Chemoselective reduction of aldehydes and ketones by potassium diisobutyl-t-butoxy aluminum hydride (PDBBA)

Article abstract of DOI:10.1016/j.tet.2018.06.048

t-Butoxy derivatives of DIBALH [lithium diisobutyl-t-butoxyaluminum hydride (LDBBA), sodium diisobutyl-t-butoxyaluminum hydride (SDBBA), and potassium diisobutyl-t-butoxyaluminum hydride (PDBBA)] were examined as chemoselective reducing agents of carbonyl compounds. Among them, PDBBA was found to be the most efficient for the reduction of aldehydes and ketones to the corresponding alcohols in the presence of ester, amide, and nitrile substituents at ambient temperature. In addition, the optimal conditions gave higher chemoselectivity for aldehydes in the presence of ketones.

Full text of DOI:10.1016/j.tet.2018.06.048

Accepted Manuscript
Chemoselective reduction of aldehydes and ketones by potassium diisobutyl-t-butoxy
aluminum hydride (PDBBA)
Joo Yeon Kim, Won Kyu Shin, Ashok Kumar Jaladi, Duk Keun An
PII:
S0040-4020(18)30748-8
10.1016/j.tet.2018.06.048
TET 29644
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 31 March 2018
Revised Date: 18 June 2018
Accepted Date: 19 June 2018
Please cite this article as: Kim JY, Shin WK, Jaladi AK, An DK, Chemoselective reduction of aldehydes
and ketones by potassium diisobutyl-t-butoxy aluminum hydride (PDBBA), Tetrahedron (2018), doi:
10.1016/j.tet.2018.06.048.
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Chemoselective reduction of aldehydes and
ketones by potassium diisobutyl-t-butoxy
aluminum hydride (PDBBA)
Leave this area blank for abstract info.
Joo Yeon Kim, Won Kyu Shin, Ashok Kumar Jaladi, Duk Keun An*
Department of Chemistry, KangwoNational University, and Institute for Molecular Science and Fusion
Technology, Chuncheon 24341, Republic of Korea

1
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Tetrahedron
journal homepage: www.elsevier.com
Chemoselective reduction of aldehydes and ketones by potassium diisobutyl-t-butoxy
aluminum hydride (PDBBA)
Joo Yeon Kim, Won Kyu Shin, Ashok Kumar Jaladi and Duk Keun An
Department of Chemistry, Kangwon National University, and Institute for Molecular Science and Fusion Technology,
Chunchon 24341, Republic of Korea. *E-mail: dkan@kangwon.ac.kr
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
t-Butoxy derivatives of DIBALH [lithium diisobutyl-t-butoxyaluminum hydride (LDBBA),
sodium diisobutyl-t-butoxyaluminum hydride (SDBBA), and potassium diisobutyl-t-
butoxyaluminum hydride (PDBBA)] were examined as chemoselective reducing agents of
carbonyl compounds. Among them, PDBBA was found to be the most efficient for the reduction
of aldehydes and ketones to the corresponding alcohols in the presence of ester, amide, and
nitrile substituents at ambient temperature. In addition, the optimal conditions gave higher
chemoselectivity for aldehydes in the presence of ketones.
Available online
Keywords:
Chemoselectivity
Reduction
PDBBA
2009 Elsevier Ltd. All rights reserved
.
