Zirconium borohydride piperazine complex, an efficient, air and thermally stable reducing agent

Article abstract of DOI:10.1016/j.tetlet.2004.02.140

A zirconium borohydride piperazine complex (Ppyz)Zr(BH₄) ₂Cl₂, obtained by the reaction of an ethereal solution of ZrCl₄ and LiBH₄ with piperazine is a stable, selective and efficient reducing agent. (Ppyz)Zr(BH₄)₂Cl ₂ reduces aldehydes, ketones, silylethers, α, β-unsaturated carbonyl compounds and esters. The reactions were performed in diethyl ether at room temperature or under reflux, and the yields of the corresponding alcohols were excellent. The selective reduction of aldehydes in the presence of ketones and complete regioselectivity in the reduction of α,β-unsaturated carbonyl groups were observed.

Full text of DOI:10.1016/j.tetlet.2004.02.140

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3295–3299
Zirconium borohydride piperazine complex, an efficient, air and
thermally stable reducing agent
a,
b
a
a
M. Tajbakhsh,a,* M. M. Lakouraj, F. Shirini, S. Habibzadeh and A. Nikdoost
*
aDepartment of Chemistry, Mazandaran University, Niroo Havaei Street, Babolsar 47416-1467, Iran
bDepartment of Chemistry, Guilan University, Rasht 41335, Iran
Received 10 November 2003; revised 2 February 2004; accepted 20 February 2004
Abstract—A zirconiumborohydride piperazine complex (Ppyz)Zr(BH 4)2Cl2, obtained by the reaction of an ethereal solution of
ZrCl4 and LiBH4 with piperazine is a stable, selective and efficient reducing agent. (Ppyz)Zr(BH4)2Cl2 reduces aldehydes, ketones,
silylethers, a,b-unsaturated carbonyl compounds and esters. The reactions were performed in diethyl ether at room temperature or
under reflux, and the yields of the corresponding alcohols were excellent. The selective reduction of aldehydes in the presence of
ketones and complete regioselectivity in the reduction of a,b-unsaturated carbonyl groups were observed.
Ó 2004 Elsevier Ltd. All rights reserved.
A number of covalent transition-metal borohydride
complexes are known, which are volatile, unstable
materials and which cannot be used as reducing agents,1
without modification, in organic synthesis. There are
only a few reports in the literature of the use of modi-
fied, stable forms of these compounds for reductive
transformations including, (Ph3P)2CuBH4,2 [(Ph3P)2Cu-
BH3CN]2,3 (C5H5)2Zr(Cl)BH4,4 Zn(BH4)2,5 DABCO
and (pyz)Zn(BH4)2,6;7 [Zr(BH4)2Cl2(dabco)2]8 and
Zr(BH4)2-crown ethers.9 Zirconiumborohydride is a
highly volatile solid, which decomposes around room
temperature, inflames in air, and which hydrolyses
explosively.10
an ethereal solution of LiBH4 with piperazine at 0–5 °C.
It is a white powder, which can be stored in a vacuum
dessicator for months without significant change in its
activity. Based on data obtained by atomic absorption
spectroscopy and borohydride content by an iodometric
titration,12 together with elemental analysis, (Ppyz)
Zr(BH4)2Cl2 was confirmed as its empirical formula.
This reagent reduces both aliphatic and aromatic alde-
hydes readily at roomtemperature in diethyl ether and
ketones at reflux (Tables 1 and 2). A comparison of
these data showed that aldehydes are reduced rapidly
and more conveniently than ketones. Therefore the
chemoselective reduction of an aldehyde in the presence
of a ketone was achieved at roomtemperature and the
unreacted ketone was recovered (Table 3). Numerous
methods exist for the chemoselective reduction of an
aldehyde in the presence of a ketone,13 but each has its
limitations and therefore this new methodology should
be of interest. Deprotection of aliphatic and phenolic
trimethylsilyl ethers to the corresponding alcohols and
phenols was achieved using (Ppyz)Zr(BH4)2Cl2 in
diethyl ether at ambient temperature (Table 4). a,b-
Unsaturated carbonyl compounds undergo regioselec-
tive 1,2-reduction to the corresponding allylic alcohols
at roomtemperature or under reflux conditions in
diethyl ether in the presence of (Ppyz)Zr(BH4)2Cl2
(Table 5).
Polymer supported zirconium borohydride complexes
have received considerable attention in recent years and
while exhibiting the advantages of polymeric reagents,
have been used for the mild and selective reduction of
organic compounds.11
Herein we report a coordination polymer of zirconium
borohydride with a bidentate ligand, piperazine, as a
new, air and thermally stable and efficient bench top
reducing agent for the reduction of a variety of organic
compounds. The zirconium borohydride piperazine
complex was easily prepared by treatment of ZrCl4 and
Keywords: Zirconiumborohydride; Piperazine; Reducing agent.
* Corresponding authors. Tel.: +98-1125234338; fax: +98-1125242002;
e-mail: tajbaksh@umz.ac.ir
An improved procedure for the reduction of the car-
bonyl group of a,b-unsaturated carbonyl compounds to
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.140

