Indium tri(isopropoxide)-catalyzed selective Meerwein-Ponndorf-Verley reduction of aliphatic and aromatic aldehydes

Article abstract of DOI:10.1021/jo300236u

Indium tri(isopropoxide)-catalyzed Meerwein-Ponndorf-Verley reduction of aliphatic and aromatic aldehydes in 2-propanol gave selectively the corresponding primary alcohols in good to excellent yields at room temperature. A wide range of functional groups including alkene, ether, ketone, ester, nitrile, and nitro were tolerated under the optimum reaction conditions. Chemoselective reductions were also achieved not only between aromatic aldehyde, aromatic ketone, and epoxide but also between aliphatic aldehyde and alkene.

Full text of DOI:10.1021/jo300236u

Note
pubs.acs.org/joc
Indium Tri(isopropoxide)-Catalyzed Selective Meerwein−Ponndorf−
Verley Reduction of Aliphatic and Aromatic Aldehydes
Jaeyoung Lee, Taekyu Ryu, Sangjune Park, and Phil Ho Lee*
Department of Chemistry, Kangwon National University, Chuncheon 200-701, Republic of Korea
S
* Supporting Information
ABSTRACT: Indium tri(isopropoxide)-catalyzed Meerwein−Ponndorf−
Verley reduction of aliphatic and aromatic aldehydes in 2-propanol gave
selectively the corresponding primary alcohols in good to excellent yields at
room temperature. A wide range of functional groups including alkene, ether,
ketone, ester, nitrile, and nitro were tolerated under the optimum reaction
conditions. Chemoselective reductions were also achieved not only between
aromatic aldehyde, aromatic ketone, and epoxide but also between aliphatic
aldehyde and alkene.
Scheme 1. MPV Reduction of Aldehydes and Ketones Using
Indium Catalyst
he reduction of aldehydes and ketones is one of the
important functional group transformations in organic
T
chemistry.1 Among the various methods for reducing carbonyl
groups, the Meerwein−Ponndorf−Verley (MPV) reduction,
first reported in 1925, has been recognized as one of most
convenient and environmentally benign processes in organic
synthesis.2 In general, the MPV reduction uses inexpensive
2-propanol as a hydride donor and aluminum tri(isopropoxide)
as a mediator.3 Because the MPV reduction is easy to operate
and convenient to scale up, it became an attractive green pro-
cess for reduction of various carbonyl compounds. However, its
synthetic utility has been rather limited mainly due to the fact
that stoichiometric or excess amounts of aluminum alkoxides
are often required at high temperatures. In addition, in situ
elimination of generated acetone needs to be carried out in
order to maximize the procduct yields in acceptable reaction
time.4 While catalytic MPV reduction was developed by using
trimethylaluminum or chlorodimethylaluminum in toluene,5 an
MPV reduction was reported to be accelerated when aluminum
tri(isopropoxide) was modified with certain additives such as
TFA, HCl, or propionic acid.2k,l,6 Despite of these recent
advances, the chemoselective catalytic MPV reduction of
carbonyl compounds is still highly desirable especially without
requiring any additives under mild reaction conditions. With
regard to this aspect, boron tri(isopropoxide) was examined in
the MPV reduction of carbonyl compounds although the
system was revealed to reduce only aliphatic aldehydes and
ketones.3c,7 In addition, because the reducing power of boron
tri(isopropoxide) is weak, stoichiometric amounts of reagents
were needed with long reaction times. Because indium metal is
one of the group 13 elements like boron and aluminum, we
envisioned that indium might be applied to the reduction of
aldehydes and ketones to produce alcohols as shown in Scheme 1.
Herein, we report our preliminary results on the development of
an indium tri(isopropoxide) reagent that can be employed for the
chemoselective catalytic MPV reduction of various aliphatic and
aromatic aldehydes under mild reaction conditions.
In order to examine the feasibility of reduction of carbonyl
compounds using indium catalyst, we first investigated a
reaction of benzaldehyde (1a) with indium tri(isopropoxide)
under nitrogen atmosphere (Table 1). When 1a was treated
with 5 mol % of In(OiPr)3 and 10 equiv of 2-propanol in
toluene, benzyl alcohol (2a) was obtained in 12% yield at 25 °C
after 1.5 h (entry 1). The use of 10 and 15 mol % of In(OiPr)3
gave 2a in 40% and 78% yields, respectively (entries 2 and 4).
