A convenient method for the synthesis of carboxamides and thioesters by using tetrakis(2-methylimidazol-1-yl)silane

Article abstract of DOI:10.3987/COM-05-S(T)31

Tetrakis(2-methylimidazol-1-yl)silane [Si(2-Me-Im)₄], a new dehydrating reagent having silicon-imidazole linkage, reacted readily with carboxylic acids at room temperature to form the corresponding 1-acyl-2-methylimidazole intermediates, which smoothly underwent subsequent condensation with nucleophiles such as amines or thiols to afford the corresponding carboxamides or thioesters in good to excellent yields, respectively.

Full text of DOI:10.3987/COM-05-S(T)31

HETEROCYCLES, Vol. 67, No. 2, 2006
629
HETEROCYCLES, Vol. 67, No. 2, 2006, pp. 629 - 641. © The Japan Institute of Heterocyclic Chemistry
Received, 12th July, 2005, Accepted, 15th September, 2005, Published online, 16th September, 2005. COM-05-S(T)31
A
CONVENIENT
METHOD
AND
FOR
THE
SYNTHESIS
BY
OF
CARBOXAMIDES
THIOESTERS
USING
TETRAKIS(2-METHYLIMIDAZOL-1-YL)SILANE
Takashi Tozawa, Yoshinobu Yamane, and Teruaki Mukaiyama*
Center for Basic Research, The Kitasato Institute, 6-15-5 (TCI), Toshima, Kita-ku,
Tokyo 114-0003, Japan and Kitasato Institute for Life Sciences, Kitasato
University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan
Dedicated to Professor Barry M. Trost on the occasion of his 65th birthday
Abstract – Tetrakis(2-methylimidazol-1-yl)silane [Si(2-Me-Im)4], a new
dehydrating reagent having silicon−imidazole linkage, reacted readily with
carboxylic acids at room temperature to form the corresponding
1-acyl-2-methylimidazole intermediates, which smoothly underwent subsequent
condensation with nucleophiles such as amines or thiols to afford the
corresponding carboxamides or thioesters in good to excellent yields, respectively.
INTRODUCTION
To form carboxylic acid derivatives such as carboxamides, thioesters, or esters is one of the most
fundamental and important synthetic steps for the synthesis of useful natural and unnatural organic
molecules, and condensation reactions between carboxylic acids and nucleophiles under mild conditions
have significantly been advanced in accordance with the development of new dehydrating reagents.1,2
Among activated derivatives of carboxylic acids, acyl azolides, particularly 1-acylimidazoles, are
versatile and have widely been used as useful synthetic intermediates for the preparation of amides,
dipeptides, esters, etc.3 The classical azolide method is carried out generally by using
1,1’-carbonyldiimidazole (CDI) as a condensation reagent and requires stepwise operation: that is, (i)
carboxylic acids are first treated with CDI in a 1 : 1 molar ratio to generate the corresponding
1-acylimidazole intermediates by the elimination of carbon dioxide and imidazole; (ii) after evolution of

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HETEROCYCLES, Vol. 67, No. 2, 2006
carbon dioxide having been stopped, an equimolar amount of amine is added. In this procedure, the use of
excess amounts of CDI should be carefully avoided since the unreacted CDI reacts directly with amine to
form undesired urea that may cause purification of the product difficult.4
Several useful methods have been developed for the preparation of carboxamides by using
silicon-containing dehydrating reagents;5 e.g., hexamethyldisilazane (HMDS),6 silicon tetrachloride
(SiCl4),7 dichlorodimethylsilane (Me2SiCl2),8 etc. These conventional reagents, however, have following
synthetic limitations: (i) in the reaction with HMDS, high reaction temperature and long reaction time are
required; (ii) in the case when chlorosilanes such as SiCl4 or Me2SiCl2 are used, the solvent has often
been limited to pyridine for neutralization of liberated hydrogen chloride. Therefore, it is still an
important topic to develop more efficient silicon-containing dehydrating reagents for the synthesis of
carboxylic acid derivatives under mild conditions. Quite recently, it was reported from our laboratory that
various imidazolylsilane derivatives were easily synthesized by trans-silylation between
1-(trimethylsilyl)imidazoles and chlorosilanes.9 It was revealed there that novel reagents having
silicon−imidazole linkage were effectively utilized as dehydrating reagents to form carboxamides from
carboxylic acids and amines via the formation of active 1-acylimidazole intermediates under mild
conditions. Although a conventional azolide method that uses CDI requires strict stepwise operation and
precise amount of CDI so as to prevent the side-reaction of forming undesired urea, the new method that
uses novel dehydrating reagents having silicon−imidazole linkage proceeds just by mixing carboxylic
acids, amines, and imidazolylsilanes at a time. Then, the desired carboxamides are afforded in high yields
without any side-products even when the amount of the dehydrating reagent is excess. Further, the
work-up procedure is quite simple and carboxamides are obtained in almost pure form if
tetrakis(2-methylimidazol-1-yl)silane [Si(2-Me-Im)4] is used since the co-products of the reaction are
2-methylimidazole and silica [(SiO2)n]. 2-Methylimidazole thus formed can be removed by washing with
dilute acid. In addition, the silica is insoluble in any common solvents and it can therefore be removed
easily just by filtration. Here, we would like to describe in detail the results of our continuous
investigations on an efficient method for the preparation of carboxamides from carboxylic acids and
amines by using easily available Si(2-Me-Im)4 as a new dehydrating reagent and also further development
of the above reaction applied to the thioesterification between carboxylic acids and thiols.
RESULTS AND DISCUSSION
Tetrakis(2-methylimidazol-1-yl)silane [Si(2-Me-Im)4] was easily synthesized in almost quantitative yield
by trans-silylation between SiCl4 and 2-methyl-1-trimethylsilyl-imidazole in the molar ratio of 1 : 4 in dry

