Solvent-free reduction of aldehydes and ketones using solid acid-activated sodium borohydride

Article abstract of DOI:10.1016/j.tet.2006.05.083

A simple and convenient procedure for the reduction of aldehydes and ketones with sodium borohydride activated by solid acids such as boric acid, benzoic acid, and p-toluenesulfonic acid monohydrate under solvent-free conditions is described.

Full text of DOI:10.1016/j.tet.2006.05.083

Tetrahedron 62 (2006) 8164–8168
Solvent-free reduction of aldehydes and ketones using solid
acid-activated sodium borohydride
a,*
a
Byung Tae Cho, Sang Kyu Kang, Min Sung Kim, Soo Ryeon Ryu and Duk Keun An
b
b
b,*
a
Department of Chemistry, Hallym University, Chunchon, Kangwondo 200-702, Republic of Korea
Department of Chemistry, Kangwon National University, Chunchon, Kangwondo 200-701, Republic of Korea
b
Received 10 May 2006; revised 26 May 2006; accepted 31 May 2006
Available online 19 June 2006
This paper is dedicated to the late Professor Herbert C. Brown and his pioneer works on the hydride reductions
Abstract—A simple and convenient procedure for the reduction of aldehydes and ketones with sodium borohydride activated by solid acids
such as boric acid, benzoic acid, and p-toluenesulfonic acid monohydrate under solvent-free conditions is described.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Solvent-free reactions are not only of interest from ecologi-
cal point of view, but in many cases, also offer considerable
synthetic advantages in terms of yield, selectivity, and sim-
2.1. Reduction of unfunctionalized aldehydes and
ketones
1
plicity of the reaction procedure. Sodium borohydride is
We initially examined solvent-free reductions of benzalde-
hyde and acetophenone using solid acid-activated sodium
borohydride. Boric acid, benzoic acid, and p-toluenesulfonic
acid were chosen as representative solid acids. We also com-
pared the same reductions using sodium borohydride itself.
The reductions were carried out by grinding a 1:1 mixture
of the aldehyde (or ketone) and sodium borohydride in theab-
sence and presence of 1 equiv of each solid acid in an agate
mortar and pestle at room temperature in air until TLC
showed complete disappearance of the starting materials.
Product alcohols were isolated by quenching the resulting
an inexpensive, safe to handle, and environmental friendly
reducing agent, which rapidly reduce aldehydes, ketones,
and acid chlorides. This reagent is commonly employed
2
in hydroxylic solvents, such as methanol, ethanol, and
2
-propanol, although it is unstable in both methanol and
2
ethanol due to solvolysis. There are few reports for the re-
duction of aldehydes and ketones with sodium borohydride
under solvent-free conditions. However, the reductions
3
have disadvantage for practical utility, requiring long reac-
tion times. For example, the reduction was complete when
a mixture of benzophenone and a 10-fold molar amount of
sodium borohydride was kept in a dry box at room temper-
ature with occasional mixing and grinding using an agate
mixture with saturated aqueous solution of NaHCO or 1 N
3
HCl solution to remove solid acid and unreacted sodium
borohydride used, followed by extraction with Et O or
2
3
a
mortar and pestle for 5 days. Very recently, we reported
the first solvent-free reduction of imines using solid acid-
activated sodium borohydride to give the corresponding
CH Cl and yields were determined by capillary GC analysis
2
2
or column chromatography. As shown in Table 1, benzalde-
hyde was rapidly reduced to benzyl alcohol even by sodium
borohydride alone in the absence of solid acids. In this reduc-
tion, effectiveness of activators examined appeared to be not
significant, although it was found that they enhanced the re-
duction. Also, meaningful differences of effects among them
were not observed (entries 1–4). Using the same methodol-
ogy, we examined the reductions of other aromatic, aliphatic,
and heterocyclic aldehydes. In all cases, the reductions
afforded the corresponding alcohols in high yields (entries
4
amines in near quantitative yields. The results prompted
us to study the solvent-free reduction of aldehydes and
ketones using the same methodology. This paper includes
chemoselective reduction of functionalized aldehydes and
ketones bearing other reducible functional groups, regiose-
lective reduction of a,b-unsaturated aldehydes and ketones,
and stereoselective reduction of cyclic ketones.
