Synthesis of 3-alkylcoumarins from salicylaldehydes and α,β-unsaturated aldehydes utilizing nucleophilic carbenes: A new umpoled domino reaction

Article abstract of DOI:10.1002/ejoc.200600718

Starting from salicylaldehydes and α,β-unsaturated aldehydes, a new coumarin synthesis in ionic liquids is presented. The key feature is the generation of N-heterocyclic carbenes (NHC) and an Umpolung reaction. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200600718

FULL PAPER
DOI: 10.1002/ejoc.200600718
Synthesis of 3-Alkylcoumarins from Salicylaldehydes and α,β-Unsaturated
Aldehydes Utilizing Nucleophilic Carbenes: A New Umpoled Domino Reaction
Jakob Toräng,[a] Sylvia Vanderheiden,[b] Martin Nieger,[c] and Stefan Bräse*[b]
Keywords: Coumarins / Ionic liquids / N-heterocyclic carbene (NHC) / Domino reaction / Umpolung
Starting from salicylaldehydes and α,β-unsaturated alde- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
hydes, a new coumarin synthesis in ionic liquids is presented.
The key feature is the generation of N-heterocyclic carbenes
(NHC) and an Umpolung reaction.
Germany, 2007)
During the last decade, N-heterocyclic carbenes (NHCs) dehydes.[11] Herein, we wish to report a novel synthesis of
have been successfully introduced as ligands for transition- 3-substituted coumarins based on NHC-promoted Umpo-
metal catalysis[1] and recently NHCs have been effectively lung of α,β-unsaturated aldehydes followed by annulation
applied as organocatalysts[2] in a large number of chemical with salicylaldehydes. Coumarins are naturally occurring
transformations, including transesterification/acylation,[3] benzopyran derivatives and have attracted intense interest
benzoin[4] and Stetter[5] reactions. The generation of homo- in recent years because of their diverse pharmacological
enolate equivalents, by NHC-catalyzed Umpolung of α,β- properties.[12] 3-Alkylcoumarins, which are important build-
unsaturated aldehydes, was independently described by ing blocks in organic synthesis, can in principle be prepared
Glorius[6] and Bode[7] in the synthesis of γ-butyrolactones. from carboxylic acids and salicylaldehydes by a modified
Subsequently, this methodology has been extended towards Perkin reaction.[13] However, so far, this method has not
the synthesis of β-lactones,[8] spiro γ-butyrolactones,[9] γ- been explored in detail leading to satisfying yields. In ad-
lactams[10] and to redox esterification of α,β-unsaturated al- dition, a larger amount of acid anhydrides is required to
Scheme 1. Reaction path a: synthesis of 2,2-dimethyl-2H-chromene-3-carbaldehydes 3 and 9-methyl-8,12-dioxatricyclo[7.3.1.02,7]trideca-
2,4,6-trien-11-ols 4.[15] Reaction path b: preliminary synthesis of coumarin 6d-H.
give moderate yields.[14] This is in sharp contrast to the well-
elaborated Knoevenagel condensation of malonates with
salicylaldehydes leading to 3-substituted coumarins.
Previously, we have reported that the base-catalyzed con-
densation of α,β-unsaturated carbonyl compound 2 with
salicylaldehydes (2-hydroxybenzaldehydes) 1 yields different
dihydrobenzopyrans 3 or 4 depending on the base used in
[a] Institut für Organische Chemie, Universität Bonn,
Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany
[b] Institut für Organische Chemie, Universität Karlsruhe (TH),
Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Fax: +49-721-608-8581
E-mail: braese@ioc.uka.de
[c] Laboratory of Ingoranic Chemistry, Department of Chemistry
P. O. Box 55, 00014 University of Helsinki, Finland
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J. Toräng, S. Vanderheiden, M. Nieger, S. Bräse
FULL PAPER
the reaction.[15] The reactions, depicted in pathway a,
Scheme 1, were performed in mixtures of dioxane and
water. Upon screening for new conditions for the base-cata-
lyzed condensation of salicylaldehydes with α,β-unsaturated
aldehydes, we observed that a new product – a coumarin –
was formed if the reactions were carried out in ionic liquids
with 2-hydroxy-6-methoxy-4-methylbenzaldehyde (1d) and
acrolein (5a) (pathway b, Scheme 1).
Although the coumarin 6d-H – (Figure 1) being unequiv-
ocally characterized by X-ray crystallography – was ob-
tained in low yield (8%), it was the only compound extract-
able from the reaction mixture by organic solvents, and the
pure product could be obtained upon filtration through a
pad of silica gel. Optimization of the reaction using 2-hy-
droxy-6-methoxy-4-methylbenzaldehyde (1d) and acrolein
(5a) as model system was initiated by a quick run through
commercially available ionic liquids (IL).[16] The screening
of various ionic liquids showed that the nature of the imid-
azolium ion is of less importance for the formation of cou-
marins, whereas some dependency on the counterion was
observed, i.e. when 1-ethyl-3-methylimidazolium thiocya-
nate was applied, a mixture of 6d-H and 3d was obtained.
Ammonium-based ionic liquids did not provide coumarins,
indicating that the formation of coumarins depends on the
deprotonation of imidazolium ions leading to NHCs.
Among the ionic liquids tested, dimethyl 1,3-dimethylimid-
azolium phosphate provided the highest yields, and was
therefore used in further optimization of the reaction be-
tween 2-hydroxy-6-methoxy-4-methylbenzaldehyde (1d) and
acrolein (5a). Next, a screening of bases was performed
(Na2CO3, K2CO3, Cs2CO3, KOH, NEt3, DMAP, DABCO,
imidazole, sodium acetate, DBU, HünigЈs base), from which
it was evident that the inorganic bases provided the highest
yields of coumarin 6d-H, with K2CO3 being the best base
tested. Imidazole provided chromene 3d in an 8% yield,
whereas DMAP gave traces of both isomers 6d-H and 3d.
Furthermore, we found that slow addition of acrolein and
higher temperature (85 °C) improved the formation of cou-
marin 6d-H to 53% (Table 2, Entry 4). Inspired by the work
Figure 1. X-ray structure of 6d-H.
Table 1. Reactions between 1d and 5a using catalytic and stoichio-
metric amounts of K2CO3 and dimethyl 1,3-dimethylimidazolium
phosphate.
Entry
Equiv.
K2CO3
Equiv.
dimethyl 1,3-dimethyl-
imidazolium phosphate
Isolated
yield [%]
1
2
3
4
5
0.1
0.2
0.5
1.0
1.0
0.1
0.2
0.5
1.0
2.0
18
24
29
46
34
of Glorius[6] and Bode,[7] the coumarin synthesis was per- yields obtained using either conditions A or B was observed
formed using catalytic amounts of carbene precursor and which likewise seems to depend on the degree of shielding
K2CO3 in toluene. These experiments were carried out in of the aromatic aldehyde. For salicylaldehyde derivatives
sealed reaction vessels at 70 °C and acrolein was added in without substituents in the 6-position, higher yields were
one portion (Table 1).
obtained using stoichiometric amounts of carbene precur-
Though the reaction displayed some catalytic character sors (condition B, Entries 1 and 5, Table 2). However, in
when 0.1 equiv. of dimethyl 1,3-dimethylimidazolium phos- the case of 3-methoxy- (1f) and 4-methoxy-salicylaldehyde
phate and of K2CO3 was applied (18% yield, Table 1, Entry (1g), no significant difference in yield was observed using
1), a considerably higher yield was obtained with stoichio- either condition A or B. The electron-deficient 4-nitrosali-
metric amounts of carbene precursors (46% yield, Table 1, cylaldehyde only provided a trace of product (data not
Entry 4). The latter result is comparable to the yield ob- shown), most likely due to the decreased nucleophilicity of
tained using excess of carbene precursor (6.75 equiv.) and the corresponding phenolate. However, an alternative ex-
slow addition of acrolein at 85 °C, and thus both conditions planation might be that electron-poor benzaldehydes are
were tested in the synthesis of coumarins 6 (Table 2).
more susceptible towards attacks from nucleophilic carb-
The results depicted in Table 2 show that the highest enes leading to non-extractable stable, zwitterionic by-prod-
yields were achieved with salicylaldehydes bearing substitu- ucts.
ents in the 6-position, thus shielding the aldehyde from un-
Next, the reactivity of α,β-unsaturated aldehydes was in-
wanted interactions with the nucleophilic carbenes (Entries vestigated. Coumarins were obtained from (E)-cinnamal-
2, 3, 4, 9 and 11, Table 2). Furthermore, a difference in dehyde (5b), (E)-2-methoxycinnamaldehyde (5c), (E)-4-
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Umpoled Domino Reaction for the Synthesis of 3-Alkylcoumarins
FULL PAPER
Table 2. Reactions of salicylaldehyde derivatives 1a–n with acrolein.[a]
[a] Conditions: A) 1 equiv. of salicylicylaldehyde 1, 6.75 equiv. of dimethyl 1,3-dimethylimidazolium phosphate, 1 equiv. of K2CO3 and
2.5 equiv. acrolein (5a) in 0.5 mL of toluene added over a period of 8 h, 85 °C, 2 d; B) biphasic system with toluene, 1 equiv. of salicylalde-
hyde, 1 equiv. of dimethyl 1,3-dimethylimidazolium phosphate and 1 equiv. of K2CO3, 2.5 equiv. of acrolein, 70 °C, 2 d. * Isolated yields.
** Analogous to condition A, but with 5 equiv. of acrolein.
methoxycinnamaldehyde (5d) and (2E,4E)-hexa-2,4-dienal again the best result was provided by salicylaldehyde 1n
(5e) (Table 3).
