Polarity reversal induced by electrochemically generated thiazol-2-ylidenes: The Stetter reaction

Article abstract of DOI:10.1016/j.electacta.2010.01.082

The inversion of the normal reactivity (umpolung) of aldehydes has been induced via N-heterocyclic carbenes (NHCs) thiazol-2-ylidenes 2a or 3a, generated by simple electrolyses of solutions containing thiazolium salt 2 or 3. Accordingly, 1,4-dicarbonyl compounds have been obtained, in mild conditions and in moderate to very high yields, via 1,4-addition of the Breslow intermediates to the suitable Michael acceptor. The procedure has been performed in classical organic solvents (VOCs) as well as in room temperature ionic liquids (RTILs). The different reactivity of aliphatic aldehydes vs the one of aromatic and heteroaromatic aldehydes has been emphasized.

Full text of DOI:10.1016/j.electacta.2010.01.082

Electrochimica Acta 55 (2010) 3511–3517
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Polarity reversal induced by electrochemically generated thiazol-2-ylidenes:
The Stetter reaction
Monica Orsinia,∗, Isabella Chiarottob, Giovanni Sotgiua, Achille Inesib,∗∗
a Dip. Elettronica Applicata, Università Roma Tre, via Vasca Navale, 84, Roma 00146, Italy
b Dip. Ingegneria Chimica Materiali Ambiente, Università “La Sapienza”, via Castro Laurenziano, 7, Roma 00161, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The inversion of the normal reactivity (umpolung) of aldehydes has been induced via N-heterocyclic
carbenes (NHCs) thiazol-2-ylidenes 2a or 3a, generated by simple electrolyses of solutions containing
thiazolium salt 2 or 3. Accordingly, 1,4-dicarbonyl compounds have been obtained, in mild conditions
and in moderate to very high yields, via 1,4-addition of the Breslow intermediates to the suitable Michael
acceptor. The procedure has been performed in classical organic solvents (VOCs) as well as in room
temperature ionic liquids (RTILs). The different reactivity of aliphatic aldehydes vs the one of aromatic
and heteroaromatic aldehydes has been emphasized.
Received 3 December 2009
Received in revised form 21 January 2010
Accepted 21 January 2010
Available online 29 January 2010
Keywords:
N-Heterocyclic carbene
Thiazolium salt
© 2010 Elsevier Ltd. All rights reserved.
Electrochemical reduction
Stetter reaction
1. Introduction
and in total absence of classic organic solvents (VOCs) and was
extended to other 1,3-dialkylimidazolium salts [12–14].
N-Heterocyclic carbenes (NHCs) are cyclic carbenes bearing at
least one ␣-amino substituent [1–4]. Stable N-heterocyclic car-
benes I (imidazol-2-ylidenes or thiazol-2-ylidenes; X = N–R1 or
X = S respectively) [5] are prepared by deprotonation at C2 carbon
atom of imidazolium salts (II; X = N–R1) or thiazolium salts [II; X = S]
[6] or by reduction of imidazolin-2-thiones [III] [7] (Scheme 1).
The deprotonation is carried out in THF or in a mixture liq-
uid ammonia/aprotic polar solvent [6,8] in the presence of a base
such as NaH, KH, KOtBu or deprotonated DMSO. Potassium hexam-
ethyldisilazide has been suggested as possible selective base. The
reduction of III has been achieved by potassium in boiling THF [8].
Some problems related to these procedures (thermal sensitivity of
free imidazol-2-ylidenes, solubility of KH and NaH, selectivity, etc.)
have been emphasized [9].
Recently, an alternative electrochemical procedure has been
reported [10,11]. 1-Butyl-3-methylimidazol-2-ylidene 1a has been
obtained by cathodic reduction of 1-butyl-3-methyl-imidazolium
cation 1b (Scheme 2).