Keywords: Solvent-free reaction; Aldehyde and ketone reduction; Sodium
borohydride.
5
–14). Unlike those of aldehydes, the reductions of ketones
using sodium borohydride itself in the absence of activators
proceeded very slowly. For example, the reduction of aceto-
phenone without activators provided 1-phenylethanol in only
*
Corresponding authors. Tel.: +82 33 248 2071; fax: +82 33 251 8491
B.T.C.); tel.: +82 33 250 8494; fax: +82 33 253 7582 (D.K.A.); e-mail
addresses: btcho@hallym.ac.kr; dkan@kangwon.ac.kr
(
0
040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.05.083

B. T. Cho et al. / Tetrahedron 62 (2006) 8164–8168
8165
a
Table 1. Solvent-free reduction of simple aldehydes and ketones with sodium borohydride in the presence of activators
b
Run
Aldehydes and ketones
CHO
Activator
None
Time (min)
Product
CH
Yield (%)
1
2
3
4
5
6
7
8
9
C
6
H
5
10
5
5
C
6
H
5
2
OH
>99
>99
>99
>99
95 (5)
>99
98 (2)
>99
96 (4)
H
3
BO
3
PhCOc
2
H
PTSA
None
PhCO
None
PhCO
None
PhCO
None
5
d
2-Naphthaldehyde
n-C 13CHO
c-C 11CHO
60
40
10
5
20
10
5
5
5
5
120
10
50
50
100
100
130
130
120
120
50
50
20
20
30
20
10
10
30
20
40
20
30
15
2-Naphthylmethanol
n-C 13CH OH
c-C 11CH OH
2
2
2
H
H
H
d
6
H
6
H
2
d
6
H
6
H
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
>99
>99
>99
>99
>99
Furfural
Furfuryl alcohol
H
3
BO
None
BO
None
BO
3
3
3
4-Pyridinecarboxaldehyde
4-Pyridinemethanol
H
3
d
C
6
H
5
COCH
3
C
6
H
5
CHOHCH
3
18 (82)
H
3
>99
>99
2
PhCOcH
PTSA
None
d
70 (30)
17 (83)
e
d
2-Acetylnaphthalene
a-Methyl-2-naphthalenemethanol
1-(4-Biphenyl)-1-ethanol
Benzhydrol
f
H
3
BO
None
BO
None
BO
None
BO
None
BO
None
BO
None
BO
None
BO
None
BO
None
BO
3
3
3
3
3
3
3
3
3
3
97
16 (84)
0
e
d
4 -Acetylbiphenyl
d
H
3
80 (20)
1 (99)
e
d
Benzophenone
f
H
3
98
5 (95)
d
a-Tetralone
1,2,3,4-Tetrahydro-1-naphthol
1-Indanol
H
3
>99
2 (98)
d
1-Indanone
H
3
>99
2 (98)
d
2-Nonanone
Cyclohexanone
2-Acetylfuran
2-Nonanol
H
3
>99
>99
>99
60 (40)
>99
27 (73)
>99
78 (22)
>99
Cyclohexanol
H
3
d
1-(2-Furyl)ethanol
1-(5-Methyl-2-furyl)ethanol
1-(4-Pyridyl)ethanol
H
3
g
d
5-Methyl-3-acetylfuran
H
3
g
d
4-Acetylpyridine
H
3
a
A 1:1 mixture of substrate and NaBH
ꢀ
4
or 1:1:1 mixture of substrate, NaBH
(ca. 25 C), unless otherwise indicated.
Determined by capillary GC analysis after quenching the reaction with a saturated aqueous of NaHCO
4
, and activator was ground in an agate mortar and pestle at room temperature
b
c
d
e
f
3
or 1 N HCl solution.
PTSA¼p-toluenesulfonic acid monohydrate.
Figures in parentheses indicate % yield of unreacted starting material.
NaBH (5 equiv) or a mixture of NaBH (5 equiv) and H BO (5 equiv) was used.
4
4
3
3
Isolated yield.