Aldehyde
Ketone
1. Introduction
DIBALH is an electrophilic reducing agent known for the
reduction of ester and nitriles to aldehydes; it can also reduce
most
carbonyl
derivatives
efficiently.11
Lithium
Reductions are fundamental and the most frequently used
chemical transformations in organic synthesis.1 Since the
invention of hydride reducing agents for functional groups like
carbonyl derivatives, there has been significant progress in the
development and identification of novel efficient reagents from
the perspectives of chemo- and stereoselectivities.1d-i The ready
availability of mild and efficient reducing agents that show good
selectivity towards multifunctional target molecules2 is also an
important aspect of basic research and development studies. To
address these issues, a wide range of reducing agents has been
designed and reported by numerous research institutions and
academies over many decades.3
pyrrolidinoborohydride (LipyrrBH3) can selectively reduce only
aldehydes and ketones in the presence of nitriles at higher
temperatures.12 Chemoselective reduction of aldehydes and
ketones over acyl chlorides and esters using LiAlH4 and silica
chloride has been reported.13 We have previously reported that
potassium diisobutyl-t-butoxyaluminum hydride (PDBBA) can
be used for the chemoselective partial reduction of esters to
aldehydes in the presence of nitriles.14
Several other chemoselective reducing agents of aldehydes
over ketones, including lithium tri-t-butoxyaluminum hydride
(LTBA)/NaBH4,15 borohydride exchange resin (BER),16
potassium triacetoxyborohydride (KBH(OAc)3)17 and zinc
The highly chemoselective reduction of aldehydes and ketones
over other carbonyl compounds has been reported widely. For
example, although lithium aluminum hydride (LiAlH4)4 is an
extremely powerful reducing agent for most organic functional
groups, it gives with no selectivity. On the other hand, sodium
borohydride (NaBH4)5 is a typical cheap and selective reducing
agent for aldehydes, ketones, and acyl chlorides. Sodium
borohydride at low temperature (−78 °C),6 with additive (excess
Na2CO3),7 resin (Dowex1-x8),8 and in polyethylene glycol
dimethyl ether (PEGDME),9 have been reported for selective
reduction of aldehydes. Generally, NaBH4 reductions involve
protic solvents such as methanol, ethanol, or mixed polar
18
borohydride Zn(BH4)2 can also be used. However, some of the
reported methods involve longer reaction times, high temperature,
or the use of additives in large excess.
DIBALH
KO-t-Bu
O
OH
PDBBA (1.1 eq)
carboxylic acid
R
Unreacted esters,
amides and nitriles
+
R
+
derivatives
0 oC / 30 min
R = H, Me
(1.0 eq)
R = H, Me
(1.0 eq)
solvents for solubility and (or) selectivity.5b,10
Scheme 1. Chemoselective reduction of aldehydes and ketones
———
Corresponding author. Tel.: +82-33-250-8494; fax: +82-33-253-7582; e-mail: dkan@kangwon.ac.kr

2
Tetrahedron
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Despite the considerable progress achieved in the past few
reduction of aldehydes and ketones
decades, there is a growing interest in identifying novel and eco-
friendly chemoselective reducing agents. As part of our ongoing
research, we have identified and reported19 several efficient
reducing agents via the simple modification of commercial
reagents. Herein, we report the chemoselective reduction of
aldehydes and ketones using PDBBA, easily prepared by the
reaction of DIBAL-H with potassium t-butoxide (Scheme 1).
2.2. Chemoselective reduction of aldehydes and ketones over
carboxylic acid derivatives.
Based on the results shown in Table 1, we chose PDBBA for
functional group screening studies. Accordingly, a series of
aldehydes and ketones (aromatic, aliphatic, and conjugated) was
treated with PDBBA in the presence of ester, amide, and nitrile
functional groups. Table 2 shows that excellent conversion was
achieved for all the studied aldehydes and ketones to the
corresponding alcohols at ambient temperature. A high degree of
chemoselectivity was achieved with both aromatic and aliphatic
functional groups. Further, conjugated aldehydes and ketones
also smoothly underwent selective reduction with PDBBA
(entries 1–14 in Table 2).
2. Results and discussion
2.1. Evaluation of chemoselective reduction with various
reducing agents
First, we screened the chemoselective reducing properties of
the t-butoxy derivatives of DIBALH, such as lithium diisobutyl-
t-butoxyaluminum hydride (LDBBA), sodium diisobutyl-t-
butoxyaluminum hydride (SDBBA), and PDBBA, and compared
the results with those obtained with commercial DIBALH and
Red-Al. Accordingly, aldehydes and ketones were reduced in the
presence of ester, amide, and nitrile functionalities. The results in
Table 1 suggest that aldehydes and ketones were reduced to the
corresponding alcohols with all the DIBALH-based reducing
agents tested (LDBBA, SDBBA and PDBBA). On the other hand,
DIBALH itself and Red-Al showed poor selectivity. LDBBA and
SDBBA showed relatively good selectivity for the reduction of
aldehyde and ketone groups over ester groups; however, ester
groups were still reduced by 12% and 8%, respectively. PDBBA
showed the best chemoselectivity towards stoichiometric
conversion to the desired product among the DIBALH-based
reducing agents tested.