The procedure was carried out via electrolysis of 1-butyl-3-
methyl-1H-imidazolium tetrafluoroborate 1 (i.e. a room tempera-
ture ionic liquid, RTIL) without any use of bases or reducing agents
During the last decade, N-heterocyclic carbenes have been
extensively proposed as excellent ligands for transition-metal
catalysis [9,15,16] and as versatile organocatalysts in a wide range
of organic reactions (benzoin condensation, Stetter reaction, trans-
esterification reaction [1,2,17], etc.). In organic synthesis, the
Stetter reaction has received considerable attention as possible
catalytic carbon–carbon bond forming reaction through uncon-
ventional mode of reactivity. In fact, the Stetter reaction is the
1,4-addition of an activated aldehyde (catalyzed by cyanide ions or
N-heterocyclic carbenes) to a suitable Michael acceptor, yielding
1,4-dicarbonyl compounds.
In the classical procedures, the Stetter reaction is performed
using thiazolium salts as precatalysts, in the presence of bases.
VOCs or RTILs [18], were used as solvents and Et3N or K2CO3
as bases, i.e. as deprotonating agents towards thiazolium salts,
according to the formation of N-heterocyclic carbenes (thiazolium-
2-ylidenes). The plausible mechanism of reaction is reported in
Scheme 3. Reaction of the carbene IV with the aldehyde gives
the zwitterionic structure V. Proton transfer affords acylanion
equivalent, commonly known as the Breslow intermetiate VI.
Carbon–carbon bond formation results from nucleophilic attack of
the acylanion equivalent into a Michael acceptor generating VII.
Proton transfer gives VIII, which leads to the 1,4-dicarbonyl com-
pound and the regeneration of the catalyst.
∗
Corresponding author. Tel.: +39 06 57337075; fax: +39 06 57337026.
Corresponding author. Tel.: +39 06 49766782; fax: +39 06 49766749.
E-mail addresses: morsini@uniroma3.it (M. Orsini), achille.inesi@uniroma1.it
As part of a program directed at the utilization of electrochemi-
cally generated N-heterocyclic carbenes in new and simpler organic
synthetic procedures [17,19–21], we have explored the reactiv-
∗∗
(A. Inesi).
0013-4686/$ – see front matter © 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.electacta.2010.01.082

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M. Orsini et al. / Electrochimica Acta 55 (2010) 3511–3517
Scheme 1.
Scheme 2.
Scheme 3.

M. Orsini et al. / Electrochimica Acta 55 (2010) 3511–3517
3513
Scheme 4.
ity of aliphatic, aromatic and heteroaromatic aldehydes 4a–j vs an
appropriate Michael acceptor (␣,␤-unsaturated carbonyl, 5) in the
presence of electrochemically reduced thiazolium salt 2 or 3 (i.e. in
the presence of thiazol-2-ylidenes 2a or 3a) (Scheme 4).
The aim of this investigation was the setting-up an alternative
electrochemical methodology of synthesis, via Stetter reaction, of
1,4-dicarbonyl compounds 6a–j, useful synthons for natural and
pharmaceutical products [2]. The procedure has been performed in
VOCs (DMF, DMSO, CH3CN) as well as in RTIL 1 (1-butyl-3-methyl-
1H-imidazolium tetrafluoroborate).
hydes 4a–j (Aldrich) and 1-buten-3-one 5 (Aldrich) were used as
received without any purification.
2.2. Instrumentation
GC–MS measurements were carried out on a SE 54 capillary
column using a Fisons 8000 gas chromatograph coupled with a
Fisons MD 800 quadrupole mass selective detector. 1H and 13C
NMR spectra were recorded using a Bruker AC 200 spectrome-
ter using CDCl3 as internal standard. Voltammetric measurements
in BMIM-BF4 were performed with an Amel System 5000 in a
three-electrode cell; acquisition software was a CorrWare for
windows version 2.8d1 Scribner. 492/GC/3 and 492/Pt/1 Amel
micro-electrodes were employed, using a platinum counter elec-
trode and a 373/SSG/6 Ag/AgCl reference electrode. Voltammetric
measurements in organic solvents (DMSO, DMF, CH3CN) were per-
formed with an Amel 552 potentiostat equipped with an Amel 566
function generator and an Amel 563 multipurpose unit in three-
electrode cell; the curves were displayed on an Amel 863 recorder.
