Novel oxygenations with IBX

Article abstract of DOI:10.1002/chem.200901867

Universal remedy: The α-hydroxylation of β-keto esters and a range of other suitably substituted carbonyl compounds can be effected in the presence of IBX (2-iodoxybenzoic acid). This novel reactivity underscores the importance of IBX as a universally applicable oxidizing agent.

Full text of DOI:10.1002/chem.200901867

COMMUNICATION
DOI: 10.1002/chem.200901867
Novel Oxygenations with IBX
Alexander Duschek and Stefan F. Kirsch*[a]
Over the past years, the value of 2-iodoxybenzoic acid[1]
(IBX, 1) as a mild, practical, and synthetically useful oxidiz-
ing agent has been continually increased.[2] Even though the
simple oxidation of alcohols to the corresponding carbonyl
compounds still remains the primary application of IBX,[3,4]
a huge variety of unique oxidative transformations has been
developed.[5] Thus, IBX has emerged as an oxidant being of
rather ubiquitous use in organic synthesis. Of particular sig-
nificance, IBX induces the dehydrogenation of simple car-
bonyl compounds as described by Nicolaou and co-work-
ers.[6] Typically, such reactions of ketones and aldehydes
with IBX require elevated temperatures (65–858C) to pro-
duce the corresponding a,b-unsaturated products.[6b] On the
other hand, the direct dehydrogenation of 2-oxonitriles pro-
ceeds smoothly at ambient temperature in a highly selective
manner and in excellent yields, as we found recently in the
case of nitrile 2 [Eq. (1)].[7] We also found in the course of
our previous investigations in the field that the behavior of
enolizable carbonyl compounds, when subjected to IBX,
strongly depends on the type of additional functional groups
in the a-position. This becomes apparent in the reactivity of
a-alkynyl carbonyl compounds, which in the presence of
IBX predominantly yield tertiary alcohols resulting from a-
oxygenation rather than undergoing dehydrogenation
[Eq.(2)].[8]
to the fact that there are rigorous structural constraints on
those carbonyl compounds that are currently known to react
this way. The true value of IBX-mediated a-hydroxylation
of carbonyls can only be garnered when the basic factors are
determined that favor the oxygenation pathway rather than
other oxidative processes such as dehydrogenation. In this
context, we expected that ketones A lacking an a-alkynyl
substituent might still be able to participate in oxygen-trans-
fer reactions with IBX provided that they are sufficiently ac-
tivated by a suitable functional group Z (Scheme 1).[12]
Herein, we present novel IBX-induced oxygenations of vari-
ous easily accessible substrate classes by use of an opera-
tionally simple and broadly applicable protocol.
In fact, oxidative processes involving the transfer of an
oxygen atom from IBX are not uncommon.[9] Hence, it
seems all the more remarkable that only the selective oxida-
tion of benzylic positions[10] and most notably the hydroxyla-
tive dearomatization of phenols[11] have attained major syn-
thetic importance. The related direct a-hydroxylation of car-
bonyl compounds upon exposure to IBX has received much
less attention [e.g., Eq.(2)].[4b,c,8] In part, this neglect is due
Scheme 1. Projected a-hydroxylations.
To probe the feasibility of the projected transformation
for Z=CO2R, we first examined the conversion of keto
ester 6a into tertiary alcohol 7a in the presence of IBX
(Table 1). Due to the low solubility of IBX in most common
solvents, conversion of 6a was only detectable when using
the polar solvent DMSO.[13] The reaction in pure DMSO
was invariably accompanied by the formation of significant
amounts of a,b-unsaturated compound 8a originating from
concomitant dehydrogenation. To our delight, addition of
[a] A. Duschek, Dr. S. F. Kirsch
Department Chemie and Catalysis Research Center
Technische Universitꢀt Mꢁnchen
Lichtenbergstr. 4, 85747 Garching (Germany)
Fax : (+49)89-28913315
E-mail: stefan.kirsch@ch.tum.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200901867.
