Coupling-isomerization synthesis of chalcones

Article abstract of DOI:10.1002/chem.200600530

The Sonogashira coupling of electron-deficient (hetero)aryl halides 1 and (hetero)aryl or alkenyl 1-propargyl alcohols 2 does not terminate at the stage of the expected internal propargyl alcohols, but rather gives rise to the formation of α,β-unsaturated ketones 3 with a variety of acceptor substituents. This new domino reaction, a coupling-isomerization reaction (CIR), can be rationalized as a sequence of rapid Pd/Cu-catalyzed alkynylation followed by a slow amine-base-catalyzed propargyl alcohol-enone isomerization. Performing the CIR in deuterated protic solvents or with a selectively deuterated propargyl alcohol revealed that the base-catalyzed isomerization step proceeds through a formal 1,3-H shift with minimal H/D exchange with the surrounding solvent. Additionally, ₁₉F NMR kinetic measurements on the isomerization step with the fluorinated propargyl alcohol 4r support the mechanistic rationale.

Full text of DOI:10.1002/chem.200600530

FULL PAPER
DOI: 10.1002/chem.200600530
Coupling–Isomerization Synthesis of Chalcones
Roland U. Braun, Markus Ansorge, and Thomas J. J. Müller*[a]
Dedicated to Professor Barry M. Trost on the occasion of his 65th birthday
Abstract: The Sonogashira coupling of
electron-deficient (hetero)aryl halides
1 and (hetero)aryl or alkenyl 1-prop-
argyl alcohols 2 does not terminate at
the stage of the expected internal prop-
argyl alcohols, but rather gives rise to
the formation of a,b-unsaturated ke-
tones 3 with a variety of acceptor sub-
stituents. This new domino reaction, a
coupling–isomerization reaction (CIR),
can be rationalized as a sequence of
rapid Pd/Cu-catalyzed alkynylation fol-
lowed by a slow amine-base-catalyzed
propargyl alcohol–enone isomerization.
Performing the CIR in deuterated
protic solvents or with a selectively
deuterated propargyl alcohol revealed
that the base-catalyzed isomerization
step proceeds through a formal 1,3-H
shift with minimal H/D exchange with
the surrounding solvent. Additionally,
19F NMR kinetic measurements on the
isomerization step with the fluorinated
propargyl alcohol 4r support the mech-
anistic rationale.
ꢀ
Keywords: C C coupling · domino
reactions
·
ketones
·
kinetics
·
synthetic methods
Introduction
In synthetic heterocyclic chemistry, as a consequence of
the bifunctional Michael system, 1,3-diaryl prop-2-en-1-ones
are important three-carbon building blocks. Among many
classes of five-, six-, and seven-membered heterocycles the
underlying principle is always the Michael addition–cyclo-
condensation sequence of chalcones and bifunctional nucle-
ophiles. Furthermore, as dienophiles and dipolarophiles,
chalcones can also participate in cycloadditions and furnish
in the case of 1,3-dipolar cycloadditions[11] with diazo al-
Chalcones, that is, 1,3-diaryl prop-2-en-1-ones, are an impor-
tant class of naturally occurring[1] and non-natural biologi-
cally active compounds. They cover a wide spectrum of
pharmacological activity[2] and their enormous potential
ranges from antibacterial, including antimycobacterial, anti-
fungal, antiviral, antiprotozoal, antioxidative, anti-inflamma-
tory, gastroprotective, to antineoplastic agents. A number of
these compounds has also proved to be highly active as anti-
plasmodial,[3] antiviral (e.g., by inhibition of HIV inte-
grase),[4] or antileishmania agents,[5] and as inhibitors of pul-
monary carcinogenesis.[6] Chalcones have also found applica-
tion in materials science. By virtue of [2p+2p] photocy-
cloaddition, some chalcones are photochromic in merocya-
nine-containing polymer matrices.[7] While 1-ferrocenyl 3-
biaryl propenones are novel types of nonlinear optical
(NLO) chromophores,[8] photorefractive polymers doped
with push/pull-substituted chalcones show remarkable elec-
trooptic responses,[9] and NLO properties of silylated chal-
cones in sol–gel matrices have been studied.[10]
AHCTREUNG
kanes pyrazolines,[12] with azides triazolines,[13] with nitrones
isoxazolidines,[14] with azomethinylides pyrrolidines,[15] and
with nitrile oxides isoxazolines.[16]
The standard synthesis of the important class of chalcones
is, as for many other a,b-unsaturated carbonyl compounds,
the aldol condensation.[17] Besides a Wittig–Horner access[18]
and the fragmentation of oxazolidines by alkylation, Hof-
mann elimination, and dimethylamine elimination,[19] also
stoichiometric organometallic processes such as the
vanadiumACHTREU(NG iii)-mediated oxidative coupling of aldehydes and
vinyl lithium or vinyl magnesium reagents[20] furnish chal-
cones. Another option is the isomerization of propargyl al-
cohols in the acid-catalyzed Meyer–Schuster rearrange-
ment.[21]
[a] Dr. R. U. Braun, Dr. M. Ansorge, Prof. Dr. T. J. J. Müller
Organisch-Chemisches Institut der Ruprecht-Karls-Universität Hei-
delberg
Although aldol condensation opens a general route to
chalcones, major shortcomings are the strongly basic or
acidic additives and reagents and the sometimes vigorous
conditions in the condensation step. Therefore, mild reaction
conditions as in transition-metal-catalyzed cross-coupling re-
actions are particularly favorable and promise a high degree
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
Fax : (+49)6221-546-579
E-mail: Thomas_J.J.Mueller@urz.uni-heidelberg.de
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2006, 12, 9081 – 9094
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9081

of functional-group tolerance. Conducting cross-coupling in
domino fashion, whereby a suitable reactive functionality is
generated en route,[22] offers the prospect of extending this
methodology to one-pot sequences and paving the way to
manifold opportunities for developing novel lead structures
of pharmaceuticals, catalysts, and even novel molecule-
based materials.
amounts of [PdCl2ACHTRE(UGN PPh3)2] and CuI in a boiling mixture of
triethylamine and THF, gave rise to formation of 1-substitut-
ed 3-(hetero)aryl propenones 3 in good to excellent yields
(Scheme 1, Tables 1 and 2). With respect to the outcome of
this process this transformation is from now on called a cou-
pling–isomerization reaction (CIR).
As part of our program to develop new multicomponent
ꢀ
methodologies initiated by transition-metal-catalyzed C C
bond formation, we have discovered and developed a new
mode of alkyne activation by a detouring outcome of Sono-
gashira coupling[23] [Eq. (1)].[24] In the past years this new
chalcone synthesis has opened an entry to novel consecutive
multicomponent syntheses of pharmaceutically relevant het-
erocycles in a one-pot fashion.[24,25] Here we report synthetic
studies on and mechanistic insights into this unusual trans-
formation of electron-deficient halides and (hetero)aryl
Scheme 1. A novel coupling–isomerization reaction (CIR) for the synthe-
sis of 1-substituted 3-(hetero)aryl propenones 3.
propargyl alcohols leading to 1,3-di
under thermal conditions.
(hetero)aryl propenones
The structures of enones 3 were unambiguously assigned
by 1H, 13C, COSY, and NOESY NMR experiments. Most
characteristically, in the 1H spectra olefinic methine resonan-
ces for the newly formed trans-configured enone double
bonds, indicated by the characteristic appearance of dou-
blets with large vicinal coupling constants (Jtrans =15.5–
18.9 Hz), are found between d=7.03 and 7.88 ppm (as far as
they are not superimposed by other aromatic protons). The
other (hetero)aromatic, olefinic, or aliphatic protons are de-
tected in the expected regions, whereas the proton signals of
the complexed arenes in complexes 3b, 3c, 3v, and 3ab are
found between d=5.67 and 6.67 ppm. Indicative for the for-
mation of a,b-unsaturated ketones are the carbonyl resonan-
ces in the 13C NMR spectra between d=182.4 and
191.0 ppm. Additionally, for fluorine-substituted derivatives
Results and Discussion
Synthetic studies: The reaction of sufficiently electron defi-
cient organic and organometallic (hetero)aryl halides 1 that
bear electron-withdrawing groups in conjugation with the
carbon–halide bond and 1-propargyl alcohols 2 with (heter-
o)aryl or alkenyl substituents in the 1-position under Sono-
gashira conditions, that is, in the presence of catalytic
1
4
3 f, 3q, and 3r the J to J carbon–fluorine couplings can be
beneficially used for the unambiguous assignment of further
aromatic methine and quaternary carbon nuclei. For the
chromium carbonyl complexes 3b, 3c, 3v, and 3ab the reso-
nances of the carbonyl nuclei bound to the chromium atom
can be detected between d=233.5 and 233.7 ppm.
