oxidative rearrangement using catalytic amounts of TEMPO
with iodosylbenzene (PhIO) as a co-oxidant in the presence
of molecular sieves 4 Å.6 Bi(OTf)3 promoted the oxidative
rearrangement of cyclic tertiary allylic alcohols, while Re2O7
was a more effective promoter for the oxidative rearrange-
ment of tertiary vinyl carbinols.
Table 1. Optimizing of Reaction Conditions
We recently reported a highly efficient and chemoselective
oxidation of various alcohols to carbonyl compounds such
as aldehydes, carboxylic acids, and ketones with powdered
Oxone (2KHSO5•KHSO4•K2SO4) in the presence of catalytic
amounts (0.05-5 mol %) of 2-iodobenzenesulfonic acid or
its sodium salt (4a) under nonaqueous conditions.7,8 Cy-
cloalkanones can be further oxidized to cycloalkenones and
lactones by controlling the amount of Oxone under the same
conditions. 2-Iodoxybenzenesulfonic acid (IBS, 3a),7,9 which
is an analogue of IBX 1, is generated in situ from 4a and
Oxone (eqs 1 and 2). IBS 3a serves as the actual catalyst
for the oxidations. As part of our continuing interest in the
use of cat. IBS with co-oxidant Oxone systems in organic
synthesis, we report here the in situ-generated IBS-catalyzed
oxidative rearrangement of tertiary allylic alcohols to ꢀ-di-
substituted R,ꢀ-unsaturated ketones with Oxone.
entry
additive
conditions
6a, yield (%)
1
2
3
-
-
-
CH3CN, 40 °C, 6 h
CH3NO2, 40 °C, 6 h
EtOAc, 40 °C, 23 h
EtOAc, 60 °C, 13 h
EtOAc, 60 °C, 13 h
EtOAc, 60 °C, 13 h
EtOAc, 60 °C, 13 h
EtOAc, 60 °C, 3 h
EtOAc, 60 °C, 3 h
messya
messya
33b
4
K2CO3 (0.5 equiv)
K2CO3 (0.5 equiv)
K2CO3 (0.5 equiv)
K2CO3 (1.5 equiv)
K2CO3 (0.5 equiv)
K2CO3 (0.5 equiv)
67
5c
6d
7
messya
messya e
,
n.r.f
84
8g
9g,c
10g
11g
63
68
67
NaHCO3 (1.0 equiv) EtOAc, 60 °C, 4 h
K2HPO4 (0.5 equiv) EtOAc, 60 °C, 4 h
a 7a was included. b 7a (both regioisomer) and unknown byproduct were
also obtained. c 2 was used instead of 4a. d PhI was used instead of 4a.
e Rearranged allylic alcohol 3-butylcyclohex-2-enol (8a) was also included,
but 6a was not obtained. f No reaction occurred. g After Oxone and inorganic
base in EtOAc were vigorously stirred in the presence of Na2SO4 for 24 h
at rt, 4a and 5a were added.
work, the selective oxidation of acid-sensitive alcohols can
be achieved in the presence of anhydrous sodium sulfate as
a dehydrating agent in ethyl acetate.7 On the basis of these
previous findings, the reaction of 5a was carried out in ethyl
acetate under the same conditions as in entries 1 and 2. After
22 h, desired 6a was obtained in 33% yield with dehydrated
products 7a and several unidentified byproducts (entry 3).
To prevent the dehydration of 5a, we examined the effect
of the addition of base to buffer the acidity of the reaction
mixture and found that 0.5 equiv of potassium carbonate was
effective as an additional base. Thus, the dehydration of 5a
was significantly suppressed and 6a was obtained in 67%
yield (entry 4). In contrast, the reaction became messy under
these conditions in the presence of 2 or iodobenzene instead
of 4a (entries 5 and 6). The amount of base was important,
and no reaction occurred when 1.5 equiv of potassium
carbonate was used (entry 7). Furthermore, 6a was obtained
in 84% yield after 3 h, when Oxone and potassium carbonate
were sufficiently premixed in the presence of anhydrous
sodium sulfate in ethyl acetate at room temperature for 24 h
before the addition of 5a and 4a (entry 8). Notably, in situ-
generated IBX 1 also showed moderate catalytic activity
under these modified conditions, but was inferior to IBS 3a
(entry 8 versus 9). Other inorganic bases such as sodium
hydrogen carbonate and dipotassium hydrogenphosphate
were inferior to potassium carbonate (entries 10 and 11).
To explore the generality of the in situ-generated IBS-
catalyzed oxidative rearrangement of tertiary allylic alcohols
with Oxone, various structurally diverse cyclic and acyclic
tertiary allylic alcohols 5b-n were examined as substrates
under the optimized conditions: powdered Oxone (1 equiv)
and potassium carbonate (0.5 equiv) in ethyl acetate were
vigorously stirred at rt for 24 h in the presence of anhydrous
Initially, we optimized the reaction conditions for the IBS-
catalyzed oxidative rearrangement with Oxone (Table 1). A
mixture of 1-butylcyclohex-2-enol (5a) and powdered Oxone
(1 equiv) in acetonitrile or nitromethane was heated at 40
°C in the presence of 5 mol % of 4a and anhydrous sodium
sulfate (entries 1 and 2). However, no desired 3-butylcyclo-
hex-2-enone (6a) was obtained. The reaction became messy
and a complex product mixture that included 7 was obtained.
It is likely that the dehydration of 5a to 7a predominantly
occurred due to the acidity of Oxone. According to our recent
(7) Uyanik, M.; Akakura, M.; Ishihara, K. J. Am. Chem. Soc. 2009, 131,
251
.
(8) For recent books and reviews focused on hypervalent iodine
chemistry, see :(a) Wirth, T., Ed. Hypervalent Iodine Chemistry. In Topics
in Current Chemistry; Springer: Berlin, 2003; p 224. (b) Wirth, T. In
Organic Synthesis Highlights V; Wiley-VCH: Weinheim, 2003; p 144. (c)
Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2002, 102, 2523. (d) Tohma, H.;
Kita, Y. AdV. Synth. Catal. 2004, 346, 111. (e) Richardson, R. D.; Wirth,
T. Angew. Chem., Int. Ed. 2006, 45, 4402. (f) Ladziata, U.; Zhdankin, V. V.
ARKIVOC 2006, ix, 26. (g) Ochiai, M. Chem. Rec. 2007, 7, 12. (h) Ciufolini,
M. A.; Braun, N. A.; Canesi, S.; Ousmer, M.; Chang, J.; Chai, D. Synthesis
2007, 3759. (i) Ladziata, U.; Zhdankin, V. V. Synlett 2007, 527. (j) Quideau,
S.; Pouysegu, L.; Deffieux, D. Synlett 2008, 467. (k) Zhdankin, V. V.; Stang,
P. J. Chem. ReV. 2008, 108, 5299. (l) Ochiai, M.; Miyamoto, K. Eur. J.
Org. Chem. 2008, 4229. (m) Uyanik, M.; Ishihara, K. Chem. Commun.
2009, 2086. (n) Dohi, T.; Kita, Y. Chem. Commun. 2009, 2073
(9) Koposov, A. Y.; Litvinov, D. N.; Zhdankin, V. V.; Ferguson, M. J.;
.
McDonald, R.; Tykwinski, R. R. Eur. J. Org. Chem. 2006, 4791
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