Formation of 1,4-diketones by aerobic oxidative C-C coupling of styrene with 1,3-dicarbonyl compounds

Article abstract of DOI:10.1002/anie.200461406

(Chemical equation presented). Convenient and direct: 1,4-Dicarbonyl compounds are readily obtained through a one-pot cerium-catalyzed oxidative C-C coupling in the presence of oxygen and subsequent fragmentation. The products are suitable precursors for

Full text of DOI:10.1002/anie.200461406

Angewandte
Chemie
À
C C Coupling
Formation of 1,4-Diketones by Aerobic Oxidative
À
C C Coupling of Styrene with 1,3-Dicarbonyl
Compounds**
Michael Rössle, Thomas Werner, Angelika Baro,
Wolfgang Frey, and Jens Christoffers*
1,4-Dicarbonyl compounds[1] are versatile precursors for the
synthesis of various heterocyclic structural motifs, for exam-
ple, furan,[2] thiophene, and pyrrole derivatives.[3] The con-
version of a-halo ketones with enolates represents a classic
route to 1,4-dicarbonyl compounds (Feist–BØnary synthesis of
furan derivatives).[4] A modern concept utilizes the umpolung
of aldehydes, for example, by application of the Stetter
reagent[5] or 1,3-dithiane derivatives.[6]
Recently, we reported the cerium-catalyzed a hydroxyl-
ation of 1,3-dicarbonyl compounds 1 (Scheme 1).[7] With
Scheme 1. Cerium-catalyzed a hydroxylation of b-oxoester 1a with O2
À
and oxidative C C coupling with styrene 3.
respect to economical and ecological considerations, the use
of molecular oxygen is superior to other reagents applied in
this type of conversion. Based on the assumption of radical
intermediates along the hydroxylation pathway, the conver-
sion has been performed in the presence of olefins such as
styrene (3), and indeed, hydroperoxides 4 were obtained as
the major products. Compounds 4 were isolated as hemi-
acetals such as 4b with an endoperoxide 1,2-dioxane ring.[8]
Surprisingly, these crystalline endoperoxides have a
remarkable stability indicated by defined melting points
between 50 and 1508C, but, unfortunately, they were obtained
as hardly separable mixtures of diastereoisomers. Thus,
purification and characterization are difficult, resulting in a
[*] M. Rössle, Dr. T. Werner, Dr. A. Baro, Dr. W. Frey, Prof. J. Christoffers
Institut für Organische Chemie, Universität Stuttgart
Pfaffenwaldring 55, 70569 Stuttgart (Germany)
Fax: (+49)711-685-4269
E-mail: jchr@oc.uni-stuttgart.de
[**] This work was generously supported by the Deutsche Forschungs-
gemeinschaft and the Fonds der Chemischen Industrie.
Angew. Chem. Int. Ed. 2004, 43, 6547 –6549
DOI: 10.1002/anie.200461406
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Communications
restricted application for further synthetic purposes. We were
Apart from carbocyclic and open-chain b-oxoesters and
1,3-diketones, heterocyclic compounds were also investi-
gated. As can be seen from Table 1, the best result was
realized for lactone 5c (87% overall yield), whereas of
cyclohexanone derivative 5e was obtained in 50% yield. All
other substrates, which include lactam 5d and carbocyclic and
open-chain derivatives, were isolated in 62–72% yield. The
reaction sequence could also be extended to the seven-
membered ring product 5 f (71%). In contrast to a hydrox-
ylations, even the a-unsubstituted substrate 1h (R’ = H)
cleanly reacted in this manner with 3 to give 5h in 72%
yield (Table 1).
To prove the utility of the 1,4-diketones 5 (which bear a
quaternary C atom) as building blocks in the synthesis of
heterocycles, compound 5a was treated with liquid NH3.
After chromatographic workup, the novel bicyclic 3,4-dihy-
dro-2H-pyrrole derivative 6 was isolated as a single diaster-
eomer in 63% yield (Scheme 2). The molecular structure of 6
therefore interested in the conversion of 1,2-dioxanes into
diastereomerically unique products, either by oxidation,
reduction or by disproportionation of the peroxide unit.[9]
After considerable experimentation with a number of tran-
sition-metal-assisted transformations,[10] we focused our inter-
est on the Kornblum–DeLaMare fragmentation mediated by