492/GC/3 and 492/Pt/1 Amel micro-electrodes were employed,
using a platinum counter electrode and the reference electrode
was a modified saturated calomel electrode. Electrolyses under
galvanostatic control were carried out with an Amel 552 poten-
tiostat equipped with an Amel 721 integrator. A two-compartment
2. Experimental
2.1. Starting material
CH3CN was distilled twice from P2O5 and CaH2; N,N-
dimethylformamide (DMF) was distilled from activated alumina
under reduced pressure; dimethylsulphoxide (DMSO) was used
without any purification; 1-butyl-3-methyl-imidazolium tetraflu-
oborate (BMIM-BF4) was heated under vacuum at 45 ◦C for
2 h. Tetraethylammonium hexafluorophosphate (TEAHFP) was
dried under high vacuum at 45 ◦C for 24 h. 3-Benzyl-5-(2-
hydroxyethyl)-4-methylthiazolium chloride 2 (Aldrich), 3-ethyl-5-
(2-hydroxyethyl)-4-methylthiazolium bromide 3 (Aldrich), alde-

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M. Orsini et al. / Electrochimica Acta 55 (2010) 3511–3517
cell was used; the cathode was a disc of reticulated vitreous car-
bon (9 mm diameter) or a Pt spiral (apparent area 1.0 cm2) and the
counter electrode was a Pt spiral (apparent area 0.8 cm2).
2.3.6. 1-Cyclohexylpentane-1,4-dione 6d [25]
1H NMR (CDCl3), ı: 1.13–1.29 (m, 5H), 1.56–1.82 (m, 5H), 2.11
(s, 3H), 2.24–2.35 (m, 1H), 2.63 (br s, 4H). 13C NMR (CDCl3), ı: 25.5,
25.7, 25.8, 28.3, 28.4, 29.9, 34.0, 36.7, 50.6, 207.4, 212.6. MS m/e
(relative intensity): M•+ absent, 139 (2), 99 (100), 83 (54).
2.3. Typical experiment
2.3.7. 7-Phenylheptane-2,5-dione 6e [22]
2.3.1. Electrolysis of thiazolium salt 2 in BMIM-BF4 followed by
the addition of benzaldehyde 4a and 1-buten-3-one 5
1H NMR (CDCl3), ı: 2.15 (s, 3H), 2.58–2.92 (m, 8H), 7.13–7.29 (m,
5H). 13C NMR (CDCl3), ı: 29.6, 29.8, 36.1, 36.8, 44.1, 126.0, 128.2,
The
methylthiazolium chloride 2 (2 mmol) in BMIM-BF4 (2.0 cm3)
was carried out under galvanostatic conditions (I = 47 mA cm−2
electrolysis
of
3-benzyl-5-(2-hydroxyethyl)-4-
128.4, 141.0, 207.2, 208.4. MS m/e (relative intensity): 204 (M•+
14), 161 (4), 146 (100), 133 (23), 105 (72), 99 (58), 91 (43), 71 (32).
,
)
with continuous nitrogen bubbling, at 65 ◦C. The anolyte (1.5 cm3 of
BMIM-BF4) was separated from the cathodic compartment through
a G-3 glass septum. At the end of the electrolysis, benzaldehyde
4a (4 mmol) and 1-buten-3-one 5 in large excess (1.0 cm3) were
added to the catholyte, the solution was stirred at 65 ◦C for 2 h
and then at r.t. for 12 h. The reaction mixture was extracted with
diethyl ether (3× 10 cm3, allowing to stand under stirring with
diethyl ether 15 min each time). After removing the solvent from
the combined ethereal layers under reduced pressure, the crude
reaction mixture was analyzed by 1H NMR.
