Tris(2,4,6-trimethoxyphenyl)phosphine: Base catalyst in the transformation of α,β-unsaturated aldehydes to saturated carboxylic-acid derivatives

Article abstract of DOI:10.1080/10426500600977296

We have focused on the basicity of Tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP) in organic synthesis. To extend the utility of TTMPP, we examined the reaction of α,β-unsaturated aldehydes with trimethylsilyl cyanide in the presence of TTMPP. Furthermore, to clarify the basic character of TTMPP, we measured ³¹P NMR of TTMPP and related compounds. First, the reaction of cinnamaldehydes with trimethylsilyl cyanide in the presence of a catalytic amount of TTMPP afforded the corresponding saturated carboxylic acids after hydrolysis with 1M HCl. Treatment of the reaction mixture with alcohols or amines instead of 1M HCl gave the corresponding saturated esters and amides, respectively. As a result of studies of the reaction mechanism, it was revealed that the reaction proceeded via silylcyanation of α,β-unsaturated aldehydes with trimethylsilyl cyanide to produce trimethylsilyl ethers of cyanohydrin and subsequent isomerization that formed α-trimethylsiloxy vinyl cyanides, which were hydrolyzed to give saturated carboxylic acids. Copyright Taylor & Francis Group, LLC.

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Tris(2,4,6-
Trimethoxyphenyl)phosphine:
Base Catalyst in the
Transformation of α,β-
Unsaturated Aldehydes to
Saturated Carboxylic-Acid
Derivatives
Masahiko Hayashi a , Hirotoshi Kawabata a , Kazuya
Yoshimoto a & Takanori Tanaka a
a Department of Chemistry , Kobe University , Kobe,
Japan
Published online: 18 Feb 2007.
To cite this article: Masahiko Hayashi , Hirotoshi Kawabata , Kazuya Yoshimoto &
Takanori Tanaka (2007) Tris(2,4,6-Trimethoxyphenyl)phosphine: Base Catalyst in
the Transformation of α,β-Unsaturated Aldehydes to Saturated Carboxylic-Acid
Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 182:2, 433-445,
DOI: 10.1080/10426500600977296
To link to this article: http://dx.doi.org/10.1080/10426500600977296
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Phosphorus, Sulfur, and Silicon, 182:433–445, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600977296
Tris(2,4,6-Trimethoxyphenyl)phosphine: Base Catalyst
in the Transformation of α, β-Unsaturated Aldehydes
to Saturated Carboxylic-Acid Derivatives
Masahiko Hayashi
Hirotoshi Kawabata
Kazuya Yoshimoto
Takanori Tanaka
Department of Chemistry, Kobe University, Kobe, Japan
We have focused on the basicity of Tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP)
in organic synthesis. To extend the utility of TTMPP, we examined the reaction of
α,β-unsaturated aldehydes with trimethylsilyl cyanide in the presence of TTMPP.
31
Furthermore, to clarify the basic character of TTMPP, we measured P NMR
of TTMPP and related compounds. First, the reaction of cinnamaldehydes with
trimethylsilyl cyanide in the presence of a catalytic amount of TTMPP afforded the
corresponding saturated carboxylic acids after hydrolysis with 1M HCl. Treatment
of the reaction mixture with alcohols or amines instead of 1M HCl gave the cor-
responding saturated esters and amides, respectively. As a result of studies of the
reaction mechanism, it was revealed that the reaction proceeded via silylcyanation
of α,β-unsaturated aldehydes with trimethylsilyl cyanide to produce trimethylsilyl
ethers of cyanohydrin and subsequent isomerization that formed α-trimethylsiloxy
vinyl cyanides, which were hydrolyzed to give saturated carboxylic acids.
Keywords Amide; base catalyst; carboxylic acid; ester; α,β-unsaturated aldehyde
INTRODUCTION
Since the report by Wada and Higashizaki in 1984, high basicity of
tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP)1 has attracted the in-
terest of synthetic organic chemists. Matsukawa et al. reported TTMPP-
catalyzed aldol reaction between ketene silyl acetals and aldehydes.2,10
Very recently, Matsukawa and Obu reported a TTMPP-catalyzed silyl
ketene acetal-imine condensation route to β-lactams.3 We also reported
Received May 18, 2006; accepted August 1, 2006.
This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas
“Advanced Molecular Transformations of Carbon Resources” and No. B17340020 from
the Ministry of Education, Culture, Sports, Science, and Technology.