Toluene was more effective for the reaction compared to other
solvents, representatively dichloromethane (entries 3 and 5).
Exposure of 1a to 20 mol % of In(OiPr)3 in the presence of
1 equiv of 2-propanol in toluene afforded 2a in 73% yield (entry 6).
Increasing the amounts of 2-propanol to 5 and 10 equiv
resulted in higher product yields of 81% and 86%, respectively,
in toluene (entries 7 and 8). Although the use of 5 and 10 mol %
of In(OiPr)3 in 2-propanol as a solvent provided 2a in low
yield (entries 9 and 10), treatment of 1a with 20 mol % of
In(OiPr)3 in 2-propanol produced 2a in 91% yield at 25 °C for
3 h (entry 11).
To demonstrate the efficiency and scope of the present
method, we applied this catalytic reduction system to a wide
range of aromatic aldehyde substrates (Table 2). When 2- and
4-tolualdehyde were treated with 20 mol % In(OiPr)3, the
corresponding alcohols were obtained in good to excellent
yields (93% and 86%) at 25 °C for 0.25 h (entries 2 and 3).
Received: February 4, 2012
Published: May 7, 2012
© 2012 American Chemical Society
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Note
2j was obtained in 41% yield together with 4-hydroxybenzalde-
hyde (47%), which was a byproduct derived from the ester
cleavage in 1j (entry 11). The presence of halide groups in the
aromatic ring did not deteriorate the reaction efficiency of the
MPV reactions (entries 12−14). The reduction of aromatic
aldehydes (1n, 1o, 1p, and 1q) having acetyl, methoxycarbonyl,
nitrile, and nitro groups provided selectively the corresponding
primary alcohols in good to excellent yields under the standard
conditions (entries 15−18). 2-Fluoro-3-methoxybenzaldehyde
(1r) was smoothly reduced to give 2r in 98% yield at 25 °C for
5 min (entry 19). Heteroaromatic aldehydes turned out to be
compatible with the employed reaction conditions. Indeed, 3-
pyridinecarboxaldehyde and 5-bromo-2-thiophenecarboxalde-
hyde were converted to the desired alcohols in 90% and 89%
yields, respectively (entries 20 and 21).5
Table 1. Optimization of Indium Tri(isopropoxide)-
Catalyzed MPV Reduction of Benzaldehyde
a
b
entry In(OiPr)3 (mol %) iPrOH (equiv) solvent time (h) yield (%)
1
2
5
10
10
15
15
20
20
20
5
10
10
10
10
10
1
toluene
toluene
CH2Cl2
toluene
CH2Cl2
toluene
toluene
toluene
iPrOH
1.5
3
12
40
3
5
37
4
5
78
5
3
72
c
c
c
6
7
73 (71)
81 (79)
86 (83)
3
7
5
5
8
10
3
9
6
Similarly, this catalytic system was successfully applied in the
reduction of a wide range of aliphatic aldehydes (Table 3). Reac-
tion of undecylenic aldehyde (3a) with 20 mol % of In(OiPr)3 in
2-propanol afforded selectively 10-undecen-1-ol (4a) in 82% yield
at 25 °C for 3 h with the double bond intact (entry 1). The
present method worked equally well with 2-ethylbutanal (3b)
and 2,6-dimethyl-5-heptenal (3c), leading to the selective forma-
tion of 2-ethyl-1-butanol (4b) and 2,6-dimethyl-5-hepten-1-ol (4c)
in 88% and 83% yields, respectively (entries 2 and 3). Cyclo-
hexanecarboxaldehyde (3d) was reduced efficiently under the
standard conditions (entry 4). Treatment of cinnamaldehyde and
2-bromocinnamaldehyde with indium catalyst produced selectively
cinnamyl alcohol and 2-bromocinnamyl alcohol in 82% and 96%
yields, respectively, at 25 °C without the reduction of conjugated
olefinic or carbon−bromine bonds (entries 5 and 6). Under the
optimum reaction conditions, (3g) was converted to the alcohol
(4g) in 81% yield (entry 7).
