N-Alkylation of carbamates and amides with alcohols catalyzed by a Cp*Ir complex

Article abstract of DOI:10.1016/j.tet.2009.03.002

New atom-economical catalytic systems consisting of [Cp^*IrCl₂]₂/NaOAc (Cp^*=pentamethylcyclopentadienyl) for the N-alkylation of carbamates and amides using alcohols as alkylating agents under solvent-free conditions have been developed. For example, the reaction of n-butyl carbamate with benzyl alcohol in the presence of [Cp^*IrCl₂]₂ (5.0 mol % Ir) and NaOAc (5.0 mol %) at 130 °C under the absence of solvent gives n-butyl N-benzylcarbamate in the yield of 94%. The present catalytic system is applicable to not only carbamates but also amides, and only harmless water is produced as co-product.

Full text of DOI:10.1016/j.tet.2009.03.002

Tetrahedron 65 (2009) 3624–3628
Contents lists available at ScienceDirect
Tetrahedron
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N-Alkylation of carbamates and amides with alcohols catalyzed
by a Cp*Ir complex
,
b
,
a
a,
*
Ken-ichi Fujita a , Atsuo Komatsubara , Ryohei Yamaguchi
*
a Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan
b Graduate School of Global Environmental Studies, Kyoto University, Kyoto 606-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
New atom-economical catalytic systems consisting of [Cp*IrCl2]2/NaOAc (Cp*¼pentamethylcyclopenta-
dienyl) for the N-alkylation of carbamates and amides using alcohols as alkylating agents under solvent-
free conditions have been developed. For example, the reaction of n-butyl carbamate with benzyl alcohol
in the presence of [Cp*IrCl2]2 (5.0 mol % Ir) and NaOAc (5.0 mol %) at 130 ꢀC under the absence of solvent
gives n-butyl N-benzylcarbamate in the yield of 94%. The present catalytic system is applicable to not
only carbamates but also amides, and only harmless water is produced as co-product.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 19 February 2009
Accepted 1 March 2009
Available online 6 March 2009
Keywords:
Iridium catalyst
N-Alkylation
Carbamate
Alcohol
1. Introduction
ologies using alcohols are apparently attractive because, (1) they do
not generate wasteful co-products (water is produced as co-prod-
Carbamates are a highly important class of compounds because
of their multiple applications as synthetic intermediates for the
production of a variety of biologically active compounds.1 Carba-
mate moiety can be found in a number of agrochemicals and
pharmaceuticals.2 Therefore, it is quite important to develop effi-
cient methods for the introduction of substituents in carbamates,
since those must provide useful protocols for rapid screening of
biologically active compounds. Meanwhile, carbamates can be
regarded as ammonia equivalents, because the protecting alkoxy
carbonyl group on nitrogen can be readily removed by simple
procedure.3 Thus, the N-alkylation on nitrogen in carbamates
would lead to an easy access to the synthesis of primary amines.
N-Alkylations of carbamates are usually performed by the re-
ductive amination with carbonyl compounds4 or the reaction with
alkyl halides.5 However, both of these reactions have some disad-
vantages from an environmental point of view, because they gen-
erate equimolar amounts of wasteful salts as co-products.
Additionally, the latter is only applicable for the alkylation of sec-
ondary carbamates.
uct), (2) alcohols are more readily available compared to other
alkylating agents such as alkyl halides and carbonyl compounds in
many cases. Several efficient systems for the alkylation of amines7 or
ammonium salts7k,m with alcohols have been reported so far. In
contrast, there have been only two reports on the catalytic N-al-
kylation of amides with alcohols, in both of which high reaction
temperature (>180 ꢀC) is needed.9 Furthermore, to the best of our
knowledge, the N-alkylation of carbamates with alcohols has not
been reported in spite of its importance as described above.
