Mn(III)-mediated radical C-C bond formation: Regioselective α′-allylation of α,β-unsaturated ketones

Article abstract of DOI:10.1016/S0040-4039(02)00726-8

Mn(OAc)₃-mediated regioselective α′-allylation of α,β-unsaturated enones is described. α′-Allyl α,β-unsaturated enones are obtained through a radical process in good yields.

Full text of DOI:10.1016/S0040-4039(02)00726-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3977–3980
Mn(III)-mediated radical CꢀC bond formation: regioselective
a%-allylation of a,b-unsaturated ketones
8
Cihangir Tanyeli* and Devrim Ozdemirhan
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Received 14 March 2002; revised 2 April 2002; accepted 12 April 2002
Abstract—Mn(OAc)3-mediated regioselective a%-allylation of a,b-unsaturated enones is described. a%-Allyl a,b-unsaturated enones
are obtained through a radical process in good yields. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Experimental studies on the synthesis of targets with
wide complexity has resulted in the development of
reactions which emphasize chemo-, regio-, and stereose-
lectivity. In defining strategies and reactions to con-
struct complex molecules, regioselectivity is required.1
Metal-mediated allylation generally has a central posi-
tion in the synthesis of various complex natural prod-
ucts. A wide variety of allylation reactions are well
known in the literature as useful methods for car-
bonꢀcarbon bond formation, i.e. metal-mediated allyl
addition to carbonyl compounds2,3 and direct allylation
on the a-position of ketones.4,5 In the last decade,
Mn(III)-based oxidative free-radical reactions have
been developed into a versatile protocol for the forma-
tion of highly functionalised products from simple pre-
cursors.6 In 1976, Williams and Hunter reported that
Mn(OAc)3·2H2O oxidation of enones in HOAc at reflux
affords a%-acetoxy enones in low yields.7 In connection
with our synthetic studies with manganese(III) acetate,8
we found that trapping the a%-keto radicals obtained
from b-alkoxy a,b-unsaturated ketones by benzene used
as a solvent is much faster than acetoxylation, affording
good yields of tandem oxidation products.8d These
interesting results prompted us towards the develop-
ment of a new method in the field of the regioselective
direct allylation of a,b-unsaturated ketones. We
describe herein the results obtained from the
Mn(OAc)3-mediated allylation of various a,b-unsatu-
rated enones and optimization of the reaction
conditions.
As a starting point, we studied the use of mangane-
se(III) acetate as a potential useful mediator for metal-
promoted regioselective a%-allylation of 3-ethoxy-5,
5-dimethylcyclohex-2-enone 1 chosen as a model com-
pound. Reaction of 1 in benzene with 2 equiv. of
Mn(OAc)3·2H2O and 1 equiv. of allyl bromide for 8 h
at reflux afforded 85% of 6-allyl-3-ethoxy-5,5-dimethyl-
cyclohex-2-enone 2 (Scheme 1).
As a natural extension of this study, we pursued a
complementary investigation aimed at subjecting vari-
ous a,b-unsaturated cyclic ketones to this reaction.
When 3-methylcyclopent-2-enone 3c was stirred with 2
equiv. of Mn(OAc)3·2H2O and 1 equiv. of allyl bromide
in benzene for 8 h at reflux, 81% of 5-allyl-3-methylcy-
clopent-2-enone 4c was isolated. When 3 equiv. of
Mn(OAc)3·2H2O was used, the isolated yield of the
allylation product drastically decreased to 53% and
25% of the a%-acetoxylation product was isolated.
Changing the amount of Mn(OAc)3·2H2O to 1 equiv.
decreased the yield of the allylation product (64%) and
no a%-acetoxylation product was observed. Subse-
quently, a variety of cyclopentenones and cyclo-
hexenones were tested with this allylation method
(Scheme 2). Selected examples are listed in Table 1.
Keywords: enones; manganese and compounds; allylation.
* Corresponding author. E-mail: tanyeli@metu.edu.tr
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00726-8

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C. Tanyeli, D. Ozdemirhan / Tetrahedron Letters 43 (2002) 3977–3980
3978
from higher ketones result in the formation of sec-
ondary radicals which dimerize or tertiary radicals
which are prone to further oxidation.10 In accordance
with this conclusion, in this study, dimerization of
product 4 was observed for entries 1, 2 and 3.
In the next step of this study, 3-methylcyclopent-2-
enone 3c (entry 3) was chosen as a model compound
and the Mn(OAc)3·2H2O-mediated allylation reaction
was performed in the presence of nitrobenzene which
was used to examine the effect of a radical scavenger on
the reaction propagation. As expected from the pro-
posed reaction mechanism, no formation of product
was observed.
Scheme 2.
The following mechanistic scheme is consistent with
these results (Scheme 3). The reaction presumably pro-
ceeds via the formation of the Mn(III) enolate 5, which
by one-electron oxidation gives the a%-keto radical 6.9
Reaction of this radical with allyl bromide then yields
the a%-allyl a,b-unsaturated cyclic ketone 4. Vinogradov
and co-workers reported that a%-keto radicals generated
In conclusion, manganese(III) acetate is highly effective
for mediating a%-allylation of a,b-unsaturated cyclic
ketones. This one-step reaction offers complete regiose-
lectivity toward a%-allylation of cyclic enones and opens
up a new class of Mn(OAc)3 reactions.
Table 1. a%-Allylation of a,b-unsaturated enones mediated with Mn(OAc)3 in benzene