10
11
10
20
iPrOH
iPrOH
3
9
c
3
91 (88)
a
Reactions were carried out with 1a (0.5 mmol) in solvent (1.5 mL)
under nitrogen atmosphere. GC yields using dodecane as an internal
standard. Isolated yields.
b
c
Table 2. Indium Tri(isopropoxide)-Catalyzed MPV
Reduction of Aryl and Heteroaryl Aldehydes
a
b
entry
Ar
time (h)
yield (%)
1
2
Ph
a
b
c
d
d
e
f
3
0.25
0.25
24
4.5
0.25
0.5
5.5
0.5
2
88
93
86
2-Me-C6H4
3
4-Me-C6H4
c
4
2,4,6-(Me)3-C6H2
2,4,6-(Me)3-C6H2
2-MeO-C6H4
3-MeO-C6H4
4-MeO-C6H4
3,5-(MeO)2-C6H3
3,4-(OCH2O)-C6H3
4-AcO-C6H4
2−Br-C6H4
3−Br-C6H4
2−I-C6H4
4−Ac-C6H4
4-MeO2C−C6H4
3-NC-C6H4
47 (42)
d
5
92
6
90
97
78
93
83
7
Next, the MPV reduction of aromatic ketone with indium
tri(isopropoxide) was briefly investigated. Although 40 mol %
of In(OiPr)3 was used, 1-phenylethanol was obtained in only
17% yield at 25 °C after 33 h (eq 1). The use of trifluoroacetic
8
g
h
i
9
10
11
12
13
14
15
16
17
18
19
20
21
e
j
24
0.5
6
41 (47)
k
l
91
89
94
87
94
90
94
98
90
89
m
n
o
p
q
r
6
1.5
0.5
1
4-O2N−C6H4
2-F-3-MeO-C6H3
3-pyridyl
3
0.08
1
s
5-Br-thienyl
t
1
a
Reactions were carried out with 1 (0.5 mmol) in 2-propanol (1.5 mL)
b
c
under nitrogen atmosphere. Isolated yield. Recovery yield of
aldehyde. Reaction was carried out at 80 °C. 4-Hydroxybenzaldehyde.
d
e
While 2,4,6-trimethylbenzaldehyde was reduced to 2d in 47%
yield at 25 °C even after 24 h presumably due to steric effect
(entry 4), the same reaction at higher temperatures (80 °C)
afforded 2d in 92% yield for 4.5 h (entry 5). Subjecting 2- and
3-methoxybenzaldehyde (1e and 1f) to indium catalyst afforded
2e and 2f in excellent yield (90% and 97%) (entries 6 and 7). 4-
Methoxybenzaldehyde required longer reaction time (5.5 h)
(entry 8). 3,5-Dimethoxybenzaldehyde was converted to the
corresponding alcohol in 93% yield (entry 9). Benzo[1,3]dioxole-
5-carbaldehyde was reduced with indium catalyst to furnish 2i in
83% yield (entry 10). However, when 4-acetoxybenzaldehyde 1j
was treated with 20 mol % of In(OiPr)3, the corresponding alcohol
acid (1 equiv) as an additive was not effective (eq 2). In
addition, treatment of acetophenone with 1 equiv of In(OiPr)3
and 1 equiv of trifluoroacetic acid in 2-propanol gave rise to
1-phenylethanol in 35% yield at 80 °C after 6 h (eq 3).
These results led us to predict that an aromatic aldehyde can
be selectively reduced in the presence of aromatic ketones
(Scheme 2). In fact, when a mixture of benzaldehyde and
acetophenone was subjected to the reaction conditions, benzyl
alcohol was selectively isolated in 88% yield at 25 °C for 3 h.
Interestingly, an exposure of a mixture of benzaldehyde and
styrene oxide to indium catalyst led to only benzyl alcohol in
83% yield without the formation of 1- or 2-phenylethanol.
