Magnesium in water: Simple and effective for pinacol-coupling

Article abstract of DOI:10.1039/a806553e

A simple and effective pinacol-coupling has been carried out with magnesium. The reaction is highly effective in water in the presence of a catalytic amount of ammonium chloride. Under these conditions, various aromatic aldehydes and ketones undergo carbonyl coupling, generating 1,2-diols in good yields. The effectiveness of the reaction is strongly influenced by the steric environment surrounding the carbonyl group. Aliphatic aldehydes appear inert under the reaction conditions.

Full text of DOI:10.1039/a806553e

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Magnesium in water: simple and effective for pinacol-coupling
Wen-Chun Zhang and Chao-Jun Li*
Department of Chemistry, Tulane University, New Orleans, LA 70118
Received (in Corvallis, OR) 10th August 1998, Accepted 19th August 1998
Table
1
Pinacol-coupling mediated by magnesium in aqueous
A simple and effective pinacol-coupling has been carried
out with magnesium. The reaction is highly effective in
water in the presence of a catalytic amount of ammonium
chloride. Under these conditions, various aromatic
aldehydes and ketones undergo carbonyl coupling,
generating 1,2-diols in good yields. The effectiveness of the
reaction is strongly influenced by the steric environment
surrounding the carbonyl group. Aliphatic aldehydes
appear inert under the reaction conditions.
medium
Yield (%)a Yield (%)a
Substrate
of pinacol of reduced
Entry (1)
product 2
product 3
threo:erythrob
CHO
CHO
1
2
88(80)
93(87)
1
0
59:41
80:20
Discovered well over a century ago, the pinacol-coupling reac-
tion is still one of the most important reactions for the form-
ation of carbon–carbon bonds.1 Previously, pinacol-couplings
have been effected by using metals such as sodium,2 lithium,3
or magnesium() iodide4 (and Reike Mg5) under strictly
anhydrous conditions. Other reagents used for such a reaction
include chromium or vanadium,6 SmI2,7 Ce–I2,8 Yb,9 Bu3SnH,10
Al(Hg),11 as well as the versatile TiCl3 based reducing agents
(the McMurry pinacol-coupling).12 Recently, pinacol coupling
reactions mediated by Ti() in aqueous media have been inten-
sively investigated.13 Other metals like Zn–Cu14 or In15 have
also been found to promote the aqueous reaction under ultra-
sonic radiation and manganese in acidic conditions.16 Herein
we report a simple and effective pinacol-coupling mediated by
magnesium in water.17
When benzaldehyde was reacted with magnesium in 0.1 M
ammonium chloride aqueous solution, the corresponding
pinacol-coupling product was obtained in high yield. The use
of water alone as the reaction solvent was also effective; how-
ever, it resulted in a low conversion of the starting material. The
use of 0.1 M HCl aqueous solution as solvent also decreased
the yield of the desired pinacol-coupling product. Other aryl
aldehydes 1 [eqn. (1)] were coupled similarly to obtain the corre-
F
F
CHO
CHO
CHO
3
90(83)
56(42)
61(50)
96(89)
(90)
6
11
27
0
54:46
54:46
52:48
61:39
50:50
Cl
4
5
6
7
Cl
CHO
H3CO
Cl
CHO
CHO
(7)
8
9
(65)
(78)
(8)
0
61:39
54:46
51:49
H3C
H3CO
CHO
CHO
10
73(67)
10
F
Cl
CHO
11
12
0
(74)
(30)
na
Cl
HO
R
OH
R
CHO
O
magnesium
H2O
(1)
(62)
30:70
R
H
1
2
13
14
quant. (92)
0
0
0
64:36
na
CHO
CHO
O
sponding diols 2 (Table 1). It is noteworthy that aromatic alde-
hydes bearing halogens (bromo, chloro, fluoro) were coupled
without any complications in product formation. Furfural
coupled equally well under the reaction conditions. The coup-
ling of aryl ketones was also successful (entries 15 and 16). On
the other hand, an aliphatic aldehyde was inert under the reac-
tion conditions (entry 14). The magnesium mediated pinacol-
coupling in water appears strongly affected by steric effects. The
positions of substituents present on the aromatic rings show a
dramatic effect on the course of the reaction. While no substan-
tial difference was observed between meta- or para-substituted
aromatic aldehydes (compare entries: 2 and 3, 4 and 7, 6 and 9),
the presence of ortho-substituents increased the formation of
reduced product (entries 5, 10 and 12). A similar increase in the
amount of the reduced product was observed on increasing the
size of the ortho-substituents. When two substituents were pres-
ent (entry 11), no pinacol-coupling product was obtained;
complete reduction of the aldehyde was observed.
O
CH3
CH3
15
16
66(59)
(41)
8
53:47
53:47
O
na
MeO
O
17
0
0
na
Reactions were carried out with carbonyl compound (1.89 mmol),
magnesium turnings (1 g) in 0.1 M aqueous ammonium chloride 10 mL
at r.t. for 12–24 h. a Measured by H NMR (isolated yields in paren-
1
theses). b threo:erythro Ratios were measured by 1H NMR based on the
intensities of benzylic protons. For entry 15, 26% of the starting
material was recovered.
In the notable report by Gomberg and Bachmann,4 the use of
a Mg–MgI2 (1:1) mixture in anhydrous benzene or ether for
carbonyl coupling was rationalized through the formation of
MgI and the coupling of radical intermediates. In the present
investigation, no magnesium salt was present, thus indicating,
apparently, the occurrence of the reaction through a different
mechanism. We tentatively rationalize the experimental results
J. Chem. Soc., Perkin Trans. 1, 1998, 3131–3132
3131

