Wet THF as a suitable solvent for a mild and convenient reduction of carbonyl compounds with NaBH4

Article abstract of DOI:10.1246/bcsj.78.307

NaBH4 in wet THF can readily reduce varieties of carbonyl compounds such as aldehydes, ketones, conjugated enones, acyloins, and α-diketones to their corresponding alcohols in good to excellent yields. Reduction reactions were performed at room temperature or under reflux condition. In addition, the chemoselective reduction of aldehydes over ketones was accomplished successfully with this reducing system.

Full text of DOI:10.1246/bcsj.78.307

Ó 2005 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 78, 307–315 (2005)
307
Wet THF as a Suitable Solvent for a Mild and Convenient Reduction
of Carbonyl Compounds with NaBH4
ꢀ
Behzad Zeynizadeh and Tarifeh Behyar
Department of Chemistry, Faculty of Sciences, Urmia University, Urmia 57159-165, Iran
Received July 5, 2004; E-mail: b.zeynizadeh@mail.urmia.ac.ir
NaBH4 in wet THF can readily reduce varieties of carbonyl compounds such as aldehydes, ketones, conjugated
enones, acyloins, and ꢀ-diketones to their corresponding alcohols in good to excellent yields. Reduction reactions were
performed at room temperature or under reflux condition. In addition, the chemoselective reduction of aldehydes over
ketones was accomplished successfully with this reducing system.
Reduction of carbonyl compounds is one of the most ubiq-
uitous reactions in organic synthesis. The discovery of NaBH4
in 1942 brought about revolutionary changes in this area. Al-
though sodium borohydride has been known as a mild reduc-
ing agent, it is still a useful reagent for the reduction of alde-
In spite of the convenient selectivity and efficiency of the
reductions with NaBH4 in aprotic solvent systems relative to
protic ones and the well-known study, performing the reduc-
tions under wet-aprotic solvent systems has been less investi-
gated and there are only a few reports in this area, e.g., the
kinetic study of reduction of carbonyl compounds was reported
1
1
hydes and ketones in alcoholic solvents. However, it should
1
0m
be pointed out that, in spite of its great convenience, this re-
agent suffers from certain limitations: e.g., essential need to
use polar and protic solvents, limited number of functional
groups that can be reduced, the sometimes low reaction rate,
and a low selectivity between carbonyl compounds. This situa-
tion made it desirable to develop means for controlling the re-
ducing power of such a reagent. Therefore, controlling the re-
ducing power of sodium borohydride has been one of the main
interests for organic chemists over many years. In fact, advan-
ces in this field have been realized by: a) substitution of the hy-
dride(s) with other groups which may exert marked steric and
electronic influences upon the reactivity of the substituted
with NaBH4 in H2O, DMSO, or their mixture as a solvent.
10n
The chemoselective reduction of diarydisulfides, and selec-
tive reduction of nitroalkenes in wet THF and reduction of
10o
0q
azides in wet toluene1 were also reported with NaBH4. In ad-
1
0p
dition, the reduction of esters in a mixture of H2O–dioxane
and phenylalanine ethyl ester in H2O–THF1 are other reports
which have dealt with this reducing agent. So, in the line of our
outlined strategies and our ongoing attention to the develop-
ment of new modified hydroborate agents in organic synthesis,
here we report an extensive and efficient protocol for reduction
of varieties of carbonyl compounds with NaBH4 under wet
THF conditions.
0r
2
complex ion; b) variation in the alkali metal cation and metal
cation in the complex hydride which would alter the reducing
Results and Discussion
3
power of the reagent; c) by concurrent cation and hydride
4
Reduction of Aldehydes and Ketones. Transformation of
aldehydes and ketones to their alcohols is one of the easiest
exchange; d) use of ligands to alter behavior of the metal
5
1
hydrides; e) combination of borohydrides with metal, metal
6
ways for the preparation of alcohols in organic synthesis. Hy-
salts, Lewis acids, and some other agents; f) changing the cat-
7
dride transferring agents such as lithium aluminum hydride
and sodium borohydride are the reagents commonly used for
these purposes. LiAlH4 as a powerful reducing agent shows
poor selectivity for the reduction of multifunctional molecules.