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Note
a
Table 3. Indium Tri(isopropoxide)-Catalyzed MPV Reduction of Aliphatic Aldehydes
a
b
c
Reactions were carried out with 3 (0.5 mmol) in solvent (1.5 mL) under nitrogen atmosphere. Isolated yield. GC yield using naphthalene as an
d
internal standard. Reaction was carried out at 80 °C.
mixture was quenched with 1 N HCl solution (4 mL). The aqueous
layer was extracted with ethyl acetate (3 × 10 mL), and the combined
organic layers were washed with brine (10 mL), dried over MgSO4,
filtered, and concentrated under reduced pressure. The residue was
purified by silica gel column chromatography (EtOAc/hexane = 1:5)
to give benzyl alcohol (2a) (47.7 mg, 88%):8 colorless liquid; 1H
NMR (400 MHz, CDCl3, 25 °C, TMS) δ 7.37−7.34 (m, 4H), 7.32−
7.25 (m, 1H), 4.69 (d, J = 5.9 Hz, 2H), 1.73 (d, J = 5.6 Hz, 1H);
13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ 141.3, 129.0, 128.1,
127.4, 65.8; IR (film) 3230 (OH), 3056, 3012, 2982, 1610, 1589, 1219,
1005 cm−1.
Scheme 2. Selective Reduction between Aldehyde and
Ketone or Epoxide
2-Methylbenzyl alcohol9 (2b): white solid; mp = 30−35 °C; 1H
NMR (400 MHz, CDCl3, 25 °C, TMS) δ 7.36−7.33 (m, 1H), 7.23−
7.16 (m, 3H), 4.69 (d, J = 3.7 Hz, 2H), 2.35 (s, 3H); 13C NMR (100
MHz, CDCl3, 25 °C, TMS) δ 139.1, 136.5, 130.8, 128.2, 128.0, 126.5,
64.0, 19.1; IR (film) 3248 (OH), 3032, 2936, 2912, 1557, 1446, 1154,
788 cm−1.
In summary, we have developed a new indium catalyst
system for the selective Meerwein-Ponndorf-Verley reduction
of aliphatic and aromatic aldehydes in 2-propanol to give the
corresponding primary alcohols in good to excellent yields at
room temperature. A wide range of functional groups such as
alkene, ether, ketone, ester, nitrile, and nitro are tolerated under
the optimized reaction conditions. Chemoselective reductions
were also achieved not only between aromatic aldehyde,
aromatic ketone, and epoxide but also between aliphatic
aldehyde and alkene.
8
1
4-Methylbenzyl alcohol (2c): white solid; mp = 58−63 °C; H
NMR (400 MHz, CDCl3, 25 °C, TMS) δ 7.25 (d, J = 8.0 Hz, 2H),
7.17 (d, J = 7.9 Hz, 2H), 4.64 (s, 2H), 2.35 (s, 3H); 13C NMR (100
MHz, CDCl3, 25 °C, TMS) δ 138.3, 137.8, 129.7, 127.5, 65.7, 21.6; IR
(film) 3348 (OH), 3022, 2956, 2920, 1517, 1446, 1034, 808 cm−1.
8
1
Mesitylmethanol (2d): white solid; mp = 85−90 °C; H NMR
(400 MHz, CDCl3, 25 °C, TMS) δ 6.87 (s, 2H), 4.71 (d, J = 3.3 Hz,
2H), 2.39 (s, 6H), 2.27 (s, 3H), 1.21 (s, 1H); 13C NMR (100 MHz,
CDCl3, 25 °C, TMS) δ 138.2, 137.7, 134.1, 129.6, 59.6, 21.4, 19.8; IR
(film) 3280 (OH), 3000, 2970, 2915, 1613, 1445, 992, 851 cm−1.
2-Methoxybenzyl alcohol10 (2e): colorless liquid; 1H NMR (400
MHz, CDCl3, 25 °C, TMS) δ 7.31−7.26 (m, 2H), 6.94 (t, J = 7.4 Hz,
1H), 6.89 (d, J = 8.2 Hz, 1H), 4.69 (d, J = 5.0 Hz, 2H), 3.87 (s, 3H),
2.31 (s, 1H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ 157.9,
EXPERIMENTAL SECTION
■
Indium Tri(isopropoxide)-Catalyzed MPV Reduction of
Benzaldehyde. Benzaldehyde (53.1 mg, 0.5 mmol) was added to a
solution of In(OiPr)3 (29.2 mg, 0.1 mmol, 20 mol %) purchased from
a commercial supplier in 2-propanol (1.5 mL) under nitrogen atmo-
sphere. The reaction mixture was stirred at 25 °C for 3 h. The reaction
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Note
129.43, 129.40, 129.2, 121.1, 110.6, 63.6, 55.7; IR (film) 3374 (OH),
2938, 2836, 1602, 1492, 1242, 1030, 754 cm−1.