Abstract in German: Die Sonogashira-Kupplung von elek-
tronenarmen (Hetero)Arylhalogeniden 1 und (Hetero)Aryl-
oder Alkenyl-1-propargylalkoholen 2 endet nicht auf der
Stufe der erwarteten Kupplungsprodukte, sondern führt zu
a,b-ungesättigten Ketonen 3 mit einer ganzen Palette an Ak-
zeptorsubstituenten. Diese neue Domino-Reaktion, eine Kup-
plungs-Isomerisierungs-Reaktion (CIR, coupling isomeriza-
tion reaction), kann als eine Sequenz aus einer raschen Pd-
Cu-katalysierten Alkinylierung gefolgt von einer langsamen
aminbasekatalysierten Propargylalkohol-Enon-Isomerisier-
ung aufgefasst werden. Führt man die CIR in deuterierten
protischen Solventien oder mit einem selektiv deuterierten
Propargylalkohol durch, so wird offenbar, dass der basenka-
talysierte Isomerisierungsschritt unter einer formalen 1,3-H-
Verschiebung und mit minimalem H/D-Austausch mit dem
umgebenden protischen Solvens abläuft. 19F NMR-kinetische
Messungen des Isomerisierungsschrittes mit dem fluorierten
Propargylalkohol 4r stützen das vorgeschlagene mechanisti-
sche Szenario.
In the IR spectra the carbonyl stretching vibrations for
the enones can be found between 1656 and 1675 cmꢀ1. In
addition, for the chromium carbonyl complexes 3b, 3c, 3v,
and 3ab the diagnostic two carbonyl vibrations appear at
1959–1969 cmꢀ1 and 1876–1890 cmꢀ1. Furthermore, the
structure of 3 was unambiguously supported by an X-ray
crystal structure analysis of 3q (Figure 1, Table 3).[26]
Figure 1. Molecular structure of chalcone 3q in the solid state.
9082
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 9081 – 9094

Synthesis of Chalcones
FULL PAPER
Table 1. Synthesis of 1-phenyl 3-(hetero)aryl propenones 3 by CIR.
partner, the 1-substituted prop-
argyl alcohol 2, can be varied
in its structure and electronic
nature (Table 2). Aryl substitu-
ents with various electronic na-
tures (entries 1–5), even with
further halide substituents, are
tolerated and can be carried
through the sequence. Further-
more, electroneutral and elec-
tron-rich heterocyclic substitu-
ents (entries 6–11) are fully
compatible with the CIR, and
also alkenyl-substituted prop-
argyl alcohols (entries 12–14)
give the expected enones in
good yields. As a restriction it
became evident that propargyl
alcohols with alkyl substituents
do not furnish enones, and the
reaction halted at the stage of
the coupled propargyl alco-
hol.[24] Besides THF as cosol-
vent, other solvents such as
ethanol, methanol, acetonitrile,
DMF (at 508C), and toluene
can be successfully applied. It
is also possible to conduct the
CIR in pure base. Amine
bases, such as triethylamine, di-
ethylamine, and pyrrolidine,
turned out to be favorable.
Methodologically, this new
enone synthesis is an alterna-
tive versatile access to chal-
cones and related derivatives
and has paved the way to con-
secutive multicomponent syn-
theses of various heterocycle
classes.[24,25]
Entry
A
Propargylic alcohol 2
Enone 3
Yield [%]
82
1
1a
1b
2a
3a
3b
2
3
2a
2a
79
75
1c
3c
4[a]
1d
1e
1 f
1g
1h
1i
2a
2a
2a
2a
2a
2a
3d
3e
3 f
3g
3h
3i
96
62
75
58
58
57
5
6
7[a]
8[b]
9
10[a]
11
1j
1k
1l
2a
2a
2a
3j
3k
3l
77
85
75
12
13
14
1m
1n
2a
2a
3m
3n
89
90
Prior to our studies, this un-
usual reaction was only ob-
served and discussed by
Minn[27] and Kundu and Das[28]
for the coupling of 2-halo-sub-
stituted pyrimidines with 1-
[a] In THF/NEt3 (1:1). [b] In HNEt2.
The scope of this novel enone synthesis is relatively
broad. As shown in preliminary experiments[24] a sufficiently
electron-withdrawing halide 1 is necessary to trigger the
CIR, since in cases in which electroneutral halides were ap-
plied the sequence stopped after the Sonogashira coupling.
With respect to the electron-deficient halide 1 (Table 1) the
scope ranges from strongly electron-withdrawing aryl hal-
ides and Cr(CO)3-complexed chloroarenes (entries 2 and 3)
to systems with reduced acceptor capacity, such as amides
(entry 10), 2-bromothiazole (1l) (entry 12), and vinylogous
esters and ketones (entries 13 and 14). The other coupling
phenyl propargyl alcohol. Therefore, Kundu and Das specu-
lated on the mechanism by assuming coordination of an in-
termediate during a hydropalladation–dehydropalladation
catalytic cycle to the heterocyclic nitrogen atom.[28b] Howev-
er, due to a lack of heteroatom coordination in many of our
examples, this explanation fails for the formation of enones
3. Furthermore, we could now show that isomerization ex-
clusively occurs as a base-catalyzed second step.[24] All this
prompted us to investigate the CIR mechanistically and pro-
pose a reasonable general mechanistic picture of the impor-
tant sequence.
Chem. Eur. J. 2006, 12, 9081 – 9094
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9083

T. J. J. Müller et al.
Table 2. Synthesis of 1-substituted 3-(hetero)aryl propenones 3 by CIR.
Mechanistic studies: Prelimi-
nary studies indicated that the
CIR occurs by fast Sonoga-
shira coupling followed by
Entry
A
Propargylic alcohol 2
Enone 3
Yield [%]
98
1
1d
2b
3o
rate-determining
base-cata-
lyzed isomerization. After re-
action of the halide 1d and
propargyl alcohol 2a in a boil-
ing mixture of NEt3 and meth-
anol for 30 min, the presumed
coupled propargylic alcohol 4
was isolated in 80% yield
[Eq. (2)]. However, analysis of
the crude reaction mixture re-
vealed that chalcone 2d had
already formed to some
extent. As expected, as isomer-
ization proceeds, the ratio be-
tween chalcone 2d and cou-
pled propargylic alcohol 4d in-
creases with time. Therefore, it
seemed also possible to decou-
ple the fast coupling from the
slow isomerization for a thor-
ough investigation of the prop-
argylic alcohol–enone isomeri-
zation.
2
3
4
1a
1d
1d
2c
2d
2e
3p
3q
3r
80
93
96
5[a]
1d
1a
2 f
2g
3s
3t
83
95
6
It is reasonable to assume
that several intermediates in
the CIR are alcohols, which fi-
nally furnish an a,b-unsaturat-
ed ketone as the end of the se-
quence. Hence, performing the
above reaction under deuteri-
um-exchange conditions could
give insight into in which inter-
molecular H/D exchange pro-
7
8
1n
1b
2g
3u
3v
95
57
2g
2g
9
1m
1a
3w
3x
90
84
AHCTREcUNG esses could be involved. On
reaction of p-bromobenzoni-
trile (1d) and the propargyl al-
cohol 2a in a boiling mixture
of NEt3 and CH3OD, deuterat-
ed chalcone [2-D]-3d was ob-
tained in 91% yield [Eq. (3)].
10
2h
2i
11[b]
1d
3y
79
Interestingly,
triethylamine-
catalyzed isomerization of pre-
sumed and actual intermediate
4d under the same conditions
gave [2-D]-3d in 93% yield
[Eq. (4)]. A Heck-type path-
way consisting of an insertion–
b-hydride elimination scenario
could be excluded, since no
substantial transformation of
1d and 2a was observed if CuI
was omitted from the reaction
mixture.
12[a]
13[c]
1d
1d
2j
3z
68
66
2k
3aa
14
1b
2l
3ab
41
[a] In THF/NEt3 (1:1). [b] In EtOH/NEt3 (1:1.8). [c] In CH3CN/NEt3 (1:1).
9084
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 9081 – 9094

Synthesis of Chalcones
FULL PAPER
Table 3. Crystal data and structure refinement for 3q.
ed chalcone [3-D]-3d was ob-
tained in 90% yield with 82%
deuteration (determined by
mass spectrometry, no bis-
deuteration was found) at the
formula
Mr
C16H10FNO
251.25
1calcd [gcmꢀ3
]
1.339
0.094
0.53”0.40”0.20
2.96–23.97
2117
m [mmꢀ1
]
T [K]
l [Š]
crystal system
space group
Z
a [Š]
b [Š]
c [Š]
a [8]
293(2)
crystal size [mm]
q range [8]
0.71073
triclinic
reflections collected
independent reflections
absorption correction
max./min. transmission
refinement method
parameter
¯
position b to the carbonyl
group [Eq. (5)].
