Cerium-catalyzed, aerobic oxidative synthesis of 1,2-dioxane derivatives from styrene and their fragmentation into 1,4-dicarbonyl compounds

Article abstract of DOI:10.1002/ejoc.200500487

1,4-Diketones were prepared by cerium-catalyzed oxidative coupling of styrene with molecular oxygen and 1,3-dicarbonyl compounds. This two-step sequence was performed as a one-pot procedure without isolation of the intermediate products. The first step is

Full text of DOI:10.1002/ejoc.200500487

FULL PAPER
DOI: 10.1002/ejoc.200500487
Cerium-Catalyzed, Aerobic Oxidative Synthesis of 1,2-Dioxane Derivatives
from Styrene and Their Fragmentation into 1,4-Dicarbonyl Compounds
Michael Rössle,[a] Thomas Werner,[a] Wolfgang Frey,[a] and Jens Christoffers*[a]
Keywords: Catalysis / Cerium / Oxidation / 1,4-diketones / C–C bond formation / Peroxides
1,4-Diketones were prepared by cerium-catalyzed oxidative
coupling of styrene with molecular oxygen and 1,3-dicar-
bonyl compounds. This two-step sequence was performed as
a one-pot procedure without isolation of the intermediate
products. The first step is a metal-catalyzed radical reaction
yielding 3-hydroxy-1,2-dioxane derivatives being the cyclo-
tautomers of initially formed 4-hydroperoxy ketones. In the
second step of this sequence, these endoperoxides are con-
verted with AcCl–pyridine by Kornblum–DeLaMare frag-
mentation into the 1,4-dicarbonyl motif. Several intermediate
1,2-dioxane derivatives could be isolated and structurally
characterized by X-ray crystallography.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
(Scheme 1) and trapping of the intermediate radical by mo-
lecular oxygen.[10] This development is clearly a result of
our earlier observation, that β-dicarbonyl compounds 6 are
cleanly α-hydroxylated in the presence of molecular oxygen
and catalytic amounts of cerium salts (Scheme 2).[11] Our
mechanistic proposal for this α-hydroxylation process in-
volves the formation of a radical species 4b (X = ester or
ketone) by ligand-to-metal charge-transfer of β-diketonato
cerium() complexes 4a as shown in Scheme 2. While the
overall mechanistic view of these processes is still not com-
pletely clear and presently under investigation in our
laboratories, we aimed to utilize the radical species 4 for
the C–C coupling reaction with styrene (5) (Scheme 1). A
subsequent Kornblum–DeLaMare fragmentation leads to
1,4-dicarbonyl compounds 2.[12] Oxidative coupling of sty-
rene (5) might herein be regarded as an alternative to the
application of phenacylhalides.[13]
Introduction
In 1951 Kornblum and DeLaMare reported on base-in-
duced fragmentations of dialkyl peroxides into ketones and
alcohols.[1] Since then, this process has received much atten-
tion from synthetic organic chemists. Of particular interest
is the selective conversion of endoperoxides to hydroxy
ketones.[2] According to this fragmentation, 1,4-dicarbonyl
compounds 2 are obtained after activation of the OH group
by acetylation[3] from 3-hydroxy-1,2-dioxane derivatives 1.
The latter can be regarded as the cyclotautomers of γ-hy-
droperoxy ketones 3. Therefore, a simple access of these
peroxides could be the basis for a valuable synthetic route
to 1,4-diketones,[4] an important structural motif for the
preparation of heterocyclic compounds.[5]
In contrast to 1,3- and 1,5-dicarbonyl compounds being
accessible by Claisen or Michael reactions,[6] the synthesis
of 1,4-dicarbonyl functionalized carbon skeletons requires
an Umpolung strategy, carried out by either the classic utili-
zation of α-halo ketones[7] or more modern strategies in-
volving 1,3-dithian derivatives.[8] Both methodologies are
multistep sequences and require stoichiometric amounts of
reagents, such as halogen sources or bases. They are there-
fore with regard to economical and ecological considera-
tions not very attractive. An atom-economic Umpolung
strategy, however, is the use of the Stetter reagent or other
organocatalytic systems.[9]
In order to contribute to the field of 1,4-dicarbonyl com-
pounds 2, we have developed a process leading to γ-hydro-
peroxy ketones 3 by attack of an α-radical 4 to styrene 5
[a] Institut für Organische Chemie der Universität Stuttgart,
Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: +49-711-685-4269
Scheme 1. Transformation of 3-hydroxy-1,2-dioxane derivatives
into 1,4-dicarbonyl compounds by Kornblum–DeLaMare frag-
mentation; R, RЈ = alkyl, cycloalkyl; X = ester, ketone.
E-mail: jchr@oc.uni-stuttgart.de
Eur. J. Org. Chem. 2005, 5031–5038
© 2005 Wiley-VCH Verlag GmbH & Co. KgaA, Weinheim
5031

M. Rössle, T. Werner, W. Frey, J. Christoffers
FULL PAPER
acyclic compounds. For cyclic β-keto esters 6a–6c as well as
the α-acetylbutyrolactone (6d), -lactam (6e), and -cyclo-
pentanone (6f) the yield of the diketone 2 was generally
good and independent of the ring size. Yields of 61–87%
over two steps implicate a range of 78–93% for each step.
For the seven-membered ring diketone 2g the yield signifi-
cantly breaks down to 14%. From this product single crys-
tals were grown, which were suitable for X-ray crystallo-
graphic analysis. An ORTEP representation of its molecular
structure is given in Figure 1.[15] The large strain around the
quaternary carbon atom is evidenced by the bending of the
C1–O1 away from the acetyl group.
Table 1. List of products 2 and yields.
Scheme 2. Proposed mechanism for the cerium-catalyzed α-hydrox-
ylation of β-dicarbonyl compounds 6.
Results and Discussion
We have already reported on the reaction of β-dicarbonyl
compounds 6 with styrene (5) in the presence of catalytic
amounts of CeCl3·7H2O under an atmosphere of air, which
gives γ-hydroperoxy ketones 3.[10b] These ketones, however,
were isolated as their cyclotautomeric 3-hydroxy-1,2-diox-
ane derivatives 1 with three stereogenic centers. Therefore,
these materials were obtained as hardly separable mixtures
of diastereoisomers, which is not acceptable from a prepara-
tive point of view. In order to transform these 1,2-dioxanes
1 to stereochemically unique materials we aimed to either
oxidize or reduce the endoperoxidic moiety. After consider-
able experimental affords with several catalytically active
transition metal compounds,[14] we finally focused on the
Kornblum–DeLaMare fragmentation, which is in our
hands best achieved with stoichiometric amounts of AcCl
and pyridine. In order to circumvent the rather tedious iso-
lation and purification procedure of the peroxides, we have
developed a two-step one-flask procedure, which is summa-
rized in Scheme 3. Use of atmospheric O2 turned out to be
optimal. If the partial pressure of oxygen is too high, the
α-hydroxylation process becomes a significant side reaction
and the respective alcohols 7 (Scheme 2) are obtained as
byproducts.
[a] Total yield over two steps.
The best yield achieved for an acyclic product was 72%
for β-keto ester 2h. Yields for this class of substrates seem
to be dependent on the steric demand of the α-alkyl substit-
uent. This is illustrated by the decrease in the order H (2h),
Me (2i),[16] Bn (2k),[17] Et (2j) from 72% to 42% yield. Re-
placement of the acetyl group in 2h by a benzoyl residue in
2l[18] lowered the yield from 72% to 56%. The α-isopropyl
derivative did not give any product under these reaction
conditions. The effect was even more drastic for the acetyl-
acetone derivatives 2m[19] and 2n.[19] Introduction of the Me
group resulted in a decrease from 28% to 10%. For the α-
benzyl-substituted β-diketone no conversion was observed.