2.3.8. Mixture of 6-phenylheptane-2,5-dione 6f and
2-methyl-2-phenyl-1,5-hexanedione 6ꢀf [24,26]
6f 1H NMR (CDCl3), ı: 1.36 (d, 3H, J = 7.0 Hz), 2.10 (s, 3H),
2.45–2.70 (m, 4H), 3.78 (q, 1H, J = 7.0 Hz), 7.15–7.36 (m, 5H). 13C
NMR (CDCl3), ı: 17.4, 29.8, 34.7, 37.1, 52.8, 127.1, 127.8, 128.8,
140.6, 207.2, 209.5. MS m/e (relative intensity): M•+ absent, 105
(10), 99 (100), 71 (11), 43 (8).
6ꢀf 1H NMR (CDCl3), ı: 1.41 (s, 3H), 2.03 (s, 3H), 2.16–2.26 (m,
4H), 7.15–7.36 (m, 5H), 9.46 (s, 1H). 13C NMR (CDCl3), ı: 17.3, 29.4,
29.8, 38.4, 53.1, 127.0, 127.5, 129.0, 139.1, 201.8, 207.8. MS m/e
(relative intensity): M•+ absent, 174 (2), 118 (100), 99 (6), 43 (36).
2.3.2. Electrolysis of thiazolium salts 2 or 3 in organic solvent
VOCs followed by the addition of aldehydes 4a–j and
1-buten-3-one 5
2.3.9. 1-[4-(Fluoro)-phenyl]pentane-1,4-dione 6g [27]
1H NMR (CDCl3), ı: 2.23 (s, 3H), 2.86 (t, 2H, J = 6.2 Hz), 3.21 (t,
2H, J = 6.2 Hz), 7.10 (app. t, 2H, J = 8.7 Hz), 7.98 (dd, 2H, J = 8.7 Hz
and J = 5.5 Hz). 13C NMR (CDCl3), ı: 30.0, 32.2, 37.0, 115.6 (d,
2J = 21.9 Hz), 130.6 (d, 3J = 9.3 Hz), 133.0 (d, 4J = 3.0 Hz), 165.7 (d,
The electrolysis of solvent–0.4 mol dm−3 thiazolium salt 2 or 3
solution (5.0 cm3) was carried out under galvanostatic conditions
(I = 47 mA cm−2) with continuous nitrogen bubbling, at 65 ◦C. The
anodic solution (DMF–0.1 mol dm−3 TEAHFP) was separated from
the cathodic compartment through a porous glass plug filled with
methylcellulose in DMF–TEAHFP.
1J = 254.7 Hz), 196.9, 207.2. MS m/e (relative intensity): 194 (M•+
7), 179 (54), 151 (30), 123 (100), 71 (10), 43 (13).
,
At the end of the electrolysis, aldehydes 4a–j (4 mmol) and 1-
buten-3-one 5 in large excess (1.0 cm3) were added to the catholyte,
the solution was stirred at 65 ◦C for 2 h and then at r.t. for 12 h. When
DMF and DMSO were used as solvent, the catholyte was poured into
water (150 ml) and extracted with diethyl ether (3× 30 cm3). When
CH3CN was used, the solvent was evaporated under reduced pres-
sure and the residue extracted with diethyl ether (3× 30 cm3). After
removing the solvent from the combined ethereal layers under
2.3.10. 1-[4-(Methyl)-phenyl]pentane-1,4-dione 6h [28]
1H NMR (CDCl3), ı: 2.22 (s, 3H), 2.37 (s, 3H), 2.84 (t, 2H,
J = 6.4 Hz), 3.22 (t, 2H, J = 6.4 Hz), 7.22 (d, 2H, J = 8.0 Hz), 7.85 (d, 2H,
J = 8.0 Hz). 13C NMR (CDCl3), ı: 21.6, 30.1, 32.2, 37.0, 128.1, 129.2,
134.1, 143.9, 198.1, 207.5.
