru(CO)2
(R1 = PhCH2CH2)
Ru
(CO)2
CO
1
Run
R3SiH
Concn
Time (h)
Yield
Scheme 3. Possible generation of ionic species in the hydrosilane reduction catalyzed
by a ruthenium cluster 1.
4a (%)
5a (%)
1
2
3
4
5
6
EtMe2SiH
TMDS
PhMe2SiH
Et3SiH
EtMe2SiH
EtMe2SiH
Neat
Neat
Neat
Neat
5 Ma
1 Ma
1
0.5
2
24
3
95
79
94
0
0
0
Typical related examples are ring-opening polymerization of
cyclic ethers,11a addition polymerization of vinyl ethers12 and
deprotection of tert-butyl esters and Boc,13 which are induced by
hydrosilanes activated by 1 under similar conditions to the re-
duction of carbonyl compounds. If the cationic intermediates are
involved in the hydrosilane reduction of carbonyl compounds with
1(Scheme 4, Eq. 1), it would be trapped by carbonucleophiles. In
this paper, we wish to report that this working hypothesis actually
works well in primary-alkylation of electron-rich aromatics shown
in Scheme 4, Eq. 2, in which reductively generated ‘RCH2-’ group
98
0
63b
51b
37b
49b
24
a
The reaction was carried out in tetrahydropyran (THP).
Determined by 1H NMR.
b
The results changing the esters are shown in Table 2. The re-
actions were carried out using EtMe2SiH as the hydrosilane.
Treatment of 3 with the ester (1.2 equiv to 3) and EtMe2SiH
(4.8 equiv to 3) at rt resulted in selective formation of the mono-
alkylating product 4aei. Although the reaction time of 5 h is long
enough for giving the product listed in Table 2 in high yields, steric
hindrance around the C]O group of the ester somewhat lowered
the yield of the product as shown in runs 7 and 8. Lower reactivity
was significantly observed when ethyl pivaloate was used as the
ester; no reaction took place under the same conditions as above.
Alkoxy moiety of the ester did not affect the rate and the yield of
the product; the ethylation of 3 with EtOAc, i-PrOAc, PhOAc, or
MeOCH2CH2OAc smoothly took place to give 4b quantitatively. The
esters containing a halogen atom in the molecule reacted with 3 to
give the product with the halogen group remaining intact (runs 3
and 4). The reaction of ethyl benzoate required longer reaction time
R1
OR2
1
R1
OSiR3
+
R1
OR2
(eq. 1)
R3SiH
O
MeO
OMe
MeO
R1
OMe
R1
OR2
1
+
(eq. 2)
R3SiH
O
OMe
3
OMe
4
2
Scheme 4. Ruthenium-catalyzed reduction (Eq. 1) and reductive alkylation (Eq. 2) of
esters by hydrosilanes.

H. Nagashima et al. / Tetrahedron 67 (2011) 7667e7672
7669
Table 2
Z
OMe
Monoalkylation of 1,3,5-trimethoxybenzene (3) by ethyl alkanoate and EtMe2SiH
CO2Et
CO2Et
1
1
(1 mol %)
(eq. 6)
MeO
R1
OMe
O
O
EtMe2SiH (4.8 equiv)
TMDS
Z = H, OMe
R1 OEt
O
MeO
MeO
MeO
MeO
+
3
sluggish
OMe
neat
rt, 5 h
4
OMe
OMe
1
R1
Product
Yield (%)
(eq. 7)
Run
TMDS
N
N
1
2
3
4
5
6
7
8
9
PhCH2CH2
Me
ClCH2CH2
BrCH2CH2
i-Bu
4a
4b
4c
4d
4e
4f
4g
4h
4i
95
99
96
95
98
99
88
76
66a
Ts
Ts
9 (74%)
Scheme 6. Intramolecular reaction.
