Arylation of α-substituted acrylates in ionic liquids catalyzed by a Pd-benzothiazole carbene complex

Article abstract of DOI:10.1016/S0040-4039(01)00795-X

A Pd-catalyst with benzothiazole carbene as ligands allows, in tetrabutylammonium bromide melt as solvent, very fast and efficient reactions of bromoaromatics with 3-hydroxy-2-methylenealkanoates to give β-arylketones.

Full text of DOI:10.1016/S0040-4039(01)00795-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4701–4703
Arylation of a-substituted acrylates in ionic liquids catalyzed by
a Pd–benzothiazole carbene complex
Vincenzo Calo`,* Angelo Nacci, Luigi Lopez and Annalisa Napola†
Centro CNR ‘MISO’, Dipartimento di Chimica, Universita` di Bari, Via Amendola, 173-70126 Bari, Italy
Received 8 March 2001; accepted 11 May 2001
Abstract—A Pd-catalyst with benzothiazole carbene as ligands allows, in tetrabutylammonium bromide melt as solvent, very fast
and efficient reactions of bromoaromatics with 3-hydroxy-2-methylenealkanoates to give b-arylketones. © 2001 Published by
Elsevier Science Ltd.
The Heck reaction and related chemistry occupy a
special place among basic types of palladium-catalyzed
reactions.1–3 In most of the papers dedicated to the
Heck reaction, only a few examples have been reported
which deal with a-substituted acrylates as olefin accep-
tors.4,5 Among these, it was reported6 that the arylation
of 3-hydroxy-2-methylenealkanoates afforded b-
oxoalkanoates (Scheme 1). Beside the harsh reaction
conditions necessary for the reaction of a-substituted
acrylates, the 3-hydroxy-2-methylenealkanoate aryla-
tion also suffers from a competitive retro-Baylis–Hill-
man reaction, as well as further arylation of the
b-oxoalkanoate end product.7–9
Catalyst 1 was stable in TBAB melt and efficiently
allowed the reaction of various p-substituted bromo-
aromatics with hydroxymethylenealkanoates 2 to give
b-arylketones 3 but not the expected Heck product,
b-oxoalkanoates6 4 (Scheme 2).
As shown in Table 1, reaction of electron-rich and
electron-poor aryl bromides gave b-aryl ketones in the
presence of 1 (2%), sodium formate as reducing agent
for palladium and sodium bicarbonate as base.12 No
palladium black deposition nor retro-Baylis–Hillman of
2 or further arylation of 3 was observed. The stability
of 1 in TBAB, in a phosphane-free environment, cannot
be regarded as simply due to the solvent polarity or
phase transfer ability.2e Indeed, it was observed (entry
2) that in a different ionic liquid such as butylpyri-
dinium tosylate bearing a poorly nucleophilic anion, 1
did not catalyze the reaction. We propose that both the
anion and the cation of TBAB exert a double role. The
bromide ion, by reaction with the rather unstable 14-
electron complex L2Pd(0), the proposed catalyst in the
Heck reaction, would lead to an anionic, more stable
Scheme 1.
To overcome these drawbacks, we report the applica-
tion of the Pd catalyst 1 with benzothiazole carbene as
ligands10,11 for an efficient Heck arylation of 3-hydroxy-
2-methylenealkanoates in the ionic liquid tetra-
butylammonium bromide (TBAB) as solvent.
and
catalytically
active
16-electron
complex
[L2Pd(0)Br](−) (+)NR4. The formation of this large com-
Keywords: b-aryl ketones; ionic liquids; carbenes; Heck reaction.
* Corresponding
author.
Tel.:
+39.080.544.20.71;
fax:
+
Scheme 2. Ar=H, p-MePh, p-MeOPh, p-AcPh, naphthyl;
R=Ph, Me, i-propyl, n-octyl.
39.080.544.29.24; e-mail: calo@chimica.uniba.it
† Thesis.
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00795-X

4702
V. Calo` et al. / Tetrahedron Letters 42 (2001) 4701–4703
Table 1. Synthesis of b-arylketones in TBAB catalyzed by the Pd–carbene complex 1a
Entry
1
Hydroxymethylene alkanoate14
Aryl bromide
Products
Time (h)
20
Yield (%)b
77
Ref.
15
2c
3
%%
%%
%%
%%
24
22
Nr
66
–
16
4
5
%%
%%
%%
14
14
78
82
17
16
6
15
6
80
79
71
77
79
66d
16
18
19
20
21
22
7
8
%%
%%
%%
%%
4
9
20
8
10
11
14
a Reaction conditions: TBAB (3 g), catalyst (0.38 mmol, 2 mol%), sodium formate (0.76 mmol), bromoarene (19 mmol), sodium bicarbonate (40
mmol) and hydroxymethylene alkanoate (27 mmol) stirred at 130°C.
b Determined by GLC.
c Performed in N-butylpyridinium tosylate as solvent.
d Total yield as sum of b-oxoalkanoate and the corresponding b-arylketone.
plex, by imposing a Coulombic barrier for collision,
would impede the formation of clusters growing further
into metal particles. This is conceivable since it was
demonstrated3,13 that halides or acetate ions stabilize
the 14-electron complex Pd(0)[P(Ph)3]2.
cycles, 8 g of bromobenzene were processed with a total
TON (turn over number) roughly equal to a very
decent value of 1720, thus making the whole process
economically viable.
The exclusive formation of 3 is probably due to a fast
decarbomethoxylation in TBAB of the b-oxoalkanoate
4. Indeed, by using a tert-butylester of 2 (entry 11), we
The stability of 1 in TBAB makes a recycling process
feasible. For example, in only 3 g of TBAB, after three

