Pinacol reduction-cum-rearrangement. A re-examination of the reduction of aryl alkyl ketones by zinc-aluminum chloride

Article abstract of DOI:10.1016/S0040-4039(02)00737-2

Reduction of alkyl phenyl ketones by zinc and aluminum chloride in acetonitrile results in pinacol condensation followed by rearrangement. The phenyl group migrates in every instance.

Full text of DOI:10.1016/S0040-4039(02)00737-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4391–4393
Pinacol reduction-cum-rearrangement. A re-examination of the
reduction of aryl alkyl ketones by zinc–aluminum chloride
Anya A. Grant, Myron Allukian and Albert J. Fry*
Chemistry Department, Wesleyan University, Middletown, CT 06459, USA
Received 4 March 2002; accepted 9 April 2002
Abstract—Reduction of alkyl phenyl ketones by zinc and aluminum chloride in acetonitrile results in pinacol condensation
followed by rearrangement. The phenyl group migrates in every instance. © 2002 Elsevier Science Ltd. All rights reserved.
We recently had need for a series of symmetrically
substituted dialkylstilbenes (2). A report that aryl alde-
hydes and ketones (1) can be condensed to the corre-
sponding alkenes 2 by a mixture of zinc and aluminum
chloride in acetonitrile1 (Eq. (1)) promised to provide a
convenient route to the desired substances. However,
we report here that in our hands little or no alkene is
formed from aryl alkyl ketones (1). Rather, the reaction
takes a quite different course leading primarily to rear-
ranged dimeric ketones (3) (Table 1).
Table 1. Reduction of phenyl ketones with zinc and alu-
minum chloride in acetonitrile
Substrate
Rearranged
Other products (%)
ketone (3) (%)
1a, R=Me
1b, R=Et
953,4
822
2a (5)
2b (4); 1-phenyl-1-propene (8.5);
11b (4.5)
2c (2);
1c, R=i-Pr
933
1-phenyl-2-methylpropene (2);
11c (3)
1d, R=n-Bu
1e, R=t-Bu
99
1-Phenyl-1-butene (1)
1e (71.3); 2e (2); 13 (20); 12 (1);
11e (2); unk (1); unk (2)
2f (4); 14 (1); 15 (tr)
A number of aryl ketones were treated with a mixture
of zinc and aluminum chloride in acetonitrile under
nitrogen under conditions previously reported to afford
substituted stilbenes1 (ketone:Zn:AlCl3=1:2:2; 70°C;
20–24 h). Reaction mixtures were analyzed by GC–MS
0.75
1f, R=C6H5
956
1
and H NMR spectroscopy. In every case, the major
product was the rearranged ketone 3, though small
amounts of other substances, including 2, were pro-
duced in most reactions (Table 1).
ketone to aluminum chloride, followed by zinc reduc-
tion and possibly metal exchange, would afford radical
4. Dimerization of 4 would lead to bridged intermediate
5; coordination of AlCl3 to 5 would then induce pina-
colic rearrangement via cations 6 and 7 to afford
ketone 3. On the other hand, reduction of 4 by zinc,
We suggest the mechanistic sequence shown in Scheme
1 to account for these results. Coordination of the
(1)
* Corresponding author. Tel.: (860) 685-2622; fax: (860) 685-2211; e-mail: afry@wesleyan.edu
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00737-2