i-Pr
Cyclopentyl
Cyclohexyl
Ph
Above results demonstrates that the ruthenium-catalyzed re-
action with hydrosilane leads to primary-alkylation of 1,3,5-
trimethoxybenzene with various esters. This is an advantage of
this reaction, because it is well known that FriedeleCrafts aromatic
substitution is a good method for introduction of tert- or sec-alkyl
groups to the aromatic ring, but not good for that of CH2R groups.14
In contrast, the arenes, which can be used in this reaction are
limited to electron-rich aromatics, and reduction of esters pre-
dominantly takes place in the case where nucleophilicity of the
arene is not strong enough to trap the intermediary cationic spe-
cies. Two side reactions are observed; one is the reaction of two
molecules of the ester with one molecule of the arene to form
dialkylated products (2:1 reaction), whereas another is that of one
molecule of the ester with two molecules of the arene (1:2 re-
action). The 2:1 reaction is typically seen in the case where the
aromatic ring is sterically less crowded, whereas the 1:2 reaction is
observed in the reaction of electron-rich aromatics. Thus, attemp-
ted alkylation of anisole, 1,2-dimethoxybenzene, and 1,4-
dimethoxybenzene resulted in reduction of esters. The reaction of
1,3-dimethoxybenzene was sluggish due to the predominance of
2:1 reaction. The reaction of 2-tert-butylfuran gave a mixture of the
1:1 and 1:2 product as shown in Scheme 7. Sakai and co-workers
reported benzylation of several aromatic compounds in the
indium-promoted reactions of benzoic acids with hydrosilanes.8b
Although benzyl cationic intermediate formed by the ruthenium-
catalyzed reaction of benzoates with hydrosilanes may promote the
benzylation of a variety of arenes; however, attempted reaction of
anisole with ethyl benzoate was failed due to the slow reaction of
benzoates with hydrosilanes as described above.
a
The reaction was performed with ethyl benzoate (4 equiv) and the hydrosilane
(16 equiv).
(48 h); the yield of the product was moderate even in the presence
of excess amounts of the ester and EtMe2SiH (run 9).
The scheme opened further possibilities for modification of the
reactions. Lactones, carboxylic acids, and aldehydes are also useful
for an alkylating reagent for 3. In typical examples, the lactone 6
was converted to the alcohol 8 as shown in Scheme 5, Eq. 3. NMR
analysis of the primary product indicated formation of the silyl
ether 7, which was treated with TBAF to give the alcohol 8 in 89%
yield from 3. Dihydrocinnamic acid is also useful for the production
of 4 (Scheme 5, Eq. 4). Since the ruthenium cluster 1 is a powerful
catalyst for dehydrogenative silylation of carboxylic acids to silyl
esters, the alkylation proceeds through the silyl ester as the inter-
mediate.11a Despite the low yield of the product, dihy-
drocinnamaldehyde also gives 4 under similar conditions (Scheme
5, Eq. 5).
1
Ph
+
CO2Et
t-Bu
O
EtMe2SiH
(eq. 8)
Ph
Ph
+
t-Bu
t-Bu
O
O
O
10a (14%)
10b (51%)
t-Bu
Scheme 7. Reaction with 2-tert-butylfuran.
Scheme 5. The reaction of 3 with a lactone, carboxylic acid, and aldehyde.
Possible mechanisms are illustrated in Scheme 8. As reported
previously, polymerization of vinyl ethers is initiated by combina-
tion of hydrosilanes and a catalytic amount of 1 under similar
conditions to those used for the aromatic alkylation presented in
this paper. Although the mechanism of hydride abstraction by 1
from hydrosilanes is not clear at present, one of the reasonable
explanations is as follows: the catalyst activates an SieH bond of
R3SiH to result in heterolytic cleavage producing R3Siþ species.
Addition of the formed silyl cation to CH2]CHOR to give a carbo-
cation stabilized by the neighboring OR group, R3SiCH2CHþOR,
Intramolecular version of this aromatic alkylation is attractive
for novel access to bicyclic aromatic compounds. Although
attempted preparation of
a dihydrochromane and a dihy-
droisochromane shown in Eq. 6 of Scheme 6 is hampered due to the
fact that the reduction of ester is faster than the cyclization, the
reaction shown in Eq. 7 gave a trihydroquinoline derivative in 74%
yield probably due to a significant steric bias of N-tosyl group. The
result indicates potential of intramolecular reaction when the ap-
propriate substrate design is performed.