(60%, Entry 9, Table 3). The methoxy groups of cinnamal-
The general trends in the obtained yields from the reac- dehydes (Entries 10 and 11, Table 3) did not influence the
tions between salicylaldehyde derivatives 1a–g,k,n and (E)- reactivity, in contrast to (E)-5-nitrocinnamaldehyde where
cinnamaldehyde are similar to those observed from reac- no product formation was observed (data not shown). In
tions with acrolein. Salicylaldehydes with substitutions in addition, no products were isolated from crotonaldehyde
the 6-position yielded the highest amounts of product, and and (E)-2-hexenal, but unexpectedly, (2E,4E)-hexa-2,4-di-
Table 3. Reaction of salicylaldehyde derivatives 1a–g,k,n with (E)-cinnamaldehyde (5b, R5 = Ph), (E)-2-methoxycinnamaldehyde (5c, R5
= 2-MeO-Ph), (E)-4-methoxycinnamaldehyde (5d, R5 = 4-MeO-Ph) and (2E,4E)-hexa-2,4-dienal (5e, R5 = 2-butenyl).
[a] A mixture of E/Z isomers was isolated.
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J. Toräng, S. Vanderheiden, M. Nieger, S. Bräse
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enal (5e) provided coumarin 6d-butenyl in 21% yield as mix- tassium carbonate in toluene, 6b-Ph was obtained in 43%
ture of E/Z isomers (Entry 12, Table 3). yield after 30 min (Table 4, Entry 1). Furthermore, 6n-Ph
In the reactions with cinnamaldehydes, the formation of could be generated in 61% yield within 30 min, nearly the
side products was observed. The side products were iden- same amount as for the standard conditions. Under micro-
tified as cis/trans isomers of a γ-butyrolactone, cis-7 and wave irradiation an increase in the yields obtained from re-
trans-7. In the absence of salicylaldehydes, without any op- actions between (E)-cinnamaldehyde (5b) and benzalde-
timization, the γ-butyrolactone was obtained in 17% yield, hydes 1a or 1d was observed. The coumarines 6b-Ph and
with the cis isomer as the major product formed 6a-Ph were formed in 50% and 36% yields, respectively.
(Scheme 2). This compliments the results reported by Glor-
ius[6] and Bode.[7] However, in these cases only carbenes
with bulky substituents led to the formation of lactones.
A proposed mechanism for the formation of coumarins
is outlined in Scheme 3.
The NHC 9, generated upon deprotonation of imid-
azolium ion 8, reacts with α,β-unsaturated aldehydes 5 re-
sulting in homoenolate equivalent 11. The protonation in
the β position of 11 leading to tautomers 12 and 13 is con-
sistent with previous reports[2a,7,18] suggesting that the use
of weak bases, like K2CO3, results in protonation and not
C–C bond formation. The salicylaldehyde 1a reacts with the
2-substituted imidazolium 13 providing 15 that, through a
condensation, yields the coumarin 6a. A side reaction leads
to the generation of propionate 14 by hydrolysis of the acti-
vated acid derivative 13, and furthermore, the salicylalde-
hyde might also be incorporated in the imidazolium by at-
tack of the carbene at the carbonyl function. The genera-
tion of polar, non-extractable compounds explains why only
small amounts of starting materials were recovered in all
reactions presented herein, with one exception, namely sali-
cylaldehyde 1n, where typically 20% could be recovered.
Unfortunately, the formation of non-extractable com-
pounds also prevents re-using the ionic liquids, which nor-
mally is an attractive feature of this class of solvents. When
the reaction was performed in the presence of 5 vol.-% D2O
a mixture of deuterium-labeled 6b-Ph* and non-labeled 6b-
Ph product (approx. 1:2) was achieved, but simultaneously
the yield dropped to 5% (Scheme 1) probably due to hydrol-
ysis of the activated acid derivatives 13. Because double-
deuterated material was not isolated, deprotonation-deuter-
ation of the coumarin after its formation is quite unlikely.
These features validate the proposed mechanism
(Scheme 4).
Scheme 2. Synthesis of γ-butyrolactones 7 from cinnamaldehyde in
dimethyl 1,3-dimethylimidazolium phosphate and toluene.
In addition, we were pleased to find that the reaction
time could be reduced when the reactions were performed
under microwave irradiation.[17] As depicted in Table 4 the
yields obtained from reactions between benzaldehyde 1a,b,d
and (E)-cinnamaldehyde (5b) either match or exceed the
yields obtained above using a conventional oil bath as heat
source.
When the reaction between benzaldehyde 1d and (E)-cin-
namaldehyde (5b) was performed under microwave radia-
In conclusion, we have demonstrated a new domino reac-
tion with 1 equiv. of carbene precursor and 1 equiv. of po- tion[19] from salicylaldehydes and α,β-unsaturated aldehydes
Table 4. Reactions between benzaldehydes 1a,b,d,n and (E)-cinnamaldehyde performed under microwave irradiation.
Entry
1
R1
R2
R3
R4
R5
Product
Isolated yield [%][a]
1
2
4
9
1a
1b
1d
1n
H
H
H
Me
H
H
Me
H
H
H
H
H
H
Ph
Ph
Ph
Ph
6a-Ph
6b-Ph
6d-Ph
6n-Ph
36
50
43
61
OMe
OMe
iPr
[a] Isolated yields after flash column chromatography.
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Umpoled Domino Reaction for the Synthesis of 3-Alkylcoumarins
FULL PAPER
Scheme 3. Mechanism for formation of coumarin 6a from α,β-unsaturated aldehydes and salicylaldehydes via NHCs.
Scheme 4. Reaction between 1b and 5b in the presence of 5 vol.-% D2O.
a Bruker DP 300 (300 MHz/75 MHz) or Bruker DP 400 (400 MHz/
leading to the formation of coumarins. To the best of our
knowledge this is the first example where NHC-generated
homoenolate equivalents have been used in a direct synthe-
sis of benzoannelated heterocycles. Although the presented
reaction suffers from moderate yields, it tolerates a broad
range of functionalities and provides coumarins from cheap
and commercial available starting materials.
100 MHz) instrument using CDCl3 as the solvent and residual
CHCl3/CDCl3 as shift reference: δ(CHCl3) = 7.28 ppm, δ(CDCl3)
= 77.00 ppm. IR spectra were recorded with the Bruker FTIR de-
vice IFS 88. EI-MS and EI-HRMS spectra were recorded with a
Finnigan MAT 90 instrument; elemental analyses were performed
using a Heraeus CHN-O-Rapid device. X-ray crystallographic
analyses were performed with a Nonius Kappa CCD or a STOE
IPDS II diffractometer with Mo-Kα radiation.
Procedure A. 5-Methoxy-3,7-dimethylchromen-2-one (6d-H): Under
argon, 0.200 g (1.20 mmol) of 2-hydroxy-6-methoxy-4-methylbenz-
aldehyde (1d) and 0.166 g (1.20 mmol) of K2CO3 were dissolved in
2.00 mL (2.47 g, 9.26 mmol) of dimethyl 1,3-dimethylimidazolium
phosphate. The reaction mixture was heated to 85 °C, after which,
0.135 g (2.40 mmol) of acrolein (5a) in 0.5 mL of toluene was added
over a period of 12 h using a syringe pump. After an additionally
36 h, the reaction mixture was cooled to room temp. and quenched
with 10 mL of water. The product was extracted with 2ϫ10 mL of
EtOAc and 1ϫ10 mL of CH2Cl2. The combined organic phases
were dried with MgSO4 and the solvent was removed under re-
Experimental Section
General: Compounds were purchased from commercial sources and
were used without further purification. Column chromatography
was performed using Macherey–Nagel silica gel 60 (230–400 mesh)
under flash conditions (EtOAc = ethyl acetate, Pent = n-pentane,
cHex = cyclohexane). For thin-layer chromatography, aluminum
foils layered with silica gel with fluorescence indicator (silica gel
60 F254) produced by Merck were employed. Melting points were
determined using a Laboratory Devices Inc. MelTemp II device
1
and were corrected. H and 13C NMR spectra were recorded with
Eur. J. Org. Chem. 2007, 943–952
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J. Toräng, S. Vanderheiden, M. Nieger, S. Bräse
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duced pressure. Purification of the crude product by column
chromatography (silica gel, 2.5ϫ20 cm, cHex/EtOAc, 5:1) yielded
the title compound (0.130 g, 53%) as colourless solid.
(40). HR-EIMS: calcd. 190.0630, found 190.0634. C10H8O2 (190 g/
mol): calcd. C 69.46, H 5.30; found C 69.25, H 5.38.
8-Bromo-5-methoxy-3-methylchromen-2-one (6c-H): Prepared ac-
cording to procedure A from 0.200 g (0.886 mmol) of 3-bromo-2-
hydroxy-6-methoxybenzaldehyde (1c), 0.120 g (0.866 mmol) of
K2CO3, 2.00 mL (2.47 g, 9.26 mmol) of dimethyl 1,3-dimethylimid-
azolium phosphate and 0.0971 g (1.73 mmol) of acrolein (5a). Puri-
fication of the crude product by column chromatography (silica gel,
2.5ϫ20 cm, cHex/EtOAc, 5:1) yielded the title compound (0.099 g,
Procedure B. 5-Methoxy-3,7-dimethylchromen-2-one (6d-H): Under
argon, 0.100 g (0.602 mmol) of 2-hydroxy-6-methoxy-4-methyl-
benzaldehyde (1d), 0.0832 g (0.602 mmol) of K2CO3, 0.0844 g
(1.51 mmol) of acrolein (5a) and 0.134 g (0.602 mmol) of dimethyl
1,3-dimethylimidazolium phosphate were suspended/dissolved in
2 mL of toluene. The reaction mixture was stirred at 70 °C for 24 h
and cooled to room temp. The reaction was quenched by the ad-
dition of 10 mL of water. The product was extracted with
2ϫ10 mL of EtOAc and 1ϫ10 mL of CH2Cl2 The combined or-
ganic phases were dried with MgSO4 and the solvent was removed
under reduced pressure. Purification of the crude product by col-
umn chromatography (silica gel, 2.5ϫ20 cm, cHex/EtOAc, 5:1)
yielded the title compound (0.057, g, 46%) as colourless solid.