NaBH (3 equiv) or a mixture of NaBH
g
4
4
(3 equiv) and H
3
BO
3
(3 equiv) was used.
1
8% yield in 120 min with recovery of the unreacted starting
to the corresponding alcohols were successfully achieved
(entries 33–38).
ketone in 82% yield. However, the presence of 1 equiv of
boric acid accelerated remarkably the reduction to give the
product alcohol in a quantitative yield in 10 min (entry 15
vs 16). Of the activators examined, boric acid provided the
best results (entries 15–18). This methodology was success-
fully applied to the reduction of other aromatic ketones such
as 2-acetylnaphthalene, 4 -acetylbiphenyl, benzophenone,
a-tetralone, and 1-indanone. Of these, 2-acetylnaphthalene,
4
the reducing agent for their complete reductions. Again,
these reductions with sodium borohydride itself were very
sluggish (entries 19–28). In the cases of aliphatic ketones,
the reduction of 2-nonanone was remarkably accelerated
by the presence of 1 equiv of boric acid, although cyclohexa-
none was smoothly reduced by sodium borohydride alone
2.2. Chemoselective reduction of functionalized alde-
hydes and ketones bearing other reducible functional
groups
0
We next examined solvent-free chemoselective reduction of
functionalized aldehydes and ketones including other reduc-
ible functional groups, such as ester, amide, cyano, bromo,
and nitro groups, using boric acid-activated sodium borohy-
dride. As shown in Table 2, benzaldehyde derivatives bearing
various functional groups were chemoselectively reduced to
the corresponding alcohols without reduction of any other
functional groups in quantitative yields (entries 1–5). To
explore the generality of this methodology, we examined
the chemoselective reductions of other functionalized
ketone analogues, such as benzoyl cyanide, methyl benzoyl-
formate, benzoylacetonitrile, ethyl benzoylacetate, ethyl
0
-acetylbiphenyl, and benzophenone required 5 equiv of
(
entries 29–32). Similarly, using boric acid-activated sodium
borohydride, the reductions of heterocyclic ketones such as
-acetylfuran, 5-methyl-2-acetylfuran, and 4-acetylpyridin
2

8166
B. T. Cho et al. / Tetrahedron 62 (2006) 8164–8168
a
Table 2. Solvent-free chemoselective reduction of aldehydes and ketones containing various functional groups with H
3
BO
3
-activated sodium borohydride
b
Run
Aldehydes and ketones
Time (min)
Product
Yield (%)
c
d
CHO
CH OH
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
X¼CO
2
Me
5 (15)
20 (40)
2
X¼CO
2
Me
X¼NHCOMe
X¼CN
>99 (>99)
e
c
d
X¼NHCOMe
X¼CN
>99 (>99)
>99 (>99)
>99 (>99)
>99 (>99)
>99 (>99)
>99 (>99)
>99 (>99)
>99 (>99)
>99 (>99)
c
d
d
d
d
d
d
d
d
5 (15)
5 (15)
c
X¼Br
X¼Br
2
c
X¼NO
2
5 (15)
10 (30)
X¼NO
X
X
e
c
4-NO
4-NCC
2
C
6
H
H
4
COCHe
3
4-NO
4-NCC
2
C
6
H
4
CH(OH)CH
3
c
6
4
COCH
3
5 (30)
30 (60)
6
H
4
CH(OH)CH
3
c
Benzoyl cyanide
Mandelonitrile
Methyl mandelate
c
Methyl benzoylformate
Benzoylacetonitrile
Ethyl benzoylacetate
Ethyl acetoacetate
2-Methoxycarbonylcycloheptanone
Benzoin
Methyl 5-acetylsalicylate
5 (15)
10 (30)
c
0
1
2
3
4
5
6
PhCH(OH)CH
PhCH(OH)CH
2
CN
CO
c
d,f
40 (60)
20 (40)
2
2
Et
Et
>99 (64)
c
d
MeCH(OH)CH
2
CO
2
>99 (>99)
>99 (>99)
>99 (>99)
c
d
d
15 (40)
40 (120)
2-Methoxycarbonylcycloheptanol
Hydrobenzoin
e
c
e
c
d,f
d,f
90 (90)
60 (60)
5-MeCH(OH)C
6
H
3
2
-2-(OH)CO Me
Br
60 (40)
50 (20)
e
Br
c
6
4-BrC H
4
COCH
2
4-BrC CH(OH)CH
6
H
4
2
a,b
c,d
e
See the corresponding footnotes in Table 1.
