A facile stereoselective synthesis of (2E)-3-silylallylic alcohols by hydromagnesiation of 1-aryl-2-silylacetylenes

Article abstract of DOI:10.1002/ejoc.200501002

Hydromagnesiation of 1-aryl-2-silylacetylenes 1 in diethyl ether gave (1E)-2-silylvinyl Grignard reagents 2, which reacted with aldehydes or ketones 3 to afford stereoselectively (2E)-3-silylallylic alcohols 4 in good to high yields. Wiley-VCH Verlag GmbH

Full text of DOI:10.1002/ejoc.200501002

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200501002
A Facile Stereoselective Synthesis of (2E)-3-Silylallylic Alcohols by
Hydromagnesiation of 1-Aryl-2-silylacetylenes
Mingzhong Cai,*[a] Zhou Zhou,[a] and Jianwen Jiang[a]
Keywords: Hydromagnesiation / 1-Aryl-2-silylacetylenes / Vinyl compounds / Grignard reaction / (2E)-Allylic alcohols /
Stereoselective synthesis
Hydromagnesiation of 1-aryl-2-silylacetylenes 1 in diethyl
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
ether gave (1E)-2-silylvinyl Grignard reagents 2, which re- Germany, 2006)
acted with aldehydes or ketones 3 to afford stereoselectively
(2E)-3-silylallylic alcohols 4 in good to high yields.
1-aryl-2-silylacetylenes and alkynylsilanes.[15] Herein we wish
to report that (2E)-3-silylallylic alcohols could be conve-
Introduction
Allylic alcohols are among the most versatile intermedi- niently synthesized by hydromagnesiation of 1-aryl-2-silyl-
ates in organic synthesis and are pervasive in natural prod- acetylenes, followed by a reaction with aldehydes or
ucts and commercially important pharmaceuticals.[1] Thus, ketones.
the stereocontrolled synthesis of allylic alcohols is of con-
siderable interest in organic chemistry.[2] Although substan-
tial progress has been made in the synthesis of (2E)-di- and
(2E)-trisubstituted allylic alcohols,[3–7] the direct synthesis
Results and Discussion
of (2E)-2,3-disubstituted allylic alcohols remains a formida-
ble challenge.[8] The stereocontrolled synthesis of allylic
alcohols containing metal or heteroatom functional groups
is also of considerable interest in organic synthesis because
many useful functional-group transformations can be
achieved by introduction and removal of metal or hetero-
atom functions. Lee et al. reported the efficient preparation
of enantiomerically pure (3E)-4-(tributylstannyl)but-3-en-2-
ol by lipase-mediated resolution.[9] The stereoselective syn-
thesis of (2Z)-2-(butylseleno)allylic alcohols,[10] (2Z)-2-(alk-
ylthio)allylic alcohols,[11] (2Z)-2-silylallylic alcohols,[12] and
(2E)-2-sulfonylallylic alcohols[13] has also been described in
the literature. Recently, Huang et al. reported an efficient
synthesis of (2Z)-2,3-difunctionalized allylic alcohols by
stereoselective Michael/aldol tandem reaction of phenylse-
lenomagnesium bromide with acetylenic sulfones and alde-
hydes.[14] However, to the best of our knowledge, there is no
report on the stereoselective synthesis of (2E)-3-silylallylic
alcohols. Hydromagnesiation has emerged as a unique hy-
drometallation with some attractive features such as the
high regioselectivity and stereoselectivity observed with
1-Aryl-2-silylacetylenes 1 were prepared according to a
literature procedure.[16] Hydromagnesiation of 1-aryl-2-si-
lylacetylenes is known to proceed with high regio- and
stereoselectivity to generate (1E)-1-aryl-2-silylvinyl Grig-
nard reagents (Scheme 1).[15] We observed that the hydro-
magnesiation of 1-aryl-2-silylacetylenes 1 at 25 °C in diethyl
ether for 6 h gave (1E)-1-aryl-2-silylvinylmagnesium bro-
mides 2, which reacted with aldehydes or ketones 3 to af-
ford stereoselectively the desired (2E)-3-silylallylic alcohols
4 (Scheme 1). Typical results are summarized in Table 1
which shows that both aldehydes and ketones could react
rapidly with the intermediates 2 under mild conditions to
give the corresponding (2E)-3-silylallylic alcohols 4 in good
to high yields. To examine the scope for this methodology,
the hydromagnesiation reactions of 1-heteroaryl-2-silylacet-
ylenes, such as 1-(2-pyridyl)-2-(trimethylsilyl)acetylene and
1-(2-furyl)-2-(trimethylsilyl)acetylene, were also investi-
gated. It was found that no desired (2E)-3-silylallylic
alcohol was formed under the same reaction conditions
since the hydromagnesiation reactions did not occur at all.
The hydromagnesiation of 1-alkyl-2-silylacetylenes could
proceed highly regio- and stereoselectively under the same
conditions to give the (1Z)-1-silylvinyl Grignard rea-
gents,[15] but it was not suitable for the preparation of (2E)-
3-silylallylic alcohols. This is the current limitation of the
method.
[a] School of Chemistry and Chemical Engineering, Jiangxi Nor-
mal University,
Nanchang 330022, P. R. China
Fax: +86-791-8120388
E-mail: caimzhong@163.com
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1400–1402