HETEROCYCLES, Vol. 67, No. 2, 2006
631
toluene (Scheme 1). After removal of the solvent and formed chlorotrimethylsilane (Me3SiCl), the
resulted solid product can be stored in a sealed bottle for several weeks without decomposition and is
used directly for condensation reactions.
Me
Me
4 Me3SiCl
SiCl4
+
+
Me3Si
N
N
Si
N
N
4
[Si(2-Me-Im)4]
(1.0 equiv.)
(4.0 equiv.)
Scheme 1.
The proposed mechanism for the formation of carboxamides from carboxylic acids and amines by using
Si(2-Me-Im)4 is as follows (Scheme 2). Carboxylic acids (1) react with Si(2-Me-Im)4 to form silyl ester
intermediates (A), which in turn are readily transformed into the corresponding
1-acyl-2-methylimidazoles (B) by either intramolecular rearrangement of A or nucleophilic attack of
liberated 2-methylimidazole to the carbonyl carbon. It is also considered that amines (2) are readily
silylated in situ by imidazolylsilanes to form silylated amines (C), which can easily undergo desilylation
to reproduce reactive free amines (2) since the intermolecular exchange is favored to shift toward free
amine (2) by the irreversible formation of carboxamides (3) and silica [(SiO2)n].
Me
O
O
X
O
X
X
O
R1
N
N
Si
R1
O
R1
OH
R1
NR2R3
1
A
B
Si(2-Me-Im)4
3
+
+
− 2-methylimidazole
+
R2R3NH
HX
X
X
R2R3NH
(SiO2)n
Si
R2R3N
X
2
+
SiX4
C
2
2-methylimidazole
X = 2-Me-Im, NR2R3
or oxygen (OCOR1, O-Si, etc.)
Scheme 2.
As a preliminary experiment, the reaction of 3-phenylpropanoic acid (1a) (1.0 equiv.) with
3-phenylpropylamine (2a) (1.2 equiv.) was examined in THF by using Si(2-Me-Im)4 (0.6 equiv.) at room
temperature. The corresponding carboxamide (3a) was obtained in 90% yield after disappearance of the
in situ formed 1-acyl-2-methylimidazole intermediate that was monitored by TLC (Table 1, Entry 1). It

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HETEROCYCLES, Vol. 67, No. 2, 2006
was found that the amount of Si(2-Me-Im)4 was reduced to 0.5 equivalents while the yield remained
(Entry 2). On the other hand, the use of larger molar amounts of Si(2-Me-Im)4 caused prolongation of
Table 1. Effect of Molar Ratios of Substrates and Si(2-Me-Im)4
Si(2-Me-Im)4
O
(Z equiv.)
O
+
H2N
Ph
Ph
N
H
Ph
Ph
OH
THF, rt, Time
1a
(X equiv.)
2a
(Y equiv.)
3a
a
Entry
X
Z
Y
Yield /%
Time /h
1.0
1.0
1.0
1.0
4
3
3
3
8
1
2
3
4
1.2
1.2
1.2
1.2
0.6
0.5
0.4
0.3
90
91
79
64
5
6
7
0.8
1.0
0.5
0.5
0.5
57 (78)b
53
1.0
1.0
1.0
1.1
1.2
1.2
1.2
1.0
1.0
1.0
8
3
90
96
3
3
8
9
99
a
b
Isolated yield. Reaction was carried out for 24 h.
Table 2. Effect of Solvents
Si(2-Me-Im)4
O
(0.5 equiv.)
Solv., rt, 3 h
O
+
H2N
Ph
Ph
Ph
N
H
Ph
OH
1a
2a
(1.0 equiv.)
3a
(1.2 equiv.)
a
Solv.
Entry
Yield /%
THF
Et2O
1
2
99
92
DMF
MeCN
CH2Cl2
toluene
3
4
5
6
90
96
96
82 (96)b
a
b
Isolated yield. Reaction was carried out for 9 h.

