Notes
Synthesis of 2-Acyl-1,4-diketones via the Diacylation of
r,-Unsaturated Ketones
Nan-Sheng Li, Su Yu, and George W. Kabalka*
Departments of Chemistry and Radiology, The University of Tennessee,
Knoxville, Tennessee 37996-1600
Received April 22, 1998
Summary: The first example of a diacylation of the
carbon-carbon double bond in R,-unsaturated ketones
is described. The reaction of acylcyanocuprate reagents
with R,-unsaturated ketones, followed by C-acylation,
produces 2-acyl-1,4-diketones in good yields (50-89%).
Introduction
The introduction of two carbonyl groups to the carbon-
carbon double bond of R,-unsaturated carbonyl com-
pound provides an effective route to 2-acyl-1,4-dike-
tones, which are useful reaction intermediates in the
syntheses of cyclopentenone systems
1
as well as het-
erocyclic compounds.
2
It has been reported that some
simple 2-acyl-1,4-diketones can be prepared by the
thiazolium-salt-catalyzed addition of aldehydes to 2-acyl-
conjugated enones
2a
or by the reaction of 1,3-diketones
with R-haloketones,
3
1-nitroalkenes,
1
or enamines.
2c
The
scope of these reactions is limited by the fact that the
structure of the product 2-acyl-1,4-diketones depends
on the starting materials, 1,3-diketones.
The nucleophilic 1,4-addition of an acyl anion to
conjugated enones has been of interest to organic
chemists. Acyl anion intermediates generated by the
addition of an organolithium or Grignard reagent to
transition-metal carbon monoxide complexes such as
nickel carbonyl,
4
iron carbonyl,
5
or cobalt carbonyl
6
react
with R,-unsaturated ketones to give 1,4-diketones. The
acyl anion generated by reaction of an alkyl halide with
Na
2
Fe(CO)
4
also reacts with R,-unsaturated ketones
to produce 1,4-diketones.
7
Seyferth reported an efficient
method for generating acyllithium by reacting alkyl-
lithium reagents with carbon monoxide at low (-100
to -135 °C) temperature. The acyllithium generated
by this method can react in situ with various electro-
philes to afford acylated products.
8
The reagent reacts
with conjugated enones to give the 1,2-addition product
predominately.
9a
Seyferth also reported the direct
nucleophilic 1,4-acylation of R,-unsaturated carbonyl
compounds using acylcuprate reagents prepared via the
carbonylation of alkylcyanocuprates with carbon mon-
oxide.
9
Lipshutz reported the 1,4-acylation of conju-
gated enones by allylic cuprates in the presence of
carbon monoxide.
10
The 1,4-addition of organocuprate
reagents to conjugated enones, followed by trapping of
the enolate intermediates with various electrophiles, is
one of the most useful synthetic reactions.
11-13
How-
ever, to the best of our knowledge, 1,4-acylation followed
by trapping of the enolate intermediates with acid
chloride has not been reported.
Results and Discussion
In a continuation of our studies focused on acyl anion
chemistry,
14
we found that the intermediates generated
in the reaction of acylcyanocuprates with conjugated
(1) Yanami, T.; Ballatore, A.; Miyashita, M.; Kato, M.; Yoshikoshi,
A. Synthesis 1980, 407.
(2) (a) Stetter, H.; Jonas, F. Chem. Ber. 1981, 114, 564. (b) Harigaya,
Y.; Yamamoto, T.; Okawara, M. Chem. Lett. 1974, 101. (c) Chiba, T.;
Okimoto, M.; Nagai, H.; Takata, Y. J. Org. Chem. 1979, 44, 3519.
(3) (a) Stetter, H.; Jonas, F. Tetrahedron Lett. 1981, 22, 4945. (b)
Boya, M.; Moreno-Manas, M.; Prior, M. Tetraheron Lett. 1975, 1727.
(c) Gu, X.-P.; Nishida, N.; Ikeda, I.; Okahara, M. J. Org. Chem. 1987,
52, 3192.
(4) Corey, E. J.; Hegedus, L. S. J. Am. Chem. Soc. 1969, 91, 4926.
(5) Thomas, S. E. J. Chem. Soc., Chem. Commun. 1987, 226.
(6) Hegedus, L. S.; Perry, R. J. J. Org. Chem. 1985, 50, 4955.
(7) Cooke, M. P., Jr.; Parlman, R. M. J. Am. Chem. Soc. 1977, 99,
5222.
(8) (a) Seyferth, D.; Weinstein, R. M.; Hui, R. C.; Wang, W.-L.;
Archer, C. M. J. Org. Chem. 1992, 57, 5620 and references therein.
(b) Hui, R. C.; Seyferth, D. Org. Synth. 1990, 69, 114.
(9) (a) Seyferth, D.; Hui, R. C. J. Am. Chem. Soc. 1985, 107, 4551.
(b) Seyferth, D.; Hui, R. C. Tetrahedron Lett. 1986, 27, 1473.
(10) Lipshutz, B. H.; Elworthy, T. R. Tetrahedron Lett. 1990, 31,
477.
(11) Chapdelaine, M. J.; Hulce, M. Org. React., 1990, 38, 225.
(12) For examples of 1,4-addition reactions involving enones and
organocuprates, followed by acylation of the enolate, see: (a) Ber-
nasconi, S.; Gariboldi, P.; Jommi, G.; Sisti, M. Tetrahedron Lett. 1980,
21, 2337. (b) Tanaka, T.; Kurozumi, S.; Toru, T.; Kobayashi, M.; Miura,
M.; Ishimoto, S. Tetrahedron 1975, 16, 1535. (c) Tanaka, T.; Kurozumi,
S.; Toru, T.; Kobayashi, M.; Miura, S.; Ishimoto, S. Tetrahedron 1977,
33, 1105. (d) Naf, F.; Decorzant, R. Helv. Chim. Acta 1974, 57, 1317.
(e) Bernasconi, S.; Ferrari, M.; Gariboldi, P.; Jommi, G.; Sisti, M.;
Destro, R. J. Chem. Soc., Perkin Trans 1 1981, 1994.
(13) The ratio of C- and O-acylated products was reported to be
dependent on both the solvent and the acylating agent. See ref 12d.
Scheme 1
3815 Organometallics 1998, 17, 3815-3818
S0276-7333(98)00303-3 CCC: $15.00 © 1998 American Chemical Society
Publication on Web 07/18/1998