catalytic use of DDQ in the presence of a less expensive
stoichiometric co-oxidant. Recently, Floreancig reported
the use of catalytic amounts of DDQ in the presence of
excess MnO2 for other types of oxidative transforma-
tions, including cyclizations of ether-containing enol
esters to form pyranones, aromatizations, and O-PMB
deprotections.7 Mn(OAc)3, which functions as a mild
single electron acceptor,8 has also been used for regenera-
tion of DDQ in the removal of PMB protecting groups.9
While this previous work did not include the oxidation of
alcohols, we wished to determine whether this or a similar
protocol would be amenable to our needs. As a result of
investigating this question, we are now pleased to report a
new, modified catalytic oxidation procedure that is simple
to perform, provides short reaction times, utilizes a readily
prepared co-oxidant, and is not only selective for allylic
and benzylic alcohols but which also exhibits selectivity for
allylic alcohols in the presence of benzylic alcohols.
Table 1. Optimization of DDQ Oxidation
DDQ
Mn(OAc)3
(equiv)
time
(h)
yielda
(%)
entry
(mol %)
1
2
3
4
5
6
7
8
110
50
20
15
10
5
0
3
3
3
3
3
6
6
0.2
12
12
12
12
12
3
95b
55
45
37
20
<10
20
0
100 (79)b
0
12
a Yield based on 1H NMR analysis using 1,3,5-trimethoxybenzene as
an internal standard. b Isolated, purified yield.
Based upon the preceding background, we chose to
employ Mn(OAc)3 as the co-oxidant along with catalytic
DDQ. While the cost of commercially available Mn(OAc)3
is rather high, we routinely prepare batches of greater than
40 g from inexpensive Mn(OAc)2.10 The reagent is air- and
moisture-stable and can be stored in ordinary glassware
exposed to air for months at a time.
systems, i.e., those bearing electron-donating groups,
underwent faster conversions and gave higher overall
yields than unactivated systems (compare entries 1 and
2). Very activated systems, such as p-dimethylamino-
phenylpropanol (entry 3), gave superior results; high
yields were obtained in reaction times of typically 6 h or
less. A biphenyl substrate (entry 4) underwent smooth
oxidation to provide the ketone product in good yield,
and 9-hydroxyfluorene (entry 5) gave a very high yield
of product after 6 h. The reaction failed in the presence
of chlorine and nitro substituents and for the hetero-
cyclic systems that were tested (entries 6-9). Allylic
alcohols serve as especially good substrates for this
oxidation procedure (entries 10-13).6 We were pleased
to observe the clean, complete conversion of cinnamyl
alcohol to cinnamaldehyde (entry 10). 2-Cyclohexenol
underwent clean oxidation in approximately 90% yield
(entry 11). An acyclic secondary allylic alcohol proved
to be a very good substrate (entry 13).
Having observed that allylic alcohols in general and some
benzylic alcohols are good substrates for the DDQ/Mn-
(OAc)3 oxidation, we next conducted competition studies
to determine chemoselectivity patterns for different classes
of alcohols. Use of a mixture of 2-cyclohexenol and cyclo-
hexanol (eq 2) demonstrates that an aliphatic alcohol
remains unchanged while the allylic alcohol is oxidized to
the enone in excellent yield. Furthermore, an electron-rich
benzylic alcohol is selectively oxidized in the presence of a
nonactivated benzylic alcohol (eq 3). Finally, we conducted
intermolecular and intramolecular competition studies
between benzylic and allylic alcohols (eqs 4 and 5).
Due to its sensitivity, the enal product formed in eq 5 was
characterized as the corresponding methyl ester (see
Supporting Information).11 A very clear chemoselectivity
is seen for the oxidation of allylic alcohols.
Our studies began with the aforementioned oxidation of
1-(4-methoxyphenyl)ethanol, an electron-rich benzylic alco-
hol, with 1.1 mol equiv of DDQ by itself as a benchmark
(Table 1, entry 1). We then examined systematically the effect
ofMn(OAc)3, beginning with the use of 3 mol equiv of this co-
oxidant. As expected, decreasing the amount of DDQ resulted
in a drastic decrease of product yield (entries 2-6). Even
DDQ loadings as high as 50 mol % did not lead to significant
product formation. We therefore examined the effect of
doubling the amount of Mn(OAc)3 to 6 mol equiv. Under
these conditions, we could lower the amount of DDQ
necessary for the reaction to 20 mol % (entry 7). Lower
catalyst loadings of DDQ resulted in lower yields. To demon-
strate which species is the active oxidant, we conducted the
same reaction without DDQ (entry 8). No oxidation product
was observed, even after extended reaction times, indicating
that DDQ is the active oxidant in the reaction mixture and
that the Mn(OAc)3 does indeed serve to regenerate the
benzoquinone. It is noteworthy that the loadings of DDQ
(20 mol %) and co-oxidant (6 mol equiv) are equal to those
reported by Floreancig for quite different transformations.7
Under these conditions, we obtained consistently reproduci-
ble results when Mn(OAc)3 was used free from excess acetic
acid remaining from the preparation of the reagent.10
Having optimized this initial example of the catalytic
DDQ oxidation, we next tested the scope and limita-
tions of these conditions for benzylic and allylic alco-
hols. As can be seen in Table 2, a distinct pattern of
reactivity emerges for benzylic alcohols. Activated
(7) Liu, L.; Floreancig, P. E. Org. Lett. 2010, 12, 4686–8689.
(8) Snider, B. B. Chem. Rev. 1996, 96, 339–363.
(9) Sharma, G. V. M.; Lavanya, B.; Mahalingam, A. K.; Krishna,
P. R. Tetrahedron Lett. 2000, 41, 10323–10326.
(10) Melikyan, G. G. Synthesis 1993, 833–850.
€
ꢀ
(11) Riihimaki-Lampen, L. H.; Vainio, M. J.; Vahermo, M.; Pohjala,
L. L.; Heikura, J. M. S.; Valkonen, K. H.; Virtanen, V. T.;
Yli-Kauhaluoma, J. T.; Vuorela, P. M. J. Med. Chem. 2010, 53, 514–518.
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Org. Lett., Vol. 13, No. 8, 2011
Cosner, Casey C.