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C. Tanyeli, D. Ozdemirhan / Tetrahedron Letters 43 (2002) 3977–3980
3979
3.1.3. 1,1%-Diallyl-4,4%-dimethylbicyclopentyl-3,3%-diene-
2,2%-dione dimerized product of 4c. IR: 3059, 2910, 2874,
1
1703, 1635 cm−1. H NMR: l 2.10 (s, 6H), 2.60 (dd,
J=6.2 and 14.1 Hz, 2H), 2.76 (dd, J=7.4 and 14.1 Hz,
2H), 3.03 (s, 4H), 5.15 (d, J=10.1 Hz, 2H), 5.16 (d,
J=16.6 Hz, 2H), 5.64–5.77 (m, 2H), 5.97 (s, 2H). 13C
NMR: l 19.8, 43.8, 49.4, 60.7, 120.3, 127.3, 132.7,
174.8, 203.4. HRMS m/e (observed): 270.1614, (calcu-
lated): 270.1620.
Acknowledgements
We thank the Middle East Technical University for the
grants (no. AFP-2001-01-03-04 and AFP-2001-07-02-
00-22) and the Turkish Scientific and Technical
Research Council for
(100T026)].
a grant [no. TBAG-1883
Scheme 3.
References
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3.1. General procedure for the Mn(OAc)3-mediated
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allylation of a,b-unsaturated ketones 3
A mixture of Mn(OAc)3·2H2O (3.25 g, 14.0 mmol) in
benzene (or another similar solvent) (150 ml) was
refluxed for 45 min using a Dean–Stark trap. The
mixture was cooled to room temperature and the a,b-
unsaturated ketone (7.0 mmol) and allyl bromide (0.85
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 chromatogra-
phy using ethyl acetate/hexane as eluent to afford the
product.
3.1.1. 6-Allyl-3-ethoxy-5,5-dimethylcyclohex-2-enone 2.
(1.24 g, 85%). IR: 3019, 2960, 1740, 1640, 1598, 1456,
1
1372 cm−1. H NMR: l 0.93 (s, 3H), 1.02 (s, 3H), 1.29
(t, J=7.1 Hz, 3H), 1.99–2.03 (m, 1H), 2.15 (d, J=17.6
Hz, 1H), 2.24–2.31 (m, 2H), 2.55 (d, J=17.6 Hz, 1H),
3.82 (q, J=7.1 Hz, 2H), 4.90 (d, J=10.3 Hz, 1H), 4.94
(d, J=17.2 Hz, 1H), 5.21 (s, 1H), 5.76–5.87 (m, 1H).
13C NMR: l 14.4, 14.5, 31.2, 35.5, 42.4, 57.3, 61.8, 64.4,
101.1, 115.5, 138.1, 174.6, 201.6. HRMS m/e
(observed): 208.1463, (calculated): 208.1464.
6. (a) Demir, A. S.; Jeganathan, A. Synthesis 1992, 235; (b)
Melikyan, G. G. Synthesis 1993, 833; (c) Snider, B. B.
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3.1.2. 5-Allyl-3-methylcyclopent-2-enone 4c. (0.77 g,
1
81%). IR: 3066, 2973, 1690, 1648 cm−1. H NMR: l
2.12 (s, 3H), 2.13–2.14 (m, 1H), 2.29 (d, J=18.1 Hz),
2.49–2.63 (m, 2H), 2.69 (dd, J=6.3 and 18.1 Hz, 1H),
5.03 (d, J=10.5 Hz, 1H), 5.07 (d, J=17.3 Hz), 5.70–
5.79 (m, 1H), 5.92 (s, 1H). 13C NMR: l 19.7, 35.9, 39.2,
46.1, 117.0, 130.2, 135.7, 178.0, 211.4. HRMS m/e
(observed): 136.0893, (calculated): 136.0888.

8
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C. Tanyeli, D. Ozdemirhan / Tetrahedron Letters 43 (2002) 3977–3980
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11. All the products were characterized by 1H, 13C NMR,
IR and HRMS.