42%) as colourless solid; m.p. 171–173 °C. – Rf (cHex/EtOAc, 5:1)
1
= 0.19. IR (KBr): ν = 1718 (s, νC=O) cm–1. H NMR (400 MHz,
˜
4
CDCl3): δ = 2.15 (d, J = 1.4 Hz, 3 H, CH3), 3.92 (s, 3 H, OCH3),
6.61 (d, J = 8.8 Hz, 1 H, C6-H), 7.56 (d, 3J = 8.8 Hz, 1 H, C7-
3
H), 7.84 (qt, J = 1.4 Hz, 1 H, C4-H) ppm. 13C NMR (75 MHz,
4
CDCl3): δ = 17.2 (+, CH3), 56.2 (+, OCH3), 100.6 (q, C-8), 106.2
(+, C-6), 111.4 (q, C-4a), 124.6 (q, C-3), 133.8 (+, C-4), 133.9 (+,
C-7), 150.6 (q, C-5), 154.8 (q, C-8a), 161.2 (q, C-2) ppm. MS (EI):
m/z (%) = 268/270 (100/98, M+), 225/227 (36/34) [M+ – CO – CH3].
HR-EIMS: calcd. 267.9735, found 267.9739. C11H9BrO3 (268 g/
mol): calcd. C 49.10, H 3.37; found C 48.74, H 3.49.
Procedure C. 3-Benzyl-5-methoxy-7-methylchromen-2-one (6d-Ph):
Under argon, 0.100 g (0.602 mmol) of 2-hydroxy-6-methoxy-4-
methylbenzaldehyde (1d), 0.0832 g (0.602 mmol) of K2CO3, 0.199 g
(1.51 mmol) of (E)-cinnamaldehyde and 0.134 g (0.602 mmol) of
dimethyl 1,3-dimethylimidazolium phosphate were suspended/dis-
5-Methoxy-3,7-dimethylchromen-2-one (6d-H): Prepared according
solved in 2 mL of toluene. The reaction mixture was stirred at to procedure B from 0.100 g (0.602 mmol) of 2-hydroxy-6-methoxy-
100 °C for 24 h and cooled to room temp. The reaction was
quenched upon addition of 10 mL of water. The product was ex-
tracted with 2ϫ10 mL of EtOAc and 1ϫ10 mL of CH2Cl2. The
combined organic phases were dried with MgSO4 and the solvent
was removed under reduced pressure. Purification of the crude
product by column chromatography (silica gel, 2.5ϫ20 cm, cHex/
EtOAc, 5:1) yielded the title compound (0.071 g, 42%) as colour-
less solid.
4-methylbenzaldehyde (1d), 0.0832 g (0.602 mmol) of K2CO3,
0.0844 g (1.51 mmol) of acrolein (5a) and 0.134 g (0.602 mmol) of
dimethyl 1,3-dimethylimidazolium phosphate in 2 mL of toluene.
Purification of the crude product by column chromatography (silica
gel, 2.5ϫ20 cm, cHex/EtOAc, 5:1) yielded the title compound
(0.065 g, 53%) as colourless solid; m.p. 109–112 °C. Rf (cHex/
EtOAc, 5:1) = 0.29. IR (KBr): ν = 1709 (s, νC=O) cm–1. 1H NMR
˜
4
(400 MHz, CDCl3): δ = 2.18 (d, J = 1.1 Hz, 3 H, CH3), 2.40 (s, 3
H, C7-CH3), 3.90 (s, 3 H, OCH3), 6.50 (s, 1 H, C6-H), 6.72 (s, 1
H, C8-H), 7.83 (qt, 4J = 0.63 Hz, 1 H, C4-H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 17.2 (+, CH3), 22.3 (+, CH3), 55.9 (+,
OCH3), 106.2 (+, C-8) 107.9 (q, C-4a), 109.1 (+, C-6), 122.4 (q, C-
3), 134.4 (+, C-4), 142.1 (q, C-7), 154.3 (q, C-8a), 155.2 (q, C-5),
162.6 (q, C-2) ppm. MS (EI): m/z (%) = 204 (100) [M+], 176 (24)
[M+ – CO], 161 (36) [M+ – CO – CH3]. HR-EIMS: calcd. 204.0786,
found 204.0791. C12H12O3 (204 g/mol): calcd. C 70.57, H 5.92;
found C 70.14, H 6.24.
3-Methylchromen-2-one[20] (6a-H): Prepared according to pro-
cedure B from 0.200 g (1.64 mmol) of salicylaldehyde (1a), 0.227 g
(1.64 mmol) of K2CO3, 0.230 g (4.10 mmol) of acrolein (5a) and
0.364 g (1.64 mmol) of dimethyl 1,3-dimethylimidazolium phos-
phate in 3 mL of toluene. Purification of the crude product by col-
umn chromatography (silica gel, 2.5ϫ20 cm, cHex/EtOAc, 5:1)
yielded the title compound (0.069 g, 26%) as colourless solid; m.p.
87–90 °C. R (cHex/EtOAc, 5:1) = 0.24. IR (KBr): ν = 1707 (s, ν
˜
f
C=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.22 (d, 4J = 1.3 Hz,
3 H, CH3), 7.26 (dt, 4J = 1.1 Hz, J = 7.6 Hz, 1 H, C6-H), 7.31 (d,
6-Methoxy-3-methylchromen-2-one (6e-H):[21] Was prepared ac-
3
4J = 8.3 Hz, 1 H, C8-H), 7.40–7.50 (m, 2 H, C5-H, C7-H), 7.52 cording to procedure B from 0.250 g (1.64 mmol) of 2-hydroxy-5-
(qt, J = 1.4 Hz, 1 H, C4-H) ppm. 13C NMR (100 MHz, CDCl3): methoxybenzaldehyde (1e), 0.227 g (1.64 mmol) of K2CO3, 0.230 g
4
δ = 17.2 (+, CH3), 116.5 (+, C-8), 119.6 (q, C-4a), 124.3 (+, C-6),
125.6 (q, C-3), 127.0 (+, C-5), 130.4 (+, C-7), 139.2 (+, C-4), 153.3
(q, C-8a), 162.3 (q, C-2) ppm. MS (EI): m/z (%) = 160 (100) [M+],
131 (64). HR-EIMS: calcd. 160.0524, found 160.0526.
(4.10 mmol) of acrolein (5a) and 0.364 g (1.64 mmol) of dimethyl
1,3-dimethylimidazolium phosphate in 3 mL of toluene. Purifica-
tion of the crude product by column chromatography (silica gel,
2.5ϫ20 cm, cHex/EtOAc, 5:1) yielded the title compound (0.091 g,
29%) as light yellow solid; m.p. 112–115 °C. – Rf (cHex/EtOAc,
5-Methoxy-3-methylchromen-2-one (6b-H): Prepared according to
procedure A from 0.183 g (1.20 mmol) of 2-hydroxy-6-methoxy-
benzaldehyde (1b), 0.166 g (1.20 mmol) of K2CO3, 2.00 mL (2.47 g,
9.26 mmol) of dimethyl 1,3-dimethylimidazolium phosphate and
0.135 g (2.40 mmol) of acrolein (5a). Purification of the crude prod-
uct by column chromatography (silica gel, 2.5ϫ20 cm, cHex/
EtOAc, 5:1) yielded the title compound (0.120 g, 53%) as colour-
5:1) = 0.20. IR (KBr): ν = 1708 (s, ν C=O) cm–1. 1H NMR
˜
4
(300 MHz, CDCl3): δ = 2.20 (d, J = 1.3 Hz, 3 H, CH3), 3.83 (s, 3
4
4
H, CH3), 6.84 (d, J = 2.8 Hz, 1 H, C5-H), 7.03 (dd, J = 3.0 Hz,
3J = 9.1 Hz, 1 H, C7-H), 7.22 (d, J = 9.1 Hz, 1 H, C8-H), 7.45 (s,
3
1 H, C4-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 17.3 (+, CH3),
55.8 (+, OCH3), 109.4 (+, C-5), 117.4, (+, C-8), 118.0 (+, C-7),
120.0 (q, C-4a), 126.2 (q, C-3), 139.1 (+, C-4), 147.7 (q, C-8a),
156.0 (q, C-6), 162.4 (q, C-2) ppm. MS (EI): m/z (%) = 190 (100)
[M+], 175 (20) [M+ – CH3], 147 (18) [M+ – CO – CH3]. HR-EIMS:
calcd. 190.0630, found 190.0633. C11H10O3 (190 g/mol): calcd. C
69.46, H 5.30; found C 69.27, H 5.44.