P1
1936 (RACHTRENU(G int)=0.0652)
semi-empirical from equivalents
2
6.964(2)
8.6064(12)
10.536(2)
91.367(13)
95.30(2)
97.24(2)
623.3(2)
0.9914/0.9324
A high degree of retention
of deuteration in the enone
can be interpreted as minimal
H/D exchange of the propar-
gylic proton (deuteron) with
the protic medium. This is par-
ticularly interesting, since the
isomerization is an amine-
full-matrix least-squares on F2
172
1.014
0.0494
0.0637
0.190/ꢀ0.256
GOF on F2
b [8]
final R index [I>2s(I)]
g [8]
Rw(F2)
V [Š3]
largest diff. peak/hole [eŠ ]
ꢀ3
base-catalyzed process, whereas the 1,3-shift of the propar-
gylic proton (deuteron) to become a b-methine proton (deu-
teron) seems to be the result of an intramolecular proton
transfer. As 1,3-H shifts are orbital-symmetry forbidden and
concerted suprafacial processes and antarafacial transfer are
geometrically not accessible,[31] a plausible explanation for
this unusual 1,3-H shift is deprotonation of propargyl alco-
hol [1-D]-4d at the propargylic position to generate contact
ion pair 5d in a solvent cage in which H/D exchange of the
triethylammonium cation with the protic medium is consid-
erably slower than reprotonation. Hence, allenol 6d be-
comes the short-lived isomerization product that undergoes
rapid and irreversible tautomerism to the thermodynamic
sink of the isomerization sequence and conclusively rational-
izes the generation of chalcone 3d. Therefore, the mechanis-
tic rationale of the CIR can be described as in Scheme 2. So-
4 d NEt , MeOD, D, 14 h ½2-DŠ-3 d ð93 %, 86 % DÞ
ƒƒƒƒƒƒƒƒƒƒ!
ð4Þ
3
The selectivity of deuteration was finally determined by
mass spectrometry. For the CIR and the isomerization step
86% deuterium incorporation was found (along with 9% of
bis-deuteration). Interestingly, by integration of the reso-
nance of the residual methine proton in the position a to
1
the carbonyl group at d=7.59 ppm in the H NMR spectrum
of [2-D]-3d as a doublet (3J=15.8 Hz) a 95% degree of
deuteration was determined. The connectivity of [2-D]-3d
was unambiguously established by an HMBC NMR spec-
trum, in which the resonance of the methine proton in the
position
b to the carbonyl group appeared at d=
7.78 ppm.[29]
As a key experiment to find out to what extent H/D ex-
change of the propargylic proton is involved in isomeriza-
tion of the intermediate propargyl alcohol 4d to enone 3d,
we selectively subjected deuterated propargyl alcohol [1-D]-
2a[30] (97% deuterium labeling) to CIR with p-bromobenzo-
nitrile (1d). After reaction of 1d and propargyl alcohol [1-
D]-2a in a boiling mixture of NEt3 and methanol, deuterat-
Scheme 2. Mechanistic rationale of the CIR.
nogashira coupling of halide 1 and terminal propargyl alco-
hol 2 furnishes internal propargyl alcohol 4, which is depro-
tonated to give the propargyl anion–triethylammonium con-
tact ion pair 5 as a short-lived intermediate. Protonation of
the anion either gives propargyl alcohol 4 or allenol 6. The
latter isomerizes to enone 3.
Hence, this mechanistic scenario inevitably explains that
H/D exchange in deuterated solvents is possible at the
stages of alcohols 2, 4, and 6, and therefore selective deuter-
Chem. Eur. J. 2006, 12, 9081 – 9094
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9085

T. J. J. Müller et al.
ation in the position a to the carbonyl group becomes evi-
dent.
Now two scenarios can be envisioned depending on the
rates of the first two elementary steps. For kꢀ1 !k2 Equa-
tion (7) simplifies to a second-order rate law in which depro-
tonation of 4r is the rate-determining step [Eq. (8)]. For
kꢀ1 @k2 Equation (7) turns into a rate law in which rapid de-
protonation pre-equilibrium precedes rate-determining pro-
tonation of contact ion pair 5r to give allenol 6r [Eq. (9)].
Finally, kinetic investigations were performed to gain
more insight into the rate-determining isomerization step.
The timescale of the propargyl alcohol–enone isomerization
is evidently suited to NMR kinetics studies, and therefore
isomerization of fluoro-substituted propargyl alcohol 4r to
enone 3r became the model of choice [Eq. (6)], since the
d½4 rŠ
ð8Þ
ð9Þ
ꢀ
ꢀ
¼ k1½4 rŠ½NEt3Š
dt
d½4 rŠ
dt
¼ Kk2½4 rŠ½NEt3Š
However, the rate constants for protonation of contact
ion pair 5r to starting material 4r (kꢀ1) or to allenol 6r (k2)
should be of comparable magnitude. Therefore, it is reason-
able to treat the empirical rate constants in the sense of kobs
[Eq. (10)] in which kobs is k1 or Kk2.
19F NMR spectra of 4r and 3r display clearly separated sin-
glets at d=ꢀ139.1 (4r) and ꢀ130.4 ppm (3r), and because
various amines and solvents without specific labeling can be
applied. Initial qualitative kinetic measurements revealed
that the isomerization with DBU (pKa =12) as base was al-
ready complete when the sample was placed in the spec-
trometer. Triethylamine (pKa =10.8), as used in the synthet-
ic studies, takes several hours for complete conversion,
whereas no isomerization was detected even after 12 h when
pyridine (pKa =5.2) was used.
d½4 rŠ
ð10Þ
ꢀ
¼ kobs½4 rŠ½NEt3Š
dt
Further simplification is achieved by using an excess of
triethylamine, as in the synthetic studies, which gives a
pseudo-first-order rate law with kobs’ =[NEt3]kobs that is suit-
able for
[Eq. (11)].
a
straightforward mathematical treatment
This indicates a strong dependence on the basicity of the
applied amine. Therefore, the mechanistic working hypothe-
sis of propargyl alcohol–enone isomerization gives three ele-
mentary steps (Scheme 3). Assuming slow deprotonation of
d½4 rŠ
ð11Þ
ꢀ
¼ kobs0 ½4 rŠ
dt
Since formation of chalcone 3r was quantitative in the
synthetic studies, integration of the two fluorine resonances
was used to determine the concentration of propargyl alco-
hol 4r and to monitor its decay. Hence, kinetic studies with
a stock solution of 4r (c
observed rate constants kobs’ in dependence on solvent, tri-
ethylamine concentration, and temperature (Table 4). In-
(4r)=0.20 molLꢀ1) furnished the
0ACHTREUNG
AHCTREUNG
creasing the solvent polarity under pseudo-first-order condi-
tions with respect to triethylamine concentration enhances
the rate of the isomerization process by one order of magni-
Table 4. Dependence of rate constants kobs’ (kinetics at
c0ACHTREUNG(4r)=
Scheme 3. Presumed elementary steps of the propargyl alcohol–enone
isomerization.
0.20 molLꢀ1) on solvent, base concentration, and temperature.
Entry
Solvent
T [K]
kobs’ [mol2 Lꢀ2 sꢀ1
]
1
2
3
4
5
6
7
8
9
triethylamine (neat)
toluene/triethylamine (1:1)
ethanol/triethylamine (1:1)
348
348
348
348
348
348
348
348
328
338
348
358
2.27”10ꢀ5
2.42”10ꢀ5
5.23”10ꢀ5
2.01”10ꢀ4
2.01”10ꢀ4
1.97”10ꢀ4
1.19”10ꢀ4
6.86”10ꢀ5
4.80”10ꢀ5
8.85”10ꢀ5
1.90”10ꢀ4
5.44”10ꢀ4
4r and of short-lived allenol 6r, rapid protonation of contact
ion pair 5r, low steady-state concentrations of 5r and 6r,
that is, Bodensteinꢁs stationary-state approximation,[32] and
rapid and irreversible tautomerism of 6r to give enone 3r
leads to a simplification of the rate law for the decay of the
concentration of propargyl alcohol 4r, which can be moni-
tored by 19F NMR spectroscopy [Eq. (7)].
acetonitrile/triethylamine (1:1)
acetonitrile/triethylamine (1:1)[a]
acetonitrile/triethylamine (5:1)[b]
acetonitrile/triethylamine (10:1)[c]
acetonitrile/triethylamine (14:1)[d]
acetonitrile/triethylamine (1:1)
acetonitrile/triethylamine (1:1)
acetonitrile/triethylamine (1:1)
acetonitrile/triethylamine (1:1)
10
11
12
d½4 rŠ
dt
k1k2
kꢀ1 þ k2
[a] c
G
.
[b] c
N
.