The figures in parentheses indicated reaction time and yield obtained, respectively, when the reaction was carried out with NaBH
NaBH (3 equiv) or a 1:1 mixture of NaBH (3 equiv) and H BO (3 equiv) was used.
Unreacted ketones were recovered.
4
alone.
4
4
3
3
f
Table 3. Solvent-free regioselective reduction of a,b-unsaturated aldehydes
and ketones using solid acid-activated sodium borohydride
acetoacetate, and 2-ethoxycarbonylcycloheptanone, using
the same methodology. In all cases, the reductions provided
the corresponding alcohols in high yields and chemoselectiv-
ities. The same reductions using sodium borohydride itself
with no aid of boric acid underwent more slowly (entries
a
Run Aldehydes and Activator Time
ketones
Product
Yield
(%)
b
(min)
1
2
None
BO
10
10
98
98
CHO
O
CH OH
2
Ph
Ph
8
–13). For the complete reduction of 4-acetamidobenzal-
H
3
3
c
dehyde, 4-nitroacetophenone, 4-cyanoacetophenone, and
benzoin, 3 equiv of the activated borohydride was required
3
4
5
None
BO
PhCO
60
10
30
96
98
OH
c
H
3
3
c
96
Ph
Ph
Ph
H
(
5
entries 2, 6, 7, and 14). However, the reductions of methyl
-acetylsalicylate and 4 -bromophenacyl bromide under the
2
0
same conditions were very sluggish (entries 15 and 16).
O
OH
Ph
d
6
7
None
H
120
60
8e
3
BO
3
98
Ph
O
Ph
OH
8
9
None
BO
60
10
27
98
2.3. Regioselective reduction of a,b-unsaturated
aldehydes and ketones
H
3
3
O
OH
f
As shown in Table 3, the solvent-free reduction of an a,b-un-
saturated aldehyde, (E)-cinnamaldehyde using sodium boro-
hydride in the absence and presence of boric acid provided
10
1
None
BO
30
10
1
H
3
3
98
(
E)-cinnamyl alcohol (1,2-addition product) without the for-
mation of saturated alcohols (1,4-addition product) in quan-
O
OH
f
1
1
2
3
None
BO
60
60
e
48
H
3
3
5
a
titative yield. In this reaction, boric acid did not seem to
play a significant role as activator for the reduction (entries
O
OH
d
1 and 2). However, this activator was highly effective for
accelerating dramatically the reduction of a,b-unsaturated
14
15
None
BO
120
90
8e
H
3
3
98
5
b
ketones such as (E)-4-phenyl-3-butene-2-one, 1-acetyl-1-
5
c
O
OH
cyclohexene, and 2-cyclohexenone, comparing the same
reductions without the activator. The reductions were com-
plete within 10 min to give only 1,2-addition products in
quantitative yields (entries 3, 4, and 8–11). For the complete
reductions of (E)-chalcone and b-ionone to give the corre-
sponding allylic alcohols was required 2 equiv of boric
acid-activated borohydride. However, the reduction of iso-
phorone under the identical conditions was more sluggish.
Despite use of a large excess of sodium borohydride
d
1
1
6
7
None
BO
90
40
15
98
e
Ph
Ph
H
3
3
3
Ph
Ph
O
OH
d
18
1
None
BO
90
40
21
99
e
Ph
Ph
9
H
3
Bu-n
Bu-n
a,b
c
See the corresponding footnotes in Table 1.
Isolated yield.
d
e
f
NaBH
A mixture of NaBH
A mixture of 1,2- and 1,4-reduction products was produced.
4
(5 equiv) was used.
