Ultrasound-promoted reduction of conjugated enones, α-diketones and acyloins with NaBH4 under aprotic condition

Article abstract of DOI:10.1515/znb-2004-0611

A variety of conjugated enones are reduced regioselectively to their corresponding allylic alcohols with NaBH₄ under ultrasound irradiation. Reduction reactions were performed in THF at room temperature and the product alcohols were obtained in high to excellent yields. This system is also efficient for the reduction of α-diketones and acyloins to vicinal diols.

Full text of DOI:10.1515/znb-2004-0611

Ultrasound-Promoted Reduction of Conjugated Enones, α-Diketones and
Acyloins with NaBH4 under Aprotic Condition
Behzad Zeynizadeh and Saiedeh Yahyaei
Department of Chemistry, Faculty of Sciences, Urmia University, Urmia 57159-165, Iran
Reprint requests to Prof. Dr. B. Zeynizadeh. E-mail: b.zeynizadeh@mail.urmia.ac.ir
Z. Naturforsch. 59b, 699 – 703 (2004); received December 28, 2003
A variety of conjugated enones are reduced regioselectively to their corresponding allylic alco-
hols with NaBH4 under ultrasound irradiation. Reduction reactions were performed in THF at room
temperature and the product alcohols were obtained in high to excellent yields. This system is also
efficient for the reduction of α-diketones and acyloins to vicinal diols.
Key words: Ultrasound, Borohydride Reduction, Conjugated Enones, α-Diketones, Acyloins
Introduction
Results and Discussion
Regioselective 1,2-reduction of α,β-unsaturated
aldehydes and ketones with metal hydride reducing
agents due to competing 1,2- vs. 1,4-attack by hydride
is often difficult to achieve in organic synthesis [1].
Reduction of conjugated enones: Selective 1,2-
reduction of α,β-unsaturated carbonyl compounds
is usually achieved by using modified hydroborate
agents which are formed: a) by the replacement of hy-
In spite of the substantial evidence, the tendency for dride(s) with sterically bulky substituents or electron-
sodium borohydride to reduce enones in a conjugate
sense is highly solvent-dependent [2] and often ig-
withdrawing/releasing groups in order to discriminate
between the structural and electronic environments
nored, but the requirement for reduction to correspond- of the carbonyl groups [2c, 5, 6, 11], b) combination
ing allylic alcohols has led to the development of sev- with Lewis acids [7, 8] and mixed solvent systems
eral new specific reagents. Among the various reduc-
ing systems which have been developed for 1,2-re-
[2a – c, 11e], c) using of transition metal hydroborates
and its new modifications [12, 13] d) use of quater-
duction of conjugated enones, the reagents such as nary ammonium [14] and phosphonium tetrahydrob-
diisobutylaluminum hydride (DIBAL-H) [3], triisobu-
tylaluminum (TIBAL) [4], lithium aluminum hydride
[2a], 9-borabicyclo[3.3.1]nonane (9-BBN) [5], lithium
n-butylborohydride [6] and sodium borohydride in the
presence of lanthanides [7] and calcium chloride [8]
are generally the most efficient and convenient.
Nowadays, acceleration of reactions by using ultra-
sound irradiation is an interesting strategy in organic
synthesis: numerous reviews and papers have demon-
strated its importance [9]. Sonic condition not only
accelerates chemical reactions but also it reduces the
number of steps which are required using normal con-
ditions, cruder reagents can be used and reactions can
be initiated without any additives. The chemical effects
of ultrasound are due to the phenomena of acoustic
cavitations [9d] and the primary chemical reactions re-
sult from a transient state of higher temperatures and
pressures [10].
orates [15], and e) immobilization on an anionic ex-
change resin [16].
As far as we know, the application of ultrasound
in regioselective 1,2-reduction of conjugated enones
has not been reported yet. Therefore, in the line of
outlined strategies and ongoing attention to prepara-
tion and application of modified hydroborate agents
[12, 17] in organic synthesis, we decided to evalu-
ate the influence of ultrasound irradiation in reduc-
tion of conjugated enones with commercially avail-
able sodium borohydride under aprotic conditions.
Our preliminary observations reveal that when cin-
namaldehyde as a model compound is reduced with
NaBH4 in THF, the selectivity ratio of 1,2- vs. 1,4-
reduction is 95:5 at room temperature within 3 h,
whereas this reaction under sonication shows a perfect
selectivity for 1,2-reduction in shorter reaction time
(Scheme 1).
c
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B. Zeynizadeh – S. Yahyaei · Reduction of Conjugated Enones, α-Diketones and Acyloins with NaBH4
Table 1. Reduction of conjugated enones with NaBH4-ultrasound systema.