7670
H. Nagashima et al. / Tetrahedron 67 (2011) 7667e7672
which reacts with another molecule of CH2]CHOR to initiate the
addition polymerization.12 When similar mechanisms are applied
to the reaction presented in this paper, a sequence of the reactions
involving activation of C]O or CeO bonds by R3Siþ followed by
attack of the ruthenium hydride results in formation of the in-
termediates A and A0 from the ester used. As shown in path A, the
hydride attack to the intermediate A accomplishes the reduction of
esters. In the meantime, the cationic intermediates A and A0 have
lifetime enough to trap an electron-rich aromatic compound 3,
leading to the aromatic substitution (Path B).15 The resulting benzyl
silyl ether undergoes the above described R3Siþ activation/hydride
reduction sequence to form the final product 4. A possible side
reaction is further alkylation of 4 giving rise to the 2:1 reaction.
Another possible side reaction is trapping of the benzyl cation B by
aromatic compounds leading to the 1:2 reaction. This has never
been observed in the reactions of 3; two OMe groups at the ortho
positions sterically presumably prevent the access of the second
molecule of 3 to the cationic intermediate B. However, the 1:2 re-
action actually takes place in the reactions of sterically less crowded
tert-butylfuran and 1,3-dimethoxybenzene.
shifts (d values) were given in parts per million relative to the
solvent signal (7.26 ppm for CDCl3). Chemical shifts for 13C NMR
were expressed in parts per million in CDCl3 as an internal standard
(
d
¼77.1). HRMS analysis was performed at the Analytical Center in
Institute for Materials Chemistry and Engineering, Kyushu Univer-
sity. IR spectra were measured on JASCO FT/IR-550 and 4200
spectrometers. Analytical thin-layer chromatography (TLC) was
performed on glass plates and aluminum sheets precoated with
silica gel (Merck, Kieselgel 60 F254, layer thickness 0.25 and 0.2 mm,
respectively). Visualization was accomplished by UV light (254 nm),
anisaldehyde, and phosphomolybdic acid. (m3, , , h
h2 h3 5-acenaph-
thylene)Ru3(CO)7(1) was prepared by our method.11
3.2. General procedure
The Ru catalyst 1 (0.005 mmol), ethyl 3-phenylpropanate (2)
(0.6 mmol), and 1,3,5-trimethoxybenzene (3) (0.5 mmol) were se-
quentially added to a reaction tube equipped with a stirring bar and
a
septum under an argon atmosphere. Ethyldimethylsilane
(2.4 mmol) was added by a syringe. After 5 h, the reaction was
quenched with MeOH, and the volatiles were removed in vacuo.
The residue was purified by chromatography (silica-gel) eluting
with hexane/EtOAc to afford the product.
3.3. Spectral data of the products
3.3.1. 1-(3-Phenylpropyl)-2,4,6-trimethoxybenzene (4a). Mp 46.0 ꢀC;
IR (KBr)
1061, 949, 750, 700 cmꢁ1; 1H NMR (396 MHz, CDCl3)
2.59e2.68 (m, 4H), 3.78 (s, 6H), 3.80 (s, 3H), 6.13 (s, 2H), 7.10e7.33
(m, 5H); 13C NMR (99.5 MHz, CDCl3)
22.6, 31.0, 36.0, 55.4, 55.7,
n
2935, 2834, 1609, 1595, 1497, 1455, 1416, 1204, 1150, 1118,
d
1.79 (m, 2H),
d
90.5,111.5,125.4,128.1,128.4,143.2,158.9,159.2; HRMS (EI) calcd for
C18H22O3 286.1569, found 286.1564.
3.3.2. 1-Ethyl-2,4,6-trimethoxybenzene (4b)16. IR (neat)
2937, 2835, 1609, 1497, 1455, 1417, 1314, 1225, 1204, 1148, 1057, 946,
n 2960,
810 cmꢁ1; 1H NMR (396 MHz, CDCl3)
d
1.04 (t, J¼7.2 Hz, 3H), 2.58 (q,
J¼7.2 Hz, 2H), 3.799 (s, 6H), 3.803 (s, 3H), 6.14 (s, 2H); 13C NMR
(99.5 MHz, CDCl3)
d 14.2, 16.0, 55.3, 55.7, 90.7, 113.4, 158.7, 159.1;
HRMS (EI) calcd for C11H16O3 196.1099, found 196.1101.