(
5 equiv), these reductions in the absence of activator
4
(2 equiv) and boric acid (2 equiv) was used.
proceeded very slowly with recovery of unreacted starting
ketones (entries 6, 7, and 12–15). In the cases of 2-cyclo-
hexenone and isophorone, the reductions with sodium boro-
hydride alone provided a mixture of 1,2- and 1,4-addition
products (entries 10 and 12). On the other hand, the acti-
vated borohydride also reduced a,b-ynones such as
diphenylpropynone and 1-phenyl-2-heptyn-1-one to the
corresponding propargylic alcohols in high yields and regio-
selectivities (entries 16 and 19).

B. T. Cho et al. / Tetrahedron 62 (2006) 8164–8168
8167
2
.4. Stereoselective reduction of cyclic ketones
is not critical for the reduction. This hydride species of the
mixture were stable in air at least for few hours with no
loss of hydride activity. Although the structure of this reduc-
Using the same methodology, solvent-free stereoselective
reductions of cyclic ketones, namely 2-methylcyclohexa-
none, 2-tert-butylcyclohexanone, 2-phenylcyclohexanone,
7
ing species of solid acid-activated sodium borohydride and
the mechanism of this reduction are unclear so far, it appears
that a eutectic temperature with melting point lower than the
ambient temperature exists in each case. In fact, the reaction
mixture became oily or sticky during grinding the mixtures
even though they are in powder states before grinding.
3
-methylcyclohexanone, and 4-tert-butylcyclohexanone,
were studied. As shown in Table 4, all the ketones examined
were smoothly reduced to the corresponding alcohols in
quantitative yields. All the reductions with one exception
were satisfactorily accomplished even by sodium boro-
hydride alone in the absence of activators. The reduction
of 2-tert-butylcyclohexanone with sodium borohydride
alone was very sluggish, giving the product alcohol in only
3. Conclusion
We have established a convenient solvent-free reduction of
aldehydes and ketones using solid acid-activated sodium
borohydride. The reductions provided not only high chemo-
selectivity for functionalized aldehydes and ketones includ-
ing other reducible functional groups, but also high
regioselectivity for a,b-unsaturated aldehydes and ketones
to give only the corresponding allylic alcohols. This is the
first example for highly effective reduction of aldehydes
and ketones under solvent-free conditions.
5
% yield in 210 min. However, the same reduction with
boric acid-activated sodium borohydride was completed in
20 min (entries 3 and 4). Comparing effectiveness of activa-
1
tors for the reduction of 2-phenylcyclohexanone and 4-tert-
butylcyclohexanone, boric acid among solid acids selected
provided the best results (entries 6–8 and 12–14). With re-
spect to the stereoselection of product alcohols, all the reduc-
tion of cyclic ketones examined predominantly produced
thermodynamically more stable alcohols, such as the ratio
of 65% for trans-2-methylcyclohexanol, 40% for trans-
2
-tert-butylcyclohexanol, 65% for trans-2-phenylcyclo-
4. Experimental
4.1. General
hexanol, 86% for cis-3-methylcyclohexanol, and 92% for
trans-4-tert-butylcyclohexanol. The results indicate that
the reducing agents used preferentially attacks unhindered
6
site of the carbonyl group of cyclic ketones examined.
The reactions were monitored by TLC using silica gel plates.
GC analyses were performed on a Donam DS 6200 FID
chromatograph, using a HP-1 (crosslinked methyl siloxane)
capillary column (30 m). All GC yields were determined
with use of a suitable internal standard and authentic
Comparing the stereoselective ratios of product alcohols ob-
tained, the effect of activators on the stereoselective reduc-
tion of the ketones examined was not significant.
1
13
On the other hand, in all the solvent-free reductions exam-
ined above, it was found that the order of mixing of the re-
actants had no discernible effects on the rate of reduction,
yields, and the chemoselectivity, regioselectivity, and stereo-
selectivity of products. Also, the presence of moisture in air
mixture. H NMR and C NMR spectra were recorded
on a Bruker DPX FT (400 MHz) or Bruker Avance
(300 MHz) spectrometer. The chemical shifts are expressed
as units with Me Si as the internal standard in CDCl . IR-
4
3
spectra were recorded on a JASCO FTIR-460 and absorp-
tions are reported in wave numbers (cm ).