We have recently revealed the high catalytic performance of
[Cp*IrCl2]2 (Cp*¼pentamethylcyclopentadienyl) in the hydrogen
transfer reactions,6b,d and developed catalytic systems for the
N-alkylation of amines and ammonium salts using alcohols as
alkylating agents.7l,m We report here the first catalytic system for
the N-alkylation of carbamates catalyzed by [Cp*IrCl2]2, which can
be conducted without solvent under relatively mild conditions (at
130 ꢀC). The N-alkylation of amides is also demonstrated.
2. Results and discussion
Recently, much attention has been focused on the transition
metal-catalyzed N-alkylation reactions using alcohols as alkylating
agents based on the catalytic hydrogen transfer.6–8 Such method-
Initially, we examined the reactions of n-butyl carbamate (1)
with benzyl alcohol (2a) under various conditions. The results are
summarized in Table 1. When the reaction of 1 (1.0 mmol) and 2a
(2.0 mmol) was carried out in the presence of [Cp*IrCl2]2 (5.0 mol %
Ir) at 130 ꢀC for 17 h, n-butyl N-benzylcarbamate 3a was formed in
57% yield (entry 1). The reaction was selective for mono-alkylation;
no dialkylated product was observed. Other catalysts, [IrCl(cod)]2,
* Corresponding authors. Fax: þ81 75 753 6634.
E-mail addresses: fujitak@kagaku.mbox.media.kyoto-u.ac.jp (K.-i. Fujita), yama@
kagaku.mbox.media.kyoto-u.ac.jp (R. Yamaguchi).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.03.002

K.-i. Fujita et al. / Tetrahedron 65 (2009) 3624–3628
3625
Table 1
Table 2
N-Alkylation of n-butyl carbamate (1) with benzyl alcohol (2a) under various
N-Alkylation of n-butyl carbamate (1) and methyl carbamate (4) with various
conditionsa
alcoholsa
Entry
1
Carbamate
Alcohol
Product
Yieldb (%)
87 (94c)
Entry
Catalyst
Base
Temp (ꢀC)
Yieldb (%)
1
2
3
4
5
6
7
8
[Cp IrCl2]2
None
None
None
None
NaHCO3
t-BuONa
NaOAc
NaOAc
NaOAc
NaOAc
130
130
130
130
130
130
130
120
140
130
57 (46c)
Trace
Trace
17
72
71
78
59
46
94
*
R1¼n-Bu (1)
3a
[IrCl(cod)]2
[Cp RhCl2]2
*
RuCl2(PPh3)3
[Cp IrCl2]2
*
2
R1¼n-Bu (1)
R1¼n-Bu (1)
R1¼n-Bu (1)
R1¼n-Bu (1)
R1¼n-Bu (1)
R1¼n-Bu (1)
R1¼n-Bu (1)
R1¼n-Bu (1)
R1¼n-Bu (1)
3b
3c
3d
3e
3f
92
67
55
67
58
53
57
69
50
[Cp IrCl2]2
*
[Cp IrCl2]2
*
[Cp IrCl2]2
*
9
[Cp IrCl2]2
*
10d
[Cp IrCl2]2
3
*
a
The reaction was carried out with
1 (1.0 mmol), 2a (2.0 mmol), catalyst
(5.0 mol % metal), and base (5.0 mol %) for 17 h.
b
Determined by GC.
Isolated yield.
4.0 mmol of 2a was used.
4
c
d
5d
6d
7
[Cp*RhCl2]2, and RuCl2(PPh3)3, which have been used as catalysts in
hydrogen transfer reactions, showed inferior activity for the pres-
ent reaction at 130 ꢀC (entries 2–4). The reaction was considerably
accelerated by the addition of a base. When the reaction was car-
ried out in the presence of NaHCO3 (5.0 mol %), the yield of 3a was
improved to 72% (entry 5). Stronger base (t-BuONa) was also ef-
fective (entry 6). We finally found that NaOAc was the base of
choice, and the yield of 3a was increased up to 78% (entry 7). The
optimum reaction temperature was 130 ꢀC; the reactions at lower
(120 ꢀC) or higher (140 ꢀC) temperatures resulted in the lower
yields (entries 8 and 9). An excellent yield of 3a (94%) was obtained
by the reaction using 4 equiv of 2a (entry 10).10
On the basis of the optimization of the reaction conditions, the
N-alkylation reactions of 1 with various primary alcohols were
conducted. The results are summarized in Table 2. The reactions
with benzyl alcohols bearing electron-donating (2b,c) and elec-
tron-withdrawing (2d–h) substituents at the aromatic ring pro-
ceeded to give the corresponding products (3b–h) in moderate to
good yields (entries 2–8), although the higher catalyst loadings
(10 mol % Ir) were required in some cases (entries 5, 6, and 8).