7.54 (d, J = 8.9 Hz, 2H), 4.84 (d, J = 5.5 Hz, 2H), 1.90 (t, J = 5.7 Hz,
1H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ 148.1, 147.4,
127.0, 123.8, 64.1; IR (film) 3521 (OH), 3110, 3070, 2944, 2869,
1509, 1345, 1056, 735 cm−1.
3-Methoxybenzyl alcohol11 (2f): colorless liquid; 1H NMR (400
MHz, CDCl3, 25 °C, TMS) δ 7.29−7.25 (m, 1H), 6.94 (d, J = 7.4 Hz,
2H), 6.83 (dd, J = 7.1, 2.1 Hz, 1H), 4.67 (s, 2H), 3.82 (s, 3H); 13C
NMR (100 MHz, CDCl3, 25 °C, TMS) δ 160.3, 142.9, 130.0, 119.5,
113.7, 112.7, 65.7, 55.6; IR (film) 3356 (OH), 2938, 2835, 1601, 1488,
1263, 1039, 782 cm−1.
2-Fluoro-5-methoxybenzyl alcohol18 (2r): colorless liquid; H
1
NMR (400 MHz, CDCl3, 25 °C, TMS) δ 6.99−6.94 (m, 2H), 6.79−
6.75 (m, 1H), 4.73 (s, 2H), 3.79 (s, 3H); 13C NMR (100 MHz,
CDCl3, 25 °C, TMS) δ 156.4, 156.22, 156.20, 154.0, 128.9, 128.8,
116.3, 116.1, 114.6, 114.5, 114.25, 114.21, 59.9, 59.8, 56.2; IR (film)
3398 (OH), 2942, 2837, 1740, 1504, 1203, 1033, 811, 711 cm−1.
3-Pyridinemethanol8 (2s): light yellow liquid; 1H NMR (400
MHz, CDCl3, 25 °C, TMS) δ 8.45 (s, 1H), 8.38 (d, J = 4.0 Hz, 1H),
7.72 (d, J = 7.9 Hz, 1H), 7.26 (dd, J = 7.8, 4.9 Hz, 1H), 4.68 (s, 2H);
13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ 148.5, 148.3, 137.6,
135.6, 124.0, 62.4; IR (film) 3210 (OH), 3066, 3000, 2949, 2866,
1600, 1583, 1450, 1190, 1042, 800 cm−1.
4-Methoxybenzyl alcohol8 (2g): colorless liquid; 1H NMR (400
MHz, CDCl3, 25 °C, TMS) δ 7.30 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6,
Hz, 2H), 4.62 (s, 2H), 3.81 (s, 3H); 13C NMR (100 MHz, CDCl3,
25 °C, TMS) δ 159.6, 133.5, 129.1, 114.4, 65.5, 55.7; IR (film) 3352
(OH), 3030, 3000, 2956, 2934, 1612, 1512, 1247, 1032, 816 cm−1.
3,5-Dimethoxybenzyl alcohol12 (2h): pale yellow solid; mp =
1
40−45 °C; H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 6.52 (d, J =
2.2 Hz, 2H), 6.39 (t, J = 2.3 Hz, 1H), 4.63 (s, 2H), 3.79 (s, 3H); 13C
NMR (100 MHz, CDCl3, 25 °C, TMS) δ 161.4, 143.8, 105.1, 100.0,
65.8, 55.8; IR (film) 3397 (OH), 3000, 2938, 2838, 1598, 1463, 1205,
1060, 834 cm−1.
(5-Bromothiophen-2-yl)methanol19 (2t): yellow liquid; 1H
NMR (400 MHz, CDCl3, 25 °C, TMS) δ 6.92 (d, J = 3.8 Hz, 1H),
6.76 (d, J = 3.5 Hz, 1H), 4.75 (s, 2H); 13C NMR (100 MHz, CDCl3,
25 °C, TMS) δ 146.1, 1300, 1261, 1127, 60.6; IR (film) 3347 (OH),
3088, 3044, 2926, 2866, 1440, 1357, 1014, 795 cm−1.
