Synthesis of 4-arylidenecyclohexane-1,3-diones from the Baylis-Hillman acetates

Article abstract of DOI:10.1016/S0040-4039(03)00397-6

Synthesis of 4-arylidenecyclohexane-1,3-dione derivatives was carried out from the Baylis-Hillman acetates. The potential utility of the prepared compounds for the synthesis of cyclohexanedione oxime ether herbicides was examined.

Full text of DOI:10.1016/S0040-4039(03)00397-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2987–2990
Synthesis of 4-arylidenecyclohexane-1,3-diones from the
Baylis–Hillman acetates
Yang Jin Im,a Chang Gon Lee,a Hyoung Rae Kimb and Jae Nyoung Kima,*
aDepartment of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
bMedicinal Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yusong, Taejon 305-600,
Republic of Korea
Received 4 December 2002; revised 27 January 2003; accepted 7 February 2003
Abstract—Synthesis of 4-arylidenecyclohexane-1,3-dione derivatives was carried out from the Baylis–Hillman acetates. The
potential utility of the prepared compounds for the synthesis of cyclohexanedione oxime ether herbicides was examined. © 2003
Elsevier Science Ltd. All rights reserved.
Cyclohexane-1,3-dione derivatives play an important
role in organic synthesis due to their usefulness in the
preparation of many biologically important com-
pounds.1 Many herbicides having cyclohexane-1,3-
dione backbone such as tralkoxydim, sethoxydim or
clethodim are well known.1 Many methods have been
published for the preparation of cyclohexane-1,3-dione
moiety.2 However, synthesis of cyclohexane-1,3-dione
derivatives with double bonds at the exo-position was
not reported in the literature (Scheme 1).3
deacetylated 4a as a mixture.4,5 One of the acetyl group
was removed by simply elevating the reaction tempera-
ture as previously reported.4a Whereas, the reaction of
1a and 2a in DMF in the presence of K2CO3 gave
allylic substitution product 3a without deacetylation in
good yield (82%) as expected.5 However, as shown in
Scheme 2, conversion of 3a into cyclohexane-1,3-dione
derivative I or resorcinol derivative II with various
bases was failed. Intractable mixtures of products were
observed on TLC. Whereas, the deacetylated com-
pound 4a can be converted into the corresponding
4-benzylidenecyclohexane-1,3-dione (5a) in moderate
yield (71%) by using lithium hexamethyldisilizide (LiH-
MDS) in THF. Thus, we wish to report herein the
preparation of 4-arylidenecyclohexane-1,3-dione deriva-
tives for the first time. The results from 2,4-pentane-
dione (2a, entries 1–4) and 3-methyl-2,4-pentanedione
(2b, entry 5) are summarized in Table 1.
Chamakh and Amri have reported the synthesis of
4-arylidene-2-cyclohexen-1-ones from Baylis–Hillman
acetate in ethanol via the tandem three-step process,
allylic substitution, deacetylation and cyclization.4a
Recently, we have published an interesting result from
the same reaction, which was carried out in N,N-
dimethylformamide to afford 2-hydroxyacetophen-
ones.5 As a continuous work, we intended to prepare
2,4-dihydroxyacetophenone derivative II in order to
prepare multifunctional oxotocopherol-type antioxidant
III (vide infra, see Scheme 2).6
The similar reaction of the Baylis–Hillman acetate 1f,
derived from methyl vinyl ketone, with diethyl mal-
onate (2c) gave the similar substitution product 3f.
However, the following decarbethoxylation of 3f was
more difficult than the deacetylation for the above
mentioned compounds (for 4a–e). Thus, in these cases
(for 4f and 4g) we used the method involving the use of
DMAP in refluxing xylene, which was used successfully
in our previous paper.7 The cyclization reaction of 4f
with LiHMDS gave 5a in a similar yield (entry 6).
As shown in Scheme 1, the reaction of the Baylis–Hill-
man acetate 1a, derived from ethyl acrylate, and 2,4-
pentanedione (2a) in the presence of potassium
carbonate in ethanol at room temperature afforded the
corresponding allylic substitution product 3a and some
Keywords:
acetates; antioxidants.
* Corresponding author. Fax: +82-62-5303389; e-mail: kimjn@
chonnam.chonnam.ac.kr
cyclohexane-1,3-dione;
herbicides;
Baylis–Hillman
As shown in Scheme 1, the reaction mechanism can be
postulated as follows. The reaction of the Baylis–Hill-
man acetates 1 and b-diketone or malonate esters 2
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00397-6