3.3.3. 1-(4-Chlorobutyl)-2,4,6-trimethoxybenzene (4c). IR (neat)
n
2938, 1595, 1497, 1455, 1416, 1321, 1204, 1149, 1115, 060, 949,
811 cmꢁ1 1H NMR (396 MHz, CDCl3)
1.58 (m, 2H), 1.77 (m, 2H),
2.58 (t, J¼7.2 Hz, 2H), 3.56 (t, J¼7.2 Hz, 2H), 3.79 (s, 6H), 3.80 (s, 3H),
6.12 (s, 2H); 13C NMR (99.5 MHz, CDCl3)
21.6, 26.7, 32.5, 45.4, 55.4,
55.7, 90.5, 111.0, 158.9, 159.3; HRMS (EI) calcd for C13H19ClO3
258.1023, found 258.1021.
Scheme 8. Possible mechanisms.
;
d
Despite the limitation of aromatic compounds, the results
clearly demonstrate that combination of hydrosilanes, esters, and
the ruthenium cluster provides a good method for introduction of
primary-alkyl group to the electron-rich aromatic ring and the
same catalyst system realizes the CeC bond forming reaction. In
a series of our works, we have been showing that hydrosilanes
activated by 1 not only behave as an efficient reducing reagent for
carbonyl compounds but also contributed to achievement of other
organic transformations, such as dehydration13a and depro-
tection.13b The possible mechanisms suggest that appropriate de-
sign of the reaction considering the intermediary cationic species
would give a clue for developing further novel organic trans-
formations, in which we are currently investigating.
d
3.3.4. 1-(4-Bromobutyl)-2,4,6-trimethoxybenzene (4d). IR (neat)
n
2937, 1595, 1497, 1455, 1204, 1148, 810 cmꢁ1 1H NMR (396 MHz,
;
CDCl3)
d
1.58 (m, 2H), 1.85 (m, 2H), 2.58 (t, J¼7.5 Hz, 2H), 3.43 (t,
J¼7.2 Hz, 2H), 3.79 (s, 6H), 3.80 (s, 3H), 6.12 (s, 2H); 13C NMR
(99.5 MHz, CDCl3) d 21.4, 28.0, 32.7, 34.2, 55.4, 55.7, 90.5,110.9,158.9,
159.3; HRMS (EI) calcd for C13H19BrO3 302.0518, found 302.0515.
3.3.5. 1-(3-Methylbutyl)-2,4,6-trimethoxybenzene (4e)17. IR (neat)
n
2953, 2835,1609,1497,1465,1455,1416,1206,1142,1082,1061, 950,
909, 810, 733 cmꢁ1; 1H NMR (396 MHz, CDCl3)
0.92 (d, J¼6.8 Hz,
6H),1.30 (m, 2H), 1.55 (sept, J¼6.8 Hz,1H), 2.54 (m, 2H), 3.79 (s, 6H),
3.80 (s, 3H), 6.13 (s, 2H); 13C NMR (99.5 MHz, CDCl3)
20.6, 22.7,
d
3. Experimental section
3.1. General methods
d
38.9, 55.3, 55.7, 90.6, 112.4, 158.8, 159.0; HRMS (EI) calcd for
C14H22O3 238.1569, found 238.1568.
All reactions were carried out under a nitrogen or argon atmo-
sphere. 1H and 13C NMR spectra were measured on JEOL GSX-270
(270 MHz) and ECA-600 (600 MHz) spectrometers. Chemical
3.3.6. 1-(2-Methylpropyl)-2,4,6-trimethoxybenzene (4f)17. IR (neat)
n
2954, 2835, 1610, 1497, 1464, 1416, 1218, 1204, 1142, 1078, 952,

H. Nagashima et al. / Tetrahedron 67 (2011) 7667e7672
7671
811 cmꢁ1
(sept, J¼6.8 Hz, 1H), 2.43 (d, J¼7.2 Hz, 2H), 3.77 (s, 6H), 3.81 (s, 3H),
6.13 (s, 2H); 13C NMR (67.8 MHz, CDCl3)
22.6, 28.6, 31.4, 55.3, 55.6,
;
1H NMR (396 MHz, CDCl3)
d
0.85 (d, J¼6.8 Hz, 6H), 1.81
1030, 1012, 948, 802, 781, 743, 700 cmꢁ1; HRMS (EI) calcd for
C17H22O242.1671, found 242.1671. Compound 10b: 1H NMR (CDCl3,
d
395 MHz, rt) d 7.33e7.25 (m, 2H), 7.22e7.14 (m, 3H), 5.90 (d,
90.5, 111.2, 159.1, 159.2; HRMS (EI) calcd for C13H20O3 224.1412,
found 224.1412.
