Gold(III) Chloride-Catalyzed Addition Reactions of Electron-Rich Arenes to Methyl Vinyl Ketone

Article abstract of DOI:10.1002/adsc.200303098

For the reaction of α,β-unsaturated ketones with electron-rich arenes catalyzed by gold(III) chloride both, a Friedel-Crafts-type mechanism and an initial metallation, are evaluated. Gold(III) chloride has proven to be an efficient catalyst under very mod

Full text of DOI:10.1002/adsc.200303098

FULL PAPERS
Gold(III) Chloride-Catalyzed Addition Reactions of Electron-
Rich Arenes to Methyl Vinyl Ketone
Gerald Dyker,a,* Enrico Muth,a A. Stephen K. Hashmi,b,* Li Dingb
a
Department ofChemistry, Ruhr-University Bochum, Universit‰tsstrasse 150, 44780 Bochum, Germany
Fax: ( ‡ 49)-234-32-14353, e-mail gerald.dyker@ruhr-uni-bochum.de
b
Institut f¸r Organische Chemie, Universit‰t Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: ( ‡ 49)-711-685-4321, e-mail hashmi@hashmi.de
Received: May 22, 2003; Accepted: August 8, 2003
Abstract: For the reaction of a,b-unsaturated ketones sterically demanding products HBF4 turned out to be
with electron-rich arenes catalyzed by gold(III) the superior catalyst.
chloride both, a Friedel Crafts-type mechanism and
an initial metallation, are evaluated. Gold(III) chlor-
ide has proven to be an efficient catalyst under very Keywords: acids; aromatic substitution; gold; homo-
moderate reaction conditions, however, in the case of geneous catalysis; Lewis acids; Michael acceptors
Introduction
C/C-bond forming processes under CH-activation at
arenes are ofgeneral preparative interest. Besides the
classical Friedel Crafts reactions transition metal-cata-
lyzed methods featuring outstanding regio- or even
stereoselectivities have emerged in recent years. In the
case ofcoupling reactions with a,b-unsaturated carbon-
yl compounds two general mechanistic pathways can be
distinguished: the transition metal either works as a
Lewis acid, thus increasing the electrophilicity ofthe
carbonyl compound (regarded as a Friedel Crafts-type
process), or a direct metallation ofthe arene takes place.
In the latter case C/C-bond formation subsequently
proceeds by a carbometallation ofthe a,b-unsaturated
carbonyl compounds, a process that might be classified
as a case ofMichael addition reaction.
Typical examples are presented in Scheme 1: in the
Pd-catalyzed vinylation of2-methylfuran 1 according to
Tsuji et al.[1] the heterocycle is metallated in the first
reaction step; a carbopalladation followed by b-hydride
elimination leads to the formation of product 3. In this
case the peracid ester is a necessary reagent for the
crucial regeneration ofthe active Pd(II) catalyst rfom
Pd(0). For the formation of adduct 6 the authors also
favor a mechanism with an initial metallation;[2] how-
Scheme 1. Friedel Crafts-type and Michael-type addition
reactions ofelectron-rich arenes to a,b-unsaturated carbonyl
compounds.
ever, in our opinion the alternative Friedel Crafts-type known as a very active catalyst for various C/C-bond and
mechanism under these strongly acidic conditions (tri- C/heteroatom-bond forming processes.[4]
fluoroacetic acid as solvent) is not strictly ruled out by
the experiments. For the enantioselective formation of 9
it is clear that the chiral Cu catalyst (with a bisoxazoline Results and Discussion
ligand) works as a Lewis acid activating the olefin 8.[3]
Related reactions of 1 with MVK used either copper[9a] We found that gold(III) chloride indeed nicely catalyzes
or gold catalysts.[4a] Recently, gold(III) chloride became the addition of2-methylfuran 1 to methyl vinyl ketone
Adv. Synth. Catal. 2003, 345, 1247 1252
DOI: 10.1002/adsc.200303098
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1247

Gerald Dyker et al.
FULL PAPERS
(MVK), a clean and fast reaction with a required
amount ofcatalyst ofabout 1% (Table 1, entry 1).
Monitoring the conversion by 1H NMR proved an
essentially quantitative conversion, the lower isolated
yields are caused by the work-up due to the relatively
high volatility ofthe product. NMR experiments gave
hints for a direct interaction of gold(III) chloride with 2-
methylfuran 1. When one equivalent ofAuCl was
3
added to a solution of 1 in acetonitrile, an immediate
reaction took place. The resonance ofthe proton at the
5-position of the furan ring disappeared and for the two
resonances ofthe hydrogen atoms at the 3- and 4-
positions only broad signals were observed. Upon
standing for a longer time in the absence of MVK the
spectra finally only showed very broad signals of
undefined material. On the other hand the addition of
one equivalent ofgold(III) chloride to an acetonitrile
solution ofMVK caused no change in the 1H NMR
spectrum. The gold(I) complexes PEt3AuCl and
THTAuCl (THTˆ tetrahydrothiophene) were initially
inactive in the reactionof 1with MVK, after the addition
ofone equivalent ofAgBF
(the latter alone was
4
inactive) an 80% conversion was observed in the first
case and a 90% conversion in the second (entries 2 and
3). This led to the initial working hypothesis that an
electrophilic CH-activation might be the crucial reac-
tion step.