HETEROCYCLES, Vol. 67, No. 2, 2006
633
reaction time because an excess amount of Si(2-Me-Im)4 reacted directly with amine (2a) to form
silylated amine intermediates and to suppress the desired condensation (Entries 5 and 6). After the molar
ratios of carboxylic acid, amine, and Si(2-Me-Im)4 were respectively examined in detail, it was revealed
that the desired product was obtained in nearly quantitative yield by employing a slightly excess amount
of the carboxylic acid (Entries 8 and 9).
Next, effect of solvents including polar and nonpolar ones were examined by taking the reaction of 1a
with 2a in the presence of Si(2-Me-Im)4 under the optimized conditions (Table 2). It was found that a
wide range of solvents such as THF, Et2O, DMF, MeCN, CH2Cl2, and toluene were successfully used in
Table 3. Synthesis of various carboxamides by using Si(2-Me-Im)4
Si(2-Me-Im)4
(0.5 equiv.)
O
O
HNR2R3
+
R1
NR2R3
R1
OH
Solv., rt, Time
1
2
3
(1.2 equiv.)
(1.0 equiv.)
a
Entry
Carboxylic acid
Ph(CH2)2CO2H
Yield /%
Amine
Solv.
Time /h Product
Ph(CH2)3NH2
1
2
3
THF
3a
99
(1a)
(2a)
3
quant.
PhCH2NH2
Ph2CHNH2
3b
1a
1a
(2b)
(2c)
THF
THF
3
24
12
12
6
3c
84
93
PhCHMeNH2
PhCH2NHMe
Piperidine
3d
1a
1a
1a
(2d)
(2e)
(2f)
(2g)
(2h)
4
5
6
THF
THF
THF
3e
3f
99
96
3g
3h
3g
PhNH2
7
8
1a
1a
THF
24
12
71
77
EtNH2・HCl
CH2Cl2
PhNH2・HCl
CH2Cl2
CH2Cl2
71
9
10
11
1a
1a
(2i)
(2j)
24
24
24
b
Gly-OEt・HCl
88
3i
3j
c-C6H11CO2H
93
(1b)
2a
THF
3k
3l
12
13
14
15
16
1b
77
78
84
87
93
2f
2a
2b
2a
2f
THF
THF
THF
THF
THF
24
24
12
24
6
t-BuCO2H
(1c)
(1d)
3m
3n
3o
1c
PhCO2H
1d
a
b
Isolated yield. Amine・HCl (1.2 equiv.) was added to the mixture of carboxylic acid (1.0 equiv.) and
Si(2-Me-Im)4 (0.6 equiv.)

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HETEROCYCLES, Vol. 67, No. 2, 2006
this reaction and the reactions mostly proceeded smoothly to provide the desired carboxamide (3a) in
high yields except toluene which required longer reaction time due to the poor solubility of Si(2-Me-Im)4.
Several examples of carboxamides (3a−o) obtained by using Si(2-Me-Im)4 as a dehydrating reagent are
listed in Table 3, which clearly shows the efficiency and general applicability of the present method. It is
noted that hydrogen chloride salts of amines (2h−j) instead of free amines are directly used in this
procedure in the absence of other bases such as triethylamine to capture liberated hydrogen chloride since
in situ formed 2-methylimidazole works as a hydrogen chloride scavenger (Entries 8–10).
In order to further demonstrate the synthetic utility and versatility of this novel dehydrating reagent,
Si(2-Me-Im)4, it was applied to the synthesis of thioesters from carboxylic acids and thiols. Then,
thioesterification of carboxylic acids (1) (1.0 equiv.) with thiols (4) (1.0 equiv.) was tried in CH2Cl2 by
using Si(2-Me-Im)4 (0.6 equiv.) at room temperature (Table 4). In most cases, the reactions proceeded
smoothly under mild conditions to afford the corresponding thioesters (5) in good to excellent yields.
Table 4. Synthesis of various thioesters by using Si(2-Me-Im)4
Si(2-Me-Im)4
(0.6 equiv.)
O
O
R4SH
+
R1
SR4
R1
OH
CH2Cl2, rt, Time
1
4
5
(1.0 equiv.)
(1.0 equiv.)
a
Entry
Carboxylic acid
Product
Yield /%
Thiol
Time /h
Me(CH2)7SH
(1a)
(4a)
Ph(CH2)2CO2H
5a
5b
5c
5d
5e
5f
1
2
3
24
6
86
98
73
97
83
98
86
93
PhCH2SH (4b)
1a
c-C6H11SH
(4c)
(4d)
1a
1a
24
3
PhSH
4b
4
5
6
c-C6H11CO2H
(1b)
(1d)
6
1b
PhCO2H
1d
4d
6
5g
6
4b
7
8
4d
5h
3
a
Isolated yield.
Thus, a novel dehydrating reagent having silicon−imidazole linkage, Si(2-Me-Im)4, was easily prepared
by trans-silylation between SiCl4 and 2-methyl-1-trimethylsilylimidazole, and was used very
conveniently for the preparation of various carboxamides directly from free carboxylic acids and amines