Chloro- and bromo-substituents were tolerant in this catalytic
system, which is promising for further transformation of the
products. Other aromatic alcohols such as 2-naphthylmethanol (2i)
and 2-pyridylmethanol (2j), and an aliphatic alcohol such as 1-
butanol (2k) could be also used as alkylating agents (entries 9–11).
We also carried out the reaction of methyl carbamate (4) with 2a,
which gave methyl N-benzylcarbamate (5a) in 46% yield (entry
12).11 The reactions of 1 with secondary alcohols (1-phenylethanol,
1-phenyl-2-propanol, and 2-butanol) were also attempted, but the
alkylation did not proceed in such reactions.
3g
3h
3i
8d
9
10d
11d
3j
R1¼n-Bu (1)
R1¼Me (4)
3k
5a
65
46
12
a
The reaction was carried out with carbamate (1.0 mmol), alcohol (4.0 mmol),
[Cp*IrCl2]2 (5.0 mol % Ir), and NaOAc (5.0 mol %) at 130 ꢀC for 17 h.
b
Isolated yield.
GC yield.
c
d
[Cp IrCl2]2 (10 mol % Ir) and NaOAc (10 mol %) were used.
*
The n-butoxycarbonyl moiety in the N-alkylated n-butyl carba-
mate could be easily removed by simply refluxing in MeOH/H2O
under the basic condition (Eq. 1). Thus, n-butyl carbamate (1) can
be regarded as an ammonia equivalent, and the present catalytic
system provides a new protocol for the transformation of an alcohol
to a primary amine.
of benzamide (6) with benzyl alcohol (2a) was conducted in the
presence of [Cp*IrCl2]2 (5.0 mol % Ir) and NaOAc (5.0 mol %) at
130 ꢀC for 17 h, N-benzylbenzamide (8a) was obtained in the iso-
lated yield of 81% (entry 1). The reaction of 6 with 40-methylbenzyl
alcohol (2b) also gave 8b in excellent yield (entry 2). Other benzyl
alcohols bearing electron-donating and electron-withdrawing
substituent (2c and 2d) could be also used as alkylating agents
(entries 3 and 4). Similar reactions of 6 with aliphatic primary al-
cohols such as 1-butanol (2k), 1-hexanol (2l), and 3-methyl-1-bu-
tanol (2m) also proceeded to give the corresponding N-alkylated
benzamides in moderate to high yields (entries 5–7). The reactions
of acetamide (7) with 2a and 2b were also carried out. The products
ð1Þ
We next studied the N-alkylation of amides (6 and 7) with al-
cohols. The results are summarized in Table 3.11 When the reaction

3626
K.-i. Fujita et al. / Tetrahedron 65 (2009) 3624–3628
Table 3
N-Alkylation of benzamide (6) and acetamide (7) with various alcoholsa
Entry
1
Carbamate
Alcohol
Product
Yieldb (%)
81
R1¼Ph (6)
8a
2
R1¼Ph (6)
8b
91
3
R1¼Ph (6)
R1¼Ph (6)
8c
59
67
Scheme 1.
4c
8d
(5.0 mol % Ir) and NaOAc (5.0 mol %) in toluene at 130 ꢀC for 17 h, N-
benzylbenzamide (8a) was formed in 78% yield (Eq. 2). This result
indicates that the iminic species D would be incorporated in the
catalytic cycle, supporting the proposed reaction pathway.