less solid; m.p. 123–128 °C.Rf (cHex/EtOAc, 5:1) = 0.26. IR (KBr):
1
ν = 1707 (s, νC=O) cm–1. H NMR (400 MHz, CDCl ): δ = 2.20
˜
3
(d, 4J = 1.3 Hz, 3 H, CH3), 3.92 (s, 3 H, OCH3), 6.69 (d, 3J =
8.3 Hz, 1 H, C6-H), 6.90 (d, 3J = 8.4 Hz, 1 H, C8-H), 7.35 (t, 3J =
8.4 Hz, 1 H, C7-H), 7.88 (qt, 4J = 1.3 Hz, 1 H, C4-H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 17.3 (+, CH3), 56.0 (+, OCH3), 105.0 7-Methoxy-3-methylchromen-2-one (6f-H): Prepared according to
(+, C-8), 108.9 (+, C-6), 110.2 (q, C-4a), 123.8 (q, C-3), 130.8 (+, procedure A from from 0.250 g (1.64 mmol) of 2-hydroxy-4-meth-
C-7), 134.3 (+, C-4), 154.3 (q, C-8a), 155.5 (q, C-5), 162.3 (q, C-2) oxybenzaldehyde (1f), 0.227 g (1.64 mmol) of K2CO3, 2.00 mL
ppm. MS (EI): m/z (%) = 190 (100) [M+], 162 (20) [M+ – CO], 147
(2.47 g, 9.26 mmol) of dimethyl 1,3-dimethylimidazolium phos-
948
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 943–952

Umpoled Domino Reaction for the Synthesis of 3-Alkylcoumarins
FULL PAPER
(m, 2 H, 2ϫCAr-H), 8.22 (d, J = 8.1 Hz, 1 H, C9-H), 8.28 (br. s,
1 H, C4-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 17.6 (+, CH3),
113.5 (q, C-4a), 116.9 (+, C-10), 121.5 (+, C-6), 125.1 (q, C-3),
125.8 (+, C-7), 127.9 (+, C-8), 128.7 (q, C-8a), 129.0 (+, C-5), 130.3
3
phate and 0.230 g (4.1 mmol) of acrolein (5a). Purification of the
crude product by column chromatography (silica gel, 2.5ϫ20 cm,
cHex/EtOAc, 5:1) yielded the title compound (0.038 g, 12%) as
colourless solid; m.p. 148–154 °C. – Rf (cHex/EtOAc, 5:1) = 0.23.
IR (KBr): ν = 1704 (s, νC=O) cm–1. 1H NMR (400 MHz, CDCl ): (q, C-4b), 131.7 (+, C-4), 135.1 (+, C-9), 152.6 (q, C-10), 162.3 (q,
˜
3
4
δ = 2.10 (d, J = 1.3 Hz, 3 H, CH3), 3.84 (s, 3 H, OCH3), 6.79 (d,
C-2) ppm. MS (EI): m/z (%) = 210 (16) [M+], 182 (8) [M+ – CO],
144 (100), 115 (28). HR-EIMS: calcd. 210.0681, found 210.0682.
4J = 2.4 Hz, 1 H, C8-H), 6.81 (dd, J = 2.4 Hz, J = 8.4 Hz, 1 H,
4
3
3
4
C6-H), 7.29 (d, J = 8.4 Hz, 1 H, C5-H), 7.44 (qt, J = 1.1 Hz, 1 C14H10IO2 (210 g/mol): calcd. C 79.98, H 4.79; found C 79.98, H
H, C4-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 17.0 (+, CH3),
55.7 (+, OCH3), 100.6 (+, C-8), 112.3 (+, C-6), 113.2 (q, C-4a),
122.2 (q, C-5), 139.4 (+, C-4), 154.9 (q, C-8a), 161.8 (q, C-2), 162.6
4.89.
6-Bromo-8-methoxy-3-methylchromen-2-one (6m-H): Prepared ac-
cording to procedure B from 0.138 g (0.602 mmol) of 5-bromo-2-
hydroxy-3-methoxybenzaldehyde (1m), 0.0832 g (0.602 mmol) of
K2CO3, 0.0844 g (1.51 mmol) of acrolein (5a) and 0.134 g
(0.602 mmol) of dimethyl 1,3-dimethylimidazolium phosphate in
2.00 mL of toluene. Purification of the crude product by column
chromatography (silica gel, 2.5ϫ20 cm, cHex/EtOAc, 5:1) yielded
the title compound (0.060 g, 37%) as colourless solid; m.p. 128–
(q, C-7) ppm. MS (EI): m/z (%) = 190 (100) [M+], 162 (28) [M+
–
CO], 147 (48) [M+ – CO – CH3]. HR-EIMS: calcd. 190.0630, found
190.0631. C10H8O2 (190 g/mol): calcd. C 69.46, H 5.30; found C
69.26, H 5.37.
8-Methoxy-3-methylchromen-2-one (6g-H):[22] Prepared according
to procedure A from 0.250 g (1.64 mmol) of 2-hydroxy-3-methoxy-
benzaldehyde (1g), 0.227 g (1.64 mmol) of K2CO3, 2.00 mL (2.47 g,
9.26 mmol) of dimethyl 1,3-dimethylimidazolium phosphate and
0.230 g (4.1 mmol) of acrolein (5a). Purification of the crude prod-
uct by column chromatography (silica gel, 2.5ϫ20 cm, cHex/
133 °C. R (cHex/EtOAc, 5:1) = 0.11. IR (KBr): ν = 1719 (s, νC=O)
˜
f
1
4
cm–1. H NMR (400 MHz, CDCl3): δ = 2.20 (d, J = 1.4 Hz, 3 H,
4
CH3), 3.93 (s, 3 H, OCH3), 7.07 (d, J = 2.1 Hz, 1 H, C5-H), 7.10
(d, 4J = 2.1 Hz, 1 H, C7-H), 7.37 (qt, 4J = 1.3 Hz, 1 H, C4-H)
EtOAc, 5:1) yielded the title compound (0.099 g, 32%) as colour- ppm. 13C NMR (100 MHz, CDCl3): δ = 17.3 (+, CH3), 56.5 (+,
less solid; m.p. 80–82 °C. Rf (cHex/EtOAc, 5:1) = 0.19. IR (KBr):
OCH3), 115.6 (+, C-7), 116.5 (q, C-4a), 120.7 (+, C-5), 121.2 (q,
C-6), 127.6 (q, C-3), 138.0 (+, C-4), 142.0 (q, C-8a), 147.7 (q, C-
8), 161.0 (q, C-2) ppm. MS (EI): m/z (%) = 268/270 (100/98) [M+].
HR-EIMS: calcd. 267.9735, found 267.9736. C11H9BrO3 (269 g/
mol): calcd. C 49.10, H 3.37; found C 48.91, H 3.48.
1
ν = 1714 (s, ν C=O) cm–1. H NMR (400 MHz, CDCl ): δ = 2.21
˜
3
(d, 4J = 1.3 Hz, 3 H, CH3), 3.95 (s, 3 H, OCH3), 6.98 (dd, 4J =
1.3 Hz, 3J = 7.8 Hz, 1 H, C7-H), 7.01 (dd, 4J = 1.1 Hz, 3J = 8.2 Hz,
1 H, C5-H), 7.16 (dd, J = 8.1 Hz, J = 7.9 Hz, 1 H, C6-H), 7.48
3
3
4
(qt, J = 1.3 Hz, 1 H, C4-H) ppm. 13C NMR (75 MHz, CDCl3): δ
5-Isopropyl-3,8-dimethylchromen-2-one (6n-H): Prepared according
to procedure A from 0.214 g (1.20 mmol) of 2-hydroxy-6-isopropyl-
3-methylbenzaldehyde (1n), 0.166 g (1.20 mmol) of K2CO3,
2.00 mL (2.47 g, 9.26 mmol) of dimethyl 1,3-dimethylimidazolium
phosphate and 0.336 g (6.0 mmol) of acrolein (5a). Purification of
the crude product by column chromatography (silica gel,
2.5ϫ20 cm, cHex/EtOAc, 5:1) yielded the title compound (0.147 g,
57%) as colourless solid; m.p. 102–104 °C. Rf (cHex/EtOAc, 5:1) =
= 17.2 (+, CH3), 56.2 (+, OCH3), 112.5 (+, C-7), 118.5 (+, C-6),
120.3 (q, C-4a), 124.1 (+, C-5), 126.2 (q, C-3), 139.4 (+, C-4), 142.9
(q, C-8a), 147.1 (q, C-8), 161.7 (q, C-2) ppm. MS (EI): m/z (%) =
190 (100) [M+], 162 (10) [M+ – CO], 147 (10) [M+ – CO – CH3].
HR-EIMS: calcd. 190.0630, found 190.0633. C10H8O2 (190 g/mol):
calcd. C 69.46, H 5.30; found C 69.24, H 5.32.
