Polymer-supported PPh3 as a reusable organocatalyst for the Mukaiyama aldol and Mannich reaction

Article abstract of DOI:10.1039/c4ra03394a

An easily accessible and user-friendly polymer-supported phosphine PS-PPh₃ catalyzes the aldol reaction of aldehydes and imines. A broad range of aldehydes and imines could be applied under mild conditions using 5-10 mol% PS-PPh₃. PS-PPh₃ was easily recovered and reused with minimal loss of activity. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra03394a

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Polymer-supported PPh3 as a reusable
organocatalyst for the Mukaiyama aldol and
Cite this: RSC Adv., 2014, 4, 27780
Mannich reaction†
*
Satoru Matsukawa, Kazuki Fukazawa and Junya Kimura
Received 14th April 2014
Accepted 10th June 2014
An easily accessible and user-friendly polymer-supported phosphine PS-PPh3 catalyzes the aldol reaction
of aldehydes and imines. A broad range of aldehydes and imines could be applied under mild conditions
using 5–10 mol% PS-PPh3. PS-PPh3 was easily recovered and reused with minimal loss of activity.
DOI: 10.1039/c4ra03394a
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via activation of the electrophiles or by a Lewis base via activa-
tion of the nucleophiles. For example, the reaction could be
catalyzed by uoride,14 phosphines,15 lithium amides,16 lithium
Introduction
Polymer-supported catalysts have attracted much attention in
recent decades due to their inherent advantages in synthetic
chemistry, e.g., simplication of reaction procedures including
easy recovery of the catalyst by ltration, application to auto-
mated systems, and recycling of the catalyst.1 Polymer-sup-
ported organobases have attracted much attention in recent
years. For example, polymer-supported bicyclic guanidine,
1,5,7-triazabicyclo[4,4,0]dec-5-ene polystyrene (PS-TBD), acts
as a good catalyst for the Henry reaction,2 ring-openings of
epoxides,3,4 aldol-type condensations and Michael additions.3
acetate,17 lithium alkoxides,18 quaternary ammonium den-
drimers,19 ammonium phenoxide,20 N-oxides,21 N-methyl imid-
azole,22 sodium phenoxide–phosphine oxides,23 N-heterocyclic
carbenes,24 Verkade superbases25 and dendritic HMPA.26
Herein, we report that easily accessible and user-friendly poly-
mer-supported phosphine PS-PPh3 acts as an efficient and
reusable catalyst for the Mukaiyama aldol and Mannich
reactions.27,28
Polymer-supported
formamides,
phosphoramide,
dia-
Results and discussion
zaphosphorine (PS-BEMP) and phosphine (PS-PPh3) also act as
good catalysts for carbon–carbon bond forming reactions
including Michael additions,5 ring-openings of epoxides,6 cya-
nosilylation,7 allylation of aldehydes with allyltrichlorosilane
and aldol reactions with trichlorosilyl enol ethers.8,9 Recently,
we have also reported cyanosilylation of aldehydes, ketones,
imines and aziridines catalyzed by PS-TBD.10 In an effort to
apply polymer-supported organobases to other useful reactions,
Mukaiyama aldol reactions of aldehydes and imines were
examined.
The aldol reaction has become a fundamental method for
forming carbon–carbon bonds in modern organic synthesis.
One of the most commonly used and best understood is the
Mukaiyama aldol reaction (addition of silyl enol ethers to
carbonyl compounds).11,12 This method has many advantages
over the previous aldol reactions, such as mild reaction condi-
tions, nonreversibility and lower production of side products.
Therefore, several efficient catalysts have been developed in the
last 40 years to realize high yields and selectivities of this
reaction.13 This reaction can be catalyzed either by a Lewis acid
First, we examined the catalytic activity of various commercially
available polymer-supported bases (Fig. 1) in the reaction of 4-
methoxybenzaldehyde with a trimethylsilyl enol ether derived
from methyl isobutyrate. The reaction was carried out by adding
the trimethylsilyl enol ether and aldehyde to DMF containing 5
mol% of the polymer-supported base at room temperature. The
reaction was monitored by TLC. Aer the reaction was
completed, EtOAc was added to the mixture and the polymer-
supported base was removed by ltration. The ltrate was
concentrated under vacuum and puried by column chroma-
tography to afford the pure product. The results are
Department of Science Education, Faculty of Education, Ibaraki University, Ibaraki,
310-8512 Japan. E-mail: smatsuka@mx.ibaraki.ac.jp; Fax: +81 29 228 8234
† electronic supplementary information (ESI) available: Copies of 1H and 13C
NMR Spectra of products 3a–3l, 5a–5b, 7a–7f. See DOI: 10.1039/c4ra03394a
Fig. 1 Polymer-supported bases.