On the other hand, NaBH4 is a mild reducing agent and is used
for the reduction of a few organic functional groups with some
restrictions, which were mentioned above. To overcome the
limitations and to facilitate reduction reactions of sodium
borohydride with desired selectivity and efficiency, many im-
ion to quaternary and phosphonium borohydrides; and finally,
g) use of polymers or solid beds for supporting the hydride
8
species. The preparation and application of modified hydrobo-
rate agents in organic synthesis have been reviewed extensive-
5
d,9
ly.
Performing of the reductions with NaBH4 in protic solvents,
especially MeOH, is the commonly used procedure.1
However, the presence of some drawbacks for this reducing
agent in protic solvents has led the chemists to use aprotic sys-
a,b,10a,b
provements such as new combination systems of NaBH4 have
5d,9
tems or mixtures of protic–aprotic solvent systems10d–i for
different reduction purposes. In addition, to reach the desired
selectivity and efficiency in the reductions with NaBH4 while
raising the solubility behavior of reaction components, re-
1
0c
been announced in the literature.
NaBH4 in mixed solvents,
especially MeOH-containing systems,1
for some reduction purposes; however, for the reduction of
0d–f,h,i,l
has been used
carbonyl compounds under wet-aprotic solvent systems, as
10m,11
10j–l
search groups were also attracted to apply wet-protic
wet-aprotic
and
solvent systems as efficient media for reduc-
tion of functional groups.
far as we know, there are only two reports.
In addition
1
0m–r
to the kinetic study of reduction of carbonyl compounds in
wet DMSO,1 very recently, this transformation has been also
0m
Published on the web February 11, 2005; DOI 10.1246/bcsj.78.307

3
08 Bull. Chem. Soc. Jpn., 78, No. 2 (2005)
Wet THF as a Suitable Solvent for Reduction
Table 1. Optimization of Reaction Conditions and Water Amount as a Co-solvent in the Reduction of Benzaldehyde
and Benzophenone with NaBH4
Reaction components
Molar ratio
Entry
Solvent/mL
Condition
Time/min
Conversion/%
1
2
3
4
5
6
7
8
9
PhCHO/NaBH4 (1:1)
PhCHO/NaBH4 (1:1)
PhCHO/NaBH4 (1:0.5)
PhCHO/NaBH4 (1:0.5)
PhCHO/NaBH4 (1:0.5)
PhCHO/NaBH4 (1:0.5)
PhCHO/NaBH4 (1:0.4)
PhCHO/NaBH4 (1:0.25)
PhCHO/NaBH4 (1:0.5)
PhCOPh/NaBH4 (1:2)
Dry THF (3 mL)
RT
RT
RT
RT
RT
RT
RT
RT
80
90
20
5
4
2
15
3 h
10
50
100
100
100
100
100
100
100
90
Dry CH3CN (3 mL)
THF–H2O (3:0.05 mL)
THF–H2O (3:0.1 mL)
THF–H2O (3:0.2 mL)
THF–H2O (3:1 mL)
THF–H2O (3:0.1 mL)
THF–H2O (3:0.05 mL)
CH3CN–H2O (3:0.1 mL)
THF–H2O (3:0.1 mL)
RT
Reflux
100
100
1
0
reported with NaBH4 in the presence of a polymeric solid–
liquid phase transfer catalyst under wet THF condition.11
Our successes in finding new combination systems of
NaBH45b–g,12 and the lack of systematic information on the
reduction of carbonyl compounds with sodium borohydride
in a wet-aprotic solvent system without using any other agents,
encouraged us to focus on this subject and to investigate the
influence of water as a wet species in this transformation.
Our preliminary experiments showed that reduction of benz-
aldehyde as a model compound with one molar amount of
NaBH4 took place within 80–90 min in dry THF or CH3CN
at room temperature. When this reaction was carried out in
the presence of a small amount of water, however, the rate
of reduction was dramatically accelerated and the reaction
was completed in 5 min while using lower amounts of reduc-
ing agent (Table 1).
These results prompted us to investigate the optimum reac-
tion conditions for the influence of water as a co-solvent. For
the selection of appropriate solvent(s) and water amounts in
such reductions, we examined a set of experiments on the re-
duction of benzaldehyde and benzophenone as model com-
pounds with NaBH4 in wet THF or CH3CN (Table 1). The re-
sults showed that the reduction of benzaldehyde at room tem-
perature with 0.5 molar amount of NaBH4 in a mixture of
50 min (Table 1, entry 10). To clarify the influence of water in
this reduction, we carried out reduction of benzophenone with
3 molar amounts of NaBH4 under refluxing dry THF for 12 h.
