A new method for the chemoselective reduction of aldehydes and ketones using boron tri-isopropoxide, B(OiPr)3: Comparison with boron tri-ethoxide, B(OEt)3

Article abstract of DOI:10.1007/s12039-011-0116-1

A chemoselective Meerwein-Ponndorf-Verley reduction process of various aliphatic and allylic α,β-unsaturated aldehydes and ketones is described. This chemoselective reduction is catalysed by boron triisopropoxide B(Oⁱ Pr)₃. Kinetics of reduction of aldehydes and ketones to corresponding alcohols were also examined and rate constant of each carbonyl compounds were measured. Rate constant and reduction yield of each carbonyl compounds in the presence of B(Oⁱ Pr)₃ were compared with those in the presence of B(OEt)₃. The alcohols that are the reduction product were analysed by GC-MS. The rate constants and alcohol yields were found to be higher with B(OEt)₃ than with B(Oⁱ Pr) ₃. The mechanism proposed involves a six-membered transition state in which both the alcohol and the carbonyl are coordinated to the same boron centre of a boron alkoxide catalyst. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-011-0116-1

J. Chem. Sci. Vol. 123, No. 5, September 2011, pp. 681–685. ꢀc Indian Academy of Sciences.
A new method for the chemoselective reduction of aldehydes and ketones
i
using boron tri-isopropoxide, B(O Pr) : Comparison with boron
3
tri-ethoxide, B(OEt)3
∗
BURCU UYSAL and BIRSEN S OKSAL
Department of Chemistry, Akdeniz University, 07058, Antalya, Turkey
e-mail: bbirsen@akdeniz.edu.tr
MS received 24 September 2010; revised 13 April 2011; accepted 6 June 2011
Abstract. A chemoselective Meerwein–Ponndorf–Verley reduction process of various aliphatic and allylic
α,β-unsaturated aldehydes and ketones is described. This chemoselective reduction is catalysed by boron tri-
i
isopropoxide B(O Pr)3. Kinetics of reduction of aldehydes and ketones to corresponding alcohols were also
examined and rate constant of each carbonyl compounds were measured. Rate constant and reduction yield of
i
each carbonyl compounds in the presence of B(O Pr)3 were compared with those in the presence of B(OEt)3.
The alcohols that are the reduction product were analysed by GC-MS. The rate constants and alcohol yields
i
were found to be higher with B(OEt)3 than with B(O Pr)3. The mechanism proposed involves a six-membered
transition state in which both the alcohol and the carbonyl are coordinated to the same boron centre of a boron
alkoxide catalyst.
Keywords. Boron tri-iso-propoxide; boron tri-ethoxide; chemoselective reduction; allylic alcohols;
Meerwein–Ponndorf–Verley reduction.
1
. Introduction
readily scalable. These apparent practical advantages
make the MPV reduction a particularly attractive
green-chemistry approach for reduction of carbonyl
Aldehydes and ketones have long been known to be
effectively reduced to corresponding alcohols by metal
alkoxides and alcohols. Usually, metal sec-alkoxides
are used as homogeneous catalysts in reductions of
the carbonyl compounds.1,2 The process is commonly
termed the Meerwein–Pondorf–Verley (MPV) reduc-
tion. The MPV reduction of carbonyl substrates to pri-
8
compounds.
MPV reactions are usually catalysed homogeneously
by metal alkoxides such as aluminum isopropoxide
i
7
(
Al(O Pr) ). The catalytic activity of these catalysts is
3
related to their Lewis acidic character in combination
9
with their ligand exchange ability. The hydrogen donor
3
–5
mary and secondary alcohols, discovered in 1925,
is usually a secondary alcohol such as 2-propanol. The
classical MPV reduction reaction provides an interest-
ing pathway for the reduction of aldehydes and ketones
to alcohols.
is a useful method for the reduction of carbonyl com-
pounds because of its chemoselectivity. The chemose-
lectivity of the reducing agent is very important because
reduction of the carbonyl group without affecting the
other reducible groups in the molecule is difficult. The
MPV process provides a highly selective reduction of
the carbonyl group in the presence of other reducible
sites, so the risk of reducing or oxidizing functions other
than the carbonyl group is minimal.6,7
Essentially, the reaction proceeds by a hydride trans-
fer to the carbonyl compound from the alcohol, which
is coordinated to the metal center as an alkoxide.10
A
ketone (acetone), is formed as a volatile side product,
can easily be removed.