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Table 2 PS-PPh3 catalyzed Mukaiyama aldol reaction of various
aldehydes
summarized in Table 1. Good product yields were obtained in
the presence of a catalytic amount of the PS-PPh3. Interestingly,
the product was obtained in lower yields when PS-TBD and PS-
BEMP, which have higher basicity than PS-PPh3, were used as
catalysts. PS-DMAP was also used as a catalyst, however chem-
ical yields were low. The reactions performed in THF, MeCN,
CH2Cl2 and toluene were inferior when compared to that per-
formed in DMF. Solvent free conditions (SFC) were also effec-
tive. However, a longer reaction time was required to obtain the
product in a good yield.
The recovery and reuse of PS-PPh3 are illustrated in Scheme 1
for the reaction of 4-methoxybenzaldehyde with a trimethylsilyl
enol ether. Aer the reaction was completed, ethyl acetate was
added to the reaction mixture and the catalyst was recovered by
ltration. The recovered catalyst was washed (H2O, NH3,
acetone), dried and then reused. The catalyst maintained its
catalytic activity aer three runs.
Entry
1
Aldehyde
Product
Time
8 h
Yield (%)a
94
3a
2
3
3b
3c
8 h
4 h
91
95
In order to clarify the scope of this reaction, several alde-
hydes were examined in the presence of 10 mol% PS-PPh3
(Table 2). Aromatic aldehydes with either electron-donating or
Table 1 Optimization of the reaction conditions
4
5
6
7
3d
3e
3f
6 h
8 h
8 h
8 h
88
85
90
86
Entry
Base
Solvent
Yield (%)
a
1
2
3
PS-PPh3
PS-TBD
DMF
DMF
DMF
DMF
94
63
55
35
45
36
25
20
60
81e
PS-BEMPb
PS-DMAPc
3g
4
5
6
CH3CN
THF
7
8
9
CH2Cl2
Toluene
SFCd
8
9
3h
3i
4 h
8 h
95
93
10
SFC
a
b
PS-PPh3:
diphenylphosphino-polystyrene.
PS-BEMP:
2-tert-
butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphor-
c
ine polystyrene. PS-DMAP: N-(methyl polystyrene)-4-(methylamino)
pyridine. d SFC: solvent free condition. e Reaction time: 24 h.
10
11
3j
24 h
24 h
4 h
87
91
84
3k
3l
12
a
Isolated yield.
Scheme 1 Reuse of recovered PS-PPh3.
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electron-withdrawing groups afforded the corresponding prod- entries 1 vs. 2, 3). We also examined three component Mannich
ucts in high yields. Compared with the aromatic aldehyde, the reaction between silyl enol ether 1, benzaldehyde (2b) and
aliphatic aldehyde required a longer reaction time, which was tosylamine, unfortunately the product was obtained as a
similar to that for other Lewis base catalysts. Heteroaromatic mixture of aldol product 3b and Mannich product 7b.
aldehydes also worked well.
A possible mechanism is illustrated in Scheme 2. First,
This PS-PPh3 catalyzed Mukaiyama aldol reaction was also phosphorus atom of PS-PPh3 coordinates the silicon atom of the
examined by using other silyl enol ethers (Table 3). Good silyl enol ether to form activated hexa coordinated silicon
product yields were obtained trimethylsilyl enol ether derived species A or penta coordinated silicon species A0 and the O–Si
from ethyl acetate. In this case, the reaction also proceeded bond is activated. Next, the nucleophilicity of the enol ether is
smoothly when 1 mol% of PS-PPh3 was used. Moderate syn- enhanced and readily reacts with an electrophile to produce the
diastereoselectivity was observed irrespective of the geometry of alkoxide or amino ion B and silylphosphonium salt. Finally,
the silyl enol ether derived from methyl propionate. This trend immediate silylation occurs to give the silylated adduct C with
is the same as previous reports. Unfortunately, we had no regeneration of PS-PPh3. This mechanism is similar to that of
success with ketone silyl enol ethers under these conditions.