5
R1¼Ph (6)
8k
82
6
7
R1¼Ph (6)
R1¼Ph (6)
8l
66
70
ð2Þ
8m
In summary, we have developed new atom-economical catalytic
systems for the N-alkylation of carbamates and amides using al-
cohols as alkylating agents under solvent-free conditions. The
present study is, to the best of our knowledge, the first example of
the N-alkylation of carbamates with alcohols. Additionally, the N-
alkylation of amides were also achieved under relatively mild
conditions (at 130 ꢀC) compared to the known systems catalyzed by
ruthenium.
8
R1¼Me (7)
R1¼Me (7)
9a
9b
64
66
9
a
The reaction was carried out with amide (1.0 mmol), alcohol (4.0 mmol),
[Cp IrCl2]2 (5.0 mol % Ir), and NaOAc (5.0 mol %) at 130 ꢀC for 17 h.
*
b
Isolated yield.
c
[Cp IrCl2]2 (10 mol % Ir) and NaOAc (10 mol %) were used.
*
3. Experimental section
3.1. General
9a and 9b were obtained in 64 and 66% yield, respectively (entries 8
and 9), which were slightly lower than those in the corresponding
reactions of 6.
All reactions and manipulations were carried out under an at-
mosphere of argon by means of standard Schlenk techniques. 1H
and 13C NMR spectra were recorded on JEOL A-500 and EX-270
spectrometers. Gas chromatography (GC) analyses were performed
on a GL-Sciences GC353B gas chromatograph with a capillary col-
umn (GL-Sciences TC-17). Column chromatography was carried out
by using Wako-gel C-200. Elemental analyses were carried out at
the Microanalysis Center of Kyoto University. Solvents were dried
by standard procedures and distilled prior to use. The catalyst
[Cp*IrCl2]2 (Cp*¼pentamethylcyclopentadienyl) was prepared
according to the literature method.15 All other reagents are com-
mercially available and were used as received.
Although the mechanism for the present reaction is not com-
pletely clear yet, a possible reaction pathway is shown in Scheme 1.
A similar reaction mechanism has been proposed for the ruthe-
nium-catalyzed N-alkylation of amides with alcohols by Watanabe
et al.9a,12 The first step of the reaction would involve the hydrogen
transfer oxidation of a primary alcohol through an alkoxo iridium
species A to the corresponding aldehyde B accompanied by the
formation of a hydrido iridium species C.13 Then, the condensation
of the aldehyde B with a carbamate or an amide would occur to
afford an N-acyl imine D.14 Addition of the hydrido iridium C to
a carbon–nitrogen double bond of D would occur to give an amido
iridium species E. The species E would react with an alcohol to give
the product and regenerate the catalytically active alkoxo iridium
species A. The base (NaOAc) would stimulate the formation of the
alkoxo iridium species A by trapping hydrogen chloride generated
at the first step of the reaction.
3.2. Optimization of the reaction of n-butyl carbamate (1)
with benzyl alcohol (2a) (Table 1)
In a heavy-walled glass reactor under an atmosphere of argon
were placed the catalyst (5.0 mol % metal), base (5.0 mol %), 1
(1.0 mmol), and 2a (2.0 mmol). The mixture was stirred at 130 ꢀC
for 17 h in the sealed reactor. The yield of n-butyl N-benzylcarba-
mate (3a) was determined by GC analysis using undecane as an
internal standard.
To support the proposed reaction pathway shown above, the
transfer hydrogenation of N-benzylidenebenzamide 10 (this cor-
responds to the possible intermediate D) using an alcohol as a hy-
drogen source was carried out. When the reaction of 10 with
3 equiv of 2-propanol was conducted in the presence of [Cp*IrCl2]2

K.-i. Fujita et al. / Tetrahedron 65 (2009) 3624–3628
3627
3.3. N-Alkylation of carbamates with various alcohols
(Table 2)
(t, J¼8 Hz, 2H, OCH2), 1.61 (m, 2H, CH2), 1.37 (m, 2H, CH2), 0.93
(t, J¼8 Hz, 3H, CH3). 13C NMR (CDCl3)
d 156.8, 141.0, 130.4, 130.3,
130.1, 126.0, 122.6, 65.0, 44.3, 30.1, 19.0, 13.7. Anal. Calcd for
C12H16BrNO2: C, 50.37; H, 5.64; N, 4.89. Found: C, 51.06; H, 5.69; N,
4.84.