4392
A. A. Grant et al. / Tetrahedron Letters 43 (2002) 4391–4393
Scheme 1.
followed by protonation of the resulting intermediate
(probably by adventitious water) would afford interme-
diate 8, which could afford monomeric alkenes (10) by
AlCl3-induced elimination to cation 9, followed by rear-
rangement in favorable cases and in any event by final
loss of a proton. Alternatively, reduction of 8 by zinc
would lead to alkanes (11). Pivalophenone (1e) consti-
tuted an exception to the trends exhibited by the other
ketones examined; it reacted slowly under our standard
conditions; unreacted 1e constituted the primary con-
stituent of the reaction mixture after 20 h. The major
product at this point was 2-methyl-3-phenyl-2-butene
(13), accompanied by 2e, small amounts of two uniden-
tified isomers of 13, and neopentylbenzene (11e). Very
likely, dimerization of 4 is slowed sterically in this case,
leading to a preponderance of products (13 and its
isomers and 11e) arising from reduction of 4 by zinc. 1e
also produced a very small amount of dealkylated
ketone 12; this might have arisen by loss of t-butyl
cation from intermediate 7 to form a metallo enol,
which would be converted to 12 during the hydrolytic
workup. Benzophenone (1f) afforded small amounts of
tetraphenylethylene (2f), tetraphenylethane (14), and
triphenylmethane (15) in addition to the major product,
benzpinacolone (3f). The quality of the aluminum chlo-
ride employed turned out to have a pronounced influ-
ence on the course of these reactions. The most efficient
conversion of 1 to 3 took place using a freshly opened
bottle of aluminum chloride. Aged samples of AlCl3
afforded large amounts of unreacted starting material
and (only) in the case of benzophenone, an increased
amount (25% yield) of alkene 2f. Although we have not
observed formation of substituted stilbenes as the pre-
dominant products under any conditions, it is possible
that the previous literature report3 involved a different
grade of AlCl3 or a sample with a different storage
history.
Summary
Aryl alkyl ketones undergo pinacol-type condensation
and in situ rearrangement to the corresponding rear-
ranged ketones (3) with exclusive migration of the
phenyl group when heated with a mixture of zinc and
aluminum chloride in acetonitrile.7,8 This observation is
in fact consistent with an earlier report that substituted
benzophenones undergo transformation to 3 by the
action of zinc and aluminum chloride under ultrasonic
irradiation.6 Similar tandem coupling/rearrangement
sequences have been observed with aryl ketones and
NbCl3(DME).4
Acknowledgements
Financial support by the National Science Foundation
(Grant c CHE-0100727) is gratefully acknowledged.

A. A. Grant et al. / Tetrahedron Letters 43 (2002) 4391–4393
4393
References
mass spectrum m/z (intensity): 307 (m-1, <0.1), 223 (100),
180 (18), 166 (72), 119 (29) and 91 (70); 1H NMR spec-
trum (300 MHz, CDCl3): l 7.2–7.6 (m, 10H), 2.3 (t, 2H),
0.9–1.4 (m, 10H), 0.9 (t, 3H), 0.8 (t, 3H).
1. Dutta, D. K.; Konwar, D. Tetrahedron Lett. 2000, 41,
6227.
8. Reductive coupling of 1a (representative experiment). Anhy-
drous AlCl3 (2.67 g, 20 mmol) and Zn (1.30 g, 20 mmol)
were stirred under N2. Acetonitrile (60 ml) was added. The
mixture was allowed to cool, then acetophenone (1a) (1.20
g, 10 mmol) was added and the mixture was heated to
70°C and refluxed for 20 h. It was then cooled, diluted
with cold water and extracted with dichloromethane. After
drying and evaporation, analysis by GC–MS revealed a
mixture consisting of ketone 3a (95%) and 2,3-diphenyl-2-
butene (2a) (5%).
2. Yamazaki, T.; Saito, S.-i.; Ohwada, T.; Shudo, K. Tetra-
hedron Lett. 1995, 36, 5749.
3. Leimner, J.; Weyerstahl, P. Chem. Ber. 1982, 115, 3697.
4. Szymoniak, J.; Besancon, J.; Moise, C. Tetrahedron 1992,
48, 3867–3876.
5. Di Vona, M. L.; Rosnati, V. Main Group Met. Chem.
1999, 22, 469.
6. Sato, R.; Nagaoka, T.; Saito, M. Tetrahedron Lett. 1990,
31, 4165.
7. Ketones 3 are all known compounds,4–8 except for 3d,