Vanadium-catalyzed pinacol coupling reaction in water

Article abstract of DOI:10.1021/jo051213f

A catalytic pinacol coupling using water as a solvent was performed by a catalytic amount of vanadium(III) chloride and metallic Al as a co-reductant. A combination forms a binary catalytic system, being a sharp contrast to the reaction in organic solvent, which requires a chlorosilane as an additive. Various aromatic aldehydes underwent the reductive coupling to give the corresponding 1,2-diols in moderate to good yields.

Full text of DOI:10.1021/jo051213f

ganic reaction in water or aqueous media has attracted
great interest in organic synthesis from the vantage
points of its cost, safety, and environmental concern.11
Therefore, the development of an efficient synthetic
methodology to form a carbon-carbon bond in water or
aqueous media appears to be very important. On the
basis of this contract, the pinacol coupling reaction has
been accomplished using water or aqueous media as a
solvent, but these protocols require a stoichiometric
metallic reductant with an acid or base activator, or a
stoichiometric metallic reductant generated by treatment
with a metallic co-reductant.3c,d,5d,6a,7a,b,8a,d,9,10 Upon check-
ing the literature, we found no examples for a catalytic
system to induce the pinacol coupling in water. Recently,
we have successfully developed a catalytic pinacol cou-
pling for the first time using a ternary catalytic system
consisting of a vanadium or titanium catalyst, a metallic
co-reductant, and a chlorosilane (eq 1).12 The presence
of a chlorosilane is essential to recycle a catalyst. A
catalytic system working in water should be developed
from these points of view. We herein describe the
catalytic pinacol coupling reaction in water using a binary
catalytic system.
Vanadium-Catalyzed Pinacol Coupling
Reaction in Water
Xiaoliang Xu and Toshikazu Hirao*
Department of Applied Chemistry, Graduate School of
Engineering, Osaka University, Yamada-oka,
Suita, Osaka 565-0871, Japan
hirao@chem.eng.osaka-u.ac.jp
Received June 15, 2005
A catalytic pinacol coupling using water as a solvent was
performed by a catalytic amount of vanadium(III) chloride
and metallic Al as a co-reductant. A combination forms a
binary catalytic system, being in sharp contrast to the
reaction in organic solvent, which requires a chlorosilane
as an additive. Various aromatic aldehydes underwent the
reductive coupling to give the corresponding 1,2-diols in
moderate to good yields.
The pinacol coupling is a powerful synthetic method
for constructing vicinally functionalized carbon-carbon
bonds.1 Various low-valent metals such as Al-Hg,2 Sm,3
V,4 Mg,5 Ti,6 Zn,7 Mn,8 Al,9 and In10 have been used to
promote this reductive coupling reaction. Recently, or-
Using vanadium or titanium salts as a stoichiometric
promoter, we studied first the effect of metallic co-
reductants and solvent on the pinacol coupling reaction
of benzaldehyde (eq 2 and Table 1). No reaction occurred
only with metallic Zn or Al in water (entries 1 and 2).
When 1 mmol of NH4VO3, Ti(OPr-i)4, or VOSO4‚(2-3
H2O) was combined with 3 mmol of co-reductant Zn, most
of the benzaldehyde (1 mmol) remained without reduction
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10.1021/jo051213f CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/13/2005
8594
J. Org. Chem. 2005, 70, 8594-8596