In this case, the progress of reduction was very poor (5–8%)
and the unreacted starting material was recovered from the
reaction mixture.
The utility of this reducing system was further explored with
the reduction of structurally different aliphatic and aromatic
ketones by using 2–3 molar amounts of NaBH4 in THF–H2O
(3:0.1 mL) under reflux condition. Such reductions were also
efficient and the corresponding secondary alcohols were ob-
tained in high to excellent yields (85–99%) (Table 3). The
work-up procedure of the reductions was simple: adding dis-
tilled water to the reaction mixture and then extracting with
CH2Cl2 afforded the crude product alcohols for further purifi-
cation by a short column chromatography on silica gel.
The chemoselective reduction of one functional group with-
out affecting the other one is a well-known strategy for prepar-
ing of the molecules with ever-increasing complexity in organ-
ic synthesis. This subject is of great interest13 and numerous
modified hydroborate systems have been reported for
5,7a,b,12–15
it.
Since under the defined conditions, reduction of al-
dehydes and ketones with sodium borohydride under wet THF
condition is temperature-dependent, therefore, we thought that
this system can have a chemoselectivity towards reduction of
aldehydes over ketones. This fact was demonstrated with the
selective reduction of benzaldehyde in the presence of aceto-
phenone using 0.5 molar amount of NaBH4 at room tempera-
ture (Scheme 1).
The chemoselectivity of the reduction was perfect and ben-
zyl alcohol was obtained as the sole product besides acetophe-
none as an intact material (Table 4). The usefulness of this
process was further examined with the reduction of benzalde-
hyde in the presence of other ketones such as benzophenone or
cyclohexanone. We also observed that either aldehyde is re-
duced exclusively or nearly so. In the next attempt, we applied
this procedure for the reduction of two ketones such as 9-fluo-
renone or 4-phenyl-2-butanone versus acetophenone; here, it
was found that 9-fluorenone and 4-phenyl-2-butanone were
reduced in high chemoselectivity (Table 4).
3
:0.1, 3:0.2, and 3:1 mL of THF–H2O was very efficient. How-
ever, we found that the existing of additional amounts of water
in the reaction mixture decreased the selectivity in the reduc-
tions. Therefore, a mixture of THF–H2O (3:0.1 mL) was se-
lected as best for reduction of aldehydes (Table 1, entry 4). Re-
duction reaction in a mixture of CH3CN–H2O (3:0.1 mL) was
also efficient but wet THF provided faster reaction rate. We
then applied this optimal condition for the reduction of struc-
turally different aliphatic and aromatic aldehydes. All the reac-
tions were performed with 0.5–0.8 molar amounts of NaBH4 at
room temperature and their primary alcohols were obtained in
high to excellent yields (83–99%) (Table 2).
Next, we turned our attention to the reduction of ketones
with the experiment in which benzophenone was used as a
model compound. The low reactivities of ketones relative to
those of aldehydes led us to perform reduction reactions in a
drastic condition: the reductions were performed with 2 molar
amounts of NaBH4 in refluxing wet THF or wet CH3CN. Be-
cause of the faster reaction rate, a mixture of THF–H2O (3:0.1
mL) was also a suitable solvent; the reaction was completed in
Regioselective 1,2-Reduction of Conjugated Carbonyl
Compounds. Regioselective 1,2-reduction of ꢀ,ꢁ-unsaturat-
ed aldehydes and ketones to allylic alcohols is a widely utiliz-
ed procedure in organic synthesis; considerable interest have

B. Zeynizadeh et al.
Bull. Chem. Soc. Jpn., 78, No. 2 (2005)
309
aÞ
Table 2. Reduction of Aldehydes to Their Alcohols with NaBH4 in Wet THF
Molar ratio
NaBH4/Subs.