Scheme 2. Substrates and products ofthe addition reactions
ofmethyl vinyl ketone (MVK) to electron-rich arenes.
However, in the literature it was known that 14 can be
prepared from 1 and MVK in SO2 or with HCl as a
catalyst.[5] Further experiments with HCl in acetonitrile course rather uneconomically with a significant amount
prove that this clearly Br˘nsted acidic catalyst also of4-chlorobutan-2-one as byproduct. Also ofr the
formed 14 in a fast reaction, but only 50% conversion coupling reaction with the somewhat acid sensitive
were reached and 4-chlorobutan-2-one[6] was formed as azulenes 10 and 11 AuCl3 is by far the superior catalyst:
a side product (entry 4). The latter addition ofHCl is a
because ofthe moderate reaction conditions, no sub-
competing reaction that consumes the catalyst and thus sequent decomposition occurs when the work-up is
circumvents a complete conversion. This was further delayed. In contrast, with HCl as catalyst it is crucial to
supported by the reaction ofMVK with a sub-stoichio-
interrupt the reaction after just two minutes by adsorp-
metric amount ofAlCl 3 which only led to 4-chlorobutan- tive filtration through a pad of silica.
2-one.[7] Since this addition should completely be sup-
Starting from 1,3-dimethoxybenzene 7 an excellent
pressed by a non-nucleophilic counterion, we then yield ofthe double addition product 17 is obtained with
tested p-TsOH which indeed allowed a fast and 1% ofAuCl 3 as catalyst (entry 17). Again, with a large
complete conversion (entry 5) similar to AuCl3. The excess ofMVK and one equivalent ofHCl a comparable
only differences were small amounts of side products yield ofthe ifnal product can be achieved (entry 18).
visible in the crude spectra ofthe p-TsOH-catalyzed Most interestingly, the AuCl3-catalyzed reaction with
reaction.
1,3,5-trimethoxybenzene (12) stops at the stage ofthe
Then various electron-rich arenes were tested for the mono addition product 19 with tremendous selectivity
addition reactions to MVK as model compound: (entry 19). Obviously the reaction with this catalyst is
H[AuCl4] and dilute hydrochloric acid were chosen for rather sensitive against steric hindrance. With HCl as
this comparison, since the hydrolysis products ofAuCl 3
the similar H[AuCl3OH] and ofcourse HCl are serious
catalyst also the double addition product 18 is accessible
(entries 20 and 21). HBF4 applied as 50% aqueous
candidates for active Br˘nsted acidic catalysts under the solution in one equivalent turned out to be even more
reaction conditions. reactive, producing 18 in excellent yield. In addition, this
In the case of2-methylfuran 1 both HAuCl4 and HCl catalyst is also superior to HCl because ofthe non-
(entries 4 10) proved to be much less effective than nucleophilic counterion, thus avoiding by-products.
AuCl3. However, under forced reaction conditions
equivalent ofHCl and MVK in a large excess as solvent
1
(Warning! Do not apply HBF4 in this reaction without
enough additional solvent: a complete clean-up ofthe
a comparable yield of 14 can be achieved, although of hood would be the least harmful consequence of the
1248
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 1247 1252

Addition Reactions ofElectron-Rich Arenes to Methyl Vinyl Ketone
FULL PAPERS
Table 1. Results ofthe addition reactions ofmethyl vinyl ketone (MVK) to electron-rich arenes at room temperature.
[a]
Entry
Arene
Equivs. ofMVK
Catalyst (mol %)
Solvent[b]
Reaction Time
Products (yield)[c]
1
1
1
1
1
1
1
1
1
1
1
1
1
AuCl3 (1%)
PEt3AuCl/AgBF4 (1%)
THTAuCl/AgBF4 (1%)
HCl (30%)
p-TsOH (3%)
HAuCl4 (1%)
HAuCl4 (1%)
HCl (5%)
HCl (100%)
HCl (100%)
AuCl3 (1%)
HCl (5%)
HCl (100%)
AuCl3 (1%)
HCl (5%)
HCl (100%)
AuCl3 (1%)
HCl (100%)
AuCl3 (1%)
HCl (50%)
HCl (100%)
HBF4 (100%)
AuCl3 (1%)
HCl (100%)
HBF4 (100%)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
neat
MeCN
MeCN
neat
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
40 min
1 d
1 d
1 h
1 h
14 (80 90%)
14 (80%)
14 (90%)
14 (50%)
14 (90%)
2[d]
3[d]
4[d]
5[d]
6
1
10
100
10
10
100
4
4
10
2
2
10
4
100
2
10
100
100
4
40 min
40 min
40 min
40 min
40 min
2 min 3 d
2 min
2 min
2 min
2 min
2 min
1 d
40 min
1 d
40 min
40 min
40 min
1 d
14 (10 15%)
14 (10 15%)
14 (40 50%)
14 (40 50%)
14 (80 90%)
15 (50 55%)
15 (45 50%)
15 (0%)
16 (50 55%)
16 (45 50%)
16 (0%)
17 (90 95%)
17 (90 95%)
18 (0%), 19 (99%)
18 ( < 5%), 19 (95%)
18 (65%), 19 (35%)
18 (95%), 19 ( < 5%)
20 (0%)
7
8
9
1
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
10
10
10
11
11
11
7
7
12
12
12
12
13
13
13
100
100
40 min
40 min
20 (5%)
20 (40 50%)
[a]
HCl was applied as 33% aqueous solution and HBF4 as 60% aqueous solution.