In these cases, however, the low yields might also be due to
the instability of the products 6 under basic reaction condi-
tions. It is well known, that aliphatic 1,3-diketones tend to
Scheme 3. Formation of 1,4-dicarbonyl compounds 2 by a two-step
one-pot reaction consisting of cerium-catalyzed C–C coupling with
styrene (5) and subsequent Kornblum–DeLaMare fragmentation.
In Table 1 products 2 are listed together with their yields decompose according to a retro-Claisen reaction.
over two steps in the one-flask procedure. Acyclic (right While peroxide formation from cyclic β-keto esters 6a–
column) and cyclic starting materials (left) have been inves- 6c as well as from lactone 6d and lactam 6e was reported
tigated; yields for the latter are generally higher than for the earlier,[10b] respective experimental and characterization
5032
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 5031–5038

Cerium-Catalyzed, Aerobic Oxidative Synthesis of 1,2-Dioxane Derivatives
FULL PAPER
Scheme 4. Conversion of α-acetylcycloalkanones to 1,2-dioxane de-
rivatives 1.
The only monocyclic 3-hydroxy-1,2-dioxane derivative
we were able to characterize so far is compound 1d
(Scheme 5), which was prepared from β-keto ester 6j by ap-
plication of our standard protocol. Unfortunately, this ma-
terial was obtained as a mixture of three diastereoisomers.
Repeated chromatographic separations, however, lead to
Figure 1. ORTEP view of the structure of triketone 2g in the solid
state.
data for products of cyclic diketones as well as acyclic β-
keto esters and β-diketones are included in this article. Con-
version of α-acetylcyclopentanone (6f) and -cyclohexanone
(6o) with 5 mol-% of cerium catalyst, an excess of styrene
(5) and O2 (air) gave spirocyclic 1,2-dioxane derivatives 1a
(19%) and 1b (33%) as the major products (Scheme 4). In
the case of the five-membered ring, an annulated cyclotau-
tomer 1c (5%) and the 1,4-diketone 2f (9%) were isolated
as byproducts. The constitution of the isomers 1a and 1c
1
can be clearly assigned by the shifts in the H NMR spec-
tra. For the six-membered ring starting material 6o no for-
mation of a 1,4-diketone or an annulated 1,2-dioxane was
observed, but 1b was obtained as a mixture of two dia-
stereoisomers (dr = 71:29). For all three 1,2-dioxanes 1a,
Scheme 5. Synthesis of a monocyclic 1,2-dioxane 1d and consti-
1b, and 1c the relative configuration could not be assigned. tutions of annulated 1,2-dioxanes 1e and 1f.
Figure 2. ORTEP view of the structure of monocyclic 1,2-dioxane 1d in the solid state.
Eur. J. Org. Chem. 2005, 5031–5038
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5033

M. Rössle, T. Werner, W. Frey, J. Christoffers
FULL PAPER
unique species, although this purification resulted in a very respectively 6c and styrene (5) and α-methylstyrene was re-
low overall yield (18%). We were able to grow single crystals ported earlier.[10b] Graphic representations of their solid-
that were suitable for X-ray structure analysis from one of state structures are given in Figure 3 and Figure 4. Com-
these isomers. A representation of the molecular structure pound 1e consists of two cis-annulated six-membered rings
is given in Figure 2. The three larger substituents at each both in the chair conformation. The phenyl and the OH
stereogenic center occupy equatorial positions (OH at C1, group are in equatorial conformation. In contrast to 1d the
EtO2C at C2, and Ph at C4, atom numbering according intermolecular H-bond of compound 1f is formed to the
to Figure 2). The six membered ring is clearly in a chair ester-carbonyl oxygen O5. In compound 1f the six- and
conformation. Intermolecular H-bonding between the OH seven-membered rings are trans-annulated. In this case the
proton and the O3 oxygen atom of the peroxide unit is sta- H-bond is intermolecular. The 1,2-dioxane ring is in chair
bilizing the solid-state structure.
conformation, however, the phenyl group is in distorted ax-
We thought that the conformation of the peroxo unit ial position due to strain with the axial ester moiety and
might be of interest. Fortunately, we were also able to grow the axial lone pair at O3.
single crystals of two other 1,2-dioxane derivatives 1e and
1f, which are annulated by a six- and seven-membered ring.
The preparation of these compounds from β-keto esters 6b
Conclusions
In contrast to 1,3- and 1,5-dicarbonyl compounds, which
are accessible by Claisen or Michael reaction, the direct
synthesis of 1,4-dicarbonyl compounds is still a challenging
task and commonly requires α-halogenation of ketones or
other Umpolung strategies. With regard to atom economy,
however, both methods are not optimal.
In the present publication we report on a cerium-cata-
lyzed C–C coupling of 1,3-dicarbonyl compounds with sty-
rene and oxygen yielding 4-hydroperoxy ketones, which ex-
ist as 3-hydroxy-1,2-dioxane derivatives. Base-induced
Kornblum–DeLaMare fragmentation of these intermediate
products afford compounds with a 1,4-dicarbonyl moiety.
Since these endoperoxides are obtained as not easy to pu-
rify mixtures of diastereoisomers, this sequence is per-
formed as a two-step one-pot procedure. Starting from sim-
ple starting materials and utilizing atmospheric oxygen as
oxidant, these results can – in terms of economical and eco-
logical considerations – be regarded as a starting point for
further developments.
Figure 3. ORTEP view of the structure of cis-annulated 1,2-dioxane
1e in the solid state.
Experimental Section
General: Melting points were measured on a Büchi 510 and are
uncorrected. Column chromatography was carried out using Merck
SiO2 60 with hexanes (PE, b.p. 40–60°C) and ethyl acetate (EA) as
eluents. 1H NMR spectra were recorded on a Bruker ARX 500
(500 MHz) or a Bruker ARX 300 (300 MHz). 13C NMR spectra
were recorded on a Bruker ARX 500 (125 MHz), a Bruker ARX
300 (75 MHz) or a Bruker AC 250 (62 MHz). Multiplicities were
determined with DEPT experiments. The β-dicarbonyl compounds
6a, 6b, 6c, 6d, 6f, 6h, 6l, 6m, 6n, and 6o were commercially available.
The starting materials 6e,[11b] 6g,[20] 6i,[21] 6j,[22] and 6k,[22] were
prepared according to literature procedures.
General Procedure A for 1,4-Diketone Formation: Freshly distilled
styrene (5) (2.0 equiv.) and the respective β-dicarbonyl compound
6 (1 mmol, 1.0 equiv.) were added to a suspension of CeCl3·7H2O
(0.05 or 0.1 equiv.) in iPrOH (0.65 mL/1 mmol of 6) and the re-
sulting mixture was stirred at 23°C. In some cases another portion
of styrene (5) (1.0 equiv.) was added after 4 h, and the reaction
mixture was stirred for a further 20 h at ambient temperature. All
volatile materials were removed in vacuo, and the residue was sus-
pended in CH2Cl2 (2 ml/mmol of 6). Pyridine (5.0 equiv.) and ace-
Figure 4. ORTEP view of the structure of trans-annulated 1,2-diox-
ane 1f in the solid state.
5034
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 5031–5038

Cerium-Catalyzed, Aerobic Oxidative Synthesis of 1,2-Dioxane Derivatives
FULL PAPER
tyl chloride (6.0 equiv.) were added at 0°C, and the resulting mix-
ture stirred for 16 h at 23°C. After filtration through a short plug
of SiO2 (PE/EA, 2:1) and evaporation of the solvents the residue
was chromatographed on SiO2 (PE/EA, 5:1) to give the 1,4-dike-
tones 2 as the major products.
