Iodobenzene-catalyzed α-acetoxylation of ketones. In situ generation of hypervalent (diacyloxyiodo)benzenes using m-chloroperbenzoic acid

Article abstract of DOI:10.1021/ja0542800

Reported here for the first time is the iodobenzene-catalyzed α-oxidation of ketones, in which diacyloxy(phenyl)-λ³-iodanes generated in situ act as real oxidants of ketones and m-chloroperbenzoic acid serves as a terminal oxidant. Oxidation of a ketone with m-chloroperbenzoic acid in acetic acid in the presence of a catalytic amount of iodobenzene, BF₃·Et₂O, and water at room temperature under argon affords an α-acetoxy ketone in good yield. p-Methyl- and p-chloroiodobenzene also serve as efficient catalysts in this direct oxidation. We found that when the reaction was carried out in the absence of a catalytic amount of iodobenzene, Baeyer-Villiger oxidation of a ketone took place. It is noted that use of water and BF₃·Et₂O is crucial to the success of this α-acetoxylation. Copyright

Full text of DOI:10.1021/ja0542800

Published on Web 08/16/2005
Iodobenzene-Catalyzed r-Acetoxylation of Ketones. In Situ Generation of
Hypervalent (Diacyloxyiodo)benzenes Using m-Chloroperbenzoic Acid
Masahito Ochiai,* Yasunori Takeuchi, Tomoko Katayama, Takuya Sueda, and Kazunori Miyamoto
Faculty of Pharmaceutical Sciences, UniVersity of Tokushima, 1-78 Shomachi, Tokushima 770-8505, Japan
Received June 29, 2005; E-mail: mochiai@ph.tokushima-u.ac.jp
Hypervalent aryl-λ3-iodanes (ArILL′) with two heteroatom
Scheme 1
ligands on iodine(III) undergo oxidation of a broad range of diverse
functional groups.1 In the oxidation, these heteroatom ligands serve
as leaving groups in both the ligand exchange step on iodine(III)
and the reductive elimination process of λ3-iodanyl groups.1c
Introduction of oxygen functionalities to R-carbons of carbonyl
compounds by aryl-λ3-iodanes has been extensively investigated
by the Moriarty and Koser groups and has broad synthetic utility.2,3
Facile reduction of iodine(III) to univalent iodide in the reductive
elimination step constitutes a driving force for the oxidation.
Table 1. Effects of Water and Iodobenzene on R-Acetoxylation of
Stoichiometric amounts of λ3-iodanes are required in the oxidation,
Acetophenonea
and hence, the reaction produces equimolecular amounts of aryl
amt of
PhI
amt of
H2O
amt of
PhI
amt of
H2O
iodides as a waste. It occurred to us that if an aryl iodide is
reoxidized to a hypervalent aryl-λ3-iodane under these conditions,
the oxidation needs only a catalytic amount of the expensive aryl-
λ3-iodane or aryl iodide (Scheme 1). Such a catalytic cycle has
never been realized except for electrochemical oxidations.4 We
report herein for the first time a catalytic R-oxidation of ketones in
which diacyloxy(phenyl)-λ3-iodanes act as real oxidants of ketones
and m-chloroperbenzoic acid (m-CPBA) serves as a terminal
oxidant.
yield
(%)b
yield
(%)b
entry
(equiv)
(equiv)
entry
(equiv)
(equiv)
1
2
3
4
5
6
7
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0
3
4
5
6
7
8
5
35
61
84
73
55
55
8
9
10
11
12
13
0.1
0.1c
1
0.2
0.05
10
5
5
5
5
49
86
83
83
75
0d
5
Alkyl iodides are smoothly oxidized by m-CPBA at room
temperature, yielding alcohols and/or their derivatives or olefins,
depending upon the conditions and the substrate structures, in which
initial formation of labile alkyl-λ3-iodanes is involved.5 m-CPBA
(4 equiv) also oxidizes iodobenzene in methanol and affords a
λ5-iodane, iodoxybenzene,5d suggesting the possible use of m-CPBA
as a terminal oxidant in the catalytic R-oxidation of carbonyl
compounds.
Exposure of acetophenone to dried m-CPBA6 (1.4 equiv) in acetic
acid in the presence of a catalytic amount (10 mol %) of
iodobenzene, BF3‚Et2O (3 equiv), and water (5 equiv) at room
temperature under argon afforded R-acetoxyacetophenone in 84%
yield (Table 1, entry 4). It is noted that addition of water is crucial
to the success of R-acetoxylation of acetophenone (entries 1-8);
in the absence of water, the R-oxidation was almost inhibited with
95% of the recovered ketone. Larger amounts (7-10 equiv) of
added water also led to a decreased yield (ca. 50%) of the product.