Chem. Eur. J. 2009, 15, 10713 – 10717
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Table 1. IBX-mediated oxygenations of 6a under various reaction condi-
Table 2. Scope of the IBX-mediated oxidation of 6.[a]
tions.[a]
Entry
Substrate
Product
Yield [%][b]
1
6b
7b
72
Entry
Solvent
t
T
[8C]
Yield [%][b]
[h]
6a[c]
7a
8a
1
2
3
4
CH2Cl2
DMSO
DMSO/THF (1:2)
DMSO/tBuOH (1:1)
DMSO/H2O (3:1)
DMSO/H2O (3:1)
72
6.5
20
6.5
6.5
14
23
23
23
23
23
50
>99
16
9
13
15
0
0
51
49
57
72
80
0
6
3
0
0
0
2[c]
3[d]
4[e]
6c
6d
6e
7c
7d
7e
78
86
61
5[d]
6[d]
[a] Conditions: 6a (0.5m), IBX (1.5 equiv), solvent. [b] Isolated yield
after column chromatography. [c] Recovered starting material. [d] c=
0.27m.
5
6 f
6g
7 f
7g
85
77
water was found to completely suppress this competing reac-
tion pathway. In particular, a 3:1-mixture of DMSO and
water turned out to be best, while a higher water content re-
sulted in practical problems due to poor solubility of both
the substrate and IBX. Despite the significant rate enhance-
ment observed in this solvent mixture, the reaction still
failed to reach full conversion at 238C when employing
1.5 equivalents of IBX.[14] Increasing the reaction tempera-
ture to 508C led to the anticipated increase in reaction rate
(Table 1, entry 6). The use of basic additives such as
NaOAc, imidazole, or CsF resulted in decomposition of IBX
or retarded the formation of 7a.
Since IBX is soluble in aqueous urea solution (50%) up
to a concentration of approximately 0.3m at ambient tem-
perature, hydroxylation of 6a is also feasible in the complete
absence of DMSO [Eq. (3)]. Nevertheless, the yield of terti-
ary alcohol 7a was substantially reduced, which might be at
least partially attributable to the diminished solubility of
both the starting material and the product under these reac-
tion conditions. To perform the reaction 6a!7a in THF,
IBX ester 9[15] can be employed as an alternative. In this
case, prior activation with trifluoroacetic anhydride is re-
quired [Eq. (4)].
6[f]
7
6h
7h
38
8
9
6i
7i
86
76
88
6j
6k
7j
7k
10
[a] Conditions:
6 (0.27m), IBX (1.5 equiv), 508C, DMSO/H2O (3:1).
[b] Isolated yield after column chromatography. [c] dr=8:2. [d] dr=9:1.
[e] Olefin 8c was isolated in 9% yield. [f] @ 85% conversion.
tertiary alcohols 7 is that the reaction 6!7 is performed
under experimentally simple conditions not requiring inert
gas techniques. The high practicability comes along with the
fact that the oxidizing agent IBX is readily obtained in large
quantities without any need for toxic metals following the
cost-efficient Santagostino protocol.[1b] In addition, direct a-
hydroxylation[16,17] of 6 often proceeds in higher yields than
alternative multistep protocols that involve the reaction of
enolates[18] or silyl enol ethers[19] with sources of electro-
AHCTUNGTRENNUNG
be synthetically viable. For instance, treatment of 6l with
IBX for 20 h gave rise to the desired alcohol 7l in only 26%
yield (Scheme 2). On the other hand, expanded reaction
times in conjunction with elevated temperatures and a large
excess of IBX merely led to extensive decomposition. Inter-
estingly, addition of 20 mol% of a suitable Lewis acid such
The broad applicability of the IBX-mediated oxygenation
of b-oxo esters 6 is shown in Table 2. A wide range of acyclic
and cyclic systems were efficiently converted into the corre-
sponding tertiary alcohols 7. As expected for IBX oxida-
tions, the reaction conditions tolerate the presence of vari-
ous functional groups such as esters, ethers, acetals, alkynes,
and tertiary alcohols. A special feature of this novel route to
as Yb
N
ACHTUNGTRENNUNG
yields (Zn
N
ACHTUNGTRENNUNG
10714
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Oxidation Reactions
COMMUNICATION
Scheme 2. Effect of added YbACTHNUTRGENUG(N OTf)3.