Entry
Substrate
Product
Molar ratio
NaBH4/Substrate 1,2:1,4
Ratio
Time Yield
(h)
M.p. or B.p. (◦C)
(%)b found
calcd.
1
2
3
1:1
1:1
1:1
100:0
100:0
100:0
0.3
96
97
98
34 – 35
33 – 35 [21a]
33 – 34 [21b,c]
55 – 57 [18d]
0.92
0.83
33 – 34
56 – 57
4
5
1:1
1:1
100:0
100:0
0.4
92
90
164 – 165 164 – 166 [21a]
0.32
–
–
6
1:1
1:1
100:0
100:0
1.1
95
96
229 – 230 229 – 230 [21a]
107/3 [21d]
107/3
7
1.33
(mmHg)
a
All reactions were performed in THF at room temperature;b yields refer to isolated pure products.
Scheme 2.
Scheme 1.
showed that the selectivity ratio for reduction of alde-
hyde over ketone was 80:20 within 18 min (Scheme 2).
Accordingly, we decided to apply this procedure to
other enones. We turned our attention to the reduction
To highlight the efficiency of the NaBH4-ultrasound
of benzalacetone as a conjugated ketone at the same system for the reduction of conjugated enones,
condition. The reaction was also easily performed with we compared our results with those obtained with
an equimolar amount of NaBH4 at room temperature. other reagents such as NaBH4 [17a], NaBH4/
The corresponding secondary allylic alcohol was ob- Dowex1-x8 [17a], NaBH3(OAc) [2c], NaBH3CN
tained regioselectively in excellent yield (Table 1, entry [11e], Li (n-BuBH3) [6], (i-PrO)2TiBH4 [13a], and
2). The usefulness of this utility was demonstrated by (Ph3PMe)BH4 [15]. Investigation of the results show
regioselective 1,2-reductionof other enones with 1 mo- that with respect to efficiency and regioselectivity, our
lar equivalent of NaBH4 under ultrasound irradiation system is either more efficient or comparable (Table 2).
in THF. In these cases, the observed selectivity for 1,2-
Reduction of α-diketones and acyloins: The syn-
reduction was also excellent and the corresponding al-
lylic alcohols were obtained in high to excellent yields
(90– 99%) (Table 1).
thetic utilities of vicinal diols are well known in or-
ganic synthesis and their preparation from the reduc-
tion of acyloins or α-diketones has attracted a great
Since aldehydes are generally more reactive than deal of attention. Reduction of α-diketones usually
ketones, this subject encouraged us to investigate the gives a mixture of α-hydroxyketones and vicinal diols.
chemoselectivity for reduction of conjugated aldehy- Selective reduction of α-diketones to acyloins [18] or
des over ketones. Therefore, in a typical reaction we vicinal diols [19] can be achieved with some chemical
performed the competitive reduction of a mixture of an or biochemical reagents. Reduction of α-diketones to
equimolar amount of cinnamaldehyde and benzalace- vicinal diols with modified hydroborate agents is also
tone with NaBH4 under sonication. The experiment a subject of interest [12,17a] and this goal is easily
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B. Zeynizadeh – S. Yahyaei · Reduction of Conjugated Enones, α-Diketones and Acyloins with NaBH4
701
Table 2. Comparison of 1,2-reduction of conjugated enones with the NaBH4-ultrasound system and other reported reagents.
Entry Substrate
Molar ratioa, Time (h), Yield (%) and Ratio of 1,2:1,4
I
II [17a]
1(0.3)(96) 1(0.7)(96) 1(3)(93)
(100:0) (100:0) (95:5)
III [17a]
IV [2c]
1.67(20)(70) 2(1.5)(80)
(99:1) (100:0)
V [11e]
VI [6]
VII [13a]
VIII [15]
1(0.08)(90) 1(b)(95)
(> 99 :< 1) (100:0)
1
2
3
–
1(0.92)(97) 1(1.4)(98) 1(2.8)(96) 1.67(20)(70) 2(1.5)(77) 1(2)(98) 1(0.08)(97) 1(3.5)(90)
(100:0)
(100:0)
(95:5)
(96:4)
(100:0)
(100:0)
(> 99 :< 1) (100:0)
1(0.83)(98) 1(0.7)(95) 1(1.7)(95)
(100:0) (100:0) (90:10)
3(2.5)(0)
1(2)(99)
(100:0)
1.2(6)(90)
–
–
(100:0)
–
1(1.1)(95) 1(1.3)(94) 1(2.8)(90) 1.67(20)(86)
1(0.08)(95)
(< 99 :< 1)
4
5
–
–
(100:0)
(100:0)
(99:1)
(99:1)
1(1.33)(96) 1(2.2)(91) 1(3)(80)
(100:0) (100:0) (95:5)
2(2)(88)
(100:0)
1(2)(98)
(100:0)
1(6)(71)
(100:0)
–
–
1(0.4)(92) 1(0.8)(89) 1(1)(85)
(100:0) (100:0) (80:20)
1.67(20)(32)
(99:1)
1(2)(84)
(92:8)
6
–
–
–
I
II
III
IV
V
VI
VII
VIII
NaBH4/ultrasound; NaBH4/Dowex1-x8; NaBH4;
NaBH3(OAc); NaBH3CN;
Li (n-Bu-BH3);
(i-PrO)2TiBH4;
(Ph3-
PMe)BH4; a Reducting agent:substrate; b immediate reaction.