Furthermore, we have extended the present catalytic system
to the reaction with imines (Mannich reaction).29–31 The corre-
sponding b-amino esters were obtained in moderate to good
yields in the presence of 10 mol% PS-PPh3 (Table 4). In this
case, the reaction rates were inuenced by the type of substit-
uent on the benzene ring. When aromatic aldimines having
electron-donating groups were used, the reaction proceeded
more slowly compared with those using aldimines having
electron-withdrawing groups. The product was obtained in
lower yields when other polymer-supported organobases such
as PS-TBD and PS-BEMP were used instead of PS-PPh3 (Table 4,
previously reported Lewis base catalyzed aldol reactions.13a,16-25,31
Experimental
All reactions were performed under an argon atmosphere using
oven-dried glassware. Flash column chromatography was per-
formed using silica gel Wakogel C-200. Preparative thin-layer
chromatography was carried out on silica gel Wakogel B-5F.
Dehydrate DMF, THF, toluene and CH3CN were purchased from
Wako Chemical. Other commercially available reagents was
used as received without further purication. Yields refer to
isolated compounds estimated to be >95% pure, as determined
Table 3 PS-PPh3 catalyzed aldol reaction of various silyl enol ethers
Entry
Silyl enol ethers
Time
Products
Yield (%)a,b (syn–anti)
1
0.5 h
8 h
85
84
2c
3
4 h
90, (66 : 34)
4
5
4 h
74, (70 : 30)
Trace
24 h
6
24 h
Trace
a
Isolated yield. b In this case, silyl ether product was unstable, then product was obtained as OH form aer hydrolysis. c 1 mol% of PS-PPh3 was
used.
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by 1H NMR spectroscopy. IR spectra were recorded on a JUSCO
FT/IR-430 spectrometer.1H and 13C NMR spectra were deter-
mined for solutions in CDCl3 with Me4Si as internal standard
on a Bruker Avance III instrument. HRMS data were measured
on a JEOL JMS-700 mass spectrometer.
Table 4 PS-PPh3 catalyzed aldol reaction of various Imines
General procedure for PS-PPh3 catalyzed Mukaiyama aldol
reaction of aldehyde with silyl ketene acetals
Entry Aldehyde
Temperature Time Yielda (%)
To a suspension of PS-PPh3 (0.05 mmol) in DMF (1 mL) was
added aldehyde (1.0 mmol) and silyl ketene acetal (1.25 mmol)
at room temperature. Aer the reaction was complete (as
determined by TLC), EtOAc (5 ml) was added to the mixture and
PS-PPh3 was separated by ltration. The ltrate was concen-
trated under vacuum and puried by column chromatography
on silica gel (EtOAc : hexane ¼ 1 : 3) to give the corresponding
product. The recovered catalyst is reusable aer washing
(acetone, NH4OH and water) and drying in vacuo.
1
r.t
r.t.
r.t.
18 h 85 (7a)
18 h 33 (7a)
18 h 20 (7a)
2b
3c
4
5
40 ꢀ
r.t.
C
12 h 82 (7b)
12 h 90 (7c)
General procedure for PS-PPh3 catalyzed Mannich reaction of
imine with silyl ketene acetals
To a suspension of PS-PPh3 (0.10 mmol) in DMF (1 mL) was
added imine (1.0 mmol) and silyl ketene acetal (1.25 mmol) at
room temperature or 30 ꢀC. Aer the reaction was complete (as
determined by TLC), EtOAc (15 ml) was added to the mixture
and PS-PPh3 was separated by ltration. The ltrate was washed
with brine and water and dried over anhydrous Na2SO4, then
evaporated. The crude mixture was puried by preparative TLC
(EtOAc : hexane ¼ 1 : 1) to afford the corresponding product.