30.0 mmol) in CH2Cl2 (10.0 mL) were converted according to the
General Procedure A. Chromatography (SiO2, PE/EA, 2:1) fur-
nished 1,4-diketone 2e [1.21 g, 3.60 mmol, 72%, Rf(PE/EA, 2:1) =
0.21] as a colorless oil. All spectroscopic data were in accordance
with the literature.[10b]
2-Acetyl-2-(2-oxo-2-phenylethyl)cyclopentanone (2f): Diketone 6f
(625 mg, 4.95 mmol), CeCl3·7H2O (93 mg, 0.25 mmol), styrene (5)
(1.15 mL, 10.0 mmol and 0.58 mL, 5.1 mmol) in iPrOH (3.3 mL)
and pyridine (2.03 mL, 25.0 mmol), AcCl (2.15 mL, 30.0 mmol) in
CH2Cl2 (10.0 mL) were converted according to the General Pro-
cedure A. Chromatography (SiO2, PE/EA, 5:1) furnished 1,4-dike-
tone 2f [740 mg, 3.03 mmol, 61%, Rf(PE/EA, 2:1) = 0.40] as a col-
orless oil. 1H NMR (CDCl3, 500 MHz): δ = 1.85–1.95 (m, 1 H),
2.02–2.08 (m, 2 H), 2.21 (s, 3 H), 2.36–2.48 (m, 1 H), 2.52–2.60 (m,
1 H), 2.84 (dt, J = 5.0, J = 13.5 Hz, 1 H), 3.50 (d, J = 18.5 Hz, 1
H), 3.80 (d, J = 18.5 Hz, 1 H), 7.45–7.49 (m, 2 H), 7.57–7.61 (m,
1 H), 7.92–7.94 (m, 2 H) ppm. 13C{1H} NMR (CDCl3, 62 MHz):
δ = 19.71 (CH2), 26.37 (CH3), 31.94 (CH2), 38.13 (CH2), 44.47
(CH2), 65.70 (C), 128.08 (CH), 128.76 (CH), 133.70 (CH), 136.14
Ethyl
2-Oxo-1-(2-oxo-2-phenylethyl)cyclopentane-1-carboxylate
(2a): β-Keto ester 6a (781 mg, 5.00 mmol), CeCl3·7H2O (185 mg,
0.497 mmol), styrene (5) (1.15 mL, 10.0 mmol and 0.58 mL,
5.1 mmol) in iPrOH (3.3 mL) and pyridine (2.03 mL, 25.0 mmol),
AcCl (2.15 mL, 30.0 mmol) in CH2Cl2 (10.0 mL) were converted
according to the General Procedure A. Chromatography (SiO2, PE/
EA, 5:1) furnished 1,4-diketone 2a [945 mg, 3.45 mmol, 69%,
Rf(PE/EA, 2:1) = 0.47] as a colorless oil. C16H18O4 (274.31): calcd.
C 70.06, H 6.61; found C 69.57, H 6.62. All spectroscopic data
were in accordance with the literature.[10b]
Ethyl 2-Oxo-1-(2-oxo-2-phenylethyl)cyclohexane-1-carboxylate (2b):
β-Keto ester 6b (851 mg, 5.00 mmol), CeCl3·7H2O (93 mg,
0.25 mmol), styrene (5) (1.15 mL, 10.0 mmol and 0.58 mL,
5.1 mmol) in iPrOH (3.3 mL) and pyridine (2.03 mL, 25.0 mmol),
AcCl (2.15 mL, 30.0 mmol) in CH2Cl2 (10.0 mL) were converted
according to the General Procedure A. Chromatography (SiO2, PE/
EA, 10:1) furnished 1,4-diketone 2b [878 mg, 3.05 mmol, 61%
Rf(PE/EA, 2:1) = 0.51] as a colorless solid, m.p. 90°C. C17H20O4
(288.34): calcd. C 70.81, H 6.99; found C 70.92, H 7.05. All spectro-
scopic data were in accordance with the literature.[10b]
(C), 196.57 (C), 202.77 (C), 215.61 (C) ppm. IR (ATR): ν = 1736
˜
(vs), 1700 (vs), 1680 (vs), 1351 (m), 1219 (m), 1155 (m), 1105 (m)
cm–1. HRMS (70 eV, EI): calcd. 244.1099 (for C15H16O3), found
244.1099 [M+]. C15H16O3 (244.28): calcd. C 73.75, H 6.60; found
C 73.71, H 6.80.
2-Acetyl-2-(2-oxo-2-phenylethyl)cycloheptanone (2g): Diketone 6g
(308 mg, 2.00 mmol), CeCl3·7H2O (74 mg, 0.20 mmol), styrene (5)
(0.46 mL, 4.0 mmol and 0.23 mL, 2.0 mmol) in iPrOH (1.3 mL)
and pyridine (0.81 mL, 10.0 mmol), AcCl (0.86 mL, 12.0 mmol) in
CH2Cl2 (4.0 mL) were converted according to the General Pro-
cedure A. Chromatography (SiO2, PE/EA, 5:1) furnished 1,4-dike-
tone 2g [74 mg, 0.27 mmol, 14%, Rf(PE/EA, 2:1) = 0.43] as a color-
less solid, which contained single crystals suitable for X-ray struc-
Methyl 2-Oxo-1-(2-oxo-2-phenylethyl)cycloheptane-1-carboxylate
(2c): β-Keto ester 6c (340 mg, 2.00 mmol), CeCl3·7H2O (37 mg,
0.10 mmol), styrene (5) (0.46 mL, 4.0 mmol and 0.23 mL,
2.0 mmol) in iPrOH (1.3 mL) and pyridine (0.81 mL, 10.0 mmol),
AcCl (0.86 mL, 12.0 mmol) in CH2Cl2 (4.0 mL) were converted ac-
cording to the General Procedure A. Chromatography (SiO2, PE/
EA, 5:1) furnished 1,4-diketone 2c [410 mg, 1.42 mmol, 71%,
Rf(PE/EA, 2:1) = 0.45] as a colorless oil. 1H NMR (CDCl3,
300 MHz): δ = 1.29–1.37 (m, 1 H), 1.53–1.63 (m, 2 H), 1.69–1.79
(m, 2 H), 1.81–1.91 (m, 1 H), 2.14 (ddd, J = 0.9, J = 9.6, J =
15.2 Hz, 1 H), 2.35 (dd, J = 9.6, J = 15.0 Hz, 1 H), 2.59 (ddd, J =
2.7, J = 8.4, J = 14.5 Hz, 1 H), 2.90 (ddd, J = 2.9, J = 10.5, J =
11.5 Hz, 1 H), 3.29 (d, J = 17.7 Hz, 1 H), 3.74 (s, 3 H), 3.87 (d, J
= 17.7 Hz, 1 H), 7.43–7.48 (m, 2 H), 7.53–7.58 (m, 1 H), 7.95–7.97
(m, 2 H) ppm. 13C{1H} NMR (CDCl3, 125 MHz): δ = 25.11 (CH2),
26.34 (CH2), 31.87 (CH2), 34.56 (CH2), 41.39 (CH2), 43.21 (CH2),
54.03 (CH3), 61.59 (C), 128.07 (CH), 128.58 (CH), 133.20 (CH),
1
ture analysis. M.p. 85°C. H NMR (CDCl3, 500 MHz): δ = 1.13–
1.21 (m, 1 H), 1.41–1.54 (m, 3 H), 1.78–1.83 (m, 2 H), 1.98 (dd, J
= 8.8, J = 15.3 Hz, 1 H), 2.17 (s, 3 H), 2.43–3.48 (m, 2 H), 2.78
(dt, J = 2.6, J = 11.7 Hz, 1 H), 3.34 (d, J = 18.3 Hz, 1 H), 4.02
(dd, J = 0.9, J = 18.3 Hz, 1 H), 7.46–7.49 (m, 2 H), 7.57–7.60 (m,
1 H), 7.97–7.99 (m, 2 H) ppm. 13C{1H} NMR (CDCl3, 125 MHz):
δ = 24.49 (CH2), 26.56 (CH3), 26.78 (CH2), 30.38 (CH2), 30.93
(CH2), 41.17 (CH2), 43.29 (CH2), 69.24 (C), 128.15 (CH), 128.69
(CH), 133.46 (CH), 136.56 (C), 197.66 (C), 204.92 (C), 210.64 (C)
ppm. IR (ATR): ν = 2929 (m), 2862 (m), 1742 (m), 1703 (s), 1692
˜
(vs), 1677 (vs), 1596 (m), 1579 (m), 1445 (s), 1361 (s), 1342 (s), 1180
(m), 1156 (vs), 1035 (m), 882 (m), 817 (m) cm–1. HRMS (CI, CH4):
calcd. 273.1481 (for C17H21O3), found 273.1472 [MH+].