In all cases with MeCN as solvent the concentration was 0.5 mmol arene/mL solvent.
in general each reaction was performed 2 4 times, therefore a range of reproducible isolated yields is given.
NMR test tube experiments.
Plus 25% 4-chlorobutan-2-one as by-product.
[b]
[c]
[d]
[e]
uncontrollable reaction which then starts). With 1,2,3- that the reaction with cyclopentenone was also highly
trimethoxybenzene 13 aqueous HBF4 was the only selective while with cyclohexenone side-products could
catalyst tested which produced acceptable amounts of also be detected. Again literature known methods using
the addition product 20. No reaction was observed with copper catalysts deliver only 53 55% yield.[9]
AuCl3 in this case (entry 23); this result is in accord with
the influence of steric hindrance pointed out above.
Also the limits ofHBF as catalyst were tested: with Conclusion
4
ferrocene a small yield of the mono-addition product 21
was obtained (5 10%), and no reaction was observed at The experiments clearly show that not only AuCl3 but
room temperature with 1,4-dimethoxybenzene (4), under appropriate conditions also Br˘nsted acids with a
pyrene and tetrakis(4-methoxyphenyl)porphyrin. The non-nucleophilic counterion can selectively catalyze the
latter is also true for AuCl3 as the catalyst and 4 or even reactions between Michael acceptors and electron-rich
less electron-rich arenes like anisole, toluene and aromatic systems. This suggests that with the gold
acceptor-substituted arenes like acetophenone.
catalyst in the presence ofwater a Br˘nsted acid with
In addition, some other Michael acceptors were an aurate counterion might be the active species, too. On
tested: AuCl3-catalysis ofthe addition of 1 to mesityl the other hand the different selectivities observed with
oxide delivered 75% of 22 in a slow but selective Br˘nsted acids and gold catalysts can either be ex-
reaction (Table 2, entry 1). This is superior to published plained by specific acid catalysis or by a direct partic-
methods which yield only about 34% of 22.[8] The ipation ofthe metal. Thus these experiments do not rule
transoid Michael acceptors cyclopentenone and cyclo- out a CH-activation ofthe aromatic system by the gold
hexenone also reacted smoothly (Table 2, entries 2 and catalysts, but they show how much care in the interpre-
1
3). The H NMR spectra ofthe crude material proved
tation ofthe results obtained with transition metals in
Adv. Synth. Catal. 2003, 345, 1247 1252
asc.wiley-vch.de
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1249

Gerald Dyker et al.
FULL PAPERS
Table 2. AuCl3-catalyzed reaction ofdiferent a,b-unsaturated ketones with 1.
Entry
Ketone
Catalyst (mol %)
Solvent
Reaction Time
Products (yield)
1
2
3
Mesityl oxide
cyclopentenone
cyclohexenone
AuCl3 (0.5%)
AuCl3 (1%)
AuCl3 (1%)
MeCN
MeCN
MeCN
14 d
1 d
1 d
22 (75%)
23 (87%)
24 (74%)
(10 mmol, 1 mol %) THTAuCl were added. No reaction was
observed after 6 hours in the 1H NMR. Then 1.95 mg
(10.0 mmol, 1 mol %) AgBF4 were added. After 1 d the
1H NMR showed a highly selective conversion to 14, but only
90% conversion could be reached.
d) Reaction of 1 with MVK and HCl: 82.1 mg (1.00 mmol) 1
and 70.0 mg (1.00 mmol) MVK in 500 mL acetonitrile-d3 were
placed in an NMR tube and 11.0 mg (303 mmol, 30 mol %) HCl
(from 37% HCl in water) were added. After 1 h the 1H NMR
showed a 50% conversion to 14, but in addition 25% of4-
chlorobutan-2-one[10] had been formed and the remaining
starting material did not react any further.
e) Reaction of 1 with MVK and AlCl3: 82.1 mg (1.00 mmol) 1
and 70.0 mg (1.00 mmol) MVK in 500 mL acetonitrile-d3 were
placed in an NMR tube and 44.4 mg (333 mmol) AlCl3 were
added. After 1 d the 1H NMR showed starting material and a
40% conversion to 4-chlorobutan-2-one.[6] No 14 could be
detected.
acidic media is necessary. The mechanism ofthe gold-
catalyzed reaction is under further investigation, the
preparation ofaurated electron-rich arenes and the
investigation oftheir reaction with MVK is the major
challenge in this field.