6
7
40 ꢀ
C
C
24 h 74 (7d)
24 h 56 (7e)
40 ꢀ
Methyl
3-(4-methoxyphenyl)-2,2-dimethyl-3-trimethylsily-
loxy-propionate (3a).32 Colorless oil; yield: 303 mg (94%); 1H
NMR (500 MHz, CDCl3): d 0.09 (s, 9H), 0.93 (s, 3H), 1.06 (s, 3H),
3.63 (s, 3H), 3.75 (s, 3H), 4.88 (s, 1H), 6.77 (d, J ¼ 8.6 Hz, 5H),
7.13 (d, J ¼ 8.6 Hz, 5H); 13C NMR (125 MHz, CDCl3) d ¼ 0.0,
19.1, 21.7, 49.1, 51.6, 55.2, 78.8, 112.8, 128.8, 133.0, 158.9, 177.4;
HRMS (FAB): m/z: calcd for C16H27O4Si: 323.1679; found:
323.1961 [M + H]+.
8
r.t.
18 h 82 (7f)
a
b
c
Isolated yield. PS-TBD was used instead of PS-PPh3. PS-BEMP was
used instead of PS-PPh3.
Methyl 2,2-dimethyl-3-phenyl-3-trimethylsilyloxypropionate
1
(3b).17c Colorless oil; yield: 255 mg (91%); H NMR (500 MHz,
CDCl3): d 0.04 (s, 9H), 0.97 (s, 3H), 1.11 (s, 3H), 3.66 (s, 3H), 4.96
(s, 1H), 4.92 (s, 1H), 7.22–7.32 (m, 5H); 13C NMR (125 MHz,
CDCl3) d ¼ 0.0, 19.0, 22.0, 49.1, 51.7, 79.2, 127.4, 127.8, 140.7,
177.3; HRMS (FAB): m/z: calcd for C15H25O3Si: 281.1573; found:
281.1568 [M + H]+.
Methyl 3-(4-chlorophenyl)-2,2-dimethyl-3-trimethylsilyloxy-
propionate (3c).17c White solid; m.p. 53 ꢀC; yield: 299 mg (95%);
1H NMR (500 MHz, CDCl3): d 0.06 (s, 9H), 0.94 (s, 3H), 1.08 (s,
3H), 3.64 (s, 3H), 7.18 (d, J ¼ 8.4 Hz, 5H), 7.23 (d, J ¼ 8.6 Hz, 5H);
13C NMR (125 MHz, CDCl3) d ¼ 0.0, 19.2, 21.4, 48.9, 51.7, 78.5,
127.6, 129.2, 133.1, 139.5, 177.0; HRMS (FAB): m/z: calcd for
C
15H24ClO3Si: 315.1183; found: 315.1175 [M + H]+.
Methyl 3-(4-methylphenyl)-2,2-dimethyl-3-trimethylsilyloxy-
1
propionate (3d).33 Colorless oil; yield: 259 mg (88%); H NMR
(500 MHz, CDCl3): d 0.07 (s, 9H), 0.96 (s, 3H), 1.09 (s, 3H), 2.30
(s, 3H), 3.65 (s, 3H), 4.91 (s, 1H), 7.05 (d, J ¼ 8.0 Hz, 5H), 7.13 (d,
J ¼ 8.0 Hz, 5H); 13C NMR (125 MHz, CDCl3) d ¼ 0.0, 19.1, 21.1,
21.7, 49.0, 51.6, 79.0, 127.7, 128.1, 136.9, 137.8, 177.5; HRMS
Scheme 2 Proposed mechanism.
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(FAB): m/z: calcd for C16H27O3Si: 295.1729; found: 295.1727 9.1 Hz, 1H); 13C NMR (125 MHz, CDCl3) d ¼ 0.7, 14.1, 20.1, 21.6,
[M + H]+.
22.6, 27.0, 29.2, 29.5, 29.7, 31.8, 32.8, 48.2, 51.5, 77.7, 177.8;
Methyl 2,2-dimethyl-3-(4-nitromethoxyphenyl)-3-trimethyl- HRMS (FAB): m/z: calcd for C17H37O3Si: 317.2512; found:
silyloxypropionate (3e).33 White solid; m.p. 116 ꢀC; yield: 275 mg 317.2523 [M + H]+.
