Rapid selective defunctionalization of the carbonyl group of α,β-unsaturated ketones with trialkoxylsilane/ZnX2

Article abstract of DOI:10.1080/10426507.2010.536188

Reduction of the carbonyl group of ketones to a methylene unit is widely applied in organic syntheses. In this article, we report that trialkoxylsilane/Zn-based catalyst systems may be applied in the reduction of the carbonyl groups of α,β-unsaturated ketones to methylene units under very mild conditions. In comparison with other Zn-based catalysts, excellent rates and high conversions of,-unsaturated ketones to methylene units are obtained using trialkoxylsilane/ZnI₂ or ZnCl₂. And the same time, the hydrosilylation reaction product could only be detected when using CuI, CuCl, or FeCl3. No reaction could be conducted by using trialkoxylsilane/CoCl₂ or NiCl₂, in comparison with Zn-based catalysts. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor &Francis Group, LLC.

Full text of DOI:10.1080/10426507.2010.536188

Phosphorus, Sulfur, and Silicon, 186:1621–1625, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.536188
RAPID SELECTIVE DEFUNCTIONALIZATION OF THE
CARBONYL GROUP OF α,β-UNSATURATED KETONES
WITH TRIALKOXYLSILANE/ZnX2
Jiayun Li, Jiajian Peng, Ying Bai, Lingzhen Chen,
and Guoqiao Lai
Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry
of Education, Hangzhou Normal University, Hangzhou, People’s Republic of China
GRAPHICAL ABSTRACT
Abstract Reduction of the carbonyl group of ketones to a methylene unit is widely applied in
organic syntheses. In this article, we report that trialkoxylsilane/Zn-based catalyst systems may
be applied in the reduction of the carbonyl groups of α,β-unsaturated ketones to methylene
units under very mild conditions. In comparison with other Zn-based catalysts, excellent
rates and high conversions of α,β-unsaturated ketones to methylene units are obtained using
trialkoxylsilane/ZnI2 or ZnCl2. And the same time, the hydrosilylation reaction product could
only be detected when using CuI, CuCl, or FeCl3. No reaction could be conducted by using
trialkoxylsilane/CoCl2 or NiCl2, in comparison with Zn-based catalysts.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Defunctionalization of carbonyl group; trialkoxylsilane/ZnX2; α,β-unsaturated
ketone
INTRODUCTION
Reduction of the carbonyl group of ketones to a methylene unit is widely applied in
organic syntheses.1 However, only a few protocols for the defunctionalization of a carbonyl
group to a methylene group have been reported. These include the Clemmensen reduction,2
Wolff−Kishner reduction, and Wolff−Kishner−Huang reduction,3 all of which require
Received 26 August 2010; accepted 27 October 2010.
We are grateful to the Fund of Zhejiang province (2008C14041) and Technologies R&D Program of
Hangzhou city (20100331T16) for financial support.
Address correspondence to Jiajian Peng and Guoqiao Lai, Key Laboratory of Organosilicon Chemistry
and Material Technology of Ministry of Education, Hangzhou Normal University, Hangzhou 310012, People’s
Republic of China. E-mail: jjpeng@hznu.edu.cn; gqlai@hznu.edu.cn
1621

