Direct α-oxytosylation of ketones by using pentavalent organobismuth reagents

Article abstract of DOI:10.1246/cl.2008.388

A new method for the preparation of α-tosyloxy ketones by a direct oxytosylation of ketones using a combination of heterocyclic pentavalent organobismuth compounds and p-toluenesulfonic acid monohydrate is described. Copyright

Full text of DOI:10.1246/cl.2008.388

388
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

Chemistry Letters Vol.37, No.4 (2008)
389
Table 3. ꢀ-Oxytosylation of various ketones
Finally, various ketones were examined under the optimized
conditions (see Table 3). Then, electron-rich aromatic ketones,
methylacetophenones or methoxyacetophenones, gave the corre-
sponding ꢀ-tosyloxy ketones 6b–6e in moderate to good yields
(Entries 1–4). While the yields of electron-poor aromatic and
heteroaromatic ketones were also acceptable (6f–6i, Entries 5–
8). Acetone, a typical aliphatic ketone, is also applied to this re-
action (Entry 9). Concerning regioselectivity of nonsymmetrical
ketones, it was noteworthy that the primary center was more
favorable than the secondary one (5.5:1) as shown in the reaction
of 2-butanone (Entry 10). This tendency of regioselectivity is
opposite to that of 1:1.57 obtained by using hypervalent iodine
system,2c and that this bismuth system showed higher selectivity
in comparison with 2.6:1 observed in the case of N-methyl-O-
tosylhydroxyamine.5
4f (1.5 equiv)
TsOH•H2O (5 equiv)
O
O
R'
R'
R
CH3CN, rt, 72 h
R
5b−5k
6b−6l
OTs
Yield/%a
Entry
Ketone
O
Product
O
OTs
6b
1
82
67
5b
5c
Me
Me
O
O
OTs
6c
2
3
4
5
Me
Me
O
O
It is noted that a new direct ꢀ-oxytosylation of ketones using
heterocyclic organobismuth compound 4f was established. To
the best of our knowledge, this is the first report on ꢀ-oxytosy-
lation of ketones by utilizing oxidizing ability of pentavalent
organobismuth compound, and various ketones including
methoxyacetophenones were successfully applied to the present
reaction. It is interesting to note that reverse regioselectivity
was observed different from that of using hypervalent iodine
system when the nonsymmetrical keotone such as 2-butanone
was examined in this bismuth system. Further investigation
including the reaction mechanism is currently under way in
our laboratory.
OTs
6d
64 (78b)
80 (84b)
5d
5e
MeO
MeO
MeO
MeO
O
O
O
OTs
6e
O
OTs
OTs
84
83
74
5f
6f
F
F
Cl
O
O
O
6
7
8
5g
5h
6g
References and Notes
Cl
1
a) K. C. Nicolaou, T. Montagnon, T. Ulven, P. S. Baran, Y.-L.
Zhong, F. Sarabia, J. Am. Chem. Soc. 2002, 124, 5718. b) O.
Prakash, N. Saini, P. K. Sharma, Heterocycles 1994, 38, 409.
a) G. F. Koser, Aldrichimica 2001, 34, 89. b) R. M. Moriarty,
R. K. Vaid, G. F. Koser, Synlett 1990, 365. c) G. F. Koser,
A. G. Relenyi, A. N. Kalos, L. Rebrovic, R. H. Wettach, J.
Org. Chem. 1982, 47, 2487.
O
OTs
6h
2
O2N
O2N
O
O
OTs
6i
81
5i
S
S
3
4
a) Y. Yamamoto, Y. Kawano, P. H. Toy, H. Togo, Tetrahedron
2007, 63, 4680. b) Y. Yamamoto, H. Togo, Synlett 2006, 798.
c) R. D. Richardson, T. K. Page, S. Altermann, S. M. Paradine,
A. N. French, T. Wirth, Synlett 2007, 538.
a) H. Hamamoto, G. Anilkumar, H. Tohma, Y. Kita, Chem.—
Eur. J. 2002, 8, 5377. b) T. Kitamura, Yuki Gosei Kagaku
Kyokaishi 1995, 53, 893. c) G. F. Koser, R. H. Wettach,
J. Org. Chem. 1980, 45, 1543. d) O. Y. Neiland, B. Y. Karele,
J. Org. Chem., USSR (Engl. Transl.) 1970, 6, 889.
O
O
O
66 (79b)
9
OTs
5j
6j
O
O
52
10
OTs
(6k/6l =
44/8c)
6k
6l
5k
OTs
aIsolated yield. The reaction was carried out at 45 ꢀC for 20 h
b
5
6
O. R. S. John, N. M. Killeen, D. A. Knowles, S. C. Yau, M. C.
Bagley, N. C. O. Tomkinson, Org. Lett. 2007, 9, 4009.
a) L. D. Freedman, G. O. Doak, Chem. Rev. 1982, 82, 15. b)
D. H. R. Barton, J.-P. Finet, Pure Appl. Chem. 1987, 59,
937. c) J.-P. Finet, Chem. Rev. 1989, 89, 1487. d) V. A.
Dodonov, T. I. Starostina, Y. L. Kuznetsova, A. V. Gushchin,
Russ. Chem. Bull. 1995, 44, 151. e) H. Suzuki, T. Ogawa, N.
Komatsu, Y. Matano, T. Murafuji, T. Ikegami, Organobismuth
Chemistry, Elsevier, Amsterdam, 2001. f) K. Ikegai, Y.
Nagata, T. Mukaiyama, Bull. Chem. Soc. Jpn. 2006, 79, 761.
g) N. Sakurai, K. Ikegai, T. Mukaiyama, Arkivoc 2007, 7, 254.
S. Imachi, T. Mukaiyama, Chem. Lett. 2007, 36, 718.
a) N. Sakurai, T. Mukaiyama, Chem. Lett. 2007, 36, 928. b) N.
Sakurai, T. Mukaiyama, Heterocycles 2007, 74, 771.
Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
c
.
using 2 equiv of 4f and 4.2 equiv of TsOH H2O. Yields of 6k
and 6l were determined by the integrated ratio of 1H-NMR from
the mixture of two compounds.
be the most potential aryl group (Entries 3–5). In addition, it re-
tarded the side reaction and the formation of 4-fluorophenyl to-
sylate was less than 10%. The yield of 6a decreased considerably
to 4% when the amount of TsOH H2O was reduced to 1 equiv
for 4f (Entry 6). Concerning effects of the amounts of TsOH
H2O, more than 2 equiv were then needed for bismuth com-
pounds to exchange the two carboxylate ligands. Then, it
was found that the combined use of 1.5 equiv of 4f and 5 equiv
.
.
7
8
.
of TsOH H2O gave 6a in 82% yield (Entry 8). Although the
desired reaction proceeded faster at the elevated temperatures,
it became slightly complicated because of side reactions, and
thus 6a was obtained in 75% yield (Entry 9).
9
Published on the web (Advance View) March 1, 2008; doi:10.1246/cl.2008.388