1
(85%); H NMR (500 MHz, CDCl3): d 0.04 (s, 9H), 0.97 (s, 3H),
Methyl
3-(2-furyl)-2,2-dimethyl-3-trimethylsilyloxy-propio-
1.11 (s, 3H), 3.65 (s, 3H), 5.03 (s, 1H), 7.43 (d, J ¼ 8.5 Hz, 5H), nate (3l).17c Colorless oil; yield: 242 mg (84%); 1H NMR (500
8.13 (d, J ¼ 8.5 Hz, 5H); 13C NMR (125 MHz, CDCl3) d ¼ 0.0, MHz, CDCl3): d 0.00 (s, 9H), 1.04 (s, 3H), 1.23 (s, 3H), 3.68 (s,
19.7, 21.3, 49.1, 52.0, 78.3, 122.8, 128.5, 147.4, 148.7, 176.5.; 3H), 5.00 (s, 1H), 6.20 (d, J ¼ 3.2 Hz, 1H), 6.31 (d, J ¼ 3.2 Hz, 1H),
HRMS (FAB): m/z: calcd for C15H24NO5Si: 326.1424; found: 7.32–7.34 (m, 1H); 13C NMR (125 MHz, CDCl3) d ¼ ꢁ0.3, 19.6,
326.1417 [M + H]+.
21.2, 48.6, 51.8, 73.5, 107.9, 109.9, 141.5, 154.4, 176.8; HRMS
Methyl 3-[4-(dimethylamino)phenyl]-2,2-dimethyl-3-tri- (FAB): m/z: calcd for C13H23O4Si: 271.1366; found: 271.1363
methyl-silyloxypropionate (3f).17c White solid; m.p. 76 ꢀC; yield: [M + H]+.
291 mg (90%); 1H NMR (500 MHz, CDCl3): d 0.08 (s, 9H), 0.94 (s,
Ethyl 3-3-hydroxy-3-phenylpropionate (5a).33 Colorless oil;
3H), 1.07 (s, 3H), 2.92 (S, 6H), 3.64 (s, 3H), 4.86 (s, 1H), 6.55–6.70 yield: 165 mg (85%); 1H NMR (500 MHz, CDCl3): d 1.26 (t, J ¼ 7.2
(m, 2H), 7.05–7.15 (m, 2H); 13C NMR (125 MHz, CDCl3) d ¼ 0.0, Hz, 3H), 2.70 (dd, J ¼ 3.9, 16.4 Hz, 1H), 2.76 (dd, J ¼ 9.0, 16.4 Hz,
18.9, 21.9, 40.7, 49.2, 51.7, 79.1, 111.4, 128.7, 149.8, 177.6; 1H), 3.30-–3.34 (brs, 3H), 4.18 (q, J ¼ 7.2 Hz, 2H), 5.13 (dd, J ¼
HRMS (FAB): m/z: calcd for C17H30NO3Si: 324.1995; found: 2.8, 8.8 Hz, 1H), 7.28–7.31 (m, 1H), 7.35–7.39 (m, 4H); 13C NMR
324.2007 [M + H]+.
Methyl
loxy-propionate (3g).34 Colorless oil; yield: 285 mg (86%); 1H found: 195.1010 [M + H]+.
(125 MHz, CDCl3) d ¼ 14.1, 43.2, 60.9, 70.3, 125.6, 127.8, 128.5,
2,2-dimethyl-3-(naphthalene-1-yl)-3-trimethylsily- 142.4, 172.4; HRMS (FAB): m/z: calcd for C11H15O3: 195.1021;
NMR (500 MHz, CDCl3): d ꢁ0.11 (s, 9H), 0.93 (s, 3H), 1.21 (s,
Methyl 3-3-hydroxy-2-methyl-3-phenylpropionate (5b).17c
3H), 3.64 (s, 3H), 6.00 (s, 1H), 7.40–7.51 (m, 3H), 7.69 (d, J ¼ 7.4 syn–anti mixture: colorless oil; yield: 175 mg (90%); HRMS
Hz, 1H), 7.76 (d, J ¼ 8.2 Hz, 1H), 7.82 (d, J ¼ 7.4 Hz, 1H), 8.15 (d, (FAB): m/z: calcd for C11H15O3: 195.1021; found: 195.1033
J ¼ 8.2 Hz, 1H); 13C NMR (125 MHz, CDCl3) d ¼ ꢁ0.1, 18.5, 23.0, [M + H]+. syn Isomer: 1H NMR (500 MHz, CDCl3): d 1.12 (d,
50.0, 51.8, 72.9, 123.2, 124.8, 125.0, 125.7, 127.0, 127.9, 128.8, J ¼ 7.2 Hz, 3H), 2.78 (dq, J ¼ 4.1, 7.2 Hz, 1H), 2.93–2.98 (brs, 3H),
131.6, 133.2, 136.8, 177.5; HRMS (FAB): m/z: calcd for 3.67 (s, 3H), 5.10 (d, J ¼ 4.0 Hz, 1H), 7.23–7.30 (m, 1H), 7.31–7.39
C
19H27O3Si: 331.1729; found: 331.1736 [M + H]+.