TABLE 1. Effect of Vanadium or Titanium Salt, Metallic Co-Reductant, and Solvent on the Stoichiometric Pinacol
Coupling of Benzaldehydea
entry
metallic salt
metallic co-reductant
solvent (mL)
time (h)
yield (%)
dl/mesob
1
-
-
Zn
Al
H2O (8)
36
36
36
36
48
40
40
40
41
48
36
48
48
48
0
2
H2O (8)
0
3
NH4VO3
Ti(OPr-i)4
VOSO4‚(2-3H2O)
VCl3
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Mg
Mn
Al
H2O (8)
H2O (8)
<5
<5
trace
65
32
76
81
86
95
80
62
92
4
5
H2O (4), DMF (4)
H2O (4), THF (4)
H2O (0.2), THF (0.8)
H2O (6), DMF (6)
H2O (6), MeOH (6)
H2O (8)
6
72/28
67/33
66/34
62/38
64/36
57/43
50/50
58/42
65/35
7
VCl3
8
VCl3
9
VCl3
10
11
12
13
14
VCl3
VBr3
H2O (8)
VCl3
H2O (8)
VCl3
H2O (8)
VCl3
H2O (8)
a Benzaldehyde, 1 mmol; metallic salt, 1 mmol; metallic Zn, Mg, Mn, or Al, 3 mmol; vigorous stirring; room temperature. b Based on
the analysis of 1H NMR of the crude products.
TABLE 2. Effect of Additives on the Stoichiometric Pinacol Coupling of Benzaldehydea
entry
metallic co-reductant
additive (mmol)
solvent (mL)
time (days)
yield (%)
dl/mesob
1
2
3
4
5
Zn
Zn
Zn
Al
ethylene glycol (1)
2,2′-dipyridyl (1)
Me2NCH2CH2NMe2 (1)
R-CD (1)
H2O (2)
1.5
1.5
2
63
95
51
74
74
60/40
56/44
52/48
66/34
69/31
H2O (2)
H2O (2)
H2O (10)
H2O (3), MeCN (3)
4
Al
â-CD (0.2)
3
1
a Benzaldehyde, 1 mmol; VCl3, 1 mmol; metallic Zn or Al, 3 mmol; vigorous stirring; room temperature. b Based on the analysis of H
NMR of the crude products.
TABLE 3. Cat. VCl3/Al Catalyzed the Pinacol Couplinga
entry
substrate 1
metallic co-reductant
solvent (mL)
time (days)
product and isolated yield (%)
dl/meso
1
PhCHO
Zn
Al
Al
Al
Al
Al
Al
Al
Al
Al
Alc
Alc
Alc
H2O (2)
3
2a, 75b
2a, 92b, 72
2b, 79
2c, 84
2d, 62
2e, 53
2f, 68
2g, 51
2h, 62
0
51/49
56/44
45/55
62/38
42/58
56/44
54/46
59/41
71/29
-
2
PhCHO
H2O (2)
3
3
3-ClPhCHO
4-MePhCHO
2-ClPhCHO
2-BrPhCHO
4-ClPhCHO
4-MeOPhCHO
2-furaldehyde
PhCOCH3
H2O (2)
4
4
H2O (2)
4
5
H2O (2)
4
6
H2O (2)
5
7
H2O (1), THF (1)
H2O (2)
3.5
4
8
9
H2O (1)
3
10
11
12
13
H2O (2)
3
PhCHO
3-ClPhCHO
4-MePhCHO
H2O (2)
3
2a, 65
2b, 66
2c, 59
59/41
50/50
62/38
H2O (2)
3
H2O (2)
4
a Aldehyde or ketone, 1 mmol; vanadium(III) chloride, 0.33 mmol unless otherwise stated; metallic Zn or Al, 3 mmol; vigorous stirring;
room temperature. b Based on the analysis of 1H NMR of the crude product. c Vanadium(III) chloride, 0.2 mmol.
and the yield of the pinacol was less than 5% or trace
(entries 3-5). Gratifying results were obtained in the
case of VCl3, which promoted the reductive coupling
reaction in the presence of Zn to give the pinacol in 86%
yield with 64/36 ratio of the dl and meso isomers (entry
10). Although several cosolvents, such as H2O-DMF,
H2O-THF, and H2O-MeOH, were surveyed using VCl3/
Zn as a promoter, no improvement was observed in both
the yield and dl/meso selectivity (entries 6-9). As com-
pared with VCl3, VBr3 gave a slightly better yield (entry
11). Since VBr3 is expensive, three metallic Al, Mg, and
Mn were employed in the presence of VCl3 to show that
metallic Al was more efficient as a co-reductant (entries
12-14).
Several types of additives were also surveyed when a
stoichiometric amount of VCl3 was used in the presence
of a metallic co-reductant (Table 2). As shown in Table
2, use of additives such as ethylene glycol and Me2NCH2-
CH2NMe2 resulted in lower yields as compared with 2,2′-
dipyridyl (entries 1-3). When R-CD or â-CD was used
as an additive, the yield was moderate with a little higher
dl selectivity (entries 4 and 5).
From the above two tables, the combination of VCl3
and Al was found to be a more efficient system to promote
the pinacol coupling in water although the effect of
several additives was tried. To increase the reaction
efficiency, the amount of VCl3 was reduced to 0.33 mmol
(eq 3 and Table 3). It should be noted that the catalytic
pinacol coupling reaction successfully proceeded in water
even in the absence of a chlorosilane. It is in sharp
contrast to the reaction in organic solvent, which requires
a chlorosilane as an essential additive. This finding
J. Org. Chem, Vol. 70, No. 21, 2005 8595