Scheme 4. Hydroxylations with Z=CONR2 and Z=COR.
20 h), presumably due to increased substrate enolization.
Proper choice of the Lewis acid additive is indeed essential,
as exemplified by the retarding effect of added Sc
(Sc(OTf)3: 16% after 20 h).
ACHTUNGERTN(NUNG OTf)3
ACHTUNGTRENNUNG
As illustrated in Scheme 3 for the reaction 10!7m, the
capability of IBX to directly convert products of simple
aldol reactions into the corresponding tertiary alcohols is of
Scheme 5. Direct access to triketones and diketo esters by IBX oxidation.
The hydrate forms are omitted for clarity.
tion. Then, ketone 19 is generally isolated as a mixture that
contains varying amounts of the corresponding hydrate form
(see Supporting Information). Due to the fact that vicinal
tricarbonyl compounds such as 19b und 19c are accessed in
a straightforward manner starting from b-keto esters, the
novel route to this preparatively useful class of compounds
is of particular attraction. Established synthetic routes to vi-
cinal tricarbonyl compounds are typically accomplished via
construction of b-oxo esters containing an additional a-
phosporanylidene unit that is subsequently subjected to oxi-
dative cleavage.[22]
In conclusion, we have shown an efficient and operation-
ally simple method that allows the selective a-hydroxylation
of b-keto esters and other suitably substituted carbonyl com-
pounds. As readily available and easily handled oxygen
donor, IBX is employed.[1b,23] The reaction leads to the crea-
tion of tertiary hydroxy groups or vicinal tricarbonyl units as
central structural motifs. Moreover, it should be pointed out
that the ease with which these oxygenations can be coupled
with other oxidative processes significantly expands the
value of IBX as unique and powerful tool in chemical syn-
thesis. Future studies will focus on the development of new
synthetic routes to well-established product classes through
combination of oxidative processes.
Scheme 3. Direct oxidation of b-hydroxy esters.
primary use. This unique oxidative transformation requires
neither the isolation of intermediates nor the sequential ad-
dition of different oxidants. Accordingly, the IBX-mediated
hydroxylation of b-keto esters can be combined with the de-
protection of dithianes[5c] [Eq. (5)] or with the conversion of
thioamides into their carbonyl counterparts [Eq. (6)]. The
latter constitutes a novel reactivity of IBX which has not
been described previously.[21]
The IBX-mediated a-hydroxylation of ketones is not con-
fined to substrates possessing an ester moiety in the a-posi-
tion (Z=CO2R). In preliminary studies, it was discovered
that, for instance, amides and ketones react in an analogous
manner (Scheme 4), albeit in slightly reduced yields com-
pared to the corresponding reactions of b-keto esters.