6-Iodo-3-methylchromen-2-one (6h-H): Prepared according to pro-
cedure B from 0.215 g (1.64 mmol) of 2-hydroxy-5-iodobenzal-
dehyde (1h), 0.227 g (1.64 mmol) of K2CO3, 0.230 g (4.10 mmol) of
acrolein (5a) and 0.364 g (1.64 mmol) of dimethyl 1,3-dimethyl-
imidazolium phosphate in 3 mL of toluene. Purification of the
crude product by column chromatography (silica gel, 2.5ϫ20 cm,
cHex/EtOAc, 5:1) yielded the title compound (0.075 g, 30%) as
0.40. IR (KBr): ν = 1719 (s, νC=O) cm–1. 1H NMR (300 MHz,
˜
CDCl3): δ = 1.29 (d, 3J = 6.8 Hz, 6 H, 2ϫCH3), 2.25 (d, 4J =
3
1.3 Hz, 3 H, CH3), 2.41 (s, 3 H, CAr-CH3), 3.36 (sept, J = 6.8 Hz,
1 H, Caliph-H), 7.08 (d, 3J = 7.9 Hz, 1 H, C6-H), 7.27 (d, 3J =
7.7 Hz, 1 H, C7-H), 7.82 (d, 4J = 0.9 Hz, 1 H, C4-H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 15.5 (+, CH3), 17.6 (+, CH3), 23.7
(+, 2ϫCH3), 28.3 (+, CH), 116.8 (q, C-4), 120.1 (+, C-6), 123.3
(q, C-3), 124.5 (q, C-8), 131.8 (+, C-7), 136.0 (+, C-4), 143.2 (q, C-
colourless solid; m.p. 158–162 °C. Rf (cHex/EtOAc, 5:1) = 0.34. IR
1
(KBr): ν = 1723 (s, νC=O) cm–1. H NMR (300 MHz, CDCl ): δ
˜
3
4
3
= 2.22 (d, J = 1.3 Hz, 3 H, CH3), 7.07 (d, J = 8.6 Hz, 1 H, C8- 5), 152.1 (q, C-8a), 162.2 (q, C-2) ppm. MS (EI): m/z (%) = 216 (44)
4
H), 7.41 (qt, J = 0.9 Hz, 1 H, C4-H), 7.70–7.73 (m, 2 H, C5-H,
[M+], 201 (100) [M+ – CH3]. HR-EIMS: calcd. 216.1150, found
C7-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 17.3 (+, CH3), 87.1
216.1154. C14H16O2 (216 g/mol): calcd. C 77.75, H 7.46; found C
(q, C-6), 118.5 (+, C-8), 121.7 (q, C-4a), 127.1 (q, C-3), 135.4 (+, 77.71, H 7.36.
C-5), 137.7 (+, C-7), 139.0 (+, C-4), 152.4 (q, C-8a), 161.5 (q, C-
3-Benzylchromen-2-one (6a-Ph):[24] Prepared according to pro-
2) ppm. MS (EI): m/z (%) = 286 (100) [M+], 258 (16) [M+ – CO].
HR-EIMS: calcd. 285.9491, found 285.9492. C10H7IO2 (286 g/
mol): calcd. C 41.99, H 2.47; found C 41.83, H 2.55.
cedure C from 0.200 g (1.64 mmol) of salicylaldehyde (1a), 0.227 g
(1.64 mmol) of K2CO3, 0.542 g (4.10 mmol) of (E)-cinnamaldehyde
(5b) and 0.364 g (1.64 mmol) of dimethyl 1,3-dimethylimidazolium
phosphate in 3 mL of toluene. Purification of the crude product by
column chromatography (silica gel, 2.5ϫ20 cm, pent/Et2O, 4:1 and
then cHex/EtOAc, 5:1) yielded the title compound (0.069 g, 18%)
as colourless solid; m.p. 110–113 °C. – Rf (cHex/EtOAc, 5:1) =
2-Methylbenzo[f]chromen-3-one (6k-H):[23] Prepared according to
procedure A from 0.292 g (1.64 mmol) of 2-hydroxynaphthalene-1-
carbaldehyde (1k), 0.227 g (1.64 mmol) of K2CO3, 2.00 mL (2.47 g,
9.26 mmol) of dimethyl 1,3-dimethylimidazolium phosphate and
0.230 g (4.1 mmol) of acrolein (5a). Purification of the crude prod-
uct by column chromatography (silica gel, 2.5ϫ20 cm, cHex/
0.40. IR (KBr): ν = 1712 (s, νC=O) cm–1. 1H NMR (400 MHz,
˜
CDCl3): δ = 3.82 (s, 2 H, CH2), 7.20–7.38 (m, 9 H), 7.44–7.48 (m,
EtOAc, 5:1) yielded the title compound (0.116 g, 34%) as colour- 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 36.6 (-, CH2), 116.5
less solid; m.p. 140–150 °C. Rf (cHex/EtOAc, 5:1) = 0.26. IR (KBr):
(+, C-8), 119.5 (q, C-4a), 124.3 (+), 126.9 (+), 127.4 (+), 128.8 (+,
2ϫCbenzyl), 129.4 (+, 2ϫCbenzyl), 129.5 (q, C-3), 130.8 (+), 137.7
1
ν = 1703 (s, νC=O) cm–1. H NMR (300 MHz, CDCl ): δ = 2.33
˜
3
(d, 4J = 1.3 Hz, 3 H, CH3), 7.44 (d, 3J = 8.9 Hz, 1 H, C10-H), (q), 139.3 (+, C4), 153.1 (q, C-8a), 161.7 (q, C-2) ppm. MS (EI):
7.53–7.57 (m, 1 H, CAr-H), 7.64–7.68 (m, 1 H, CAr-H), 7.88–7.92 m/z (%) = 236 (100) [M+], 207 (40), 131 (18). HR-EIMS: calcd.
Eur. J. Org. Chem. 2007, 943–952
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
949

J. Toräng, S. Vanderheiden, M. Nieger, S. Bräse
FULL PAPER
236.0837, found 236.0835. C16H12O2 (236 g/mol): calcd. C 81.34,
H 5.12; found C 81.17, H 5.16.
(%) = 344/346 (100/98) [M+], 315/317 (14/12), 165 (12). HR-EIMS:
calcd. 344.0048, found 344.0043. C17H13BrO3 (344 g/mol): calcd. C
59.15, H 3.80; found C 59.33, H 3.76.
3-Benzyl-5-methoxychromen-2-one (6b-Ph): Prepared according to
procedure C from 0.250 g (1.64 mmol) of 2-hydroxy-6-methoxy-
benzaldehyde (1b), 0.227 g (1.64 mmol) of K2CO3, 0.542 g
(4.10 mmol) of (E)-cinnamaldehyde (5b) and 0.364 g (1.64 mmol)
of dimethyl 1,3-dimethylimidazolium phosphate in 3 mL of tolu-
ene. Purification of the crude product by column chromatography
(silica gel, 2.5ϫ20 cm, pent/Et2O, 4:1 and then cHex/EtOAc, 5:1)
yielded the title compound (0.153 g, 35%) as colourless solid; m.p.
3-Benzyl-5-methoxy-7-methylchromen-2-one (6d-Ph): Prepared ac-
cording to procedure C from 0.100 g (0.602 mmol) of 2-hydroxy-6-
methoxy-4-methylbenzaldehyde (1d), 0.0832 g (0.602 mmol) of
K2CO3, 0.199 g (1.51 mmol) of (E)-cinnamaldehyde (5b) and
0.134 g (0.602 mmol) of dimethyl 1,3-dimethylimidazolium phos-
phate in 2 mL of toluene. Purification of the crude product by col-
umn chromatography (silica gel, 2.5ϫ20 cm, pent/Et2O, 4:1 and
then cHex/EtOAc, 5:1) yielded the title compound (0.071 g, 42%)
as colourless solid; m.p. 122–125 °C. Rf (cHex/EtOAc, 5:1) = 0.33.
IR (KBr): ν = 1709 (s, νC=O) cm–1. 1H NMR (300 MHz, CDCl ):
118–121 °C. R (cHex/EtOAc, 5:1) = 0.30. IR (KBr): ν = 1721 (s,
˜
f
νC=O) cm–1. 1H NMR (300 MHz, CDCl3): δ = 3.88 (s, 3 H,
4
4
3
˜
OCH3), 3.89 (d, J = 0.9 Hz, 2 H, CH2), 6.67 (dd, J = 0.6 Hz, J
= 8.3 Hz, 1 H, C6-H), 6.90 (d, J = 8.3 Hz, 1 H, C8-H), 7.22–7.34
3
3
δ = 2.40 (s, 3 H, CH3), 3.85 (s, 3 H, OCH3), 3.87 (br. s, 2 H, CH2),
6.48 (s, 1 H, C6-H), 6.72 (s, 1 H, C8-H), 7.21–7.35 (m, 5 H, CAr
(m, 5 H, CAr-H), 7.38 (t, 3J = 8.3 Hz, 1 H, C7-H), 7.78 (d, 4J =
0.6 Hz, 1 H, C4-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 36.8
(–, CH2), 55.9 (+, OCH3), 104.97 (+, C-8), 108.9 (+, C-6) ppm.
110.1 (q, C-4a), 126.7 (+), 127.2 (q, C-3), 128.7 (+, 2ϫCbenzyl),
129.2 (+, 2ϫCbenzyl), 131.3 (+), 134.5 (+), 138.2 (q), 154.2 (q, C-
8a), 155.7 (q, C-5), 161.8 (q, C-2). MS (EI): m/z (%) = 266 (100)
[M+], 237 (16). HR-EIMS: calcd. 266.0943, found 266.0947.
C17H14O3 (266 g/mol): calcd. C 76.68, H 5.30; found C 76.14, H
5.33.
-
H), 7.72 (br. s, 1 H, C4-H) ppm. 13C NMR (75 MHz, CDCl3): δ =
22.4 (+, CH3), 36.8 (–, CH2), 55.8 (+, CH3), 106.2 (+, C-8), 107.8
(q, C-4a), 109.1 (+, C-6), 125.9 (q, C-3), 126.6 (+), 128.6 (+,
2ϫCbenzyl), 129.2 (+, 2ϫCbenzyl), 134.6 (+, C-4), 138.4 (q), 142.6
(q, C-7), 154.3 (q, C-8a), 155.4 (q, C-5), 162.1 (q, C-2) ppm. MS
(EI): m/z (%) = 280 (100) [M+], 251 (16). HR-EIMS: calcd.
280.1099, found 280.1105. C18H16O3 (280 g/mol): calcd. C 77.12,
H 5.75; found C 77.11, H 5.628.