2.3.11. 1-(2-Furyl)-pentane-1,4-dione 6i [29]
1H NMR (CDCl3), ı: 2.18 (s, 3H), 2.82 (d, 2H, J = 6.4 Hz), 3.08 (d,
2H, J = 6.4 Hz), 6.48 (dd, 1H, J = 3.6 Hz and J = 1.4 Hz), 7.16 (d, 1H,
J = 3.6 Hz), 7.53 (d, 1H, J = 1.4 Hz). 13C NMR (CDCl3), ı: 29.9, 32.0,
36.6, 112.2, 117.1, 146.3, 152.3, 187.7, 207.1.
reduced pressure, the crude reaction mixture was analyzed by 1
NMR.
H
All products were purified by flash chromatography, using n-
hexane–ethyl acetate 95:5 as eluent and they were identified by
comparison of their spectra data with data reported in literature.
2.3.12. 1-(2-Thiophen)-pentane-1,4-dione 6j [22]
1H NMR (CDCl3), ı: 2.19 (s, 3H), 2.82 (t, 2H, J = 6.4 Hz), 3.17 (t,
2H, J = 6.4 Hz), 7.08 (app. t, 1H, J = 4.9 Hz) 7.58 (dd, 1H, J = 4.9 Hz and
J = 1.2 Hz), 7.71 (d, 1H J = 3.6 Hz). 13C NMR (CDCl3), ı: 30.0, 32.9, 37.0,
128.1, 132.0, 133.5, 143.6, 191.4, 207.1.
2.3.3. Phenyl-pentane-1,4-dione 6a [22]
1H NMR (CDCl3), ı: 2.23 (s, 3H), 2.86 (t, 2H, J = 6.0 Hz), 3.25 (t,
2H, J = 6.0 Hz), 7.38–7.53 (m, 3H), 7.95 (d, 2H, J = 7.0 Hz). 13C NMR
(CDCl3), ı: 30.1, 32.4, 36.9, 128.0, 128.5, 133.1, 136.5, 198.5, 207.5.
MS m/e (relative intensity): 176 (M•+, 5), 161 (21), 105 (100), 77
(3).
2.3.13. 2-Hydroxy-1,2-diphenylethanone 7a [30]
1H NMR (CDCl3), ı: 4.25 (br s, 1H), 5.94 (s, 1H), 7.25–7.41 (m,
8H), 7.90 (d, 2H, J = 7.3 Hz). 13C NMR (CDCl3), ı: 76.2, 127.7, 128.5,
128.6, 129.1, 133.6, 133.8, 139.0, 199.0.
2.3.4. n-Decane-2,5-dione 6b [23]
1H NMR (CDCl3), ı: 0.76 (t, 3H, J = 6.2 Hz), 1.10–1.17 (m, 4H),
1.38–1.52 (m, 2H), 2.06 (s, 3H), 2.32 (t, 2H, J = 7.4 Hz). 13C NMR
(CDCl3), ı: 13.8, 22.3, 23.3, 29.8, 31.2, 35.9, 36.7, 42.6, 207.1, 209.5.
2.3.14. 1,2-Bis-[(4-fluoro)-phenyl]-2-hydroxyethanone 7g [31]
1H NMR (CDCl3), ı: 4.54 (d, 1H, J = 5.6 Hz), 5.88 (d, 1H, J = 5.6 Hz),
6.94-7.09 (m, 4H), 7.24–7.31 (m, 2H), 7.87–7.94 (m, 2H). 13C
NMR (CDCl3), ı: 75.3, 116.0 (d, 2J = 22.1 Hz), 116.2 (d, 2J = 21.8 Hz),
129.5 (d, 3J = 8.3 Hz), 131.8 (d, 3J = 9.6 Hz), 134.7, 134.8, 161.8 (d,
1J = 162.3 Hz), 166.9 (d, 1J = 171.5 Hz), 197.1.