Table 2. Chemoselective reduction of aldehydes and ketones
over several carboxylic acid derivatives
Substrate
Aldehyde
or
Ketone
Carboxylic acid derivatives
(1.0 eq)
PDBBA (1.1 eq)
+
Product
THF, 0 oC / 30 min
(1.0 eq)
Yield(%)a
Carboxylic acid
derivatives
Entry
Substrate
Substrate
Carboxylic acid derivatives
S.M / RCHO / ROH
S.M / ROH
O
O
O
0 /100
99 / 0 / 0
99 / 0 / 0
99 / 0 / 0
99 / 0 / 0
100 / 0 / 0
98 / 0 / 0
99 / 0 / 0
99 / 0 / 0
99 / 0 / 0
99/ 0 / 0
H
1
O
O
O
O
0 /99
0 / 97
0 /99
H
H
2
3
Table 1. Evaluation of reducing agents for the chemoselective
O
O
O
N
O
H
H
4
5
O
O
O
O
0 / 98
0 / 99
9 / 91
0 / 99
0 / 99
0 / 92
0 /99
O
O
H
H
N
6
7
N
O
O
O
8
9
O
O
O
O
O
O
10
O
O
99 / 0 / 0
100 / 0 / 0
98 / 0 / 0
99 / 0 / 0
N
11
12
O
O
0 / 98
0 / 99
5 / 94
O
O
O
O
N
13
14
N
aYields were determined by GC using authentic samples.

3
Next, the chemoselective reduction of aldehydes and ketones was
performed in multifunctionalized compounds (Table 3).
Accordingly, substrates containing ester, amide, and nitrile
moieties along with aldehydes or ketones were reduced using
PDBBA under optimized conditions (0 °C, 30 min). As expected,
the aldehydes and ketones furnished the corresponding primary
and secondary alcohols with good yields (88–94%) in the
presence of other tested functional groups (entries 1–6 in Table
3). An ꢀ,ꢁ-unsaturated ketone having an ester moiety, ethyl (E)-
4-oxo-4-phenylbut-2-enoate was treated with PDBBA. This
reaction results in formation of a mixture of products which upon
purification leads only to the isolation of the major product 4-
oxo-4-phenylbut-2-enoate in 55% yield (entry 7 in Table 3). For
4-oxopentanoate, the corresponding lactone was produced after
reduction followed by in situ cyclization in 68% yield (entry 8 in
Table 3).
alcohols was obtained). Therefore, further optimization was
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required to achieve better selectivity. We assumed that the
reduction of the aldehyde in the presence of the ketone was
mainly influenced by the temperature and solvent. To confirm
this, we performed a model reaction using benzaldehyde (1
mmol) and acetophenone (1 mmol) with PDBBA for 30 min at
−78 °C. From the H NMR spectra, it was observed that, even at
−78 °C with 5 mL THF, the reduction furnished primary and
secondary alcohols in 84% and 11% yields, respectively.
Next, the volume of solvent was increased, and the ratio of
the primary and secondary alcohols was measured. Surprisingly,
upon increasing the volume of THF (10 mL), formation of the
secondary alcohol was not observed, and a stoichiometric
conversion to the primary alcohol was obtained (Table 4).
1
Table 4. Optimization of solvent for chemoselective reduction of
aldehyde over ketone.
Table 3. Chemoselective reduction of multifunctionalized
compounds with PDBBA
PDBBA (1.3 eq)
Compound
(1.0eq)
Product
THF, 0 oC / 1 h
Isolated yield (%)
Entry
1
Compound
Product
O
OH
H
H
92
OMe
OMe
O
O
Using these modified conditions, we elaborated the scope of
the chemoselective reduction of various aldehydes in the
presences of ketones (Scheme 2). Electron-rich and -deficient
aldehydes were treated with PDBBA, affording good to excellent
selectivities with reasonable yields (73% and 81%, respectively,
for entries a and b in Scheme 2). An aromatic aldehyde
(benzaldehyde) was successfully reduced to the corresponding
alcohol with a high degree of selectivity in the presence of the
aliphatic ketone heptan-2-one (94%, entry c in Scheme 2). Next,
an aliphatic aldehyde (hexanal) was smoothly and selectively
reduced in the presence of either aromatic or aliphatic ketones,
furnishing the primary alcohol in good yield (83% and 84%,
entries d and e in Scheme 2).
