Carbonyl ylide reactions of α-benzylidene-β-dicarbonyl compounds: competitive formation of dihydrofurans and dihydrobenzoxepines

Article abstract of DOI:10.1016/j.tetlet.2007.11.197

α-Benzylidene-β,β′-biscarbonyl compounds were reacted with dimethyl diazomalonate using Cu(II) acetylacetonate as a catalyst. Dihydrofurans or mixtures of dihydrofurans and dihydrobenzoxepines were obtained depending on the nature of the carbonyl group present in the starting material.

Full text of DOI:10.1016/j.tetlet.2007.11.197

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1062–1065
Carbonyl ylide reactions of a-benzylidene-b-dicarbonyl compounds:
competitive formation of dihydrofurans and dihydrobenzoxepines
*
¨
¨
Olcay Anaßc , Ozkan Sezer, Ozlem Candan, Fusun Sßeyma Gungo¨r, M. Sßerif Cansever
¨
¨
Istanbul Technical University, Faculty of Science and Letters, Department of Chemistry, 34469 Maslak, Istanbul, Turkey
Received 15 October 2007; revised 19 November 2007; accepted 30 November 2007
Available online 4 December 2007
Abstract
a-Benzylidene-b,b0-biscarbonyl compounds were reacted with dimethyl diazomalonate using Cu(II) acetylacetonate as a catalyst.
Dihydrofurans or mixtures of dihydrofurans and dihydrobenzoxepines were obtained depending on the nature of the carbonyl group
present in the starting material.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Carbene; 1,5-Electrocyclization; 1,7-Electrocyclization; Dihydrofuran; Dihydrobenzoxepine
During the past decade, we have been studying the
formal 1,5-electrocyclization reactions of carbonyl ylides
derived from metallo-carbenoid species and a,b-unsatu-
rated carbonyl compounds with alkyl or aryl groups as a
b-substituent.1 Cu(II) acetylacetonate catalyzed decompo-
sitions of diacyl diazo compounds, such as dimethyl diazo-
malonate, in the presence of a,b-unsaturated carbonyl
compounds, such as a,b-unsaturated ketones and esters,
were reported to yield mainly dihydrofuran derivatives.
For the reactions to proceed as described, it was reported
that the unsaturated carbonyl compounds must be mono-
substituted at their b-position with trans geometry. For
the formation of dihydrofurans, they should favor the
s-cis conformation. The products were reported to be
capable of further reactions, as well. Similar formal electro-
cyclizations were also reported by the Hamaguchi group2
and more recently by Sliwinska and Warkentin3 Our
results with esters were in contrast to the results of other
researchers who obtained only cyclopropanes4 and other
products.5 Since furan derivatives are among the most
significant heterocycles in natural products, these reactions
possess synthetic value. In recent articles by our group, we
reported an unusual 1,3-dioxole formation from a strained
bicyclic ketone.6 We realized that the reactions of a,b-
enaminones7 were in contrast to the studies of Maas and
Muller;8 we reported the presence of significant amounts
¨
of dihydrofurans under our reaction conditions. Novel
3-anilino-4-oxo-1,4-dihydronaphthalene derivatives were
also obtained from an unusual insertion into the benzoyl
ring in the case of aniline derivatives. In this study, we
compared the reactivities of a,b-unsaturated esters and
ketones in these reactions with ylides.
Z- and E-ethyl acetobenzylidene acetates 1a and 1b9
were treated with dimethyl diazomalonate (dmdm) in the
presence of Cu(acac)2 to compare the reactivities of conju-
gated ketone and ester functions toward ylide formation
and the reactivities of these ylides in the formal 1,5-electro-
cyclization reactions. Product distributions were deter-
mined by GC–MS and 1H NMR spectroscopy. The
experiments were also repeated using two other E/Z mix-
tures (1:1.9 and 2.5:1 by NMR). We obtained the same
two products 3a and 4a (which are identical to 2b and
5b, respectively) only, approximately in the same ratios
(Scheme 1 and Table 1). Contrary to our previous experi-
ence, 2a (or 3b), which would result from the respective
keto-ylides, was not found in the reactions. On the other
*
Corresponding author. Tel.: +90 212 2853229; fax: +90 212 2856386.
E-mail address: anac@itu.edu.tr (O. Anaßc).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.197