3-Benzyl-6-methoxychromen-2-one (6e-Ph): Prepared according to
procedure C from 0.250 g (1.64 mmol) of 2-hydroxy-5-methoxy-
benzaldehyde (1e), 0.227 g (1.64 mmol) of K2CO3, 0.542 g
(4.10 mmol) of (E)-cinnamaldehyde (5b) and 0.364 g (1.64 mmol)
of dimethyl 1,3-dimethylimidazolium phosphate in 3 mL of tolu-
ene. Purification of the crude product by column chromatography
(silica gel, 2.5ϫ20 cm, pent/Et2O, 4:1 and then cHex/EtOAc, 5:1)
yielded the title compound (0.117 g, 27%) as colourless solid; m.p.
3-(Deuteriophenylmethyl)-5-methoxychromen-2-one (6b-Ph*): Pre-
pared according to procedure C from 0.300 g (1.97 mmol) of 2-
hydroxy-6-methoxybenzaldehyde (1b), 0.272 g (1.97 mmol) of
K2CO3, 0.651 g (4.93 mmol) of (E)-cinnamaldehyde (5b), 0.438 g
(1.97 mmol) of dimethyl 1,3-dimethylimidazolium phosphate in
6 mL of toluene and 300 µL D2O. Purification of the crude product
by column chromatography (silica gel, 2.5ϫ20 cm, pent/Et2O, 4:1
and then cHex/EtOAc, 5:1) yielded a 0.5:1 mixture, respectively,
of the title compound 6b-Ph* and non-deuterated product 6b-Ph
(0.025 g, 5%) as colourless solid; m.p. 114–117 °C. Rf (cHex/
125–130 °C. R (cHex/EtOAc, 5:1) = 0.40. IR (KBr): ν = 1708 (s,
˜
f
νC=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 3.80 (s, 3 H,
4
OCH3), 3.89 (br. s, 2 H, CH2), 6.89 (d, J = 2.9 Hz, 1 H, C5-H),
EtOAc, 5:1) = 0.33. IR (KBr): ν = 1723 (s, νC=O) cm–1. 1H NMR
˜
7.04 (dd, 4J = 2.9 Hz, J = 9.1 Hz, 1 H, C7-H), 7.21–7.38 (m, 7 H)
3
(300 MHz, CDCl3): δ = 3.88 (br. s, 5 H, CH2/CHD, OCH3), 6.67
(d, 3J = 8.3 Hz, 1 H, C7-H), 6.90 (d, 3J = 8.5 Hz, 1 H, C8-H),
7.22–7.40 (m, 6 H, C7-H, 5ϫHbenzyl), 7.77 (s, 1 H, C4-H) ppm.
13C NMR (75 MHz, CDCl3): δ = 36.7 (–, 1J = 19.7 Hz, C-D), 55.9
(+, OCH3), 105.0 (+, C-8), 108.9 (+, C-6), 110.1 (q, C-4a), 126.7
(+), 127.2 (q, C-3), 128.7 (+, 2ϫCbenzyl), 129.2 (+, 2ϫCbenzyl),
131.3 (+, C-7), 134.5 (+, C-4), 138.2 (q), 154.2 (q, C-8a), 155.7 (q,
C-5), 161.8 (q, C-2) ppm. MS (EI): m/z (%) = 267 (7) [M+6b–Ph*],
266 (8) [M+6b–Ph], 240 (12), 239 (15), 234 (16), 204 (16), 203 (100),
190 (20), 138 (20), 127 (28), 126 (40), 125 (20), 106 (20), 105 (22),
97 (10), 96 (14).
ppm. 13C NMR (100 MHz, CDCl3): δ = 36.6 (–, CH2), 55.8 (+,
CH3), 109.5 (+, C-5), 117.5 (+, C-8), 118.6 (+, C-7), 119.8 (q, C-
4a), 126.9 (+), 128.8 (+, 2ϫCbenzyl), 129.5 (+, 2ϫCbenzyl), 129.9
(q, C-3), 137.7 (q), 139.1 (+, C-4), 147.5 (q, C-8a), 156.0 (q, C-6),
161.9 (q, C-2) ppm. MS (EI): m/z (%) = 266 (100) [M+], 237 (20),
104 (56). HR-EIMS: calcd. 266.0943, found 266.0945. C17H14O3
(266 g/mol): calcd. C 76.68, H 5.30; found C 76.56, H 5.43.
3-Benzyl-7-methoxychromen-2-one (6f-Ph):[25] Prepared according
to procedure C from 0.250 g (1.64 mmol) of 2-hydroxy-4-methoxy-
benzaldehyde (1f), 0.227 g (1.64 mmol) of K2CO3, 0.542 g
(4.10 mmol) of (E)-cinnamaldehyde (5a) and 0.364 g (1.64 mmol)
of dimethyl 1,3-dimethylimidazolium phosphate in 3 mL of tolu-
ene. Purification of the crude product by column chromatography
(silica gel, 2.5ϫ20 cm, pent/Et2O, 4:1 and then cHex/EtOAc, 5:1)
yielded the title compound (0.049 g, 11%) as colourless solid; m.p.
3-Benzyl-8-bromo-5-methoxychromen-2-one (6c-Ph): Prepared ac-
cording to procedure C from 0.379 g (1.64 mmol) of 3-bromo-2-
hydroxy-6-methoxybenzaldehyde (1c), 0.227 g (1.64 mmol) of
K2CO3, 0.542 g (4.10 mmol) of (E)-cinnamaldehyde (5b) and
0.364 g (1.64 mmol) of dimethyl 1,3-dimethylimidazolium phos-
phate in 3 mL of toluene. Purification of the crude product by col-
umn chromatography (silica gel, 2.5ϫ20 cm, pent/Et2O, 4:1 and
then cHex/EtOAc, 5:1) yielded the title compound (0.225 g, 40%)
as colourless solid; m.p. 154–159 °C. Rf (cHex/EtOAc, 5:1) = 0.24.
99–103 °C. R (cHex/EtOAc, 5:1) = 0.29. IR (KBr): ν = 1704 (s,
˜
f
νC=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 3.83 (s, 3 H,
OCH3), 3.84 (br. s, 2 H, CH2), 6.78–6.80 (m, 2 H), 7.22–7.36 (m,
7 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 36.4 (–, CH2), 55.8
(+, OCH3), 100.5 (+, C-8), 112.4 (+, C-6), 113.1 (q, C-4a), 125.8
(q, C-3), 126.8 (+), 128.3 (+), 128.8 (+, 2ϫCbenzyl), 129.4 (+,
2ϫCbenzyl), 138.1 (q), 139.4 (+, C-4), 154.8 (q, C-8a), 162.1 (q),
162.1 (q) ppm. MS (EI): m/z (%) = 266 (100) [M+], 237 (20). HR-
EIMS: calcd. 266.0943, found 266.0948. C17H14O3 (266 g/mol):
calcd. C 76.68, H 5.30; found C 76.64, H 5.55.
IR (KBr): ν = 1716 (s, νC=O) cm–1. 1H NMR (400 MHz, CDCl ):
˜
3
3
δ = 3.87 (s, 3 H, OCH3), 3.89 (s, 2 H, CH2), 6.58 (d, J = 8.8 Hz,
1 H, C6-H), 7.23–7.34 (m, 5 H, CAr-H), 7.56 (d, J = 8.8 Hz, 1 H,
3
C7-H), 7.72 (t, 4J = 1.3 Hz, 1 H, C4-H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 36.7 (–, CH2), 56.1 (+, OCH3), 100.5 (q, C-8), 106.2
(C-6), 111.3 (q, C-4a), 126.8 (+), 128.1 (q, C-3), 128.8 (+,
2ϫCbenzyl), 129.3 (+, 2ϫCbenzyl), 134.1 (+), 134.2 (+), 137.9 (q),
150.5 (q, C-5), 155.1 (q, C-8a), 160.7 (q, C-2) ppm. MS (EI): m/z
3-Benzyl-8-methoxychromen-2-one (6g-Ph): Prepared according to
procedure C from 0.250 g (1.64 mmol) of 2-hydroxy-3-methoxy-
950
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 943–952

Umpoled Domino Reaction for the Synthesis of 3-Alkylcoumarins
FULL PAPER
benzaldehyde (1g), 0.227 g (1.64 mmol) of K2CO3, 0.542 g
(4.10 mmol) of (E)-cinnamaldehyde (5b) and 0.364 g (1.64 mmol)
of dimethyl 1,3-dimethylimidazolium phosphate in 3 mL of tolu-
ene. Purification of the crude product by column chromatography
(silica gel, 2.5ϫ20 cm, pent/Et2O, 4:1) yielded the title compound
namaldehyde (5c) and 0.267 g (1.20 mmol) of dimethyl 1,3-dimeth-
ylimidazolium phosphate in 3 mL of toluene. Purification of the
crude product by column chromatography (silica gel, 2.5ϫ20 cm,
cHex/EtOAc, 5:1) yielded the title compound (0.154 g, 42%) as
colourless solid; m.p. 136–139 °C. Rf (cHex/EtOAc, 5:1) = 0.18. IR
1
(0.127 g, 29%) as light yellow solid; m.p. 85–87 °C. Rf (cHex/ (KBr): ν = 1718 (s, νC=O) cm–1. H NMR (400 MHz, CDCl ): δ
˜
3
EtOAc, 5:1) = 0.22. IR (KBr): ν = 1719 (s, νC=O) cm–1. 1H NMR
= 2.42 (s, 3 H, CH3), 3.84 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3),
˜
(300 MHz, CDCl3): δ = 3.90 (br. s, 2 H, CH2), 3.95 (s, 3 H, OCH3), 3.90 (br. s, 2 H, CH2), 6.50 (s, 1 H, C6-H), 6.74 (s, 1 H, C8-H),
6.92 (dd, 4J = 1.3 Hz, 3J = 7.7 Hz, 1 H, C7-H), 7.01 (dd, 4J =
6.93 (d, 3J = 7.9 Hz, 1 H, C-Hbenzyl), 6.95 (dt, 4J = 1.0 Hz, 3J =
7.4 Hz, 1 H, C-Hbenzyl), 7.26–7.30 (m, 2 H, 2ϫC-Hbenzyl), 7.67 (d,
4J = 0.6 Hz, 1 H, C4-H) ppm. 13C NMR (100 MHz, CDCl3): δ =
3
3
1.3 Hz, J = 8.1 Hz, 1 H, C5-H), 7.13 (t, J = 8.1 Hz, 1 H, C6-H),
7.23–7.37 (m, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 36.5
(-, CH2), 56.3 (+, OCH3), 112.8 (+, C-7), 118.9 (+, C-6), 120.1 (q, 22.3 (+, CH3), 30.9 (-, CH2), 55.4 (+, OCH3), 55.8 (+, OCH3),
C-4a), 124.1 (+, C-5), 126.8 (+), 128.8 (+, 2ϫCbenzyl), 129.5 (+, 106.2 (+), 108.0 (q, C-4a), 109.1 (+), 110.6 (+), 120.6 (+), 125.2
2ϫCbenzyl), 129.8 (q, C-3), 137.7 (q), 139.4 (+, C-4), 142.8 (q, C- (q), 126.6 (q), 128.1 (+), 131.0 (+), 134.3 (+), 142.2 (q, C-7), 154.1
8a), 147.1 (q, C-8), 161.2 (q, C-2) ppm. MS (EI): m/z (%) = 266
(q, C-8a), 155.4 (q, C-OMe), 157.7 (q, C-OMe), 162.3 (q, C-2) ppm.