O
OH
2
3
88
85
O
O
O
O
O
O
O
O
O
OH
O
OH
H
H
4
5
93a
N
N
O
O
O
OH
94a
H
H
OH
O
O
O
H
N
N
N
+
H
PDBBA
a)
b)
+
H3CO
H3CO
-78 oC, 30 min
THF
O
OH
H3CO
H3CO
>99%a
73%a
OH
93a
6
7
O
O
O
H
N
+
H
PDBBA
+
Br
Br
-78 oC, 30 min
THF
Br
Br
O
O
77%a
10
O
81%a
OH
55a
O
O
O
OH
PDBBA
(1.1 eq)
O
H
O
+
H
c)
d)
O
-78 oC, 30 min
THF
+
O
68a
O
O
8
94%b
O
94%b
O
O
O
OH
a PDBBA used 1.5 eq.
PDBBA
+
+
H
H
-78 oC, 30 min
THF
2.3. Chemoselective reduction of aldehydes over ketones
94%b
O
83%b
Under optimized conditions, aldehydes and ketones were
reduced chemoselectively using PDBBA in the presence of ester,
tertiary amide, and nitrile functional groups with good to
excellent conversion at 0 °C for 30 min (by GC). Next, we
probed the chemoselective reduction of aldehydes in the presence
of ketones. Accordingly, benzaldehyde (1 mmol) and
acetophenone (1 mmol) were treated with PDBBA under the
optimized conditions. However, we could not obtain significant
selectivity for the reduction of the aldehyde over the ketone
under these conditions (a 1:1 ratio of primary and secondary
OH
O
O
+
PDBBA
+
H
H
-78 oC, 30 min
THF
e)
84%b
80%b
aYields were determined by 1H NMR using internal standerd. bYields were determined by GC using
authentic samples.
Scheme 2. Intermolecular chemoselective reduction of aldehydes
over ketones with PDBBA.
These results encouraged us to carry out the intramolecular
chemoselective reduction of 4-acetylbenzaldehyde (Scheme 3).

4
Tetrahedron
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We easily obtained the desired product in 93% yield,
colorless homogeneous solution. The concentration of PDBBA
suggesting that PDBBA can be an alternative chemoselective
reducing agent for aldehydes over ketones.
solution in THF-hexane was measured gasometrically by
hydrolysis of an aliquot of the solution with a hydrolyzing
mixture of t-butyl alcohol-THF (1:1) at 0 °C.
4.3 Determination of PDBBA concentration by gas burette
experiment
The concentration of the prepared reducing agent (PDBBA)
was measured using a gas burette apparatus as the following
procedure.
Scheme 3. Intramolecular chemoselective reduction of 4-
A two necked round bottom flask with condenser was
connected to gas burette using a laboratory Tygon tube. All the
joints were double-sealed with vacuum grease and para-films.
After argon gas was introduced into the measuring apparatus
through round bottom flask for 5 minutes (total apparatus was
filled with argon), a solution of t-butanol and THF in 1:1 ratio
was added to the reaction vessel. To this 1 mmol of PDBBA was
added with continuous stirring. The amount of hydrogen gas
liberated was measured to determine the concentration of the
PDBBA (experiment was repeated 3 times for consistent results).
acetylbenzaldehyde with PDBBA
3. Conclusion
In summary, we have demonstrated that recently prepared t-
butoxy derivatives of DIBALH, such as LDBBA, SDBBA, and
PDBBA, can be used as chemoselective reducing agents for
aldehydes and ketones in the presence of esters. From the
experimental results, we concluded that PDBBA was the most
efficient and selective reagent among the reagents studied herein.
In addition, higher chemoselectivity was achieved with the
modified DIBALH-based reducing agents (LDBBA, SDBBA,
and PDBBA) than those obtained with commercial reducing
4.4 Chemoselective reduction of aldehydes and ketones with
PDBBA (Table 1 and 2)
agents. Furthermore,
the value of this approach lies in the
A dry and argon-flushed flask, equipped with a magnetic
stirring bar and a septum, was charged with aldehyde or ketone
(0.5 mmol), carboxylic acid derivative (0.5 mmol) and 5 mL
THF. After cooling to 0 °C, PDBBA (0.55 mmol) was added
dropwise and stirred for 30 min at same temperature. The
reaction was stopped by the addition of aqueous 1 N HCl (5 mL)
and extracted with diethyl ether (2 x 10 mL). The combined
organic layers were dried over MgSO4 and GC analysis. All
products in Table 2 were confirmed through comparison with GC
data of authentic sample.
selective reduction of aldehydes in the presence of ketones using
the modified reaction conditions. Therefore, the readily prepared
novel reagent (PDBBA) seems to be a valuable alternative to
existing hydride reagents.