J¼3.4 Hz, 2H), 5.85 (d, J¼3.4 Hz, 2H), 4.01 (t, J¼7.2 Hz, 1H), 2.62 (t,
J¼7.2 Hz, 2H), 2.27 (dt, J¼7.2, 7.2 Hz, 2H), 1.27 (s, 18H); 13C NMR
(CDCl3, 67.8 MHz, rt)
d 162.8, 153.4, 142.2, 128.5, 128.3, 125.8, 105.7,
3.3.7. 1-(Cyclopentylmethyl)-2,4,6-trimethoxybenzene (4g). IR (neat)
102.0, 38.6, 35.2, 32.6, 29.1; IR (NaCl) 3028, 2965, 2931, 2905, 2867,
1604, 1557, 1496, 1476, 1458, 1362, 1279, 1261, 1227, 1194, 1127, 1031,
1014, 950, 785, 749, 699 cmꢁ1; HRMS (EI) calcd for C25H32O2
364.2402, found 364.2405.
n
2949, 2864, 1610, 1496, 1455, 1416, 1318, 1204, 1153, 1110, 1062,
950, 811 cmꢁ1 1H NMR (396 MHz, CDCl3)
;
d
1.16e1.29 (m, 2H),
1.41e1.52 (m, 2H), 1.53e1.69 (m, 4H), 2.05 (m, 1H), 2.55 (d, J¼7.2 Hz,
2H), 3.78 (s, 6H), 3.80 (s, 3H), 6.13 (s, 2H); 13C NMR (99.5 MHz,
benzene-d6)
d 25.4, 28.5, 32.8, 41.1, 54.8, 55.1, 90.9, 111.7, 159.5,
Acknowledgements
159.8; HRMS (EI) calcd for C15H22O3 250.1569, found 250.1571.
This work was supported by Grant-in-Aid for Science Research
on Priority Areas (No. 18064014, Synergy of Elements) from Min-
istry of Education, Culture, Sports, Science, and Technology, Japan
and Grant-in-Aid for Young Scientists (Start-up) (22850014).
3.3.8. 1-(Cyclohexylmethyl)-2,4,6-trimethoxybenzene(4h). Mp 68.8 ꢀC;
IR (KBr)
n
2923, 2846, 1600, 1496, 1467, 1413, 1324, 1232, 1147, 1103,
0.91e1.04 (m, 2H),
1058, 952, 806 cmꢁ1; 1H NMR (396 MHz, CDCl3)
d
1.10e1.20 (m, 3H), 1.45 (m, 1H), 1.55e1.69 (m, 5H), 2.43 (d, J¼7.2 Hz,
2H), 3.78 (s, 6H), 3.80 (s, 3H), 6.12 (s, 2H); 13C NMR (99.5 MHz, CDCl3)
Supplementary data
d
26.6, 26.8, 30.1, 33.3, 38.1, 55.3, 55.7, 90.5, 110.8, 159.0, 159.2; HRMS
These data include experimental details, copies of 1H and 13C
NMR spectra. Supplementary data related to this article can be
found online at doi:10.1016/j.tet.2011.08.033.
(EI) calcd for C16H24O3 264.1725, found 264.1718.