This way of reducing C=O bonds is highly attrac-
tive on account of its high selectivity towards carbonyl
groups. In fact, other reducible functions such as C=C
The process generally uses inexpensive and envi-
i
ronmentally friendly isopropyl alcohol ( PrOH) as a
hydride source and aluminum alkoxides as catalysts.
The reaction is chemoselective, easy to operate, and
1
1
and C–halogen bonds are left untouched.
i
In addition to the classical (Al(O Pr) ) catalyst, cat-
3
alytic applications of other isopropoxides, such as
1
2,13
zirconium(IV) isopropoxide
and lanthanide iso-
∗
14
For correspondence
propoxides, in the MPV reaction have been reported.
681

682
Burcu Uysal and Birsen S Oksal
In recent years, MPV reduction of carbonyl com- during the reduction reaction time slow stream of dry
pounds to the corresponding alcohols has been one nitrogen was passed just over the surface of reaction
of the standard procedures for the selective reduc- mixture. In this way, arising acetone was removed
tion of unsaturated carbonyls in laboratories and indus- by nitrogen flow. Thus the equilibrium reaction was
15–21
tries.
Extensive studies have been carried out to slipped to the right hand.
expand the potential of the classical MPV reduction.
Heterogenous catalysts for these reductions are supe- temperature (27 C) as the most suitable reduction time
rior to homogenous ones from the viewpoint of cost for 2-cyclohexen-1-one was found to be 9 h.
The resulting solution was stirred for 9 h at room
◦
and are utilized for the industrial scale reduction of
At regular times which last for 1 h, 1 μl of solution
carbonyls in many applications.22 However, heteroge- was removed and injected into water-isopropanol (1 ml
i
nous catalysts are poor for the selective reduction of H O/1 ml PrOH) solution. In this case, boron alkoxide
2
unsaturated carbonyls to unsaturated alcohols.2
3
was hydrolysed to boric acid (H BO ) and dissolved
3 3
In a previous study, the effects of the catalytic char- in water. For separate water and organic phase, water
acteristics of two kinds of boron alkoxides, boron phase was saturated with K CO . Thus, yield of alco-
2
3
i
tri-isopropoxide B(O Pr) and boron tri sec-butoxide hol and unreducted ketone remain in organic phase. The
B(O Bu) , on the reduction of aliphatic and aromatic rate of reaction was followed by removing aliquots at
aldehydes and ketones were showed. In this paper regular intervals during the course of the reaction and
3
s
3
24
i
s
B(O Pr) and B(O Bu) were prepared in situ from analysing by GC-MS.
3
3
corresponding alcohols and borane (BH3.THF). On
Analyses were performed on a Varian CP 3800 gas-
the other hand, recently, it was shown that (B(OEt) ) chromatograph equipped with a Varian Saturn 2200 MS
3
reduces some aliphatic aldehydes and ketones.2 MPV- detector (Walnut Creek, CA, USA) and a VF-5 ms cap-
5
type reduction mechanism was proposed for these illary column (30 m length and 0.25 mm I.D., 0.25 μm
chemoselective reductions.
film thickness) (Palo Alto, CA, USA).
There are no available data in literature concerning
the kinetics of chemoselective MPV reduction of vari- aldehydes and the ketones in the presence of B(O Pr) .
The same procedure was used to reduce all the other
i
3
ous aliphatic and allylic α,β-unsaturated aldehydes and At first, suitable reduction time for each aldehydes and
i
ketones with B(O Pr) as catalyst. In this paper, an effi- ketones was examined. Then kinetics of each aldehydes
3
cient and selective method for the reduction of alde- and ketones was studied.
hydes and ketones such as 1-hexanal, 1-pentanal, 2-
pentanone, 2-butanone, cyclopentanone, geranial, neral, Aldrich, and used as received. All reactions were car-
-methyl-2-butenal, 2-cyclohexen-1-one, 4-Phenyl-3- ried out under a nitrogen atmosphere using modified
All chemicals were purchased from Merck, Fluka or
3
buten-2-one, cinnamaldehyde using (B(OPr) ) as the Schlenk techniques.