O. Anaßc et al. / Tetrahedron Letters 49 (2008) 1062–1065
1063
E
E
O
O
E
E
O
O
R1
R2
R2
R1
R1
R2
dmdm
Ph
R2
O
Ph
R1
O
Cu(acac)2
Ph
Ph
R1
R2
O
O
O
O
E
E
E: COOMe
1
2
3
E
E
5
4
E
E
E
Ph
O
COOEt
E
OEt
6
7
Scheme 1. The reactions of bis-carbonyl compounds and dmdm.
Table 1
Product distribution in the reactions of bis-carbonyl compounds and dmdm
Enone
R1
R2
Product distribution
2
3
4
5
1a
1b
1c
1d
6
Me
OEt
OEt
Me
OEt
Me
OEt
Me
—
1.0 (=2b)
—
(2c)
1.0 (=5b)
—
—
1.5 (=5d)
—
—
1.0 (=3a)
1.0 (=3c)1d
1.0 (=3d)
1.0 (=4a)
—
(4d)
(2d)
Ethyl cinnamate
7:1.0
hand, the formation of a dihydrobenzoxepine product
showed that a 1,7-electrocyclization also took place under
these conditions, obviously via the corresponding E-keto-
ylides. This was not observed in our previous studies.1
The reactions of the ene–diester 1c (diethyl benzylidene-
malonate) did not yield dihydrobenzoxepines.1d We per-
formed the same reaction using ethyl cinnamate (6), a
simpler mono-ester analogue, and the results were
unchanged (Table 1). This suggested that the formation
of dihydrobenzoxepines is restricted to substrates with
ketone functions only.
the rotation of the carbonyl ylides came from the fact that
both E- and Z-acetoacetates yielded the same mixture of
products with the same ratios.
The 1,7-cyclization step is most likely a concerted reac-
tion11,12 (but in such strongly polarized systems, charge
control may also be a possibility). If the cyclization step
is a pericyclic mechanism, then there is competition
between the 6p 1,5- and the 8p 1,7-cyclization of the conju-
gated carbonyl ylide intermediates derived from the ester-
and keto-ylides, respectively, to the b- or ortho carbon of
the phenyl ring. As discussed,11–13 if the possibility of both
To gain more information on this novel dihydrobenzoxe-
pine formation, we reacted benzylidene acetylacetone (1d)
with dmdm under the same conditions and obtained 4d as
the major product. The structure of 4d was determined by
crystallographic analysis (Fig. 1).
According to our previous proposals, the transforma-
tions 1a?3a and 1b?3b are not expected unless the reac-
tion proceeds in a stepwise manner. In other words, 1b
should only yield 2b (3a) and no products originating from
a keto-ylide. At this point, we eliminated the possibility of
E–Z interconversion.10 In light of this data, we propose
that the overall reaction steps for the formation of com-
pounds 4a and 4d are as follows: (i) formation of a keto-
ylide, (ii) rotation around formal C@C bonds in the fully
conjugated dicarbonyl derivatives (not observed in the
corresponding mono-carbonyls) (Scheme 2), (iii) 1,7-cycli-
zation, and (iv) a [1,5]-hydrogen shift. The evidence for
CCDC-662876 (4d) contains the supplementary crystallographic data
for this Letter. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Fig. 1. The X-ray structure of 4d.