In a heavy-walled glass reactor under an atmosphere of argon
were placed [Cp*IrCl2]2 (0.025 mmol, 5.0 mol % Ir), NaOAc
(0.050 mmol, 5.0 mol %), carbamate 1 or 4 (1.0 mmol), and alcohol
(4.0 mmol). The mixture was stirred at 130 ꢀC for 17 h in the
sealed reactor. After cooled to room temperature, the products
were isolated by column chromatography (eluent: hexane/ethyl
acetate). The products 3a,16 3k,17 and 5a18 were known com-
pounds, which were identified by spectral comparison with lit-
erature data. The NMR and elemental analysis data of other
products are as follows.
3.3.8. n-Butyl N-(2-naphthylmethyl)carbamate (3i)
1H NMR (CDCl3)
d 7.82–7.70 (m, 3H, aromatic), 7.70 (s, 1H, aro-
matic), 7.48–7.38 (m, 3H, aromatic), 5.08 (br s, 1H, NH), 4.51 (d,
J¼5 Hz, 2H, NCH2), 4.11 (t, J¼8 Hz, 2H, OCH2), 1.63 (m, 2H, CH2), 1.37
(m, 2H, CH2), 0.93 (t, J¼8 Hz, 3H, CH3). 13C NMR (CDCl3)
d 156.8,
136.0, 133.3, 132.7, 128.4, 127.7, 127.6, 126.2, 126.0, 125.8, 125.7, 65.0,
45.2, 31.1, 19.0, 13.7. Anal. Calcd for C16H19NO2: C, 74.68; H, 7.44; N,
5.44. Found: C, 74.70; H, 7.51; N, 5.35.
3.3.1. n-Butyl N-(40-methylbenzyl)carbamate (3b)
1H NMR (CDCl3)
d
7.24–7.10 (m, 4H, aromatic), 5.06 (br s, 1H,
3.3.9. n-Butyl N-(2-pyridylmethyl)carbamate (3j)
NH), 4.29 (d, J¼6 Hz, 2H, NCH2), 4.07 (t, J¼7 Hz, 2H, OCH2), 2.32 (s,
1H NMR (CDCl3)
d
8.53 (d, J¼5 Hz, 1H, aromatic), 7.69–7.63 (m,
3H, Me), 1.58 (m, 2H, CH2), 1.37 (m, 2H, CH2), 0.92 (t, J¼8 Hz, 3H,
1H, aromatic), 7.29 (d, J¼8 Hz, 1H, aromatic), 7.20–7.16 (m, 1H, ar-
omatic), 5.96 (br s, 1H, NH), 4.49 (d, J¼6 Hz, 2H, NCH2), 4.09
(t, J¼6 Hz, 2H, OCH2), 1.61 (m, 2H, CH2), 1.37 (m, 2H, CH2), 0.92
CH3). 13C NMR (CDCl3)
d 156.6, 136.9, 135.5, 129.1, 127.3, 64.8, 44.7,
31.1, 21.1, 19.1, 13.8. Anal. Calcd for C13H19NO2: C, 70.56; H, 8.65; N,
6.33. Found: C, 70.81; H, 8.50; N, 6.25.
(t, J¼7 Hz, 3H, CH3). 13C NMR (CDCl3)
d 157.2, 156.9, 149.0, 136.7,
122.2,121.7, 64.8, 45.9, 31.0,19.0,13.6. Anal. Calcd for C11H16N2O2: C,
63.44; H, 7.74; N, 13.45. Found: C, 63.14; H, 7.53; N, 13.31.