Benzo[1,3]dioxolo-5-methanol8 (2i): yellow solid; mp = 50−
55 °C; 1H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 6.86 (s, 1H), 6.80
(dd, J = 8.0, 1.4 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H), 5.94 (s, 2H), 4.56
(s, 2H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ 148.2, 147.5,
135.3, 120.9, 108.6, 108.3, 101.4, 65.6; IR (film) 3321 (OH), 3078,
3011, 2989, 2905, 1489, 1444, 1252, 807 cm−1.
Undec-10-en-1-ol20 (4a): colorless liquid; H NMR (400 MHz,
1
CDCl3, 25 °C, TMS) δ 5.87−5.76 (m, 1H), 5.02−4.97 (m, 1H),
4.95−4.91 (m, 1H), 3.66−3.62 (m, 2H), 2.07−2.01 (m, 2H), 1.58−
1.53 (m, 2H), 1.39−1.29 (m, 12H), 1.24−1.22 (m, 1H); 13C NMR
(100 MHz, CDCl3, 25 °C, TMS) δ 139.2, 114.1, 63.1, 33.8, 32.8, 29.5,
29.4, 29.1, 28.9, 25.7; IR (film) 3245 (OH), 3078, 3000, 2905, 2855,
1624, 1425, 1305 cm−1.
4-Acetoxybenzyl alcohol13 (2j): white solid; mp = 30−35 °C;
1H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 7.38 (d, J = 8.6 Hz, 2H),
7.07 (d, J = 8.5 Hz, 2H), 4.68 (s, 2H), 2.30 (s, 3H); 13C NMR (100
MHz, CDCl3, 25 °C, TMS) δ 170.0, 150.5, 138.9, 128.5, 122.1, 65.1,
21.5; IR (film) 3336 (OH), 3059, 3005, 2845, 1699, 1678, 1266, 1204,
825 cm−1.
2-Ethyl-1-butanol21 (4b): colorless liquid; H NMR (400 MHz,
1
2-Bromobenzyl alcohol14 (2k): pale brown solid; mp = 75−
80 °C; 1H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 7.55 (dd, J = 8.0,
1.0 Hz, 1H), 7.49 (dd, J = 7.6, 1.4 Hz, 1H), 7.34 (ddd, J = 7.5, 7.5, 1.2
Hz, 1H), 7.17 (ddd, J = 7.7, 7.7, 1.6 Hz, 1H), 4.76 (d, J = 6.4 Hz, 2H),
2.00 (t, J = 6.5 Hz,1H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ
139.7, 132.6, 129.1, 128.9, 127.7, 122.6, 65.1; IR (film) 3204 (OH),
3066, 2913, 2858, 1456, 1442, 1055, 1024, 749 cm−1.
CDCl3, 25 °C, TMS) δ 3.56 (d, J = 3.0 Hz, 2H), 1.67 (s, 1H), 1.41−
1.32 (m, 4H), 1.25 (s, 1H), 0.92−0.88 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3, 25 °C, TMS) δ 64.5, 43.4, 22.7, 11.0; IR (film)
3336 (OH), 2962, 2932, 2875, 1461, 1380, 1112, 1052, 1010 cm−1.
2,6-Dimethylhept-5-en-1-ol22 (4c): colorless liquid; 1H NMR
(400 MHz, CDCl3, 25 °C, TMS) δ 5.13−5.09 (m, 1H), 3.54−3.41 (m,
2H), 2.08−1.95 (m, 2H), 1.69 (s, 3H), 1.66−1.63 (m, 1H), 1.61 (s,
3H), 1.48−1.39 (m, 1H), 1.20−1.11 (m, 1H), 0.93 (d, J = 6.6 Hz,
3H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ 131.5, 124.6, 68.3,
35.3, 33.2, 25.7, 25.4, 17.7, 16.5; IR (film) 3339 (OH), 2965, 2915,
2873, 1453, 1376, 1041 cm−1.
3-Bromobenzyl alcohol15 (2l): pale yellow liquid; 1H NMR
(400 MHz, CDCl3, 25 °C, TMS) δ 7.53 (s, 1H), 7.42 (d, J = 7.8 Hz,
1H), 7.29−7.21 (m, 2H), 4.68 (d, J = 5.1 Hz, 2H), 1.79 (t, J = 5.6 Hz,
1H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ 143.5, 131.1,
130.5, 130.3, 125.7, 123.1, 64.9; IR (film) 3323 (OH), 3055, 2934,
2873, 1570, 1428, 1069, 777 cm−1.