136.77 (C), 172.49 (C), 197.33 (C), 209.02 (C) ppm. IR (ATR): ν
˜
= 2939 (m), 1733 (vs), 1706 (vs), 1686 (vs), 1448 (m), 1219 (m),
1201 (m), 1167 (m), 1154 (m) cm–1. MS (70 eV, EI): m/z (%) = 288
(1) [M+], 270 (4), 256 (30), 168 (38), 137 (18), 120 (17), 105 (100),
77 (38). C17H20O4 (288.34): calcd. C 70.81, H 6.99; found C 70.74,
H 7.01.
Methyl 2-Acetyl-4-oxo-4-phenylbutyrate (2h): β-Keto ester 6h
(232 mg, 2.00 mmol), CeCl3·7H2O (75 mg, 0.20 mmol), styrene (5)
(0.46 mL, 4.0 mmol and 0.23 mL, 2.0 mmol) in iPrOH (1.3 mL)
and pyridine (0.81 mL, 10.0 mmol), AcCl (0.87 mL, 12.0 mmol) in
CH2Cl2 (4.0 mL) were converted according to the General Pro-
cedure A. Chromatography (SiO2, PE/EA, 5:1) furnished 1,4-dike-
tone 2h [338 mg, 1.44 mmol, 72%, Rf(PE/EA, 2:1) = 0.44] as a col-
orless oil. 1H NMR (CDCl3, 500 MHz): δ = 2.44 (s, 3 H), 3.54 (dd,
J = 5.4, J = 18.3 Hz, 1 H), 3.73 (dd, J = 8.3, J = 18.4 Hz, 1 H),
3.78 (s, 3 H), 4.24 (dd, J = 5.6, J = 8.2 Hz, 1 H), 7.45–7.49 (m, 2
H), 7.55–7.60 (m, 1 H), 7.95–7.99 (m, 2 H) ppm. 13C{1H} NMR
(CDCl3, 125 MHz): δ = 30.29 (CH3), 37.48 (CH2), 52.75 (CH),
53.67 (CH3), 128.14 (CH), 128.65 (CH), 133.54 (CH), 136.06 (C),
2-Acetyl-2-(2-oxo-2-phenylethyl)-4-butanolide (2d): Lactone 6d
(110 mg, 0.859 mmol), CeCl3·7H2O (15 mg, 0.040 mmol), styrene
(5) (176 mg, 1.69 mmol) in iPrOH (0.25 mL) and pyridine
(0.36 mL, 4.35 mmol), AcCl (0.37 mL, 5.22 mmol) in CH2Cl2
(1.7 mL) were converted according to the General Procedure A.
Chromatography (SiO2, PE/EA, 2:1) furnished 1,4-diketone 2d
(184 mg, 0.747 mmol, 87%) as a yellowish oil. All spectroscopic
data were in accordance with the literature.[10b]
3-Acetyl-1-benzyl-3-(2-oxo-2-phenylethyl)pyrrolidin-2-one (2e): Lac- 169.44 (C), 197.08 (C), 202.25 (C) ppm. IR (ATR): ν = 1742 (s),
˜
tam 6e (1.09 g, 5.00 mmol), CeCl3·7H2O (185 mg, 0.497 mmol),
styrene (5) (1.15 mL, 10.0 mmol and 0.58 mL, 5.1 mmol) in iPrOH
(3.3 mL) and pyridine (2.03 mL, 25.0 mmol), AcCl (2.15 mL,
1717 (s), 1685 (s), 1597 (m), 1449 (m), 1435 (m), 1353 (m), 1265
(s), 1170 (s), 1069 (m), 1001 (m) cm–1. MS (EI, 70 eV): m/z (%) =
234 (1) [M+], 216 (2), 203 (7), 192 (37), 174 (14), 105 (100), 87 (37),
Eur. J. Org. Chem. 2005, 5031–5038
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5035

M. Rössle, T. Werner, W. Frey, J. Christoffers
FULL PAPER
77 (27), 43 (35). C13H14O4 (234.25): calcd. C 66.66, H 6.02; found
C 66.41, H 6.02.
(0.46 mL, 4.0 mmol and 0.23 mL, 2.0 mmol) in iPrOH (1.3 mL)
and pyridine (0.81 mL, 10.0 mmol), AcCl (0.86 mL, 12.0 mmol) in
CH2Cl2 (4.0 mL) were converted according to the General Pro-
cedure A. Chromatography (SiO2, PE/EA, 10:1) furnished 1,4-dike-
tone 2l [323 mg, 1.04 mmol, 56%, Rf(PE/EA, 2:1) = 0.55] as a col-
Ethyl 2-Acetyl-2-methyl-4-oxo-4-phenylbutyrate (2i): β-Keto ester 6i
(288 mg, 2.00 mmol), CeCl3·7H2O (75 mg, 0.20 mmol), styrene (5)
(0.46 mL, 4.0 mmol and 0.23 mL, 2.0 mmol) in iPrOH (1.3 mL)
and pyridine (0.81 mL, 10.0 mmol), AcCl (0.87 mL, 12.0 mmol) in
CH2Cl2 (4.0 mL) were converted according to the General Pro-
cedure A. Chromatography (SiO2, PE/EA, 2:1) furnished 1,4-dike-
tone 2i [356 mg, 1.36 mmol, 68%, Rf(PE/EA, 2:1) = 0.50] as a col-
1
orless oil. H NMR (CDCl3, 500 MHz): δ = 1.17 (t, J = 7.1 Hz, 3
H), 3.73 (dd, J = 6.0, J = 18.1 Hz, 1 H), 3.82 (dd, J = 7.6, J =
18.1 Hz, 1 H), 4.16 (q, J = 7.2 Hz, 2 H), 5.12 (dd, J = 6.1, J =
7.5 Hz, 1 H), 7.45–7.52 (m, 4 H), 7.56–7.62 (m, 2 H), 7.99–8.01 (m,
2 H), 8.09–8.10 (m, 2 H) ppm. 13C{1H} NMR (CDCl3, 62 MHz):
δ = 13.85 (CH3), 38.17 (CH2), 48.87 (CH), 61.79 (CH2), 128.23
(CH), 128.67 (CH), 128.71 (CH), 128.97 (CH), 133.52 (CH), 133.58
(CH), 136.11 (2 C), 169.38 (C), 194.82 (C), 196.91 (C) ppm. IR
1
orless oil. H NMR (CDCl3, 500 MHz): δ = 1.24 (t, J = 7.2 Hz, 3
H), 1.57 (s, 3 H), 2.34 (s, 3 H), 3.62 (d, J = 18.2 Hz, 1 H), 3.68 (d,
J = 18.2 Hz, 1 H), 4.21 (q, J = 7.1 Hz, 2 H), 7.44–7.48 (m, 2 H),
7.55–7.59 (m, 1 H), 7.95–7.98 (m, 2 H) ppm. 13C{1H} NMR
(CDCl3, 125 MHz): δ = 13.98 (CH3), 20.76 (CH3), 26.47 (CH3),
44.64 (CH2), 57.35 (C), 61.61 (CH2), 128.09 (CH), 128.65 (CH),
133.37 (CH), 136.67 (C), 162.49 (C), 172.37 (C), 197.12 (C) ppm.