[c] cACHTREUNG(NEt3)=
ð7Þ
ꢀ
¼
½4 rŠ½NEt3Š
0.65 molLꢀ1. [d] c
A
9086
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 9081 – 9094

Synthesis of Chalcones
FULL PAPER
Aldrich, Fluka, or Merck and used without further purification. Methyl
cis-3-bromoacrylate[35] (1m) and 3-bromo-cyclohexenone[36] (1n) were
synthesized by literature procedures. Triethylamine and THF were dried
and distilled according to standard procedures.[37] Propargyl alcohols 2
were prepared in analogy to literature procedures[38] by addition of
ethynyl magnesium bromide to the corresponding aldehydes. 10-Hexyl-
phenothiazine-3-carbaldehyde was prepared by Vilsmeier formylation.[39]
Column chromatography: silica gel 60 M (230–400 mesh), Macherey-
Nagel, Düren, or silica gel 60 (70–230 mesh), Merck, Darmstadt. TLC:
silica gel plates (60 F254 Merck, Darmstadt). Melting points (uncorrected
values): Büchi Melting Point B-540. 1H and 13C NMR spectra: Bruker
ARX250, Bruker DRX 300, Bruker ARX 300, Varian VXR 400S, Bruker
DRX500, or Bruker AC300 with [D6]acetone, CDCl3, or [D6]DMSO as
solvent. The assignments of quaternary C, CH, CH2, and CH3 were made
by using DEPT spectra. IR: Bruker Vector 22 FT-IR or Perkin–Elmer
Model Lambda 3. UV/Vis: Hewlett Packard HP8452A. MS: Finnigan
MAT 90, MAT 95 Q, Jeol JMS-700, and Finnigan TSQ 700. Elemental
analyses were carried out in the Microanalytical Laboratories of the Or-
ganisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, and
of the Department Chemie, Ludwig-Maximilians-Universität München.
tude (entries 1–4). Thus, dipolar aprotic solvents such as ace-
tonitrile are clearly favored over apolar solvents such as tol-
uene or neat triethylamine. Between triethylamine concen-
trations of 0 and 1.2 molLꢀ1, a second-order rate law applies
best, first-order in the concentration of 4r and first-order in
the concentration of triethylamine, and a reduced rate con-
stant
k
obs =1.66·10ꢀ4 molLꢀ1 sꢀ1 can be determined (en-
tries 6–8). However, increasing the triethylamine concentra-
tion above 1.2 molLꢀ1 leads to the regime of pseudo-first-
order conditions (entry 5). As expected, the temperature-de-
pendent kinetics (at 55, 65, 75, and 858C) under pseudo-
first-order conditions (entries 9–12) is well suited to furnish
the desired activation parameters. Thus, the Arrhenius
plot[33] gives
a
pre-exponential factor of A=0.69”
108 mol2 Lꢀ2 sꢀ1 and an activation energy of Ea =
76.6 kJmolꢀ1, and the Eyring plot[34] furnishes an activation
enthalpy of DHꢀ =73.7 kJmolꢀ1 and an activation entropy
of DSꢀ =ꢀ104.5 JKꢀ1 molꢀ1. The large negative activation
entropy is consistent with a highly ordered late transition
state that, according to the Hammond postulate, may well
be a contact ion pair in a solvent cage.
1-(3-Thienyl)propyn-1-ol (2g):
A solution of (trimethylsilyl)acetylene
(6.93 mL, 49.0 mmol) in THF (50 mL) was cooled to ꢀ788C under nitro-
gen, a 1.6m solution of nBuLi in hexanes (30.7 mL, 49.0 mmol) added
dropwise, and the mixture stirred for 60 min at ꢀ788C. A solution of thi-
ophene-3-carbaldehyde (5.00 g, 44.6 mmol) in THF (10 mL) was added
dropwise, and then the mixture was allowed to warm to room tempera-
ture over 60 min by removing the cooling bath. A saturated aqueous so-
AHCTRElUNG ution of ammonium chloride (20 mL) was added to the reaction mixture,
Conclusion
which was exhaustively extracted with diethyl ether. The combined or-
ganic layers were dried with anhydrous magnesium sulfate and the sol-
vents were removed in vacuo.
Starting from electron-deficient (hetero)aryl halides and
(hetero)aryl or alkenyl 1-propargyl alcohols, the Sonoga-
shira coupling–isomerization reaction (CIR) provides gener-
al access to a,b-unsaturated ketones with a variety of ac-
ceptors, such as esters, amides, ketones, nitriles, nitro, and
trifluoromethyl groups; electron-deficient heterocycles; and
tricarbonylchromium-complexed arenes. Amines with com-
parable pKb, such as HNEt2, NEt3, and pyrrolidine, can be
applied as suitable bases. Favorable solvents for this domino
reaction are ethanol, methanol, THF, acetonitrile, DMF (at
508C), and toluene, as well as neat amine base. Coupling–
isomerization reactions in deuterated protic solvents or with
a selectively deuterated propargyl alcohol reveal that the
base-catalyzed isomerization step proceeds through a formal
1,3-H shift with minimal H/D exchange with the surround-
ing solvent. Furthermore, kinetic investigations on the rate-
determining isomerization step support the mechanistic ra-
tionale. Although the postulated allenol intermediate, which
leads to the enone by isomerization, is elusive, further devel-
opment of CIR as an initiator of new domino processes
could be based on the exploitation of allene intermediates.
Studies expanding the methodological scope of CIR and the
generation of sequences initiated by CIR are currently
under investigation.
For desilylation the residue was dissolved in methanol (100 mL) and 2n
sodium hydroxide solution (112 mL) was added. After stirring for 60 min
at room temperature the solution was extracted with diethyl ether. The
organic phase was washed twice with deionized water, dried with anhy-
drous magnesium sulfate, and then the solvents were removed in vacuo.
The residue was distilled at 888C (2.7”10ꢀ1 mbar) to give 3.96 g (64%)
of 2g as a colorless solid. M.p. 57–598C; 1H NMR (CDCl3, 300 MHz):
d=7.40 (dd, J=3.0, 0.9 Hz, 1H), 7.30 (dd, J=5.0, 3.0 Hz, 1H), 7.20 (dd,
J=5.0, 1.2 Hz, 1H), 5.48 (m, 1H), 2.64 (d, J=2.2 Hz, 1H), 2.38 ppm (m,
1H); 13C NMR (CDCl3, 75 MHz): d=141.1 (Cquat), 126.2 (CH), 126.1
(CH), 122.9 (CH), 83.3 (Cquat), 74.0 (CH), 60.3 ppm (CH); IR (KBr): n˜ =
3401, 2117, 1781, 1637, 1533 cmꢀ1; MS (EI, 70 eV): m/z (%): 138 (100)
[M+]; elemental analysis (%) calcd for C7H6OS (138.2): C 60.84, H 4.37,
S 23.20; found: C 60.98, H 4.38, S 23.12.
1-(10-Hexyl-10H-phenothiazin-3-yl)-prop-2-yn-1-ol (2i): According to the
literature procedure[38] 2i (4.11 g, 76%) was obtained as an orange-red
resin. 1H NMR (CDCl3, 300 MHz): d=7.10–7.14 (m, 2H), 6.87–6.93 (m,
1H), 6.81–6.86 (m, 2H), 5.35 (d, J=2.2 Hz, 1H), 3.80–3.85 (m, 2H), 2.65
(d, J=2.2 Hz, 1H), 1.37–1.44 (m, 2H), 1.25–1.31 (m, 6H), 0.87 ppm (t,
J=6.9 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d=145.4 (Cquat), 144.8
(Cquat), 133.9 (Cquat), 127.2 (CH), 127.1 (CH), 125.5 (CH), 125.5 (CH),
125.1 (Cquat), 124.3 (Cquat), 122.3 (CH), 115.2 (CH), 115.0 (CH), 83.2
(Cquat), 74.6 (CH), 63.5 (CH), 47.3 (CH2), 31.2 (CH2), 26.6 (CH2), 26.4
(CH2), 22.4 (CH2), 13.7 ppm (CH3); IR (neat): n˜ =1604, 2856, 2928, 2954,
3292 cmꢀ1
;
UV/Vis (CHCl3): lmax (e)=308 (6200), 260 nm
(30500 molꢀ1 m3 cmꢀ1); MS (FAB, NBA): m/z (%): 337 (100) [M+], 320
(14) [M+ꢀOH], 266 (12) [M+ꢀC5H11], 252 (11) [M+ꢀC6H13]; HRMS
(FAB, NBA) calcd for C21H23NOS: 337.1500; found: 337.1465.
1-(4-Bromophenyl)prop-2-yn-1-ol (2j): According to the literature proce-
dure[38] 2j (6.58 g, 78%) was obtained as beige crystals. M.p. 48–498C;
1H NMR (CDCl3, 300 MHz): d=7.50 (d, J=8.6 Hz, 2H), 7.41 (d, J=
8.5 Hz, 2H), 5.41 (s, 1H), 2.67 (d, J=2.2 Hz, 1H), 2.47 ppm (br, 1H);
13C NMR (CDCl3, 75 MHz): d=139.0 (Cquat), 131.7 (CH), 128.3 (CH),
122.5 (Cquat), 83.0 (Cquat), 75.2 (CH), 63.7 ppm (CH); IR (KBr): n˜ =1590,
2122, 3284 cmꢀ1; MS (EI, 70 eV): m/z (%): 212 (34) [81Br-M+], 210 (46)
Experimental Section
General considerations: All reactions involving palladium–copper cataly-
sis were performed in degassed oxygen-free solvents under a nitrogen at-
mosphere using Schlenk and syringe techniques. Halogen compounds 1,
[79Br-M+], 188 (18) [81Br-M+ꢀC=C], 186 (18) [79Br-M+ꢀC=C], 131 (68)
+
ꢀ
[PdCl
(PPh3)2], and CuI were purchased in reagent grade from ACROS,
[M+ꢀBr], 53 (100) [C=C CO ]; elemental analysis (%) calcd for
Chem. Eur. J. 2006, 12, 9081 – 9094
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9087

T. J. J. Müller et al.
C9H7BrO (211.1): C 51.22, H 3.34, Br 37.86; found: C 51.18, H 3.32, Br
37.65.
