Chromium-catalyzed pinacol coupling of benzaldehyde in water

Article abstract of DOI:10.1016/j.tetlet.2009.10.027

The pinacol coupling of benzaldehyde (0.25 M or 1.25 M) in water was catalyzed by 5-25 mol % CrCl₂ in the presence of Zn-dust or Al-dust at 20 °C or 60 °C. In all cases at most 50% of the pinacol coupling product, 1,2-diphenyl-1,2-ethanediol, w

Full text of DOI:10.1016/j.tetlet.2009.10.027

Tetrahedron Letters 50 (2009) 7172–7174
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Chromium-catalyzed pinacol coupling of benzaldehyde in water
*
Ronald L. Halterman , Jessica P. Porterfield, Shekar Mekala
Department of Chemistry and Biochemistry, 620 Parrington Oval, University of Oklahoma, Norman, OK 73019, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The pinacol coupling of benzaldehyde (0.25 M or 1.25 M) in water was catalyzed by 5–25 mol % CrCl in
2
Received 14 September 2009
Revised 5 October 2009
Accepted 6 October 2009
Available online 13 October 2009
the presence of Zn-dust or Al-dust at 20 °C or 60 °C. In all cases at most 50% of the pinacol coupling prod-
uct, 1,2-diphenyl-1,2-ethanediol, was obtained with the major product, benzyl alcohol, being formed by a
À
competitive 2e reduction of the carbonyl. The dl- to meso-diastereoselectivity of the pinacol products
ranged from 0.6:1 to nearly 1:1.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Pinacol coupling
Catalysis in water
Chromium catalysis
Benzaldehyde
Stereoselectivity
The pinacol coupling reaction of aldehydes to form vicinal diols
is developing into a versatile method for carbon–carbon bond for-
mation. Several low valent metals have been employed in stoichi-
in the presence of Al, Zn, or Mn.8 Hirao’s most effective catalytic
system for the coupling of aromatic aldehydes in water was the
1
3
use of 33 mol % VCl with stoichiometric aluminum at room tem-
ometric amounts to reduce aldehydes to ketyl radicals that can
then dimerize to form meso- or dl-isomers of 1,2-diol products.
perature for 3 days.
1
a
In order to extend the scope of reductive couplings in aqueous
media, we have initiated an investigation of the use of chromium
salts as catalysts for the pinacol reaction. Chromium complexes
have been effectively used in ternary catalytic systems for both
More desirable catalytic versions of the pinacol and related reac-
tions are also being developed.2 Good progress for the catalytic
3
coupling of aldehydes has been achieved using chromium, vana-
4
5
2,3
dium, or titanium salts in aprotic solvents by employing stoichi-
ometric reducing metals such as Mn or Zn and chlorosilanes to
recycle the catalytic metal. A schematic catalytic cycle for this ter-
nary system is shown in Figure 1. The key aspects of this cycle are
the reduction of the vanadium centers in postulated intermediate
A and the replacement of the alkoxide–vanadium bond with an
alkoxide–silicon bond.
pinacol and pinacol-type reactions in aprotic solvents. Since a
good variety of low valent chromium–ligand complexes are
9
known, it is likely that we could attach appropriate chromium
species to heterogeneous supports. The use of heterogeneous cata-
lysts in aqueous reactions would facilitate the removal of the
catalyst and potentially improve the cost effectiveness and envi-
ronmental impact of chromium in pinacol coupling reactions.
Herein we report preliminary results for the coupling of our
initially studied substrate, benzaldehyde.
Much of the emphasis of studies involving ternary catalyst
systems has been on improving catalytic turnovers, controlling
the dl-/meso-diastereomeric ratio of the 1,2-diol products and on
inducing enantioselectivity in the coupling reaction.6 In order to
extend the practicality and potentially the scope of the pinacol
coupling reaction, recent efforts have started to focus on the devel-
opment of binary catalyst systems that do not require chlorosil-
anes to release the catalyst from the diol.1a Due to potential
advantages in terms of safety, cost, and biocompatibility, develop-
ment of reactions that proceed efficiently in aqueous media has
received increased attention.7 Hirao has investigated a vana-
dium-catalyzed pinacol coupling of aromatic aldehydes in water
We initially examined the reductive coupling of benzaldehyde
[0.25 M] in water with 10 mol % CrCl
2
and excess Zn-dust at
*
Corresponding author. Tel.: +1 405 325 4836; fax: +1 405 325 6411.
E-mail address: RHalterman@ou.edu (R.L. Halterman).
n
Figure 1. Pinacol coupling by V /Zn(0)/R
3
SiCl-ternary catalyst system.
0
040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.027

