First oxidative cyclization of 1,3-bis(trimethylsilyloxy)buta-1,3-dienes

Article abstract of DOI:10.1039/b004387g

The first oxidative cyclizations of 1,3-bis(trimethylsilyloxy)-buta-1,3-dienes, electroneutral 1,3-dicarbonyl dianion synthons, result in regioselective formation of functionalized 1,4-dihydroquinones.

Full text of DOI:10.1039/b004387g

First oxidative cyclization of 1,3-bis(trimethylsilyloxy)buta-1,3-dienes
Peter Langer* and Valentin Köhler
Institut für Organische Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen,
Germany. E-mail: planger@uni-goettingen.de
Received (in Cambridge, UK) 1st June 2000, Accepted 26th July 2000
The first oxidative cyclizations of 1,3-bis(trimethylsilyloxy)-
buta-1,3-dienes, electroneutral 1,3-dicarbonyl dianion syn-
thons, result in regioselective formation of functionalized
1,4-dihydroquinones.
Formation of 4a can be explained by the following working
hypothesis (Scheme 2): SET-oxidation of 3a affords the radical-
cation A. Formation of a ceric enolate, supported by the
chelating nature of the two oxygen atoms, can not be
excluded.11 Cleavage of the Si–O bond and NaHCO3-assisted
extrusion of a silyl-cation results in formation of radical B
which subsequently attacks the terminal carbon atom of a
second molecule of 3a to give intermediate C. Radical B should
be more stable than the isomeric, cross-conjugated radical BA.
Oxidation and extrusion of the second silyl group affords
intermediate D. Oxidation of the latter and extrusion of the third
silyl group results in formation of intermediate E. Cyclization,
oxidation and extrusion of the fourth silyl group affords
intermediate F which is subsequently oxidized to give the final
product 4a.
The development of new, preparatively useful single-electron-
transfer (SET) reactions is of considerable current interest.
Although SET-oxidations of monoanions have been extensively
studied,1 little is known about dianion oxidations.2 Herein, we
wish to report, to the best of our knowledge, the first oxidative
cyclizations of 1,3-bis(trimethylsilyloxy)buta-1,3-dienes which
represent electroneutral 1,3-dicarbonyl dianion synthons.3 This
methodology provides a direct, mild and regioselective synthe-
sis of 2,3-acceptor-substituted 1,4-dihydroquinones which can
be regarded as products of a formal oxidative cyclization of
1,3-dicarbonyl dianions.4 These products, which have been
previously prepared by multi-step syntheses under drastic
conditions,5 represent useful intermediates in organic synthesis.
2,3-Acceptor-substituted 1,4-dihydroquinones are present in a
variety of polyketide-derived natural products, such as derica-
mycin A and the related fredericamycin A,5a or prominent
enediynes, such as calicheamicin, esperamicin, neocarzinosta-
tin chromophore or dynemicin A.6a Simple 1,4-dihydroquinone-
2,3-dicarbonyl derivatives have proven biologically active
against murine tumors.6b
The ‘head–head’ regioselectivity may be rationalized by
considering that attack at the g-position of radical B leads to the
most stabilized carbonyl conjugated a-silyloxy radical C.
Radical C is probably formed through a transition state less
Oxidation of the dianion7,8 of ethyl acetoacetate with iodine
or bromine in the presence of catalytic amounts of copper( )
I
chloride has been reported to afford the open-chain dimerization
product 2 rather than a cyclization product (Scheme 1).9 The use
of 1,2-dibromoethane, CuCl2 and Cu(OTf)2 as the oxidizing
agents resulted in formation of complex mixtures. The main
problem associated with the oxidative cyclization of dianions is
the fact that, due to electrostatic repulsion, dimerization of the
radical anionic intermediates is slow and many side-reactions,
such as deprotonation of the solvent (THF), can occur.
Our concept to overcome these problems was to study the
oxidative dimerization of 1,3-bis(trimethylsilyloxy)buta-
1,3-dienes 3.10 Slow addition of an acetonitrile solution of CAN
to an acetonitrile solution of NaHCO3 and diene 3a3c resulted in
formation of the ester-substituted 1,4-dihydroquinone 4a,
however, in only low yield. Much to our satisfaction, employ-
ment of an inverse addition protocol resulted in an increase of
the yield. Optimal yields (up to 56%) were obtained when an
acetonitrile solution of 3a (2 eq.) was slowly added to a solution
of CAN (6 eq.) and NaHCO3 (12 eq.) at 245 °C.†
Scheme 1
Scheme 2
DOI: 10.1039/b004387g
Chem. Commun., 2000, 1653–1654
This journal is © The Royal Society of Chemistry 2000
1653

