Speedy and regioselective 1,2-reduction of conjugated α,β-unsaturated aldehydes and ketones using NaBH4/I2

Article abstract of DOI:10.1081/SCC-120015699

Synthesis of allylic alcohols from α,β-unsaturated aldehydes/ketones has been achieved in excellent yields utilizing NaBH₄ and iodine. This reducing agent is mild and tolerant to a number of functional groups.

Full text of DOI:10.1081/SCC-120015699

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Speedy and Regioselective 1,2-Reduction of
Conjugated α,β-Unsaturated Aldehydes and Ketones
Using NaBH4/I2
Jasvinder Singh a b , Irvinder Kaur a , Jasamrit Kaur a , Aman Bhalla a & Goverdhan L. Kad a
a Department of Chemistry, Panjab University, Chandigarh, India
b Department of Chemistry, Panjab University, Chandigarh, 160 014, India
Published online: 21 Aug 2006.
To cite this article: Jasvinder Singh , Irvinder Kaur , Jasamrit Kaur , Aman Bhalla & Goverdhan L. Kad (2003) Speedy
and Regioselective 1,2-Reduction of Conjugated α,β-Unsaturated Aldehydes and Ketones Using NaBH4/I2 , Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:2, 191-197, DOI:
10.1081/SCC-120015699
To link to this article: http://dx.doi.org/10.1081/SCC-120015699
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 2, pp. 191–197, 2003
Speedy and Regioselective 1,2-Reduction of
Conjugated a,b-Unsaturated Aldehydes and
Ketones Using NaBH4/I2
*
Jasvinder Singh, Irvinder Kaur, Jasamrit Kaur,
Aman Bhalla, and Goverdhan L. Kad
Department of Chemistry, Panjab University, Chandigarh, India
ABSTRACT
Synthesis of allylic alcohols from a,b-unsaturated aldehydes/ketones
has been achieved in excellent yields utilizing NaBH4 and iodine.
This reducing agent is mild and tolerant to a number of functional
groups.
Key Words: Regioselective; 1,2-reduction; a,b-unsaturated car-
bonyl compounds; NaBH4/I2.
*Correspondence: Jasvinder Singh, Department of Chemistry, Panjab University,
Chandigarh 160 014, India. Fax: þ91172-545074; E-mail: kadgl@rediffmail.com.
191
DOI: 10.1081/SCC-120015699
Copyright & 2003 by Marcel Dekker, Inc.
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192
Singh et al.
The reduction of unsaturated carbonyl compounds (both 1,2- and
1,4-) has attracted a great deal of interest especially those employing
metal hydrides. Reduction of such systems involving sodium borohydride,
most widely used reducing agent, is highly solvent dependent and does
not lead to high regioselectivity. It has already been known that
treatment of borohydride with a controlled amount of acetic acid
affords a weaker and hence more selective reducing agent. Sodium
[2]
has
monoacetoxyborohydride[1] and Sodiumtriacetoxyborohydride
been found to be highly regioselective reagents, leads to the formation
of corresponding allylic alcohols (Sch. 1). A variety of other selective
reducing agents such as NaBH4 in the presence of lanthanoid chlorides,[3]
NaBH3CN,[4]
NaBH4/LnCpCl2(THF)3,[5]
9-BBN,[6]
NiCRA,[7]
(EtO)3SiH, Me(EtO)2SiH,[8] are available for 1,2-reduction of carbonyl
functionality of aldehydes and ketones to the corresponding alcohol.
In continuation with our work on the regioselective 1,2-reduction of
a,b-unsaturated carbonyl compounds,[2] we report herein the use of a
[9]
highly versatile, selective and cheap reagent namely NaBH4/I2 for this
purpose. This reagent is very effective as regioselective reduction of the
conjugated aldehydes and ketones have been brought about in the pre-
sence of a number of different functionalities like carbon–carbon double
bond, hydroxy, ester, alkoxy, ketal, acetoxy, halide, tosyl, and mesyl
groups. This selective addition of borane to the carbonyl moiety may
be attributed due to the slow release of borane by controlled addition
of iodine to sodiumborohydride. The reaction proceeds with excellent
yield of the products (as shown in the Table 1), which do not
require further purification. Interestingly this reagent is known to
bring about the reduction[10] of amides, nitriles, esters, carboxylic acids
and hydroboration of alkenes. However we have observed that in
the presence of an isolated carbon–carbon double bond (Entry 3) or
an estereal functionality (Entry 2) the reagent preferentially attacks the
carbonyl group of conjugated enone. Reduction of neither the isolated
(or conjugated double bond), nor of the estereal carbonyl group
takes place.
Scheme 1.