ꢁ
1
Table 4. Solvent-free stereoselective reduction of cyclic ketones using solid
acid-activated sodium borohydride
a
4.2. Materials
b
Run Ketone
Activator Time (min) Product alcohol Yield (%)
Most of the organic compounds utilized in this study were
commercial products of the highest purity. They were further
purified by distillation when necessary. Sodium boro-
hydride, p-toluenesulfonic acid monohydrate, and benzoic
acid were purchased from Aldrich or Lancaster and used
without further purification.
cis
trans
O
1
2
None
BO
45
15
38
35
62
65
>99
>99
H
3
3
O
3
4
None
210
120
53
56
47
43
5
>99
Bu-t
4.2.1. Solvent-free reduction of aldehydes and ketones
using solid acid-activated sodium borohydride.
H
3
BO
3
5
6
7
8
O
None
BO
PhCO
30
20
20
30
31
35
38
36
69
65
62
64
>99
>99
>99
>99
4.2.1.1. General procedure. A mixture of aldehyde or
ketone (10 mmol), NaBH4 (10 mmol), and boric acid,
benzoic acid, or p-toluenesulfonic acid monohydrate
H
3
3
Ph
2
c
H
PTSA
(10 mmol) was ground with an agate mortar and pestle until
O
TLC showed complete disappearance of the starting mate-
rial. The mixture was quenched with a saturated aqueous so-
lution of NaHCO or 1 N HCl solution, followed by filtration
9
1
None
20
10
83
86
16
14
>99
>99
0
H
3
BO
3
3
O
of the resultant suspension to give product alcohol. When the
product was liquid, it was isolated from extraction with
CH Cl or Et O instead of filtration. All products were char-
acterized by IR, H, and C NMR spectra. In the case of
known compounds, their spectra were compared with those
of authentic samples.
1
1
1
1
1
2
3
4
None
BO
20
10
10
10
8
8
7
8
92
92
93
92
>99
>99
>99
80 (20)
H
3
3
PhCO
PTSA
2
H
2
2
2
c
d
1
13
Bu-t
a–d
See the corresponding footnotes in Table 1.

8168
B. T. Cho et al. / Tetrahedron 62 (2006) 8164–8168
1
4.2.1.2. 1-(5-Methyl-2-furyl)ethanol (Table 1, entry
6). IR (neat, cm ): 3349, 2979, 2924, 2884, 1564,
1668, 1437, 1366, 1293, 1166, 1137, 1096, 1060, 1007; H
NMR (CDCl ): d 5.67 (s, 1H), 4.17 (q, J¼6.4 Hz, 1H),
ꢁ
1
3
3
1
1
517, 1450, 1370, 1319, 1289, 1221, 1078, 1017; H NMR
1.97–2.05 (m, 4H), 1.53–1.67 (m, 4H), 1.26 (d, J¼6.5 Hz,
1
3
(
CDCl ): d 6.10 (d, J¼3.1 Hz, 1H), 5.91–5.89 (m, 1H),
3H); C NMR (CDCl ): d 21.52, 22.61, 22.67, 23.67,
3
3
4
.82 (q, J¼6.6 Hz, 1H), 2.28 (s, 3H), 1.98 (br s, 1H), 1.52
24.90, 72.18, 121.54, 141.27.
1
3
(
d, J¼6.6 Hz, 3H); C NMR (CDCl ): d 13.53, 21.17,
3
6
3.62, 105.81, 105.96, 151.67, 155.81.
