Facile solid-phase synthesis of aliphatic aldehydes using novel polymer-supported phenylselenomethyltrimethylsilane

Article abstract of DOI:10.1080/00397910500383451

Treatment of a novel polymer-supported phenylselenomethyltrimethylsilane reagent with LDA followed by alkylation and oxidative deselenation efficiently afforded aliphatic aldehydes in moderate to good yields with excellent purities. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500383451

Synthetic Communicationsw, 36: 429–434, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500383451
Facile Solid-Phase Synthesis of Aliphatic
Aldehydes Using Novel Polymer-Supported
Phenylselenomethyltrimethylsilane
Shou-Ri Sheng, Qiu-Ying Wang, Yi-Xiang Huang, Qin Xin,
and Xiao-Ling Liu
College of Chemistry and Chemical Engineering, Jiangxi Normal
University, Nanchang, China
Abstract: Treatment of a novel polymer-supported phenylselenomethyltrimethylsilane
reagent with LDA followed by alkylation and oxidative deselenation efficiently
afforded aliphatic aldehydes in moderate to good yields with excellent purities.
Keywords: Aliphatic aldehyde, polystyrene-supported phenylselenomethyltrimethyl-
silane, solid-phase organic synthesis
Solid-phase methodology has been rapidly and extensively applied to prep-
aration of small organic molecules in recent years. Polymer-supported
reagents have attracted growing interest because they can provide attractive
and practical methods for combinatorial chemistry and solid-phase
synthesis.[1] Synthesis on a polymer support shows a number of advantages
as compared to solution chemistry. The most salient one is the possibility to
apply excesses of reagents and remove them without using time-consuming
separation techniques. Aldehydes are very useful materials and intermediates
in organic synthesis. Transformation of organic halides to the corresponding
aldehydes is one of important procedures for the synthesis of aldehydes,[2]
Received in Japan June 27, 2005
Address correspondence to Shou-Ri Sheng, College of Chemistry and Chemical
Engineering, Jiangxi Normal University, Nanchang, 330027, China. E-mail:
shengsr@163.com
429

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S.-R. Sheng et al.
Scheme 1.
among them the oxidation of 1-trimethylsilyl-1-phenylselenoalkane.[3]
However, organic selenium reagents are highly malodorous, generally unplea-
sant, and difficult to handle, especially because of their toxicity. Recently,
several groups have developed organoselenium resins as convenient
linkers.[4] The use of the selenium reagents immobilized on polymer resin
has provided significant advantages, including decreased volatility and simpli-
fication of product workup. In continuation of our interest in solid-phase orga-
noselenium chemistry,[5] we herein report a facile synthetic approach to
aliphatic aldehydes from novel polystyrene-supported phenylselenomethyltri-
methylsilane 3 (Scheme 1).
The resin 3 was prepared conveniently in a nearly quantitative yield by
the reaction of cross-linked (1%) polystyrene-supported lithium selenide
2[4a] with chloromethyltrimethylsilane. The FT-IR spectrum of resin 3 con-
taining 1.19 mmol of Si/g (by elemental analysis) exhibited a characteristic
Si-C absorption at 1250 cm21. Resin 3 appeared to be quite stable in the air
at ambient temperature for a long time without diminution of capacity or
the liberation of disagreeable odors.
As illustrated, reaction of the lithio derivative of resin 3 with primary
alkyl halides 4a–4 h furnished the a-phenylselenoalkyltrimethylsilane resin
(5a–5 h), which could not be reliably analyzed with FT-IR. Hence we next
carried out a cleavage reaction directly after washing the resin 5 using
solvents. Treatment of resin 5 with 30% hydrogen peroxide at 08C and then
at room temperature afforded the corresponding aliphatic aldehydes
(6a–6 h) in good yields (77–88%) and with excellent purities of crude
materials (94–97%). The residual resin, polystyrene-supported phenylseleni-
nic acid, was obtained as a by-product whose infrared data was identical to the
previously reported data[6] and which showed no residual Si-C absorption,
which indicated the oxidative cleavage was complete. The results of a repre-
sentative series are summarized in Table 1. However, when secondary halides
such as 2-bromoheptane was used, the aldehyde (6i) formed with only
moderate yield under similar conditions (entry 9, Table 1), perhaps owing
to the elimination reaction of 2-bromoheptane (4i). Furthermore, when
using tertiary halides such as t-butyl chloride, the corresponding aldehydes
were not obtained.

