Methyltrichlorosilane as an effective activation agent for swern oxidation

Article abstract of DOI:10.1080/00397911.2014.912328

A practical and efficient alternative version of the Swern oxidation has been successfully developed. Methyltrichlorosilane was used as an efficient activator of dimethylsulfoxide, which could oxidize a wide range of primary and secondary alcohols to the corresponding carbonyl compounds with good to excellent yields.

Full text of DOI:10.1080/00397911.2014.912328

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Methyltrichlorosilane as an Effective
Activation Agent for Swern Oxidation
Yuanxun Wang a b , Chao Wang a & Jian Sun a
a Natural Products Research Center , Chengdu Institute of Biology,
Chinese Academy of Sciences , Chengdu , China
b University of Chinese Academy of Sciences , Beijing , China
Accepted author version posted online: 10 Jun 2014.Published
online: 08 Aug 2014.
To cite this article: Yuanxun Wang , Chao Wang & Jian Sun (2014) Methyltrichlorosilane as an
Effective Activation Agent for Swern Oxidation, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 44:20, 2961-2965, DOI:
10.1080/00397911.2014.912328
To link to this article: http://dx.doi.org/10.1080/00397911.2014.912328
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Synthetic Communications1, 44: 2961–2965, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2014.912328
METHYLTRICHLOROSILANE AS AN EFFECTIVE
ACTIVATION AGENT FOR SWERN OXIDATION
Yuanxun Wang,1,2 Chao Wang,1 and Jian Sun1
1Natural Products Research Center, Chengdu Institute of Biology,
Chinese Academy of Sciences, Chengdu, China
2University of Chinese Academy of Sciences, Beijing, China
GRAPHICAL ABSTRACT
Abstract A practical and efficient alternative version of the Swern oxidation has been
successfully developed. Methyltrichlorosilane was used as an efficient activator of dimethyl-
sulfoxide, which could oxidize a wide range of primary and secondary alcohols to the
corresponding carbonyl compounds with good to excellent yields.
Keywords Alcohols; carbonyl compounds; MeSiCl3–DMSO; silicon reagents; Swern
oxidation
INTRODUCTION
Carbonyl compounds are of great importance in organic synthesis because
they can be transformed into various functionalized compounds through many
different reactions.[1] For the preparation of carbonyl compounds, oxidation of the
corresponding alcohols is one of the most important and frequently used transforma-
tions.[2] So far numerous methods have been developed to implement this transform-
ation, among which the metal-free Swern oxidation represents the most widely used
one. Typically, the Swern oxidation uses a strong electrophile such as oxaly chloride
as the activator of dimethylsulfoxide (DMSO).[3,4] Recently, we demonstrated that
methyltrichlorosilane (MeSiCl3) could serve as an effective activator of both DMSO
Received January 24, 2014.
Address correspondence to Jian Sun or Chao Wang, Natural Products Research Center, Chengdu
Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China. E-mail: sunjian@cib.ac.cn;
wangchao@cib.ac.cn
2961

2962
Y. WANG, C. WANG, AND J. SUN
Scheme 1. Proposed mechanism for the oxidation of alcohols by MeSiCl3–DMSO system.
and sodium phenylsulfonate (PhSO2Na), on the basis of which highly efficient
methods for chlorination of enamides and sulfinylation of enecarbamates have been
developed.[5] We speculated that MeSiCl3 could also be used as an activator of DMSO
for the Swern oxidation and that an alternative recipe for the Swern oxidation could
be developed (Scheme 1).
Initially, we tested the Swern oxidation of benzyl alcohol using MeSiCl3 as the
activator of DMSO. The reaction was carried out at different temperatures with
triethylamine as base and dichloromethane as solvent. To our delight, the desired
product benzaldehyde was obtained in moderate yield if the temperature was main-
tained at ꢀ20 ꢁC during the whole reaction process (Table 1, entry 1). The yields
were further increased to 76% and 80% when the temperatures for the oxidation step
Table 1. Screening of reaction conditionsa
Entry
Temp. (ꢁC)
Chlorosilaneb
Yield (%)c
1
2
ꢀ20
MeSiCl3
MeSiCl3
MeSiCl3
MeSiCl3
MeSiCl3
SiCl4
52
<5
76
80
90
85
85
79
78
10
ꢀ78
3
ꢀ20 to ꢀ40
ꢀ20 to ꢀ60
ꢀ20 to ꢀ78
ꢀ20 to ꢀ78
ꢀ20 to ꢀ78
ꢀ20 to ꢀ78
ꢀ20 to ꢀ78
ꢀ20 to ꢀ78
4
5
6
7
AllylSiCl3
HSiCl3
8
9
10
Me2SiCl2
Me3SiCl
aConditions: [1] ¼ 0.3 M, [chlorosilane] ¼ 0.3 M, [DMSO] ¼ 1.2 M, [Et3N] ¼ 2.4 M.
bAll chlorosilanes were used directly without purification.
cThe yield was determined with HPLC.