.2.1.3. 4-Methoxycarbonylbenzyl alcohol (Table 2,
entry 1). IR (KBr, cm ): 3308, 3210, 3015, 2914, 2861,
4.2.1.10. 3,5,5-Trimethyl-2-cyclohexen-1-ol (Table 3,
entry 13). IR (neat, cm ): 3324, 3035, 2952, 2825,
2724, 1673, 1455, 1437, 1364, 1284, 1200, 1170, 1129,
1100, 1043, 1020; H NMR (CDCl ): d 5.43 (s, 1H), 4.20–
ꢁ
1
4
ꢁ1
1
3
1
1
721, 1448, 1433, 1415, 1312, 1284, 1193, 1111, 1049; H
4.27 (m, 1H), 1.64–1.88 (m, 4H), 1.68 (s, 3H), 1.23 (dd,
J¼9.1, 12.4 Hz, 1H), 0.99 (s, 3H), 0.88 (s, 3H); C NMR
1
3
NMR (CDCl ): d 8.03 (d, J¼8.3 Hz, 2H), 7.43 (d,
3
J¼8.6 Hz, 2H), 4.77 (s, 2H), 3.92 (s, 3H), 1.99 (br s, 1H);
(CDCl ): d 23.54, 26.20, 31.07, 31.24, 44.12, 45.24, 66.84,
3
1
3
C NMR (CDCl ): d 52.13, 64.70, 126.47, 129.32,
3
123.65, 136.02.
1
29.86, 145.98, 166.98.
4.2.1.11. 1,3-Diphenylpropyn-1-ol (Table 3, entry
17). IR (neat, cm ): 3549, 3365, 3062, 3031, 2871,
ꢁ
1
4.2.1.4. 4-Acetamidobenzyl alcohol (Table 2, entry
). IR (KBr, cm ): 3421, 3246, 3188, 3126, 3074, 2924,
ꢁ
1
1
2
2
1
2228, 1598, 1490, 1455, 1443, 1305, 1190, 1070, 1030; H
NMR (CDCl ): d 7.62–7.49 (m, 10H), 5.68 (s, 1H), 2.43
882, 1670, 1608, 1549, 1517, 1411, 1371, 1323, 1273,
211, 1002; H NMR (DMSO): d 9.88 (s, 1H), 7.50 (d,
3
13
1
(br s, 1H); C NMR (CDCl ): d 65.10, 86.66, 88.70,
3
J¼8.5 Hz, 2H), 7.21 (d, J¼8.5 Hz, 2H), 5.08 (s, 1H), 4.41
122.40, 126.74, 128.31, 128.44, 128.61, 128.67, 131.75,
140.62.
1
3
(
s, 2H), 2.01 (s, 3H); C NMR (DMSO): d 23.92, 62.60,
18.67, 126.86, 137.03, 137.91, 168.08.
1
4.2.1.12. 1-Phenyl-2-heptynol (Table 3, entry 19). IR
(neat, cm ): 3365, 3063, 3031, 2957, 2933, 2872, 2227,
1603, 1493, 1455, 1135, 1003; H NMR (CDCl ): d 7.55–
3
ꢁ
1
4.2.1.5. 4-Cyanobenzyl alcohol (Table 2, entry 3). IR
neat, cm ): 3838, 3419, 2975, 2929, 2881, 2229, 1610,
ꢁ
1
1
(
1
1
503, 1451, 1407, 1370, 1287, 1206, 1119, 1090, 1013; H
7.41 (m, 5H), 5.46 (s, 1H), 2.28 (dt, J¼2.0, 6.9 Hz, 2H),
NMR (CDCl ): d 7.64 (d, J¼8.4 Hz, 2H), 7.49 (d,
1.93 (br s, 1H), 1.89–1.56 (m, 4H), 0.92 (t, J¼7.2 Hz, 3H);
3
1
3
J¼8.1 Hz, 2H), 4.97 (q, J¼6.5 Hz, 1H), 2.13 (s, 1H), 1.50
C NMR (CDCl ): d 13.59, 18.51, 21.99, 30.66, 64.81,
3
1
3
(
1
d, J¼6.5 Hz, 3H); C NMR (CDCl ): d 25.42, 69.66,
79.95, 87.65, 125.92, 126.64, 128.18, 128.42, 128.52,
141.31.
3
11.07, 118.87, 126.07, 136.36, 151.12.
4.2.1.6. 2-Methoxycarbonylcycloheptanol (Table 2,
entry 13). IR (neat, cm ): 3481, 2928, 2859, 1723,
ꢁ
1
References and notes
1
1
4
1
436, 1263, 1198, 1127, 1034; H NMR (CDCl ): d 4.24–
3
.19 (m, 1H), 3.71 (s, 3H), 2.84 (s, 1H), 2.62 (dt, J¼2.6,
1. Tanaka, K. Solvent-free Organic Synthesis; Wiley-VCH:
Weinheim, 2003.