3.3.2. n-Butyl N-(30-methoxylbenzyl)carbamate (3c)
1H NMR (CDCl3)
d
7.24 (t, J¼8 Hz, 1H, aromatic), 6.88–6.79 (m,
3H, aromatic), 5.05 (br s,1H, NH), 4.33 (d, J¼6 Hz, 2H, NCH2), 4.09 (t,
3.4. Conversion of n-butyl N-benzylcarbamate (3a) to
benzylamine (Eq. 1)
J¼7 Hz, 2H, OCH2), 3.79 (s, 3H, OMe), 1.61 (m, 2H, CH2), 1.37 (m, 2H,
CH2), 0.92 (t, J¼7 Hz, 3H, CH3). 13C NMR (CDCl3)
d 159.8,156.8,140.2,
129.6, 119.6, 113.0, 112.8, 64.9, 55.1, 44.9, 31.0, 19.0, 13.7. Anal. Calcd
for C13H19NO3: C, 65.80; H, 8.07; N, 5.90. Found: C, 65.97; H, 7.94; N,
5.77.
In a flask, 3a (227.2 mg, 1.096 mmol), NaOH (991.2 mg,
24.8 mmol), methanol (3.0 mL), and water (3.0 mL) were placed.
The mixture was heated under reflux for 41 h. After cooled to room
temperature, the product was extracted with dichloromethane. The
yield of benzylamine was determined by GC analysis using unde-
cane as an internal standard.
3.3.3. n-Butyl N-(40-chlorobenzyl)carbamate (3d)
1H NMR (CDCl3)
d 7.30–7.19 (m, 4H, aromatic), 5.14 (br s,1H, NH),
4.30 (d, J¼6 Hz, 2H, NCH2), 4.07 (t, J¼7 Hz, 2H, OCH2), 1.61 (m, 2H,
CH2), 1.37 (m, 2H, CH2), 0.92 (t, J¼7 Hz, 3H, CH3). 13C NMR (CDCl3)
3.5. N-Alkylation of amides with various alcohols (Table 3)
d
156.6, 137.1, 133.0, 128.65, 128.55, 65.0, 44.3, 31.1, 19.1, 13.8. Anal.
Calcd for C12H16ClNO2: C, 59.63; H, 6.67; N, 5.79. Found: C, 59.58; H,
6.47; N, 5.73.
In a heavy-walled glass reactor under an atmosphere of argon
were placed [Cp*IrCl2]2 (0.025 mmol, 5.0 mol % Ir), NaOAc
(0.050 mmol, 5.0 mol %), amide 6 or 7 (1.0 mmol), and alcohol
(4.0 mmol). The mixture was stirred at 130 ꢀC for 17 h in the sealed
reactor. After cooled to room temperature, the products were iso-
lated by column chromatography (eluent: hexane/ethyl acetate).
The products 8a,19 8b,20 8d,21 8k,22 8l,9a 8m,23 9a,24 and 9b25 were
known compounds, which were identified by spectral comparison
with literature data. The NMR data of 8c26 are as follows.
3.3.4. n-Butyl N-(30-chlorobenzyl)carbamate (3e)
1H NMR (CDCl3)
d 7.27–7.16 (m, 4H, aromatic), 5.20 (br s, 1H,
NH), 4.32 (d, J¼6 Hz, 2H, NCH2), 4.08 (t, J¼7 Hz, 2H, OCH2), 1.59 (m,
2H, CH2), 1.37 (m, 2H, CH2), 0.92 (t, J¼7 Hz, 3H, CH3). 13C NMR
(CDCl3)
