that new reaction conditions need to be found which reduce
the emission of volatile organic solvents and the use of
hazardous toxic chemicals. In this connection, organic
reactions in aqueous media have attracted considerable recent
interest because water is considered to be a safe and
KF, the reaction gave a high yield of the pinacol (2, R )
Ph) as a nearly 1:1 mixture of dl and meso isomers. However,
the reduction product, benzyl alcohol (3, R ) Ph) was formed
to a significant extent as well.
(2) Unexpectedly, the cation of the fluoride salt has an
effect on the partition of the products. Using the series of
alkali metal fluoride salts under otherwise identical reaction
6
environmentally benign solvent. We are therefore interested
in exploring metal reduction reactions in water, but without
the use of mercury amalgams due to the known toxicity of
mercury. We have chosen to examine the potential of
aluminum metal in view of its low cost and ready availability.
Aluminum has a low first ionization potential of 5.986 eV,
and this should render it among the most reducing metals.
On the other hand, aluminum is resistant to water because it
9
conditions, the yield of the reduction product 3 as a
percentage of the total (2 plus 3) declined progressively from
24% to 8% as the cation changed from Li to Cs (entries
1-5, Table 2). We attributed this change to the size of the
2 3
forms readily a thin film of insoluble Al O as an armor to
Table 2. Al/MF Promoted Pinacol Coupling of Carbonyl
prevent itself from further reaction. The challenge here is to
find ways to overcome the well-known insolubility of
aluminum oxide in water that so far precluded the use of
Compounds in Watera
yield
7
time
(h)
(%) of 2
(meso:dl)b (%) of 3
yield
aluminum in aqueous media.
8
entries
aldehydes
PhCHO
PhCHO
PhCHO
PhCHO
PhCHO
PhCHO
m-ClPhCHO
m-ClPhCHO
promoter
Reports that the presence of trace amount of fluoride
b
24b
16b
13b
10b
8b
anion in water dramatically increased the corrosion of
aluminum metal drew our attention to the possibility of using
fluoride salts to activate aluminum metal in water. Using
benzaldehyde as the prototypal aldehyde, we examined its
reaction with aluminum in aqueous media with various
fluoride salts. The results are summarized in the following
general conclusions.
1
2
3
4
5
6
7
8
9
LiF
NaF
KF
RbF
CsF
Bu4NF
KF
5 days 76 (1.1:1)
2 days 84 (1:1.0)
16
b
b
87 (1:1.0)
b
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
90 (1:1.1)
b
92 (1:1.0)
b
1b
99 (1:1.5)
5b
75 (1:1.2)
95 (1:2.2)
100 (1:1.3)
97 (1:2.5)
92 (1:1.2)
76 (1:2.3)
90 (1:1.1)
93 (1:1.1)
94 (1:2.2)
76 (1:2.1)
60 (1:1.5)
/
6b
Bu4NF
(1) It is clear that fluoride salts have a special activating
p-CF PhCHO KF
/
2b
7b
5b
8b
6b
5b
10b
18b
10b
/
3
effect on aluminum metal in aqueous media. Comparing the
series of KF, KCl, KBr, and KI (entries 1-4, Table 1), only
10
p-CF3PhCHO Bu4NF
1
1
1
1
1
1
2
3
4
5
p-CH3PhCHO KF
p-CH3PhCHO Bu4NF
m-CH3PhCHO KF
o-CH3PhCHO KF
o-CH3PhCHO Bu4NF
PhCOCH3
PhCOCH3
c-C6H11CHO
c-C6H11CHO
cyclohexanone KF
Table 1. Effects of Halide Ions on the Reaction of
Benzaldehyde with Al/KX in Watera
16
Bu4NF
KF
KF
1
7
products, %b
time
(h)
convn
(%)b
18
19
entries
reagent
meso-2 dl-2
3
Bu4NF
/
/
/
2
2
0
1
/
/
1
2
3
4
5
6
7
8
9
2.5Al/1 M KF
2.5Al/1 M KCl 16
2.5Al/1 M KBr 16
2.5Al/1 M KI
2.5Al/H2O
2.5Al/2 M KF
2.5Al/3 M KF
2.5Al/4 M KF
2.5Al/5 M KF
16
100
0
0
0
0
100
0
0
41
0
0
0
0
42
0
0
45
0
0
0
0
42
0
0
13
0
0
0
0
13
0
0
cyclohexanone Bu4NF
a
For experimental conditions, see ref 9. b On the basis of the analysis
1
of H NMR of crude product.
16
1 week
16
16
16
16
cation. Consistent with this rationale, we found that when
tetrabutylammonium fluoride (TBAF) was used as salt, the
product was almost exclusively the pinacol 2 (entry 6).
Other substituted benzaldehydes can be similarly coupled
in high yields (entries 7-15) using either KF or TBAF as
the activating agent. Acetophenone reacted as well to give
mainly the pinacol product (entries 16 and 17). In all these
cases, the pinacol product 2 was formed as a mixture of dl
0
0
0
0
10
a
For experimental conditions, see ref 9. b On the basis of the analysis
1
of H NMR of crude product.
the addition of KF to Al/H
dehyde. Furthermore, in the absence of KF, Al/H
2
O led to reaction with benzal-
O is
9
2
completely inactive (entry 5). On the other hand, too high a
concentration of KF (greater than 3 M) also prevented the
reaction from occurring (entries 7-9). With 1 M or 2 M
(
7) Pinacol coupling of carbonyl compounds with Al powder in methanol
promoted by KOH or NaOH had been reported: Khurana, J. M.; Sehgal,
A. J. Chem. Soc., Chem. Commun. 1994, 571. Khurana, J. M.; Sehgal, A.;
Gogia, A.; Manian, A.; Maikap, G. C. J. Chem. Soc., Perkin Trans. 1 1996,
2
213. Sahade, D. A.; Mataka, S.; Sawada, T.; Tsukinoki, T.; Tashiro, M.
(6) For reviews, see: (a) Li, C. J.; Chan, T. H. Organic Reactions in
Tetrahedron Lett. 1997, 38, 3745.
Aqueous Media; John Wiley & Sons Inc.; New York, 1993. (b) Li, C. J.
Chem. ReV. 1993, 93, 2023. (c) Chan, T. H.; Li, C. J.; Lee, M. C.; Wei, Z.
Y. Can. J. Chem. 1994, 72, 1181. (d) Lubineau, A.; Auge, J.; Queneau, Y.
Synthesis 1994, 741. (e) Li, C. J. Tetrahedron 1996, 52, 5643. (f) Chan, T.
H.; Issac, B. M. Pure Appl. Chem. 1996, 68, 919.
(8) (a) Tennakone, K.; Wickramanayake, S. Nature 1987, 325, 202. (b)
Hurlen, T.; Johansen, K. H. Acta Chem. Scand., Ser. A 1985, A39, 545. (c)
Foley, R. T.; Trzaskoma, P. P. Corrosion (Houston) 1977, 33, 435. (d)
Tennakone, K.; Wickramanayake, S.; Fernando, C. A. N. EnViron. Pollut.
1988, 49, 133. (e) Valand, T.; Nilsson, G. Corros. Sci. 1977, 17, 449.
1130
Org. Lett., Vol. 2, No. 8, 2000