Stereoselective Synthesis of (2E)-3-Silylallylic Alcohols
SHORT COMMUNICATION
General Procedure for the Synthesis of (2E)-3-Silylallylic Alcohols
4a–j: To a solution of isobutylmagnesium bromide (4.5 mmol) in
diethyl ether (7 mL) was added Cp2TiCl2 (50 mg, 0.2 mmol) at 0 °C
under Ar, and the mixture was stirred at that temperature for 30
min. To this solution was added 1-aryl-2-silylacetylene
1
(4.0 mmol), and the mixture was stirred at 25 °C for 6 h. After be-
ing cooled to 0 °C, aldehyde or ketone 3 (3.5 mmol) was added and
the mixture was stirred at 25 °C for 2 h, quenched with satd. aq.
NH4Cl solution (25 mL), and extracted with Et2O (2×30 mL). The
combined organic layers were washed with satd. aq. NH4Cl solu-
tion (20 mL) and water (3×20 mL) and dried (MgSO4). Removal
of the solvent under reduced pressure gave an oil, which was puri-
fied by column chromatography on silica gel (eluent: light petro-
leum ether/EtOAc, 12:1).
Scheme 1.
Supporting Information (for details see the footnote on the first
page of this article): Characterization data (IR, 1H NMR, 13C
NMR, mass spectra, and elemental analyses) of (2E)-3-silylallylic
alcohols 4a–j.
Table 1. Synthesis of (2E)-3-silylallylic alcohols 4a–j.
Entry Ar
R1
R2
Product
Yield[a] (%)
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
CH3
Ph
Ph
n-C6H13
3,4-CH2O2C6H3
CH3
Ph
CH3
H
CH3
H
H
CH3
H
H
CH3
CH3
4a
4b
4c
4d
4e
4f
4g
4h
4i
82
85
79
80
83
89
84
81
78
90
Acknowledgments
Ph
We thank the National Natural Science Foundation of China (Pro-
ject No. 20462002) and the Natural Science Foundation of Jiangxi
Province in China (0420015) for financial support.
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-CH3OC6H4 Ph
4-CH3OC6H4 CH3
3,4-CH2O2C6H3
10
4j
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Investigations of the crude products 4 by 1H NMR spec-
troscopy (400 MHz) showed their isomeric purities to be
Ͼ 97%. One olefinic proton signal of compounds 4a–j ap-
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taken place with strong preference for the addition of the
magnesium atom at the carbon atom adjacent to the aryl
group.
Conclusion
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Experimental Section
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Eur. J. Org. Chem. 2006, 1400–1402
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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M. Cai, Z. Zhou, J. Jiang
SHORT COMMUNICATION
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Received: December 22, 2005
Published Online: January 30, 2006
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1400–1402