Address correspondence to Masahiko Hayashi, Kobe University, Department of Chem-
istry, Faculty of Science, Kobe, 657-8501, Japan. E-mail: mhayashi@kobe-u.ac.jp
433

434
M. Hayashi et al.
the use of TTMPP as a selective deacetylation catalyst.4 Since then,
we have focused on the utility of TTMPP as a base in organic syn-
thesis, and we found that TTMPP catalyzed the conversion of α,β-
unsaturated aldehydes to saturated carboxylic acid via trimethylsilyl
ethers of cyanohydrins. That is, treatment of α,β-unsaturated aldehy-
des with trimethylsilyl cyanide in the presence of a catalytic amount
of TTMPP afforded the corresponding saturated carboxylic acids after
hydrolysis.5
In 1991, Kobayashi et al. reported that Lewis bases served as effi-
cient catalysts for the addition reaction of trimethylsilyl cyanide with
some aldehydes to afford the corresponding cyanohydrin trimethylsilyl
ether in an excellent yield.6 The Lewis bases they employed were
amines (Et3N, i-Pr2NEt, i-Pr2NH, 1-ethylpiperidine, N,N,N ꢀ,Nꢀ-
tetramethylethylenediamine, 2,2,6,6-tetramethylpiperidine), phos-
phines (n-Bu3P, Ph3P), arsine (Ph3As), and antimony (Ph3Sb). In all
cases they examined, the reaction products were trimethylsilyl ethers
of cyanohydrin.
We found, however, (E)-cinnamaldehyde (1) was converted to 3-
phenylpropionic acid (3) in the presence of 20 mol% TTMPP under mild
conditions. With respect to such direct conversion of α,β-unsaturated
aldehydes to corresponding saturated carboxylic acids, several ruthe-
nium complex-catalyzed reactions have been reported. In a report by
Murahashi et al., the action of a catalytic amount of RuH2(PPh3)4
upon crotonaldehyde in the presence of water in 1,2-dimethoxyethane
at 180◦C afforded butyric acid in a 68% yield (91% conversion).7 By
using a similar type of reaction, (E)-cinnamaldehyde (1) was con-
verted to a mixture of 3-phenylpropionic acid (3) (46% yield) and (E)-
cinnamic acid (15% yield) at 180◦C by a catalytic system that consisted
of RuCl3 · nH2O and tricyclohexylphosphine (PCy3).8 In this system, a
high temperature was necessary, and the yields of saturated acids were
only moderate. For the related reactions, Hu¨nig et al. reported stepwise
conversion of α,β-unsaturated aldehydes or saturated acyl chlorides to
1-alkylated α,β-unsaturated carbonyl compounds or 3-alkylated sat-
urated carboxylic acid derivatives through common ambident anions,
which were 1-cyano-3-aryl-1-(trimethylsiloxy)allylic anions.9 By their
methods, cyanohydrin trimethylsilyl ethers were isolated, and then
the isolated intermediates were treated with a strong Lewis base
such as lithium diisopropylamide, lithium bis(trimethylsilyl)amide,
and sodium bis(trimethylsilyl)amide to generate allylic anion. Here we
report the mild and direct transformation of cinnamaldehydes into sat-
urated carboxylic acids, esters, and amides catalyzed by TTMPP; we
also include a discussion on details of the reaction mechanism.

Tris(2,4,6-Trimethoxyphenyl)phosphine
435
RESULTS AND DISCUSSION
During the course of our own Lewis base–catalyzed silylcyanation of
aldehydes, we examined the effect of the nature of Lewis base cata-
lysts on the reactions. We found in some cases the reaction products
were not only cyanohydrin trimethylsilyl ethers but also saturated car-
boxylic acid. The results of the reactions of (E)-cinnamaldehyde (1)
with trimethylsilyl cyanide in the presence of a catalytic amount of
several Lewis bases followed by hydrolysis by 1M HCl are shown in
Table I.
Among the Lewis bases we examined, TTMPP was found to be
the most effective for the conversion of (E)-cinnamaldehyde (1) to
3-phenylpropionic acid (3). That is, the reaction of 1 with trimethylsi-
lyl cyanide in the presence of 20 mol% of TTMPP in acetonitrile
at r.t. for 3.5 h, followed by hydrolysis with 1M HCl, afforded sat-
urated acid 3 in 90% yield (Table I, Entry 6). When other Lewis
bases such as triphenylphosphine, tris(4-methoxyphenyl)phosphine
(TMPP),
tris(2,6-dimethoxyphenyl)phosphine
(TDMPP),
and
TABLE I Reaction of (E)-Cinnamaldehyde With Me3SiCN
Catalyzed by a Variety of Lewis Basesa
OH
1) cat.