Methyl
(m, 4H); 13C NMR (125 MHz, CDCl3) d ¼ 10.6, 46.3, 51.8, 73.5,
2,2-dimethyl-3-(naphthalene-2-yl)-3-trimethylsily- 125.9, 127.5, 128.2, 141.3, 176.2.; anti Isomer: 1H NMR (500
loxy-propionate (3h).35 White solid; m.p. 70 ꢀC; yield: 315 mg MHz, CDCl3): d 1.00 (d, J ¼ 7.2 Hz, 3H), 2.83 (dq, J ¼ 7.2, 8.4 Hz,
(95%); 1H NMR (500 MHz, CDCl3): d ꢁ0.05 (s, 9H), 1.02 (s, 3H), 1H), 2.90–3.05 (brs, 3H), 3.72 (s, 3H), 4.74 (d, J ¼ 8.4 Hz, 1H),
1.15 (s, 3H), 3.67 (s, 3H), 5.13 (s, 1H), 7.40–7.47 (m, 3H), 7.67 (d, 7.25–7.30 (m, 1H), 7.31–7.42 (m, 4H); 13C NMR (125 MHz,
J ¼ 4.4 Hz, 1H), 7.74 (d, J ¼ 8.5 Hz, 1H), 7.81 (d, J ¼ 7.4 Hz, 2H); CDCl3) d ¼ 14.4, 47.1, 51.8, 76.4, 126.6, 128.1, 128.5, 141.5,
13C NMR (125 MHz, CDCl3) d ¼ 0.0, 19.2, 21.8, 49.3, 51.7, 79.3, 176.3.
125.7, 125.9, 126.1, 126.6, 127.0, 127.6, 128.0, 132.8, 133.0,
Methyl 4-chlorophenyl-2,2-Dimethyl-3-(tosylamino)-propio-
1
138.5, 177.3; HRMS (FAB): m/z: calcd for C19H27O3Si: 331.1729; nate (7a).31e White solid; m.p. 145 C; yield: 332 mg (84%); H
ꢀ
found: 331.1715 [M + H]+.
NMR (500 MHz, CDCl3): d 1.03 (s, 3H), 1.31 (s, 3H), 2.30 (s, 3H),
Methyl (4E)-2,2-dimethyl-5-phenyl-3-trimethylsilyloxypent-4- 3.58 (s, 3H), 4.27 (d, J ¼ 9.5 Hz, 1H), 6.13 (d, J ¼ 9.5 Hz, 1H), 6.82
1
enoate (3i).33 Colorless oil; yield: 285 mg (93%); H NMR (500 (d, J ¼ 8.5 Hz, 2H), 6.94–7.00 (m, 4H), 7.35 (d, J ¼ 8.5 Hz, 2H);
MHz, CDCl3): d 0.00 (s, 9H), 1.02 (s, 3H), 1.11 (s, 3H), 3.59 (s, 13C NMR (125 MHz, CDCl3) d ¼ 21.3, 22.5, 24.9, 46.9, 52.2, 64.3,
3H), 4.40 (d, J ¼ 7.0 Hz, 1H), 6.03 (dd, J ¼ 7.0, 16.0 Hz, 1H), 6.41 126.8, 128.0, 129.1, 129.3, 135.7, 137.5, 143.0, 176.4; HRMS
(d, J ¼ 16.0 Hz, 1H), 7.16 (d, J ¼ 7.4 Hz, 1H), 7.24 (dd, J ¼ 7.2, 7.5 (FAB): m/z: calcd for C19H23ClNO4S: 396.1036; found: 396.1022
Hz, 2H), 7.28 (d, J ¼ 7.2 Hz, 2H); 13C NMR (125 MHz, CDCl3) d ¼ [M + H]+.
