Hypervalent iodine-catalyzed oxylactonization of ketocarboxylic acids to ketolactones

Article abstract of DOI:10.1016/j.bmcl.2009.03.148

The hypervalent iodine-catalyzed oxylactonization of ketocarboxylic acids to ketolactones was achieved in the presence of iodobenzene (10 mol %), p-toluenesulfonic acid monohydrate (20 mol %) and meta-chloroperbenzoic acid as a stoichiometric co-oxidant.

Full text of DOI:10.1016/j.bmcl.2009.03.148

Bioorganic & Medicinal Chemistry Letters 19 (2009) 3848–3851
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Bioorganic & Medicinal Chemistry Letters
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Hypervalent iodine-catalyzed oxylactonization of ketocarboxylic acids
to ketolactones
*
Muhammet Uyanik, Takeshi Yasui, Kazuaki Ishihara
Graduate School of Engineering, Nagoya University, Chikusa, Nagoya 464-8603, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The hypervalent iodine-catalyzed oxylactonization of ketocarboxylic acids to ketolactones was achieved
in the presence of iodobenzene (10 mol %), p-toluenesulfonic acid monohydrate (20 mol %) and meta-
chloroperbenzoic acid as a stoichiometric co-oxidant.
Received 26 February 2009
Revised 14 March 2009
Accepted 31 March 2009
Available online 5 April 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Over the past two decades, hypervalent iodine compounds have
been the focus of great attention due to their mild and chemoselec-
tive oxidizing properties and their environmentally benign nature in
contrast to toxic metal reagents.1 In particular, the reactivities of tri-
valent iodines resemble those of Hg(II), Tl(III) and Pb(IV).1 In 2004,
Kita’s group introduced meta-chloroperbenzoic acid (m-CPBA) as a
co-oxidant for the preparation of iodine(III) compounds.2 The next
year, Ochiai’s group3 and Kita’s group4 independently, reported the
first hypervalent iodine-catalyzed oxidative coupling reactions with
the successful use of m-CPBA as a co-oxidant. Ochiai’s group devel-
First, we examined the oxylactonization of 5-oxo-5-phenylpen-
tanoic acid (3a) to 5-benzoyldihydrofuran-2(3H)-one (4a) under
Kita’s spirocyclization conditions (Scheme 3).4 However, undesired
Baeyer–Villiger oxidation proceeded, and desired 4a was not
obtained.
Next, we examined the oxylactonization of 3a under modified
conditions that originated in Ochiai’s
4).3 Dichloromethane was used as a solvent instead of acetic acid
to prevent the -oxyacetylation of 3a. Fortunately, 4a was
a-oxyacetylation (Scheme
a
oped the in situ-generated iodine(III)-catalyzed
a-oxyacetylation
(a) Ochiai's work3
of ketones in the presence of 10 mol % of iodobenzene (1a), 3 equiv
of BF3ÁEt2O, 5 equiv of water and 2 equiv of m-CPBA in acetic acid
(Scheme 1a).3 On the other hand, Kita’s group developed the in
situ-generated iodine(III)-catalyzed oxidative spirocyclization of
phenol derivatives in the presence of 5 mol % of 4-iodotoluene
(1b), 1 equiv of trifluoroacetic acid (TFA) and 1.5 equiv of m-CPBA
in dichloromethane (Scheme 1a).4 Since 2005, rapid progress has
been made in the development of hypervalent iodine(III or V)-cata-
lyzed oxidation reactions.5 Very recently, we reported the 2-iodoxy-
benzenesulfonic acid (IBS)-catalyzed highly efficient and
chemoselective oxidation of alcohols to carbonyl compounds with
Oxone.6
Lactones are abundant in nature and the lactonization method-
ology plays an important role in synthetic organic chemistry.7 In
1990, Moriarty’s group reported the [hydroxy(tosyloxy)iodo]ben-
zene (2a, HTIB or Koser’ reagent)-promoted oxylactonization of
ketocarboxylic acids 3 to ketolactones 4 (Scheme 2).8 In connection
with our ongoing study of hypervalent iodine-catalyzed oxidations,
we have been interested in the development of a catalytic oxylact-
onization of ketocarboxylic acids. To the best of our knowledge,
there are no successful examples of a catalytic hypervalent iodine
system for oxylactonization.9,10
PhI (1a, 10 mol%)
BF3·Et2O (3 equiv), H2O (5 equiv)
O
m-CPBA (2 equiv)
O
R2
OAc
R2
R1
R1
AcOH, rt
43—84%
(b) Kita's work4
OH
O
4-Me-C6H4I (1b, 5 mol%)
TFA (1 equiv)
R1
R2
R1
R3
R2
m-CPBA (1.5 equiv)
CH2Cl2, rt
O
CO2H
R3
R4
66—91%
O
R4
Scheme 1. In situ-generated iodine(III)-catalyzed oxidative coupling reactions.