In addition, oxidation of diketones and keto esters not
bearing an additional substituent in a-position proceeds
smoothly under standard reaction conditions (IBX, 508C,
DMSO/H2O 3:1; Scheme 5). It is assumed that a secondary
hydroxy group is installed first followed by further oxida-
Experimental Section
Oxidation of 6a to 7a: A solution of 1 (187 mg, 0.668 mmol, 1.50 equiv)
and 6a (75.7 mg, 0.445 mmol) in DMSO (1.25 mL) and H2O (0.42 mL)
was heated to 508C for 14 h. The reaction mixture was then diluted with
CH2Cl2 (15 mL) and stirred vigorously at 238C for 20 min. The precipi-
tate was removed by filtration and the solid residue was washed with
CH2Cl2 (4ꢃ5 mL). The combined filtrates were washed with saturated
aqueous NaHCO3 (1ꢃ25 mL), the phases were separated and the aque-
ous layer was extracted with CH2Cl2 (2ꢃ5 mL). The combined organic
layers were washed with H2O (1ꢃ30 mL) and brine (1ꢃ30 mL), dried
Chem. Eur. J. 2009, 15, 10713 – 10717
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10715

S. F. Kirsch and A. Duschek
over Na2SO4, and concentrated under reduced pressure. Purification of
the residue by flash chromatography on silica gel (pentanes/Et2O 7:3)
gave 7a[16l] as a pale yellow liquid (66.3 mg, 0.356 mmol, 80%). Rf =0.43
(P/Et2O=1:1); 1H NMR (360 MHz, CDCl3): d=1.29 (t, J=7.0 Hz, 3H),
1.61–1.92 (m, 4H), 2.00–2.09 (m, 1H), 2.51–2.72 (m, 3H), 4.24 (q, J=
7.0 Hz, 2H), 4.31 ppm (s, 1H); 13C NMR (90.6 MHz, CDCl3): d=14.0,
22.0, 27.0, 37.7, 38.9, 62.1, 80.7, 170.0, 207.3 ppm.
Angew. Chem. 2007, 119, 8779; Angew. Chem. Int. Ed. 2007, 46,
8625; c) O. Iwamoto, R. Shinohara, K. Nagasawa, Chem. Asian J.
2009, 4, 277.
[5] Oxidations leading to carboxylic acids: a) R. Mazitschek, M. Mꢁlba-
ier, A. Giannis, Angew. Chem. 2002, 114, 4216; Angew. Chem. Int.
Ed. 2002, 41, 4059; b) A. Schulze, A. Giannis, Adv. Synth. Catal.
2004, 346, 252; oxidation of amines: c) K. C. Nicolaou, C. J. N. Ma-
thison, T. Montagnon, J. Am. Chem. Soc. 2004, 126, 5192; oxidative
deprotection of dithianes: d) Y. Wu, X. Shen, J.-H. Huang, C.-J.
Tang, H.-H. Liu, Q. Hu, Tetrahedron Lett. 2002, 43, 6443; e) K. C.
Nicolaou, C. J. N. Mathison, T. Montagnon, Angew. Chem. 2003,
115, 4211; Angew. Chem. Int. Ed. 2003, 42, 4077; f) see referen-
ce [5c]; aromatization of dihydropyridines: g) J. S. Yadav, B. V. S.
Reddy, A. K. Basak, G. Baishya, A. V. Narsaiah, Synthesis 2006, 451;
oxidative multicomponent reactions: h) T. Ngouansavanh, J. Zhu,
Angew. Chem. 2007, 119, 5877; Angew. Chem. Int. Ed. 2007, 46,
5775; oxidative cyclization of anilides: i) K. C. Nicolaou, P. S. Baran,
Y.-L. Zhong, S. Barluenga, K. W. Hunt, R. Kranich, J. A. Vega, J.
Am. Chem. Soc. 2002, 124, 2233; generation of radicals: j) B. Janza,
A. Studer, J. Org. Chem. 2005, 70, 6991; rearrangement of thioke-
tals: k) V. G. Shukla, P. D. Salgaonkar, K. G. Akamanchi, Synlett
2005, 1483.