V. Calo` et al. / Tetrahedron Letters 42 (2001) 4701–4703
4703
observed, beside 3, 30% of the corresponding b-
oxoalkanoate which slowly underwent decarbobutoxy-
lation to the corresponding ketone.
10. Calo`, V.; Del Sole, R.; Nacci, A.; Schingaro, E.; Scordari,
F. Eur. J. Org. Chem. 2000, 869–871.
11. Calo`, V.; Nacci, A.; Lopez, L.; Mannarini, N. Tetra-
hedron Lett. 2000, 41, 8973–8976.
Studies of the factors which govern the efficiency of
metal–carbene complexes as catalysts in ionic liquids
are underway.
12. Typical procedure: A pyrex reaction flask was charged
with tetrabutylammonium bromide (3 g) and heated at
130°C. To the stirred molten salt were added in strict
order the catalyst (250 mg, 0.38 mmol), sodium formate
(52 mg, 0.76 mmol), bromoarene (19 mmol), sodium
bicarbonate (3.4 g, 40 mmol) and hydroxymethylene
alkanoate (3.4 g, 27 mmol). The reaction yields were
determined by GLC integrated with diethylene glycol
dibutyl ether as internal standard. After completion of
the reaction, the mixture was extracted in a Soxhlet
apparatus with cyclohexane for 1 h. After evaporation of
the solvent, the pure product was isolated in a 60–80%
yield. The ionic liquid and the catalyst were then
recycled.
Acknowledgements
This work was financially supported in part by Minis-
tero dell’Universita` e della Ricerca Scientifica e Tecno-
logica, Rome, and the University of Bari (National
Project: ‘Stereoselezione in Sintesi Organica: Metodolo-
gie ed Applicazioni’).
13. Neghishi, E.-I.; Takahashi, T.; Akiyoshi, K. J. Chem.
Soc., Chem. Commun. 1986, 1338–1339.
References
14. Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed.
Engl. 1983, 22, 795–796.
15. Alonso, F.; Yus, M. Tetrahedron 1998, 54, 1921–1928.
16. Ohta, H.; Konishi, J.; Gen-Ichi Agric. Biol. Chem. 1985,
49, 665–670.
17. Borsche, S. Justus Liebigs Ann. Chem. 1942, 553, 260–
270.
18. Mino, T.; Hirota, T.; Fujita, N.; Yamashita, M. Synthesis
1999, 12, 2024–2026.
1. Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5518–5526.
2. For recent reviews, see: (a) de Meijer, A.; Meyer, F. E.
Angew. Chem. 1994, 106, 2473–2506; Angew. Chem., Int.
Ed. Engl. 1994, 33, 2379–2411; (b) Cabri, W.; Candiani, I.
Acc. Chem. Res. 1995, 28, 2–7; (c) Crisp, G. T. Chem.
Soc. Rev. 1998, 27, 427–436; (d) Genet, J. P.; Savignac,
M. J. Organomet. Chem. 1999, 576, 305–317; (e) Belet-
skaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100,
3009–3066.
3. For a recent mechanistic study on Heck reaction, see:
Amatore, C.; Jutand, A. J. Organomet. Chem. 1999, 576,
254–278.
4. Beller, M.; Riermeier, T. H. Tetrahedron Lett. 1996, 37,
6535–6538.
19. Mattson, M. N.; Rapoport, H. J. Org. Chem. 1996, 61,
6071–6074.
20. Bursey., et al. Org. Mass. Spect. 1970, 4, 157–159.
21. Nimgirawath, S., et al. Aust. J. Chem. 1973 26, 183–193.
1
22. Spectral data for the t-butyl ester: H NMR (500 MHz,
CDCl3) l: 1.27 (9H, s, t-butyl), 3.28 (2H, d, J 7.5 Hz,
CH2), 4.50 (1H, t, J 7.5 Hz, CH), 7.14–7.27 (6H, m, Ph),
7.39–7.56 (4H, m, Ph); 13C NMR l: 27.65, 34.45, 57.22,
81.97, 126.42, 128.36, 128.48, 128.97, 133.21, 136.22,
136.43, 138.61, 168.30, 194.74; MS (EI) m/z 310 (M+, 1),
254 (20), 236 (6), 209 (11), 149 (42), 131 (24), 105 (100),
91 (7), 77 (45), 57 (58), 51 (20), 41 (50); IR (liquid film)
w: 3087, 3063, 3028, 2978, 2933, 1734, 1687, 1589, 1582,
1486, 1478, 1450, 1369, 1240, 1147, 1080, 1056, 1030,
5. Gu¨rtler, C.; Buchwald, S. L. Chem. Eur. J. 1999, 5,
3107–3112.
6. Basavaiah, D.; Muthukumaran, K. Tetrahedron 1998, 54,
4943–4948.
7. Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1740–1742.
8. Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997,
119, 11108–11109.
9. Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997,
119, 12382–12383.
1003, 971, 944, 893, 844, 778, 745, 739, 688 cm−1
.
.