mmol, 6 eq., 4.20 g) was slowly added a CH3CN solution (2 ml) of
1,3-bis(trimethylsilyloxy)buta-1,3-diene 3a (2.55 mmol, 2 eq., 0.7 g) at
245 °C. The temperature of the reaction mixture was allowed to rise to 20
°C during 2 h. After stirring for 1 h at 20 °C a saturated aqueous solution of
brine was added, the organic layer was separated and the aqueous layer was
repeatedly extracted with ether. The combined organic extracts were dried
(MgSO4), filtered and the solvent of the filtrate was removed in vacuo. The
residue was purified by column chromatography (silica gel, ether–petrol
ether = 1+1; (CDCl3, 250 MHz) dH 1.34 (t, 6 H, J = 7, CH3), 4.34 (q, 4 H,
J = 7, OCH2), 7.07 (s, 2 H, CH), 8.85 (s, 2 H, OH; (CDCl3, 62.5 MHz) dC
13.98, 62.01, 112.66, 123.83, 152.29, 168.98; MS (70 eV) 254 (22, M+),
208 (40), 180 (100), 162 (58); Anal. calcd. for C12H14O6: C, 56.69; H, 5.55.
Found: C, 56.42; H, 5.68. All compounds were characterized by
spectroscopic methods and gave correct elemental analyses and/or high
resolution mass spectra.
Scheme 3
Table 1 Oxidative cyclization of 1,3-bis(trimethylsilyloxy)buta-1,3-dienes
3
4
R1
R2
yield (%)a
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
H
H
OEt
OMe
56
55
52
54
54
26
41
28
38
41
29
18
1 (a) T. Linker and M. Schmittel, ‘Radikale und Radikalionen in der
Organischen Synthese’, Wiley-VCH, Weinheim, New York, 1998; (b)
R. D. Guthrie, in ‘Studies in Organic Chemistry, 5, Comprehesive
Carbanion Chemistry, Part A’, eds. E. Buncel and T. Durst, Elsevier/
North-Holland, New York, 1980, ch. 5, p. 197.
2 For the oxidative cyclization of dianions, see: (a) R. B. Bates, F. A.
Camou, V. V. Kane, P. K. Mishra, K. Suvannachut and J. J. White,
J. Org. Chem., 1989, 54, 311; (b) M. A. Fox and C.-C. Chen, J. Chem.
Soc., Chem. Commun., 1985, 23; (c) O. Witt, H. Mauser, T. Friedl, D.
Wilhelm and T. Clark, J. Org. Chem., 1998, 63, 959; for other
oxidations of dianions, see: (d) R. B. Bates and T. J. Siahaan, J. Org.
Chem., 1986, 51, 1432; (e) R. B. Bates and C. A. Ogle, J. Org. Chem.,
1982, 47, 3949; (f) J. J. Bahl, R. B. Bates, W. A. Beavers and N. S. Mills,
J. Org. Chem., 1976, 41, 1620.
O(i-Pr)
O(CH2)2OMe
O(i-Bu)
O(t-Bu)
OCH2Ph
Me
OMe
OEt
OMe
Me
Me
Et
OMe
CO2Me
j
k
l
a Isolated yields.
3 We and others consider dienes 3 as dianion synthons knowing that they
represent electroneutral bis-silyl enol ethers. From a preparative
viewpoint, 1,3-dicarbonyl dianions and dienes 3 show the same
regioselectivity in reactions with electrophiles: (a) P. Brownbridge,
T.-H. Chan, M. A. Brook and G. J. Kang, Can. J. Chem., 1983, 61, 688;
(b) T.-H. Chan and P. Brownbridge, J. Am. Chem. Soc., 1980, 102,
3534; (c) G. A. Molander and K. O. Cameron, J. Am. Chem. Soc., 1993,
115, 830.
energetic than that leading to the respective unconjugated a-
silyloxy radical (by attack of the central carbon atom of
intermediate B onto 3a), assuming the addition step possesses a
substantial product-like character. This suggestion is supported
by the regioselectivity observed for the alkoxy radical catalyzed
auto-oxidation of 1,4-dienes.12 It is noteworthy, that the open-
chain dimer 2 was isolated as a side-product in low yield. This
result supports the assumption that bis-silyl enol ether D
represents an intermediate of the reaction.
4 For the oxidative dimerization of malonic esters to give acceptor-
substituted alkenes, see: T. Linker and U. Linker, Angew. Chem., 2000,
112, 934; Angew. Chem., Int. Ed., 2000, 39, 902.
In order to study the preparative scope of our new cyclization
reaction, the substituents of the 1,3-bis(trimethylsilyloxy)buta-
1,3-dienes were systematically varied (Table 1). Oxidation of
the dienes derived from ethyl-, methyl-, iso-propyl-, methoxy-
