Efficient role of Mg-ZnCl2 for selective reduction of α,β-unsaturated carbonyl compounds in aqueous medium

Article abstract of DOI:10.1055/s-2005-862355

A facile strategy for the convenient reduction of α,β- unsaturated carbonyl compounds and conjugated alkynes has been accomplished by Mg-ZnCl₂ system in aqueous medium. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-862355

LETTER
523
Efficient Role of Mg-ZnCl2 for Selective Reduction of a,b-Unsaturated
Carbonyl Compounds in Aqueous Medium
M
g-ZnC
l
for Sele
n
ctive Reduction of
a,
b
-Unsatura
t
S
ed Carbonyl
C
a
ompoundsikia, Madan Gopal Barthakur, Romesh Chandra Boruah*
2
Medicinal Chemistry Division, Regional Research Laboratory, Jorhat-785006, India
E-mail: rc_boruah@yahoo.co.in
Received 28 October 2004
In a typical experimental procedure, a suspension of a,b-
unsaturated carbonyl compound 1a (Scheme 1), magne-
sium turnings and zinc chloride was stirred in distilled wa-
ter at room temperature. Soon after stirring was initiated,
gas and heat were evolved resulting in a grey mixture con-
taining no residual magnesium turnings. Extraction of the
reaction mixture with dichloromethane and usual work af-
forded the corresponding reduced product 2a in excellent
yield.19 A wide range of a,b-unsaturated carbonyl com-
pounds comprising chalcones 1b–g, benzylideneacetone
1h, cinnamic esters 1i,j, steroidal enone 1m and cyclic
enones 1n,o were selectively reduced to their correspond-
ing carbonyl compounds 2b–j and 2m–o in high yields
(Table 1). Substituents of the aromatic ring showed little
influence on the reduction of chalcones and benzylidene-
acetones (entries 2–8).7,20 However, the reduction of b-
heteroaryl substituted propenones 1k,l afforded 2k,l in
comparatively low yields due to formation of polymeric
side products (entry 11) and recovery of unreacted starting
material (entry 12). Similarly, the reduction of arylidene-
malononitrile 1p,q did not go to completion and gave cor-
responding reduced products 2p,q in the moderate yields
(entries 16, 17). Interestingly, the reduction of conjugated
alkynes 1r,s in the presence of excess of reagents also led
to corresponding alkanones 2i,j in high yields (entries 18,
19).
Abstract: A facile strategy for the convenient reduction of a,b-un-
saturated carbonyl compounds and conjugated alkynes has been
accomplished by Mg-ZnCl2 system in aqueous medium.
Key words: a,b-unsaturated carbonyl compounds, reduction, mag-
nesium, zinc chloride, aqueous reaction
The selective reduction of a,b-unsaturated carbonyl com-
pounds is a topic of immense interest of organic chem-
ists.1 The carbon-carbon double bond of a,b-unsaturated
carbonyl compounds can be selectively reduced by
PhSeH,2 NaSeH,3 LiSeH,3 NaTeH,4 PhSiH3,5 CuH,6 In,7
9
Zn-Cu,8 Zn-NiCl2 and Zn-CH3COOH,10 however, these
methods suffer disadvantages such as use of excess re-
ducing agent, harsh reaction conditions, complicated ma-
nipulations, low yields and functional selectivity. The
preparation of a highly reactive form of zinc is important,
providing the possibility to prepare difficult to access or
sometimes inaccessible organozinc reagents under normal
conditions.11 Representative activation protocols for zinc
normally involve treatment of commercial zinc metal with
aqueous ammonium chloride,12 1,2-dibromoethane–
TMSCl,13 catalytic iodine14 and microwave activation of
Zn-Cu couple.15 Although, the activated form of zinc
(Reike powder) is accomplished from reduction of zinc
salts with monovalent alkali metals, it has limited scope
because of the need for strictly anhydrous conditions.16
Recently, the study of organic reactions in aqueous media
has gained considerable attention due to the environmen-
tally benign reaction conditions.17,18 Herein, we wish to
report a facile and efficient preparation of a highly reac-
tive form of zinc from Mg and ZnCl2 in aqueous medium
and its application for the selective reduction of the car-
bon-carbon double bond of a,b-unsaturated carbonyl
compounds.
The mechanism of the reaction is not clear at this stage,
however, the involvement of zero valent zinc resulting
from the transmetallation of zinc chloride with magne-
sium metal may be presumed.21 Neither magnesium metal
nor magnesium chloride participated in the reduction re-
action of a,b-unsaturated carbonyl compounds under the
reaction conditions supporting the involvement of zero
valent zinc. Similarly, an attempt at the reduction reaction
using Al-ZnCl2 or Cu-ZnCl2 afforded negative result.
In summary, we have demonstrated that Mg-ZnCl2 can be
efficiently employed in aqueous medium for selective re-
duction of conjugated carbon-carbon double and triple
bonds. Our methodology provides the first example for in
situ generation and utilization of an activated form of zinc
for reduction in aqueous medium. The protocol benefits
from reduced reaction time, operational simplicity, avoid-
ance of flammable or anhydrous organic solvents and
reduced environmental and economic impacts. Further
work on the application of activated zinc in aqueous
media is in progress.
Scheme 1
SYNLETT 2005, No. 3, pp 0523–0525
Advanced online publication: 04.02.2005
1
6.
0
2.
2
0
0
5
DOI: 10.1055/s-2005-862355; Art ID: D32504ST
© Georg Thieme Verlag Stuttgart · New York