HETEROCYCLES, Vol. 67, No. 2, 2006
635
under mild conditions. In addition, this method was efficiently applied also to the thioesterification
between carboxylic acids and thiols.
EXPERIMENTAL
All melting points were measured on a micro melting point apparatus (Yanaco MP-S3) and were not
corrected. IR spectra were recorded on a SENSIR TECHNOLOGIES TravelIR Portable FT-IR
1
spectrometer (Attenuated Total Reflection). H NMR spectra were recorded on a JEOL JNM-EX270L
(270 MHz) spectrometer; chemical shifts ( δ) are reported in parts per million relative to
tetramethylsilane. Splitting patterns are designated as s, singlet; d, doublet; t, triplet; q, quartet; m,
13
multiplet; br, broad. C NMR spectra were recorded on a JEOL JNM-EX270L (68 MHz) spectrometer
with complete proton decoupling. Chemical shifts are reported in parts per million relative to
tetramethylsilane with the solvent resonance as the internal standard (CDCl3; δ = 77.0 ppm). The
optical rotations were measured with a JASCO P-1020 polarimeter. HRMS spectra were recorded on a
JEOL JMS-700 mass spectrometer. Analytical TLC was performed on Merck preparative TLC plates
(silica gel 60 GF254, 0.25 mm). Preparative thin-layer chromatography (PTLC) was carried out on silica
gel Wakogel B-5F. Dry solvents were purchased from Kanto Chemical. All reagents were purchased from
Tokyo Kasei Kogyo, Kanto Chemical, Kokusan Chemical, Wako Pure Chemical Industries, or Aldrich
Chemical. 2-Methyl-1-trimethylsilyl-imidazole was prepared according to the literature procedures.10
Preparation of tetrakis(2-methylimidazol-1-yl)silane [Si(2-Me-Im)4].
To a solution of 2-methyl-1-trimethylsilyl-imidazole (10.0 g, 64.8 mmol) in toluene (5.0 mL) was added
slowly SiCl4 (1.86 mL, 16.2 mmol) at rt under argon. The precipitation of a white solid was observed.
After the mixture was stirred at 80 °C for 1 h, the generated Me3SiCl and the solvent were removed under
reduced pressure to give a white powder in almost quantitative yield (5.71 g). The reagent can be handled
for brief periods in the air though it is sensitive to moisture. 1H NMR (270 MHz, CDCl3) δ 7.18 (s, 4H),
6.84 (s, 4H), 2.09 (s, 12H). 13C NMR (67.8 MHz, CDCl3) δ 149.7, 132.3, 120.9, 15.4. HRMS (EI+) calcd
for C16H20N8Si [M]+ 352.1580, found m/z 352.1582.
Typical experimental procedure for the preparation of carboxamides by using Si(2-Me-Im)4 (Table
3, Entry 1).
To a stirred suspension of Si(2-Me-Im)4 (88.0 mg, 0.25 mmol) in THF (0.75 mL) were successively
added 3-phenylpropanoic acid (1a) (90.1 mg, 0.6 mmol) and a solution of 3-phenylpropylamine (2a)
(67.6 mg, 0.5 mmol) in THF (0.75 mL) at rt. The reaction mixture was stirred for 3 h at the same
temperature, followed by the addition of water. Precipitated silica was filtered off and washed with