bÞ
Entry
Substrate
Product
Time/min
Yield/%
94
1
2
CHO
CH OH
0.5:1
0.5:1
5
3
2
Cl
CHO
CHO
Cl
CH OH
96
2
CH OH
2
3
4
0.5:1
0.5:1
2
2
96
95
Cl
Cl
CHO
CH OH
2
Cl
Cl
5
6
Me
CHO
CHO
CHO
Me
CH OH
0.5:1
0.5:1
8
98
99
2
MeO
MeO
CH OH
12
2
CH OH
2
7
8
9
0.5:1
0.8:1
0.5:1
6
20
3
95
93
96
MeO
HO
MeO
HO
CHO
CH OH
2
CHO
CH OH
2
CHO
CH OH
2
1
1
1
1
0
1
2
3
0.5:1
0.5:1
0.7:1
0.5:1
3
2
3
2
91
94
94
96
O N
O N
2
2
CHO
NO2
CHO
CHO
OH
CH OH
2
NO2
CH OH
2
CH OH
2
Br
Br
Br
OH
CHO
CHO
OH
CH OH
2
CH OH
2
Br
OH
1
1
4
5
0.7:1
0.5:1
3
2
92
95
CHO
NO2
CH OH
2
NO2
MeO
CHO
MeO
CH OH
2
HO
HO
OHC
CHO
Ph
HOH C
CH OH
2
2
1
1
6
7
0.7:1
0.5:1
3
1
96
96
Ph
Ph
Ph
O
O
CHO
CH OH
2
N
Cl
N
Cl
O
1
1
8
9
CH OH
0.5:1
0.5:1
15
5
90
83
2
H
CHO
CH OH
2
a) All reactions were performed in THF–H2O (3:0.1 mL) at room temperature. b) Yields refer to isolated
pure products.

3
10 Bull. Chem. Soc. Jpn., 78, No. 2 (2005)
Wet THF as a Suitable Solvent for Reduction
aÞ
Table 3. Reduction of Ketones to Their Alcohols with NaBH4 in Wet THF
Molar ratio
NaBH4/Subs.
bÞ
Entry
Substrate
Product
Time/min
Yield/%
96
Ph
Ph
Ph
Ph
O
OH
1
2
2:1
2:1
20
50
COCH3
CH(OH)CH3
90
COCH3
CH(OH)CH3
Cl
3
2:1
20
92
Cl
COCH CH
4
5
6
Cl
Cl
CH(OH)CH CH3
2:1
2:1
3:1
15
15
25
98
94
95
2
3
2
COCH3
CH(OH)CH3
HO
COPh
HO
CH(OH)Ph
OH
O
7
8
9
2:1
2:1
2:1
12
20
15
99
94
96
O
OH
O
HO
Cl OH OH
Cl
O
OH
10
2:1
10
93
CH3
CH3
1
1
1
2
O
OH
2:1
2:1
5
85
93
O
OH
10
Ph
CH3
Ph
CH3
OH
1
1
3
4
2:1
2:1
8
96
90
O
O
45
OH
a) All reactions were performed in THF–H2O (3:0.1 mL) under reflux condition. b) Yields refer to isolated pure
products.
CHO
CH OH
100%
0%
2
THF-H O (3:0.1 ml), RT, 5 min.
2
NaBH /aldehyde/ketone
4
COCH3
CH(OH)CH3
(0.5:1:1)
Scheme 1.
been shown in the development of various hydride transferring
1
potential and selectivity of NaBH4 into regioselective 1,2-
reduction of conjugated enones, numerous hydroborate agents
have been developed in the following ways: a) by the replace-
ment of hydride(s) with sterically bulky substituents or elec-
tron-withdrawing/releasing groups in order to discriminate be-
agents. Reduction of unsaturated carbonyl compounds with
sodium borohydride, one of the most widely utilized reducing
agents, is highly solvent dependent and generally does not re-
To control the reducing
sult in a useful regioselectivity.1
0l,16,17

B. Zeynizadeh et al.
Bull. Chem. Soc. Jpn., 78, No. 2 (2005)
311
aÞ
Table 4. Competitive Reduction of Aldehydes and Ketones to Their Alcohols with NaBH4 in Wet THF
bÞ
cÞ
cÞ
Entry
1
Substrate 1
Substrate 2
Molar ratio
0.5:1:1
Condition Time/min Conv. 1/%
Conv. 2/%
0
CHO
COCH3
RT
RT
RT
5
5
6
100
100
100
Ph
O
CHO
CHO
2
3
0.5:1:1
0.5:1:1
0
Ph
O
10
COCH3
4
5
2:1:1
2:1:1
Reflux
Reflux
15
10
100
100
12
8
O
Ph
CH3
COCH3
O
a) All reactions were performed in THF–H2O (3:0.1 mL) at room temperature or under reflux condition. b) Molar
ratio as NaBH4/Subs. 1/Subs. 2. c) Conversions refer to TLC monitoring and isolated pure products.
aÞ
Table 5. Reduction of Conjugated Carbonyl Compounds with NaBH4 in Wet THF
Molar ratio
NaBH4/Subs.