524
A. Saikia et al.
LETTER
Table 1 Selective Reduction of Conjugated Enones by Mg-ZnCl2 in Aqueous Medium
Entrya a,b-Unsaturated compound
Product
Reaction
time (min)
Yield (%)c
1
2
PhCH=CHCOPh
1a
1b
1c
1d
1e
1f
PhCH2CH2COPh
2a
2b
2c
2d
2e
2f
20
20
25
25
20
25
30
30
20
25
25
94
92
90
86
95
90
89
85
90
88
64
p-ClC6H4CH=CHCOPh
p-CH3OC6H4CH=CHCOPh
PhCH=CHCOC6H4Cl-p
p-ClC6H4CH=CHCOC6H4Cl-p
p-CH3OC6H4CH=CHCOC6H4OMe-p
p-CH3OC6H4CH=CHCOC6H4Me-p
PhCH=CHCOCH3
p-ClC6H4CH2CH2COPh
p-CH3OC6H4CH2CH2COPh
PhCH2CH2COC6H4Cl-p
p-ClC6H4CH2CH2COC6H4Cl-p
p-CH3OC6H4CH2CH2COC6H4OMe-p
p-CH3OC6H4CH2CH2COC6H4Me-p
PhCH2CH2COCH3
3
4
5
6
7
1g
1h
1i
2g
2h
2i
8
9
PhCH=CHCOOCH3
PhCH2CH2COOCH3
10
11
PhCH=CHCOOC2H5
1j
PhCH2CH2COOC2H5
2j
1k
2k
12
13
1l
2l
25
35
60
90
1m
2m
14
15
1n
1o
2n
2o
30
35
74
77
16
p-ClC6H4CH=CH(CN)2
p-MeOC6H4CH=CH(CN)2
PhC≡CCOOCH3
1p
1q
1r
1s
p-ClC6H4CH2CH2(CN)2
p-MeOC6H4CH2CH2(CN)2
PhCH2CH2COOCH3
2p
2q
2i
60
60
30
30
40
42
88
85
17
18b
19b
PhC≡CCOOC2H5
PhCH2CH2COOC2H5
2j
a All reaction (entries 1–15) were carried using a,b-unsaturated carbonyl compounds (5 mmol), magnesium turning (7.5 mmol), zinc chloride
(7.5 mmol) and distilled H2O (20 mL).
b a,b-Unsaturated carbonyl compounds (5 mmol), magnesium turning (15 mmol), zinc chloride (15 mmol) and distilled H2O (10 mL).
c Isolated yields.
Acknowledgment
References
We thank the Department of Science & Technology, New Delhi, for
financial support of this project. We also thank Dr. P. G. Rao, Di-
rector of this institute for his keen interest.
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LETTER
Efficient Role of Mg-ZnCl2 for Selective Reduction of a,b-Unsaturated Carbonyl Compounds
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Synlett 2005, No. 3, 523–525 © Thieme Stuttgart · New York