2.3.5. n-Dodecane-2,5-dione 6c [24]
1H NMR (CDCl3), ı: 0.85 (t, 3H, J = 6.4 Hz), 1.24 (br s, 8H),
1.51–1.59 (m, 2H), 2.16 (s, 3H), 2.42 (t, 2H, J = 7.4 Hz), 2.56–2.70 (m,
4H). 13C NMR (CDCl3), ı: 13.9, 22.5, 23.8, 28.9, 29.1, 29.8, 31.6, 36.0,
36.8, 42.8, 207.1, 209.5. MS m/e (relative intensity): M•+ absent, 155
(2), 127 (15), 114 (100), 99 (35), 71 (69), 57 (44), 43 (7).
2.3.15. 1,2-Bis-[(4-methyl)-phenyl]-2-hydroxyethanone 7h [30]
1H NMR (CDCl3), ı: 2.26 (s, 3H), 2.33 (s, 3H), 4.51 (1br s), 5.90
(s, 1H), 7.12–7.27 (m, 6H), 7.81 (d, 2H, J = 8.2 Hz). 13C NMR (CDCl3),

M. Orsini et al. / Electrochimica Acta 55 (2010) 3511–3517
3515
ꢀ = 0.2 V s−1, r.t.) show a single irreversible and diffusion controlled
wave related to the monoelectronic reduction of cations 1b, 2b
and 3b to carbenes 1a, 2a and 3a respectively and dihydrogen
(Schemes 2 and 4, react. 1).
The values of the peak potentials of 2 and 3 are strongly more
positive with respect to the one of 1 (Ep2 = −1.63 V, Ep3 = −1.66 V,
Ep1 = −2.55 V, vs SCE, c = 5.0 × 10−3 mol dm−3, DMSO as solvent, vit-
reous carbon cathode, ꢀ = 200 mV s−1, T = 25.0 ◦C). These values are
moderately affected by the nature of the solvent and of the cathodic
material (C, Pt).
Likewise, the voltammetric curves of 2 and 3, recorded for the
solutions of RTIL 1 as solvent, show a single irreversible mono-
electronic wave (Ep∗2 = −1.50 V and Ep∗3 = −1.60 V vs reference
Ag/AgCl, ꢀ = 200 mV s−1, T = 50.0 ◦C, Fig. 1). Therefore, the selective
cathodic reduction of 2 and 3 to thiazol-2-ylidenes 2a and 3a, can
be performed in organic solvent as well as in ionic liquid 1.
These remarks suggested to study the Stetter reaction with the
following procedure: the solutions of 2 or 3 (in organic solvents or
in RTIL 1), previously electrolyzed under galvanostatic conditions,
were added of aldehydes 4 and 1-buten-3-one 5 and stirred, at con-
trolled temperature, for a prefixed interval of time. The workup
of the resulting solutions afforded 1,4-dicarbonyl compounds 6. In
addition, as byproducts, ␣-hydroxyketones 7 might be obtained.
N-Heterocyclic carbenes 2a and 3a are catalysts able to induce
the inversion of the normal reactivity (reverse polarity or umpol-
ung) of an aldehyde 4 via formation of an acylanion equivalent
4ꢀ (Breslow intermediate). The acylanion equivalent performs a
nucleophilic attack to the Michael acceptor 5, added to the reac-
tion mixture (Stetter reaction), or to another aldehyde molecule
(benzoin condensation).
Fig. 1. Cyclic voltammetric curves for RTIL
1
(curve a), for RTIL
1 con-
taining
2
(c = 1.0 × 10−2 mol dm−3
,
curve b) and for RTIL containing 3
1
(c = 1.0 × 10−2 mol dm−3, curve c). Vitreous carbon cathode, ꢀ = 200 mV s−1, reference
Ag/AgCl, T = 50.0 ◦C.
ı: 21.6, 21.7, 75.7, 127.6, 129.2, 129.3, 129.8, 130.2, 136.3, 138.3,
144.6, 198.5.
Therefore, in any setting-up of new procedures of synthesis of
1,4-dicarbonyl compounds 6 via Stetter reaction, the possible pres-
ence of ␣-hydroxyketones 7 as byproducts (benzoin condensation)
must be controlled (Scheme 5).