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J. Li ET AL.
rather drastic reaction conditions. Other methods, including catalytic hydrogenation,4 re-
duction with trialkylsilanes/trifluoroacetic acid5 or trichlorosilane/trialkylamine6, and metal
hydride reductions,7 have been successfully applied more specifically to aryl aldehydes and
ketones. Recently, Chandrasekhar et al.8 reported the polymethylhydrosiloxane/B(C6F5)3
combination to be a versatile carbonyl defunctionalization system. In this article, we report
that trialkoxylsilane/ZnX2 systems may be applied in the reduction of the carbonyl groups
of α,β-unsaturated ketones to methylene units under very mild conditions.
RESULTS AND DISCUSSION
The use of zinc species in hydrosilylation reactions has become an interesting re-
search field.9–11 In a previous paper,11 we showed zinc salts to be very effective catalysts
for the hydrosilylation of ketones. Interestingly, when chalcone was used as a carbonyl
substrate under similar conditions, the carbonyl group was reduced to a methylene unit.
First, the reaction of (E)-chalcone 1 with trimethoxysilane was investigated as a model
reaction. A series of different transition metal salts or complexes was screened at room
temperature (Scheme 1), and the results are summarized in Table 1. Among the zinc salts
tested, ZnCl2, ZnI2, and Zn3[Fe(CN)6]2 showed excellent catalytic activity, while ZnF2
and Zn(CF3CO3)2 showed comparatively low catalytic activity. ZnCl2 and ZnI2 showed
higher catalytic activity than Zn3[Fe(CN)6]2. Hydrosilylation was the main reaction when
Zn[OOCCH(C2H5)C4H9]2 was used as catalyst. When triethoxysilane was used in place of
trimethoxysilane as the hydride, excellent conversion was also obtained. However, when
trimethoxysilane or triethoxysilane was replaced with triethylsilane or diphenylsilane as the
hydride, lower conversions were obtained, even after extended reaction times. Furthermore,
the catalytic activities and selectivities of different transition metal halides, i.e., CuI, CuCl,
FeCl3, CoCl2, and NiCl2, were tested in the reaction of chalcone with trimethoxysilane. The
hydrosilylation reaction product could only be detected when using CuI, CuCl, or FeCl3.
No reaction could be conducted by using CoCl2 or NiCl2. See Table 1.
Scheme 1 Reaction of chalcone with trimethoxysilane catalyzed by metal salts.
In order to investigate the scope and limitation of the trialkoxylsilane/zinc halide-
catalyzed reduction of the carbonyl group of α,β-unsaturated ketones to a methylene
unit, reactions of other α,β-unsaturated ketones were tested. As substrates, we chose
4-phenylbut-3-en-2-one, 4-(4-nitrophenyl)but-3-en-2-one, 1,3-bis(4-nitrophenyl)prop-2-
en-1-one, 1-phenyl-3-p-tolylprop-2-en-1-one,3-(4-nitrophenyl)-1-phenylprop-2-en-1-one,
3-(4-bromophenyl)-1-phenylprop-2-en-1-one,
3-(4-nitrophenyl)-1-p-tolylprop-2-en-1-
one, and 1,5-diphenylpenta-1,4-dien-3-one (Scheme 2). Though excellent conversions
were obtained with trimethoxysilane, two reduced isomers involving double-bond transfer
were observed, the isomer distributions of which were controlled by the nature of the
substituent on the phenyl ring (Table 2).

SELECTIVE REDUCTION OF CARBONYL GROUP TO METHYLENE
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Table 1 Reduction of chalcone catalyzed by different catalysts
Select. (%)
Entry
Silane
Catalyst
Time (h)
Conv. (%)
3
2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
(CH3O)3SiH
(CH3O)3SiH
(CH3O)3SiH
(CH3O)3SiH
(CH3O)3SiH
(CH3O)3SiH
(CH3CH2O)3SiH
Ph2SiH2
(CH3CH2)3SiH
(CH3O)3SiH
(CH3O)3SiH
(CH3O)3SiH
(CH3O)3SiH
(CH3O)3SiH
ZnF2
ZnCl2
ZnI2
Zn3[Fe(CN)6]2
Zn(CF3CO3)2
Zn[OOCCH(C2H5)C4H9]2
ZnI2
ZnI2
ZnI2
17 min
5 min
5 min
2
6
2
5 min
12
12
2
46
100
100
100
62.0
72
100
6.2
1.5
98.0
96.8
100
—
100
100
100
100
100
35.5
100
100
100
—
—
—
—
—
—
64.5
—
—
—
CuI
100
100
100
—
CuCl
FeCl3
CoCl2
NiCl2
2
—
—
—
—
15 min
6
6
—
—
Reaction conditions: r.t.; (E)-chalcone 5 mmol; hydrosiloxane 10 mmol; catalyst: 3 mol% based on (E)-
chalcone. 3: (E)-1,3-diphenylprop-1-ene; 2: (E)-(1,3-diphenylallyl)trimethoxysilane.
Scheme 2 Zinc chloride–catalyzed reduction of α,β-unsaturated ketones.
In a previous article, we reported a proposed mechanism for the zinc-catalyzed
hydrosilylation of ketones.11 Also, a reaction mechanism for the FeCl3 catalyzed allylic re-
duction of allylic alcohol with benzyl alcohol is reported by Wang et al.12 A proposed mech-
anism for the ZnI2-catalyzed reduction of α,β-unsaturated ketones is shown in Scheme 3.
It is postulated that σ-bond metathesis between ZnI2 and the hydrosilylation reagent takes
Table 2 Reduction of α,β-unsaturated ketones catalyzed by ZnCl2
α,β-Unsaturated ketone
R1
Select. (%)
Entry
R2
Conv. (%)
4
5
1
2
3
4
5
6
7
8
Phenyl
Methyl
Methyl
4-Nitrophenyl
Phenyl
Phenyl
Phenyl
P-Tolyl
1-Styryl
100
100
100
100
100
100
100
100
100
100
100
45.0
71.4
85.2
89.8
—
—
—
—
55.0
28.6
14.8
10.2
100
4-Nitrophenyl
4-Nitrophenyl
p-Tolyl
4-Nitrophenyl
4-Bromophenyl
4-Nitrophenyl
Phenyl
Reaction conditions: r.t.; α,β-unsaturated ketone 5 mmol, HSi(OMe)3 10 mmol, ZnCl2 3 mol% based on
α,β-unsaturated ketone, 1 h. 4: ; 5:
.