3296
M. Tajbakhsh et al. / Tetrahedron Letters 45 (2004) 3295–3299
Table 1. Reduction of aldehydes with (Ppyz)Zr(BH4)2Cl2 in diethyl ethera
Entry
Substrate
Product
Time (min)
Reagent/substrate
Yield (%)b
OH
O
CH2
H
1
60
1
97
OH
O
CH2
H
2
3
45
45
1
1
98
96
Cl
Br
Cl
Br
OH
O
CH2
H
OH
O
O
CH2
H
4
75
1
90
OMe
OMe
OH
CH2
H
H
5
6
240
2
1
95
98
OH
OH
OH
O
CH2
20
NO2
NO2
7
8
PhCH2CHO
CH3(CH2)4CHO
PhCH2CH2OH
CH3(CH2)4CH2OH
45
30
1
1
95
100c
a Reductions were performed at room temperature.
b The yields refer to isolated products.
c GC yield.
a
Table 2. Reduction of ketones with (Ppyz)Zr(BH4)2Cl2
Entry
Substrate
Product
Time (h)
Reagent/substrate
Yield (%)b
1
2
3
PhCOPh
PhCOCH3
(PhCH2)2CO
PhCHOHPh
PhCHOHCH3
(PhCH2)2CHOH
5
3
1
1
90
95
95
8
2.5
90c
95c
OH
4
2.5
2.5
1
1
O
5
CH3(CH2)5COCH3
CH3(CH2)5CHOHCH3
a Reactions were performed in diethyl ether under reflux.
b Yields refer to isolated products.
c GC yields.
allylic alcohols has long been a desired synthetic trans-
formation, since this reaction frequently results in
undesired 1,4-reduction products.14 Several methods are
known to bring about such a conversion but these

M. Tajbakhsh et al. / Tetrahedron Letters 45 (2004) 3295–3299
3297
Table 3.
Reduction
of
aldehydes
versus
ketones
with
methods call for the use of an excess of the reagents
and can result in over-reduction products.15;16
(Ppyz)Zr(BH4)2Cl2 in diethyl ethera
Entry
1
Starting mixture
Time (min)
25
Yield (%)b
In addition, aliphatic and aromatic carboxylic acid
esters are also reduced to the corresponding alcohols in
excellent yields (Table 6). Nitriles, amides and nitro
compounds are completely unaffected by this reagent.
In order to show the advantages and the drawbacks
of (Ppyz)Zr(BH4)2Cl2 for the reduction of carbonyl
groups, we compared our results with examples reported
for other modified borohydride reagents (Table 7).
2-Nitrobenzaldehyde
Acetophenone
Hexanal
100
0
2
3
30
45
100
0
Benzophenone
4-Bromobenzaldehyde
Cyclohexanone
100
0
a Reactions were performed under room temperature using a 1:1 molar
ratio of substrate to reducing agent.
b Yields refer to isolated product alcohols.
a
Table 4. Deprotection of trimethylsilyl ethers with (Ppyz)Zr(BH4)2Cl2
Entry
Substrate
Product
Time (h)
Yield (%)b
1
2
PhCH2CH2OSiMe3
ClCH2CH2OSiMe3
PhCH2CH2OH
ClCH2CH2OH
3
8
93
90
Ph
Ph
3
4
8
2
88
OSiMe3
Ph
OH
Ph
98c
Cl
Cl
OH
OSiMe3
Cl
Cl
OH
5
6
9
4
98
95
OSiMe3
OH
OSiMe3
a Reactions were carried out at room temperature using a 1:1 molar ratio of substrate to reducing agent.
b Yields refer to isolated products.
c The reaction was conducted at reflux temperature.
a
Table 5. Regioselective reduction of a,b-aldehydes and ketones with (Ppyz)Zr(BH4)2Cl2
Entry
Substrate
Product
Time (h)
Yield (%)b
O
C
1
2
CH
C
0.25
2
93c
95c
CH
CH CH
H
H2OH
Citral
(CH3)2C@CH(CH2)2C(CH3)@CHCH2OH
90c
OH
3
3
O
OH
O
Me
4
5
4
5
85
Me
Cl
Cl
OH
O
PhCH
CH
86
C H
CH3
PhCH
CH
CH3
C
(continued on next page)