d 156.6, 140.7, 134.3, 129.7, 127.4, 127.3, 125.4, 65.0, 44.4,
31.0, 19.1, 13.8. Anal. Calcd for C12H16ClNO2: C, 59.63; H, 6.67; N,
5.79. Found: C, 59.56; H, 6.66; N, 5.80.
3.5.1. N-(30-Methoxylbenzyl)benzamide (8c)
3.3.5. n-Butyl N-(30,40-dichlorobenzyl)carbamate (3f)
1H NMR (CDCl3)
d
7.78 (d, J¼7 Hz, 2H, aromatic), 7.51–7.37
1H NMR (CDCl3)
d
7.39–7.10 (m, 3H, aromatic), 5.15 (br s,1H, NH),
(m, 3H, aromatic), 7.25 (t, J¼8 Hz, 1H, aromatic), 6.93–6.81 (m, 3H,
4.30 (d, J¼6 Hz, 2H, NCH2), 4.08 (t, J¼7 Hz, 2H, OCH2), 1.61 (m, 2H,
aromatic), 6.62 (br s, 1H, NH), 4.59 (d, J¼6 Hz, 2H, CH2), 3.78 (s, 3H,
CH2), 1.38 (m, 2H, CH2), 0.93 (t, J¼7 Hz, 3H, CH3). 13C NMR (CDCl3)
OMe).13C NMR (CDCl3)
d 167.3,159.9,139.8,134.3,131.5,129.7,128.5,
d
156.6, 139.1, 132.6, 131.3, 130.5, 129.2, 126.7, 65.1, 43.8, 31.0, 19.0,
126.9, 120.0, 113.4, 112.9, 55.2, 44.0. Anal. Calcd for C15H15NO2: C,
74.67; H, 6.27; N, 5.81. Found: C, 74.55; H, 6.32; N, 5.66.
13.7. Anal. Calcd for C12H15Cl2NO2: C, 52.19; H, 5.47; N, 5.07. Found:
C, 52.16; H, 5.37; N, 5.02.
3.6. Preparation of N-benzylidenebenzamide (10)
3.3.6. n-Butyl N-(40-bromobenzyl)carbamate (3g)
1H NMR (CDCl3)
d
7.43 (d, J¼8 Hz, 2H, aromatic), 7.16 (d, J¼8 Hz,
In a flask, benzamide (2.03 g, 16.8 mmol), PhSO2Na (5.54 g,
33.7 mmol), methanol (16 mL), and water (32 mL) were placed.
Benzaldehyde (3 mL) was then added in one portion, followed by
formic acid (1.3 mL). The mixture was stirred at 50 ꢀC for 120 h. The
precipitate was isolated by Bu¨chner funnel filtration and purified by
washing with water. Then, the white solid was transferred to
a flask, K2CO3 (1.89 g, 13.7 mmol), Na2SO4 (2.29 g, 16.1 mmol), and
toluene (30 mL) were added. The mixture was heated under reflux
for 15 h. After the mixture was filtered through a pad of Celite and
evaporation of the filtrate gave 10 (161.7 mg, 0.7730 mmol, 4.6%).
2H, aromatic), 5.02 (br s,1H, NH), 4.30 (d, J¼6 Hz, 2H, NCH2), 4.08 (t,
J¼6 Hz, 2H, OCH2), 1.62 (m, 2H, CH2), 1.37 (m, 2H, CH2), 0.92 (t,
J¼7 Hz, 3H, CH3). 13C NMR (CDCl3)
d 156.6, 137.6, 131.6, 129.0, 121.1,
65.0, 44.4, 31.1, 19.1, 13.8. Anal. Calcd for C12H16BrNO2: C, 50.37; H,
5.64; N, 4.89. Found: C, 50.56; H, 5.52; N, 4.92.
3.3.7. n-Butyl N-(30-bromobenzyl)carbamate (3h)
1H NMR (CDCl3)
d
7.43–7.37 (m, 2H, aromatic), 7.27–7.18 (m, 2H,
aromatic), 5.14 (br s, 1H, NH), 4.32 (d, J¼5 Hz, 2H, NCH2), 4.09

3628
K.-i. Fujita et al. / Tetrahedron 65 (2009) 3624–3628
P. Eur. J. Inorg. Chem. 2004, 524; (g) Cami-Kobeci, G.; Slatford, P. A.; Whittlesey,
1H NMR (CDCl3)
d
8.77 (s, 1H, iminic CH), 8.17 (d, J¼7 Hz, 2H, aro-
M. K.; Williams, J. M. J. Bioorg. Med. Chem. Lett. 2005, 535; (h) Tillack, A.;
Hollmann, D.; Michalik, D.; Beller, M. Tetrahedron Lett. 2006, 47, 8881; (i) Ha-
mid, M. H. S. A.; Williams, J. M. J. Chem. Commun. 2007, 725; (j) Hollmann, D.;
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Hamid, M. H. S. A.; Williams, J. M. J. Tetrahedron Lett. 2007, 48, 8263; (l) Fujita,
K.; Enoki, Y.; Yamaguchi, R. Tetrahedron 2008, 64, 1943; (m) Yamaguchi, R.;
Kawagoe, S.; Asai, C.; Fujita, K. Org. Lett. 2008, 10, 181; (n) Balcells, D.; Nova, A.;
Clot, E.; Gnanamgari, D.; Crabtree, R. H.; Eisenstein, O. Organometallics 2008, 27,
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(p) Tillack, A.; Hollmann, D.; Mevius, K.; Michalik, D.; Ba¨hn, S.; Beller, M. Eur. J.