Lewis base
CHO
CO2H
CN
+ Me3SiCN
+
2) 1lM HC
1
2
3
Products
(% Yield)b
Entry
Catalyst (mol%)
Temp/◦C
Time/h
2
3
1
2
3
4
5
6
7
8
PPh3 (20)
TMPP (20)
TDMPP (20)
TTMPP (5)
TTMPP (10)
TTMPP (20)
n-Bu3P (20)
DABCO (5)
DABCO (10)
DBU (5)
28
31
31
32
32
29
31
20
20
25
28
25
3.5
3.5
3.5
2
46
87
23
10
7
0
4
11
0
0
0
0
70
86
87
90
74
80
85
79
91
94
2
3.5
2.5
6
6
2
9
10
11
12
DBU (10)
DBU (20)
2
2
0
0
a
All reactions were carried out in CH3CN with 1.2 equiv. Me3SiCN.
Yields of products were isolated ones after hydrolysis with 1M HCl.
b

436
M. Hayashi et al.
tri-n-butylphosphine were employed, the products were only un-
saturated cyanohydrin 2 or a mixture of 2 and 3 (Table I, Entries 1–3
and 7). It should be mentioned that even in the reaction of TTMPP, the
use of less amount of TTMPP led to the formation of a small amount of
cyanohydrin (Table I, Entries 4 and 5). The tendency for the preference
of the formation of saturated acid 3 approximately correlates with
the basicity of phosphines. That is, the values of pKa of conjugated
acids of each base are as follows: Ph3PH+ = 2.73, TMPPH+ = 4.59,
n-Bu3PH+ = 8.43, TDMPPH+ = 9.33, and TTMPPH+ = 11.2.10 This
basicity also correlates with the chemical shifts of 31P NMR shown in
Figure 1.
It was considered that basicity would play an important role to pro-
mote isomerization of the intermediate as discussed below. It is worth
noting that this order of basicity also was consistent with the deacety-
lating ability of acetate that was previously reported by us.4
The nature of the solvent also affected distribution of cyanohydrin
2 and acid 3 in the reactions catalyzed by TTMPP (Table II). Among
the TTMPP–catalyzed reactions, the reaction in acetonitrile produced
MeO
MeO
Me
P
OMe
P
P
OMe
P
MeO
MeO
TPP
TMPP
TTP
TDMPP
TTMPP
31P NMR in CDCl3 ; Chemical shift (PAr3 - PPh3)
TPP TMPP TTP
TPP TMPP
TTP
FIGURE 1

Tris(2,4,6-Trimethoxyphenyl)phosphine
437
TABLE II Solvent Effect on the Distribution of 2 and
3 in the Reaction of (E)-Cinnamaldehyde With
Me3SiCN in the Presence of 20 mol% TTMPPa
Products (% Yield)b
Entry
Solvent
2
3
1
2
3
4
5
6
7
CH3CN
THF
toluene
CH2Cl2
DMF
0
90
76
74
51
14
1
15
14
42
74
96
56
Et2O
EtOH
0
a
All reactions were carried out in the presence of TTMPP (20
mol%) with 1.2 equiv. Me3SiCN at r.t. for 2–3.5 h.
bYields of products were the isolated ones after hydrolysis.
only propionic acid (3) in a high yield (Table II, Entry 1). Reactions in
other solvents except for acetonitrile afforded a mixture of unsaturated
cyanohydrin 2 and saturated acid 3. In contrast with the reaction in
acetonitrile, the reaction in diethyl ether afforded cyanohydrin 2 exclu-
sively (Table II, Entry 6).
When the reaction was carried out in CH2Cl2 or DMF in the pres-
ence of a catalytic amount of TTMPP, the yield of 3 was significantly
reduced and that of 2 was raised (Table II, Entries 4 and 5). In a reaction
in ethanol catalyzed by TTMPP, cyanohydrin 2 was produced in a 56%
yield after 1M HCl work-up and 3 was not obtained. This result would
attributable to the lack of a trimethylsilyl group, which would necessary
for the critical rearrangement of cyanohydrin to α-siloxyvinyl cyanide,
due to the action of ethanol with trimethylsilyl cyanide to yield HCN
and trimethylsilyl ether of ethanol. Actually, treatment of cyanohy-
drin with 20 mol% of TTMPP did not afford 3 after hydrolysis. The
result that stoichiometric amount of trimethylsilyl cyanide is needed
to obtain saturated acid 3 from cyanohydrin indicates that trimethylsi-
lyl either protection of cyanohydrin is necessary for TTMPP-catalyzed
isomerization.
Reactions of α,β-unsaturated aldehydes other than cinnamaldehyde
1 were also examined. 2- and 4-methoxy-(E)-cinnamaldehyde were con-
verted to the corresponding saturated acid 4 and 5 in a high yield by
the aid of TTMPP (92% and 77% yield, respectively) (Eqs. 1 and 2).