Synthesis of Aliphatic Aldehydes
431
Table 1. Yields and purities of aliphatic aldehydes (6a–6i)
Yielda
(%)
Purityb
(%)
Entry
R1
R2
X (4)
Product
1
2
3
4
5
6
7
8
9
C6H5
H
H
Cl (4a)
Br (4b)
Br (4c)
Br (4d)
Br (4e)
Br (4f)
I (4g)
6a
6b
6c
6d
6e
6f
80
81
84
78
78
86
88
77
60
95
95
95
96
94
97
96
94
94
p-CH3C6H4
p-CH3OC6H4
p-ClC6H4
H
H
p-NO2C6H4
CH3(CH2)2
CH3(CH2)4
Cyclohexyl
CH3(CH2)4
H
H
H
6g
6h
6i
H
CH3
Br (4h)
Br (4i)
aYields were based on the functional loading of resin 3.
bPurities of crude products were determined by HPLC.
In conclusion, we have developed a facile methodology for the solid-
phase synthesis of aliphatic aldehydes in moderate to good yields and with
excellent purities based on a polymeric selenium reagent. Although an
excess amount of reagents is required, simple workup procedures take the
place of the time-consuming isolation and purification steps in the correspond-
ing solution-phase synthesis.
EXPERIMENTAL
Melting points were not corrected. 1H NMR spectra were recorded on a Bruker
Avance 400-MHz spectrometer in CDCl3 with TMS as internal standard.
FT-IR spectra were taken on a Perkin Elmer One instrument. THF was
newly distilled from sodium/benzophenone before use. Reagents such as
lithium diisopropylamide (LDA), chloromethyltrimethyl silane, and organic
halides were obtained from commercial suppliers and used without further
purification. Polystyrene (100–200 mesh, cross-linked with 1% divinylben-
zene) was used for the preparation of polystyrene-supported selenium
bromide according to the procedure described by Nicolaou et al.[4a]
Procedure for the Synthesis of Polymer-Supported
Phenylselenomethyltrimethylsilane 3
NaBH4 (3 mmol) was added to polystyrene-supported selenium bromide 1
(1.0 g, 1.20 mmol Br/g; the loading of functional Br was analyzed by elemen-
tary analysis) swelled in THF (10 mL) and DMF (2 mL) for 30 min under
nitrogen. After 6 h with stirring at room temperature, a solution of chloro-
methyltrimethylsilane (2 mmol) in 2 mL of THF was added slowly, and the

432
S.-R. Sheng et al.
mixture was stirred for 6 h. The resin was collected on a filter and washed
successively with H2O, CH3OH, and CH2Cl2 (2 Â 3 mL of each) and then
dried under vacuum to afford resin 3 containing 1.19 mmol of Si/g as
yellow beads. FT-IR (KBr): 3025, 2921, 1600, 1495, 1450, 1250, 1028,
850, 757, 740, 700, 541 cm21; anal calcd. Si, 3.33%. Found Si, 3.30%.
General Procedure for the Preparation of Aliphatic Aldehydes 6a–6i
Resin 3 (1.0 mmol) was swelled in THF (10 mL) at room temperature for
30 min. After cooling to 2788C, a solution of LDA (0.6 mL, 2.0 M, in
hexane) was added under nitrogen, and the mixture was stirred at the same
temperature for 60 min. Then a solution of primary or secondary alkyl
halide 4a–4i (1.5 mmol) in THF (2 mL) was added dropwise. After 2 h, the
reaction mixture was warmed up gradually to room temperature and kept
standing for 5 h. After the addition of ether–water (5 mL) to the mixture,
the resins 5a–5i were collected on a filter and washed successively with
H2O, THF, and Et2O (3 Â 5 mL of each) and then suspended in THF
(10 mL) at 08C and treated with 0.5 mL (5.3 mmol) of 30% H2O2. After
stirring for 20 min at 08C, and then at room temperature for 40 min, the
residual resin was collected by filtration and washed with CH2Cl2
(4 Â 5 mL). The filtrate was washed with water (2 Â 30 mL), dried over
magnesium sulfate, and concentrated in vacuo, and the crude products
1
6a–6i were obtained and directly analyzed by H NMR and HPLC without
further purification.
Data
1
Phenylacetaldehyde (6a):[7] Colorless oil; H NMR d 9.75 (t, J ¼ 1.68 Hz,
1H), 7.34–7.11 (m, 5H), 3.88 (d, J ¼ 1.68 Hz, 2H); IR (film) nmax 3030,
2926, 2722, 1703, 1495, 1451, 1359, 1150, 740, 700 cm21
.
p-Methylphenylacetaldehyde (6b):[7] Colorless oil; 1H NMR d 9.70
(t, J ¼ 1.68 Hz, 1H), 7.22 (d, J ¼ 7.92 Hz, 2H), 7.08 (d, J ¼ 7.92 Hz, 2H),
3.85 (d, J ¼ 1.68 Hz, 2H), 2.20 (s, 3H); IR (film) nmax 3029, 2925, 2721,
1708, 1495, 1452, 1375, 1152, 745, 699 cm21
.
p-Methoxyphenylacetaldehyde (6c):[8] Colorless oil; 1H NMR d 9.65
(t, J ¼ 1.67 Hz, 1H), 7.20 (d, J ¼ 7.90 Hz, 2H), 7.04 (d, J ¼ 7.90 Hz, 2H),
3.85 (d, J ¼ 1.67 Hz, 2H), 3.78 (s, 3H); IR (film) nmax 3032, 2927, 2723,
1710, 1500, 1455, 1378, 1155, 826, 746, 697 cm21
.
p-Chlorophenylacetaldehyde (6d):[7] Colorless oil; 1H NMR d 9.71
(t, J ¼ 1.69 Hz, 1H), d 7.85 (d, J ¼ 8.56 Hz, 2H), 7.32 (d, J ¼ 8.56 Hz, 2H),