Table 3. Reduction of α-diketones
and acyloins with NaBH4-
ultrasound systema.
Entry
1
Substrate
Product
Molar ratio
NaBH4/Substrate
Time Yield
(min) (%)b
1.2:1
12
95
a
All reactions were performed in THF
b
at room temperature; yields refer to
isolated pure products.
2
3
4
1:1
10
18
17
98
96
96
1.2:1
1.2:1
5
6
1.2:1
1:1
20
14
98
94
7
8
1.2:1
1:1
12
8
92
95
achieved by the NaBH4-ultrasound system. This sys- in THF at room temperature and with short reaction
tem readily reduces α-diketones to their vicinal diols times (12– 20 min). For completion of the reactions,
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B. Zeynizadeh – S. Yahyaei · Reduction of Conjugated Enones, α-Diketones and Acyloins with NaBH4
1.2 molar equivalents of NaBH4 are sufficient and the Experimental Section
product diols are obtained in 92– 98% yields (Table 3).
Sonication was performed by using a Cole Palmer high
Under different conditions, our attempts to reduce α-
diketones to acyloins were unsatisfactory and only vic-
inal diols were identified as the sole products.
intensity ultrasonic processor (600 W, 20 KHz) via a mi-
crotip probe and 30% amplitude. THF was dried prior to
use by standard methods. The products were characterized
by a direct comparison on TLC with authentic samples, melt-
ing/boiling points or their 1H NMR and IR spectra. All yields
refer to isolated pure products (> 97%). TLC accomplished
the purity determination of the substrates, products and re-
actions monitoring over silica gel PolyGram SILG/UV254
plates.
Reduction of cinnamaldehyde to cinnamyl alcohol with
NaBH4-ultrasound system, general procedure: In a round-
bottom flask (10 ml) equipped with magnetic stirrer, NaBH4
(0.037 g, 1 mmol) was added to the solution of cinnamalde-
hyde (0.132 g, 1 mmol) in THF (5 ml). The stirred reac-
tion mixture was irradiated with ultrasound waves at room
temperature. Sonication was continued for 18 min, and the
progress of the reaction was monitored by TLC (eluent:
CCl4/Et2O (5/2)). At the end of reaction, distilled water
(5 ml) was added to the reaction mixture which was stirred
for additional 5 min. The mixture was extracted with CH2Cl2
(3×10 ml) and dried over anhydrous sodium sulfate. Evapo-
ration of the solvent and short column chromatography of the
resulting crude material over silica gel (eluent: CCl4/Et2O
(5/2)) afforded pure liquid cinnamyl alcohol (0.l28 g, 96%
yield, Table 1).
In addition, reduction of acyloins to vicinal diols
is also a subject of interest in organic synthesis. The
application of non-hydridic reductants [20] and mod-
ified hydroborate agents [12,17a] have been reported
for such a transformation. We also found that this goal
is easily achieved by the NaBH4-ultrasound system.
The influence of ultrasound irradiation effectively ac-
celerates reduction of benzoin to hydrobenzoin with
sodium borohydride in THF. Some acyloin compounds
are easily reduced to their corresponding vicinal diols
in high to excellent yields with this system (Table 3).
In conclusion, we have shown that NaBH4 in com-
bination with ultrasound irradiation reduces a variety
of conjugated enones regioselectively to their corre-
sponding allylic alcohols in high to excellent yields
and with short reaction times. Reduction reactions
were performed at room temperature under aprotic
condition in THF. The NaBH4-ultrasound system is
also efficient for the reduction of acyloins or α-
diketones to their corresponding vicinal diols. The
cheapness and availability of the reagent, simple work-
up procedure as well as the above advantages could Acknowledgement
make this procedure an attractive and synthetically
useful addition to the present methodologies.
The authors gratefully acknowledge the Research Council
of Urmia University (RCUU) for supports of this work.
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