O
O
HO
I OTs
HO
O
+
R
R
O
O
CH2Cl2
reflux
n
n
3
4
Koser's Reagent 2a
36—81% yield
(1 equiv)
* Corresponding author. Tel.: +81 52 789 3331; fax: +81 52 789 3222.
E-mail address: ishihara@cc.nagoya-u.ac.jp (K. Ishihara).
Scheme 2. HTIB 2a-promoted oxylactonization of 3.
0960-894X/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2009.03.148

M. Uyanik et al. / Bioorg. Med. Chem. Lett. 19 (2009) 3848–3851
3849
Table 1
O
Optimization of in situ-generated hypervalent iodine-catalyzed oxylactonization of
O
3a to 4aa
Ph
O
O
1b (5 mol%), TFA (1 equiv)
m-CPBA (1.5 equiv)
1 (10 mol %), acid (20 mol%)
m-CPBA (1.0 equiv)
HO
4a 0%
Ph
O
3a
4a
CH2Cl2, rt, 24 h
solvent, 50 ºC
O
3a
HO
Entry
ArI 1
Acid
Solvent, time (h)
4a, convb (%)
PhO
O
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16e
17e
C6H5I (1a)
TsOHÁH2O
TsOHÁH2O
TsOHÁH2O
TsOHÁH2O
TsOHÁH2O
TsOHÁH2O
TsOHÁH2O
TsOHÁH2Od
Tf2NH
TFE, 3
TFE, 4
TFE, 4
TFE, 4
73 (69)
57
49
36%
4-Me–C6H4I (1b)
4-MeO–C6H4I (1c)
4-CF3–C6H4I (1d)
3,5-(CF3)2–C6H4I (1e)
2-HO2C–C6H4I (1f)
2-HO3S–C6H4I (1g)
Scheme 3. Oxylactonization of 3a under Kita’s coupling conditions.4
74
TFE, 4
48
TFE, 10
TFE, 10
TFE, 3
0c
0c
1a (10 mol%)
BF3·Et2O (3 equiv), H2O (5 equiv)
m-CPBA (2 equiv)
1a
1a
1a
1a
1a
1a
1a
1a
1a
1af
19
63
52
42
TFE, 3
Tf3CH
TFE, 3
4a
3a
HBF4
TFE, 3
CH2Cl2, rt, 22 h
BF3ÁEt2O
TFE, 3
TFE, 8
60
50% yield
TFA
0c
Scheme 4. Oxylactonization of 3a under Ochiai’s coupling conditions.3
TsOHÁH2O
TsOHÁH2O
TsOHÁH2O
TsOHÁH2Of
CH3CN, 22
CH3NO2, 6
CH3NO2, 23
CH3NO2, 28
59
70
99 (90)
86 (80)
obtained in 50% yield along with several byproducts (Baeyer–Vil-
liger oxidation products, etc.).
a
Unless otherwise noted, a mixture of 3a (0.5 mmol) and m-CPBA (0.5 mmol) in
the solvents (2.5 mL) described in the table was heated at 50 °C in the presence of 1
(0.05 mmol) and acid (0.1 mmol).
According to Togo’s report,11,12 various [hydroxy(sulfonyl-
oxy)iodo]arenes (2) can be efficiently prepared from a mixture of
iodoarenes (1), m-CPBA and sulfonic acids at room temperature
(Scheme 5).
1H NMR analysis. The isolated yields of analytically pure product 4a are shown
b
in parentheses.
c
Baeyer–Villiger oxidation compounds of 3a were obtained as main products.
Based on Togo’s significant findings,11 we examined Moriarty’s
oxylactonization of 3a in the catalytic manner of 2a (Scheme 6).
When 3a was heated in the presence of 1 equiv of m-CPBA,
10 mol % of 1a and 20 mol % of p-toluenesulfonic acid monohy-
drate (TsOHÁH2O) in dichloromethane at 50 °C for 22 h, 4a was ob-
tained in 55% conversion. The oxylactonization reaction proceeded
more rapidly in 2,2,2-trifluoroethanol (TFE), and 4a was obtained
in 73% conversion.13 In contrast, Baeyer–Villiger oxidation prod-
ucts were obtained instead of 4a in the absence of 1 or TsOHÁH2O.