Ratio
1,2:1,4
bÞ
Time/min Yield/%
Entry
1
Substrate
Product
Condition
RT
O
CH OH
1:1
2:1
2:1
1:1
100:0
100:0
100:0
100:0
1
8
92
95
97
90
2
Ph
Ph
Ph
H
Ph
Ph
O
O
OH
CH3
OH
Ph
2
3
4
Reflux
Reflux
RT
CH3
12
12
Ph
Ph
O
CH OH
2
H
O
OH
CH
5
CH3
3
2:1
Reflux
100:0
15
93
a) All reactions were performed in THF–H2O (3:0.1 mL) at room temperature or under reflux condition. b) Yields refer to
isolated pure products.
tween the structural and electronic environments of carbonyl
showed that our procedure was also regioselective and effi-
cient, but reduction reactions were performed by using 2 molar
amounts of NaBH4 under reflux condition. Regioselective 1,2-
reductions of benzalacetone, benzalacetophenone and ꢁ-ion-
one were achieved successfully, with high to excellent yields
of the corresponding allylic alcohols (Table 5).
1
7–20
21–23
groups;
solvent systems;
and their new modifications;5
b) combination with Lewis acids
and mixed
1
0l,16
c) use of transition metal hydroborates
c–e,24
d) use of quaternary ammo-
7
nium and phosphonium tetrahydroborates; and finally, e) im-
mobilization on an anion exchange resin.25
The usefulness of this reducing system was further investi-
gated with the regioselective 1,2-reduction of ꢀ,ꢁ-unsaturated
carbonyl compounds. We first examined reduction of cinnam-
aldehyde as a model compound with sodium borohydride un-
der wet condition. The reduction reaction took place with
one molar amount of NaBH4 in THF–H2O (3:0.1 mL) at room
temperature. The reaction was completed in one minute with a
perfect regioselectivity. The product cinnamyl alcohol was ob-
tained in high yield (Table 5, entry 1). This procedure was also
applied for the reduction of citral at room temperature and ger-
aniol was obtained regioselectively in 90% yield. In the next
attempt, we examined the reductions of conjugated enones
with sodium borohydride under wet condition. The results
The chemo- and regioselectivity of this procedure were
demonstrated by a competitive reduction of cinnamaldehyde
over benzalacetone (Scheme 2). In addition, selective reduc-
tion of cinnamaldehyde and citral over ꢁ-ionone were achiev-
ed successfully with this reducing system at room temperature
(Table 6).
Reduction of ꢀ-Diketones and Acyloins. Synthetic utilit-
ies of vicinal diols are well known and their preparations from
the reduction of acyloins or ꢀ-diketones have attracted a great
deal of attention. Reduction of ꢀ-diketones usually gives a
mixture of ꢀ-hydroxy ketones and vicinal diols. Selective re-
26
27
duction of ꢀ-diketones to acyloins or vicinal diols can be
undergone with some chemical or biochemical reagents. Re-

3
12 Bull. Chem. Soc. Jpn., 78, No. 2 (2005)
Wet THF as a Suitable Solvent for Reduction
O
CH OH
2
100%
0%
Ph
Ph
H
Ph
Ph
THF-H O (3:0.1 ml), RT, 2 min
2
O
NaBH /aldehyde/ketone
OH
CH
4
CH3
(
1:1:1)
3
Scheme 2.
aÞ
Table 6. Competitive Reduction of Conjugated Carbonyl Compounds with NaBH4 in Wet THF
bÞ
cÞ
cÞ
Entry
1
Substrate 1
Substrate 2
Molar ratio
1:1:1
Time/min
2
Conv. 1/%
100
Conv. 2/%
0
O
O
Ph
H
H
Ph
CH3
O
O
2
3
CH3
1:1:1
1:1:1
2
100
100
0
5
Ph
O
O
CH3
15
H
a) All reactions were performed in THF–H2O (3:0.1 mL) at room temperature. b) Molar ratio as NaBH4/Subs. 1/Subs. 2.
c) Conversions refer to TLC monitoring and isolated pure products.
duction of ꢀ-diketones to vicinal diols with modified hydrobo-
yields. Therefore, we think that, in the aspects of high efficien-
cy, chemoselectivity, and a perfect regioselectivity which have
been achieved by this reducing system, this procedure can be
attractive for a synthetically useful addition to the present
methodologies.