Cyclohexanemethanol14 (4d): pale brown liquid; 1H NMR (400
MHz, CDCl3, 25 °C, TMS) δ 3.44 (d, J = 6.43 Hz, 2H), 1.78−1.65
(m, 5H), 1.51−1.44 (m, 1H), 1.34 (bs, 1H), 1.30−1.11 (m, 3H),
0.98−0.88 (m, 2H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ
69.2, 40.9, 30.0, 27.0, 26.2; IR (film) 3335 (OH), 2945, 2855, 1420,
788 cm−1.
2-Iodobenzyl alcohol16 (2m): pale yellow solid; mp = 90−95 °C;
1H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 7.83 (dd, J = 7.8, 1.0 Hz,
11H), 7.47 (dd, J = 7.6, 1.5 Hz, 1H), 7.37 (ddd, J = 7.5, 7.5, 0.9 Hz,
1H), 7.01 (ddd, J = 7.6, 7.6, 1.6 Hz, 1H), 4.69 (d, J = 6.1 Hz, 2H), 1.98
(t, J = 6.3 Hz, 1H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ
143.0, 139.6, 129.8, 128.92, 128.90, 97.9, 69.8; IR (film) 3187 (OH),
3060, 2897, 1458, 1434, 1036, 1012, 740 cm−1.
8
1
Cinnamyl alcohol (4e): white solid; mp = 30−35 °C; H NMR
(400 MHz, CDCl3, 25 °C, TMS) δ 7.40−7.38 (m, 2H), 7.34−7.29 (m,
2H), 7.26−7.22 (m, 1H), 6.62 (d, J = 15.9 Hz, 1H), 6.37 (dt, J = 16.0,
5.7 Hz, 1H), 4.33 (dd, J = 5.3, 1.3 Hz, 2H)), 1.48 (br s, 1H); 13C
NMR (100 MHz, CDCl3, 25 °C, TMS) δ 137.1, 131.6, 129.0, 128.9,
128.1, 126.9, 64.2; IR (film) 3323 (OH), 3058, 3025, 2862, 1493,
1448, 1009, 967, 734, 692 cm−1.
4-Acetylbenzyl alcohol17 (2n): yellow solid; mp = 30−35 °C; 1H
NMR (400 MHz, CDCl3, 25 °C, TMS) δ 7.92 (d, J = 8.2 Hz, 2H),
7.44 (d, J = 8.0 Hz, 2H), 4.76 (s, 2H), 2.59 (s, 3H); 13C NMR (100
MHz, CDCl3, 25 °C, TMS) δ 198.6, 146.8, 136.6, 129.0, 127.0, 64.9,
27.0; IR (film) 3434 (OH), 3050, 3005, 2956, 2926, 1653, 1266, 1048,
814 cm−1.
β-Bromocinnamyl alcohol23 (4f): colorless liquid; 1H NMR
(400 MHz, CDCl3, 25 °C, TMS) δ 7.63 (d, J = 1.5 Hz, 2H), 7.39−
7.35 (m, 2H), 7.34−7.32 (m, 1H), 7.09 (s, 1H), 4.42 (d, J = 5.9 Hz,
2H), 2.14 (br s, 1H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS) δ
135.4, 129.4, 128.6, 128.3, 125.7, 69.8; IR (film) 3341 (OH), 3050,
3014, 2920, 2837, 1652, 1069, 878, 745 cm−1.
4-Methoxycarbonyl benzyl alcohol8 (2o): white solid; mp =
1
45−50 °C; H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 8.02 (d, J =
8.3 Hz, 2H), 7.43 (d, J = 8.2 Hz, 2H), 4.76 (s, 2H), 3.91 (s, 3H); 13C
NMR (100 MHz, CDCl3, 25 °C, TMS) δ 167.4, 146.4, 130.2, 129.7,
126.9, 65.0, 52.5; IR (film) 3225 (OH), 3077, 3022, 3010, 2956, 1725,
1619, 1278, 1010, 823 cm−1.