(21300molꢀ1 dm3 cmꢀ1); MS (EI): m/z (%): 344 (13) [M+], 288 (6) [M+
ꢀ2CO], 260 (100) [M+ꢀ3CO], 208 (8) [M+ꢀCr(CO)3], 52 (28) [Cr+];
elemental analysis (%) calcd for C18H12CrO4 (344.3): C 62.79, H 3.51.
Found: C 63.28, H 3.43.
General procedure for the synthesis of chalcones 3 by CIR: [PdCl2-
ACHTREUNG(PPh3)2] (14.0 mg, 0.02 mmol) and CuI (1.9 mg, 0.01 mmol) were added
to a degassed solution of a (hetero)aryl halide 1 (1.00 mmol) and a prop-
argylic alcohol 2 (1.05 mmol) in a mixture of the solvent indicated and
triethylamine (or other amine base). The reaction mixture was heated to
reflux for 14 h. After cooling to room temperature the formed triethyl-
{h6-[(E)-3-phenylprop-1-en-3-onyl]-2-methylbenzene}chromi-
TricarbonylACHTREUNG
um(0) (3c): This compound was prepared according to the general proce-
dure; purification by chromatography on silica gel (pentane/diethyl
ether) and crystallization from pentane/diethyl ether gave an orange-red
solid. M.p. 90–938C; 1H NMR ([D6]DMSO, 300 MHz): d=8.13 (d, J=
7.5 Hz, 2H), 7.87 (d, J=15.3 Hz, 1H), 7.67 (t, J=7.3 Hz, 1H), 7.57 (t, J=
7.4 Hz, 2H), 7.55 (d, J=15.0 Hz, 1H), 6.67 (d, J=6.8 Hz, 1H), 5.96 (t,
J=6.3 Hz, 1H), 5.67–5.69 (m, 2H), 2.34 ppm (s, 3H); 13C NMR
([D6]DMSO, 75 MHz): d=233.7 (Cquat), 188.6 (Cquat), 138.3 (CH), 137.3
(Cquat), 133.6 (CH), 128.8 (CH), 129.0 (CH), 124.1 (CH), 96.9 (CH), 100.1
(Cquat), 91.8 (CH), 94.5 (CH), 95.4 (CH), 18.8 ppm (CH3); IR (KBr): n˜ =
1574, 1588, 1661, 1876, 1959 cmꢀ1; UV/Vis (DMSO): lmax (e)=452 (5200),
275 nm (19600 molꢀ1 dm3 cmꢀ1); MS (EI): m/z (%): 358 (14) [M+], 302
(5) [M+ꢀ2CO], 274 (100) [M+ꢀ3CO], 222 (5) [M+ꢀCr(CO)3], 52 (25)
[Cr+]; elemental analysis (%) calcd for C19H14CrO4 (358.3): C 63.69,
H 3.94; found: C 64.00, H 4.11.
ACHTREUNGammonium salt was precipitated with diethyl ether (15 mL). After filtra-
tion the solvents were removed in vacuo and the residue was purified by
recrystallization and/or chromatography on silica gel (for experimental
details see Table 5).
3-(4-Nitrophenyl)-1-phenylprop-2-en-1-one (3a): This compound was
prepared according to the general procedure; purification by trituration
with ethanol and recrystallization from ethanol gave a yellow powder.
M.p. 163–1648C (lit.[40] 1648C); 1H NMR (CDCl3, 300 MHz): d=8.26 (d,
J=8.8 Hz, 2H); 8.01–8.04 (m, 2H), 7.81 (d, J=15.6 Hz, 1H), 7.78 (d, J=
8.7 Hz, 2H), 7.64 (d, J=15.7 Hz, 1H), 7.59–7.64 (m, 1H), 7.49–7.55 ppm
(m, 2H); 13C NMR (CDCl3, 75 MHz): d=189.6 (Cquat), 148.6 (Cquat),
141.5 (CH), 141.0 (Cquat), 137.5 (Cquat), 133.3 (CH), 128.9 (CH), 128.8
(CH), 128.6 (CH), 125.7 (CH), 124.2 ppm (CH).
3-(4-Cyanophenyl)-1-phenylprop-2-en-1-one (3d): This compound was
prepared according to the general procedure; purification by recrystalli-
zation from ethanol gave a colorless fluffy solid. M.p. 159–1608C (lit.[46]
TricarbonylACHTREUNG
{h6-[(E)-3-phenylprop-1-en-3-onyl]benzene}chromium(0)
(3b): This compound was prepared according to the general procedure;
purification by chromatography on silica gel (pentane/diethyl ether) and
crystallization from pentane/diethyl ether gave an orange-red solid. M.p.
156–1598C; 1H NMR ([D6]DMSO, 300 MHz): d=8.12 (d, J=7.3 Hz,
2H), 7.86 (d, J=15.6 Hz, 1H), 7.67 (t, J=7.3 Hz, 1H), 7.56 (t, J=7.7 Hz,
2H), 7.36 (d, J=15.6 Hz, 1H), 6.40 (d, J=6.3 Hz, 2H), 5.87 (t, J=6.1 Hz,
1H), 5.80 ppm (t, J=5.9 Hz, 2H); 13C NMR ([D6]DMSO, 75 MHz): d=
233.5 (Cquat, CO), 188.7 (Cquat), 141.5 (CH), 137.3 (Cquat), 133.6 (CH),
129.0 (CH), 128.7 (CH), 123.2 (CH), 101.4 (Cquat), 95.9 (CH), 95.9 (CH),
94.0 ppm (CH); IR (KBr): n˜ =3079, 2924, 2853, 1966, 1608, 1577, 1504,
1447, 1384, 1332, 1287, 1217, 1179, 1159, 1033, 1018, 995, 817, 777, 704,
685, 658, 629, 617 cmꢀ1; UV/Vis (DMSO): lmax (e)=452 (5100), 274 nm
1
156–1578C); H NMR (CDCl3, 300 MHz): d=8.00–8.04 (m, 2H), 7.76 (d,
J=15.8 Hz, 1H), 7.67–7.73 (m, 4H), 7.59 (d, J=15.8 Hz, 1H), 7.57–7.64
(m, 1H), 7.48–7.54 ppm (m, 2H); 13C NMR (CDCl3, 75 MHz): d=189.7
(Cquat), 142.0 (CH), 139.2 (Cquat), 137.6 (Cquat), 133.2 (CH), 132.6 (CH),
128.7 (CH), 128.6 (CH), 128.5 (CH), 125.1 (CH), 118.3 (Cquat), 113.5 ppm
(Cquat); MS (FD+): m/z (%): 235 (5) [M+], 234 (22) [M+], 233 (100)
[M+].
AHCTRE[GNU 2-D]-3-(4-Cyanophenyl)-1-phenylprop-2-en-1-one ([2-D]-3d): This com-
pound was prepared according to the general procedure; purification by
recrystallization from ethanol gave a colorless fluffy solid. M.p. 1598C
(lit. for all-proton 3d[46] 156–1578C); 1H NMR (CDCl3, 300 MHz): d=
Table 5. Experimental details for CIR enone synthesis.