Oxidation of 18b to 19b: A solution of 1 (336 mg, 1.20 mmol, 2.50 equiv)
and 18b (92.6 mg, 0.482 mmol) in DMSO (2.25 mL) and H2O (0.75 mL)
was heated to 508C for 24 h. The reaction mixture was then diluted with
CH2Cl2 (25 mL) and stirred vigorously at 238C for 20 min. The precipi-
tate was removed by filtration and the solid residue was washed with
CH2Cl2 (4ꢃ5 mL). The combined filtrates were washed with saturated
aqueous NaHCO3 (1ꢃ50 mL), the phases were separated, and the aque-
ous layer was extracted with CH2Cl2 (2ꢃ10 mL). The combined organic
layers were washed with H2O (1ꢃ60 mL) and brine (1ꢃ60 mL), dried
over Na2SO4, filtered, and concentrated under reduced pressure. Purifica-
tion of the residue by flash chromatography on silica gel (pentanes/Et2O
3:2) gave 19b (1:2 mixture of ketone and hydrate)[24] as a yellow oil
(73.1 mg, 0.335 mmol, 70%). Rf =0.35 (P/Et2O=1:1); Ketone: 1H NMR
(250 MHz, CDCl3): d=1.39 (t, J=7.3 Hz, 3H), 4.42 (q, J=7.1 Hz, 2H),
7.43–7.75 (m, 3H), 7.97–8.02 ppm (m, 2H); 13C NMR (90.6 MHz,
CDCl3): d=13.9, 63.3, 129.1, 130.0, 131.4, 131.5, 160.5, 183.7, 190.2 ppm;
Hydrate: 1H NMR (250 MHz, CDCl3): d=1.08 (t, J=7.1 Hz, 3H), 4.21
(q, J=7.1 Hz, 2H), 5.31 (s, 2H), 7.43–7.75 (m, 3H), 8.04–8.10 ppm (m,
2H); 13C NMR (90.6 MHz, CDCl3): d=13.6, 63.1, 91.6, 128.7, 130.1,
134.6, 135.5, 169.8, 191.6 ppm.
[6] a) K. C. Nicolaou, Y.-L. Zhong, P. S. Baran, J. Am. Chem. Soc. 2000,
122, 7596; b) K. C. Nicolaou, T. Montagnon, P. S. Baran, Y.-L.
Zhong, J. Am. Chem. Soc. 2002, 124, 2245; c) K. C. Nicolaou, T.
Montagnon, P. S. Baran, Angew. Chem. 2002, 114, 1035; Angew.
Chem. Int. Ed. 2002, 41, 993; d) K. C. Nicolaou, D. L. F. Gray, T.
Montagnon, S. T. Harrison, Angew. Chem. 2002, 114, 1038; Angew.
Chem. Int. Ed. 2002, 41, 996.
[7] Details of this hitherto unknown direct transformation of 2-oxoni-
triles into their unsaturated counterparts will be discussed in an up-
coming publication.
[8] a) S. F. Kirsch, J. Org. Chem. 2005, 70, 10210; b) B. Crone, S. F.
Kirsch, Chem. Commun. 2006, 764; c) S. F. Kirsch, J. T. Binder, C.
Liꢄbert, H. Menz, Angew. Chem. 2006, 118, 6010; Angew. Chem. Int.
Ed. 2006, 45, 5878; d) J. T. Binder, B. Crone, S. F. Kirsch, C. Liꢄbert,
H. Menz, Eur. J. Org. Chem. 2007, 1636.
Acknowledgements
This project was supported by the Deutsche Forschungsgemeinschaft
(DFG). The authors thank Prof. Dr. T. Bach for helpful ideas and great
support.
[9] a) M. Shibuya, S. Ito, M. Takahashi, Y. Iwabuchi, Org. Lett. 2004, 6,
4303; b) reference [4b].
[10] a) Reference [6b]; b) J. T. Binder, S. F. Kirsch, Org. Lett. 2006, 8,
2151.
Keywords: alcohols
compounds · iodine · iodoxybenzoic acid · oxidation
·
hydroxylation
·
hypervalent
[11] a) Reference [6b]; b) D. Magdziak, A. A. Rodriguez, R. W. Van De
Water, T. R. R. Pettus, Org. Lett. 2002, 4, 285; c) A. Ozanne, L.