0.3, 19.8, 21.2, 48.5, 51.8, 78.5, 126.4, 127.6, 128.6, 128.8, 132.0,
Methyl 2,2-dimethyl-3-phenyl-3-(tosylamino)propionate
1
136.8, 177.1; HRMS (FAB): m/z: calcd for C17H27O3Si: 307.1729; (7b).31e White solid; m.p. 130 C; yield: 285 mg (82%); H NMR
ꢀ
found: 307.1740 [M + H]+.
(500 MHz, CDCl3): d 1.08 (s, 3H), 1.26 (s, 3H), 2.24 (s, 3H), 3.60
Methyl 2,2-dimethyl-5-phenyl-3-trimethylsilyloxypentanoate (s, 3H), 4.38 (d, J ¼ 9.9 Hz, 1H), 6.30 (d, J ¼ 9.9 Hz, 1H), 6.88 (d,
(3j).33 Colorless oil; yield: 268 mg (87%); 1H NMR (500 MHz, J ¼ 7.0 Hz, 2H), 6.93 (d, J ¼ 8.0 Hz, 2H), 9.68–7.10 (m, 5H), 7.39
CDCl3): d 0.14 (s, 9H), 1.08 (s, 3H), 1.16 (s, 3H), 1.61–1.66 (m, (d, J ¼ 8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) d ¼ 21.2, 221,
2H), 2.40–2.55 (m, 2H), 3.64 (s, 3H), 3.97 (d, J ¼ 12.0 Hz, 1H), 24.2, 41.3, 52.0, 64.5, 126.7, 127.2, 127.7, 127.8, 128.9, 136.9,
7.16–7.22 (m, 2H), 7.24–7.29 (m, 2H); 13C NMR (125 MHz, 137.4, 142.5, 176.4; HRMS (FAB): m/z: calcd for C19H24NO4S:
CDCl3) d ¼ 0.9, 20.3, 21.6, 33.5, 35.2, 48.4, 51.8, 77.5, 125.8, 362.1426; found: 362.1429 [M + H]+.
128.3, 128.4, 142.2, 177.6; HRMS (FAB): m/z: calcd for
17H29O3Si: 309.1886; found: 309.1876 [M]+.
Methyl 2,2-dimethyl-3-(4-nitrophenyl)-3-(tosylamino)-propi-
C
onate (7c).31e White solid; m.p. 180 ꢀC; yield: 365 mg (90%); 1H
Methyl 2,2-dimethyl3-trimethylsilyloxy-dodecanoate (3k).17c NMR (500 MHz, CDCl3): d 1.05 (s, 3H), 1.33 (s, 3H), 2.26 (s, 3H),
Colorless oil; yield: 288 mg (91%); 1H NMR (500 MHz, CDCl3): d 3.59 (s, 3H), 4.39 (d, J ¼ 9.3 Hz, 1H), 6.30 (d, J ¼ 9.3 Hz, 1H), 6.98
0.09 (s, 9H), 0.85 (t, J ¼ 8.1 Hz, 3H), 1.04 (s, 3H), 1.11 (s, 3H), (d, J ¼ 8.0 Hz, 2H), 7.12 (d, J ¼ 8.5 Hz, 2H), 7.39 (d, J ¼ 8.0 Hz,
1.11–1.45 (m, 12H), 1.53–1.64 (m, 2H), 3.64 (s, 3H), 3.83 (d, J ¼ 2H), 7.88 (d, J ¼ 8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) d ¼
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21.4, 22.5, 24.9, 46.8, 52.4, 64.2, 123.0, 126.8, 129.0, 129.2, 137.3,
815–838; (j) T. E. Kristensen and T. Hansen, Eur. J. Org.
Chem., 2010, 17, 3179–3204; (k) Y. Zhang and S. N. Riduan,
Chem. Soc. Rev., 2012, 41, 2093–2094.
143.4, 144.7, 147.1, 176.1; HRMS (FAB): m/z: calcd for
C
19H23N2O6S: 407.1277; found: 407.1273 [M + H]+.
