Manganese(III) acetate based selective oxidation of the tertiary α′-position on various cyclic α,β-unsaturated ketones

Article abstract of DOI:10.1016/S0040-4039(01)01262-X

We describe the preliminary results of manganese(III) acetate based selective oxidation of various α′-methyl 2-cyclohexenone and 2-cyclopentenone derivatives to afford the corresponding α′-acetoxy-α′-methyl substituted oxidation products in good yields.

Full text of DOI:10.1016/S0040-4039(01)01262-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6397–6399
Manganese(III) acetate based selective oxidation of the tertiary
a%-position on various cyclic a,b-unsaturated ketones
:
Cihangir Tanyeli,* Bengu¨ Sezen, C¸ igdem Iyigu¨n and Olcay Elmalı
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Received 14 May 2001; accepted 12 July 2001
Abstract—We describe the preliminary results of manganese(III) acetate based selective oxidation of various a%-methyl 2-cyclo-
hexenone and 2-cyclopentenone derivatives to afford the corresponding a%-acetoxy-a%-methyl substituted oxidation products in
good yields. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Synthetic methods for the selective oxidation of com-
mon functional groups possess a central position in the
synthesis of various complex natural products. In par-
ticular, a%-hydroxy-a,b-unsaturated cyclic ketones are
appealing synthons.1 In 1976, Williams and Hunter
reported that the manganese(III) acetate oxidation of
enones affords modest yields of a%-acetoxy enones.2
Watt et al. reinvestigated this procedure and obtained
acceptable yields of the desired a%-acetoxy enones.3–6 So
far, studies on the selective oxidation of cyclic enones in
the literature have been concerned with substrates that
are unsubstituted at the a%-positions except for one
example of a steroidal substrate involving a tertiary
a%-position. In this exceptional study, Ahmad et al.
reported that they obtained unexpected products other
than a%-acetoxyenones with very low yields.7 However,
various naturally occuring compounds such as esters of
phorbol and ingenol possess an a%-tert-hydroxy-a,b-
unsaturated cyclic ketone moiety in their structures.8
The lack of a selective oxidation method for the a%-tert-
position of a,b-unsaturated cyclic ketones prompted us
toward the development of a new method. In connec-
tion with our synthetic studies with manganese(III)
acetate,9–12 we attempted to prepare a%-acetoxy-a%-
methyl substituted a,b-unsaturated cyclic ketones via a
Mn(OAc)3 acetoxylation method. We describe herein
the results obtained from the Mn(OAc)3 oxidation of
various a%-methyl a,b-unsaturated cyclic ketones and
optimization of the reaction conditions.
a%-Methyl a,b-unsaturated cyclic ketones 1 were pre-
pared from the corresponding a,b-unsaturated cyclic
ketones using slightly modified literature procedures13
and allowed to react with Mn(OAc)3. a%-Methyl a,b-
unsaturated cyclic ketones 1 (with benzene as the sol-
vent) underwent a selective oxidation with Mn(OAc)3
to afford products 2. Characterization of the products
revealed the introduction of an acetoxy moiety at the
a%-position (Scheme 1). The results are summarized in
Table 1.
The reaction presumably proceeds via the formation of
the Mn(III) enolate 3, which loses Mn(II) upon one-
electron oxidation to give the a%-keto radical 415
(Scheme 2). The resultant tertiary radical 4 is prone to
further oxidation by another equivalent of Mn(OAc)3.
The final oxidation step provides a%-acetoxy a%-methyl
a,b-unsaturated ketones 2.
In the next step of this study, 3,6-dimethyl-2-cyclo-
hexenone was chosen as a model compound. The
Mn(OAc)3 oxidation was performed in nitrobenzene
Keywords: enones; manganese and compounds; oxidation.
* Corresponding author. E-mail: tanyeli@metu.edu.tr
Scheme 1.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01262-X

6398
C. Tanyeli et al. / Tetrahedron Letters 42 (2001) 6397–6399
Table 1. Selective oxidation of a%-methyl a,b-unsaturated ketones with Mn(OAc)3 in benzene
Reactant
Product14
Yield (%)
64
Time (h)
10
78
81
10
12
76
72
10
8
68
8
which was used to examine the effect of a radical
scavenger on the reaction propagation. As expected from
the proposed reaction mechanism, no formation of
product 2 was observed.
In conclusion, an exciting and synthetically valuable
Mn(OAc)3 based oxidation is demonstrated. The appli-
cability of this one-pot oxidation method is attractive for
further use in synthesis.
3. Experimental
1H NMR spectra were recorded in CDCl3 on Bruker
Spectrospin Avance DPX 400 spectrometers. Chemical
shifts are given in ppm from tetramethylsilane. IR spectra
were obtained using a Perkin–Elmer Model 1600 series
FT-IR spectrometer and are reported in cm−1. Mass
spectra were recorded with a Varian MAT 212.
Scheme 2.

C. Tanyeli et al. / Tetrahedron Letters 42 (2001) 6397–6399
6399
3.1. General procedure for the Mn(OAc)3 oxidation of
b-alkoxy a,b-unsaturated ketones 2
tific and Technical Research Council for a grant [no.
TBAG-1883 (100T026)].
A mixture of Mn(OAc)3 (3.25 g, 14.0 mmol) in ben-
zene (or corresponding solvent) (150 ml) was refluxed
for 45 min using a Dean–Stark trap. Then the mix-
ture was cooled to room temperature and the a%-
methyl a,b-unsaturated ketone (7.0 mmol) was
gradually added. The mixture was allowed to reflux
until the dark brown color disappeared and 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 chro-
matography using ethyl acetate/hexane as eluent to
afford the product.
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1
yield). H NMR: l 0.79 (s, 3H), 1.02 (s, 3H), 1.36 (s,
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Acknowledgements
1
14. All the products were characterized by H, 13C NMR, IR
and HRMS.
We thank the Middle East Technical University for a
grant (no. AFP-2000.01.03.06) and the Turkish Scien-
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