However, AuCl3 as well as aqueous HCl and HBF4
represent a very useful set of acidic catalysts for
Michael-type addition reactions, although they are not
the only ones. They give a range ofreactivities rfom
moderate to very high and regularly show different
selectivities.
Experimental Section
f) Reaction of
1 with MVK and p-TsOH: 82.1 mg
General Remarks
(1.00 mmol) 1 and 70.0 mg (1.00 mmol) MVK in 500 mL
acetonitrile-d3 were placed in an NMR tube and 5.00 mg
(28.6 mmol, 3 mol%) p-TsOH ¥ H2O were added. After 1 h the
1H NMR showed a complete conversion to 14, but in addition
small amounts of different side-products were visible in the
crude NMR.
M.p. (uncorrected): Reichert Thermovar. IR: Perkin Elmer
841. NMR: Bruker DRX 400; H NMR spectra (400 MHz)
1
were recorded in CDCl3 or acetonitrile-d3 with TMS as the
internal standard. 13C NMR spectra (100.6 MHz) were meas-
ured by using CDCl3 as the solvent and the internal standard.
MS: MAT 700 ITD (70 eV) and Varian MAT 311 A. For
analytical TLC precoated plastic sheets ™POLYGRAM SIL G/
UV254∫ from ™Macherey-Nagel∫ were used. EA: Elementar/
Hanau Vario EL.
2. Preparative Reactions
1,3-Bis(3-oxobutyl)azulene (15):
A mixture of211 mg
(3.00 mmol) ofMVK, 950 mg ofacetonitrile and 300 mg
(10 mmol, 0.2 mol %) ofAuCl 3 was slowly added under argon to
a vigorously stirred solution of193 mg (1.50 mmol) ofazulene
(10) in 2 mL ofacetonitrile. After 1 d at room temperature the
reaction mixture was filtered through a small pad of silica (2 g)
with additional 5 mL ofacetonitrile as eluent. The solvent was
removed under vacuum at 508C (from 15 mbar to 0.2 mbar)
and the residue purified by flash chromatography on silica gel
(petroleum ether/tert-butyl methyl ether, 2:1; Rf ˆ 0.10).
Recrystallization from CH2Cl2/diethyl ether afforded 15 as
dark blue-green crystals; yield: 201 mg (50%), mp 638C; IR
1. NMR Test Tube Experiments
a) Reaction of 1 with MVK and AuCl3: 82.1 mg (1.00 mmol) 1
and 70.0 mg (1.00 mmol) MVK in 500 mL acetonitrile-d3 were
placed in an NMR tube and 3.03 mg (10 mmol, 1 mol %) AuCl3
were added. The 1H NMR showed a highly selective and
quantitative conversion to 14. The spectroscopic data of14
were known.[9]
b) Reaction of 1 with MVK and PEt3AuCl: 82.1 mg
(1.00 mmol) 1 and 70.0 mg (1.00 mmol) MVK in 500 mL
acetonitrile-d3 were placed in an NMR tube and 3.51 mg
(10 mmol, 1 mol %) PEt3AuCl were added. No reaction was
observed after 6 hours in the 1H NMR. Then 1.95 mg
(10.0 mmol, 1 mol %) AgBF4 were added. After 1 d the
1H NMR showed a highly selective conversion to 14, but only
80% conversion could be reached.
Ä
(KBr): n ˆ 3029 (m), 2928 (m), 2889 (m), 1971 (w), 1707 (s),
1568 (s), 1529 (w), 1516 (w), 1433 (m), 1409 (s), 1361 (s), 1320
(m), 1303 (w), 1267 (w), 1228 (w), 1175 (m), 1160 (m), 1132 (w),
1052 (w), 947 (w), 851 (w), 737 (s), 717 cmÀ1 (w); UV
(acetonitrile, c ˆ 1.04 ¥ 10À4 mol/L): lmax (log e) ˆ 202 (3.98),
214 (3.98), 240 (4.12), 282 (4.64), 349 (3.60), 366 (3.47), 627 nm
(2.19); 1H NMR (CDCl3, 500 MHz): d ˆ 2.12 (s, 6H), 2.87 (m,
4H), 3.31 (m, 4H), 7.00 (t, J ˆ 9.9 Hz), 7.49 (t, J ˆ 9.9 Hz), 7.60
(s, 1H), 8.17 (d, J ˆ 9.9 Hz); 13C NMR (CDCl3, 125 MHz): d ˆ
c) Reaction of 1 with MVK and THTAuCl: 82.1 mg
(1.00 mmol) 1 and 70.0 mg (1.00 mmol) MVK in 500 mL
acetonitrile-d3 were placed in an NMR tube and 3.21 mg
1250
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 1247 1252

Addition Reactions ofElectron-Rich Arenes to Methyl Vinyl Ketone
21.17 (t), 30.11 (q), 45.16 (t), 121.12 (d), 127.12 (s), 133.07 (d),
FULL PAPERS
2,4-Bis(2-oxobutan-4-yl)-1,3,5-trimethoxybenzene (18): A
135.92 (s), 136.47 (d), 137.73 (d), 208.42 (s); MS (EI, 70 eV,
mixture of701 mg (10.0 mmol) ofMVK and 420 mg
(2.50 mmol) of 12 in 10 mL ofacetonitrile was cooled to 0 8C
under argon. A solution 1.76 g (10.0 mmol) of50% aqueous
HBF4 in 2 mL ofacetonitrile was added slowly under vigorous
stirring. After 40 min at room temperature the reaction
mixture was filtered through a small pad of silica (4 g) with
additional 10 mL ofacetonitrile as eluent. The solvent was
removed under vacuum at 508C (from 15 mbar to 0.2 mbar)
and the residue purified by flash chromatography on silica gel
(petroleum ether/tert-butyl methyl ether, 2:1; Rf ˆ 0.10).