2988
Y. J. Im et al. / Tetrahedron Letters 44 (2003) 2987–2990
Scheme 1.
Scheme 2.
afforded the corresponding allylic substitution products
3. From these compounds we could prepare the desired
starting materials 4 either (i) by simply heating in
ethanol in the presence of K2CO3, or (ii) by the DMAP
catalyzed thermal decarbethoxylation. Finally, treat-
ment of 4 with LiHMDS (THF, 0°C to rt) afforded the
desired 4-arylidenecyclohexane-1,3-diones 5.
DMAP as previously reported in a similar system to
give 7 in 42% yield.8 Synthesis of the potential oxime
ether herbicide 8 was carried out with O-ethylhydroxyl-
amine hydrochloride in 92% yield.9 Further transforma-
tion of 7 into other oxime ether herbicides and the
study on their herbicidal activity are underway.
As shown in Scheme 3, 4-benzylidenecyclohexane-1,3-
dione (5a) could be converted into O-acetylated deriva-
tive 6 in good yield (95%). The structure of 6 was
confirmed by NOE as shown. Migration of the acetyl
group to carbon from oxygen was performed by
Acknowledgements
This work was supported by the grant (R05-2000-000-
00074-0) from the Basic Research Program of the
Korea Science & Engineering Foundation.

Y. J. Im et al. / Tetrahedron Letters 44 (2003) 2987–2990
Table 1. Synthesis of 4-arylidenecyclohexane-1,3-diones 5
2989
Scheme 3.