(ATR): ν = 1732 (s), 1678 (vs), 1596 (m), 1580 (m), 1448 (m), 1329
˜
(m), 1270 (m), 1243 (m), 1216 (s), 1181 (m), 1001 (m) cm–1. MS
(70 eV, EI): m/z (%) = 310 (0.2) [M+], 292 (0.3), 265 (2), 233 (2),
205 (2), 188 (13), 105 (100), 77 (18). C19H18O4 (310.35): calcd. C
73.53, H 5.85; found C 73.54, H 5.98.
IR (ATR): ν = 2982 (m), 1735 (s), 1714 (vs), 1688 (s), 1449 (m),
˜
1355 (m), 1226 (m), 1186 (m), 1101 (m) cm–1. HRMS (CI, CH4):
calcd. 263.1283 (for C15H19O4), found 263.1275 [MH+].
3-Acetyl-1-phenylpentane-1,4-dione (2m): Acetylacetone (6m)
(200 mg, 2.00 mmol), CeCl3·7H2O (74 mg, 0.20 mmol), styrene (5)
(0.46 mL, 4.0 mmol and 0.23 mL, 2.0 mmol) in iPrOH (1.3 mL)
and pyridine (0.81 mL, 10.0 mmol), AcCl (0.86 mL, 12.0 mmol) in
CH2Cl2 (4.0 mL) were converted according to the General Pro-
cedure A. Chromatography (SiO2, PE/EA, 5:1) furnished 1,4-dike-
tone 2m [123 mg, 0.564 mmol, 28%, Rf(PE/EA, 2:1) = 0.22] as a
Ethyl 2-Acetyl-2-ethyl-4-oxo-4-phenylbutyrate (2j): β-Keto ester 6j
(790 mg, 5.00 mmol), CeCl3·7H2O (186 mg, 0.497 mmol), styrene
(5) (1.15 mL, 10.0 mmol and 0.58 mL, 5.1 mmol) in iPrOH
(3.3 mL) and pyridine (2.03 mL, 25.0 mmol), AcCl (2.13 mL,
30.0 mmol) in CH2Cl2 (10.0 mL) were converted according to the
General Procedure A. Chromatography (SiO2, PE/EA, 10:1) fur-
nished 1,4-diketone 2j [575 mg, 2.08 mmol, 42%, Rf(PE/EA, 2:1) =
1
yellowish oil. H NMR (CDCl3, 500 MHz): δ = 2.36 (s, 6 H), 3.59
1
0.62] as a colorless oil. H NMR (CDCl3, 500 MHz): δ = 0.84 (t,
(d, J = 6.9 Hz, 2 H), 4.39 (t, J = 6.9 Hz, 1 H), 7.45–7.49 (m, 2 H),
7.57–7.60 (m, 1 H), 7.95–7.98 (m, 2 H) ppm. 13C{1H} NMR
(CDCl3, 125 MHz): δ = 30.01 (CH3), 37.77 (CH2), 52.67 (C), 62.59
(CH), 128.16 (CH), 128.73 (CH), 133.63 (CH), 136.02 (C), 162.46
J = 7.6 Hz, 3 H), 1.23 (t, J = 7.0 Hz, 3 H), 2.09 (qd, J = 7.6, J =
15.0 Hz, 1 H), 2.18 (qd, J = 7.7, J = 15.3 Hz, 1 H), 2.37 (s, 3 H),
3.63 (d, J = 18.5 Hz, 1 H), 3.68 (d, J = 18.5 Hz, 1 H), 4.20 (q, J =
7.0 Hz, 2 H), 7.44–7.48 (m, 2 H), 7.55–7.59 (m, 1 H), 7.96–7.98 (m,
2 H) ppm. 13C{1H} NMR (CDCl3, 125 MHz): δ = 9.00 (CH3),
14.00 (CH3), 26.90 (CH2), 27.31 (CH3) 41.19 (CH2), 61.40 (CH2),
61.69 (C), 128.07 (CH), 128.62 (CH), 133.30 (CH), 136.58 (C),
(C), 196.97 (C), 202.99 (C) ppm. IR (ATR): ν = 1726 (m), 1700
˜
(s), 1681 (vs), 1596 (m), 1580 (m), 1448 (m), 1419 (m), 1356 (s),
1254 (m), 1212 (s), 1156 (s), 1001 (m) cm–1. MS (CI, CH4): m/z (%)
= 219 (100) [MH+], 201 (79), 177 (12), 158 (49), 105 (30), 77 (5).
C13H14O3 (218.25): calcd. C 71.54, H 6.47; found C 71.22, H 6.46.
171.94 (C), 197.46 (C), 205.73 (C) ppm. IR (ATR): ν = 2977 (m),
˜
1729 (s), 1710 (vs), 1684 (vs), 1597 (m), 1581 (m), 1448 (s), 1354
(s), 1218 (vs), 1180 (vs), 1101 (m), 1017 (m) cm–1. MS (CI, CH4):
m/z (%) = 277 (45) [MH+], 259 (84), 234 (60), 231 (100), 216 (5),
187 (59), 159 (14), 129 (21), 105 (66), 101 (15), 77 (18). C16H20O4
(276.33): calcd. C 69.55, H 7.30; found C 69.57, H 7.40.
3-Acetyl-3-methyl-1-phenylpentane-1,4-dione (2n): β-Diketone 6n
(228 mg, 2.00 mmol), CeCl3·7H2O (74 mg, 0.20 mmol), styrene (5)
(0.46 mL, 4.0 mmol and 0.23 mL, 2.0 mmol) in iPrOH (1.3 mL)
and pyridine (0.81 mL, 10.0 mmol), AcCl (0.86 mL, 12.0 mmol) in
CH2Cl2 (4.0 mL) were converted according to the General Pro-
cedure A. Chromatography (SiO2, PE/EA, 5:1) furnished 1,4-dike-
tone 2n [46 mg, 0.198 mmol, 10%, Rf(PE/EA, 2:1) = 0.31] as a col-
Ethyl 2-Acetyl-2-benzyl-4-oxo-4-phenylbutyrate (2k): β-Keto ester
6k (440 mg, 2.00 mmol), CeCl3·7H2O (74 mg, 0.497 mmol), styrene
(5) (0.46 mL, 4.0 mmol and 0.23 mL, 2.0 mmol) in iPrOH (1.3 mL)
and pyridine (0.81 mL, 10.0 mmol), AcCl (0.86 mL, 12.0 mmol) in
CH2Cl2 (4.0 mL) were converted according to the General Pro-
cedure A. Chromatography (SiO2, PE/EA, 10:1) furnished 1,4-dike-
tone 2k [360 mg, 1.06 mmol, 53%, Rf(PE/EA, 2:1) = 0.59] as a
colorless oil. 1H NMR (CDCl3, 500 MHz): δ = 1.23 (t, J = 7.1 Hz,
3 H), 2.46 (s, 3 H), 3.35 (d, J = 13.9 Hz 1 H), 3.50 (d, J = 18.5 Hz,
1 H), 3.56 (d, J = 13.9 Hz, 1 H), 3.57 (d, J = 18.5 Hz, 1 H), 4.20
(q, J = 7.1 Hz, 2 H), 6.94–6.96 (m, 2 H), 7.19–7.21 (m, 3 H), 7.42–
7.45 (m, 2 H), 7.55–7.57 (m, 1 H), 7.87–7.89 (m, 2 H) ppm.
13C{1H} NMR (CDCl3, 125 MHz): δ = 13.95 (CH3), 27.51 (CH3),
39.29 (CH2), 41.87 (CH2), 61.64 (CH2), 62.33 (C), 127.15 (CH),
128.05 (2 CH), 128.48 (CH), 128.60 (CH), 129.77 (CH), 133.39
(CH), 136.06 (C), 136.38 (C), 171.26 (C), 197.75 (C), 205.03 (C)
1
orless solid. M.p. 59°C. H NMR (CDCl3, 250 MHz): δ = 1.56 (s,
3 H), 2.22 (s, 6 H), 3.71 (s, 2 H), 7.47–7.50 (m, 2 H), 7.56–7.60 (m,
1 H), 7.95–7.99 (m, 2 H) ppm. 13C{1H} NMR (CDCl3, 62 MHz):
δ = 19.60 (CH3), 26.50 (CH3), 44.85 (CH2), 64.54 (C), 128.14 (CH),
128.73 (CH), 133.60 (CH), 136.44 (C), 197.28 (C), 206.21 (C) ppm.