4. Experimental
4.1 General methods
All glassware used was dried thoroughly in an oven,
assembled hot, and cooled under a stream of dry nitrogen prior to
use. All reactions and manipulations of air- and moisture
sensitive materials were carried out using standard techniques for
the handling of air-sensitive materials. All chemicals were
commercial products of the highest purity which were further
purified before use by standard methods. THF was dried over
sodium-benzophenone and distilled. DIBALH, esters, aldehydes,
and alcohols were purchased from Aldrich Chemical Company,
4.5 Chemoselective reduction of dicarbonyl compounds with
PDBBA (Table 3)
A dry and argon-flushed flask, equipped with a magnetic
stirring bar and a septum, was charged with dicarbonyl
compound (1.0 mmol) and 10 mL THF. After cooling to 0 °C,
PDBBA (1.3 mmol) was added dropwise and stirred for 1 h at
same temperature. The reaction was stopped by the aqueous 1 N
HCl (10 mL) and extracted with diethyl ether (2 x 10 mL). The
combined organic layers were dried over MgSO4, filtered and
concentrated under reduced pressure. Purification of the residue
by column chromatography on silica gel afforded the desired
product.
Methyl 4-(hydroxymethyl)benzoate (1): 1H-NMR (400 MHz,
CDCl3) δ: 8.02 (2H, d, J = 8.2 Hz), 7.43 (2H, d, J = 8.0 Hz), 4.76
(2H, d, J = 5.9 Hz), 3.90 (3H, s); 13C NMR (100 MHz, CDCl3) δ:
167.0, 146.0, 129.9, 129.4, 126.5, 64.81, 52.2; HRMS (EI+):
calcd for C9H10O3, 166.0630; found 166.0630.
1
Alfa Aesar and Tokyo Chemical Industry Company (TCI). H-
NMR spectra were measured at 400 MHz with CDCl3 as a
solvent at ambient temperature unless otherwise indicated and the
chemical shifts were recorded in parts per million downfield
from tetramethylsilane (δ = 0 ppm) or based on residual CDCl3 (δ
= 7.26 ppm) as an internal standard. 13C NMR spectra were
recorded at 100 MHz with CDCl3 as a solvent and referenced to
the central line of the solvent (δ = 77.0 ppm). The coupling
constants (J) are reported in Hertz. Analytical thin-layer
chromatography (TLC) was performed on glass precoated with
silica gel (Merck, silica gel 60 F254). Column chromatography
was carried out using 70–230 mesh silica gel (Merck) at normal
pressure. GC analyses were performed on a Younglin Acme
6100GC and 6500GC FID chromatography, using an HP-5
capillary column (30m). All GC yields were determined with the
use of naphthalene as internal standard and authentic samples.
Ethyl 4-(1-hydroxyethyl)benzoate (2): 1H-NMR (400 MHz,
CDCl3) δ: 7.99-7.91 (2H, m), 7.43-7.34 (2H, m), 4.94-4.83 (2H,
m), 4.36-4.27 (2H, m), 1.49-1.40 (3H, m), 1.41-1.30 (3H, m); 13
C
NMR (100 MHz, CDCl3) δ: 166.6, 151.0, 129.8, 125.3, 69.9,
61.0, 25.3, 14.3; HRMS (EI+): calcd for C11H14O3, 194.0943;
found 194.0944.
Ethyl 2-hydroxy-2-phenylacetate (3): 1H-NMR (400 MHz,
CDCl3) δ: 7.44-7.29 (5H, m), 5.15 (1H, s), 4.31-4.10 (2H, m),
1.21 (3H, t, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3) δ: 173.8,
138.4, 128.6, 128.5, 126.6, 72.9, 62.3, 14.1; HRMS (EI+): calcd
for C10H12O3, 180.0786; found 180.0788.
4.2 Preparation of PDBBA
A dry and argon-flushed flask, equipped with a magnetic
stirring bar and a septum, was charged with potassium t-butoxide
(5.89 g, 52.5 mmol) and 50 mL THF. After cooling to 0 °C,
DIBALH (50 mL, 1.0 M in hexane, 50 mmol) was added
dropwise and stirred for 2 h at room temperature to give a

5
1
L.; Goralski, C. T.; Singaram, B. Org. Process Res.