1064
O. Anaßc et al. / Tetrahedron Letters 49 (2008) 1062–1065
E
E
E
O
E
O
O
E
O
O
E
O
O
Me
O
Me
R
Me
R
Me
R
1a (R = OEt)
1b (R = OEt)
E
O
E
Et
C
O
R
O
Me
Me
O
O
Et
E
O
E
1d (R = Me)
8π−
E
E
D
O
O
O
R
Me
R
O
E
3
5a (4b)
R
~ [1,5] - H
2
4
4a (5b)
4d (5d)
1
Me
5
Me
E
O
O
H
E
E
E
E
B
A
Scheme 2. Formation of dihydrobenzoxepines from conjugated dicarbonyls.
1,5- and 1,7-electrocyclization existed, the latter is often
preferred because of the larger orbital coefficients at the
termini of the conjugated system involving the 8p electrons.
According to our results, the ester–ylides preferred forma-
tion of dihydrofurans, whereas keto-ylides showed prefer-
ence for 7-membered rings.14 In conclusion, we suggest
that these initially formed carbonyl-ylides are highly polar-
ized and need not undergo electrocyclization reactions
directly, but may rather undergo a rotation around their
C(a)–C(b) bonds leading to the two different ring closure
reaction products.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2007.
11.197.
References and notes
1. (a) Anaßc, O.; Daut, A. Liebigs Ann. Recl. 1997, 1249–1254; (b) Anaßc,
¨
¨
O.; Daut-Ozdemir, A.; Sezer, O. Helv. Chim. Acta 2003, 86, 290–297;
(c) Anaßc, O.; Gungo¨r, F. Sß.; Kahveci, C¸ .; Cansever, M. Sß. Helv. Chim.
¨
Typical procedure1 for the reaction of a-benzylidene b-
dicarbonyl compounds with dmdm: To a solution of the
enone substrate (1.5 equiv) in benzene (10 mL) was added
Cu(acac)2 (0.007 equiv), and the mixture was heated at
reflux. A solution of dmdm (1 equiv) in benzene (4 mL)
was added to this solution over 2.5 h under an N2 atmo-
sphere. When the IR spectrum of the reaction mixture indi-
cated total consumption of dimethyl diazomalonate
(absence of the characteristic diazo band at 2130 cmꢀ1),
the mixture was filtered, evaporated, and purified by col-
umn chromatography or preparative TLC.
Acta 2004, 87, 408–415; (d) Anaßc, O.; Gungo¨r, F. Sß.; Merey, G. Helv.
¨
Chim. Acta 2006, 89, 1231–1240.
2. Hamaguchi, M.; Matsubara, H.; Nagai, T. J. Org. Chem. 2001, 66,
5395–5404.
3. Sliwinska, A.; Warkentin, J. Org. Lett. 2007, 9, 2605–2607.
4. (a) Charette, A. B.; Janes, M. K.; Lebel, H. Tetrahedron: Asymmetry
2003, 14, 867–872; (b) Miller, J. A.; Jin, W.; Nguyen, S. T. Angew.
Chem., Int. Ed. 2002, 41, 2953–2956; (c) Aggarwal, V. K.; Alonso, E.;
Fang, G.; Ferraro, M.; Hynd, G.; Porcelloni, M. Angew. Chem., Int.
Ed. 2001, 40, 1433–1436; (d) Schinnerl, M.; Bo¨hm, C.; Seitz, M.;
Reiser, D. Tetrahedron: Asymmetry 2003, 14, 765–771; (e) Temme, O.;
Taj, S. A.; Anderson, P. G. J. Org. Chem. 1998, 63, 6007–
6015.
5. (a) Padwa, A.; Precedo, L.; Semones, M. A. J. Org. Chem. 1999, 64,
4079–4088; (b) Padwa, A.; Boonsombat, P.; Rashatasakhon, P.;
Willis, J. Org. Lett. 2005, 7, 3725–3727.
¨
6. C¸ elik, M. A.; Yurtsever, M.; Tuzun, N. Sß.; Gungo¨r, F. Sß.; Sezer, O.;
Acknowledgments
¨ ¨
¨
Anaßc, O. Organometallics 2007, 26, 2978–2985.
¨
7. Gungo¨r, F. Sß.; Anaßc, O.; Sezer, O. Tetrahedron Lett. 2007, 48, 4883–
¨
The authors would like to thank the I.T.U.
Research Fund (32003) and The Scientific and Technological
Research Council of Turkey (TUBITAK) (TBAG-
105T418).
4886.
8. Maas, G.; Muller, A. . J. Prakt. Chem. 1998, 340, 315–322.
¨
9. Ethyl acetobenzylidene acetate was obtained as a mixture of Z and E
isomers (1.90:1) after distillation. After chromatographic separation,

O. Anaßc et al. / Tetrahedron Letters 49 (2008) 1062–1065
1065
the structures of the E- and Z-isomers were clarified from their
NOESY spectra.
11. Huisgen, R. Angew. Chem., Int. Ed. Engl. 1980, 19, 947–1034.
12. Zecchi, G. Synthesis 1991, 181–188.
10. We determined that (E)-1b was only partially (ca. 10%) converted to
(Z)-1a at room temperature after seven months. Refluxing pure (Z)-
1a in benzene for 5 h also resulted in negligible amounts of
conversion. Besides, the 65:35 Z/E ratio observed after the distillation
in the synthetic procedure also indicates that the starting compound
alone did not exhibit a facile Z to E conversion.
13. Eberbach, W.; Hadicke, E.; Trostmann, U. Tetrahedron Lett. 1981,
22, 4953–4956.
14. Preliminary geometry optimization studies suggested that the prob-
able structure C was significantly more stable than structure D in
Scheme 2, whereas structures A and B in Scheme 2 had just about the
same energies.