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Chemistry Letters Vol.37, No.4 (2008)
Direct ꢀ-Oxytosylation of Ketones by Using Pentavalent Organobismuth Reagents
Naoto Sakurai1 and Teruaki MukaiyamaÃ1;2
1Center for Basic Research, The Kitasato Institute, 6-15-5 (TCI) Toshima, Kita-ku, Tokyo 114-0003
2Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
(Received January 18, 2008; CL-080060; E-mail: mukaiyam@abeam.ocn.ne.jp)
A new method for the preparation of ꢀ-tosyloxy ketones by
ditriflates,7 and the ligand coupling reactions of pentavalent
bismuth disulfonates.8 In this communication, we would like
to report a new direct ꢀ-oxytosylation of ketones by utilizing
unique oxidation behavior of heterocyclic organobismuth
compounds.
a direct oxytosylation of ketones using a combination of hetero-
cyclic pentavalent organobismuth compounds and p-toluenesul-
fonic acid monohydrate is described.
In the first place, reactivities of pentavalent bismuth dicar-
boxylates (1–3 and 4a, Figure 1) were examined in the ꢀ-oxyto-
sylation of acetophenone in CH3CN at room temperature (see
Table 1).9 Those bismuth compounds were easily prepared from
the corresponding trivalent bismuth ones8a,8b on treatment with
a combination of m-chloroperoxybenzoic acid (MCPBA) and
m-chlorobenzoic acid. While the use of triphenylbismuth com-
pound 1 did not give the desired ꢀ-tosyloxyketone 6a (Entry
1), heterocyclic bismuth compounds 2, 3, and 4a provided 6a
(Entries 2–4), and the best result was obtained in the case of us-
ing 4a. However, PhOTs was formed in 42% yield as by-product
due to the ligand coupling reaction of in situ generated pentava-
lent bismuth ditosylate (Entry 4).
In order to inhibit this side reaction caused by the ligand
coupling reaction, effects of aryl group on the reactivity of the
bismuth compounds 4b–4f were next examined, and reaction
conditions were optimized (see Table 2). When 2-methoxyphen-
yl group was introduced, the yield of 6a was poor because of the
decrease in solubility of the corresponding bismuth ditosylate to
CH3CN (Entry 1). In the case of 4-methoxyphenyl group, 6a was
obtained in 57% yield along with the by-product, 4-methoxy-
phenyl tosylate, in less than 10% (Entry 2). After screening
various halophenyl groups, 4-fluorophenyl group turned out to
ꢀ-Tosyloxy ketones are known as very useful reagents for
the synthesis of heterocyclic compounds such as thiazoles, imi-
dazoles, oxazoles, pyrazoles, etc., and they excel in stability and
toxicity in comparison with the frequently used ꢀ-halo ketones.1
Preparation of ꢀ-tosyloxy ketones via a direct oxytosylation
of ketones is generally carried out by employing hypervalent
iodine such as [hydroxy(tosyloxy)iodo]benzene (Koser’s re-
agent).2 Although several efficient methods by using catalytic
amounts of PhI were recently reported,3 examples that applied
this iodine system to electron-rich aromatic ketones such as
methoxyphenyl ketones were only a few because sometimes
undesirable side reactions proceeded at the same time.4 In a very
recent report on ꢀ-oxytosylation of ketones by using N-methyl-
O-tosylhydroxylamine, there were no examples of methoxy-
phenyl ketones.5
In organic transformation, pentavalent organobismuth com-
pounds are often used as mild oxidants and arylation reagents.6 It
was recently reported from our laboratory that the reactivity of
pentavalent heterocyclic bismuth compounds was quite different
from the noncyclic ones: for example, oxidative coupling
reactions of carbonyl compounds using pentavalent bismuth
O
Ph
X
Ph
X
Table 2. Effects of aryl group and reaction condition
Cl
O
Bi
X =
O
O
O
O
Ph
1
S
O
X
O
O
X =
S
Bi
Cl
X
X
4
O
O
Ar
Bi
Bi
Bi
X
X
TsOH•H2O
Ar
X
X
X
OTs
2
3
CH3CN, rt, 24 h
4a
Ph
5a
Ph
Ph
Ph
Ph
6a
Figure 1.
TsOH•H2O
/equiv
Yield/%a
BiV/equiv
Entry
2-MeOC6H4
4-MeOC6H4
4-BrC6H4
4-ClC6H4
4-FC6H4
4b/1.1
4c/1.1
4d/1.1
4e/1.1
4f/1.1
4f/1.1
4f/1.5
4f/1.5
4f/1.5
1
2.5
2.5
2.5
2.5
2.5
1.1
3.3
5.0
5.0
6
57
49
56
62
4
Table 1. Effects of organobismuth(V) reagents
BiV reagent
2
O
O
(1.1 equiv)
3
TsOH•H2O
(2.5 equiv)
OTs
4
CH3CN, rt, 24 h
Ph
Ph
5a
6a
5
Entry
BiV reagent
Yield/%a
4-FC6H4
6
1
2
3
4
1
2
3
NDb
trace
17
7b
8b
9c
75
82
75
4-FC6H4
4-FC6H4
4a
35c
4-FC6H4
aIsolated yield. bNot detected. cPhOTs was obtained in 42%
yield as by-product.
aIsolated yield. bThe reaction was carried out at rt for 72 h. cThe
reaction was carried out at 45 ꢀC for 20 h.
Copyright Ó 2008 The Chemical Society of Japan