(100) [M+], 237 (12). HR-EIMS: calcd. 266.0943, found 266.0946.
MS (EI): m/z (%) = 310 (100) [M+], 279 (22) [M+ – OCH3], 203
C17H14O3 (266 g/mol): calcd. C 76.68, H 5.30; found C 76.31, H (56). HR-EIMS: calcd. 310.1205, found 310.1207. C19H18O4 (310 g/
5.64.
mol): calcd. C 73.53, H 5.85; found C 73.23, H 5.82.
2-Benzylbenzo[f]chromen-3-one (6k-Ph):[26] Prepared according to
procedure C from 0.282 g (1.64 mmol) of 2-hydroxy-naphthalene-
1-carbaldehyde (1k), 0.227 g (1.64 mmol) of K2CO3, 0.542 g
(4.10 mmol) of (E)-cinnamaldehyde (5b) and 0.364 g (1.64 mmol)
of dimethyl 1,3-dimethylimidazolium phosphate in 3 mL of tolu-
ene. Purification of the crude product by column chromatography
(silica gel, 2.5ϫ20 cm, pent/Et2O, 4:1 and then cHex/EtOAc, 5:1)
yielded the title compound (0.183 g, 39%) as colourless solid; m.p.
5-Methoxy-3-(4-methoxybenzyl)-7-methylchromen-2-one (6d-p-anis-
yl): Prepared according to procedure C from 0.200 g (1.20 mmol)
of 2-hydroxy-6-methoxy-4-methylbenzaldehyde (1d), 0.166 g
(1.20 mmol) of K2CO3, 0.487 g (3.00 mmol) of (E)-4-methoxycin-
namaldehyde (5d) and 0.267 g (1.20 mmol) of dimethyl 1,3-dimeth-
ylimidazolium phosphate in 3 mL of toluene. Purification of the
crude product by column chromatography (silica gel, 2.5ϫ20 cm,
cHex/EtOAc, 5:1) yielded the title compound (0.149 g, 40%) as
colourless solid; m.p. 140–143 °C. Rf (cHex/EtOAc, 5:1) = 0.20. IR
158–161 °C. R (cHex/EtOAc, 5:1) = 0.27. IR (KBr): ν = 1714 (s,
˜
f
1
(KBr): ν = 1706 (s, νC=O) cm–1. H NMR (400 MHz, CDCl ): δ
νC=O) cm–1. 1H NMR (300 MHz, CDCl3): δ = 4.01 (d, 4J =
˜
3
3
= 2.40 (s, 3 H, CH3), 3.80 (br. s, 5 H, CH2, OCH3), 3.86 (s, 3 H,
0.8 Hz, 2 H, CH2), 7.28–7.41 (m, 5 H), 7.45 (d, J = 9.1 Hz, 1 H,
4
3
OCH3), 6.48 (s, 1 H, C6-H), 6.71 (s, 1 H, C8-H), 6.85–6.88 (m, 2
C10-H), 7.50–7.64 (m, 2 H), 7.88 (dd, J = 1.1 Hz, J = 8.1 Hz, 1
4
H), 7.92 (d, J = 9.1 Hz, 1 H, C9-H), 8.05 (d, 3J = 8.3 Hz, 1 H),
3
H, 2ϫC-Hbenzyl), 7.20–7.24 (m, 2 H, 2ϫC-Hbenzyl), 7.69 (d, J =
0.5 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.4 (+,
CH3), 35.9 (-, CH2), 55.3 (+, OCH3), 55.8 (+, OCH3), 106.2 (+, C-
8), 107.9 (q, C-4a), 109.1 (+, C-6), 114.1 (+, 2ϫCbenzyl), 126.3 (q,
C-3), 130.3 (+, 2ϫCbenzyl), 130.4 (q, Cbenzyl), 134.4 (+, C-4), 142.5
(q, C-7), 154.2 (q, C-8a), 155.4 (q, C-OMe), 158.3 (q, C-OMe),
162.1 (q, C-2) ppm. MS (EI): m/z (%) = 310 (76) [M+], 296 (72),
134 (100). HR-EIMS: calcd. 310.1205, found 310.1206. C19H18O4
(310 g/mol): calcd. C 73.53, H 5.85; found C 73.54, H 5.82.
8.10 (br. s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 37.0
(-, CH2), 113.4 (q, C-4a), 116.8 (+), 125.9 (+), 126.9 (+), 127.9
(+), 128.9 (+), 128.5 (q), 128.9 (+, 2ϫCbenzyl), 129.0 (+), 129.4 (+,
2ϫCbenzyl), 130.3 (q), 132.3 (+), 135.2 (+), 137.9 (q), 152.6 (q, C-
10a), 161.8 (q, C-2) ppm. MS (EI): m/z (%) = 286 (100) [M+], 257
(28), 181 (16). HR-EIMS: calcd. 286.0994, found 286.0992.
3-Benzyl-5-isopropyl-8-methylchromen-2-one (6n-Ph): Prepared ac-
cording to procedure C from 0.214 g (1.20 mmol) of 2-hydroxy-6-
isopropyl-3-methylbenzaldehyde (1n), 0.166 g (1.20 mmol) of
K2CO3, 0.396 g (3.00 mmol) of (E)-cinnamaldehyde (5b) and
0.267 g (1.20 mmol) of dimethyl 1,3-dimethylimidazolium phos-
phate in 3 mL of toluene. Purification of the crude product by col-
umn chromatography (silica gel, 2.5ϫ20 cm, cHex/EtOAc, 5:1)
yielded the title compound (0.211 g, 60%) as colourless solid; m.p.
3-(But-2-enyl)-5-methoxy-7-methylchromen-2-one (6d-butenyl): Pre-
pared according to procedure C from 0.200 g (1.20 mmol) of
2-hydroxy-6-methoxy-4-methylbenzaldehyde
(1d),
0.166 g
(1.20 mmol) of K2CO3, 0.288 g (3.00 mmol) of (2E,4E)-hexa-2,4-
dienal (5e) and 0.267 g (1.20 mmol) of dimethyl 1,3-dimethylimid-
azolium phosphate in 3 mL of toluene. Purification of the crude
product by column chromatography (silica gel, 2.5ϫ20 cm, pent/
Et2O, 4:1 and then cHex/EtOAc, 5:1) yielded a mixture of E/Z
isomers of the title compound (0.063 g, 21%) as light yellow solid;
83–86 °C. R (cHex/EtOAc, 5:1) = 0.41. IR (KBr): ν = 1718 (s,
˜
f
νC=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.21 (d, 3J =
3
6.9 Hz, 6 H, 2ϫCH3), 2.40 (s, 3 H, CH3), 3.19 (sept, J = 6.9 Hz,
m.p. 140–144 °C. R (cHex/EtOAc, 5:1) = 0.34. IR (KBr): ν = 1715
˜
1 H, Caliph-H), 3.92 (br. s, 1 H, CH2), 7.04 (d, 3J = 7.8 Hz, 1 H,
C6-H), 7.24–7.34 (m, 6 H, C7-H, 5ϫC-Hbenzyl), 7.63 (br. s, 1 H,
C4-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.4 (+, CH3), 23.5
(+, 2ϫCH3), 28.4 (+, CH), 36.9 (-, CH2), 116.7 (q, C-4a), 120.1
(+, C-6), 123.4 (q, C-3), 126.8 (+), 128.0 (q, C-8), 128.7 (+,
2ϫCbenzyl), 129.2 (+, 2ϫCbenzyl), 132.1 (+), 136.3 (+, C-4), 138.2
(q), 143.5 (q, C-5), 152.0 (q, C-8a), 161.6 (q, C-2) ppm. MS (EI):
m/z (%) = 292 (100) [M+], 277 (52) [M+ – OCH3]. HR-EIMS: calcd.