5c–e,12a–c
rate agents is also a subject of interest
and this goal
was easily achieved by NaBH4 in wet THF. Mixtures of
THF–H2O (3:0.1 mL) are suitable solvents for the reduction
of ꢀ-diketones to their vicinal diols with NaBH4 (2 molar
amounts) under reflux condition. Reduction reactions were
performed efficiently in shorter reaction times (1–5 min)
Experimental
(
92–98%) (Table 7). Under different conditions, our attempts
General. All substrates and reagents were obtained from com-
mercial sources with highest quality and were used without further
purification. The products were characterized by a comparison
with authentic samples (melting or boiling points) and their
to reduce ꢀ-diketones into acyloins were unsatisfactory and
only vicinal diols were identified as the sole products.
In addition, reduction of acyloins to vicinal diols is also
a subject of interest in organic synthesis. The applications
of non-hydridic reductants28 and modified hydroborate
1
H NMR or IR spectral data. Organic layers were dried with anhy-
drous sodium sulfate before concentration in vacuo. All yields re-
fer to isolated pure products. TLC was applied for reaction mon-
itoring and for the purity determination of substrates or products
over silica gel PolyGram SILG/UV-254 plates.
5
c–e,12a–c
agents
have been also reported for such reduction.
Using NaBH4 (1 molar amount) in THF–H2O (3:0.1 mL) also
easily provided this transformation under reflux condition. Un-
der the defined condition, conversion of benzoin to hydro-
benzoin was efficiently performed in one minute (Table 7).
Other acyloin compounds were also reduced readily to their
corresponding vicinal diols in high to excellent yields with this
reducing system (95–96%) (Table 7).
A Typical Procedure for Reduction of Aldehydes to Alco-
hols with NaBH4 in Wet THF. In a round-bottomed flask (10
mL) equipped with a magnetic stirrer and charged with a solution
of benzaldehyde (0.106 g, 1 mmol) in THF–H2O (3:0.1 mL),
NaBH4 (0.019 g, 0.5 mmol) was added. The resulting mixture
was stirred magnetically at room temperature for 5 min. TLC
monitored the progress of the reaction (eluent; CCl4/Et2O: 5/2).
After completion of the reaction, distilled water (3 mL) was added
to the reaction mixture and this solution was then stirred for an ad-
ditional 5 min. The mixture was extracted with CH2Cl2 (3 ꢁ 8
mL) and dried over anhydrous sodium sulfate. Evaporation of
the solvent and short column chromatography of the resulting
crude material over silica gel (eluent; CCl4/Et2O: 5/2) afforded
the pure liquid benzyl alcohol (0.102 g, 94% yield, Table 2).
A Typical Procedure for Reduction of Ketones to Alcohols
with NaBH4 in Wet THF. In a round-bottomed flask (10 mL)
equipped with a magnetic stirrer and a condenser, a solution of
Conclusion
In this article we have shown that the presence of a small
amount of water in THF dramatically accelerates the rates of
reduction of carbonyl compounds with NaBH4. Reduction of
aldehydes was carried out at room temperature and reduction
of ketones under reflux condition. The chemoselective reduc-
tion of aldehydes over ketones was achieved successfully with
this reducing system. Regioselectivity of this system was also
investigated with exclusive 1,2-reduction of conjugated car-
bonyl compounds to their corresponding allylic alcohols in
high to excellent yields. The usefulness of this process was fur-
ther shown with the reduction of acyloins and ꢀ-diketones to
their vicinal diols in shorter reaction times and excellent
9-fluorenone (0.18 g, l mmol) in THF–H O (3:0.1 mL) was pre-
2
pared and NaBH (0.076 g, 2 mmol) was then added. The result-
4
ing mixture was heated magnetically to gentle reflux. TLC moni-

B. Zeynizadeh et al.
Table 7. Reduction of ꢀ-Diketones and Acyloins with NaBH4 in Wet THF
Bull. Chem. Soc. Jpn., 78, No. 2 (2005)
313
aÞ
Molar ratio
NaBH4/Subs.