Pouysꢄgu, D. Depernet, B. Francois, S. Quideau, Org. Lett. 2003, 5,
2903; d) N. Lebrasseur, J. Gagnepain, A. Ozanne-Beaudenon, J.-M.
Lꢄger, S. Quideau, J. Org. Chem. 2007, 72, 6280; e) L. Pouysꢄgu, S.
Chassaing, D. Dejugnac, A.-M. Lamidey, K. Miqueu, J.-M. Sotiro-
poulos, S. Quideau, Angew. Chem. 2008, 120, 3608; Angew. Chem.
Int. Ed. 2008, 47, 3552; f) J. K. Boppisetti, V. B. Birman, Org. Lett.
2009, 11, 1221; g) S. Quideau, G. Lyvinec, M. Marguerit, K. Bathany,
A. Ozanne-Beaudenon, T. Buffeteau, D. Cavagnat, A. Chꢄnedꢄ,
Angew. Chem. 2009, 121, 4675; Angew. Chem. Int. Ed. 2009, 48,
4605, and references therein.
[12] The viability of alkynyl substituents Z in IBX-mediated oxygena-
tions was found to be limited due to facile double bond isomeriza-
tion to the corresponding allenes.
[13] For reactions in other solvents at elevated temperatures, see: a) ref-
erence [3c]; tetrafluoro-IBX is highly soluble and reactive: b) R. D.
Richardson, J. M. Zayed, S. Altermann, D. Smith, T. Wirth, Angew.
Chem. 2007, 119, 6649; Angew. Chem. Int. Ed. 2007, 46, 6529.
[14] Concurrently, IBX was slowly reduced to IBA by DMSO; see also:
Reference [6b].
[1] For the synthesis of IBX, see: a) C. Hartmann, V. Meyer, Chem.
Ber. 1893, 26, 1727; b) M. Frigerio, M. Santagostino, S. Sputore, J.
Org. Chem. 1999, 64, 4537.
[2] For recent reviews, see: a) T. Wirth, Angew. Chem. 2001, 113, 2893;
Angew. Chem. Int. Ed. 2001, 40, 2812; b) V. V. Zhdankin, P. J. Stang,
Chem. Rev. 2002, 102, 2523; c) I. Kumar, Synlett 2005, 1488; d) T.
Wirth, Angew. Chem. 2005, 117, 3722; Angew. Chem. Int. Ed. 2005,
44, 3656; e) Top. Curr. Chem. 2003, 224, edited by T. Wirth; f) R. M.
Moriarty, J. Org. Chem. 2005, 70, 2893; g) M. Uyanik, K. Ishihara,
Chem. Commun. 2009, 2086; h) V. V. Zhdankin, P. J. Stang, Chem.
Rev. 2008, 108, 5299; i) R. D. Richardson, T. Wirth, Angew. Chem.
2006, 118, 4510; Angew. Chem. Int. Ed. 2006, 45, 4402.
[3] For selected examples, see: a) M. Frigerio, M. Santagostino, Tetrahe-
dron Lett. 1994, 35, 8019; b) S. De Munari, M. Frigerio, M. Santagos-
tino, J. Org. Chem. 1996, 61, 9272; c) J. D. More, N. S. Finney, Org.
Lett. 2002, 4, 3001; d) A. P. Thottumkara, M. S. Bowsher, T. K.
Vinod, Org. Lett. 2005, 7, 2933; e) A. Schulze, A. Giannis, Synthesis
2006, 257; f) P. C. B. Page, L. F. Appleby, B. R. Buckley, S. M. Allin,
M. J. McKenzie, Synlett 2007, 1565; polymer-bound IBX: g) G. Sorg,
A. Mengel, G. Jung, J. Rademann, Angew. Chem. 2001, 113, 4532;
Angew. Chem. Int. Ed. 2001, 40, 4395; h) M. Mꢁlbaier, A. Giannis,
Angew. Chem. 2001, 113, 4530; Angew. Chem. Int. Ed. 2001, 40,
4393; i) M. Mꢁlbaier, A. Giannis, ARKIVOC 2003, 228.