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HETEROCYCLES, Vol. 67, No. 2, 2006
EtOAc, and then the filtrate was extracted with EtOAc. The organic layer was washed with 1 M HCl aq,
saturated NaHCO3 aq, and brine, dried over anhydrous Na SO . After filtration, the solvent was removed
2
4
under reduced pressure to give 3-Phenyl-N-(3-phenylpropyl)propanamide (3a) (132 mg, 99%) in almost
pure form.
3-Phenyl-N-(3-phenylpropyl)propanamide (3a).2a
Colorless crystals, mp 55–56 °C. IR (ATR) 3306, 1629, 1537, 1452 cm–1. 1H NMR (270 MHz, CDCl3) δ
7.28–7.09 (m, 10H), 5.64 (br s, 1H), 3.25–3.17 (m, 2H), 2.92 (t, J = 7.6 Hz, 2H), 2.54 (t, J = 7.6 Hz, 2H),
13
2.40 (t, J = 7.6 Hz, 2H), 1.76–1.70 (m, 2H). C NMR (68 MHz, CDCl3) δ 171.8, 141.2, 140.7, 128.3,
128.2, 128.1, 126.0, 125.8, 39.1, 38.4, 33.2, 31.7, 31.0. Anal. Calcd for C18H21NO: C, 80.86; H, 7.92; N,
5.24. Found: C, 80.89; H, 8.17; N, 5.26.
N-Benzyl-3-phenylpropanamide (3b).2a
Colorless crystals, mp 81–82 °C. IR (ATR) 3290, 1638, 1541, 1453 cm–1. 1H NMR (270 MHz, CDCl3) δ
7.27–7.07 (m, 10H), 6.14 (br s, 1H), 4.31 (d, J = 5.9 Hz, 2H), 2.92 (t, J = 7.6 Hz, 2H), 2.46 (t, J = 7.6 Hz,
13
2H). C NMR (68 MHz, CDCl3) δ 171.8, 140.6, 138.0, 128.4, 128.3, 128.2, 127.4, 127.1, 126.0, 43.4,
38.2, 31.7. Anal. Calcd for C16H17NO: C, 80.30; H, 7.16; N, 5.85. Found: C, 80.10; H, 7.22; N, 5.82.
N-(Diphenylmethyl)-3-phenylpropanamide (3c).2a
Colorless crystals, mp 146–147 °C. IR (ATR) 3306, 1642, 1534, 1494 cm–1. 1H NMR (270 MHz, CDCl3)
δ 7.30–7.07 (m, 15H), 6.26–6.15 (m, 1H), 6.12 (br s, 1H), 2.96 (t, J = 7.3 Hz, 2H), 2.52 (t, J = 7.3 Hz,
13
2H). C NMR (68 MHz, CDCl3) δ 170.8, 141.2, 140.5, 128.4, 128.3, 127.2, 127.2, 126.1, 56.8, 38.4,
31.6. Anal. Calcd for C22H21NO: C, 83.78; H, 6.71; N, 4.44. Found: C, 83.66; H, 6.78; N, 4.47.
3-Phenyl-N-[(1S)-1-phenylethyl]propanamide (3d).2a
29
1
Colorless crystals, [α]D = −63.9° (c 1.02 EtOH). mp 83–84 °C. IR (ATR) 3306, 1635, 1535 cm–1. H
NMR (270 MHz, CDCl3) δ 7.29–7.12 (m, 10H), 5.96 (br s, 1H), 5.08–5.02 (m, 1H), 2.92 (t, J = 7.6 Hz,
2H), 2.43 (t, J = 7.6 Hz, 2H), 1.36 (d, J = 6.8 Hz, 3H). 13C NMR (68 MHz, CDCl3) δ 170.9, 142.9, 140.6,
128.3, 128.3, 128.2, 127.0, 126.0, 125.9, 48.5, 38.4, 31.7, 21.6. Anal. Calcd for C17H19NO: C, 80.60; H,
7.56; N, 5.53. Found: C, 80.39; H, 7.55; N, 5.41.
N-Benzyl-N-methyl-3-phenylpropanamide (3e).2a
1
Colorless oil, a mixture of two stereoisomers A and B. IR (ATR) 1641, 1452, 1403 cm–1. H NMR (270
MHz, CDCl3) δ 7.27–7.07 (m, 10H, A+B), 4.58 (s, 2aH, A), 4.44 (s, 2bH, B), 3.02–2.96 (m, 2H, A+B),
2.93 (s, 3bH, B), 2.82 (s, 3aH, A), 2.70–2.63 (m, 2H, A+B). 13C NMR (68 MHz, CDCl3) δ 172.2, 171.9,
141.1, 141.0, 137.1, 136.3, 128.7, 128.3, 128.2, 128.2, 127.8, 127.3, 127.1, 126.0, 125.9, 125.9, 53.1, 50.7,
35.7, 35.3, 34.9, 34.7, 33.9, 31.5, 31.3. HRMS (DEI+) calcd for C17H19NO [M]+ 253.1467, found m/z
253.1467.
1-(3-Phenylpropanoyl)piperidine (3f).2a