3.3.9. Benzyl-2,4,6-trimethoxybenzene (4i)17. IR (neat)
n 2959, 2835,
1596, 1495, 1454, 1416, 1321, 1207, 1151, 1120, 1060, 950, 816,
735 cmꢁ1; 1H NMR (396 MHz, CDCl3)
3.78 (s, 6H), 3.81 (s, 3H), 3.93
(s, 2H), 6.15 (s, 2H), 7.06e7.25 (m, 5H); 13C NMR (67.8 MHz, CDCl3)
28.4, 55.4, 55.7, 90.7, 110.2, 125.3, 128.0, 128.5, 142.3, 158.9, 159.7;
d
References and notes
d
1. (a) Ojima, I. In The Chemistry of Organic Silicon Compounds; Patai, S., Rappoport,
Z., Eds.; Wiley: New York, NY, 1989; Part 2, Chapter 25, pp 1479e1526; (b)
Marciniec, B. Comprehensive Handbook on Hydrosilylation; Pergamon: Oxford,
HRMS (EI) calcd for C16H18O3 258.1256, found 258.1253.
ꢀ
1992; (c) Marchiniec, B.; Gulinski, J. J. Organomet. Chem. 1993, 446, 15e23; (d)
3.3.10. 2-(4-Hydroxyundecyl)-1,3,5-trimethoxybenzene (8). IR (NaCl)
Marciniec, B. In Applied Homogeneous Catalysis with Organometallic Compounds;
Cornils, B., Herrmann, W. A., Eds.; Wiley-VCH: Weinheim, 1996; Vol. 1, Chapter
2; (e) Hydrosilylation: A Comprehensive Review on Recent Advances (Advances in
n
3424, 2925, 2853, 1609, 1597, 1497, 1459, 1228, 1206, 1087,
806 cmꢁ1; 1H NMR (396 MHz, CDCl3)
d
6.13 (s, 2H), 3.80 (s, 3H), 3.79
€
Silicon Science); Marciniec, B., Ed.; Springer: Berlin, 2008; (f) Vorbruggen, H.
(s, 6H), 3.70e3.60 (m, 1H), 2.57 (t, J¼6.8 Hz, 2H), 1.66e1.20 (m, 19H),
Silicon-Mediated Transformations of Functional Groups; Wiley-VCH: Weinheim,
2004; (g) Modern Reduction Methods; Andersson, P. G., Munslow, I. J., Eds.;
Wiley-VCH: Weinheim, 2008, Chapters 4 and 8.
2. Typical examples for acid-mediated hydrosilane reduction, which is so-called
‘Ionic Hydrogenation’ conditions: (a) For a review, Kursanov, D. A.; Parnes, Z.
N.; Loim, N. M. Synthesis 1974, 633e651; (b) West, C. T.; Donnelly, S. J.; Kooistra,
D. A.; Doyle, M. P. J. Org. Chem. 1973, 38, 2675e2681; (c) Mayr, H.; Dogan, B.
Tetrahedron Lett. 1997, 38, 1013e1016.
3. Typical examples for Lewis acid-mediated hydrosilane reduction: (a) Doyle, M.
P.; McOsker, C. C.; West, C. T. J. Org. Chem. 1977, 42, 1922e1928; (b) Fujita, M.;
Hiyama, T. J. Org. Chem. 1988, 53, 5405e5415; (c) Smounou, I. Tetrahedron Lett.
1994, 35, 2071e2074; (d) Nummagadda, R. D.; McRae, C. Tetrahedron Lett. 2006,
47, 5755e5758 See, also Ref. 7.
0.88 (t, J¼6.8 Hz, 3H); 13C NMR (67.8 MHz, CDCl3)
d 159.1, 158.7,
111.4, 90.4, 71.8, 55.6, 55.3, 37.3, 37.0, 31.8, 29.7, 29.3, 25.7, 25.4, 22.6,
22.1, 14.1; HRMS (EI) calcd for C20H34O4 0.338.2457, found 338.2458.
Reaction with carboxylic acid (Eq. 4): Following the general
procedure, using 3-phenylpropionic acid (0.6 mmol), EtMe2SiH
(3.0 mmol), Ru catalyst 1(0.0025 mmol) for 8 h, yielded 4a (94%).
Reaction with aldehyde (Eq. 5): Following the general procedure,
using 3-phenylpropionaldehyde (0.6 mmol), EtMe2SiH (1.5 mmol),
Ru catalyst 1(0.0025 mmol) for 1 h, yielded 4a (35%).