These results mean that the combination of both 1 and acid catal-
ysis is essential for the present reaction.
d
10 mol % of TsOHÁH2O was used.
e
m-CPBA (1.3 equiv) was added portion-wise (6 portions were added as
0.2 equiv per 2 h, and finally 0.1 equiv was added).
f
2 mmol scale of 3a; 1a (2 mol %) and TsOHÁH2O (10 mol %) were used.
to 1a (entries 2 and 3). In contrast, the catalytic activity of 4-CF3–
C6H4I (1d) was similar to that of 1a (entry 4). However, the use of
3,5-(CF3)2–C6H4I (1e) gave 4a in modest yield (entry 5). Interest-
ingly, 2-(HO2C)–C6H4I (1f) and 2-(HO3S)–C6H4I (1g) were inert (en-
tries 6 and 7).
The addition of 20 mol % of TsOHÁH2O was required to promote
the oxylactonization efficiently (entry 1). When 10 mol % of
TsOHÁH2O was used, the reaction was quite slow (entry 8). Other
Brønsted or Lewis acids were also screened under the conditions
in entry 1. Although superacids such as Tf2NH and Tf3CH showed
higher reactivity than TsOHÁH2O at the initial stage, the decompo-
sition of m-CPBA was also accelerated under these conditions (en-
tries 9 and 10). HBF4 and BF3ÁEt2O were inferior to TsOHÁH2O
(entries 11 and 12). TFA was inert (entry 13).
As our experimental results shown in Schemes 3, 4 and 6,
TsOHÁH2O was more effective than BF3ÁEt2O–H2O as a co-activator
for the iodine(III)-catalyzed oxylactonization of 3a. Thus, the reac-
tion conditions shown in Scheme 6 were optimized (Table 1). Ini-
tially, we investigated the substituent effect of iodobenzene 1a in
TFE (entries 1–7). Electron-donating group-substituted iodobenz-
enes such as 4-Me–C6H4I (1b) and 4-MeO–C6H4I (1c) were inferior
Although TFE was a suitable solvent,13 the TFE ester of 3a was
also obtained in 2–18% yield (entries 1–12). Thus, other solvents
were screened. Acetonitrile as well as dichloromethane was less
effective than TFE (entry 14). We found that the decomposition
of m-CPBA was much slower in nitromethane than in the other sol-
vents screened,14 and 4a was obtained in 70% yield after 6 h (entry
15). However, the decomposition of m-CPBA was still competitive
under the conditions in entry 15.14 When 1.3 equiv of m-CPBA
was added portion-wise, 4a was obtained in 90% isolated yield (en-
try 16). Thus, the catalyst loadings of 1 and TsOHÁH2O could be re-
duced to 2 mol % and 10 mol %, respectively, to give 4a in 80% yield
(86% conv., TON of 1a = 43; entry 17).
To explore the generality and the substrate scope of the in situ-
generated iodine(III)-catalyzed oxylactonization, several ketocarb-
oxylic acids 3 were prepared by standard methods15 and examined
as substrates under optimized conditions: 1a (10 mol %), TsOHÁH2O
(20 mol %) and portion-wise addition of m-CPBA (Table 2). 1-Nap-
thyl and 2-napthyl ketones 3b and 3c gave corresponding ketolac-
tones 4b and 4c in good yields (entries 1 and 2). 2-Fluorophenyl
O3SR
I
m-CPBA (1.1 equiv)
+
ArI
RSO3H
(1.1 equiv)
Ar
1
CHCl3, rt
OH
2
75—99% yield
Scheme 5. Facile preparation of 2.10
1a (10 mol %), TsOH·H2O (20 mol%)
m-CPBA (1.0 equiv)
3a
4a
solvent (bath temp. 50 ºC)
Conditions
a. CH2Cl2, 22 h
b. CF3CH2OH (TFE), 3 h
c. without TsOH·H2O, TFE, 24 h trace
55% conv.
73% conv. (69% yield)
d. without 1a, TFE, 24 h
0% yield
Scheme 6. Catalytic use of 1a and TsOHÁH2O for the oxylactonization of 3a.