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J. Li ET AL.
Scheme 3 Proposed mechanism.
place, generating an active zinc hydride species. This forms an adduct with the carbonyl
of the substrate, thereby forming intermediate state (3) in the first step. Intermediate state
(3) is then converted into intermediate state (5). Hydride attack on the activated carbonyl
of (3) gives a reduced intermediate state (10), from which the hydrosilylation product is
formed. However, the attack of R3SiH on the activated carbonyl double bond of (5) leads
to intermediate state (6), from which defunctionalized carbonyl to methylene products are
formed. Two reduced isomers involving double-bond transfer were observed in the study.
CONCLUSION
In summary, zinc-catalyzed reduction of the carbonyl group of α,β-unsaturated ke-
tones to a methylene unit with trialkoxysilane proceeds smoothly under mild conditions. In
comparison with other Zn-based catalysts, excellent rates and high conversions are obtained
with ZnI2 or ZnCl2.
EXPERIMENTAL
All substances were purchased from Aldrich and were used as received. Other infor-
mation is as follows: Gas chromatography (GC): TRACE DSQ GC; column DB-5 30 m ×
2.5 mm × 0.25 µm; split 50:1; flow rate 1 mL/min constant flow; inlet temperature 260◦C;
column temperature 50◦C for 1 min then 15◦C/min increase to 260◦C (held for 10 min).
1H NMR spectra were measured using a Bruker AV 400 MHz spectrometer operating
1
at 400.13. Chemical shifts for H spectra were recorded (in ppm) relative to the residual
proton of CDCl3. 1H NMR δ 7.24.

SELECTIVE REDUCTION OF CARBONYL GROUP TO METHYLENE
1625
General Procedure for the Reduction of an α,β-Unsaturated Ketone
A 50-mL vial equipped with a magnetic stirrer bar was charged with zinc iodide (48
mg, 0.3 mmol, 3 mol%) and triethoxysilane (1.5 mL, 10.0 mmol). After stirring at room
temperature for 10 min, the α,β-unsaturated ketone (5.0 mmol) was added. The reaction
was allowed to proceed at room temperature and was monitored by TLC. Conversions were
determined by GC analysis. After complete consumption of the starting α,β-unsaturated
ketone or no further conversion, the reaction mixture was treated with 10% NaOH (2 mL),
and the organic product was extracted with diethyl ether (3 × 10 mL). The combined extracts
were washed sequentially with saturated aqueous NaHCO3 solution and water, dried with
anhydrous sodium sulfate, filtered, and concentrated in vacuum to obtain the crude product.
The residue was purified by column chromatography (petroleum ether:EtOAc, 5:1) to
afford the product. All of the prepared compounds showed spectroscopic data (1H NMR)
in accordance with the proposed structures.8,12
The NMR characterization of the alkene products is given in a Supplemental Materials
file (available online).
REFERENCES
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2. Clemmensen, E. Ber. Deutsch. Chem. Ges. 1913, 46, 1837–1843.
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4. Lee, W. Y.; Park, C. H.; Kim, H. J.; Kim, S. J. Org. Chem. 1994, 59, 878–884.
5. Smonou, I. Tetrahedron Lett. 1994, 35, 2071–2074.
6. Benkeser, R. A. Acc. Chem. Res. 1971, 4, 94–100.
7. Bette, V.; Mortreux, A.; Ferioli, F.; Martelli, G.; Savoia, D.; Carpentier, J. Eur. J. Org. Chem.
2004, 3040–3045.
8. Chandrasekhar, S.; Reddy, Ch. R.; Babu, B. N. J. Org. Chem. 2002, 67, 9080–9082.
9. Gajewy, J.; Marcin, K.; Gawron´ski, J. Adv. Synth. Catal. 2009, 351, 1055–1063.
10. Mimoun, H.; de Saint Laumer, J. Y.; Giannini, L.; Scopelliti, R.; Floriani, C. J. Am. Chem. Soc.
1999, 121, 6158–6166.
11. Chen, L. Z.; Peng, J. J.; Li, J. Y.; Bai, Y.; Qiu, H. Y.; Wu, H.; Lai, G. Q. Lett. Org. Chem. 2008,
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