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M. Tajbakhsh et al. / Tetrahedron Letters 45 (2004) 3295–3299
Table 5. (continued)
Entry
Substrate
Product
Time (h)
Yield (%)b
OH
O
CH
CH
6
5
3
82
80
(PhCH
CH
(
7
PhCH
)
CHOH
CH
)
CO
2
2
a Reactions were conducted in diethyl ether under reflux using a 1:1 molar ratio of substrate to reducing agent.
b Yields refer to isolated products.
c Roomtemperature.
a
Table 6. Reduction of esters with (Ppyz)Zr(BH4)2Cl2
Entry
Ester
Product
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
CH3COO(CH2)3CH3
CH3COOC2H5
CH3CH2OH
CH3CH2OH
4
4
8
8
9
8
4
5
95
94
90
92
90c
50
90
92
PhCH2COOC2H5
PhCH2COOCH2Ph
PhCH(COOC2H5)2
PhCOOPh
PhCH2CH2OH
PhCH2CH2OH
PhCH(CH2OH)2
PhCH2OH
CH3CH2COOCH3
CH3CH@CHCOOCH3
CH3CH2CH2OH
CH3CH@CHCH2OH
a Reactions were conducted in diethyl ether under reflux using a 1:1 molar ratio of substrate to reducing agent.
b Yields refer to isolated products.
c Using a 1:2 mole ratio.
Table 7. Comparison of (Ppyz)Zr(BH4)2Cl2 with other zirconiumborohydride reagents for the reduction of aldehydes and ketones to the cor-
responding alcohols
Entry
Substrate
(Ppyz)Zr(BH4)2Cl2
ZrBDCa
Cp2Zr(BH4)Clb
[XP4–Zr(BH4)4]c
Time (h)/
yield (%)
Condi-
tions
Time (h)/
yield (%)
Conditions
Time (h)/
yield (%)
Condi-
tions
Time (h)/
yield (%)
Condi-
tions
1
2
3
4
Benzaldehyde
1/97
Et2O, rt
3.5/80
2/79
2.2/92
i-C3H7OH (Ref. 8)
H2O (Ref. 8)
i-C3H7OH (Ref. 8)
4/96
THF, rt
––
–/96
––
C6H6, rt
4-Chlorobenz-
aldehyde
Cyclohexanone
0.75/98
2.5/90
Et2O, rt
––
––
Et2O,
reflux
Et2O, rt
2.8/86
i-C3H7OH (Ref. 8)
––
––
15/80
6/95
THF, rt
THF, rt
Phenylcinnam-
aldehyde
0.75/90
2.7/92
0.7/90
i-C3H7OH (Ref. 8)
H2O (Ref. 8)
–/49
C6H6, rt
5
Acetophenone
8/95
Et2O,
reflux
8/90
H2O (Ref. 8)
0.2/98
C6H6, rt
12/80
THF, rt
a Dichlorobis[1,4-diazabicyclo(2,2,2)octane]-(tetrahydroborato)zirconium.8
b Bis(cyclopentadienyl)chlorotetrahydroborato zirconium(IV).4
c Polyvinylpyridiniumsupported zirconiumborohydride.
11
In conclusion, (Ppyz)Zr(BH4)2Cl2, unlike its unmodified
form, zirconium borohydride, is a stable bench top
reducing agent. Its mildness, chemo- and regio-selec-
tivity and high reaction yields make this new reagent
useful for organic synthesis.
flame dried under a stream of nitrogen. To this cooled
assembly, a solution of zirconium tetrachloride (2.5 g,
8.91 mmol) in diethyl ether (15 mL) was added followed
by a solution of lithium borohydride (1.2 g, 44.8 mmol)
in diethyl ether (30 mL). The resulting mixture was
stirred for 1 h at 0–5 °C and then centrifuged to give a
clear ethereal solution. To this clear solution piperazine
(0.6 g, 6.6 mmol) in dichloromethane (10 mL) was added
dropwise. The white precipitate, which formed imme-
Preparation of the zirconium borohydride–piperazine
complex: A 500 mL round bottomed flask equipped with
a magnetic pellet and fitted with a reflux condenser was