Recrystallization from diethyl ether afforded 18 as colorless
crystals; yield: 732 mg (95%), mp 858C; IR (KBr): n ˆ 3411 (w,
br), 2940 (s, sh), 2841 (m, sh), 1712 (s), 1677 (w), 1605 (s), 1587
(s), 1487 (m, sh), 1454 (s), 1410 (s), 1364 (s), 1319 (s), 1285 (w),
1257 (w), 1219 (m), 1188 (s), 1163 (s), 1127 (s), 1105 (s), 1038
(s), 1026 (m), 953 (w), 879 (w), 809 (s), 691 (w), 653 cmÀ1 (w);
UV (acetonitrile, c ˆ 2.43 ¥ 10À4 mol/L): lmax (log e) ˆ 281 nm
(3.96); 1H NMR (CDCl3, 400 MHz): d ˆ 2.15 (s, 6H), 2.64 (m,
4H), 2.81 (m, 4H), 3.68 (s, 3H), 3.80 (s, 6H), 6.26 (s, 1H);
13C NMR (CDCl3, 100.6 MHz): d ˆ 18.03 (t), 29.45 (q), 43.67
(t), 55.31 (q), 61.65 (q), 91.32 (d), 114.33 (s), 156.96 (s), 157.49
(s), 208.95 (s); MS (EI, 70 eV, 558C): m/z (%) ˆ 310 (2), 309
‡
1058C): m/z (%) ˆ 269 (7), 268 (32, M ), 212 (15), 211 (100),
167 (17), 165 (8), 154 (29), 153 (14), 152 (11), 43 (7), 40 (6); anal.
calcd. for C18H20O2 (268.35 g/mol): C 80.57, H 7.51; found: C
80.68, H 7.49.
1,4-Dimethyl-7-(1-methylethyl)-3-(3-oxobutyl)-azulene
(16): A mixture of140 mg (2.00 mmol) ofMVK, 950 mg of
acetonitrile and 300 mg (10 mmol, 0.3 mol %) ofAuCl was
3
slowly added under argon to a vigorously stirred solution of
198 mg (1.00 mmol) guaiazulene (11) in 2 mL ofacetonitrile.
After 1 d at room temperature the reaction mixture was
filtered through a small pad of silica (2 g) with additional 5 mL
ofacetonitrile as eluent. The solvent was removed under
vacuum at 508C (from 15 mbar to 0.2 mbar) and the residue
purified by flash chromatography on silica gel (petroleum
ether/tert-butyl methyl ether, 2:1; Rf ˆ 0.50). Recrystallization
from CH2Cl2/diethyl ether afforded 16 as dark blue crystals;
Ä
yield: 148 mg (55%), mp 688C; IR (KBr): n ˆ 2961 (s), 2921(s),
2890 (s), 2295 (w), 1710 (s), 1601 (w), 1535 (m), 1445 (w), 1415
(m), 1400 (s), 1377 (m), 1355 (s), 1297 (w), 1264 (w), 1202 (w),
1180 (w), 1158 (s), 1091 (w), 1077 (w), 1054 (w), 1032 (w), 933
(w), 916 (w), 870 (w), 827 cmÀ1 (w); UV (acetonitrile, c ˆ 5.96 ¥
10À5 mol/L): lmax (log e) ˆ 219 (4.09), 248 (4.32), 288 (4.61), 305
(4.15, sh), 352 (3.72), 369 (3.64), 622 nm (2.56); 1H NMR
(CDCl3, 500 MHz): d ˆ 1.32 (d, J ˆ 6.9 Hz, 6H), 2.16 (s, 3H),
2.59 (s, 3H), 2.84 (m, 2H), 2.94 (s, 3H), 3.00 (sep, J ˆ 6.9 Hz,
1H), 3.49 (m, 2H), 6.81 (d, J ˆ 10.7 Hz, 1H), 7.24 (dd, J ˆ
‡
(11), 308 (60, M ), 251 (100), 58 (21), 43 (58).