4. Fluoride mediated hydrosilane reduction: Fujita, M.; Hiyama, T. J. Am. Chem.
Soc. 1984, 106, 4629e4630.
3.3.11. 1,2,3,4-Tetrahydro-5,7-dimethoxy-1-(p-toluenesulfonyl)quin-
oline (9). Following the general procedure, using ester shown in Eq.
9 (0.25 mmol), TMDS (2.0 mmol), Ru catalyst 1(0.0025 mmol),
benzene at 50 ꢀC for 5 h, yielded the product 9 (62.3 mg, 74%), IR
5. Typical examples for transition metal catalyzed hydrosilylation of ketones; [Pt].
(a) Yamamoto, K.; Hayashi, T.; Kumada, M. J. Organomet. Chem. 1976, 112,
253e262 [Rh]; (b) Ojima, I.; Kogure, T. Organometallics 1982, 1, 1390e1399 [Rh];
(c) Nagashima, H.; Tatebe, K.; Ishibashi, T.; Nakaoka, A.; Sakakibara, K.; Itoh, K.
Organometallics 1995, 14, 2868e2879 [Ru]; (d) Semmelhack, M. F.; Misra, R. N. J.
Org. Chem. 1982, 47, 2469e2471 [Ti]; (e) Buchwald, S. L.; Reding, M. T. J. Org.
Chem. 1995, 60, 7884e7890.
(neat)
n
2940, 2839, 1611, 1589, 1492, 1462, 1421, 1350, 1341, 1285,
1203, 1163, 1031, 942, 815, 772 cmꢁ1
;
1H NMR (396 MHz, CDCl3)
d
1.49e1.59 (m, 2H), 2.35 (t, J¼7.2 Hz, 2H), 2.38 (s, 3H), 3.75 (s, 3H),
6. Gevorgyan, V.; Rubin, M.; Benson, S.; Liu, J.-X.; Yamamoto, Y. J. Org. Chem. 2000,
65, 6179e6186 and references cited therein.
7. For a review, Auge, J.; Lubin-Germain, N.; Uziel, J. Synthesis 2007, 1739e1764.
8. (a) Onishi, Y.; Ito, T.; Yasuda, M.; Baba, A. Tetrahedron 2002, 58, 8227e8235; (b)
Sakai, N.; Kawana, K.; Ikeda, R.; Nakaike, Y.; Konakahara, T. Eur. J. Org. Chem.
2011, 3178e3183; (c) Nishimoto, Y.; Babu, S. A.; Yasuda, M.; Baba, A. J. Org.
Chem. 2008, 73, 9465e9468.
3.77e3.81 (m, 2H), 3.81 (s, 3H), 6.26 (d, J¼2.4 Hz, 1H), 7.05 (d,
ꢀ
J¼2.4 Hz, 1H), 7.20 (d, J¼8.2 Hz, 2H), 7.54 (d, J¼8.2 Hz, 2H); 13C NMR
(99.5 MHz, CDCl3)
d 20.2, 20.4, 21.5, 46.5, 55.4, 55.5, 95.4, 100.6,
111.3, 127.1, 129.6, 137.2, 138.1, 143.5, 157.9, 158.2; HRMS (EI) calcd
for C18H21NrO4S 347.1191, found 347.1191.
9. Augustine, J. K.; Naik, Y. A.; Mandal, A. B.; Alagarsamy, P.; Akabote, V. Synlett
2008, 2429e2432.
€
10. (a) Muther, K.; Oestreich, M. Chem. Commun. 2011, 334e336; (b) Park, S.;
3.3.12. Reaction with furan (10). Following the general procedure,
using ethyl 3-phenylpropionate (1.0 mmol), 2-tert-butylfuran
(0.5 mmol), EtMe2SiH (4.0 mmol), Ru catalyst 1 (0.0025 mmol) at rt
for 5 h, yielded the product (14% 10a, 51% 10b). Compound 10a: 1H
Brookhart, M. Organometallics 2010, 29, 6057e6064.
11. (a) Nagashima, H.; Suzuki, A.; Iura, T.; Ryu, K.; Matsubara, K. Organometallics
2000, 19, 3579e3590; (b) Matsubara, K.; Iura, T.; Maki, T.; Nagashima, H. J. Org.