R. L. Halterman et al. / Tetrahedron Letters 50 (2009) 7172–7174
7173
1
0
2
0 °C. We were gratified to observe the formation of diol 1 in a
product ratio of 37% in a dl-/meso-diastereomeric ratio of 0.7:1
along with the direct reduction product benzyl alcohol 2 in 63%
product ratio (Fig. 2). Some unreacted benzaldehyde (ca. 5%) was
1
also observed. An H NMR spectrum of a reaction mixture is shown
in Figure 3 in which the dl-1 and meso-1 product signals for the
benzylic CH groups are well separated, but the benzylic methylene
signal of benzyl alcohol 2 is quite near the meso-1 signal. The par-
tial overlap of the latter signals contributes to some uncertainty in
determining product ratios.
According to the catalytic scheme depicted in Figure 4,1b,3,5,8
Cr(II) can initially reduce the aldehyde (step a) to form radical
intermediate B. The reactive carbon site in B can combine with a
second aldehyde unit (either before or after its reduction) as in step
b to form coupled product C. Hydrolysis to release the 1,2-diol and
reduction of the chromium species back to a lower valent metal as
in step c completes the desired catalytic cycle. However, interme-
diate B can be further reduced by a second electron from coordi-
nated chromium or by an electron from an external metal as in
step d. This competitive side reaction can lead to the formation
of the undesired reduced benzyl alkoxide D that can hydrolyze to
form benzyl alcohol 2.
Figure 4. Catalytic cycle for Cr(II)/Zn(0)-catalyzed pinacol reaction with compet-
itive benzaldehyde reduction.
reductant on the formation of the desired 1,2-diol product were
studied. The results are summarized in Table 1 in which product
ratios are given. Since the benzyl alcohol product requires only
one benzaldehyde per molecule product, but the pinacol diols
require 2 equiv of benzaldehyde per product molecule, the actual
percent yields of the pinacol products would require doubling the
product ratios of 1 and renormalizing them. In control reactions
with no chromium catalyst present neither reduction nor pinacol
coupling products were observed in the presence of Zn-dust
The effects of varying the concentration of the reacting species,
the ratio of catalyst, the temperature, and the stoichiometric
(
entries 1 and 2). During the standard reaction time of 20 h the
reactions consumed nearly all benzaldehyde at 20 °C or at 60 °C
in the presence of Zn-dust (entries 3–8) when the starting benz-
aldehyde concentration was 0.25 M in water. When the concen-
tration of the reagents and catalyst were increased fivefold, the
reactions proceeded to complete consumption of benzaldehyde
at 20 °C (compare entries 9–11 with 3–5). In the presence of Al
as the stoichiometric reductant, only the reaction at 60 °C was
effective (entries 12 and 13). We noted incomplete reactions
when the heterogeneous reaction mixtures were not vigorously
stirred.
Figure 2. Pinacol coupling of benzaldehyde by Cr(II)/Zn(0) catalyst system in water.
In terms of the chemical selectivity for the pinacol coupling ver-
sus reduction to form benzyl alcohol, the benzyl alcohol was al-
ways the major product under all conditions studied. Under most
conditions, the ratio of pinacol to benzyl alcohol varied from 1:1
to 1:2. We noted that at higher temperature with a higher ratio
of starting chromium catalyst, a lower selectivity for the pinacol
coupling was obtained.
The catalytic reactions produced both diastereomeric pinacol
products dl-1 and meso-1 with the meso-product favored in ratios
from 0.6:1 to nearly 1:1. The stereoselectivity in the presence of
aluminum as the stoichiometric reductant was similar to when
zinc-dust was used.
In summary, we have shown that chromium salts will cata-
lyze the pinacol coupling of benzaldehyde in water in the pres-
ence of zinc or aluminum as terminal reductants. Gratifyingly,
the best pinacol/benzyl alcohol ratios were obtained with the
lowest chromium catalyst ratios. It was still disappointing that
the benzyl alcohol reduction product was in each case the major
product of the reaction. Given this promising entry into a cata-
lytic coupling reaction in water, we are next pursuing the reac-
tivity of different ligand systems on chromium to see if the
changes in the metal ligation can lead to more selectivity for
the coupling reaction. We also plan to extend our investigation
to include the coupling of different aromatic as well as aliphatic
aldehydes.
Figure 3. 1H NMR spectrum of pinacol reaction mixture.