[15] Synthesis and structure: a) V. V. Zhdankin, D. N. Litvinov, A. Y. Ko-
posov, T. Luu, M. J. Ferguson, R. McDonald, R. R. Tykwinski,
Chem. Commun. 2004, 106; selective oxidations of sulfides to sulfox-
ides: b) A. Y. Koposov, V. V. Zhdankin, Synthesis 2005, 22; oxidation
of alcohols: c) V. V. Zhdankin, A. Y. Koposov, D. N. Litvinov, M. J.
Ferguson, R. McDonald, T. Luu, R. R. Tykwinski, J. Org. Chem.
2005, 70, 6484.
[4] For selected applications in total synthesis, see: a) S. Kirsch, T.
Bach, Angew. Chem. 2003, 115, 4833; Angew. Chem. Int. Ed. 2003,
42, 4685; b) O. Iwamoto, H. Koshino, D. Hashizume, K. Nagasawa,
10716
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Oxidation Reactions
COMMUNICATION
[16] Alternative strategies for the direct a-hydroxylation of carbonyl
compounds are available; for reviews, see: a) J. Christoffers, A.
Baro, T. Werner, Adv. Synth. Catal. 2004, 346, 143; b) B. Plietker,
Tetrahedron: Asymmetry 2005, 16, 3453; for catalyzed examples with
molecular oxygen, see: b) J. Christoffers, T. Werner, W. Frey, A.
Baro, Eur. J. Org. Chem. 2003, 4879; c) J. Christoffers, T. Werner, W.
Frey, A. Baro, Chem. Eur. J. 2004, 10, 1042; d) J. Christoffers, T.
Kauf, T. Werner, Eur. J. Org. Chem. 2006, 2601; e) P. Y. Toullec, C.
Bonaccorsi, A. Mezzetti, A. Togni, Proc. Natl. Acad. Sci. USA 2004,
101, 5810; f) V. Lecomte, C. Bolm, Adv. Synth. Catal. 2005, 347,
1666; g) W. Adam, F. Prechtl, Chem. Ber. 1991, 124, 2369; h) K.
Hiroya, K. Ogasawara, Chem. Commun. 1999, 2197; i) J. Christoff-
ers, T. Werner, Synlett 2002, 0119; j) T. Ishimaru, N. Shibata, J.
Nagai, S. Nakamura, T. Toru, S. Kanemasa, J. Am. Chem. Soc. 2006,
128, 16488; k) J. Christoffers, T. Werner, S. Unger, W. Frey, Eur. J.
Org. Chem. 2003, 425; l) X. Baucherel, E. Levoirier, J. Uziel, S. Juge
Tetrahedron Lett. 2000, 41, 1385; hydroxy ketones are also accessible
by ketohydroxylation of alkenes or selective oxidation of diols—for
a review, see: m) B. Plietker, Synthesis 2005, 2453, and references
therein.
Clark, A. Kumar, B.-C. Chen, J. Org. Chem. 1994, 59, 1184; c) M. T.
Crimmins, J. M. Pace, P. G. Nantermet, A. S. Kim-Meade, J. B.
Thomas, S. H. Watterson, A. S. Wagman, J. Am. Chem. Soc. 2000,
122, 8453; d) D. Ichinari, T. Ueki, K. Yoshihara, T. Kinoshita, Chem.
Commun. 1997, 1743.
[19] a) R. Z. Andriamialisoa, N. Langlois, Y. Langlois, Tetrahedron Lett.
1985, 26, 3563; b) J. G. Allen, S. J. Danishefsky, J. Am. Chem. Soc.
2001, 123, 351.