3. Results and discussion
To optimize the procedure, as concerns both yield and selectiv-
ity, i.e. 6 vs 7, several experiments were performed using different:
(a) reaction time and temperature, (b) number of Faradays, con-
sumed at the electrodes, per mol of aldehyde 4 added to the
3.1. Preliminary voltammetric investigation
The voltammetric curves of the solutions containing 1, 2 or 3
(DMF, DMSO, CH3CN as solvent, Et4NPF6 as supporting electrolyte,
Scheme 5.

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M. Orsini et al. / Electrochimica Acta 55 (2010) 3511–3517
Table 1
Reactivity of benzaldehyde 4a vs Michael acceptor 5 in electrolyzed solutions of thiazolium salt 2 (0.4 mol dm−3)a. Solvent: DMF, CH3CN, DMSO, and BMIM-BF4. Effect of
solvent, time and temperature reaction and Q on the yield and selectivity.
Entry
Solvent
Qb (F mol−1
)
Time and temp.c
Products (yields %)d
6a selectivity (%)e
4a
6a
7a
1
2
3
4
5
6
7
8
9f
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
DMSO
BMIM-BF4
0.25
0.25
0.10
0.20
0.25
0.40
0.25
0.25
0.25
A
B
C
C
C
C
C
C
C
74
36
64
30
20
31
48
14
35
14
36
14
34
46
38
14
62
46
4
7
4
20
23
13
19
16
13
78
83
78
63
67
75
44
79
78
a
Electrolyses were carried out under galvanostatic control (I = 47 mA cm−2) in a divided cell, reticulated C cathode, Pt anode.
Number of Faradays supplied to the electrodes per mole of 4a.
Benzaldehyde 4a and 1-buten-3-one 5 were added to the cathodic compartment at the end of the electrolysis, afterwards the cathodic solution was stirred for 20 h at r.t.
b
c
(A) or 48 h at r.t. (B) or 2 h at 65 ◦C and 12 h at r.t. (C).
d
Yield calculated with respect to benzaldehyde 4a and determined by 1H NMR spectrum of crude reaction mixture.
e
Selectivity towards the formation of 6a evaluated as [6a/(6a + 7a)] × 100.
f
The cathode was a Pt spiral.
electrolyzed solutions, and (c) solvents (VOCS: DMF, DMSO, CH3CN
or RTIL: 1).
Benzaldehyde 4a and thiazolium salt 2 were taken as model
substrate and model precatalyst respectively. The results, reported
in Table 1, can be summarized as follows.
ꢁ) from 0.10 to 0.25 (Table 1, entries 3–5). Further increases of Q
(Q = 0.4 Faraday mole−1) and ꢁ do not affect the yields of 6a and 7a
according to the catalytic role of the electrogenerated carbene 2a
(Table 1, entry 6).
3.4. Effect of the nature of the solvent
3.2. Reaction time and temperature
As regards the optimization of the solvent, among VOCs and
RTILs, DMSO turned to be the best solvent with respect to yield and
selectivity (Table 1, entries 5, 7, 8, and 9).
Both the yields of 6a and 7a increase on increasing reaction time
and temperature; on the contrary the selectivity of the Stetter reac-
tion decreases on increasing the temperature (Table 1, entries 1 and
2 vs 5).
In order to evaluate the generality and the synthetic poten-
tial of the procedure, the reactivity of a wide range of aldehydes
(aromatic 4a, g, h aliphatic 4b–f and heteroaromatic aldehydes 4i,
j) vs Michael acceptor 5 was investigated, in DMSO solutions, in
the presence of electrogenerated thiazol-2-ylidenes. To compare
the reactivity of different aldehydes, the investigation was car-
ried out according to the optimized conditions reported in Table 1,
entry 8. The results (yields of 1,4-dicarbonyl compounds 6a–j, ␣-
hydroxyketones 7 as well as the ones of unconverted aldehydes),
reported in Table 2, show that:
3.3. Number of Faradays per mole of aldehydes, Q
Assuming the reduction of thiazolium salt 2 to thiazol-2-
ylidenes 2a as a monoelectronic process (Scheme 3, react. 1), the
number of Faradays per mole of aldehydes consumed during the
electrolysis affects the molar ratio (ꢁ) carbene/aldehyde present in
the solution at the end of the electrolyses. The yield of 6a, as well
as the one of 7a, increases on increasing of Q (and consequently of
Table 2
Electrochemical synthesis of 1,4-dicarbonyl compounds 6a–j by electrolyses of DMSO-0.4 mol dm−3 thiazolium salt 2 followed by addition of aldehydes 4a–j and Michael
acceptor 5a.