a pyridine/acetyl chloride system.[11] Owing to the difficult
purification of the diastereomeric endoperoxide mixtures, we
À
investigated a sequential one-pot procedure for oxidative C
C bond formation and Kornblum–DeLaMare fragmentation.
Herein we report an optimized protocol as the result of these
studies.
1,3-Dicarbonyl compounds 1a–h were converted with
styrene (3) under CeCl3·7H2O catalysis (10 mol%) in 2-
propanol at ambient temperature under an atmosphere of air
as the oxidant (Table 1). Under higher partial pressures of O2
the formation of undesired a-hydroxylated products 2 is
favored.
Table 1: Formation of 1,4-dicarbonyl compounds 5 by a two-step one-pot
À
reaction consisting of cerium-catalyzed C C coupling with 3 and
subsequent Kornblum–DeLaMare fragmentation.[a]
Scheme 2. Interrupted Paal-Knorr reaction of the 1,4-dicarbonyl com-
pound 5a to pyrrole derivative 6.
was confirmed by X-ray single-crystal analysis (Figure 1)[12]
and can be seen as a product of an interrupted Paal–Knorr
pyrrole synthesis. The final elimination of water is inhibited
by the quaternary center, and the position of the formed
double bond is unexpected for this type of reaction.[4a,b]
Product
Yield [%][b]
71
Product
Yield [%][b]
50[c]
5a
5e
5b
5c
5d
62
5 f
71
68
72
87[c]
72
5g
5h
[a] See Experimental Section for reaction conditions. [b] Overall yield
over two steps. [c] 5 mol% of CeCl3·7H2O.
As 3 is partly consumed by polymerization, the reaction
was started with the addition of 2 equivalents followed by a
further 1 equivalent of 3 after 4 h. The reaction mixture was
stirred for a further 20 h, and then all volatile materials were
removed under vacuum, leaving a mixture of crude endoper-
oxides 4, polystyrene, and cerium-containing materials. This
residue was directly treated with a mixture of pyridine
(5 equiv) and AcCl (6 equiv) in CH2Cl2 and stirred for 16 h
at ambient temperature. Filtration through SiO2 and chro-
matography gave unique 1,4-diketones 5 in the range of 50–
90% overall yield over two steps (Table 1).
Figure 1. ORTEP view of 3,4-dihydro-2H-pyrrole derivative 6 drawn at
the 50% probability level.
In summary, 1,4-diketones 5 are readily accessible in a
two-step one-pot reaction in 50–87% overall yields. Our
synthetic concept, which may be a valuable alternative to
other umpolung strategies, combines an oxidative cerium-
À
catalyzed C C coupling of 1,3-dicarbonyl compounds 1 with
styrene (3) and
a pyridine/AcCl-mediated Kornblum–
DeLaMare fragmentation. A follow-up reaction of 5a with
6548
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Angewandte
Chemie
[11] a) N. Kornblum, H. E. DeLaMare, J. Am. Chem. Soc. 1951, 73,
NH3 to afford the new dihydro-2H-pyrrole derivative 6
demonstrates that 1,4-diketones 5 are suitable precursors
for heterocyclic compounds.
880 – 881; b) S. J. Blanksby, G. B. Ellison, V. M. Bierbaum, S.
Kato, J. Am. Chem. Soc. 2002, 124, 3196 – 3197.
[12] CCDC-245445 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cam-
bridge Crystallographic Data Centre, 12, Union Road, Cam-
bridge CB21EZ, UK; fax: (+ 44)1223-336-033; or deposit@
ccdc.cam.ac.uk).
Experimental Section
Typical procedure: Styrene (3; 2.0 equiv) and the respective 1,3-
dicarbonyl compound 1 (1 mmol, 1.0 equiv) were added to a stirred
suspension of CeCl3·7H2O (0.1 equiv) in iPrOH (0.65 mL/mmol 1).
After 4 h, more 3 (1.0 equiv) was added, and the reaction mixture was
stirred for a further 20 h at room temperature. All volatile materials
were removed under vacuum, and the residue was suspended in
CH2Cl2 (2 mL/mmol 1). Pyridine (5.0 equiv) and acetyl chloride
(6.0 equiv) were added at 08C, and the resulting mixture was stirred
for 16 h at room temperature. The reaction mixture was filtered
through SiO2 (petroleum ether/EtOAc 2:1) and subsequently purified
by silica-gel column chromatography (petroleum ether/EtOAc 5:1) to
give 1,4-diketones 5 as the major products.
Received: July 23, 2004
À
Keywords: dicarbonyl compounds · C C coupling · cerium ·
heterocycles · homogeneous catalysis
.
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