HETEROCYCLES, Vol. 67, No. 2, 2006
637
1
Colorless oil, IR (ATR) 2933, 1632, 1438 cm–1. H NMR (270 MHz, CDCl3) δ 7.28–7.22 (m, 5H),
3.56–3.54 (m, 2H), 3.33–3.31 (m, 2H), 2.96 (t, J = 8.0 Hz, 2H), 2.61 (t, J = 8.0 Hz, 2H), 1.66–1.44 (m,
13
6H). C NMR (68 MHz, CDCl3) δ 170.1, 141.2, 128.2, 128.2, 125.8, 46.5, 42.6, 35.1, 31.5, 26.3, 25.5,
24.5. HRMS (DEI+) calcd for C14H19NO [M]+ 217.1467, found m/z 217.1467.
N,3-diphenylpropanamide (3g).2a
1
Colorless crystals, mp 95–96 °C. IR (ATR) 3321, 1650, 1599, 1526, 1495, 1440 cm–1. H NMR (270
MHz, CDCl3) δ 7.80 (br s, 1H), 7.42 (d, J = 7.8 Hz, 2H), 7.24–7.12 (m, 7H), 7.07 (t, J = 7.3 Hz, 1H), 2.98
13
(t, J = 7.8 Hz, 2H), 2.59 (t, J = 7.8 Hz, 2H). C NMR (68 MHz, CDCl3) δ 170.6, 140.4, 137.7, 128.7,
128.4, 128.1, 126.1, 124.1, 120.0, 39.2, 31.6. Anal. Calcd for C15H15NO: C, 79.97; H, 6.71; N, 6.22.
Found: C, 79.73; H, 6.60; N, 5.90.
N-Ethyl-3-phenylpropanamide (3h).11
1
Colorless crystals, mp 55–56 °C. IR (ATR) 3298, 1638, 1550 cm–1. H NMR (270 MHz, CDCl3) δ
7.29–7.16 (m, 5H), 5.77 (br s, 1H), 3.27–3.17 (m, 2H), 2.94 (t, J = 7.8 Hz, 2H), 2.44 (t, J = 7.8 Hz, 2H),
1.05 (t, J = 7.3 Hz, 3H). 13C NMR (68 MHz, CDCl3) δ 171.8, 140.7, 128.3, 128.1, 126.0, 38.4, 34.3, 31.8,
14.8. Anal. Calcd for C11H15NO: C, 74.54; H, 8.53; N, 7.90. Found: C, 74.20; H, 8.54; N, 7.76.
Ethyl N-(3-phenylpropanoyl)glycinate (3i).
Colorless crystals, mp 50–51 °C. IR (ATR) 3313, 1722, 1635, 1546, 1298, 1253, 1228, 1038, 1028 cm–1.
1H NMR (270 MHz, CDCl3) δ 7.27–7.17 (m, 5H), 6.18 (br s, 1H), 4.18 (q, J = 7.2 Hz, 2H), 3.99 (d, J =
5.1 Hz, 2H), 2.97 (t, J = 7.8 Hz, 2H), 2.54 (t, J = 7.8 Hz, 2H), 1.26 (t, J = 7.2 Hz, 2H). 13C NMR (68 MHz,
CDCl3) δ 172.0, 169.7, 140.5, 128.3, 128.1, 126.0, 61.4, 41.3, 37.9, 31.4, 14.1. Anal. Calcd for
C13H17NO3: C, 66.36; H, 7.28; N, 5.95. Found: C, 66.33; H, 6.99; N, 5.96.
N-(3-Phenylpropyl)cyclohexanecarboxamide (3j).
1
Colorless crystals, mp 80–82 °C. IR (ATR) 3297, 2930, 2853, 1639, 1549 cm–1. H NMR (270 MHz,
CDCl3) δ 7.30–7.14 (m, 5H), 5.82 (br s, 1H), 3.30–3.22 (m, 2H), 2.62 (t, J = 7.6 Hz, 2H), 2.08–1.98 (m,
13
1H), 1.88–1.63 (m, 7H), 1.46–1.15 (m, 5H). C NMR (68 MHz, CDCl3) δ 175.9, 141.3, 128.2, 128.1,
125.7, 45.4, 38.9, 33.3, 31.2, 29.6, 25.7. Anal. Calcd for C16H23NO: C, 78.32; H, 9.45; N, 5.71. Found: C,
78.18; H, 9.09; N, 5.70.
1-(Cyclohexylcarbonyl)piperidine (3k).12
1
Colorless oil, IR (ATR) 2927, 2853, 1630, 1438, 1252, 1213 cm–1. H NMR (270 MHz, CDCl3) δ
13
3.58–3.54 (m, 2H), 3.44–3.40 (m, 2H), 2.52–3.42 (m, 1H), 1.89–1.22 (m, 16H). C NMR (68 MHz,
CDCl3) δ 174.1, 46.3, 42.6, 40.4, 29.4, 26.8, 25.9, 25.9, 25.6, 24.7. HRMS (DEI+) calcd for C12H21NO
[M]+ 195.1623, found m/z 195.1625.
2,2-Dimethyl-N-(3-phenylpropyl)propanamide (3l).
1
Colorless crystals, mp 77–78 °C. IR (ATR) 3322, 2944, 1630, 1538, 1212 cm–1. H NMR (270 MHz,
CDCl3) δ 7.30–7.15 (m, 5H), 5.72 (br s, 1H), 3.27 (q, J = 7.6 Hz, 2H), 2.64 (t, J = 7.6 Hz, 2H), 1.89–1.78