[20] For example, Rubottom oxidation of the corresponding silyl enol
ether afforded 7g in a yield of only 7% according to referen-
ce [19a].
[21] The conversion of thioamides into the corresponding carbonyl com-
pounds appears to be a general reaction. This process occurs more
rapidly than the subsequent hydroxylation:
[17] The a-oxygenation of carbonyl compounds (not the synthesis of ter-
tiary alcohols) has also been accomplished using other hypervalent
iodine reagents. Iodosobenzene: a) R. M. Moriarty, S. C. Gupta, H.
Hu, D. R. Berenschot, K. B. White, J. Am. Chem. Soc. 1981, 103,
686; iodosobenzoic acid: b) R. M. Moriarty, K.-C. Hou, Tetrahedron
[22] For reviews on vicinal tricarbonyl compounds, see: a) H. H. Wasser-
man, J. Parr, Acc. Chem. Res. 2004, 37, 687; b) M. B. Rubin, R.
Gleiter, Chem. Rev. 2000, 100, 1121; for selected examples, see:
c) H. H. Wasserman, D. S. Ennis, C. A. Blum, V. M. Rotello, Tetrahe-
dron Lett. 1992, 33, 6003; d) H. H. Wasserman, C. M. Baldino, S. J.
Coats, J. Org. Chem. 1995, 60, 8231; e) H. H. Wasserman, J.-H.
Chen, M. Xia, J. Am. Chem. Soc. 1999, 121, 1401; f) H. H. Wasser-
man, K. Lee, M. Xia, Tetrahedron Lett. 2000, 41, 2511; g) A. El-Dah-
shan, S. Weik, J. Rademann, Org. Lett. 2007, 9, 949.
[23] The reaction 6!7 also proceeds when the stabilized formulation
SIBX is employed as the oxidizing agent (A. Ozanne, L. Pouysꢄgu,
D. Depernet, B. FranÅois, S. Quideau, Org. Lett. 2003, 5, 2903);
Prof. Dr. Quideau is gratefully acknowledged for providing a gener-
ous sample of SIBX.
Lett. 1984, 25, 691; PhIACHTNUTRGNEUNG(OCOCF3)2: c) R. M. Moriarty, B. A. Ber-
glund, R. Penmasta, Tetrahedron Lett. 1992, 33, 6065; Dess–Martin
periodinane: d) M. J. Batchelor, R. J. Gillespie, J. M. C. Golec,
C. J. R. Hedgecock, Tetrahedron Lett. 1993, 34, 167; a-oxysulfonyla-
tion: e) G. F. Koser, A. G. Relenyi, A. N. Kalos, L. Rebrovic, R. H.
Wettach, J. Org. Chem. 1982, 47, 2487; catalytic asymmetric a-oxyto-
sylation: f) R. D. Richardson, T. K. Page, S. Altermann, S. M. Para-
dine, A. N. French, T. Wirth, Synlett 2007, 538; g) S. M. Altermann,
R. D. Richardson, T. K. Page, R. K. Schmidt, E. Holland, U. Mo-
hammed, S. M. Paradine, A. N. French, C. Richter, A. M. Bahar, B.
Witulski, T. Wirth, Eur. J. Org. Chem. 2008, 5315; catalytic a-oxy-
genation: h) M. Ochiai, Y. Takeuchi, T. Katayama, T. Sueda, K.
Miyamoto, J. Am. Chem. Soc. 2005, 127, 12244.
[24] A.-M. Lluch, M. Gibert, F. Sꢅnchez-Baeza, A. Messeguer, Tetrahe-
dron 1996, 52, 3973.
[18] For a review, see: a) B.-C. Chen, P. Zhou, F. A. Davis, E. Ciganek,
Org. React. 2003, 62, 1; for selected examples, see: b) F. A. Davis, C.
Received: July 6, 2009
Published online: September 16, 2009
Chem. Eur. J. 2009, 15, 10713 – 10717
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10717