Our present method is superior to the previous ruthenium-catalyzed
method in terms of yield of product and mildness of reaction conditions.
On the other hand, reactions of α-methyl-(E)-cinnamaldehyde, (E)-2-

438
M. Hayashi et al.
(1) 20 mol% TTMPP
CH3CN
25°C, 5 h
CHO
CO2H
(1)
+ Me3SiCN
(2) 1M HCl
OMe
OMe
4; 92%
(1) 20 mol% TTMPP
CH3CN
25 °C, 95 h
CO2H
CHO
(2)
+
Me3SiCN
(2) 1M HCl
MeO
MeO
5; 77%
hexenal, and (E)-2-nonenal with trimethylsilyl cyanide in the presence
of 20 mol% of TTMPP afforded trimethylsilyl ethers of cyanohydrin,
exclusively under the same reaction conditions.
As for the mechanism, the reaction was initiated by the coordination
of a Lewis base to trimethylsilyl cyanide to form hypervalent silicate,
which led to the silylcyanation of aldehydes affording trimethylsilyl
ether of cyanohydrin (Scheme 1).
The resultant cyanohydrin trimethylsilyl ether A was followed
by base-catalyzed isomerization to produce saturated acids after hy-
drolysis. Trimethylsilyl ether of cyanohydrin could also be used as
a substrate. Furthermore, before hydrolysis, the generation of 2-
(trimethylsiloxy)acrylonitrile B, which was the isomerization product of
cyanohydrin trimethylsilyl ether, was confirmed by 1H NMR and mass
spectral analyses of the reaction mixture. At this stage, acyl cyanide
and cyanohydrin trimethylsilyl ether were not observed. When (E)-
cinnamaldehyde was treated with trimethylsilyl cyanide in the pres-
ence of 5 mol% TTMPP, the ratio of E/Z isomers of α-trimethylsiloxy
1
vinyl cyanide B was 87/13 as was determined by H NMR analysis.
Aqueous work-up with 1M HCl was necessary to obtain saturated car-
boxylic acid.
O
TTMPP
OSiMe3
CN
Me
Me
Me3SiO CN
R
H
TTMPP
Si Me
CN
Me SiCN
3
+
TTMPP
isomerization
R
R
H
H+, H2O
H+, H2O
O
O
OH
CN
R
CN
R
OH
R
SCHEME 1

Tris(2,4,6-Trimethoxyphenyl)phosphine
439
CO2R
(1) 20 mol% TTMPP
+ Me3SiCN
(2) ROH
1
R = Me (6); 63% (28°C, 6 h)
R = Et (7); 69% (21°C, 4.5 h)
R = i-Pr (8); 46% (20°C, 22 h)
SCHEME 2
As an application of the presented transformation, methanolysis in-
stead of hydrolysis afforded saturated esters in good to high yield. That
is, the reaction of (E)-cinnamaldehyde (1) with trimethylsilyl cyanide by
the aid of 20 mol% TTMPP followed by the addition of methanol gave
methyl 3-phenylpropionate (6) in a 63% yield (28◦C, 3.5 h). Ethyl 3-
phenylpropionate (7) and isopropylpropyl 3-phenylpropionate (8) were
also obtained by treatment with ethanol or isopropyl alcohol (Scheme 2).
Furthermore, quenching by diethylamine or piperidine afforded cor-
responding amides (9 and 10) in 77% and 95% yields, respectively
(Eqs. 3 and 4).
O
(1) 20 mol% TTMPP
CHO
CH3CN, 25°C, 4.5 h
NEt2
(3)
+
Me3SiCN
(2) Et2NH
9; 77%
O
(1) 20 mol% TTMPP
CH3CN, 25°C, 7 h
CHO
N
(4)
Me3SiCN
+
(2) piperidine
10; 95%
In conclusion, TTMPP was found to be an effective catalyst for the
transformation of cinnamaldehydes into saturated carboxylic acids.
Treatment of the reaction mixture with alcohols or amines produced the
corresponding saturated esters or amides in a high yield, respectively.
We confirmed that the reaction proceeded through base-catalyzed silyl-
cyanation and isomerization of cyanohydrin trimethylsilyl ether, and 2-
(trimethylsiloxy)acrylonitrile was found to be a critical intermediate.11
Furthermore, 31P NMR spectra of TTMPP and related compounds also
have been disclosed for the first time.