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13
(m, 2H), 1.14 (s, 9H). C NMR (68 MHz, CDCl3) δ 178.0, 141.3, 128.3, 128.1, 125.8, 39.2, 38.5, 33.4,
31.1, 27.5. Anal. Calcd for C14H21NO: C, 76.67; H, 9.65; N, 6.39. Found: C, 76.55; H, 9.23; N, 6.36.
N-Benzyl-2,2-dimethylpropanamide (3m).13
1
Colorless crystals, mp 82–83 °C. IR (ATR) 3298, 2962, 1634, 1538, 1218 cm–1. H NMR (270 MHz,
CDCl3) δ 7.34–7.22 (m, 5H), 6.10 (br s, 1H), 4.41 (d, J = 5.4 Hz, 2H), 1.22 (s, 9H). 13C NMR (68 MHz,
CDCl3) δ 178.0, 138.5, 128.4, 127.3, 127.1, 43.4, 38.6, 27.6. Anal. Calcd for C12H17NO: C, 75.35; H,
8.96; N, 7.32. Found: C, 75.24; H, 9.35; N, 7.29.
N-(3-Phenylpropyl)benzamide (3n).14
Colorless crystals, mp 40–41 °C. IR (ATR) 3296, 1633, 1548, 1313 cm–1. 1H NMR (270 MHz, CDCl3) δ
7.69 (d, J = 7.8 Hz, 2H), 7.45–7.11 (m, 8H), 6.64 (br s, 1H), 3.47–3.39 (m, 2H), 2.66 (t, J = 7.6 Hz, 2H),
1.95–1.86 (m, 2H). 13C NMR (68 MHz, CDCl3) δ 167.3, 141.3, 134.4, 131.0, 128.3, 128.2, 128.1, 126.7,
125.7, 39.8, 33.4, 31.0. Anal. Calcd for C16H17NO: C, 80.30; H, 7.16; N, 5.85. Found: C, 80.06; H, 6.99;
N, 5.79.
1-Benzoylpiperidine (3o).15
1
Colorless crystals, mp 39–40 °C. IR (ATR) 2935, 2857, 1618, 1575, 1427, 1274 cm–1. H NMR (270
13
MHz, CDCl3) δ 7.38 (s, 5H), 3.70 (br s, 2H), 3.33 (br s, 2H), 1.75–1.45 (m, 6H). C NMR (68 MHz,
CDCl3) δ 169.9, 136.2, 129.0, 128.1, 126.5, 48.6, 43.0, 26.4, 25.5, 24.5. Anal. Calcd for C12H15NO: C,
76.16; H, 7.99; N, 7.40. Found: C, 75.93; H, 7.70; N, 7.34.
Typical experimental procedure for the preparation of thioesters by using Si(2-Me-Im)4 (Table 4,
Entry 1).
To a stirred suspension of Si(2-Me-Im)4 (88.0 mg, 0.25 mmol) in CH2Cl2 (0.75 mL) were successively
added 3-phenylpropanoic acid (1a) (90.1 mg, 0.6 mmol) and a solution of 1-octanethiol (4a) (73.1 mg,
0.5 mmol) in CH2Cl2 (0.75 mL) at rt. The reaction mixture was stirred for 24 h at the same temperature,
followed by the addition of water. Precipitated silica was filtered off and washed with EtOAc, and then
the filtrate was extracted with EtOAc. The organic layer was washed with 1 M HCl aq, saturated
NaHCO3 aq, and brine, dried over anhydrous Na SO . After filtration of the mixture and evaporation of
2
4
the solvent, the crude product was purified by thin-layer chromatography to afford S-octyl
3-phenylpropionthioate (5a) (120 mg, 86%).
S-Octyl 3-phenylpropanethioate (5a).2b
1
Colorless oil, IR (ATR) 2924, 2855, 1688, 1453, 1045, 971 cm–1. H NMR (270 MHz, CDCl3) δ
7.37–7.14 (m, 5H), 3.01–2.83 (m, 6H), 1.67–1.49 (m, 2H), 1.45–1.19 (m, 10H), 0.88 (t, J = 7.0 Hz, 3H).
13C NMR (68 MHz, CDCl3) δ 198.4, 140.0, 128.4, 128.2, 126.2, 45.5, 31.8, 31.5, 29.6, 29.2, 29.1, 29.0,
28.8, 22.7, 14.2. HRMS (DEI+) calcd for C17H26OS [M]+ 278.1704, found m/z 278.1702.
S-Benzyl 3-phenylpropanethioate (5b).16