Use of (diacetoxyiodo)benzene (10 mol %), instead of iodobenzene,
in the presence of water (5 equiv) resulted in a high yield of the
R-oxidation (entry 9).
a Reaction conditions: acetophenone (0.25 M) in acetic acid, m-CPBA
(1.4 equiv), and BF3‚Et2O (3 equiv) at 25-30 °C for 24 h under argon.
b GC yields. c Instead of PhI, (diacetoxyiodo)benzene was used. d Phenyl
acetate (38%) was obtained.
temperature without using the Lewis acid (Figure S1), R-acetoxy-
lation of acetophenone did not take place at all in the absence of
BF3‚Et2O (Table S1, entry 1). Addition of BF3‚Et2O seems to be
essential to induce the enolization of acetophenone, and only the
resulting enol will react with (diacyloxyiodo)benzenes generated
in situ;3 in fact, no enolization was observed in the absence of
BF3‚Et2O (Scheme S1 and Figure S2). Use of other acids such as
Yb(OTf)3, CF3SO3H, and HBF4‚Me2O afforded a moderate yield
(ca. 40%) of R-acetoxyacetophenone (Table S1).
Both p-methyl- and p-chloroiodobenzene also serve as efficient
catalysts for this direct oxidation, and use of 10 mol % of these
iodoarenes afforded R-acetoxyacetophenone in more than 80%
yields under similar conditions (Table S2). Introduction of powerful
electron-withdrawing (p-NO2) and electron-donating substituents
(p-MeO), however, decreased the catalytic efficiency of iodoarenes.
A variety of dialkyl and alkyl aryl ketones are smoothly oxidized
at the R-positions under our catalytic conditions and afford
R-acetoxy ketones in good yields (Table 2). Substituted aceto-
phenones with halogens (F, Cl, Br, and I) at the para position gave
comparable results, indicating the high selectivity for oxidation of
iodobenzene by m-CPBA over p-iodoacetophenone (entries 4-7).
This oxidation can be extended to R-acetoxylation of â-keto ester
(entry 11).
Use of 5 mol % of iodobenzene gave a slightly decreased yield
(75%) of the R-acetoxy ketone. Iodobenzene is indispensable for
this catalytic oxidation: thus, no formation of R-acetoxyaceto-
phenone was observed when the reaction was carried out in the
absence of iodobenzene (entry 13). In this reaction, however,
Baeyer-Villiger oxidation took place, yielding phenyl acetate in
38% yield.7
BF3‚Et2O is also essential for this direct R-oxidation of acetophe-
none. Although the oxidation of iodobenzene to (diacyloxyiodo)-
benzenes with m-CPBA rapidly proceeds in acetic acid at room
In the case of unsymmetrical ketones, oxidation of a methylene
group of linear alkyl chains is favored over that of a methyl group
(entry 12).2d,8 Entries 13 and 14 indicate that the reactivity of
9
12244
J. AM. CHEM. SOC. 2005, 127, 12244-12245
10.1021/ja0542800 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Catalytic R-Acetoxylation of Ketones with m-CPBAa
Scheme 2
(OAc)OCOAr (Ar ) m-ClC6H4).11 Ligand exchange of a (diacyl-
oxyiodo)benzene with an enol derived from a ketone through the
formation of tetracoordinated iodate1c produces an R-λ3-iodanyl
ketone, which on SN2 displacement by acetic acid affords an
R-acetoxy ketone with liberation of PhI.12 The effect of added water
in this catalytic oxidation is interesting; however, we found that
the presence of water slows down the rate of enolization of
acetophenone (Figure S2) as well as slightly decreases the rate of
oxidation of iodobenzene by m-CPBA to λ3-iodanes (Figure S3).
In summary, we have developed an efficient method for catalytic
R-oxidation of ketones. The method involves in situ generation of
hypervalent phenyl-λ3-iodanes by the oxidation of a catalytic amount
of iodobenzene with m-CPBA.
Supporting Information Available: Text giving experimental
details, Scheme S1, Figures S1-S4, and Tables S1 and S2. This material
is available free of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Varvoglis, A. The Organic Chemistry of Polycoordinated Iodine;
VCH: New York, 1992. (b) Zhdankin, V. V.; Stang, P. J. Chem. ReV.
2002, 102, 2523. (c) Wirth, T., Ed. HyperValent Iodine Chemistry; Top.
Curr. Chem. 224; Springer: Berlin, 2003.
(2) (a) Mizukami, F.; Ando, M.; Tanaka, T.; Imamura, J. Bull. Chem. Soc.