292.1463, found 292.1469. C20H20O2 (292 g/mol): calcd. C 82.16,
H 6.89; found C 81.94, H 7.01.
f
(s, νC=O) cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.69–1.73 (m, 3
H, 2ϫCH3 E/Z), 2.40 (s, 3 H, C7-CH3), 3.22, 3.29 (2ϫd, 3J = 4.4,
3J = 7.2 Hz, 2 H, CH2 E/Z), 3.89, 3.90 (2ϫs, 3 H, CH3, E/Z),
5.55–5.66, 5.70–5.77 (2ϫm, 2 H, CH=CH E/Z), 6.50 (br. s, 1 H,
C6-H), 6.72 (d, 4J = 0.6 Hz, 1 H, C8-H), 7.79 (d, 4J = 0.5 Hz, 1
H, C4-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 12.9, 18.0 (+,
2ϫCH3 E/Z), 22.4 (+, Ar-CH3), 27.8, 33.6 (–, 2ϫCH2 E/Z), 55.9
(+, OCH3), 106.2 (+, C-8), 107.9 (–, C-4a), 109.1, 109.2 (+, 2ϫC-
6 E/Z), 125.2, 125.58 (–, 2ϫC-3 E/Z), 125.63, 126.7 (+, 2ϫCH E/
Z), 127.3, 128.4 (+, 2ϫCH E/Z), 133.4, 133.8 (+, 2ϫC-4 E/Z),
5-Methoxy-3-(2-methoxybenzyl)-7-methylchromen-2-one (6d-o-anis- 142.27, 142.29 (q, 2ϫC-7 E/Z), 154.1, 154.2 (q, 2ϫC8a E/Z),
yl): Prepared according to procedure C from 0.200 g (1.20 mmol)
of 2-hydroxy-6-methoxy-4-methylbenzaldehyde (1d), 0.166 g
(1.20 mmol) of K2CO3, 0.487 g (3.00 mmol) of (E)-2-methoxycin-
155.4 (q, C-5), 162.1, 162.3 (q, 2ϫC-2 E/Z) ppm. MS (EI): m/z
(%) = 244 (100) [M+], 229 (24) [M+ – CH3], 215 (18), 203 (52), 201
(18). HR-EIMS: calcd. 244.1099, found 244.1104.
Eur. J. Org. Chem. 2007, 943–952
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
951

J. Toräng, S. Vanderheiden, M. Nieger, S. Bräse
FULL PAPER
8877; f) J. Read de Alaniz, T. Rovis, J. Am. Chem. Soc. 2005,
127, 6284–6289; g) Q. Liu, T. Rovis, J. Am. Chem. Soc. 2006,
128, 2552–2553.
Acknowledgments
We wish to thank BASF AG for the generous supply of various
ionic liquids, Dr. Klaus Massonne (BASF AG) and Dr. Marc
Uerdingen (Solvent Innovation, Cologne) for fruitful discussions
and the Deutsche Forschungsgemeinschaft (DFG) (Graduierten-
kolleg 804) for financial support. We thank the SFB 624 and the
Chemistry Department at the University of Bonn for providing the
infrastructure of the X-ray determination. We thank Prof. Dr.
Clemens Richert (University of Karlsruhe) and his group for giving
us the possibility to use the microwave instrument.
[6] C. Burstein, F. Glorius, Angew. Chem. Int. Ed. 2004, 43, 6205–
6208.
[7] S. S. Sohn, E. L. Rosen, J. W. Bode, J. Am. Chem. Soc. 2004,
126, 14370–14371.
[8] C. Burstein, S. Tschan, X. Xie, F. Glorius, Synthesis 2006,
2418–2439.
[9] V. Nair, S. Vellalath, M. Poonoth, R. Mohan, E. Suresh, Org.
Lett. 2006, 8, 507–509.
[10] M. He, J. W. Bode, Org. Lett. 2005, 7, 3131–3134.
[11] A. Chan, K. A. Scheidt, Org. Lett. 2005, 7, 905–908.
[12] a) I. Kostova, Curr. Med. Chem. Anti-Cancer Agents 2005, 5,
29–46; b) J. M. Campagne, Y. Six, Science Synth. 2004, 26,
989–1044; c) F. Borges, F. Roleira, N. Milhazes, L. Santana, E.
Uriarte, Curr. Med. Chem. 2005, 12, 887–916.
[1] For reviews on N-heterocyclic carbenes in organometallic catal-
ysis see: a) V. César, S. Bellemin-Laponnaz, L. H. Gade, Chem.
Soc. Rev. 2004, 33, 619–636; b) M. C. Perry, K. Burgess, Tetra-
hedron: Asymmetry 2003, 14, 951–961; c) W. A. Herrmann, An-
gew. Chem. Int. Ed. 2002, 41, 1290–1309.
[13] W. H. Perkin, J. Chem. Soc. 1875, 28, 11.
[14] L. A. Singer, N. P. Kong, J. Am. Chem. Soc. 1966, 88, 5213–
5219.
[2] For reviews on N-heterocyclic carbenes in organometallic catal-
ysis see: a) K. Zeitler, Angew. Chem. Int. Ed. 2005, 44, 7506–
7510; b) D. Enders, T. Balensiefer, Acc. Chem. Res. 2004, 37,
534–541; c) J. S. Johnson, Angew. Chem. Int. Ed. 2004, 43,
1326–1328.
[3] For review on transesterification/acylation reactions see: a)
G. A. Grasa, R. Singh, S. P. Nolan, Synthesis 2004, 971–985.
For reports on N-heterocyclic carbene-catalyzed transesterifi-
cation reactions see: b) G. A. Grasa, R. M. Kissling, S. P. No-
lan, Org. Lett. 2002, 4, 3583–3586; c) G. W. Nyce, J. A. Lam-
boy, E. F. Connor, R. M. Waymouth, J. L. Hedrick, Org. Lett.
2002, 4, 3587–3590; d) G. A. Grasa, T. Güveli, R. Singh, S. P.
Nolan, J. Org. Chem. 2003, 68, 2812–2819; e) R. Singh, R. M.
Kissling, M.-A. Letellier, S. P. Nolan, J. Org. Chem. 2004, 69,
209–212; f) R. Singh, S. P. Nolan, Chem. Commun. 2005, 5456–
5458.
[15] a) B. Lesch, J. Toräng, S. Vanderheiden, S. Bräse, Adv. Synth.
Catal. 2005, 347, 555–562; b) B. Lesch, J. Toräng, M. Nieger,
S. Bräse, Synthesis 2005, 1888–1900.
[16] The screening included the following ionic liquids: ethyl 1,3-
dimethylimidazolium sulfate, 1-ethyl-3-methylimidazolium hy-
drogen sulfate, 1-ethyl-3-methylimidazolium acetate, 1-ethyl-3-
methylimidazolium thiocyanate, AMMOENG 100, AMMO-
ENG 112 and AMMOENG 102.
[17] For an introduction to microwave-assisted organic chemistry
see: a) C. O. Kappe, A. Stadler, in Methods and principles in
medicinal chemistry: Microwaves in Organic and Medicinal
Chemistry (Eds.: R. Mannhold, H. Kubinyi, G. Folkers),
Wiley-VCH, Weinheim, 2005, vol. 25; b) C. O. Kappe, D. Dal-
linger, Nat. Rev. Drug Discovery 2006, 5, 51–63.
[18] S. S. Sohn, J. W. Bode, Org. Lett. 2005, 7, 3873–3876.
[19] L. F. Tietze, Chem. Rev. 1996, 96, 115–136.
[20] G. A. Cartwright, H. McNab, J. Chem. Res. 1997, 296–297.
[21] K. Sunitha, K. K. Balasubramanian, J. Org. Chem. 1985, 50,
1530–1531.
[4] For reports on carbene-catalyzed benzoin reactions see: a) D.
Enders, U. Kallfass, Angew. Chem. Int. Ed. 2002, 41, 1743–
1745; b) Y. Hachisu, J. W. Bode, K. Suzuki, J. Am. Chem. Soc.
2003, 125, 8432–8433; c) D. Enders, O. Niemeier, Synlett 2004, [22] P. T. Kaye, M. A. Musa, Synth. Commun. 2003, 33, 1755–1770.
2111–2114; d) Y. Hachisu, J. W. Bode, K. Suzuki, Adv. Synth.
Catal. 2004, 346, 1097–1100; e) D. Enders, O. Niemeier, T. Ba-
lensiefer, Angew. Chem. Int. Ed. 2006, 45, 1463–1467.
[23] R. G. Harvey, C. Cortez, T. P. Ananthanarayan, S. Schmolka,
J. Org. Chem. 1988, 53, 3936–3943.
[24] A. K. Awasthi, R. S. Tewari, Synthesis 1986, 1061–1062.
[25] N. Nirmala, V. Gore, G. Vinayak, R. S. Mali, A. C. Ranade,
Synth. Commun. 1989, 19, 1899–1910.
[26] M. Black, J. I. G. Cadogan, H. McNab, A. D. MacPherson,
V. P. Roddam, C. Smith, H. R. Swenson, J. Chem. Soc., Perkin
Trans. 1 1997, 2483–2493.
[5] For reports on carbene-catalyzed Stetter reactions see: a) R. U.
Braun, K. Zeitler, T. J. J. Müller, Org. Lett. 2001, 3, 3297–3300;
b) M. S. Kerr, J. Read de Alaniz, T. Rovis, J. Am. Chem. Soc.
2002, 124, 10298–10299; c) A. E. Mattson, A. R. Bharadwaj,
K. A. Scheidt, J. Am. Chem. Soc. 2004, 126, 2314–2315; d)
A. R. Bharadwaj, K. A. Scheidt, Org. Lett. 2004, 6, 2465–2468;
e) M. S. Kerr, T. Rovis, J. Am. Chem. Soc. 2004, 126, 8876–
Received: August 16, 2006
Published Online: December 15, 2006
952
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 943–952