3
catalyst is described and kinetics of the MPV reduction
for these compounds were examined. Also, the rate con-
stant and reduction yield of each carbonyl compounds
i
in the presence of B(O Pr) were compared with case of 3. Results and discussion
3
the presence of B(OEt)3.
Aliphatic and allylic α,β-unsaturated aldehydes and
ketones were reduced to the corresponding alcohols
i
using B(O Pr) . The rate constant of each carbonyl
3
2
. Experimental
compound was determined. All aliphatic and allylic
α,β-unsaturated aldehydes and ketones exhibited a lin-
ear correlation between the natural logarithm of the
concentration of the carbonyl group and the reaction
2.1 General procedure: MPV reduction
of 2-cyclohexen-1-one to 2-cyclohexen-1-ol
The catalytic MPV reduction reaction was conducted time. This suggests that the reaction is first order in the
in a 50 ml two-mouthed flask with a side stopcock aldehyde concentration and allowed us to calculate the
equipped with a 100 cm condenser and it was furnished rate constant from the slope of a plot of ln (c
with a magnetic stirrer. 30 mmol PrOH was placed in function of time.
/c) as a
0
i
the flask, and the flask immersed in a water bath. Then,
ln (c /c) = kt,
i
i
0
1
0 mmol B(O Pr) were added drop-wise to PrOH. The
3
solution was stirred for 5 min, then 2-cyclohexen-1- where c is the initial aldehyde concentration, c that at
0
one (30 mmol, 2.96 ml) were injected into the solution, a given time t and k is the rate constant.

Chemoselective reduction of aldehydes and ketones
Table 1. Rate constants and yields obtained in the MPV reduction of carbonyl compounds using B(O Pr)3.
683
i
−
3
−1 a
Entry
Compound
Yield of alcohol(%)
Reaction time (h)
kx10 (min
)
Product
i
i
i
by B(O Pr)3 by B(OEt)3 by B(O Pr)3 by B(Et)3 by B(O Pr)3 by B(OEt)3
1
2
3
4
5
6
7
8
9
1
1
.
.
.
.
.
.
.
.
.
1-Hexanal
1-Pentanal
87.7
87.8
85.1
86.5
89.5
84.3
83.1
87.9
88.7
86.5
86.8
88.8
89
86.6
87.1
90
86.6
85.2
88.3
89.5
87
9
9
9
9
9
20
20
15
9
14
13
8
8
8
8
8
20
20
15
9
14
13
4.163
4.02
3.53
3.748
4.47
2.052
1.948
2.478
4.155
2.258
2.43
4.378
4.128
3.713
3.858
4.563
2.470
2.280
2.54
1-hexanol
1-pentanol
2-pentanol
2-butanol
cyclopentanol
geraniol (trans)
nerol (cis)
3-Methyl-2-butenol
2-cyclohexen-1-ol
4Phenyl-3buten-2ol
cinnamalcohol
2-Pentanone
2-Butanone
Cyclopentanone
a
Geranial
Neral
b
3-methyl-2-butenal
2-cyclohexen-1-one
4.278
2.318
2.487
0. 4Phenyl-3buten-2one
1. Cinnamaldehyde
87.9
a) trans-citral; b) cis-citral
The selected carbonyl compounds, the yields of the demonstrates the same chemoselectivity for hydride
reduction products, and the rate constants of various transfer reaction of various aliphatic and allylic α,β-
aldehydes and ketones are summarized in table 1. As unsaturated aldehydes and ketones. The reduction yield
it can be seen from table 1, some differences were of carbonyl compounds with these two boron alkox-
observed in reduction yields, rate constants and reduc- ide catalysts is higher than the previously reported
27
tion times. Smaller rate constant for cinnamaldehyde, 3- aluminium alkoxide catalysts.