M. Tajbakhsh et al. / Tetrahedron Letters 45 (2004) 3295–3299
3299
3. Hutchins, R. O.; Marcowitz, M. Tetrahedron Lett. 1980,
21, 83–86.
4. Sorrell, T. N. Tetrahedron Lett. 1978, 50, 4985–4986.
5. Ranu, B. C.; Basu, M. K. Tetrahedron Lett. 1991, 32,
3243–3246.
diately was filtered and washed several times with di-
ethyl ether and dried to give a white stable powder in
96% yield.
General procedure for reduction of various organic com-
pounds: To a solution of the substrate (1.0 mmol) in
diethyl ether (10 mL) the reagent (1.0 mmol) was added
and the mixture stirred at room temperature or under
reflux for the specified time (Tables 1, 2, 4, 5 and 6).6
The progress of the reaction was followed by TLC
(eluent: CCl4/diethyl ether). On completion of the
reaction, the mixture was filtered and evaporated to
obtain the pure product.
6. Firouzabadi, H.; Adibi, N.; Zeynizadeh, B. Synth. Com-
mun. 1998, 28, 1257–1273.
7. Tamami, B.; Mansour Lakouraj, M. Synth. Commun.
1995, 25, 3089–3096.
8. Firouzabadi, H.; Iranpoor, N.; Alinejad, H. Synth. Com-
mun. 2002, 32, 3575–3586.
9. Maltseva, N. N.; Kedrova, N. S.; Gorobiskii, L. V.;
Kuznetzof, N. T. Russ. J. Coord. Chem. 2000, 26, 232–234.
10. Narasimhan, S.; Balakumar, R. Synth. Commun. 2000, 30,
941–946.
11. Tamami, B.; Goudarzian, N. J. Chem. Soc., Chem.
Commun. 1994, 1079.
12. Lattle, D. A.; Jensen, E. H.; Sturck, W. A. Anal. Chem.
1952, 24, 1843.
In a few cases, the crude products were purified by
chromatography. The products were identified by com-
parison of their spectra and physical data with those
of authentic samples.
13. (a) Rao, C. S.; Deshmuleh, A. A.; Patel, B. J. Ind. J. Chem.
1986, 25B, 626; (b) Bordaruah, M.; Barua, N. C.; Sharma,
R. P. Tetrahedron Lett. 1987, 28, 5741–5742; (c) Ranu, B.
C.; Chakraborty, R. Tetrahedron Lett. 1990, 31, 7663–
7664; (d) Nakano, T.; Umano, S.; Kino, Y.; Ishii, Y.;
Ogawa, M. J. Org. Chem. 1988, 53, 3752–3757.
14. (a) Ashbi, E. C.; Lin, J. J. Tetrahedron Lett. 1976, 17,
3865–3868; (b) Kim, S.; Moon, Y. C.; Ahn, K. H. J. Org.
Chem. 1984, 49, 17–20.
15. (a) Krishnamurthy, S.; Brown, H. C. J. Am. Chem. Soc.
1976, 94, 7159–7162; (b) Fortunato, J. M.; Ganem, B.
J. Org. Chem. 1976, 41, 2194–2200; (c) Luche, L. J. Am.
Chem. Soc. 1981, 103, 5454–5459.
Reduction of aldehydes versus ketones: To an equimolar
amount of aldehydes and ketones (4.0 mmol) in diethyl
ether (10 mL), the reagent (1.0 g, 4 mmol) was added and
the reaction mixture was stirred at room temperature for
the specified time (Table 3). The progress of the reaction
was monitored by TLC or GC. On completion of
the reaction, the mixture was purified on a silica gel
plate.
16. (a) Ranu, B. C.; Das, A. R. J. Org. Chem. 1991, 56, 4796–
4798; (b) Mittakanty, M.; Peters, J. L.; Morse, K. W.
J. Org. Chem. 1990, 55, 4464–4468; (c) Nutaitis, C. F.;
Bernardo, J. E. J. Org. Chem. 1989, 54, 5629–5630; (d)
Kaspar, J.; Trovanelli, A.; Lenarda, M.; Graziani, M.
Tetrahedron Lett. 1989, 30, 2705–2706.
References and notes
1. Marks, T. J.; Kolb, J. R. Chem. Rev. 1977, 77, 263–293.
2. Fleet, G. W. J.; Harding, P. J. C. Tetrahedron Lett. 1981,
22, 675–678.