440
M. Hayashi et al.
EXPERIMENTAL
All melting points were measured on a Yanaco MP-500D and are un-
corrected. 1H and 13C NMR spectra were recorded on a Varian UNITY
INOVA 400 (400 and 100.6 MHz, respectively), a JEOL JNM-LA 400
(400 and 100.6 MHz, respectively), or a Bruker Avance DPX 250 (250
and 62.9 MHz, respectively) using Me4Si as the internal standard in
CDCl3. IR spectra were measured on a Horiba FT-710 or Perkin-Elmer
Spectrum 1000. Elemental analyses were performed on a Yanaco CHN
Corder MT-5. Mass spectra were measured on a Shimadzu GCMS-QP
2000A. Preparative-column chromatography was carried out on a Fuji–
Devison BW-820. TLC was carried out on foil plates, Silica Gel 60 F254
(layer thickness 0.2 nm, Merck KGaA, Darmsta¨dt, Germany).
Procedure for the Transformation of Cinnamaldehyde
to Saturated Carboxylic Acids and Their Derivatives
Caution! The following reactions should be performed in a well-
ventilated hood because HCN will be produced on work-up. In a flask
were placed (E)-cinnamaldehyde (1) (1.06 g, 8.0 mmol) and CH3CN (7
mL). To this mixture were added trimethylsilyl cyanide (1.3 mL, 9.75
mmol) and TTMPP (855 mg, 1.6 mmol). The mixture was stirred at 28◦C
for 3.5 h. After confirmation of the consumption of aldehyde by TLC
analysis, the mixture was poured into the mixture of 1M HCl solution
(10 mL) and diethyl ether (10 mL) and stirred vigorously for 3 h at r.t.
Usual extractive work-up and then silica-gel column chromatography
using hexane–ethyl acetate (3/1) as an eluent gave 3-phenylpropionic
acid (3) (1.08 g, 90%).
(E)-2-Hydroxy-4-phenyl-3-butenenitrile (2)
In a flask were placed (E)-cinnamaldehyde (1) (206 mg, 1.56 mmol)
and CH3CN (2 mL). To this mixture were added trimethylsilyl cyanide
(0.25 mL, 1.87 mmol) and TMPP (109.8 mg, 0.31 mmol). The whole
was stirred at 31◦C for 3.5 h. After confirmation of the consumption of
aldehyde by TLC analysis, the mixture was poured into the mixture of
1M HCl solution (10 mL) and diethyl ether (10 mL) and stirred vigor-
ously for 3 h at r.t. Usual extractive work-up and then silica-gel column
chromatography using hexane–ethyl acetate (3/1) as an eluent gave
(E)-2-hydroxy-4-phenyl-3-butenenitrile (2) (216 mg, 87%). Rf 0.35 (3:1
hexane–ethyl acetate); m.p. 78–79◦C (lit.12 78◦C); IR (KBr): νmax (cm−1
)
3370, 3030, 2925, 2820, 2250, 1960, 1655, 1575, 1490, 1450, 1415, 1300,
1120, 1090, 1070, 1025, 975, 925, 820, 755; 1H NMR (250 MHz, CDCl3): δ
3.68 (br s, 1H), 5.13 (d, J= 6.0 Hz, 1H), 6.22 (dd, J= 15.9 Hz, J= 6.0Hz,

Tris(2,4,6-Trimethoxyphenyl)phosphine
441
1H), 6.87 (d, J= 15.9 Hz, 1H), 7.3–7.4 (m, 5H); 13C NMR (62.9 MHz,
CDCl3): δ 61.8, 118.2, 122.2, 127.0, 128.8, 129.1, 134.7, 135.3. MS m/z
(relative intensity): 159 (48.1%), 130 (100%), 115 (40.0%), 103 (61.1%),
91 (78.8%), 77 (82.1%). Anal. calcd. for C10H9NO: C, 75.45; H, 5.70; N,
8.80. Found: C, 75.61; H, 5.66; N, 8.72.
3-Phenylpropionic Acid (3)
In a flask were placed (E)-cinnamaldehyde (1) (1.06 g, 8.0 mmol)
and CH3CN (7 mL). To this mixture were added trimethylsilyl cyanide
(1.3 mL, 9.75 mmol) and TTMPP (855 mg, 1.6 mmol). The mixture
was stirred at 28◦C for 3.5 h. After confirmation of the consumption
of aldehyde by TLC analysis, the mixture was poured into the mix-
ture of 1M HCl solution (10 mL) and diethyl ether (10 mL) and stirred
vigorously for 3 h at r.t. Usual extractive work-up and then silica-gel
column chromatography using hexane–ethyl acetate (3/1) as an eluent
gave 3-phenylpropionic acid (3) (1.08 g, 90%). Rf 0.28 (3:1 hexane–ethyl
acetate); m.p. 47–49◦C (lit.13 46◦C); IR (KBr): νmax (cm−1) 3030, 2935,
2700, 2640, 2290, 1950, 1715, 1700, 1680, 1605, 1495, 1455, 1430, 410,
1305, 1220, 930, 785, 755, 725, 700, 535; 1H NMR (250 MHz, CDCl3): δ
2.72 (t, J= 7.7 Hz, 2H), 3.00 (t, J= 7.7 Hz, 2H), 7.2–7.4 (m, 5H), 11.05
(br s, 1H); 13C NMR (62.9 MHz, CDCl3): δ 30.5, 35.6, 126.3, 128.2, 128.5,
140.1, 179.2. MS m/z (relative intensity): 150 (35.6%), 104 (50.3%), 91
(100%). Anal. calcd. for C9H10O2: C, 71.98; H, 6.71. Found: C, 71.97; H,
6.74.