methyl-2-butenal, 4-phenyl-3-buten-2-one (benzalace- The MPV reduction in the presence of boron
tone) and citral (3,7-dimethyl 2,6-octadienal) can be alkoxide catalysts showed good chemoselectivity for
attributed to their steric hindrance and to the presence of allylic α,β-unsaturated aldehydes and ketones. 3-
a double bond conjugated to the carbonyl group. Ruiz methyl-2-butenal, 2-cyclohexen-1-one, benzalacetone,
and co-workers reported that the presence of a double cinnamaldehyde and citral are important allylic α,β-
bond conjugated with the carbonyl group substantially unsaturated aldehydes and ketones. These important
reduced the reaction rate.26
carbonyl compounds possess conjugated C=C and
i
It is apparent that from table 1, the simple (B(O Pr) ) C=O bonds. The C=C bonds are more readily hydro-
3
catalyst show lower activity than previously reported genated than the C=O bonds in most usual techniques.28
i
(
B(OEt) ) catalyst. In addition, (B(O Pr) ) catalyst Although reduction of the C=O bonds without affecting
3
3
Scheme 1. A proposed reaction mechanism for the reduction of aliphatic and
i
allylic α,β-unsaturated aldehydes and ketones by B(O Pr)3.

684
Burcu Uysal and Birsen S Oksal
the C=C bonds is highly difficult, C=O bond of these aldehydes and ketones were reduced to the corre-
i
compounds were reduced using B(O Pr) catalyst in this sponding alcohols, without reducing the C=C double
3
study (table 1).
bonds. The rate of the reduction of aliphatic and allylic
Conversions of citral to nerol and geraniol above α,β-unsaturated aldehydes and ketones to the corre-
8
5% within 20 h of reaction were achieved. The pref- sponding alcohols is first order. Also in these reaction
i
erential formation of geraniol as compared to nerol can conditions, B(O Pr) at room temperature, trans- and
be explained by steric hindrance of the bulky chain.
3
29
cis-citral are selectively reducted to the correspond-
The carbonyl group of the geranial is trans to the bulky ing alcohols (geraniol and nerol, respectively). Since
chain of the molecule, minimizing any steric hindrance steric hindrance of the bulky chain, the reaction rate
for the binding of C=O to the boron center. Hence, the is faster for geranial than for neral in the presence of
rate of reaction for geranial is faster than for neral.
boron alkoxide catalysts. We conclude that B(OEt) is a
3
i
The reaction mechanism for the MPV reduction in slightly good chemoselective catalyst than the B(O Pr)3
the homogeneous phase involves a cyclic six-membered for the MPV reduction and both of the boron alkox-
transition state.15 Scheme 1 shows the proposed mech- ide catalysts facilitate the chemoselective reduction of a
anism for the carbonyl compounds in the presence of variety of unsaturated ketones and aldehydes to allylic
i
B(O Pr) . First, the carbonyl compound is coordinated alcohols.
3
to the boron of the boron alkoxide. The reaction pro-
ceeds by hydride-transfer to the carbonyl compound Acknowledgement
from the alcohol, which is bound to the boron center as
The authors gratefully acknowledge The Scientific
an alkoxide. Since the reduction is reversible, the ace-
Research Projects Coordination Unit of Akdeniz Uni-
tone was removed from the medium by a slow stream
versity for financial support.
of nitrogen. The removal of the acetone from the reac-
tion solution leads to the progress of the reaction to the
right hand side (see scheme 1). The alcohol yields using References
B(OEt) catalysts were found greater than those using
3
i
B(O Pr) because of the removal of methanal are easier
than acetone.
1. Van der Waal J C, Kunkeler P J, Tan K and Van Bekkum
3
H 1998 J. Catal. 173 74
2
. Aramendía M A, Borau V, Jiménez C, Marinas J M, Ruiz
J R and Urbano F J 2001 J. Colloid Interf. Sci. 238 385
. Meerwein H and Schmidt R 1925 Justus Liebigs Ann.