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a,b-Unsaturated Aldehydes and Ketones
193
Table 1. Reduction of conjugated carbonyl compounds using NaBH4/I2.
Entry
1
Reactant (a)
Product (b)
Yield (%)
95
2
94
3
4
94
93
5
92
6
7
8
91
91
90
9
88
10
11
12
88
88
87
(continued )

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194
Singh et al.
Table 1. Continued.
Reactant (a) Product (b)
Entry
13
Yield (%)
85
14
96
15
16
95
85
17
82
18
19
80
79
EXPERIMENTAL PROCEDURE
A typical procedure of reduction is as follows. To a stirred suspen-
sion of NaBH4 (0.45 g, 12 mmol) in dry THF (10 mL) was added slowly
a solution of aldehyde (2.48 g, 10 mmol) taken in dry THF (15 mL). The
reaction mixture was cooled in an ice-bath and to it was slowly added
iodine (1.27 g, 5 mmol) in dry THF (15 mL) in a period of 30 min.
Stirring was continued further for 15 min and quenched with 3 N HCl
(2 ꢀ 5 mL), followed by extraction with diethyl ether (3 ꢀ 10 mL). The
combined organic extracts were washed with 3 N NaOH (3 ꢀ 5 mL),
brine and dried over anhyd. Na2SO4. Evaporation of the solvent
in vacuo afforded the pure alcohol (2.37 g, 95%) (as given in Table 1).
The products were identified on the basis of IR and 1H NMR
spectral data.

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a,b-Unsaturated Aldehydes and Ketones
195
In conclusion, the high yields, purity, simplicity alongwith a short
reaction time and tolerance towards a number of functional groups,
renders this a very attractive procedure for reduction of conjugated
aldehydes and ketones.
1
1b: H-NMR (ꢀ/ppm): 1.0 (d, J ¼ 6 Hz, 3H, -CHCH3), 1.3 (m, 5H,
-CH2CH(CH3)CH2-), 1.7 (s, 3H, CH3-C¼C-), 2.2 (m, 2H, -CH2-C¼), 2.9
(s, 3H, -OSO2CH3), 3.3 (bs, 1H, -OH, D2O exchangeable), 3.8 (s, 2H, -
CH2OH), 4.2 (t, J ¼ 7 Hz, 2H, -CH2OSO2-), 5.2 (t, J ¼ 6 Hz, 1H, -CH¼C-).
1
2b: H-NMR (ꢀ/ppm): 1.0 (d, J ¼ 6 Hz, 3H, -CHCH3), 1.3 (m, 5H,
-CH2CH(CH3)CH2-), 1.8 (s, 3H, CH3-C¼C-), 2.2 (m, 5H, -CH2-C¼ and
-COCH3), 3.0 (bs, 1H, -OH, D2O exchangeable), 4.1 (s, 4H,
-CH2OCOCH3 and -CH2OH), 5.2 (t, J ¼ 6 Hz, 1H, -CH¼C-).
1
3b: H-NMR (ꢀ/ppm): 1.6 and 1.7 (2s, 9H, ¼CCH3 and ¼C(CH3)2),
2.0 (m, 4H, ¼C(CH2)2-), 3.5 (bs, 1H, -OH, D2O exchangeable), 4.1 (d,
J ¼ 7.5 Hz, 2H, -CH2OH), 5.1 (t, J ¼ 6 Hz, 1H, ¼CHCH2OH), 5.5 (t,
J ¼ 6 Hz, 1H, -CH2CH¼C-).
1
4b: H-NMR (ꢀ/ppm): 1.0 (d, J ¼ 6 Hz, 3H, -CHCH3), 1.3 (m, 5H,
-CH2CH(CH3)CH2-), 1.7 (s, 3H, CH3-C¼C-), 2.3 (m, 2H, -CH2-C¼), 2.5
(s, 3H, ArCH3), 4.0 (s, 4H, -CH2OTs and -CH2OH), 4.1 (bs, 1H, -OH,
D2O exchangeable), 5.2 (t, J ¼ 6 Hz, 1H, -CH¼C-), 7.3 (d, J ¼ 6 Hz, 2H,
ArH), 7.6 (d, J ¼ 6 Hz, 2H, ArH).
1
5b: H-NMR (ꢀ/ppm): 1.2 (s, J ¼ 6 Hz, 3H,
), 1.6 (s, 3H,
CH3-C¼C-), 2.3 (m, 4H, -CH2C(CH3)- and -CH2C¼), 3.0 (bs, 1H, -
OH, D2O exchangeable), 4.0 (s, 6H, -OCH2CH2O- and -CH2OH), 5.2
(t, J ¼ 6 Hz, 1H, -CH¼C-).
1
6b: H-NMR (ꢀ/ppm): 3.5 (bs, 1H, -OH, D2O exchangeable), 4.5
(s, 2H, -CH2OH), 6.1 (m, 2H,
), 7.1 (d, J ¼ 6 Hz, 1H,
).
1
7b: H-NMR (ꢀ/ppm): 3.5 (bs, 1H, -OH, D2O exchangeable), 4.5
(s, 2H, -CH2OH), 6.1 (m, 2H,
), 7.1 (d, J ¼ 6 Hz, 1H,
).
1
8b: H-NMR (ꢀ/ppm): 3.5 (bs, 1H, -OH, D2O exchangeable), 4.8
(d, J ¼ 6 Hz, 2H, -CH2OH), 6.8 (m, 2H, -CH¼CH-), 7.1 (s, 5H, ArH).
1
9b: H-NMR (ꢀ/ppm): 1.0 (d, J ¼ 6 Hz, 3H, -CHCH3), 1.5 (bs, 14H,
-CH2CH(CH3)CH2-, ring protons and CH3C¼C-), 2.3 (m, 2H, -CH2-C¼),
3.3 (bs, 1H, -OH, D2O exchangeable), 3.5 (m, 4H, 2 ꢀ -OCH2-), 3.8 (s, 2H,
-CH2OH), 4.9 (s, 1H,
), 5.2 (t, J ¼ 6 Hz, 1H, -CH¼C-).
10b: 1H-NMR (ꢀ/ppm): 1.0 (t, J ¼ 6 Hz, 3H, -OCH2CH3), 1.2
(d, J ¼ 6 Hz, 3H, -CHCH3), 1.4 (m, 5H, -CH2CH(CH3)CH2-), 1.7 (s,
3H, CH3-C¼C-), 2.2 (m, 2H, -CH2-C¼), 3.4 (m, 4H, -CH2OCH2CH3),