2-(3-Oxobutyl)-1,3,5-trimethoxybenzene (19): A mixture of
420 mg (6.00 mmol) ofMVK, 950 mg ofacetonitrile and
300 mg (10 mmol, 0.3 mol %) ofAuCl 3 was slowly added under
argon to a vigorously stirred solution of138 mg (1.00 mmol)
1,3,5-trimethoxybenzene (12) in 2 mL ofacetonitrile. After 1 d
at room temperature the reaction mixture was filtered through
a small pad ofsilica (2 g) with additional 5 mL ofacetonitrile as
eluent. The solvent was removed under vacuum at 508C (from
15 mbar to 0.2 mbar) and the residue purified by flash
chromatography on silica gel (petroleum ether/tert-butyl
methyl ether, 2:1; Rf ˆ 0.27) to give 19 as colorless crystals;
yield: 237 mg (99.5%), mp 648C (Lit.[13] bp 140 1428C/0.1
4
4
10.7 Hz, J ˆ 2.1 Hz, 1H), 7.42 (s, 1H), 8.04 (d, J ˆ 2.1 Hz,
1H); 13C NMR (CDCl3, 125 MHz): d ˆ 12.88 (q), 24.59 (t),
25.33 (q), 26.86 (q), 30.12 (q), 37.65 (d), 47.03 (t), 124.32 (s),
126.23 (d), 126.60 (s), 132.19 (s), 133.41 (d), 134.76 (d), 137.61
(s), 138.90 (s), 139.11 (d), 145.08 (s), 208.37 (s); MS (EI, 70 eV,
‡
958C): m/z (%) ˆ 269 (7), 268 (33, M ), 212 (18), 211 (100), 196
(8), 195 (6), 181 (10), 165 (9); anal. calcd. for C19H24O (268.39 g/
mol): C 85.03, H 9.01; found: C 84.95, H 8.93.
1
1,3-Dimethoxy-4,6-bis(3-oxobutyl)benzene (17): A mixture
of420 mg (6.00 mmol) ofMVK, 950 mg ofacetonitrile and
300 mg (10 mmol, 0.3 mol %) ofAuCl 3 was slowly added under
argon to a vigorously stirred solution of138 mg (1.00 mmol)
1,3-dimethoxybenzene (7) in 2 mL ofacetonitrile. After 1 d at
room temperature the reaction mixture was filtered through a
small pad ofsilica (2 g) with additional 5 mL ofacetonitrile as
eluent. The solvent was removed under vacuum at 508C (from
15 mbar to 0.2 mbar) and the residue purified by flash
chromatography on silica gel (petroleum ether/tert-butyl
methyl ether, 2:1; Rf ˆ 0.10). Recrystallization from diethyl
ether afforded 17 as colorless crystals; yield: 265 mg (95%), mp
Torr); H NMR (CDCl3, 300 MHz): d ˆ 2.16 (s, 3H), 2.57 (m,
2H), 2.84 (m, 2H), 3.78 (s, 6H), 3.80 (s, 3H), 6.11 (s, 2H);
13C NMR (CDCl3, 125 MHz): d ˆ 17.53 (t), 29.54 (q), 43.60 (t),
55.31 (q), 55.57 (q), 90.51 (d), 109.58 (s), 158.71 (s), 159.55 (s),
209.63 (s); MS (EI, 70 eV, 808C): m/z (%) ˆ 239 (4), 238 (27,
‡
M ), 195 (5), 182 (11), 181 (100), 168 (5), 136 (10), 121 (17), 43
(5).
1-(3-Oxobutyl)-2,3,4-trimethoxybenzene (20): A mixture of
701 mg (10.0 mmol) ofMVK and 336 mg (2.00 mmol) of1,2,3-
trimethoxybenzene (13) in 10 mL ofacetonitrile was cooled to
08C under argon. A solution of1.76 g (10.0 mmol) of50%
aqueous HBF4 in 2 mL ofacetonitrile was added slowly under
vigorous stirring. After 40 min at room temperature the
reaction mixture was filtered through a small pad of silica
(4 g) with additional 10 mL ofacetonitrile as eluent. The
solvent was removed under vacuum at 508C (from 15 mbar to
0.2 mbar) and the residue purified by flash chromatography on
silica gel (petroleum ether/tert-butyl methyl ether, 2:1; Rf ˆ
0.22). Recrystallization from diethyl ether afforded 20 as
colorless crystals; yield: 229 mg (48%), mp 528C (Lit.[13] bp
Ä
578C; IR (KBr): n ˆ 3001 (m), 2939 (w), 1708 (s), 1614 (m),
1588 (w), 1515 (m), 1500 (s), 1460 (m), 1440 (s), 1405 (w), 1364
(m), 1304 (s), 1287 (w), 1263 (w), 1209 (s), 1193 (w), 1159 (s),
1114 (s), 1036 (s), 1029 (s), 841 cmÀ1 (w); UV (acetonitrile, c ˆ
2.19 ¥ 10À4 mol/L): lmax (log e) ˆ 201 (4.81), 230 (4.10, sh),
1
284 nm (3.76); H NMR (CDCl3, 300 MHz): d ˆ 2.13 (s, 6H),
2.68 (m, 4H), 2.77 (m, 4H), 3.81 (s, 6H), 6.40 (s, 1H), 6.86 (s, 1H);
13C NMR (CDCl3, 125 MHz): d ˆ 24.30 (t), 29.87 (q), 44.15 (t),
55.54 (q), 95.30 (d), 120.76 (s), 131.11 (d), 156.72 (s), 208.78 (s);
1
118 1208C/0.1 Torr); H NMR (CDCl3, 200 MHz): d ˆ 2.14
‡
MS (EI, 70 eV, 558C): m/z (%) ˆ 279 (8), 278 (40, M ), 222 (14),
(s), 2.72 (m, 2H), 2.80 (m, 2H), 3.83 (s, 3H), 3.86 (s, 3H), 3.88 (s,
221 (100), 77 (19), 163 (8), 151 (7), 149 (13), 147 (6), 91 (8), 43
(27), 40 (11); anal. calcd. for C16H22O4 (278.35 g/mol): C 69.04,
H 7.97; found: C 69.01, H 7.99.