(1R)-(−)-Myrtenol24 (4g): colorless liquid; H NMR (400 MHz,
1
8
1
3-Cyanobenzyl alcohol (2p): white solid; mp = 25−30 °C; H
NMR (400 MHz, CDCl3, 25 °C, TMS) δ 7.68 (s, 1H), 7.61−7.57 (m,
3H), 4.75 (s, 2H), 2.07 (s, 1H); 13C NMR (100 MHz, CDCl3, 25 °C,
TMS) δ 142.7, 131.6, 131.4, 1306, 129.7, 119.2, 112.9, 64.4; IR (film)
3413 (OH), 3075, 3014, 2983, 1405, 808 cm−1.
CDCl3, 25 °C, TMS) δ 5.49−5.47 (m, 1H), 3.99 (s, 2H), 2.42 (dt, J =
8.6, 5.6 Hz, 1H), 2.34−2.21 (m, 2H), 2.16−2.10 (m, 2H), 1.30 (s,
3H), 1.26 (s, 1H), 1.18 (d, J = 8.6 Hz, 1H), 0.84 (s, 3H) ; 13C NMR
(100 MHz, CDCl3, 25 °C, TMS) δ 147.8, 117.9, 66.0, 43.4, 40.9, 38.0,
31.6, 31.1, 26.1, 21.1; IR (film) 3322 (OH), 2987, 2912, 2831, 1655,
1468, 1056 cm−1.
8
1
4-Nitrobenzyl alcohol (2q): yellow solid; mp = 90−95 °C; H
NMR (400 MHz, CDCl3, 25 °C, TMS) δ 8.23 (d, J = 8.8 Hz, 2H),
4824
dx.doi.org/10.1021/jo300236u | J. Org. Chem. 2012, 77, 4821−4825

The Journal of Organic Chemistry
Note
(6) Kow, R.; Nygren, R.; Rathke, M. W. J. Org. Chem. 1977, 42, 826.
(7) (a) Cha, J. S.; Park, J. H. Bull. Korean Chem. Soc. 2002, 23, 1051.
(b) Cha, J. S.; Park, J. H. Bull. Korean Chem. Soc. 2002, 23, 1377.
(8) Shaikh, N. S.; Junge, K.; Beller, M. Org. Lett. 2007, 9, 5429.
(9) Koren-Selfridge, L.; Londino, H. N.; Vellucci, J. K.; Simmons,
B. J.; Casey, C. P.; Clark, T. B. Organometallics 2009, 28, 2085.
(10) Yates, P.; Macas, T. S. Can. J. Chem. 1988, 66, 1.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: phlee@kangwon.ac.kr.
Notes
■
(11) Mayer, T.; Maier, M. E. Eur. J. Org. Chem. 2007, 4711.
(12) Weist, S.; Kittel, C.; Bischoff, D.; Bister, B.; Pfeifer, V.;
Nicholson, G. J.; Wohlleben, W.; Sussmuth, R. D. J. Am. Chem. Soc.
̈
2004, 126, 5942.
The authors declare no competing financial interest.
(13) Jessen, H. J.; Schulz, T.; Balzarini, J.; Meier, C. Angew. Chem.,
Int. Ed. 2008, 47, 8719.
(14) Zhang, J.; Gao, X.; Zhang, C.; Ma, J.; Zhao, D. Synth. Commun.
2009, 39, 1640.
(15) Ranta, J.; Kumpulainen, T.; Lemmetyinen, H.; Efimov, A. J. Org.
Chem. 2010, 75, 5178.
ACKNOWLEDGMENTS
■
This paper is dedicated to Professor Jin Soon Cha on the occasion
of his retirement. This work was supported by the CRI Program
(2012-0001245) funded by the National Research Foundation of
Korea (NRF), by an NRF grant funded by the Korea government
(MEST) (2009-0087013), and by the second phase of the Brain
Korea 21 Program in 2009. The NMR data were obtained from
the central instrumental facility in KNU. We thank Dr. Sung Hong
Kim at the KBSI (Daegu) for obtaining the HRMS data.
(16) Vicente, J.; Saura-Llamas, I.; Grunwald, C.; Alcaraz, C.
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Organometallics 2002, 21, 3587.
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4825
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