4-(Hydroxymethyl)-N,N-dimethylbenzamide (4): H-NMR (400
ACCEPTED MANUSCRIPT
Dev., 2006, 10 (5), 959; (h) Eagon, S.; Jones, N. B.; Haddenham,
D.; Saavedra, J.; DeLieto, C.; Buckman, M.; Singaram, B.
Tetrahedraon Lett., 2010, 51 (49), 6418; (i) Magano, J.; Dunetz, J.
R. Org. Process Res. Dev. 2012, 16, 1156.
MHz, CDCl3) δ: 7.30-7.18 (4H, m), 4.57 (2H, s), 3.79 (1H, s),
3.04 (3H, s), 2.91 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 179.9,
143.3, 134.6, 127.1, 126.4, 64.2, 39.7, 35.4; HRMS (EI+): calcd
for C10H13NO2, 179.0946; found 179.0942.
2. (a) Commandeur, M.; Commandeur, C.; Cossy, J. Org. Lett.,
2011, 13, 6018; (b) Sharpe, R. J.; Malinowski, J. T.; Johnson, J. S.
J. Am. Chem. Soc., 2013, 135 (47), 17990; (c) Krishnamurthy, S.
J. Org. Chem., 1981, 46 (22), 4628.
1
4-(Hydroxymethyl)benzonitrile (5): H-NMR (400 MHz, CDCl3)
δ: 7.54 (2H, d, J = 8.0 Hz), 7.40 (2H, d, J = 8.0 Hz), 4.68 (2H, s),
3.24 (1H, s); 13C NMR (100 MHz, CDCl3) δ: 146.7, 132.3, 127.0,
119.0, 110.6, 63.9; HRMS (EI+): calcd for C8H7NO, 133.0528;
found 133.0525.
3. (a) Weissman, P. M.; Brown, H. C. J. Org. Chem., 1966, 31, 283;
(b) Yoon, N. M.; Ahn, J. H.; An, D. K.; Shon, Y. S. J. Org.
Chem., 1993, 58, 1941; (c) Brown, H. C.; Bigley, D. B.; Arora, S.
K.; Yoon, N, M. J. Am. Chem. Soc., 1970, 92, 7161; (d) Muraki,
M.; Mukaiyama, T. Chem. Lett., 1975, 215; (e) Cha, J. S.; Kwon,
S. S. J. Org. Chem., 1987, 52, 5486; (f) Cha, J. S.; Kwon, S. S. J.
Org. Chem., 1990, 55, 1692; (g) Cha, J. S. Bull. Korean Chem.
Soc., 1992, 13, 670; (h) Cha, J. S.; Kwon, O. O.; Kim, J. M.; Lee,
J. C. Bull, Korean Chem. Soc., 1994, 15, 644; (i) Nahm, S.;
Weinreb, S. M. Tetrahedron Lett., 1981, 22, 3815.
1
4-(1-Hydroxyethyl)benzonitrile (6): H-NMR (400 MHz, CDCl3)
δ: 7.58 (2H, d, J = 8.2 Hz), 7.45 (2H, d, J = 8.6 Hz), 4.91 (1H, q,
J = 6.3 Hz), 2.66 (1H, s), 1.44 (3H, dd, J = 6.5, 0.4 Hz); 13C
NMR (100 MHz, CDCl3) δ: 151.4, 132.3, 126.1, 119.0, 110.8,
69.6, 25.4; HRMS (EI+): calcd for C9H9NO, 147.0684; found
147.0688.
Ethyl (E)-4-hydroxy-4-phenylbut-2-enoate (7): 1H-NMR (400
MHz, CDCl3) δ: 7.41-7.27 (5H, m), 7.04 (1H, dd, J = 15.6, 4.8
Hz), 6.16 (1H, dd, J = 15.6, 1.7 Hz), 5.39-5.32 (1H, m), 4.18
(2H, q, J = 7.1 Hz), 2.14 (1H, d, J = 3.8 Hz), 1.27 (3H, t, J = 7.2
Hz); 13C NMR (100 MHz, CDCl3) δ: 166.5, 148.4, 140.9, 128.9,
128.5, 126.6, 120.3, 73.9, 60.6, 14.3; HRMS (EI+): calcd for
C12H14O3, 206.0943; found 206.0947.