IR (ATR): ν = 1740 (m), 1694 (vs), 1683 (s), 1595 (m), 1579 (m),
˜
1448 (m), 1368 (s), 1353 (s), 1215 (s), 1169 (s), 1092 (m), 1015 (m)
cm–1. MS (70 eV, EI): m/z (%) = 233 (0.3) [MH+], 214 (1), 190 (8),
172 (45), 147 (5), 105 (100), 85 (68), 77 (25), 57 (7). C14H16O3
(232.28): calcd. C 72.39, H 6.94; found C 72.26, H 7.00.
General Procedure B for 3-Hydroxy-1,2-dioxane Formation: The β-
dicarbonyl compound 6 (1.0 equiv.) was added to a suspension of
CeCl3·7H2O (0.05 equiv.) and styrene (5) (2.0 equiv.) in iPrOH. Af-
ter stirring the mixture for 14–16 h under an atmosphere of air and
at ambient temperature, all volatile materials were removed in
vacuo and the residue purified by chromatography on SiO2 (PE/
EA).
ppm. IR (ATR): ν = 1711 (vs), 1683 (vs), 1597 (m), 1495 (m), 1448
˜
(m), 1354 (s), 1267 (m), 1219 (s), 1181 (vs), 1082 (m), 1003 (m),
861 (m), 745 (s) cm–1. HRMS (CI, CH4): calcd. 338.1518 (for
C21H22O4), found 338.1514 [M+]; calcd. 339.1596 (for C21H23O4),
found 339.1579 [MH+].
6-Hydroxy-6-methyl-9-phenyl-7,8-dioxaspiro[4.5]decan-1-one (1a)
and 6-Acetyl-1-hydroxy-4-phenyl-2,3-dioxabicyclo[4.3.0]nonan-1-on
(1c): CeCl3·7H2O (30 mg, 0.081 mmol), styrene (5) (338 mg,
Ethyl 2-Benzoyl-4-oxo-4-phenylbutyrate (2l): β-Keto ester 6l
(358 mg, 1.86 mmol), CeCl3·7H2O (74 mg, 0.20 mmol), styrene (5)
5036
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 5031–5038

Cerium-Catalyzed, Aerobic Oxidative Synthesis of 1,2-Dioxane Derivatives
3.25 mmol) and β-diketone 6f (197 mg, 1.56 mmol) were converted [36 mg, 0.12 mmol, 7%, A/B = 53:47, Rf(SiO2, PE/EA, 5:1) = 0.28]
FULL PAPER
in 0.5 mL iPrOH according to the General Procedure B.
Chromatography (SiO2, PE/EA, 5:1) gave a first fraction with a
mixture of the title compounds 1a and 1c [90 mg, 0.34 mmol, 22%,
1a/1c 75:25, Rf(SiO2, PE/EA, 2:1) = 0.22] as a colorless solid, m.p.
102–105°C. The second fraction contained the 1,4-diketone 2f
(34 mg, 0.14 mmol, 9%) as yellowish oil. 1H NMR (500 MHz,
CDCl3), isomer 1a und 1c: δ = 1.34 (s, 3 H, CH3, isomer 1a), 1.75–
1.88 (m, 4 H), 1.89–1.95 (m, 2 H), 1.96–2.01 (m, 2 H), 2.08–2.15
(m, 1 H), 2.16–2.22 (m, 1 H), 2.21–2.37 (m, 4 H), 2.29 (s, 3 H,
was obtained as a colorless oil. The second fraction contained a
third isomer C [49 mg, 0.17 mmol, 11%, Rf(SiO2, PE/EA, 5:1) =
0.20] as colorless crystals. Single crystals were grown from isomer
1
C. Isomers A and B: H NMR (500 MHz, CDCl3): δ = 0.82 (t, J
= 7.6 Hz, 3 H, CH3, isomer B), 0.92 (t, J = 7.5 Hz, 3 H, CH3,
isomer A), 1.33 (t, J = 7.2 Hz, 3 H, CH3, isomer B), 1.38 (t, J =
7.2 Hz, 3 H, CH3, isomer A), 1.53 (s, 3 H, CH3, isomer B), 1.55–
1.61 (m, 1 H), 1.66–1.73 (m, 1 H), 1.70 (s, 3 H, CH3, isomer A),
1.92–2.02 (m, 3 H), 2.05–2.12 (m, 1 H), 2.39 (dd, J = 14.0, J =
CH3, isomer 1c), 2.46–2.52 (m, 2 H), 3.54 (br. s, 1 H, OH, isomer 2.5 Hz, 1 H, isomer B), 2.69 (dd, J = 14.1, J = 2.5 Hz, 1 H, isomer
1c), 4.28 (br. s, 1 H, OH, isomer 1c), 5.31 (dd, J = 11.4, J = 2.5 Hz, A), 3.53 (s, 1 H, OH, isomer B), 4.21–4.29 (m, 2 H, OCH2, isomer
1 H, CH, isomer 1c), 5.57 (dd, J = 11.7, J = 2.2 Hz, 1 H, CH, B), 4.29–4.42 (m, 2 H, OCH2, isomer A), 5.21 (dd, J = 11.7, J =
isomer 1a), 7.31–7.38 (m, 10 H, CH) ppm. 13C{1H} NMR
(125 MHz, CDCl3), isomer 1a: δ = 18.12 (CH2), 20.86 (CH3), 34.52
2.4 Hz, 1 H, CH, isomer A), 5.76 (dd, J = 11.6, J = 2.5 Hz, 1 H,
CH, isomer B), 7.17 (br. s, 1 H, OH, isomer A), 7.31–7.39 (m, 10
(CH2), 34.93 (CH2), 39.57 (CH2), 52.26 (C), 78.45 (CH), 100.21 H) ppm. 13C{1H} NMR (125 MHz, CDCl3), isomer A: δ = 8.87
(C), 127.14 (CH), 128.64 (CH), 128.92 (CH), 137.30 (C), 217.94 (CH3), 14.18 (CH3), 22.05 (CH3), 28.20 (CH2), 34.19 (CH2), 52.85
(C=O) ppm. Isomer 1c. δ = 19.03 (CH2), 27.17 (CH3), 30.58 (CH2),
33.07 (CH2), 35.36 (CH2), 57.44 (C), 77.26 (CH), 108.17 (C), 126.97
(CH), 128.60 (CH), 128.68 (CH), 137.57 (C), 211.67 (C=O) ppm.
(C), 61.94 (CH2), 81.19 (CH), 101.63 (C), 126.78 (CH), 128.65
(CH), 128.81 (CH), 138.14 (C), 176.34 (C=O) ppm. Isomer B: δ =
8.21 (CH3), 14.18 (CH3), 20.36 (CH3), 28.90 (CH2), 34.19 (CH2),
52.51 (C), 60.95 (CH2), 81.64 (CH), 104.53 (C), 126.96 (CH),
MS (FAB, glycerol): m/z (%) = 263 (9) [MH+], 245 (100) [M+
–
H2O], 229 (84) [M+ – H2O2], 203 (13), 187 (15), 151 (34), 105 (12). 128.65 (CH), 128.76 (CH), 137.49 (C), 172.98 (C=O) ppm. MS (EI,
IR (ATR): ν = 3385 (br. s), 1729 (vs), 1670 (vs), 1453 (m), 1376 70 eV): m/z (%) = 294 (2) [M+], 276 (3) [M+ – H2O], 262 (12) [M+
–
˜
(m), 1320 (m), 1272 (m), 1156 (s) cm–1. HRMS (CI, CH4): calcd. O2], 234 (19), 190 (8), 188 (29), 158 (53), 143 (19), 129 (32), 105
263.1283 (for C15H19O4), found 263.1280 [MH+].