Chem. 39 221
Catalysis in the perfumery industry is one of the new
research fields using hydrogenation catalysts. There are
numerous hydrogenation processes both in gas and liq-
uid phases, but most of them are not selective to target
α,β-unsaturated alcohols. Selective hydrogenation of
α,β-unsaturated aldehydes and ketones such as croton-
aldehyde, cinnamaldehyde, citral, 2-cyclohexen-1-one,
benzalacetone (trans-4-fenil-3-buten-2-on) to their cor-
responding α,β-unsaturated alcohols is highly desirable
due to the corresponding allylic alcohols are useful as
intermediates, pharmaceuticals, and as flavour chemi-
3
4. Pondorf W 1926 Angew. Chem. 39 138
5
. Verley M 1925 Bull. Soc. Chim. Fr. 37 871
6. Furnıss B S, Hannaford A J, Smith P W G, Tatchell A R
1
989 Vogel’s Bath Pres: Great Britain p 418
7
. Creyghton E J, Huskens J, Van der Waal J C, Van
Bekkum H 1997 Heterogeneous catalysis and fine chem-
icals IV, Amsterdam: Elsevier p 531–537
8. Yin J, Huffman M A, Conrad K M, Armstrong J D 2006
J. Org. Chem. 71 840
3
0–32
9. Zhu Y, Jaenicke S, Chuah G K 2003 J. Catal. 218 396
0. Liu S H, Jaenicke S, Chuah G K, 2002 J. Catal. 206 321
1. Sanchidrian C J, Hidalgo J M, Ruiz J R 2006 Appl.
Catal. A-gen. 303 23
cals.
615 kcal/mol) than that of C=O bond (715 kcal/mol),
so which makes the hydrogenation of C=O bond dif-
But the bond energy of C=C bond is smaller
1
1
(
28
ficult. In this instance, the selective reduction of 12. Ishii Y, Nakano T, Inada A, Kishigami Y, Sakurai K,
Ogawa M 1986 J. Org. Chem. 51 240
C=O bond using boron alkoxides as catalyst will be
promising process for perfumery industry.
1
1
3. Knauer B, Krohn K 1995 Liebigs Annalen. 677
4. Namy J L, Souppe J, Collin J, Kagan H B 1984 J. Org.
Chem. 49 2045
1
5. De Graauw C F, Peters J A, van Bekkum H, Huskens J
1994 Synthesis 10 1007
1
1
1
6. Cha J S 2006 Org. Proc. Res. Dev. 10 1032
7. Wilds A L 1994 Org. React. 2 178
8. Fukuzawa S, Nakano N, Saitoh T 2004 Eur. J. Org.
Chem. 2863
4
. Conclusion
Catalytic MPV reduction was successfully carried
out using B(O Pr) as catalyst. In the presence of
B(O Pr) various aliphatic and allylic α,β-unsaturated
i
3
19. Yamazaki T, Terajima T, Kawasaki-Takasuka T 2008
i
3,
Tetrahedron. 64 2419

Chemoselective reduction of aldehydes and ketones
685
2
2
2
0. Graves C R, Campbell E J, Nguyen S B T 2005 Tetrahe- 27. Campbell E J, Zhou H, Nguyen ST 2001 Org. Lett. 15
dron: Asymmetry 16 3460 2391
1. Mojtahedi M M, Akbarzadeh E, Sharifi R and Abaee MS 28. Narayanan S 2003 Bulletin of the Catalysis Society of
007 Org. Lett. 9 2791 India 2 107
2. Nishimura S 2001 Handbook of heterogeneous catalytic 29. Zhu Y, Liu S, Jaenicke S, Chuah G 2004 Catal. Today.
2
hydrogenation for organic synthesis, New York, NY:
Wiley
97 249
30. Bauer K, Garbe D, Surburg H 1997 Common fragrance
and flavor materials, Weinheim, Wiley-VCH
31. Ullmann’s Encyclopedia of Technical Chemistry, 6th
edition, electronic release, Wiley-VCH 2000
2
2
2
2
3. Gallezot P, Richard D 1998 Catal. Rev.—Sci. Eng. 40 81
4. Uysal B, Buyuktas B S 2007 Arkıvoc. 14 134
5. Uysal B and Buyuktas, B S 2010 Chem. papers 64 123
6. Ruiz J R, Sanchidrian C J, Hidalgo J M, Marinas J M 32. De bruyn M, De Vos D E, Jacobs P A 2002 Adv. Synth.
006 J. Mol. Catal. A-Chem. 246 190 Catal. 344 1120
2