5-Methyldihydrofuran-2(3H)-one (8): 1H-NMR (400 MHz,
CDCl3) δ: 4.43-4.23 (1H, m), 2.32-2.14 (2H, m), 2.13-1.98 (1H,
m), 1.62-1.45 (1H, m), 1.08 (3H, d, J = 6.6 Hz); 13C NMR (100
MHz, CDCl3) δ: 177.2, 77.1, 29.4, 28.8, 20.7; HRMS (EI+): alcd
for C5H8O2, 100.0524; found 100.0524.
4. For
a review of hydride reductions, see Brown, H. C.;
Ramachandran, P. V. in Reductions in Organic Synthesis. Recent
Advances and Practical Applications, A. F. Abdel-Magid, Ed.
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Mark, F. S.; William, T. P.; Gregory, H. R. Inorganica Chim. Acta,
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4.6 Chemoselective reduction of 4-acetylbenzaldehyde (Scheme
2)
A dry and argon-flushed flask, equipped with a magnetic
stirring bar and
a
septum, was charged with 4-
acetylbenzaldehyde (0.13 mL, 1.0 mmol) and THF (10 mL).
After cooling to −78 °C, PDBBA (1.3 mmol) was added
dropwise and the mixture was stirred for 1 h at the same
temperature. The reaction was stopped aqueous 1 N HCl (10 mL)
and extracted with diethyl ether (2 x 10 mL). The combined
organic layers were dried over MgSO4, filtered and concentrated
under reduced pressure. Purification of the residue by column
12. Christopher, J. C.; Gary, B. F.; Adeena R.; Christian T. G.;
Bakthan S. Tetrahedron Lett. 1997, 38, 529.
13. Hosseinia, A.; Khalilzadeha, M. A. Tajbakhsh, M.;
Mohannazadeh, F. J. Iran. Chem. Soc. 2008, 5, 699.
chromatography
on
silica
gel
yielded
1-(4-
(hydroxymethyl)phenyl)ethan-1-one (139 mg, 93%).
14. Chae, M. J.; Song, J. I.; An, D. K. Bull. Korean Chem. Soc. 2007,
28, 2517.
15. Sell, S. C. Aust. J. Chem. 1975, 28, 1383.
16. Yoon, N. M. Pure & Appl. Chem. 1996. 68. 843.
17. Tolstikov, G. A.; Odinokov, V. N.; Galeeva, R. I.; Bakeeva, R. S.;
Akhunova, V. R. Tetrahedron Lett. 1979, 4851.
1
1-(4-(Hydroxymethyl)phenyl)ethan-1-one : H-NMR (400 MHz,
CDCl3) δ: 7.86 (2H, d, J = 8.6 Hz), 7.38 (2H, d, J = 8.6 Hz), 4.70
(2H, s), 2.53 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 198.4,
146.6, 136.1, 128.6, 126.6, 64.4, 26.7; HRMS (EI+): calcd for
C9H10O2, 150.0681; found 150.0682.
18. Ranu, B. C. Synlett 1993, 885.
19. (a) Ahn, J. H.; Song, J. I.; Ahn, J. E.; An, D. K. Bull. Korean
Chem. Soc. 2005, 26, 377; (b) Kim, M. S.; Choi, Y. M.; An, D. K.
Tetrahedron Lett. 2007, 48, 5061; (c) Song, J. I.; An, D. K. Chem.
Lett. 2007, 36, 886; (d) Chae, M. J.; Song, J. I.; An, D. K. Bull.
Korean Chem. Soc. 2007, 28, 2517; (e) Choi, S. J.; Lee, K. J.; Lee,
G. B.; An, D. K. Bull. Korean Chem. Soc., 2008, 29, 1407; (f)
Kim, Y. R.; An, D. K. Bull. Korean Chem. Soc., 2012, 33, 4194;
(g) Jeon, A. R.; Kim, M. E.; Park, J. K.; Shin, W. K.; An, D. K.
Tetrahedron 2014, 70, 4420; (h) Shin, W. K.; Jang, H. M.; Choi,
B. H.; Yoo, J.; An, D. K. Bull. Korean Chem. Soc., 2015, 36,
1919; (i) Park, J. Y.; Shin, W. K.; Jaladi, A. K.; An, D. K.
Tetrahedron Lett. 2016, 57, 3247.
Acknowledgments
This research was supported by a National Research
Foundation of Korea Grant funded by the Korean Government
(2012R1A1B6000451).
References and notes
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