Synthesis of Aliphatic Aldehydes
433
3.88 (d, J ¼ 1.69 Hz, 2H); IR (film) nmax 3030, 2925, 2722, 1705, 1498, 1450,
1150, 745, 701 cm21
.
p-Nitrophenylacetaldehyde (6e):[7] Pale yellow solid, mp 83–858C (lit. 83–
858C); 1H NMR d 9.81 (t, J ¼ 1.72 Hz, 1H), 8.28 (d, J ¼ 8.92 Hz, 2H), 7.48
(d, J ¼ 8.92 Hz, 2H), 3.90 (d, J ¼ 1.72 Hz, 2H); IR (film) nmax 3030, 2925,
2720, 1709, 1517, 1425, 1320, 1110, 820 cm21
.
1
Pentanal (6f):[9] Colorless oil; H NMR d 9.81 (t, J ¼ 1.82 Hz, 1H), 2.43–
2.39 (m, 2H), 1.63–1.56 (m, 2H), 1.35–1.26 (m, 2H), 0.91 (t, J ¼ 7.31 Hz,
3H); IR (film) nmax 2961, 2875, 2720, 1721, 1465, 1391, 1119, 1018 cm21
.
Heptanal (6 g):[10] Colorless oil; 1H NMR d 9.78 (t, J ¼ 1.90 Hz, 1H), 2.42–
2.40 (m, 2H), 1.66–1.50 (m, 6H), 1.36–1.27 (m, 2H), 0.92 (t, J ¼ 7.31 Hz,
3H); IR (film) nmax 2960, 2878, 2721, 1722, 1464, 1390, 1120, 1019 cm21
.
Cyclohexylacetaldehyde (6 h):[10] Colorless oil; 1H NMR
d 9.76
(t, J ¼ 1.87 Hz, 1H), 2.43–2.39 (dd, J ¼ 7.28, 1.87 Hz, 2H), 0.98–1.38
(m, 11H); IR (film) nmax 2958, 2873, 2720, 1725, 1465, 1120, 1015 cm21
.
1
2-Methylheptanal (6 g):[10] Colorless oil; H NMR d 9.57 (d, J ¼ 1.12 Hz,
1H), 2.42–2.40 (m, 1H), 1.15–1.50 (m, 6H), 1.36–1.26 (m, 2H), 0.90
(t, J ¼ 7.32 Hz, 3H), 1.02 (d, J ¼ 7.40 Hz, 3H); IR (film) nmax 2961, 2878,
2722, 1726, 1464, 1391, 1120, 1021 cm21
.
ACKNOWLEDGMENT
We are grateful for the financial support from the National Natural Science
Foundation of China and of Jiangxi Province (No. 0420017).
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