ethyl-, iso-butyl-, tert-butyl- and benzyl acetoacetate afforded
the corresponding ester-substituted 1,4-dihydroquinones 4a–g
with very good regioselectivities. Dimerization of the diene
derived from acetylacetone afforded 2,3-diacetyl-1,4-dihydro-
quinone (4h). Oxidation of the 1,3-bis(trimethylsilyloxy)buta-
1,3-dienes derived from methyl 3-oxopentanoate and ethyl
3-oxohexanoate afforded the 1,4-dihydroquinones 4i–j contain-
ing two ester groups at carbons C-2 and C-3 and two alkyl
groups at carbons C-5 and C-6. Oxidation of the 1,3-bis-
(trimethylsilyloxy)buta-1,3-diene derived from methyl 4-me-
thoxyacetoacetate resulted in formation of the highly function-
alized 1,4-dihydroquinone 4k. Reaction of the diene derived
from methyl 3,5-dioxohexanoate afforded the highly function-
alized 1,4-dihydroquinone 4l.
In summary, we have developed the first oxidative cycliza-
tions of 1,3-bis(trimethylsilyloxy)buta-1,3-dienes which repre-
sent electroneutral 1,3-dicarbonyl dianion synthons. Currently,
we are studying the mechanism and preparative scope of the
new transformation.
P. L. thanks Professor A. de Meijere for his support. Financial
support from the Fonds der Chemischen Industrie (Liebig
scholarship and funds for P. L.) and from the Deutsche
Forschungsgemeinschaft is gratefully acknowledged.
5 (a) T. R. Kelly, S. H. Bell, N. Ohashi and R. J. Armstrong-Chong, J. Am.
Chem. Soc., 1988, 110, 6471; (b) M. F. Ansell, B. W. Nash and D. A.
Wilson, J. Chem. Soc., 1963, 3028; (c) J. Thiele and J. Meisenheimer,
Chem. Ber., 1900, 33, 675.
6 (a) A. G. Myers, N. J. Tom, M. E. Fraley, S. B. Cohen and D. J. Madar,
J. Am. Chem. Soc., 1988, 110, 6471 and references cited therein; (b)
E. M. Newman, A. J. Lin and A. C. Sartorelli, J. Med. Chem., 1980, 23,
627.
7 For 1,3-dicarbonyl dianions, see: (a) L. Weiler, J. Am. Chem. Soc.,
1970, 92, 6702; (b) D. Seebach and V. Ehrig, Angew. Chem., 1974, 86,
446; Angew. Chem., Int. Ed. Engl., 1974, 13, 401.
8 For recent cyclization reactions of 1,3-dicarbonyl dianion synthons with
1,2-dielectrophiles, see: (a) P. Langer and M. Stoll, Angew. Chem.,
1999, 111, 1919; Angew. Chem., Int. Ed., 1999, 38, 1803; (b) P. Langer,
T. Schneider and M. Stoll, Chem. Eur. J., 2000, in the press; (c) P.
Langer and E. Holtz, Angew. Chem., 2000, in the press; (d) P. Langer
and T. Eckardt, Angew. Chem., 2000, accepted; (e) P. Langer and T.
Krummel, Chem. Commun., 2000, 967.
9 K. G. Hampton and J. J. Christie, J. Org. Chem., 1975, 40, 3887.
10 For CAN promoted oxidations of silyl enol ethers, see: (a) E. Baciocchi,
A. Casu and R. Ruzziconi, Tetrahedron Lett., 1989, 3707; (b) A. B.
Paolobelli, D. Latini and R. Ruzziconi, Tetrahedron Lett., 1993, 721; a
TiCl4 mediated oxidative dimerization of a bis-silyl enol ether to give an
open-chain product has been previously noted: see reference 3a.
11 For the spectroscopic detection of radical cations of titanium enolates,
enols and silyl enol ethers, see: (a) M. Schmittel, G. Gescheidt and M.
Röck, Angew. Chem., 1994, 106, 2056; Angew. Chem., Int. Ed. Engl.,
1994, 33, 1961; (b) M. Schmittel, M. Keller and A. Burghart, J. Chem.
Soc., Perkin Trans. 2, 1995, 2327; (c) M. Schmittel and R. Söllner,
Angew. Chem., 1996, 108, 2248; Angew. Chem., Int. Ed. Engl., 1996,
35, 2107.
Notes and references
† Preparation of 1,4-dihydroquinone 4a. To a thoroughly degassed CH3CN
12 (a) E. N. Frankel, R. F. Garwood, J. R. Vinson and B. C. L. Weedon,
J. Chem. Soc., Perkin Trans. 1, 1982, 2707; (b) N. A. Porter, Acc. Chem.
Res., 1986, 19, 262.
solution (25 ml) of NaHCO3 (15.3 mmol, 12 eq., 1.29 g) and CAN (7.65
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Chem. Commun., 2000, 1653–1654