Entry
Aldehyde
Products (yields %)b
6 Selectivity (%)c
6
7
4
1
2
4a
4b
4b
4c
4d
4e
4f
4g
4g
4g
4h
4i
62 (6a)
73 (6b)
67 (6b)
79 (6c)
78 (6d)
93 (6e)
79 (6f)
51 (6g)
61 (6g)
71 (6g)
37 (6h)
49 (6i)
34 (6j)
16 (7a)
14 (4a)
79
100
100
100
100
100
100
62
65
75
74
100
100
–
–
–
–
–
18 (4b)
13 (4b)
20 (4c)
21 (4d)
6 (4e)
7 (4f)
17 (4g)
5 (4g)
3d
4
5
6
7e
8
–
32 (7g)
33 (7g)
24 (7g)
13 (7h)
–
9f
10d
11
12
13
4 (4g)
45 (4h)
42 (4i)
65 (4j)
4j
–
a
Electrolyses were carried out under the optimized conditions reported in Table 1, entry 8.
Yield calculated with respect to aldehyde 4 and determined by 1H NMR spectrum on crude reaction mixture.
Selectivity towards the formation of 6 evaluated as [6/(6 + 7)] × 100.
b
c
d
e
Thiazolium salt 3 instead of 2 was used in the DMSO solutions.
The formation of the byproduct 2-methyl-2-phenyl-1,5-hexanedione 6ꢀf was observed (13% of yield with respect to aldehyde 4f and determined by 1H NMR on crude
reaction mixture).
f
Temperature and reaction time 65 ◦C and 18 h.

M. Orsini et al. / Electrochimica Acta 55 (2010) 3511–3517
3517
(1) aliphatic aldehydes 4b–f furnished 1,4-dicarbonyl compounds
6b–f in high yields (93–73%) with complete selectivity (100%)
(Table 2, entries 2–7);
The procedure involves the inversion of the normal reactivity
(umpolung) of aldehydes, induced by heterocyclic carbenes 2a and
3a, generated by electrolysis of solutions of thiazolium salts 2 and
3 (VOCs or RTILs as solvents).
(2) heteroaromatic aldehydes 4i, j furnished 1,4-dicarbonyl com-
pounds 6i,
j
in moderate yields (49–34%) and complete
The nature of the aldehydes and of the solvents, the molar ratio
catalyst/substrate, the temperature and reaction time affect the
yields of the 1,4-dicarbonyl compounds and the selectivity of the
procedure, i.e. the reactivity of the Breslow intermediate vs the
Michael acceptor (Stetter reaction) or the parent aldehyde (benzoin
condensation).
selectivity (100%) (Table 2, entries 12 and 13);
(3) moderate yields (62–37%) and selectivity (79–62%) mark aro-
matic aldehydes 4a, g, h (Table 2, entries 1, 8–11).
The key step of the Stetter reaction as well as of the benzoin
condensation is the formation of the acylanion equivalent (Breslow
intermediate). Therefore the reactivity of the Breslow intermediate
4ꢀ is affected by the nature of the aldehydes:
Acknowledgements
We thank Mr. M. Di Pilato for his contribution to the experimen-
tal part of this work. This work was supported by research grants
from MURST (Prin 2006) and CNR, Roma Italy.
(i) in the case of aliphatic 4b–f and heteroaromatic 4i,
j
aldehydes, the 1,2-addition (Breslow intermediate–parent
aldehyde) is not competitive with the 1,4-addition (Breslow
intermediate–Michael acceptor);
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