(100), 77 (51). IR (ATR): ν = 3352 (br. m), 2976 (s), 2942 (m), 1724
˜
(vs), 1694 (vs), 1455 (s), 1371 (m), 1312 (m), 1234 (m), 1215 (s),
1196 (s), 1124 (m), 1036 (m) cm–1. C16H22O5 (294.34): calcd. C
65.29, H 7.53; found C 65.46, H 7.56. Isomer C: 1H NMR
(500 MHz, CDCl3): δ = 0.87 (t, J = 7.5 Hz, 3 H, CH3), 1.29 (t, J
= 7.1 Hz, 3 H, CH3), 1.58 (s, 3 H, CH3), 1.99–2.06 (m, 1 H), 2.06–
2.15 (m, 2 H), 2.73 (ddd, J = 14.8, J = 12.3, J = 1.3 Hz, 1 H), 3.50
(br. s, 1 H, OH), 4.15–4.27 (m, 2 H, CH2), 5.18 (dd, J = 12.3, J =
2.0 Hz, 1 H, CH), 7.33–7.42 (m, 5 H) ppm. 13C{1H} NMR
(125 MHz, CDCl3): δ = 9.02 (CH3), 14.18 (CH3), 20.94 (CH3),
23.70 (CH2), 29.65 (CH2), 52.17 (C), 61.16 (CH2), 78.83 (CH),
102.12 (C), 127.16 (CH), 128.64 (CH), 128.96 (CH), 137.40 (C),
173.02 (C=O) ppm. M.p. 89–92°C. C16H22O5 (294.34): calcd. C
65.29, H 7.53; found C 65.59, H 7.50.
7-Hydroxy-7-methyl-10-phenyl-8,9-dioxaspiro[5.5]undecane-1-one
(1b): CeCl3·7H2O (30 mg, 0.081 mmol), styrene (5) (333 mg,
3.20 mmol) and β-diketone 6o (226 mg, 1.55 mmol) were converted
in 0.5 mL iPrOH according to the General Procedure B.
Chromatography (SiO2, PE/EA, 5:1) gave the title compound 1b as
a mixture of diastereoisomers A and B [140 mg, 0.507 mmol, 33%;
A/B = 71:29, isomer A: Rf(SiO2, PE/EA, 2:1) = 0.38, isomer B:
Rf(SiO2, PE/EA, 2:1) = 0.42] as a colorless oil. Both isomers could
be separated by repeated chromatography. Isomer A: 1H NMR
(500 MHz, CDCl3): δ = 1.26 (qt, J = 13.6, J = 1.5 Hz, 1 H), 1.50
(qt, J = 13.5, J = 4.1 Hz, 1 H), 1.59–1.65 (m, 1 H), 1.66–1.72 (m,
1 H), 1.75–1.81 (m, 1 H), 1.84–1.88 (m, 1 H), 1.90–1.95 (m, 1 H),
2.11 (dt, J = 14.1, J = 5.1 Hz, 1 H), 2.22 (s, 3 H, CH3), 2.38 (dt, J
= 14.0, J = 3.6 Hz, 1 H), 2.51 (dd, J = 13.2, J = 11.8 Hz, 1 H),
4.22 (br. s, 1 H, OH), 5.46 (dd, J = 11.7, J = 2.5 Hz, 1 H, CH),
7.32–7.39 (m, 5 H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ =
22.24 (CH2), 22.79 (CH2), 26.14 (CH3), 30.36 (CH2), 34.58 (CH2),
36.02 (CH2), 53.38 (C), 78.22 (CH), 99.54 (C), 127.10 (CH), 128.68
Ethyl 6-Hydroxy-3-phenyl-4,5-dioxabicyclo[4.4.0]decane-1-carbox-
ylate (1e): CeCl3·7H2O (30 mg, 0.081 mmol), styrene (5) (331 mg,
3.18 mmol) and β-keto ester 6b (267 mg, 1.57 mmol) were con-
verted in 0.5 mL iPrOH according to the General Procedure B.
Chromatography (SiO2, PE/EA, 10:1) gave a mixture of two dia-
stereoisomers A and B (240 mg, 0.785 mmol, 50%, A/B = 50:50),
which were separated by repeated chromatography [isomer A:
Rf(SiO2, PE/EA, 5:1) = 0.32; isomer B: Rf(SiO2, PE/EA, 5:1) =
0.15]. Single crystals were grown from isomer A, m.p. 118°C.
C17H22O5 (306.15): calcd. C 66.65, H 7.24; found C 66.79, H 7.15.
All spectroscopic data were in accordance with the literature.[10b]
1
(CH), 129.01 (CH), 137.59 (C), 212.51 (C=O) ppm. Isomer B: H
NMR (500 MHz, CDCl3): δ = 1.60–1.74 (m, 4 H), 1.75–1.80 (m, 2
H), 1.87 (dq, J = 13.1, J = 4.6 Hz, 1 H), 2.25–2.29 (m, 1 H), 2.32
(s, 3 H, CH3), 2.41–2.54 (m, 1 H), 2.74 (dd, J = 14.7, J = 12.2 Hz,
1 H), 5.05 (dd, J = 12.0, J = 2.1 Hz, 1 H, CH), 7.16 (br. s, 1 H,
OH), 7.33–7.42 (m, 5 H) ppm. 13C{1H} NMR (125 MHz, CDCl3):
δ = 20.36 (CH2), 22.54 (CH2), 26.84 (CH3), 31.32 (CH2), 32.38
(CH2), 36.07 (CH2), 52.36 (C), 81.21 (CH), 104.19 (C), 126.75
(CH), 128.76 (CH), 129.00 (CH), 137.84 (C), 217.01 (C=O) ppm.
Methyl 7-Hydroxy-10-methyl-10-phenyl-8,9-dioxabicyclo[5.4.0]un-
decane-1-carboxylate (1f): CeCl3·7H2O (30 mg, 0.081 mmol), α-
methylstyrene (393 mg, 3.33 mmol) and β-keto ester 6c (291 mg,
1.71 mmol) were converted in 0.5 mL iPrOH according to the Ge-
neral Procedure B. Chromatography (SiO2, PE/EA, 10:1) gave a
mixture of four diastereoisomers A, B, C, and D (288 mg,
0.899 mmol, 53%, A/B/C/D = 38:25:24:16), which were partly sepa-
rated by repeated chromatography [isomer A and D: Rf(SiO2, PE/
MS (FAB, glycerol): m/z (%) = 277 (26) [MH+], 259 (100) [MH+
–
H2O], 243 (93) [MH+ – H2O2], 217 (16), 199 (20), 165 (29), 132
(56), 123 (40), 105 (26). IR (ATR): ν = 3322 (br. m), 2940 (s), 2868
˜
(m), 1685 (s), 1453 (s) cm–1. C16H20O4 (276.14): calcd. C 69.55, H
7.30; found C 69.66, H 7.28.
Ethyl 4-Ethyl-3-hydroxy-3-methyl-6-phenyl-1,2-dioxane-4-carboxyl-
ate (1d): CeCl3·7H2O (30 mg, 0.081 mmol), styrene (5) (333 mg, EA, 5:1) = 0.28; isomer B and C: Rf(SiO2, PE/EA, 5:1) = 0.34–
3.20 mmol) and β-keto ester 6j (261 mg, 1.65 mmol) were converted
in 0.5 mL iPrOH according to the General Procedure B.