SWERN OXIDATION
2963
were decreased to ꢀ40 ꢁC and ꢀ60 ꢁC, respectively (Table 1, entries 3 and 4). Some
other chlorosilanes were also found to be effective activators of DMSO, furnishing
the oxidation with moderate to good yields (Table 1, entrie 6–9). MeSiCl3 and SiCl4
showed almost identical activities and gave 86% and 85% yields, respectively.
We next explored the substrate’s scope and the limitations of the Swern
oxidation using MeSiCl3 as the activator of DMSO. The oxidations of a variety of
aryl and alkyl primary and secondary alcohols were examined under the optimal
conditions. As shown in Table 2, all the testing substrates could be efficiently
oxidized to the corresponding carbonyl compounds with good to excellent yields
Table 2. Substrate scope of the oxidationa
Entry
Substrate
Product
Yield (%)b
1
2
3
4
80
76
99
71
5
92
6
7
8
9
70
84
83 (75)c
88 (78)c
10
11
99 (83)c
96
12
96 (84)c
13
14
80 (89)c
85 (99)c
aConditions: [Alcohol] ¼ 0.5 M, [MeSiCl3] ¼ 0.5 M, [DMSO] ¼ 2 M.
bThe yield was determined with 1H NMR.
cReaction was carried out at ꢀ20 ꢁC.

2964
Y. WANG, C. WANG, AND J. SUN
(70–99%). The substituted benzylic alcohols could be oxidized to the corresponding
benzaldehydes (Table 1, entries 1–3). More interestingly, thiophen-2-ylmethanol,
which has a sulfur atom in the aromatic ring, could also be effectively oxidized to
the corresponding aldehyde with 71% yield (Table 2, entry 4). Secondary alcohols
were also tested to see if they could be oxidized to ketone in the current oxidation
system. It turned out that even greater yields could be obtained for either aryl or
alkyl secondary alcohols comparing to primary alcohols (Table 2, entries 8–14).
Notably, good yields could also be obtained for these substrates even if the tempera-
ture was maintained at ꢀ 20 ꢁC for the oxidation step.
Finally, the oxidation of alcohols by the MeSiCl3–DMSO system has been
compared with literature reports of other Swern oxidations. Results of the oxidation
of the selected relatively simple primary and secondary alcohols are summarized in
Table 3. Reactions were carried out according to the procedures described by the
original workers. No substantial difference in the yield of the different oxidation
methods has been found for the tested alcohols except 1-(pyridin-4-yl) ethanol,
which has a nitrogen atom in the aromatic ring. It seems that the MeSiCl3–DMSO
system is more suitable for the oxidation of alcohols that contain heteroaromatic
Table 3. Comparison of the alcohol oxidation by the different version of
Swern oxidation
Entry
1
Substrate
Activator
Yield (%)e
(COCl)2
TFAAb
TCTc
99[3h]
82[3j]
90[4c]
90
a
d
MeSiCl3
2
3
4
5
6
(COCl)2
TFAA
TCT
99
97
94
83
MeSiCl3
(COCl)2
TFAA
TCT
97
83
93
84
MeSiCl3
(COCl)2
TFAA
TCT
98
98
95
96
MeSiCl3
(COCl)2
TFAA
TCT
86
76
73
99
MeSiCl3
(COCl)2
TFAA
TCT
67
92
7
99
MeSiCl3
a,b,cSee Refs. [3b], [3h], and [4c] for all the reaction conditions. TCT ¼ 2,4,6-
trichloro-1,3,5-triazine.
dConditions: [alcohol] ¼ 0.5 M, [MeSiCl3] ¼ 0.5 M, [DMSO] ¼ 2 M.
eThe yield was determined with 1H NMR.

SWERN OXIDATION
2965
rings because both the thiophen-2-ylmethanol and 1-(pyridin-4-yl) ethanol could be
oxidized with good to excellent yields. In conclusion, we have developed a mild and
practical method for the oxidation of alcohols with the MeSiCl3–DMSO system. A
wide range of alcohols such as aryl and alkyl primary and secondary alcohols could
be oxidized to the corresponding aldehydes and ketones with good to excellent
yields. These results demonstrated that the MeSiCl3–DMSO could be a useful
alternative system for the Swern oxidation.
EXPERIMENTAL
DMSO (2 mmol) in DCM was added to a solution of MeSiCl3 (0.5 mmol) in
DCM at ꢀ20 ꢁC. The mixture was stirred at the same temperature for 3 h and cooled
to ꢀ78 ꢁC, followed by slow addition of 1 equivalent of alcohol in DCM. The reac-
tion continued to stir at ꢀ78 ꢁC for 3 h, and then 8 equivalents of Et3N were slowly
added. After completion of the reaction, the mixture was warmed to the room
temperature and extracted with DCM. The combined organic solvent was dried over
Na2SO4, and concentrated under vacuum. The residue was purified by flash column
chromatography. Dibromomethane or benzyl methyl ether was used as internal
1
standard for quantitative H NMR analysis.
FUNDING
This project was supported by the National Natural Science Foundation of
China (Project Nos. 91013006 and 21272227).
SUPPORTING INFORMATION
Supplemental data for this article can be accessed on the publisher’s website.
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