Methyl
3-(4-methoxyphenyl)-2,2-dimethyl-3-(tosylamino)-
2 D. Simoni, R. Rondanin, M. Morini, R. Baruchello and
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propionate (7d).31e White solid; m.p. 114 ꢀC; yield: 289 mg
1
(64%); H NMR (500 MHz, CDCl3): d 1.04 (s, 3H), 1.25 (s, 3H),
2.25 (s, 3H), 3.57 (s, 3H), 3.68 (s, 3H), 4.29 (d, J ¼ 9.2 Hz, 1H),
6.12 (d, J ¼ 9.2 Hz, 1H), 6.53 (d, J ¼ 8.8 Hz, 2H), 6.78 (d, J ¼ 8.5
Hz, 2H), 7.36 (d, J ¼ 8.8 Hz, 2H), 7.81 (dd, J ¼ 8.5, 8.8 Hz, 2H);
13C NMR (125 MHz, CDCl3) d ¼ 21.5, 22.5, 24.6, 47.6, 52.2, 55.4,
64.3, 113.1, 126.9, 129.0, 129.1, 129.4, 137.7, 142.4, 158.8, 176.4;
HRMS (FAB): m/z: calcd for C20H26NO5S: 392.1532; found:
392.1540 [M + H]+.
Methyl 3-[4-(dimethylamino)phenyl]-2,2-dimethyl-3-(tosyla-
mino)-propionate (7e).31e White solid; m.p. 155 ꢀC; yield: 226 mg
1
(56%); H NMR (500 MHz, CDCl3): d 1.04 (s, 3H), 1.25 (s, 3H),
2.23 (s, 3H), 2.82 (s, 6H), 3.57 (s, 3H), 4.23 (d, J ¼ 9.6 Hz, 1H),
5.99 (d, J ¼ 9.6 Hz, 1H), 6.34 (d, J ¼ 7.1 Hz, 2H), 6.68 (d, J ¼ 8.6
Hz, 2H), 6.91 (d, J ¼ 8.0 Hz, 2H), 7.34 (d, J ¼ 8.6 Hz, 2H); 13C
NMR (125 MHz, CDCl3) d ¼ 21.3, 22.2, 24.5, 40.4, 47.3, 51.9,
64.4, 111.9, 126.9, 128.6, 128.8, 142.0, 149.7, 162.5, 176.8; HRMS
(FAB): m/z: calcd for C20H26NO5S: 392.1532; found: 392.1540
[M + H]+.
7 G. Strappaveccia, D. Lanari, D. Gelman, F. Pizzo, O. Rosati,
M. Curini and L. Vaccaro, Green Chem., 2013, 15, 199–204.
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Methyl 2,2-dimethyl-3-phenyl-3-(phenylamino)propionate
(7f).31e Colorless oil; yield: 234 mg (82%); 1H NMR (500 MHz,
CDCl3): d 1.13 (s, 3H), 1.24 (s, 3H), 2.23 (s, 3H), 3.62 (s, 3H), 4.46
(s, 1H), 4.70 (br, 1H), 6.46 (d, J ¼ 8.5 Hz, 2H), 6.56 (dd, J ¼ 8.5, 8.8
Hz, 1H), 7.00 (d, J ¼ 8.5, 8.8 Hz, 2H), 7.20–7.28 (m, 5H). 13C NMR 10 (a) S. Matsukawa and S. Fujikawa, Tetrahedron Lett., 2012, 53,
(125 MHz, CDCl3) d ¼ 20.7, 24.5, 47.0, 52.0, 64.3, 113.3, 117.2,
127.4, 128.0, 128.2, 129.0, 139.2, 146.9, 177.0; HRMS (FAB): m/z:
calcd for C18H22NO2: 284.1651; found: 286.1648 [M + H]+.
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Conclusions
In conclusion, we demonstrated the easily accessible and user-
friendly polymer-supported phosphine PS-PPh3 catalyzed
Mukaiyama aldol and Mannich reactions. A broad range of 12 For selected reviews, see: (a) T. Mukaiyama, Org. React., 1982,
aldehydes and imines could be applied under mild conditions
using 5–10 mol% PS-PPh3. Furthermore, PS-PPh3 was easily
recovered and reused with minimal loss of activity aer three
runs. These reactions provide a simple and environmentally
friendly method for the synthesis of b-hydroxy esters and
b-amino esters.
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