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639
Colorless oil, IR (ATR) 1687, 1043, 972 cm–1. 1H NMR (270 MHz, CDCl3) δ 7.38–7.11 (m, 10H), 4.10 (s,
13
2H), 3.00–2.93 (m, 2H), 2.87–2.81 (m, 2H). C NMR (68 MHz, CDCl3) δ 197.5, 139.7, 137.4, 128.6,
128.4, 128.3, 128.1, 127.1, 126.2, 45.2, 33.1, 31.4. HRMS (DEI+) calcd for C16H16OS [M]+ 256.0922,
found m/z 256.0925.
S-Cycrohexyl 3-phenylpropanethioate (5c).2b
1
Colorless oil, IR (ATR) 2928, 2853, 1682, 1449, 1044, 970 cm–1. H NMR (270 MHz, CDCl3) δ
7.37–7.15 (m, 5H), 3.63–3.46 (m, 1H), 3.01–2.91 (m, 2H), 2.84–2.78 (m, 2H), 1.99–1.81 (m, 2H),
13
1.74–1.51 (m, 3H), 1.50–1.20 (m, 5H). C NMR (68 MHz, CDCl3) δ 198.2, 140.0, 128.3, 128.2, 126.1,
45.6, 42.3, 33.0, 31.5, 26.0, 25.6. HRMS (DEI+) calcd for C15H20OS [M]+ 248.1235, found m/z 248.1234.
S-Phenyl 3-phenylpropanethioate (5d).17
Colorless crystals, mp 44–45 °C. IR (ATR) 1712, 1048, 959 cm–1. 1H NMR (270 MHz, CDCl3) δ 7.39 (s,
13
5H), 7.36–7.18 (m, 5H), 3.04–2.92 (m, 4H). C NMR (68 MHz, CDCl3) δ 196.4, 139.8, 134.3, 129.3,
129.1, 128.4, 128.3, 127.5, 126.3, 45.2, 31.4. Anal. Calcd for C15H14OS: C, 74.34; H, 5.82. Found: C,
74.29; H, 5.85.
S-Benzyl cyclohexanecarbothioate (5e).18
Colorless oil, IR (ATR) 2929, 2854, 1684, 1450, 967 cm–1. 1H NMR (270 MHz, CDCl3) δ 7.28–7.19 (m,
5H), 4.09 (s, 2H), 2.49 (tt, J = 11.3, 3.5 Hz, 3H), 1.95–1.88 (m, 2H), 1.79–1.74 (m, 2H), 1.70–1.60 (m,
13
1H), 1.53–1.40 (m, 2H), 1.33–1.20 (m, 3H). C NMR (68 MHz, CDCl3) δ 202.1, 137.7, 128.6, 128.4,
127.0, 52.4, 32.8, 29.6, 25.7, 25.5. HRMS (DEI+) calcd for C14H18OS [M]+ 234.1078, found m/z
234.1079.
S-Phenyl cyclohexanecarbothioate (5f).19
Colorless crystals, mp 36–37 °C. IR (ATR) 2932, 2850, 1692, 1478, 1441, 960 cm–1. 1H NMR (270 MHz,
CDCl3) δ 7.38 (s, 5H), 2.65–2.55 (m, 1H), 2.03–1.96 (m, 2H), 1.86–1.77 (m, 2H), 1.70–1.61 (m, 1H),
13
1.60–1.44 (m, 2H), 1.40–1.19 (m, 3H). C NMR (68 MHz, CDCl3) δ 200.4, 134.4, 129.0, 128.9, 127.8,
52.5, 29.6, 25.6, 25.5. Anal. Calcd for C13H16OS: C, 70.87; H, 7.32. Found: C, 70.80; H, 7.00.
S-Benzyl benzenecarbothioate (5g).20
Colorless crystals, mp 36–37 °C. IR (ATR) 1651, 1206, 905 cm–1. 1H NMR (270 MHz, CDCl3) δ 7.69 (d,
13
J = 7.0 Hz, 2H), 7.56–7.20 (m, 8H), 4.31 (s, 2H). C NMR (68 MHz, CDCl3) δ 191.0, 137.3, 136.6,
133.3, 128.8, 128.5, 128.5, 127.2, 127.1, 33.3. Anal. Calcd for C14H12OS: C, 73.65; H, 5.30. Found: C,
73.64; H, 5.19.
S-Phenyl benzenecarbothioate (5h).20
1
Colorless crystals, mp 54–55 °C. IR (ATR) 1664, 1198, 1176, 890 cm–1. H NMR (270 MHz, CDCl3) δ
13
8.02 (d, J = 7.0 Hz, 2H), 7.58–7.43 (m, 8H). C NMR (68 MHz, CDCl3) δ 189.8, 136.4, 134.9, 133.5,
129.4, 129.1, 128.6, 127.3, 127.2. Anal. Calcd for C13H10OS: C, 72.87; H, 4.70. Found: C, 72.83; H, 4.79.

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ACKNOWLEDGEMENTS
This study was supported in part by the Grant of the 21st Century COE Program from the Ministry of
Education, Culture, Sports, Science and Technology (MEXT), Japan.
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