3-(2-Methoxyphenyl)propionic Acid (4)
In a flask were placed 2-methoxycinnamaldehyde (205.8 mg, 1.27
mmol) and CH3CN (2 mL). To this mixture were added trimethylsilyl
cyanide (0.2 mL, 1.52 mmol) and TTMPP (135.1 mg, 0.25 mmol). The
mixture was stirred at 29◦C for 3.5 h. After confirmation of the con-
sumption of aldehyde by TLC analysis, the mixture was poured into
the mixture of 1M HCl solution (10 mL) and diethyl ether (10 mL) and
stirred vigorously for 3 h at r.t. Usual extractive work-up and then
silica-gel column chromatography using hexane–ethyl acetate (3/1) as
an eluent gave 3-(2-methoxyphenyl)propionic acid (4) (210.8 mg, 92%).
Rf 0.30 (3:1 hexane–ethyl acetate); m.p. 90–92◦C (lit.14 91–92◦C); IR
(KBr): νmax (cm−1) 3010, 2640, 1710, 1700, 1690, 1495, 1460, 1435, 1405,
1335, 1295, 1245, 1220, 1115, 1050, 1025, 930, 760; 1H NMR (400 MHz,
CDCl3): δ 2.66 (t, J= 7.7 Hz, 2H), 2.94 (t, J= 7.7 Hz, 2H), 3.81 (s, 3H),
6.8–6.9 and 7.1–7.2 (each m, 2H), 10.99 (br s, 1H); 13C NMR (62.9 MHz,
CDCl3): δ 25.8, 33.9, 55.1, 110.1, 120.4, 127.7 and 129.9, 128.4, 157.4,
180.0. MS m/z (relative intensity): 180 (35.8%), 121 (100%), 91 (20.6%),

442
M. Hayashi et al.
77 (24.6%). Anal. calcd. for C9H10O2: C, 66.65; H, 6.71. Found: C, 66.86;
H, 6.71.
3-(4-Methoxyphenyl)propionic Acid (5)
In a flask were placed 4-methoxycinnamaldehyde (226.8 mg, 1.40
mmol) and CH3CN (2 mL). To this mixture were added trimethylsilyl
cyanide (0.22 mL, 1.68 mmol) and TTMPP (148.9 mg, 0.28 mmol). The
mixture was stirred at 25◦C for 95 h. After confirmation of the con-
sumption of aldehyde by TLC analysis, the mixture was poured into
the mixture of 1M HCl solution (10 mL) and diethyl ether (10 mL) and
stirred vigorously for 3 h at r.t. Usual extractive work-up and then
silica-gel column chromatography using hexane–ethyl acetate (3/1) as
an eluent gave 3-(4-methoxyphenyl)propionic acid (5) (195.2 mg, 77%).