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8. Transition metal-catalyzed C–C bond forming reactions using alcohols as al-
kylating agents have been also known: (a) Cho, C. S.; Kim, B. T.; Kim, T.-J.; Shim,
S. C. J. Org. Chem. 2001, 66, 9020; (b) Taguchi, K.; Nakagawa, H.; Hirabayashi, T.;
Sakaguchi, S.; Ishii, Y. J. Am. Chem. Soc. 2004, 126, 72; (c) Motokura, K.; Nishi-
mura, D.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2004,
126, 5662; (d) Fujita, K.; Asai, C.; Yamaguchi, T.; Hanasaka, F.; Yamaguchi, R. Org.
Lett. 2005, 7, 4017; (e) Black, P. J.; Cami-Kobeci, G.; Edwards, M. G.; Slatford, P.
A.; Whittlesey, M. K.; Williams, J. M. J. Org. Biomol. Chem. 2006, 4, 116; (f)
Lo¨fberg, C.; Grigg, R.; Whittaker, M. A.; Keep, A.; Derrick, A. J. Org. Chem. 2006,
71, 8023; (g) Matsu-ura, T.; Sakaguchi, S.; Obora, Y.; Ishii, Y. J. Org. Chem. 2006,
71, 8306; (h) Martı´nez, R.; Ramo´ n, D. J.; Yus, M. Tetrahedron 2006, 62, 8988.
9. (a) Watanabe, Y.; Ohta, T.; Tsuji, Y. Bull. Chem. Soc. Jpn. 1983, 56, 2647; (b)
Jenner, G. J. Mol. Catal. 1989, 55, 241.
matic), 7.97 (d, J¼7 Hz, 2H, aromatic), 7.59–7.45 (m, 6H, aromatic).
13C NMR (CDCl3)
180.9, 164.5, 134.6, 133.5, 133.4, 133.3, 130.1,
130.0, 129.0, 128.5.
d
3.7. Transfer hydrogenation of 10 catalyzed by [Cp*IrCl2]2
(Eq. 2)
In a heavy-walled glass reactor under an atmosphere of argon
were placed [Cp*IrCl2]2 (14.4 mg, 0.0181 mmol, 5.0 mol % Ir), NaOAc
(3.0 mg, 0.0366 mmol, 5.0 mol %), 10 (150.7 mg, 0.7202 mmol), 2-
propanol (128.1 mg, 2.131 mmol, 3 equiv), and toluene (1.0 mL).
The mixture was stirred at 130 ꢀC for 17 h in the sealed reactor. The
yield of 8a was determined by GC analysis using undecane as an
internal standard.
Acknowledgements
This work was partially supported by KAKENHI (No. 19550106).
We also thank Johnson Matthey, Inc., for a generous loan of iridium
trichloride.
10. Although an excess amount of an alcohol have to be used to obtain a high yield,
the unreacted alcohol could be recovered after the reaction.
11. We have also examined the reactions of tert-butyl carbamate, formamide, tri-
fluoroacetamide, and phthalimide with benzyl alcohol. However, these re-
actions gave only trace amounts of alkylated products.
References and notes
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´
´
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