3H), 6.59 (d, J ˆ 8.5 Hz, 1H), 6.82 (d, J ˆ 8.5 Hz, 1H); MS (EI,
‡
70 eV, 808C): m/z (%) ˆ 239 (4), 238 (27, M ), 192 (3), 181
(100), 167 (5), 134 (7), 125 (14), 43 (8).
Adv. Synth. Catal. 2003, 345, 1247 1252
asc.wiley-vch.de
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1251

Gerald Dyker et al.
FULL PAPERS
4-Ferrocenyl-2-butanone (21):
A
mixture of701 mg
[3] K. B. Jensen, J. Thorauge, R. G. Hazell, K. A. Jorgensen,
Angew. Chem. 2001, 113, 164 167; Angew. Chem. Int.
Ed. 2001, 40, 160 163.
(10.0 mmol) ofMVK and 372 mg (2.00 mmol) offerrocene in
10 mL ofacetonitrile was cooled to 0 8C under argon. A
solution of1.76 g (10.0 mmol) of50% aqueous HBF 4 in 2 mL
ofacetonitrile was added slowly under vigorous stirring. After
40 min at room temperature the reaction mixture was filtered
through a small pad ofsilica 4 g with additional 10 mL of
acetonitrile as eluent. The solvent was removed under vacuum
at 508C (from 15 mbar to 0.2 mbar) and the residue purified by
flash chromatography on silica gel (petroleum ether/tert-butyl
[4] A. S. K. Hashmi, L. Schwarz, J.-H. Choi, T. M. Frost,
Angew. Chem. 2000, 112, 2382 2385; Angew. Chem. Int.
Ed. 2000, 39, 2285 2288; A. S. K. Hashmi, T. M. Frost,
J. W. Bats, J. Am. Chem. Soc. 2000, 122, 11553 11554;
A. S. K. Hashmi, T. M. Frost, J. W. Bats, Org. Lett. 2001,
3, 3769 3771; A. S. K. Hashmi, T. M. Frost, J. W. Bats,
Catal. Today 2002, 72, 19 27; J. W. Dankwardt, Tetrahe-
dron Lett. 2001, 42, 5809 5812; N. Asao, K. Takahashi, S.
Lee, T. Kasahara, Y. Yamamoto, J. Am. Chem. Soc. 2002,
124, 12650 12651; A. Hoffmann-Rˆder, N. Krause, Org.
Lett. 2001, 3, 2537 2538.
ˆ
methyl ether, 2:1; Rf 0.25). Recrystallization from diethyl
ether afforded 21 as yellow-colored crystals; yield: 36 mg (7%),
1
mp 418C; H NMR (CDCl3, 200 MHz): d ˆ 2.15 (s, 3H), 2.63
(m, 4H), 4.07 (s, 4H), 4.12 (s, 5H). The spectroscopic data were
in accordance with the data in the literature.[14]
[5] K. Alder, C.-H. Schmidt, Chem.Ber. 1943, 76, 183 205.
[6] For the formation by the addition of HCl to MVK, see:
A. Treibs, Angew. Chem. 1948, 60, 289 297; J. Decombe,
C. R. Hebd. Seances Acad. Sci. 1936, 202, 1685 1687;
L. I. Smith, J. A. Sprung; J. Am. Chem. Soc. 1943, 65,
1276 1283.
4-(5-Methylfuran-2-yl)penten-2-one
(25.5 mmol) of 1 and 2.50 g (25.5 mmol) ofmesityl oxide in
10 mL ofacetonitrile were added 38 mg (0.5 mol %) ofAuCl .
(22):
To
2.09 g
3
The selective conversion was monitored by taking small
1
aliquots and measuring H NMR spectra. After 14 days the
solvent was removed under vacuum and the crude material was
purified by column chromatography on silica gel (hexanes/
ethyl acetate, 3:1) to afford 22; yield: 3.91 g (75%). The
spectroscopic data were in accordance with the literature
data.[8,9c,11]
[7] For the related reaction ofTiCl , see: T. Kataoka, H.