Chem. 2002, 67, 4985e4988; (c) Motoyama, Y.; Itonaga, C.; Ishida, T.; Takasaki,
M.; Nagashima, H. Org. Synth. 2005, 82, 188e195; (d) Motoyama, Y.; Mitsui, K.;
Ishida, T.; Nagashima, H. J. Am. Chem. Soc. 2005, 127, 13150e13151; (e) Hanada,
S.; Ishida, T.; Motoyama, Y.; Nagashima, H. J. Org. Chem. 2007, 72, 7551e7559; (f)
Sasakuma, H.; Motoyama, Y.; Nagashima, H. Chem. Commun. 2007, 4916e4918.
12. (a) Nagashima, H.; Itonaga, C.; Yasuhara, J.; Motoyama, Y.; Matsubara, K. Or-
ganometallics 2004, 23, 5779e5786; (b) Harada, N.; Yasuhara, J.; Motoyama, Y.;
Fujimura, O.; Tsuji, T.; Takahashi, T.; Takahashi, Y.; Nagashima, H. Bull. Chem.
Soc. Jpn. 2011, 84, 26e39.
NMR (CDCl3, 395 MHz, rt)
d 7.33e7.24 (m, 2H), 7.23e7.16 (m, 3H),
5.88e5.80 (m, 2H), 2.67 (t, J¼7.7 Hz, 2H), 2.62 (t, J¼7.7 Hz, 2H), 1.96
(tt, J¼7.7 Hz, 2H), 1.26 (s, 9H); 13C NMR (CDCl3, 67.8 MHz, rt)
d 162.5,
153.9, 142.2, 128.5, 128.3, 125.7, 104.8, 101.9, 35.3, 32.5, 29.8, 29.1,
27.6; IR (NaCl) 3065, 3027, 2965, 2866, 2008,1946,1604,1560,1496,
1459, 1455, 1390, 1361, 1279, 1260, 1194, 1140, 1126, 1096, 1079,

7672
H. Nagashima et al. / Tetrahedron 67 (2011) 7667e7672
13. (a) Hanada, S.; Yuasa, A.; Kuroiwa, H.; Motoyama, Y.; Nagashima, H. Eur. J. Org.
Chem. 2008, 4097e4100; (b) Hanada, S.; Yuasa, A.; Kuroiwa, H.; Motoyama, Y.;
Nagashima, H. Eur. J. Org. Chem. 2010, 1021e1025.
the reaction with aldehydes; this leads to the lower yield of 4a in Eq. 5 (35%). As
illustrated in Scheme 8, two intermediates A and A0 possibly mediated the
reductive alkylation with esters, while the reaction of aldehydes with the hy-
drosilane activated by 1 generates A as a single intermediate. It is important
that A has two pathways, reduction (path A) and reductive alkylation (Path B),
whereas A0 is able to take only Path B. One of the explanation for the lower
yield of 4a from the aldehyde than that from the ester is absence of the reaction
pathway to form 4a through A0.
14. (a) Olah, G. A. FriedeleCrafts and Related Reactions; Wiley-Interscience: New
York, NY, 1963; (b) Olah, G. A. FriedeleCrafts Chemistry; Wiley-Interscience:
New York, NY, 1973; (c) Roberts, R. M.; Khalaf, A. A. FriedeleCrafts Alkylation
Chemistry. A Century of Discovery; Marcel Dekker: New York, NY, 1984.
15. As shown in Scheme 5, Eq. 5, aldehydes also behave as a reagent for the aro-
matic alkylation. When esters are used as the alkylating reagent, the aromatic
alkylation is not seriously competitive with simple reduction of esters to silyl
ethers. In contrast, the reduction to silyl ethers is a major reaction pathway in
16. Lal, K.; Ghosh, S.; Salomon, R. G. J. Org. Chem. 1987, 52, 1072e1078.
17. Roelens, F.; Heldring, N.; Dhooge, W.; Bengtsson, M.; Comhaire, F.; Gustafsson,
J.; Treuter, E.; De Keukeleire, D. J. Med. Chem. 2006, 49, 7357e7365.