Entry
A
Propargylic alcohol 2
Solvent
Base
Yield of chalcone 3
1
1a (253 mg, 1.00 mmol)
1b (250 mg, 1.00 mmol)
1c (260 mg, 1.00 mmol)
1d (182 mg, 1.00 mmol)
1e (182 mg, 1.00 mmol)
1 f (225 mg, 1.00 mmol)
1g (229 mg, 1.00 mmol)
1h (261 mg, 1.00 mmol)
1i (370 mg, 2.00 mmol)
1j (200 mg, 1.00 mmol)
1k (192 mg, 1.00 mmol)
1l (164 mg, 1.00 mmol)
1m (165 mg, 1.00 mmol)
1n (175 mg, 1.00 mmol)
1d 182 mg, 1.00 mmol)
1a (253 mg, 1.00 mmol)
1d (182 mg, 1.00 mmol)
1d (182 mg, 1.00 mmol)
1d (182 mg, 1.00 mmol)
1a (250 mg, 1.00 mmol)
1n (175 mg, 1.00 mmol)
1b (250 mg, 1.00 mmol)
1m (165 mg, 1.00 mmol)
1a (253 mg, 1.00 mmol)
1d (182 mg, 1.00 mmol)
1d (182 mg, 1.00 mmol)
1d (182 mg, 1.00 mmol)
1b (250 mg, 1.00 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2a (270 mg, 2.10 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2a (135 mg, 1.05 mmol)
2b (235 mg, 1.05 mmol)
2c (170 mg, 1.05 mmol)
2d (150 mg, 1.05 mmol)
2e (150 mg, 1.05 mmol)
2 f (354 mg, 1.05 mmol)
2g (145 mg, 1.05 mmol)
2g (145 mg, 1.05 mmol)
2g (145 mg, 1.05 mmol)
2g (145 mg, 1.05 mmol)
2h (128 mg, 1.05 mmol)
2i (354 mg, 1.05 mmol)
2j (116 mg, 1.05 mmol)
2k (101 mg, 1.05 mmol)
2l (170 mg, 1.05 mmol)
THF (6.0 mL)
THF (10 mL)
THF (10 mL)
THF (2.5 mL)
THF (6.0 mL)
THF (6.0 mL)
THF (2.5 mL)
NEt3 (3.5 mL)
NEt3 (5 mL)
NEt3 (5 mL)
NEt3 (2.5 mL)
NEt3 (3.5 mL)
HNEt2 (3.5 mL)
NEt3 (2.5 mL)
HNEt2 (6 mL)
NEt3 (5 mL)
NEt3 (2.5 mL)
NEt3 (5 mL)
NEt3 (3.5 mL)
NEt3 (5 mL)
NEt3 (5 mL)
NEt3 (3.5 mL)
NEt3 (3.5 mL)
NEt3 (3.5 mL)
NEt3 (3.5 mL)
NEt3 (2.5 mL)
NEt3 (5 mL)
NEt3 (5 mL)
NEt3 (5 mL)
NEt3 (5 mL)
NEt3 (3.5 mL)
NEt3 (3.5 mL)
NEt3 (2.5 mL)
NEt3 (2.5 mL)
NEt3 (5 mL)
3a, 82 % (208 mg)
3b, 79% (272 mg)
3c, 75% (270 mg)
3d, 96% (223 mg)
3e, 62% (145 mg)
3 f, 75% (206 mg)
3g, 58% (163 mg)
3h, 58% (179 mg)
3i, 57% (270 mg)
3j, 77% (193 mg)
3k, 85% (206 mg)
3l, 75% (161 mg)
3m, 89% (192 mg)
3n, 90% (210 mg)
3o, 98% (320 mg)
3p, 80% (226 mg)
3q, 93% (234 mg)
3r, 96% (240 mg)
3s, 83% (258 mg)
3t, 95% (260 mg)
3u, 95% (220 mg)
3v, 57% (200 mg)
3w, 90% (200 mg)
3x, 84% (203 mg)
3y, 79% (347 mg)
3z, 68% (143 mg)
3aa, 66% (130 mg)
3ab, 41% (152 mg)
2[a]
3[b]
4
5
6
7
8
9[c]
10
THF (10 mL)
THF (2.5 mL)
THF (10 mL)
THF (6.0 mL)
THF (10 mL)
THF (10 mL)
THF (6.0 mL)
THF (6.0 mL)
THF (6.0 mL)
THF (6.0 mL)
THF (2.5 mL)
THF (10 mL)
THF (10 mL)
THF (10 mL)
THF (10 mL)
THF (6.0 mL)
EtOH (2.0 mL)
THF (2.5 mL)
MeCN (2.5 mL)
THF (10 mL)
11[d]
12
13[e]
14[e]
15
16
17
18
19
20[c]
21
22[e]
23[e]
24
25
26
27
28[a]
[a] Reaction time: 6 h. [b] Reaction time: 48 h. [c] Reaction time: 9 h. [d] Reaction time: 15 h. [e] Reaction time: 8 h.
9088
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 9081 – 9094

Synthesis of Chalcones
FULL PAPER
8.00–8.04 (m, 2H), 7.76 (s, 1H), 7.67–7.73 (m, 4H), 7.59 (5% residual
signal), 7.57–7.64 (m, 1H), 7.48–7.54 ppm (m, 2H); 13C NMR (CDCl3,
75 MHz): d=189.7 (Cquat), 142.0 (CH), 139.2 (Cquat), 137.6 (Cquat), 133.2
(CH), 132.6 (CH), 128.7 (CH), 128.6 (CH), 113.5 (Cquat), 128.5 (CH),
125.1 (br, residual signal), 118.3 ppm (Cquat); MS (FD+): m/z (%): 236 (5)
[D-M++D], 235 (32) [D-M++H], 234 (100) [D-M+], 233 (5) [M+], that
is, 5% undeuterated product, 86% monodeuteration, and 9% bis-deuter-
ation.
15.0 Hz, 1H), 7.79 (d, J=7.9 Hz, 2H), 7.64 (d, J=15.9 Hz, 1H), 7.53 (m,
2H), 7.23 ppm (t, J=6.2 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=191.4
(CH), 189.9 (Cquat), 142.7 (CH), 140.5 (Cquat), 137.7 (Cquat), 137.2 (Cquat),
133.1 (CH), 130.1 (CH), 128.8 (CH), 128.7 (CH), 128.5 (CH), 124.7 ppm
(CH); IR (KBr): n˜ =1566, 1603, 1659, 1697 cmꢀ1; UV/Vis (CHCl3): lmax
(e)=315 nm (26200 molꢀ1 dm3 cmꢀ1); MS (EI): m/z (%): 236 (100) [M+];
HRMS calcd for C16H12O2: 236.0837; found: 236.0832.
4-(3-Oxo-3-phenylprop-1-en-1-yl)benzamide (3j): This compound was
prepared according to the general procedure; purification by trituration
with 2-propanol and recrystallization from 2-propanol gave a beige solid.
M.p. 117–1188C (no melting point available[45]); 1H NMR (CDCl3,
300 MHz): d=8.16–8.19 (m, 2H), 8.01–8.04 (m, 2H), 7.93–7.96 (m, 3H),
7.83 (d, J=15.7 Hz, 1H), 7.51–7.75 ppm (m, 3H); 13C NMR (CDCl3,
75 MHz): d=189.9 (Cquat), 168.3 (Cquat), 143.6 (CH), 138.9 (Cquat), 138.7
(Cquat), 136.7 (Cquat), 133.8 (CH), 129.6 (CH), 129.3 (CH), 129.3 (CH),
129.0 (CH), 124.4 ppm (CH).
ACHTREUNG[3-D]-3-(4-Cyanophenyl)-1-phenylprop-2-en-1-one ([3-D]-3d): This com-
pound was prepared according to the general procedure; purification by
recrystallization from ethanol gave a colorless fluffy solid. M.p. 1588C
(lit. for all-proton 3d[46] 156–1578C); 1H NMR (CDCl3, 300 MHz): d=
8.00–8.04 (m, 2H), 7.76 (8%, residual signal), 7.67–7.73 (m, 4H), 7.59 (s,
1H), 7.57–7.64 (m, 1H), 7.48–7.54 ppm (m, 2H); 13C NMR (CDCl3,
75 MHz): d=189.7 (Cquat), 142.0 (br, residual signal), 139.2 (Cquat), 137.6
(Cquat), 133.2 (CH), 132.6 (CH), 128.7 (CH), 128.6 (CH), 128.5 (CH),
125.1 (CH), 118.3 (Cquat), 113.5 ppm (Cquat); MS (FD+): m/z (%): 236 (3)
[D-M++D], 235 (20) [D-M++H], 234 (100) [D-M+], 233 (21) [D-M+],
that is, 18% undeuterated product and 82% monodeuteration.
5-[(E)-3-Oxo-3-phenylpropenyl]thiophene-2-carbaldehyde (3k): This
compound was prepared according to the general procedure; purification
by chromatography on silica gel (pentane/diethyl ether) gave a pale
yellow solid. M.p. 87–908C; 1H NMR (CDCl3, 300 MHz): d=9.93 (s,
1H), 7.99–8.02 (m, 2H), 7.88 (d, J=15.5 Hz, 1H), 7.72 (d, J=3.9 Hz,
1H), 7.46–7.56 (m, 2H), 7.56–7.64 (m, 1H), 7.51 (d, J=15.4 Hz, 1H),
7.40 ppm (d, J=3.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=189.1
(Cquat), 182.8 (CH), 148.5 (Cquat), 144.6 (Cquat), 137.5 (Cquat), 136.6 (CH),
135.6 (CH), 133.3 (CH), 131.6 (CH), 128.8 (CH), 128.6 (CH), 124.4 ppm
(CH); IR (KBr): n˜ =1664, 1598, 1589, 1576, 1448, 1347, 1268, 1222, 1203,
1048, 1032, 1014, 970, 855, 817, 774, 763, 693, 666, 614 cmꢀ1; UV/Vis
(CHCl3): lmax (e)=349 nm (25300 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV): m/z
(%): 242 (100) [M+]; elemental analysis (%) calcd for C14H10O2S (242.3):
C 69.40, H 4.15, S 13.23; found: C 69.20, H 4.07, S 13.00.