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a Sustainable Environment and the Center for Photo-induced
O
Processes (NSF/LEQSF). Acknowledgement is also made to
the donors of the Petroleum Research Fund (administered by
the ACS), LEQSF and an NSF CAREER Award for partial
support of this research.
R
H
O
H
O
H
route a
O
O
–
•
pinacol
2
References
R
H
R
H
Mg
1 For recent reviews on pinacol-coupling, see: T. Wirth, Angew.
Chem., Int. Ed. Engl., 1996, 35, 61; G. M. Robertson, in Comprehen-
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3 S. K. Pradhan and K. R. Thakker, Tetrahedron Lett., 1987, 28, 1813.
4 M. Gomberg and W. E. Bachmann, J. Am. Chem. Soc., 1927, 49,
236.
Mg+•
H2O
H
route b
HO
reduction
3
Scheme 1 Postulated mechanism for magnesium-mediated pinacol
coupling and reduction of carbonyl compounds.
5 A. Fürstner, R. Csuk, C. Rohrer and H. Weidmann, J. Chem. Soc.,
Perkin Trans. 1, 1988, 1729.
6 J. B. Conant and H. B. Cutter, J. Am. Chem. Soc., 1926, 48, 1016.
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8 T. Imamoto, T. Kusumoto, Y. Hatanaka and M. Yokoyama, Tetra-
hedron Lett., 1982, 23, 1353.
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11 M. Hulce and T. LaVaute, Tetrahedron Lett., 1988, 29, 525.
12 For reviews, see: A. Fürstner and B. Bogdanovi’c, Angew. Chem.,
Int. Ed. Engl., 1996, 35, 2443; J. E. McMurry, Chem. Rev., 1989, 89,
1513; B. E. Kahn and R. D. Rieke, Chem. Rev., 1988, 88, 733.
13 A. Clerici and O. Porta, Tetrahedron Lett., 1982, 23, 3517; A. Clerici
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J. Schwartz, J. Am. Chem. Soc., 1996, 118, 5484.
as shown in Scheme 1. During the reaction, there are two poten-
tial pathways competing with each other; generating either
pinacol-coupling product (route a) or reduced product (route
b). The increase in steric hindrance around the carbonyl would
destabilize the transition-state in route a, thus favoring the
formation of the reduced product. The presence of NH4Cl
would clean the metal surface to effect further reactions.
In conclusion, we found magnesium to be effective for medi-
ating pinacol-coupling reactions in 0.1 M aqueous NH4Cl.
The product formation was strongly influenced by steric effects.
We are presently exploring this new reactivity in synthetic
applications.
Experimental
14 P. Delair and J. L. Luche, J. Chem. Soc., Chem. Commun., 1989, 398.
See also, T. Tsukinoki, T. Kawaji, I. Hashimoto, S. Mataka and
M. Tashiro, Chem. Lett., 1997, 235; K. Tanaka, S. Kishigmi and
F. Toda, J. Org. Chem., 1990, 55, 2981.
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hedron Lett., 1998, 39, 4367.
16 C. J. Li, Y. Meng, X. H. Yi, J. H. Ma and T. H. Chan, J. Org. Chem.,
1997, 62, 8632.
17 C. J. Li, Chem. Rev., 1993, 93, 2023; A. Lubineau, J. Auge and
Y. Queneau, Synthesis, 1994, 741; C. J. Li, Tetrahedron, 1996, 52,
5643; C. J. Li and T. H. Chan, Organic Reactions in Aqueous Media,
John Wiley & Sons, New York, 1997.
A sample experimental procedure follows. A suspension of
benzaldehyde (200 mg, 1.89 mmol) and magnesium turnings
(1 g, 41.67 mmol) in 0.1 M aqueous ammonium chloride
(10 mL) was stoppered and stirred overnight (vigorously) under
an atmosphere of air and at room temperature. The reaction
was quenched with 3 M aqueous HCl and extracted with ethyl
acetate (3 × 20 mL). The combined organic layers were washed
with saturated aqueous NaHCO3 solution and brine, dried over
magnesium sulfate and filtered. The filtrate was concentrated
in vacuo to give a crude material, which was purified by flash
chromatography on silica gel to afford the pinacol product (162
mg, 80%) as a white crystalline solid.
Acknowledgements
Communication 8/06553E
The research was supported by the NSF-EPA joint program for
3132
J. Chem. Soc., Perkin Trans. 1, 1998, 3131–3132