7
174
R. L. Halterman et al. / Tetrahedron Letters 50 (2009) 7172–7174
Table 1
Pinacol coupling/reduction of benzaldehyde in water
Entry
CrCl a
2
[PhCHO] (M)
Metal reductantb
Temp (°C)
Recovered PhCHO (%)
% dl-1c
%meso-1
% 2
dl-/meso-
1/2
1
2
3
4
5
6
7
8
9
0
1
2
3
0
0
5
10
25
5
10
25
5
10
25
10
10
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
1.25
1.25
1.25
0.25
0.25
3 equiv Zn
3 equiv Zn
3 equiv Zn
3 equiv Zn
3 equiv Zn
3 equiv Zn
3 equiv Zn
3 equiv Zn
3 equiv Zn
3 equiv Zn
3 equiv Zn
3 equiv Al
3 equiv Al
20
60
20
20
20
60
60
60
20
20
20
20
60
100
100
ca. 5
ca. 5
ca. 5
ca. 5
ca. 5
ca. 5
<1
<1
<1
90
ca. 5
0
0
0
0
0
0
—
—
—
—
18
14
25
19
20
6
15
14
21
n.d.
22
23
23
28
20
23
11
18
19
23
n.d.
25
59
63
47
61
57
83
67
67
56
n.d.
53
0.8
0.6
0.9
1.0
0.9
0.6
0.8
0.7
0.9
n.d.
0.9
0.7
0.6
0.8
0.7
0.8
0.2
0.5
0.5
0.8
n.d.
0.9
1
1
1
1
a
b
c
Mol % of CrCl
2
relative to benzaldehyde.
Equivalents of metal reductant relative to benzaldehyde.
Percentages of products as relative product abundance in 1H NMR spectrum (unreacted benzaldehyde not included in ratio).
Tetrahedron: Asymmetry 2000, 11, 3861–3865; (f) Bensari, A.; Renaud, J.-L.;
Riant, O. Org. Lett. 2001, 3, 3863–3865; (g) Groth, U.; Jeske, M. Angew. Chem., Int.
Ed. 2000, 39, 574–576; (h) Fukuzawa, S.-i.; Oura, I.; Shimizu, K.; Kato, M.;
Ogata, K.-i. Eur. J. Org. Chem. 2009, 2009, 716–720.
Acknowledgments
Support for this work from the Oklahoma Biofuels Center to R.L.
Halterman and K.M. Nicholas and an NSF EPSCOR fellowship to
S.M. are gratefully acknowledged.
7. (a) Matsukawa, S.; Hinakubo, Y. Org. Lett. 2003, 5, 1221–1223; (b) Wang, C.;
Pan, Y.; Wu, A. Tetrahedron 2007, 63, 429–434.
8
9
.
.
Xu, X.; Hirao, T. J. Org. Chem. 2005, 70, 8594–8596.
Smith, K. M. Coord. Chem. Rev. 2006, 250, 1023–1031.
References
10. General procedure for the catalytic pinacol coupling: A suspension of zinc powder
3.0 mmol, 196 mg) and CrCl (0.10 mmol, 12.3 mg) in water (4 mL) was stirred
at 20 °C for about 5 min under a nitrogen atmosphere. Distilled benzaldehyde
1.0 mmol, 100 L) was added to the mixture which was then stirred
(
2
1
.
(a) Hirao, T. Top. Curr. Chem. 2007, 279, 53–75; (b) Gansauer, A.; Bluhm, H.
Chem. Rev. 2000, 100, 2771–2788; (c) Chatterjee, A.; Joshi, N. N. Tetrahedron
(
l
vigorously for 20 h. (For the heated reactions, the reaction flask was placed
in a silicon oil bath at 60 °C immediately following the addition of the
benzaldehyde.) The reactions were quenched with 1 N HCl (5 mL), additional
water (4 mL) was added, and the mixture was extracted with ether
2
006, 62, 12137–12158.
2.
3.
4.
5.
Groth, U.; Junc, M.; Vogel, T. Chem. Eur. J. 2005, 11, 3127–3135.
Svatos, A.; Boland, W. Synlett 1998, 549–551.
Hirao, T.; Hatano, B.; Imamoto, Y.; Ogawa, A. J. Org. Chem. 1999, 64, 7665–7667.
Gansäuer, A.; Moschioni, M.; Bauer, D. Eur. J. Org. Chem. 1998, 1998, 1923–
(
3 Â 20 mL). The combined organic layers were dried with magnesium
sulfate and filtered. The filtrate was concentrated under reduced pressure to
1
927.
give the crude product mixture (ca. 90% mass recovery) which was analyzed by
6
.
(a) Gansäuer, A.; Lauterbach, T.; Bluhm, H.; Noltemeyer, M. Angew. Chem., Int.
Ed. 1999, 38, 2909–2910; (b) Halterman, R. L.; Zhu, C.; Chen, Z.; Dunlap, M. L.;
Khan, M. A.; Nicholas, K. M. Organometallics 2000, 19, 324–329; (c) Yang, H.;
Wang, H.; Zhu, C. J. Org. Chem. 2005, 72, 10029–10034; (d) Yang, H.; Wang, H.;
Zhu, C. J. Org. Chem. 2007, 72, 10029–10034; (e) Enders, D.; Ullrich, E. C.
1
3
H NMR spectroscopy in CDCl . The diagnostic benzylic hydrogen signals for
meso-1 at 4.84 ppm, dl-1 at 4.72 ppm, and benzyl alcohol at 4.67 ppm were
used in conjunction with the total aromatic region 7.1–7.35 ppm to calculate
product ratios.