1
3
0.0 Hz, 1H), 1.37–2.05 (m, 10H); C NMR (CDCl ):
3
d 21.94, 24.18, 26.62, 27.82, 34.94, 49.76, 51.79, 70.27,
76.79.
2. (a) Reagents for Organic Synthesis; Paquette, L., Ed.; Wiley:
New York, NY, 1995; Vol. 7, pp 4522–4528; (b) Brown, H. C.;
Krishnamurthy, S. Tetrahedron 1979, 35, 567.
3. (a) Toda, F.; Kiyoshige, K.; Yagi, M. Angew. Chem., Int. Ed.
Engl. 1989, 28, 320; (b) Merchand, A. P.; Reddy, G. M.
Tetrahedron 1991, 47, 6571; (c) Mehta, G.; Khan, F. A.;
Kashimi, K. A. Tetrahedron Lett. 1992, 33, 7977; (d) Varma,
R. S.; Saini, R. K. Tetrahedron Lett. 1997, 38, 4337.
4. (a) Cho, B. T.; Kang, S. K. Synlett 2004, 1484; (b) Cho, B. T.;
Kang, S. K. Tetrahedron 2005, 61, 5725.
5. It has been reported that the reductions of (E)-cinnamaldehyde,
(E)-4-phenyl-3-butene-2-one, and 2-cyclohexenone with so-
dium borohydride in THF, ethanol, or 2-propanol provide not
only the corresponding allylic alcohols (1,2-addition products),
but also a significant amount of saturated alcohols (1,4-addition
products): see (a) Nutaitis, C. F.; Bernardo, J. E. J. Org. Chem.
1989, 54, 5629; (b) Iqbal, K.; Jackson, W. R. J. Chem. Soc. C
1968, 616; (c) Johnson, M. R.; Rickborn, B. J. Org. Chem.
1970, 35, 1041.
1
0
ethanol (Table 2, entry 15). IR (neat, cm ): 3341,
0
4
.2.1.7. 1-(4 -Hydroxy-3 -methoxycarbonylphenyl)-
ꢁ
1
1
2
972, 1684, 1617, 1595, 1490, 1442, 1318, 1214, 1086; H
NMR (CDCl ): d 10.71 (s, 1H), 7.84 (d, J¼2.1 Hz, 1H),
3
7
.48 (dd, J¼2.2, 8.6 Hz, 1H), 6.97 (d, J¼8.6 Hz, 1H), 4.86
(
q, J¼6.4 Hz, 1H), 3.96 (s, 3H), 1.79 (br s, 1H), 1.48 (d,
1
3
J¼6.39 Hz, 3H); C NMR (CDCl ): d 25.12, 52.32,
3
6
1
9.64, 112.02, 117.76, 126.71, 133.16, 136.62, 160.96,
70.48.
0
ꢁ
4.2.1.8. 2-Bromo-1-(4 -bromophenyl)ethanol (Table 2,
entry 16). IR (KBr, cm ): 3390, 2959, 2917, 1593, 1488,
1
1
1
420, 1403, 1218, 1195, 1071, 1011; H NMR (CDCl ):
3
d 7.51 (d, J¼8.4 Hz, 2H), 7.27 (d, J¼8.1 Hz, 2H), 4.90
(
3
(
dd, J¼3.4, 8.8 Hz, 1H), 3.61 (dd, J¼3.4, 10.5 Hz, 1H),
1
3
.50 (dd, J¼8.7, 10.1 Hz, 1H), 2.59 (br s, 1H); C NMR
3
CDCl ): d 39.89, 73.10, 122.37, 127.68, 131.82, 139.21.
6. Wigfield, D. C. Tetrahedron 1979, 35, 449.
1
1
7
. IR and B NMR data of solid acid-activated sodium boro-
hydride for the characterization of reducing species were
described in Ref. 4b.
4.2.1.9. 1-(Cyclohexen-1-yl)ethanol (Table 3, entry
). IR (neat, cm ): 3349, 2972, 2929, 2858, 2837, 2661,
ꢁ1
9