3850
M. Uyanik et al. / Bioorg. Med. Chem. Lett. 19 (2009) 3848–3851
Table 2
OH
O
H+
In situ-generated hypervalent iodine-catalyzed oxylactonization of ketocarboxylic
HO
HO
acids 3 to ketolactones 4a
R
R
O
O
1a (10 mol%), TsOH·H2O (20 mol%)
m-CPBA (1.2—2.4 equiv)
3
OH
I
3
4
m-CBA
CH3NO2, 50 ºC
Ar
OTs
2
Entry
m-CPBA (equiv)a
Ketolactone 4, time (h)
Yieldb (%)
m-CPBA
O
O
TsOH
1
1.8
1.8
1.6
71
O
Ar—I 1
4b, 14 h
O
5
O
O
2
3
70
81
O
O
TsOH
4c, 14 h
6
7
O
R
O
F
O
4
O
-OTs
Ar
O
Ar
I
O
Ar
I+
O
4d, 28.5 h
I+
R
O
R
O-
R
OH
MeO
O
O
4
1.8
2.4
1.4
1.8
1.2
1.2
41c
38e
15e,f
74
O
O
O
O
5
6
7
4e, 48 h
4f, 47 h
4g, 27 h
4h, 23 h
Scheme 7. A possible catalytic cycle for in situ-generated iodine(III)-catalyzed
O
O
O
oxylactonization.
N
O
O
5d
6d
7
O
O
carboxylic acids such 3j under our conditions. The yield was very
low (<5%) and Baeyer–Villiger oxidation products were also ob-
tained (entry 9).
A proposed catalytic cycle is depicted in Scheme 7. First, iodi-
ne(III) 2 should be generated by the oxidation of 1 with m-CPBA
in the presence of TsOH. Next, the Moriarty’s intermediate 5 might
be generated via ligand exchange of 2 with an enol tautomer of 3.8
The intermediate 5 would be equilibrated with iodonium carboxyl-
ate 6 and/or iodonium tosylate 7. The reductive elimination of 5 or
SN2 substitution of iodonium intermediates 6 or 7 would give 4
and 1, which could be re-oxidized with m-CPBA to 2.
In conclusion, for the first time, we achieved the oxylactoniza-
tion of ketocarboxylic acids (3) to ketolactones (4) with hyperva-
lent iodine compounds that were prepared in situ from catalytic
amounts of iodoarenes 1 and TsOHÁH2O in the presence of m-CPBA
as a stoichiometric co-oxidant. The chiral hypervalent iodine-cata-
lyzed enantioselective oxylactonization of ketocarboxylic acids is
under investigation in our laboratories.
O
O
O
O
8
40e
<5g
O
O
O
4i, 10 h
O
O
9
4j, 12 h
a
Unless otherwise noted, m-CPBA (1.2–2.4 equiv) was added portion-wise 6–
12 Â (0.2 equiv per 2 h) to a stirring mixture of 3 (0.5 mmol), 1a (0.05 mmol) and
TsOHÁH2O (0.1 mmol) in CH3NO2 (2.5 mL) at 50 °C.
Acknowledgments
b
Isolated yields of analytically pure 4.
c
Baeyer–Villiger oxidation compounds of 3 were obtained as main products.
1a (20 mol %) and TsOHÁH2O (50 mol %) were used.
Financial support for this project was provided by JSPS.KAKEN-
HI (20245022), the GSC Project of METI, the Toray Science Founda-
tion, the General Sekiyu Research and Development
Encouragement and Assistance Foundation, the Showa Foundation,
and the Global COE program of MEXT.
d
e
Unknown products were also obtained.
Hydrolysis of 4g to hydroxycarboxylic acid was also observed.16
Compound 3j was recovered mainly. Baeyer–Villiger oxidation products of 3j
f
g
were obtained as main products.
Supplementary data
ketone 3d was transformed to 4d in 81% yield (entry 3). In contrast,
2-methoxyphenyl ketone (3e) was transformed to 4e in only 41%
yield, since Baeyer–Villiger products were obtained as main prod-
ucts (entry 4). Unfortunately, picolinoyl lactone 4f and six-mem-
bered d-lactone 4g were obtained in only 38% and 15% yield,
respectively (entries 5 and 6). Notably, the oxidation of 3h gave
spirolactone 4h in 74% yield (entry 7). Additionally, the oxylacton-
ization of 1,3-diketone 3i gave 4i in moderate yield (entry 8).
Unfortunately, no sufficient results were observed with alkyl-keto
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.bmcl.2009.03.148.
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