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Y. J. Im et al. / Tetrahedron Letters 44 (2003) 2987–2990
1612, 1219 cm−1 1H NMR (DMSO-d6) l 2.42 (t, J=6.9
References
;
Hz, 2H), 2.98 (t, J=6.9 Hz, 2H), 3.00 (br s, 1H), 5.62 (s,
1H), 7.03–7.42 (m, 6H); Mass (70 eV) m/z (rel. intensity)
102 (20), 115 (48), 129 (55), 157 (17), 199 (100), 200 (M+,
98). Selected spectroscopic data of other compounds are as
follows:
5b: mp 176–177°C; IR (KBr) 2968, 2683, 1606, 1529, 1223
cm−1; 1H NMR (DMSO-d6) l 2.30 (t, J=6.3 Hz, 2H), 2.85
(t, J=6.3 Hz, 2H), 5.43 (s, 1H), 7.25 (s, 1H), 7.43 (s, 4H),
11.26 (br s, 1H).
1. Incledon, B. J.; Hall, J. C. J. Agric. Food Chem. 1999, 47,
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2. (a) Ishikawa, T.; Kadoya, R.; Arai, M.; Takahashi, H.;
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diones in the literature (SciFinder Scholar 2002).
4. (a) Chamakh, A.; Amri, H. Tetrahedron Lett. 1998, 39,
375; (b) Bauchat, P.; Le Rouille, E.; Foucaud, A. Bull.
Chim. Soc. Fr. 1991, 267.
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5c: mp 164–165°C; IR (KBr) 3448, 2958, 2721, 2513, 1595,
1223 cm−1 1H NMR (DMSO-d6) l 2.31 (t, J=6.6 Hz,
;
2H), 2.33 (s, 3H), 2.90 (dd, J=6.6 and 1.8 Hz, 2H), 5.42
(s, 1H), 7.21–7.34 (m, 5H), 11.15 (br s, 1H); Mass (70 eV)
m/z (rel. intensity) 115 (31), 128 (31), 129 (37), 143 (22),
157 (15), 199 (100), 214 (M+, 26).
5d: IR (KBr) 3448, 2519, 1655, 1643 cm−1 1H NMR
;
(DMSO-d6) l 2.36 (t, J=6.9 Hz, 2H), 2.90 (dd, J=6.9 and
1.5 Hz, 2H), 5.64 (s, 1H), 7.34 (s, 1H), 7.90–7.97 (m, 1H),
8.40–8.47 (m, 1H), 8.75–8.78 (m, 1H), 8.93 (s, 1H).
5e: mp 163–164°C; IR (KBr) 2519, 1597, 1523, 1219 cm−1
;
1H NMR (DMSO-d6) l 0.99 (d, J=6.6 Hz, 3H), 2.32–2.40
(m, 1H), 2.53–2.62 (m, 1H), 2.98–3.06 (m, 1H), 5.37 (s,
1H), 7.29–7.42 (m, 6H); Mass (70 eV) m/z (rel. intensity)
102 (25), 115 (44), 129 (57), 143 (18), 213 (100), 214 (M+,
92).
8. (a) Kast, J.; Zierke, T.; Bratz, M.; Misslitz, U.; Meyer, N.;
Landes, A.; Rademacher, W.; Westphalen, K. O.; Walter,
H. Ger. Offen. DE 4135265, 1993; (b) Akhrem, A. A.;
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sevich, I. I. Synthesis 1978, 925; (c) Isobe, T.; Ishikawa, T.
J. Org. Chem. 1999, 64, 6984.
5f: mp 205–206°; IR (KBr) 2954, 1635, 1558, 1149, 1095
1
cm−1; H NMR (DMSO-d6) l 1.71 (s, 3H), 2.41 (t, J=6.6
9. Typical procedure for the synthesis of 4-benzylidenecyclo-
hexane-1,3-dione (5a). To a stirred solution of LiHMDS
(1.9 mL, 1.9 mmol, 3.1 equiv.) at 0°C was added dropwise
a solution of 4a (149 mg, 0.61 mmol) in dry THF (2 mL)
during 5 min. After the addition, the reaction mixture was
warmed to room temperature slowly and stirred further
for 20 h. The reaction mixture was poured into cold HCl
solution and extracted with ethyl acetate. After usual
workup and column chromatographic purification (hex-
ane/ethyl acetate, 1:1) we could obtain the desired com-
pound 5a as a white solid, 87 mg (71%). The compound 5a
existed as an enol form in DMSO-d6 based on its 1H
NMR spectrum. 13C NMR spectra of cyclohexane-1,3-
dione derivatives were very complex as reported,10 and we
did not assign them. Mp 163–164°C; IR (KBr) 3448, 2947,
Hz, 2H), 2.85 (td, J=6.6 and 1.5 Hz, 2H), 7.25–7.43 (m,
6H); Mass (70 eV) m/z (rel. intensity) 115 (49), 129 (57),
213 (96), 214 (M+, 100).
8: pale yellow oil; IR (KBr) 3448, 1655, 1624, 1539 cm−1
;
1H NMR (CDCl3) l 1.35 (t, J=7.0 Hz, 3H), 2.38 (s, 3H),
2.49 (t, J=7.0 Hz, 2H), 2.96 (t, J=7.0 Hz, 2H), 4.18 (q,
J=7.0 Hz, 2H), 7.32–7.41 (m, 5H), 7.60 (s, 1H), 14.42 (br
s, 1H); 13C NMR (CDCl3) l 14.32, 15.04, 24.59, 37.82,
70.17, 109.29, 128.19, 128.44, 129.50, 130.72, 133.64,
135.97, 160.27, 172.18, 195.75.
10.(a) Imashiro, F.; Maeda, S.; Takegoshi, K.; Terao, T.;
Saika, A. J. Am. Chem. Soc. 1987, 109, 5213; (b) Etter, M.
C.; Urbanczyk-Lipkowska, Z.; Jahn, D. A.; Frye, J. S. J.
Am. Chem. Soc. 1986, 108, 5871.