Rf 0.29 (2:1 hexane-ethyl acetate); m.p. 99–104◦C (lit.15 95–102◦C); IR
(KBr): νmax (cm−1) 2960, 2640, 1710, 1615, 1585, 1510, 1460, 1440, 1420,
1410, 1300, 1280, 1245, 1215, 1180, 1160, 1110, 1030, 960; 1H NMR (250
MHz, CDCl3): δ 2.65 (t, J= 7.6 Hz, 2H), 2.91 (t, J= 7.6 Hz, 2H), 3.79
(s, 3H), 6.84 (d, J= 8.6 Hz, 2H), 7.13 (d, J= 8.6 Hz, 2H), 12.32 (br s,
1H); 13C NMR (62.9 MHz, CDCl3): δ 29.6, 35.8, 55.2, 113.9, 129.2, 132.2,
158.0, 179.3. MS m/z (relative intensity): 180 (33.1%), 134 (20.4%), 121
(84.2%), 91 (100%), 77 (21.1%). Anal. calcd. for C9H10O2: C, 66.65; H,
6.71. Found: C, 66.62; H, 6.79.
Methyl 3-Phenylpropionate (6)
In a flask were placed (E)-cinnamaldehyde (170.7 mg, 1.29 mmol)
and CH3CN (2 mL). To this mixture were added trimethylsilyl cyanide
(0.21 mL, 1.55 mmol) and TTMPP (137.6 mg, 0.26 mmol). The mixture
was stirred at 28◦C for 6 h. After confirmation of the consumption of
aldehyde by TLC analysis, the mixture was poured into MeOH (10 mL)
and stirred vigorously for 3 h at r.t. Usual extractive work-up and then
silica-gel column chromatography using hexane–ethyl acetate (3/1) as
an eluent gave methyl 3-phenylpropionate (6) (134.2 mg, 63%). Rf 0.41
(10:1 hexane–ethyl acetate); IR (KBr): νmax (cm−1) 3030, 2950, 1740,
1730, 1700, 1685, 1655, 1635, 1495, 1455, 1435, 1365, 1295, 1200, 1160,
1
1080, 1030, 985, 840, 752, 700; H NMR (250 MHz, CDCl3): δ 2.63 (t,
J= 7.8 Hz, 2H), 2.95 (t, J= 7.8 Hz, 2H), 3.66 (s, 3H), 7.2–7.3 (m, 5H);
13C NMR (62.9 MHz, CDCl3): δ 30.8, 35.6, 51.4, 126.1, 128.1, 128.4,
140.4, 173.2. MS m/z (relative intensity): 164 (18.2%), 104 (100%), 91
(71.4%), 77 (19.6%), 65 (13.4%). Anal. calcd. for C10H12O2: C, 73.15; H,
7.37. Found: C, 72.91; H, 7.50.

Tris(2,4,6-Trimethoxyphenyl)phosphine
443
Ethyl 3-Phenylpropionate (7)
In a flask were placed (E)-cinnamaldehyde (232.0 mg, 1.76 mmol)
and CH3CN (2 mL). To this mixture were added trimethylsilyl cyanide
(0.28 mL, 2.11 mmol) and TTMPP (187.0 mg, 0.35 mmol). The mixture
was stirred at 21◦C for 4.5 h. After confirmation of the consumption of
aldehyde by TLC analysis, EtOH (2 mL) was poured into the mixture
and stirred vigorously for 3 h at r.t. Usual extractive work-up and then
silica-gel column chromatography using hexane–ethyl acetate (3/1) as
an eluent gave ethyl 3-phenylpropionate (7) (216.7 mg, 69%). Rf 0.43
(10:1 hexane–ethyl acetate); IR (KBr): νmax (cm−1) 3065, 3030, 2980,
2935, 1735, 1605, 1500, 1455, 1375, 1295, 1255, 1205, 1180, 1160, 1080,
1
1040, 750, 700; H NMR (400 MHz, CDCl3): δ 1.22 (t, J= 7.3 Hz, 3H),
2.61 (t, J= 7.7 Hz, 2H), 2.94 (t, J= 7.7 Hz, 2H), 4.11 (q, 2H, J= 7.3 Hz,
2H), 7.2–7.3 (m, 5H); 13C NMR (100.6 MHz, CDCl3): δ 14.1, 30.9, 35.9,
60.3, 126.1, 128.2, 128.4, 140.5, 172.8. MS m/z (relative intensity): 178
(16.3%), 104 (100%), 91 (65.0%), 77 (21.1%). Anal. calcd. for C11H14O2:
C, 74.13; H, 7.92. Found: C, 73.96; H, 8.01.
Isopropyl 3-Phenylpropionate (8)
In a flask were placed (E)-cinnamaldehyde (258.8 mg, 1.96 mmol)
and CH3CN (2 mL). To this mixture were added trimethylsilyl cyanide
(0.31 mL, 2.35 mmol) and TTMPP (208.6 mg, 0.39 mmol). The mixture
was stirred at 20◦C for 22 h. After confirmation of the consumption of
aldehyde by TLC analysis, i-PrOH (2 mL) was poured into the mixture
and stirred vigorously for 3 h at r.t. Usual extractive work-up and then
silica-gel column chromatography using hexane–ethyl acetate (3/1)
as an eluent gave isopropyl 3-phenylpropionate (8) (172.9 mg, 46%).
Rf 0.43 (15:1 hexane–ethyl acetate); IR (KBr): νmax (cm−1) 3090, 3065,
3030, 2980, 2935, 2875, 1725, 1500, 1470, 1455, 1375, 1290, 1260, 1210,
1180, 1145, 1110, 1080, 750, 700; 1H NMR (400 MHz, CDCl3): δ 1.20 (d,
J= 6.4 Hz, 6H), 2.58 (t, J= 7.9 Hz, 2H), 2.94 (t, J= 7.9 Hz, 2H), 5.00
(sept, J= 6.4 Hz, 1H), 7.2–7.3 (m, 5H); 13C NMR (100.6 MHz, CDCl3): δ
21.7, 30.9, 36.2, 67.7, 126.1, 128.2, 128.3, 140.5, 172.3. MS m/z (relative
intensity): 192 (5.6%), 150 (31.8%), 133 (17.7%), 104 (100%), 91 (99.9%),
77 (22.2%). Anal. calcd. for C12H16O2: C, 74.97; H, 8.39. Found: C, 74.83;
H, 8.50.
