Mn(III) acetate-mediated regioselective benzylation of various α,β-unsaturated and β-alkoxy-α,β-unsaturated ketones

Article abstract of DOI:10.1016/j.tetlet.2003.08.001

We describe herein the results of manganese(III) acetate mediated α′-benzylation of various α,β-unsaturated and β-alkoxy-α,β-unsaturated ketones in moderate yields.

Full text of DOI:10.1016/j.tetlet.2003.08.001

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7311–7313
Mn(III) acetate-mediated regioselective benzylation of various
a,b-unsaturated and b-alkoxy-a,b-unsaturated ketones
8
Cihangir Tanyeli* and Devrim Ozdemirhan
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Received 28 April 2003; revised 23 July 2003; accepted 1 August 2003
Abstract—We describe herein the results of manganese(III) acetate mediated a%-benzylation of various a,b-unsaturated and
b-alkoxy-a,b-unsaturated ketones in moderate yields.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
ated a%-benzylation of various a,b-unsaturated ketones
and b-alkoxy a,b-unsaturated ketones and the optimi-
sation of the reaction conditions.
The major problem in designing and synthesising com-
plex molecules is the development of reactions which
emphasise chemo-, regio-, and stereoselectivity. In
defining strategies and reactions to construct complex
molecules, regioselectivity is required.1 Base-induced
benzylation plays an important role in the synthesis of
some natural compounds, e.g. terpenoids2 and the
lycorine alkaloid family.3 A wide variety of benzylation
reactions are well known in the literature as useful
methods for carbonꢀcarbon bond formation, i.e. base-
induced benzylation of ketones4 and conversion of a-
benzyl ketones to a%-benzyl a,b-unsaturated ketones via
organoselenium chemistry.5,6 In these studies, the con-
trol of regioselectivity is difficult because of the high
reaction temperatures required.5 Furthermore, the
structures of the substrates are limited5 and usually
high yields of O-benzylated products are obtained when
the substrates are b-alkoxy a,b-unsaturated ketones.7
These problems encountered during the synthesis of
various a%-benzyl a,b-unsaturated ketones prompted us
towards the development a new method for the direct
benzylation of a,b-unsaturated ketones and b-alkoxy
a,b-unsaturated ketones. From our earlier studies, we
found that trapping a%-keto radicals obtained from
b-alkoxy a,b-unsaturated ketones by benzene,8 used as
a solvent, is much faster than acetoxylation, affording
good yields of tandem oxidation products9 and also the
direct allylation of various a,b-unsaturated ketones
gives good yields of a%-allylated products.10 We describe
herein the results obtained from the Mn(OAc)3-medi-
2. Results and discussion
As a starting point, we studied the use of mangane-
se(III) acetate as a potential mediator for metal pro-
moted
regioselective
a%-benzylation
of
3-methyl-2-cyclopentenone 1b chosen as a model com-
pound. Reaction of 1b in benzene with 2 equiv. of
Mn(OAc)3·2H2O and 1 equiv. of benzyl bromide for 9
h at reflux afforded a 65% yield of 5-benzyl-3-methyl-2-
cyclopentenone 2b (Scheme 1). No a%-acetoxylation was
observed. In order to increase the yield of the reaction,
3 equiv. of Mn(OAc)3·2H2O was used, however, the
isolated yield of the benzylation product was drastically
decreased to 51% and 12% of the a%-acetoxylation
product was isolated. Changing the amount of
Mn(OAc)3·2H2O to 1 equiv. decreased the yield of the
benzylation product (59%) and no a%-acetoxylation
product was observed. Subsequently, a variety of
cyclopentenones and cyclohexenones were tested with
this metal-mediated benzylation method and selected
examples are listed in Table 1.
Keywords: enones; manganese and compounds; benzylation.
* Corresponding author. E-mail: tanyeli@metu.edu.tr
Scheme 1.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.001