4
Kinoshita, T. Iwama, S.-i. Tsujiyama, T. Iwamura, S.-i.
Watanabe, O. Muraoka, G. Tanabe, Tetrahedron 2000, 56,
4725 4732.
3-(5-Methylfuran-2-yl)cyclopenten-1-one (23): To 1.18 g
(14.4 mmol) of 1 and 1.18 g (14.4 mmol) ofcyclopentenone
in 10 mL ofacetonitrile were added 43.7 mg (144 mmol,
[8] G. Dujardin, J.-M. Poirier, Bull. Soc. Chim. Fr. 1994, 131,
900 909.
[9] V. J. Bulbule, V. H. Deshpande, A. V. Bedekar, J. Chem.
Res. Synop. 2000, 5, 220 221; J.-M. Poirier, G. Dujardin,
Heterocycles 1987, 25, 399 407; G. Jenner, J. Rimmelin,
F. Antoni, S. Libs, E. Schleiffer, Bull. Soc. Chim. Fr. 1981,
2, 65 70.
[10] For spectroscopic data, see: P. Boudjouk, B.-K. Kim, B.-
H. Han, Synth. Commun. 1996, 26, 3479 3484; F.-E.
Chen, J.-D. Liu, H. Fu, Z.-Z. Peng, L.-Y. Shao, Synth.
Commun. 2000, 30, 2295 2299; T. Kataoka, H. Kinoshi-
ta, T. Iwama, S.-i. Tsujiyama, T. Iwamura, S.-i. Watanabe,
O. Muraoka, G. Tanabe, Tetrahedron 2000, 56, 4725
4731; T. Ibrahim, T. J. Grattan, J. S. Whitehurst, J.
Chem. Soc. Perkin Trans. 1 1990, 3317 3319; K. Gries-
baum, G. Kiesel, H. Mertens, P. Krieger-Beck, H. Henke,
Can. J. Chem. 1994, 72, 2198 2204; G. Just, D. Crosilla,
Can. J. Chem. 1980, 58, 2349 2357; B. M. Trost, R. A.
Kunz, J. Am. Chem. Soc. 1975, 97, 7152 7157; J.
1 mol %) ofAuCl . The selective conversion was monitored
3
by taking small aliquots and measuring 1H NMR spectra. After
1 day the solvent was removed under vacuum and the crude
material was purified by column chromatography on silica gel
using hexanes/ethyl acetate, 4:1 to afford 23; yield: 2.05 g
(87%). The spectroscopic data were in accordance with the
data in the literature.[8,9,12]
3-(5-Methylfuran-2-yl)cyclohexen-1-one (24): To 1.18 g
(14.4 mmol) of 1 and 1.34 g (14.4 mmol) ofcyclohexenone in
10 mL ofacetonitrile were added 43.7 mg (144 mmol, 1 mol %)
ofAuCl . The selective conversion was monitored by taking
3
small aliquots and measuring 1H NMR spectra. After 1 day the
solvent was removed under vacuum and the crude material was
purified by column chromatography on silica gel using
hexanes/ethyl acetate, 4:1 to afford 22; yield: 1.86 g (74%).
The spectroscopic data were in accordance with the data in the
literature.[8,9,12]
¬
Grignon, S. Fliszar, Can. J. Chem. 1974, 52, 3209 3217;
E. Brown, J. Touet, M. Ragault, Bull. Soc. Chim. Fr.
1972, 212 220; E. Rothstein, D. J. Stanbank, R. White-
ley, J. Chem. Soc. C 1968, 746 752; G. Fierz, J. F.
McGarrity, H. Dahn, Helv. Chim. Acta 1975, 58, 1058
1071; L. Simeral, G. E. Maciel, J. Phys. Chem. 1973, 77,
1590 1593.
Acknowledgements
Financial support of the Fonds der Chemischen Industrie and
the Deutsche Forschungsgemeinschaft (A.S.K.H.: Ha 1932/6
2) is gratefully acknowledged.
[11] W. Francke, W. Reith, Tetrahedron Lett. 1981, 22, 2029
2032.
[12] M. A. Tobias, J. Org. Chem. 1970, 35, 267 269.
[13] F. A. B. Aldous, B. C. Barrass, K. Brewster, D. A. Bux-
ton, D. M. Green, R. M. Pinder, P. Rich, M. Skeels, K. J.
Tutt, J. Med. Chem. 1974, 17, 1100 1111.
References and Notes
[1] J. Tsuji, H. Nagashima, Tetrahedron 1984, 40, 2699
2702.
[2] C. Jia, D. Piao, J. Oyamada, W. Lu, T. Kitamura, Y.
Fujiwara, Science 2000, 287, 1992 1995.
[14] H. Kono, M. Ishige, K. Sakai, M. Shiga, I. Motoyama, K.
Hata, Bull. Chem. Soc. Jpn. 1970, 43, 867 872.
1252
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 1247 1252