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196
Singh et al.
3.8 (s, 2H, -CH2OH), 4.0 (bs, 1H, -OH, D2O exchangeable), 5.2 (t,
J ¼ 6 Hz, 1H, -CH¼C-).
1
11b: H-NMR (ꢀ/ppm): 1.2 (d, J ¼ 7 Hz, 3H, -CH(OH)CH3), 1.6 (s,
3H, CH3-C¼C-), 2.2 (m, 4H, -CH2-C¼, CH2C(CH3)-), 2.2 (bs, 2H,
2 ꢀ -OH, D2O exchangeable), 3.7 (m, 1H, -CHOH), 3.8 (s, 2H,
-CH2OH), 5.2 (t, J ¼ 6 Hz, 1H, -CH¼C-).
1
12b: H-NMR (ꢀ/ppm): 1.0 (d, J ¼ 6 Hz, 3H, -CHCH3), 1.3 (m, 5H,
-CH2CH(CH3)CH2-), 1.7 (s, 3H, CH3-C¼C-), 2.2 (m, 2H, -CH2-C¼), 3.5
(t, J ¼ 7 Hz, 2H, -CH2CH2OH), 3.8 (s, 2H, ¼C(CH3)CH2OH), 3.9 (bs,
2H, 2 ꢀ -OH, D2O exchangeable), 5.2 (t, J ¼ 6 Hz, 1H, -CH¼C-).
1
13b: H-NMR (ꢀ/ppm): 1.0 (d, J ¼ 6 Hz, 3H, -CHCH3), 1.3 (m, 5H,
-CH2CH(CH3)CH2-), 1.7 (s, 3H, CH3-C¼C-), 2.2 (m, 2H, -CH2-C¼), 3.0
(bs, 1H, -OH, D2O exchangeable), 3.3 (t, 2H, -CH2Br), 3.9 (s, 2H,
-CH2OH), 5.2 (t, J ¼ 6 Hz, 1H, -CH¼C-).
14b: 1H-NMR (ꢀ/ppm): 3.5 (bs, 1H, -OH, D2O exchangeable), 3.7 (s,
6H, 2 ꢀ -OCH3), 5.1 (d, J ¼ 6 Hz, 1H, -CHOH), 6.3 (m, 2H, -CH¼CH-),
7.3 (m, 8H, ArH).
1
15b: H-NMR (ꢀ/ppm): 1.2 (d, J ¼ 6 Hz, 3H, -CH3), 3.5 (bs, 1H, -
OH, D2O exchangeable), 4.3 (m, 1H, -CHOH), 6.3 (m, 2H, -CH¼CH-),
7.3 (m, 5H, ArH).
1
16b: H-NMR (ꢀ/ppm): 3.7 (s, 3H, -OCH3), 4.4 (bs, 1H, -OH, D2O
exchangeable), 5.1 (d, J ¼ 6 Hz, 1H, -CHOH), 6.3 (m, 2H, -CH¼CH-),
7.2 (m, 9H, ArH).
1
17b: H-NMR (ꢀ/ppm): 2.5 (bs, 1H, -OH, D2O exchangeable), 5.2
(d, J ¼ 6 Hz, 1H, -CHOH), 6.3 (m, 2H, -CH¼CH-), 7.3 (m, 14H, ArH).
1
18b: H-NMR (ꢀ/ppm): 3.3 (bs, 1H, -OH, D2O exchangeable), 4.6
(d, J ¼ 6 Hz, 1H, -CHOH), 6.3 (m, 2H, -CH¼CH-), 7.3 (m, 8H, ArH).
1
19b: H-NMR (ꢀ/ppm): 3.4 (bs, 1H, -OH, D2O exchangeable), 5.1
(d, J ¼ 6 Hz, 1H, -CHOH), 6.3 (m, 2H, -CH¼CH-), 7.3 (m, 9H, ArH).
ACKNOWLEDGMENTS
The authors wish to thank CSIR and UGC, New Delhi for funding
this piece of research work.
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197
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Received in the Netherlands December 10, 2001

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