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C. Tanyeli, D. Ozdemirhan / Tetrahedron Letters 44 (2003) 7311–7313
7312
Table 1. a%-Benzylation of a,b-unsaturated ketones medi-
ated by Mn(OAc)3
Table 2. a%-Benzylation of b-alkoxy a,b-unsaturated
ketones mediated by Mn(OAc)3
manganese(III) acetate, in one-step, and in moderate
yields. The optimisation of the yields is ongoing.
3. Experimental
3.1. General procedure for the Mn(OAc)3 mediated
benzylation of a,b-unsaturated ketones 1 and b-alkoxy
a,b-unsaturated ketones 3
A mixture of Mn(OAc)3·2H2O (3.25 g, 14.0 mmol) in
benzene (150 ml) was refluxed for 45 min using a
Dean–Stark trap. Then the mixture was cooled to room
temperature and the a,b-unsaturated ketone (or b-
alkoxy a,b-unsaturated ketone) (7.0 mmol) and benzyl
bromide (1.20 g, 7.0 mmol) were added. The mixture
was allowed to reflux until the dark brown colour
disappeared and was also monitored by TLC. The
reaction mixture was diluted with an equal amount of
ethyl acetate and the organic phase was washed with
1N HCl followed by saturated NaHCO3 and brine. The
organic phase was dried over MgSO4 and evaporated in
vacuo. The crude product was separated by flash
column chromatography using ethyl acetate/hexane as
eluent to afford the product.
Scheme 2.
As a natural extension of this study, we pursued a
complementary investigation aimed at subjecting vari-
ous b-alkoxy a,b-unsaturated ketones to this reaction.
When 3-ethoxycyclohex-2-enone 3c was stirred with 2
equiv. of Mn(OAc)3·2H2O and 1 equiv. of benzyl bro-
mide in benzene for 14 h at reflux, a 42% yield of
6-benzyl-3-ethoxycyclohex-2-enone 4c was isolated.
Subsequently, unsubstituted 3-ethoxycyclopent-2-enone
3a and 3-ethoxy-2-methylcyclopent-2-enone 3b were
tested with this metal-mediated benzylation method
(Scheme 2). The results are listed in Table 2.
3.2. 5-Benzyl-3-methylcyclopent-2-enone 2b
(0.85 g, 65%). IR (neat): 3044, 2965, 1695 cm−1. 1H
NMR: l 2.06 (s, 3H), 2.71 (d, J=19 Hz, 1H), 2.29 (d,
J=19 Hz, 1H), 2.51–2.64 (m, 1H), 2.69–2.75 (m, 1H),
3.23 (dd, J=14 and 4 Hz, 1H), 5.92 (s, 1H), 7.15–7.48
(m, 5H). 13C NMR: l 19.8, 36.9, 39.2, 48.1, 126.2,
128.0, 128.5, 129.2, 139.1, 177.2, 210.4. HRMS m/e
(observed): 186.1052, (calculated): 186.1045.
In the next step of this study, 3-ethoxycyclohex-2-enone
3c was chosen as
a model compound and the
Mn(OAc)3·2H2O-mediated benzylation reaction was
performed in the presence of toluene and cyclohexane
as solvents which resulted in a 4 and 6% decrease in
yields, respectively. When the reaction was performed
in the presence of nitrobenzene which was used to
examine the effect of a radical scavenger on the reac-
tion propagation, no product formation was observed.
3.3. 6-Benzyl-3-ethoxycyclohex-2-en-1-one 4c
(0.68 g, 42%), IR (neat): 3010, 2945, 1675 cm−1. 1H
NMR: l 1.31 (t, J=7 Hz, 3H), 1.78–1.99 (m, 2H),
2.20–2.53 (m, 4H), 3.25 (m, 1H), 3.95 (q, J=7 Hz, 2H),
5.22 (s, 1H), 7.12 (s, 5H). 13C NMR: 15.2, 25.7, 28.1,
36.0, 47.3, 64.1, 103.0, 126.1, 128.3, 129.2, 140.6, 177.2,
201.3. HRMS m/e (observed): 230.1301, (calculated):
230.1306.
In conclusion, we have developed a new method for the
regioselective a%-benzylation of various a,b-unsaturated
ketones and b-alkoxy a,b-unsaturated ketones with

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7313
Acknowledgements
3. Wildman, W. C. In The Alkoloids; Manske, R. H. F.,
Ed.; Academic Press, 1967; Vol. VI.
We thank the Turkish Scientific and Technical
4. Chen, Y.; Mariano, P. S.; Little, M. G.; O’Brien, D.;
Huesmann, L. P. J. Org. Chem. 1981, 46, 4643.
5. Liotta, D.; Saindane, M.; Brothers, D. J. Org. Chem.
1982, 47, 1600.
Research Council for
a grant [no. TBAG-2244
(102T169)] and Turkish State Planning Organization
for a grant (no. BAP-07-02-DPT-2002 K120540-04).
6. Reich, J. H.; Renga, M. J.; Reich, L. I. J. Am. Chem.
Soc. 1975, 97, 5434.
7. Ponthieux, S.; Outurquin, F.; Paulmier, C. Tetrahedron
1997, 53, 6365.
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