Jpn. 1978, 51, 335. (b) Moriarty, R. M.; Gupta, S. C.; Hu, H.; Berenschot,
D. R.; White, K. B. J. Am. Chem. Soc. 1981, 103, 686. (c) Moriarty, R.
M.; Berglund, B. A.; Penmasta, R. Tetrahedron Lett. 1992, 33, 6065. (d)
Koser, G. F.; Relenyi, A. G.; Kalos, A. N.; Rebrovic, L.; Wettach, R. H.
J. Org. Chem. 1982, 47, 2487. (e) Koser, G. F.; Lodaya, J. S.; Ray, D.
G.; Kokil, P. B. J. Am. Chem. Soc. 1988, 110, 2987.
(3) For reviews, see: (a) Moriarty, R. M.; Prakash, O. Org. React. 1999, 54,
273. (b) Moriarty, R. M.; Vaid, R. K.; Koser, G. F. Synlett 1990, 365.
(4) (a) Fuchigami, T.; Fujita, T. J. Org. Chem. 1994, 59, 7190. (b) Fujita, T.;
Fuchigami, T. Tetrahedron Lett. 1996, 37, 4725.
(5) (a) Reich, H. J.; Peake, S. L. J. Am. Chem. Soc. 1978, 100, 4888. (b)
Cambie, R. C.; Lindsay, B. G.; Rutledge, P. S.; Woodgate, P. D. J. Chem.
Soc., Chem. Commun. 1978, 919. (c) Morris, D. G.; Shepherd, A. G. J.
Chem. Soc., Chem. Commun. 1981, 1250. (d) Davidson, R. I.; Kropp, P.
J. J. Org. Chem. 1982, 47, 1904. (e) Yamamoto, S.; Itani, H.; Tsuji, T.;
Nagata, W. J. Am. Chem. Soc. 1983, 105, 2908. (f) Morris, D. G.;
Shepherd, A. G. J. Chem. Soc., Chem. Commun. 1981, 1250. (g) Tohma,
H.; Maruyama, A.; Maeda, A.; Maegawa, T.; Dohi, T.; Shiro, M.; Morita,
T.; Kita, Y. Angew. Chem., Int. Ed. 2004, 43, 3595.
a Reaction conditions: ketone (0.25 M) in acetic acid, m-CPBA (2 equiv),
PhI (0.1 equiv), H2O (5 equiv), and BF3‚Et2O (3 equiv) at 25-30 °C for
20-48 h under argon. b Isolated yields. Parentheses are GC yields. c H2O
(3 equiv). d PhI (0.3 equiv). e m-CPBA (1.4 equiv) and PhI (0.3 equiv).
R-methylene groups toward acetoxylation decreases in the order
ethyl > pentyl > nonyl. This tendency is in good agreement with
the preferred direction for the reported acid-catalyzed enolization
of unsymmetrical ketones.9 Steric effects appear to be significant
in the oxidation of 4,4-dimethyl-2-pentanone, in which the meth-
ylene group that is flanked by a tert-butyl group is less reactive
than the methyl group (entry 15).10
A catalytic cycle for this oxidation is shown in Scheme 2. BF3‚
Et2O accelerates oxidation of iodobenzene to (diacyloxyiodo)-
benzenes by m-CPBA, being completed within 10 min under our
conditions. Because of the facile ligand exchange on iodine(III),1c
PhI(OAc)2 is produced as a major λ3-iodane in the reaction, along
with the formation of small amounts of PhI(OCOAr)2 and PhI-
(6) 1H NMR analyses showed that commercially available m-CPBA is
contaminated with a various degree (17-33%) of water and with 10-
15% of m-chlorobenzoic acid, depending on the commercial source, and
therefore it was dried under vacuum for 1 h at room temperature prior to
use, which leads to reproducible results.
(7) Renz, M.; Meunier, B. Eur. J. Org. Chem. 1999, 737.
(8) Dohi, T.; Maruyama, A.; Yoshimura, M.; Morimoto, K.; Tohma, H.; Shiro,
M.; Kita, Y. Chem. Commun. 2005, 2205.
(9) Rappe, C.; Sachs, W. H. J. Org. Chem. 1967, 32, 3700.
(10) Hatzigrigoriou, E.; Varvoglis, A.; Bakola-Christianopoulou, M. J. Org.
Chem. 1990, 55, 315.
(11) A mixture of equal amounts of PhI(OAc)2 and PhI(OCOAr)2 (Ar )
m-ClC6H4) in CDCl3 at 22 °C reaches equilibrium within 1 h via ligand
exchange, yielding a statistical 1:2:1 mixture of PhI(OAc)2, PhI(OAc)-
OCOAr, and PhI(OCOAr)2 (Figure S4).
(12) Ochiai, M.; Nishitani, J.; Nishi, Y. J. Org. Chem. 2002, 67, 4407.
JA0542800
9
J. AM. CHEM. SOC. VOL. 127, NO. 35, 2005 12245