N,N-Diethyl-3-phenylpropanamide (9)
In a flask were placed (E)-cinnamaldehyde (261.6 mg, 1.98 mmol)
and CH3CN (2 mL). To this mixture were added trimethylsilyl cyanide
(0.32 mL, 2.38 mmol) and TTMPP (210.8 mg, 0.40 mmol). The mixture
was stirred at 20◦C for 4.5 h. After confirmation of the consumption of

444
M. Hayashi et al.
aldehyde by TLC analysis, diethylamine (0.25 mL, 2.38 mmol) was
poured into the mixture and stirred vigorously for 3 h at r.t. Usual
extractive work-up and then silica-gel column chromatography us-
ing hexane–ethyl acetate (3/1) as an eluent gave N,N-diethyl-3-
phenylpropanamide (9) (312.6 mg, 77%). Rf 0.13 (6:1 hexane–ethyl ac-
etate); IR (KBr): νmax (cm−1) 3060, 3025, 2970, 2935, 2875, 1640, 1605,
1495, 1455, 1430, 1380, 1365, 1265, 1245, 1220, 1140, 1095, 1075, 755,
1
700; H NMR (400 MHz, CDCl3): δ 1.10 (t, J= 7.3 Hz, 3H), 1.11 (t,
J= 7.3 Hz, 3H), 2.59 (t, J= 7.9 Hz, 2H), 2.98 (t, JH2−H3 = 7.9 Hz, 2H),
3.22 (q, J= 7.3 Hz, 2H), 3.38 (q, J= 7.3 Hz, 2H), 7.2–7.3 (m, 5H); 13C
NMR (100.6 MHz, CDCl3): δ 12.9, 14.1, 31.5, 34.9, 40.0, 41.7, 125.9,
128.2, 128.3, 141.3, 171.0. MS m/z (relative intensity): 205 (23.9%), 114
(14.1%), 105 (21.7%), 91 (39.9%), 77 (10.5%), 74 (10.8%), 72 (37%), 58
(100%). Anal. calcd. for C13H19NO: C, 76.06; H, 9.33; N, 6.82. Found: C,
76.03; H, 9.36; N, 6.78.
1-(3-Phenylpropanoyl)piperidine (10)
In a flask were placed (E)-cinnamaldehyde (310.6 mg, 2.35 mmol)
and CH3CN (2 mL). To this mixture were added trimethylsilyl cyanide
(0.38 mL, 2.82 mmol) and TTMPP (250.3 mg, 0.47 mmol). The whole
was stirred at 25◦C for 7 h. After confirmation of the consump-
tion of aldehyde by TLC analysis, cyclohexylamine (0.28 mL, 2.82
mmol) was poured into the mixture and stirred vigorously for 3 h
at r.t. Usual extractive work-up and then silica-gel column chro-
matography using hexane–ethyl acetate (3/1) as an eluent gave 1-(3-
phenylpropanoyl)piperidine(10) (483.7 mg, 95%). Rf 0.24 (2:1 hexane–
ethyl acetate); IR (KBr): νmax (cm−1) 3025, 2935, 2855, 1645, 1605, 1495,
1470, 1435, 1280, 1250, 1220, 1140, 1025, 1010, 855, 750, 700; 1H NMR
(400 MHz, CDCl3): δ 1.4–1.6 (m, 6H), 2.62 (t, J= 7.9 Hz, 2H), 2.97 (t,
J= 7.9 Hz, 2H), 3.33 (t, J= 5.6 Hz, 2H), 3.56 (t, J= 5.6 Hz, 2H), 7.2–7.3
(m, 5H); 13C NMR (62.6 MHz, CDCl3): δ 24.3, 25.3, 26.1, 31.4, 34.9, 42.5,
46.4, 125.9, 128.2, 128.3, 141.2, 170.2. MS m/z (relative intensity): 217
(32.2%), 126 (100%), 105 (15.6%), 91 (37.1%), 84 (55.9%), 77 (11.2%).
Anal. calcd. for C14H19NO: C, 77.38; H, 8.81; N, 6.45. Found: C, 77.20;
H, 8.98; N, 6.50.
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Tris(2,4,6-Trimethoxyphenyl)phosphine
445
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