3-(2-Cyanophenyl)-1-phenylprop-2-en-1-one (3e): This compound was
prepared according to general procedure; purification by chromatogra-
phy on silica gel (petroleum ether/ethyl acetate 4:1) and recrystallization
from ethanol gave a yellow solid. M.p. 133–1348C; 1H NMR (CDCl3,
300 MHz): d=7.98–8.05 (m, 3H), 7.72–7.83 (m, 3H), 7.58–7.69 (m, 2H),
7.47–7.55 ppm (m, 3H); 13C NMR (CDCl3, 75 MHz): d=189.9 (Cquat),
139.5 (CH), 137.9 (Cquat), 137.5 (Cquat), 133.8 (CH), 133.3 (CH), 133.0
(CH), 130.1 (CH), 128.8 (CH), 128.7 (CH), 128.1 (CH), 126.8 (CH),
117.5 (Cquat), 112.5 ppm (Cquat); IR (KBr): n˜ =3064, 2223, 1664, 1613,
1592, 1577, 1477, 1448, 1340, 1317, 1281, 1213, 1183, 1159, 1034, 1015,
970, 896, 862, 816, 783, 767, 728, 691, 654, 596 cmꢀ1; UV/Vis (CHCl3):
lmax (e)=295 nm (20700 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV): m/z (%): 233
(100) [M+], 204 (65), 156 (26) [M+ꢀPh], 128 (24) [M+ꢀPhCO], 105 (84)
[PhCO+], 101 (13), 77 (57) [Ph+]; elemental analysis (%) calcd for
C16H11NO (233.3): C 82.38, H 4.75, N 6.00; found: C 81.99, H 4.72,
N 5.92.
1-Phenyl-3-(2-thiazolyl)prop-2-en-1-one (3l): This compound was pre-
pared according to the general procedure; purification by chromatogra-
phy on silica gel (petroleum ether/ethyl acetate 4:1) and recrystallization
from ethanol gave a light brown solid. M.p. 928C; 1H NMR (CDCl3,
300 MHz): d=8.06 (m, 2H), 7.98 (d, J=3.2 Hz, 1H), 7.98 (m, 2H), 7.59–
7.64 (m, 1H), 7.49–7.54 ppm (m, 3H); 13C NMR (CDCl3, 75 MHz): d=
189.6 (Cquat), 164.0 (Cquat), 144.9 (CH), 137.5 (Cquat), 134.9 (CH), 133.3
(CH), 128.8 (CH), 128.7 (CH), 125.9 (CH), 121.8 ppm (CH); IR (KBr):
n˜ =1603, 1665 cmꢀ1; UV/Vis (CHCl3): lmax (e)=328 (17000), 256 nm
(7200 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV): m/z (%): 215 (21) [M+], 186
(100), 138 (11) [M+ꢀPh], 110 (11) [M+ꢀC6H5CO], 105 (13) [C6H5CO+],
77 (19) [Ph+]; elemental analysis (%) calcd for C12H9NOS (215.3): C
66.95, H 4.201, N 6.51, S 14.89; found: C 66.87, H 4.28, N 6.55, S 14.89.
3-(4-Trifluoromethylphenyl)-1-phenylprop-2-en-1-one (3 f): This com-
pound was prepared according to the general procedure; purification by
trituration with pentane and recrystallization from ethanol gave yellow
crystals. M.p. 128–1298C (lit.[41] 116–1188C); 1H NMR (CDCl3,
300 MHz): d=8.02–8.05 (m, 2H), 7.82 (d, J=18.9 Hz, 1H), 7.66–7.77 (m,
4H), 7.49–7.65 ppm (m, 4H); 13C NMR (CDCl3, 75 MHz): d=190.0
(Cquat), 142.7 (q, 5J(C,F)=0.6 Hz, CH), 138.3 (q, 4J
ACHTREUNG ACHTRENUG
137.8 (Cquat), 133.1 (CH), 131.9 (q, 2J
ACHTREUNG
128.6 (CH), 128.5 (CH), 125.9 (q, 3J
A
1
123.8 ppm (q, J
A
AHCTRE(GNU 2E,4E)-6-Oxo-6-phenylhexa-2,4-dienoic acid methyl ester (3m): This
compound was prepared according to the general procedure; purification
by chromatography on silica gel (pentane/diethyl ether) gave a pale
yellow solid. M.p. 138–1408C; 1H NMR (CDCl3, 300 MHz): d=7.96 (d,
J=7.2 Hz, 2H), 7.29–7.62 (m, 6H), 6.34 (m, 1H), 3.77 ppm (s, 3H);
13C NMR (CDCl3, 75 MHz): d=189.7 (Cquat), 166.4 (Cquat), 141.7 (CH),
140.4 (Cquat), 137.4 (Cquat), 133.3 (CH), 131.8 (CH), 128.8 (CH), 128.7
(CH), 128.5 (CH), 51.9 ppm (CH3); IR (KBr): n˜ =1599, 1623, 1661,
1708 cmꢀ1; UV/Vis (CHCl3): lmax (e)=291 nm (28500 molꢀ1 dm3 cmꢀ1);
MS (EI, 70 eV): m/z (%): 216 (35) [M+]; elemental analysis (%) calcd
for C13H12O3 (216.2): C 72.21, H 5.59; found: C 71.74, H 5.57.
Ethyl 4-(3-oxo-3-phenylprop-1-en-1-yl)benzoate (3g): This compound
was prepared according to the general procedure; purification by tritura-
tion with 2-propanol and recrystallization from 2-propanol gave a beige
solid. M.p. 82–838C (lit.[42] 83–848C); 1H NMR (CDCl3, 300 MHz): d=
8.01–8.09 (m, 4H), 7.81 (d, J=15.5 Hz, 1H), 7.68–7.71 (m, 2H), 7.49–7.62
(m, 4H), 4.39 (q, J=6.9 Hz, 2H), 1.41 ppm (t, J=6.9 Hz, 3H); 13C NMR
(CDCl3, 75 MHz): d=190.0 (Cquat), 165.7 (Cquat), 143.1 (CH), 138.8
(Cquat), 137.7 (Cquat), 132.8 (CH), 131.7 (Cquat), 129.9 (CH), 128.5 (CH),
128.4 (CH), 128.0 (CH), 123.9 (CH), 61.0 (CH2), 14.1 ppm (CH3).
4-(3-Oxo-3-phenylprop-1-en-1-yl)-benzophenone (3h): This compound
was prepared according to the general procedure; purification by tritura-
tion with diethyl ether and recrystallization from 2-propanol gave a beige
solid. M.p. 173–1748C (lit.[43] 1748C); 1H NMR (CDCl3, 300 MHz): d=
8.04–8.06 (m, 2H), 7.80–7.87 (m, 5H), 7.74–7.76 (m, 2H), 7.62–7.66 (m,
3H), 7.48–7.59 ppm (m, 4H); 13C NMR (CDCl3, 75 MHz): d=195.8
(Cquat), 190.1 (Cquat), 143.2 (CH), 138.9 (Cquat), 138.6 (Cquat), 137.9 (Cquat),
137.3 (Cquat), 133.0 (CH), 132.6 (CH), 130.6 (CH), 130.0 (CH), 128.7
(CH), 128.5 (CH), 128.4 (CH), 128.1 (CH), 124.1 ppm (CH).
3-[(E)-3-Oxo-3-phenylpropenyl]cyclohex-2-enone (3n): This compound
was prepared according to the general procedure; purification by chro-
matography on silica gel (pentane/diethyl ether) gave a pale yellow solid.
M.p. 113–1158C; 1H NMR (CDCl3, 300 MHz): d=7.96 (d, J=7.6 Hz,
2H), 7.60 (t, J=7.5 Hz, 1H), 7.50 (dd, J=7.6 Hz, 2H), 7.45 (d, J=
15.8 Hz, 1H), 7.32 (d, J=15.7 Hz, 1H), 6.24 (s, 1H), 2.61 (m, 2H), 2.48
(m, 2H), 2.12 ppm (m, 2H); 13C NMR (CDCl3, 75 MHz): d=199.5
(Cquat), 189.7 (Cquat), 154.1 (Cquat), 144.0 (CH), 137.3 (Cquat), 133.2 (CH),
133.0 (CH), 128.7 (CH), 128.5 (CH), 121.2 (CH), 37.6 (CH2), 24.9 (CH2),
22.0 ppm (CH2); IR (KBr): n˜ =1602, 1664 cmꢀ1; UV/Vis (CHCl3): lmax
(e)=299 nm (25400 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV): m/z (%): 226 (78)
[M+]; elemental analysis (%) calcd for C15H14O2 ”0.33 H2O (226.3 +
6.0): C 77.56, H 6.36; found: C 77.68, H 6.14.