bÞ
Time/min Yield/%
Entry
1
Substrate
Product
O
O
OH
2:1
1:1
2
1
97
95
OH
OH
O
2
3
OH
OH
OH
Me
Me
Me
O
O
2:1
1:1
2:1
5
3
4
96
96
95
OH
Me
Me
Me
Me
O
OH
OH
4
5
OH
Me
OMe
OMe
OMe
OMe
O
O
OH
OH
MeO
MeO
MeO
O
OH
OH
6
7
1:1
2:1
3
4
96
93
OH
MeO
OH
O
O
OH
a) All reactions were performed in THF–H2O (3:0.1 mL) under reflux condition. b) Yields refer to isolated pure
products.
tored the progress of the reaction (eluent; CCl4/Et2O: 5/2). After
completion of the reaction within 12 min, distilled water (3 mL)
was added to the reaction mixture and it was then stirred for an
additional 5 min. The mixture was extracted with CH2Cl2
A Typical Procedure for Regioselective 1,2-Reduction of
Conjugated Carbonyl Compounds with NaBH4 in Wet THF.
In a round-bottomed flask (10 mL) equipped with a magnetic stir-
rer and a condenser, a solution of benzylideneacetone (0.146 g, 1
mmol) in THF–H2O (3:0.1 mL) was prepared and NaBH4 (0.076
g, 2 mmol) was then added. The resulting mixture was heated
magnetically to gentle reflux. TLC monitored the progress of
the reaction (eluent; CCl4/Et2O: 5/2). After completion of the re-
action within 8 min, distilled water (3 mL) was added to the reac-
tion mixture and this mixture was then stirred for an additional 5
min. The mixture was extracted with CH2Cl2 (3 ꢁ 8 mL) and
dried over anhydrous sodium sulfate. Evaporation of the solvent
and short column chromatography of the resulting crude material
over silica gel (eluent; CCl4/Et2O: 5/2) afforded the pure liquid
4-phenyl-3-buten-2-ol (0.141 g, 95% yield, Table 5).
A Typical Procedure for Reduction of ꢀ-Diketones and
Acyloins with NaBH4 in Wet THF. In a round-bottomed flask
(10 mL) equipped with a magnetic stirrer and charged with a solu-
tion of benzil (0.21 g, l mmol) in THF–H2O (3:0.1 mL), NaBH4
(0.076 g, 2 mmol) was added. The resulting mixture was stirred
under reflux condition for 2 min. TLC monitored the progress
of the reaction (eluent; CCl4/Et2O: 5/2). After completion of
the reaction, distilled water (3 mL) was added to the reaction mix-
(
3 ꢁ 8 mL) and dried over anhydrous sodium sulfate. Evaporation
of the solvent and short column chromatography of the resulting
crude material over silica gel (eluent; CCl4/Et2O: 5/2) afforded
the pure crystals of 9-fluorenol (0.18 g, 99% yield, Table 3).
A Typical Procedure for Competitive Reduction of Alde-
hydes and Ketones with NaBH4 in Wet THF. In a round-bot-
tomed flask (10 mL) equipped with a magnetic stirrer, a solution
of benzaldehyde (0.106 g, 1 mmol) and acetophenone (0.12 g, 1
mmol) in THF–H2O (3:0.1 mL) was prepared. NaBH4 (0.019 g,
0
.5 mmol) was then added and the mixture was stirred magnetical-
ly at room temperature. TLC monitored the progress of reaction.
After 5 min, the reaction mixture was quenched by addition of dis-
tilled water (3 mL) and this mixture was then stirred for an addi-
tional 5 min. The mixture was extracted with CH2Cl2 (3 ꢁ 8 mL)
and dried over anhydrous sodium sulfate. Evaporation of the sol-
vent and short column chromatography of the resulting crude ma-
terials over silica gel (eluent; CCl4/Et2O: 5/2) afforded the pure
liquid benzyl alcohol as a sole product, besides acetophenone as
an intact material (Table 4).

3
14 Bull. Chem. Soc. Jpn., 78, No. 2 (2005)
Wet THF as a Suitable Solvent for Reduction
ture and this combination was then stirred for an additional 5 min.
The mixture was extracted with CH2Cl2 (3 ꢁ 8 mL) and dried
over anhydrous sodium sulfate. Evaporation of the solvent and
short column chromatography of the resulting crude material over
silica gel (eluent; CCl4/Et2O: 5/3) afforded the pure crystals of
hydrobenzoin (0.21 g, 97% yield, Table 7).
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The authors gratefully acknowledge the financial support of
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