TABLE 4. Effect of Additives on the Catalytic Pinacol
Coupling of Benzaldehyde
to the carbonyl group. Considering that the 0.33 mmol
of VCl3 in water may be hydrolyzed to give about 1 mmol
of HCl, the combination of 3 mmol of Al and 2 mL of 0.5
N HCl was employed as a promoter using p-methylbenz-
aldehyde as a substrate (eq 5). However, the NMR yield
was very low compared with the result of entry 4 in Table
3. Although the detailed mechanism of the catalytic
reaction requires more investigation, a low-valent vana-
dium or titanium species generated by treatment with
Al is likely to be involved in a catalytic cycle.13
NMR yield
entry
additive (equiv)
solvent
(%)a
dl/meso
1
2
3
4
R-CD (1)
H2O
11
73
92
0
64/36
64/36
42/58
-
â-CD (0.2)
H2O-MeCN
2,6-di-OMe-â-CD (1)
2,3,6-tri-OMe-â-CD (1) H2O
H2O
a Based on the analysis of 1H NMR of the crude product.
provides a synthetically versatile method. Metallic Al was
found to give a better result than Zn (entries 1 and 2).
In conclusion, a catalytic pinacol coupling reaction of
aromatic aldehydes proceeds with cat. VCl3/Al in the
absence of a chlorosilane, which is considered to be of
synthetic potential as an environmentally harmonious
catalyst.
Various aromatic aldehydes underwent the reductive
coupling with the cat. VCl3/Al system in water to give
the corresponding 1,2-diols in moderate to good yields.
Interestingly, a little high dl selectivity was observed in
the case of the aromatic aldehydes bearing an electron-
donating group (entries 4 and 8). 2-Furaldehyde was also
converted to the diols with 71/29 of dl/meso ratio (entry
9). Acetophenone was not reduced under the similar
conditions. The amount of VCl3 could be decreased from
0.33 mmol to 0.2 mmol despite the comparatively lower
yields (entries 11-13).
Several kinds of cyclodextrins were added as an
additive in the catalytic pinacol coupling of benzaldehyde,
but the dl/meso selectivity was not improved with almost
the similar or lower yields (eq 4 and Table 4). Use of R-CD
resulted in only 11% yield of 2a. While 2,6-di-OMe-â-CD
gave the better result, no desired product was obtained
with 2,3,6-tri-OMe-â-CD.
Experimental Section
A General Procedure for the Pinacol Coupling Induced
by Cat. VCl3/Al. A suspension of 3 mmol (81 mg) of activated
aluminum powder and 0.33 mmol of VCl3 (52 mg) in 1-2 mL of
water was stirred for about 5 min at room temperature. Then,
1 mmol of aromatic aldehyde 1 was added to the mixture, which
was stirred vigorously for the time indicated in Table 3. The
reaction was quenched with 1 N HCl and extracted with ether
(3 × 30 mL). The combined organic layers were washed with
brine, dried over with sodium sulfate, and filtered. The filtrate
was concentrated under reduced pressure to give crude materi-
als, which were purified by column chromatography on silica
gel, eluting with hexane and ethyl acetate (3:1), to give the
purified pinacol product 2.
Supporting Information Available: Experimental pro-
cedures, compound characterization data for selected com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO051213F
(13) Another reaction path where vanadium hydroxide formed by
in situ hydrolysis acting as a Lewis acid and Al metal serves as a
reducing agent might be possible.
The reduction mechanism is generally believed to
proceed through one-electron transfer from the catalyst
8596 J. Org. Chem., Vol. 70, No. 21, 2005