Chromatography (SiO2, PE/EA, 10:1) gave two fractions with the
product. In the first a mixture of two diastereoisomers A and B
0.44]. Single crystals of isomer C were grown from a mixture with
isomer B, m.p. 124–129°C. C18H24O5 (320.38): calcd. C 67.48, H
7.55; found C 67.28, H 7.55. All spectroscopic data were in accord-
ance with the literature.[10b]
Eur. J. Org. Chem. 2005, 5031–5038
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5037

M. Rössle, T. Werner, W. Frey, J. Christoffers
FULL PAPER
[11] a) J. Christoffers, T. Werner, Synlett 2002, 119–121; b) J.
Christoffers, T. Werner, S. Unger, W. Frey, Eur. J. Org. Chem.
2003, 425–431; c) J. Christoffers, T. Werner, W. Frey, A. Baro,
Chem. Eur. J. 2004, 10, 1042–1045; d) Review: J. Christoffers,
A. Baro, T. Werner, Adv. Synth. Catal. 2004, 346, 143–151.
[12] At least to some extend 1,4-diketones might already form by
direct oxidation of the benzyl radical by CeIV species as was
observed earlier by us in certain cases.[10b] See also: a) V. Nair,
J. Mathew, J. Chem. Soc., Perkin Trans. 1 1995, 1881–1882; b)
Review: V. Nair, L. Balagopal, R. Rajan, J. Mathew, Acc.
Chem. Res. 2004, 37, 21–30.
Acknowledgments
We acknowledge the Deutsche Forschungsgemeinschaft and the
Fonds der Chemischen Industrie (fellowship for M. R.) for gener-
ous support of this work.
[1] N. Kornblum, H. E. DeLaMare, J. Am. Chem. Soc. 1951, 73,
880–881.
[2] a) B. W. Greatrex, D. K. Taylor, E. R. T. Tiekink, J. Org. Chem.
2004, 69, 2580–2583; b) B. W. Greatrex, N. F. Jenkins, D. K.
Taylor, E. R. T. Tiekink, J. Org. Chem. 2003, 68, 5205–5210; c)
G. Özer, N. Saracoglu, M. Balci, J. Org. Chem. 2003, 68, 7009–
7015.
[13]
a) E. Camacho, J. Leon, A. Carrion, A. Entrena, G. Escames,
H. Khaldy, D. Acuna-Castroviejo, M. A. Gallo, A. Espinosa,
J. Med. Chem. 2002, 45, 263–274; b) M. Van der Mey, A. Hatz-
elmann, I. J. Van der Laan, G. J. Sterk, U. Thibaut, H. Timm-
erman, J. Med. Chem. 2001, 44, 2511–2522; c) M. Yasuda, S.
Tsuji, I. Shibata, A. Baba, J. Org. Chem. 1997, 62, 8282–8283;
d) F. Ros, J. de la Rosa, J. Enfedaque, J. Org. Chem. 1995, 60,
5419–5424; e) F. F. Owings, M. Fox, C. J. Kowalski, N. H.
Baine, J. Org. Chem. 1991, 56, 1963–1966.
[3] D. R. Kelly, H. Bansal, J. J. G. Morgan, Tetrahedron Lett. 2002,
43, 9331–9333.
[4] Selection of other new 1,4-diketone syntheses: a) M. Yuguchi,
M. Tokuda, K. Orito, J. Org. Chem. 2004, 69, 908–914; b) R.
Ballini, L. Barboni, G. Giarlo, J. Org. Chem. 2003, 68, 9173–
9176; c) Y. Yamamoto, H. Maekawa, S. Goda, I. Nishiguchi,
Org. Lett. 2003, 5, 2755–2758; d) M. Yasuda, S. Tsuji, Y. Shige-
yoshi, A. Baba, J. Am. Chem. Soc. 2002, 124, 7440–7447.
[5] a) B. K. Banik, S. Samajdar, I. Banik, J. Org. Chem. 2004, 69,
213–216; b) G. Minetto, L. F. Raveglia, M. Taddei, Org. Lett.
2004, 6, 389–392; c) R. Dhawan, B. A. Arndtsen, J. Am. Chem.
Soc. 2004, 126, 468–469; d) H. S. P. Rao, S. Jothilingam, J. Org.
Chem. 2003, 68, 5392–5394; e) B. W. Greatrex, M. C. Kimber,
D. K. Taylor, E. R. T. Tiekink, J. Org. Chem. 2003, 68, 4239–
4246; f) D. S. Mortensen, A. L. Rodriguez, K. E. Carlson, J.
Sun, B. S. Katzenellenbogen, J. A. Katzenellenbogen, J. Med.
Chem. 2001, 44, 3838–3848; g) R. U. Braun, K. Zeitler, T. J. J.
Müller, Org. Lett. 2001, 3, 3297–3300.
[6] a) J. Christoffers, in: Encyclopedia of Catalysis, vol. 5 (Ed.: I.
Horvath), Wiley, New York, 2003, pp. 99–118; b) N. Krause,
A. Hoffmann-Röder, Synthesis 2001, 171–196; c) B. E. Rossiter,
N. M. Swingle, Chem. Rev. 1992, 92, 771–806.
[7] Recent examples: a) M. A. Calter, C. Zhu, Org. Lett. 2002, 4,
205–208; b) M. A. Calter, C. Zhu, R. J. Lachicotte, Org. Lett.
2002, 4, 209–212; c) F. Stauffer, R. Neier, Org. Lett. 2000, 2,
3535–3537.
[14]
a) J.-Q. Yu, E. J. Corey, J. Am. Chem. Soc. 2003, 125, 3232–
3233; b) B. Greatrex, M. Jevric, M. C. Kimber, S. J. Krivickas,
D. K. Taylor, E. R. T. Tiekink, Synthesis 2003, 668–672; c)
B. W. Greatrex, M. C. Kimber, D. K. Taylor, G. Fallon,
E. R. T. Tiekink, J. Org. Chem. 2002, 67, 5307–5314; d) M. C.
Kimber, D. K. Taylor, J. Org. Chem. 2002, 67, 3142–3144; e)
T. D. Avery, G. Fallon, B. W. Greatrex, S. M. Pyke, D. K. Tay-
lor, E. R. T. Tiekink, J. Org. Chem. 2001, 66, 7955–7966; f) J.
Yoshida, S. Nakatani, K. Sakaguchi, S. Isoe, J. Org. Chem.
1989, 54, 3383–3389.
[15]
[16]
CCDC-276598 (for 2g), -276597 (for 1d), -276595 (for 1e), and -
276596 (for 1f) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
G. Bar, A. F. Parsons, C. B. Thomas, Synlett 2002, 1069–1072.
[17] M. T. M. Clements, T. B. H. McMurry, Can. J. Chem. 1987, 65,
1810–1813.
[18] Y. Liu, Y. Zhang, Tetrahedron 2003, 59, 8429–8437.
[19] P.-K. Chiu, M. P. Sammes, Tetrahedron 1988, 44, 3531–3538.
[20] J. P. Sestelo, M. del Mar Real, L. A. Sarandeses, J. Org. Chem.
2001, 66, 1395–1402.
[8] Review: A. B. Smith III, C. M. Adams, Acc. Chem. Res. 2004,
37, 365–377.
[9] Review: D. Enders, T. Balensiefer, Acc. Chem. Res. 2004, 37,
534–541.
[10] a) M. Rössle, T. Werner, A. Baro, W. Frey, J. Christoffers, An-
gew. Chem. 2004, 116, 6709–6711; Angew. Chem. Int. Ed. 2004,
43, 6547–6549; b) J. Christoffers, T. Werner, W. Frey, A. Baro,
Eur. J. Org. Chem. 2003, 4879–4886.
[21] K. Nakamura, T. Miyai, A. Nagar, S. Oka, A. Ohno, Bull.
Chem. Soc. Jpn. 1989, 62, 1179–1187.
[22] H. G. O. Becker, K. Schwetlick, Autorenkollektiv, Organikum,
20th ed., Wiley-VCH, Weinheim, 1999, pp. 593.
Received: July 1, 2005
Published Online: October 19, 2005
5038
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 5031–5038