4-[(E)-3-Oxo-3-phenylpropenyl]-benzaldehyde (3i): This compound was
prepared according to the general procedure; purification by trituration
with diethyl ether and recrystallization from 2-propanol gave a beige
solid. M.p. 125 C (lit.[44] 1258C); 1H NMR (CDCl3, 300 MHz): d=10.0 (s,
1H), 8.04 (d, J=7.2 Hz, 2H), 7.93 (d, J=8.3 Hz, 2H), 7.83 (d, J=
Chem. Eur. J. 2006, 12, 9081 – 9094
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9089

T. J. J. Müller et al.
3-(4-Cyanophenyl)-1-(4-phenoxyphenyl)prop-2-en-1-one (3o): This com-
pound was prepared according to the general procedure; purification by
recrystallization from ethanol gave light beige crystals. M.p. 178–1798C
(lit.[46] 175–1778C); 1H NMR (CDCl3, 300 MHz): d=8.00–8.05 (m, 2H),
7.77 (d, J=15.8 Hz, 1H), 7.68–7.71 (m, 4H), 7.59 (d, J=15.6 Hz, 1H),
7.38–7.44 (m, 2H), 7.19–7.24 (m, 1H), 7.03–7.10 ppm (m, 2H); 13C NMR
(CDCl3, 75 MHz): d=188.4 (Cquat), 162.7 (Cquat), 155.7 (Cquat), 142.0
(CH), 139.7 (Cquat), 133.1 (CH), 132.5 (Cquat), 131.3 (CH), 130.5 (CH),
129.0 (CH), 125.3 (CH), 125.2 (CH), 120.6 (CH), 118.8 (Cquat), 117.9
(CH), 113.8 ppm (Cquat).
128.9 (CH), 127.3 (CH), 126.9 (CH), 126.4 (CH), 124.2 ppm (CH); IR
(KBr): n˜ =1593, 1606, 1658 cmꢀ1; UV/Vis (DMSO): lmax (e)=317 nm
(22400 molꢀ1 dm3 cmꢀ1); MS (EI): m/z (%): 259 (100) [M+]; elemental
analysis (%) calcd for C13H9NO3S·0.33CH3CH2OH (259.3+15.5):
C
59.77, H 4.04, N 5.10, S 11.67; found: C 59.67, H 3.74, N 4.71, S 11.32.
3-[(E)-3-Oxo-3-thiophen-3-ylpropenyl]cyclohex-2-enone (3u): This com-
pound was prepared according to the general procedure; purification by
chromatography on silica gel (pentane/diethyl ether) gave a pale yellow
solid. M.p. 127–1308C; 1H NMR (CDCl3, 300 MHz): d=8.13 (dd, J=1.3,
2.9 Hz, 1H), 7.62 (dd, J=1.2, 5.1 Hz, 1H), 7.46 (d, J=16.1 Hz, 1H), 7.38
(dd, J=2.9, 5.2 Hz, 1H), 7.18 (dd, J=0.5, 15.6 Hz, 1H), 6.25 (s, 1H), 2.60
(m, 2H), 2.49 (m, 2H), 2.13 ppm (m, 2H); 13C NMR (CDCl3, 75 MHz):
d=199.6 (Cquat), 183.1 (Cquat), 154.1 (Cquat), 143.4 (CH), 142.5 (Cquat),
133.0 (CH), 132.7 (CH), 127.8 (CH), 127.3 (CH), 126.8 (CH), 37.7 (CH2),
25.0 (CH2), 22.0 ppm (CH2); IR (KBr): n˜ =1580, 1594, 1661 cmꢀ1; UV/
Vis (CHCl3): lmax (e)=299 nm (30300 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV):
m/z (%): 232 (82) [M+]; elemental analysis (%) calcd for C13H12O2S
(232.3): C 67.21, H 5.20; found: C 66.91, H 5.28.
1-(4-Methoxyphenyl)-3-(4-nitrophenyl)-prop-2-en-1-one (3p): This com-
pound was prepared according to the general procedure; purification by
chromatography on silica gel (petroleum ether/ethyl acetate 4:1) and re-
crystallization from ethanol gave a red-brown solid. M.p. 168–1698C
(lit.[47] 168–1698C); 1H NMR (CDCl3, 300 MHz): d=8.25 (d, J=8.9 Hz,
2H), 8.04 (d, J=8.9 Hz, 2H), 7.78 (d, J=15.9 Hz, 1H), 7.76 (d, J=
8.8 Hz, 2H), 7.64 (d, J=15.7 Hz, 1H), 6.98 (d, J=8.9 Hz, 2H), 3.89 ppm
(s, 3H); 13C NMR (CDCl3, 75 MHz): d=187.6 (Cquat), 163.7 (Cquat), 148.2
(Cquat), 141.1 (Cquat), 140.5 (CH), 131.1 (CH), 130.8 (Cquat), 128.6 (CH),
125.5 (CH), 124.0 (CH), 113.8 (CH), 55.5 ppm (CH3).
Tricarbonyl
A
chromi-
um(0) (3v): This compound was prepared according to the general proce-
dure; purification by chromatography on silica gel (pentane/diethyl
ether) and crystallization from pentane/diethyl ether gave an orange-red
3-(4-Cyanophenyl)-1-(2-fluorophenyl)prop-2-en-1-one (3q): This com-
pound was prepared according to the general procedure; purification by
recrystallization from ethanol gave pale yellow crystals. M.p. 121–1228C;
1H NMR (CDCl3, 300 MHz): d=7.85 (dt, J=1.9, 7.6 Hz, 1H), 7.72 (dd,
J=1.7, 15.8 Hz, 1H), 7.70 (m, 4H), 7.55–7.60 (m, 1H), 7.48 (dd, J=3.0,
15.8 Hz, 1H), 7.30 (dd, J=0.9, 7.7 Hz, 1H), 7.19 ppm (ddd, J=0.9, 8.3,
1
solid. M.p. 141–1438C; H NMR ([D6]DMSO, 300 MHz): d=8.78 (s, 1H),
7.76 (d, J=15.5 Hz, 1H), 7.64–7.68 (m, 2H), 7.32 (d, J=15.4 Hz, 1H),
6.36 (d, J=6.1 Hz, 2H), 5.79–5.86 ppm (m, 3H); 13C NMR ([D6]DMSO,
75 MHz): d=233.5 (Cquat), 182.4 (Cquat), 142.7 (Cquat), 140.5 (CH), 134.9
(CH), 128.1 (CH), 127.2 (CH), 124.3 (CH), 101.6 (Cquat), 95.8 (CH), 95.7
(CH), 94.1 ppm (CH); IR (KBr): n˜ =1598, 1656, 1883, 1969 cmꢀ1; UV/Vis
(DMSO): lmax (e)=446 (4700), 276 nm (18600 molꢀ1 dm3 cmꢀ1); MS (EI):
m/z (%): 350 (17) [M+], 294 (11) [M+ꢀ2CO], 266 (100) [M+ꢀ3CO],
214 (14) [M+ꢀCr(CO)3], 52 (24) [Cr+]; elemental analysis (%) calcd for
C16H10CrO4S (350.3): C 54.85, H 2.87, S 9.15; found: C 55.59, H 3.26,
S 9.49.
11.0 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=188.5 (d, 3J
quat, CO), 161.9 (d, 1J(C,F)=252.7 Hz, Cquat), 142.2 (d, 5J
CH), 139.5 (Cquat), 135.0 (d, 3J
(C,F)=8.7 Hz, CH), 133.1 (CH), 131.5 (d,
4J(C,F)=2.6 Hz, CH), 129.2 (CH), 128.9 (d, 3J
(C,F)=7.3 Hz, CH), 126.9
(d, 2J(C,F)=12.8 Hz, Cquat), 125.1 (d, 4J
(C,F)=3.5 Hz, CH), 118.7 (Cquat),
117.0 (d, 2J
(C,F)=23.0 Hz, CH), 114.0 ppm (Cquat); IR (KBr): n˜ =1602,
1611, 1660, 2228 cmꢀ1
UV/Vis (CHCl3): lmax (e)=305 nm
ACHTREUNG
C
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
A
ACHTREUNG
ACHTREUNG
;
(30900 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV): m/z (%): 251 (100) [M+], 222
(17), 156 (18), 128 (13) [M+ꢀFC6H4CO], 123 (22) [FC6H4CO+], 95 (13)
[C6H4F+]; elemental analysis (%) calcd for C16H10NOF (251.3): C 76.48,
H 4.01, N 5.57; found: C 76.38, H 4.00, N 5.56.
AHCTRE(GNU 2E,4E)-6-Oxo-6-thiophen-3-yl-hexa-2,4-dienoic acid methyl ester (3w):
This compound was prepared according to the general procedure; purifi-
cation by chromatography on silica gel (pentane/diethyl ether) gave a
pale yellow solid. M.p. 137–1388C; 1H NMR (CDCl3, 300 MHz): d=8.11
(dd, J=1.2, 2.8 Hz, 1H), 7.61 (dd, J=1.3, 5.1 Hz, 1H), 7.43 (dd, J=2.9,
10.2 Hz, 1H), 7.43 (d, J=10.7 Hz, 1H), 7.37 (dd, J=2.8, 5.1 Hz, 1H),
7.13 (m, 1H), 6.29 (m, 1H), 3.80 ppm (s, 3H); 13C NMR (CDCl3,
75 MHz): d=183.1 (Cquat), 166.4 (Cquat), 142.5 (Cquat), 141.5 (CH), 139.7
(CH), 132.7 (CH), 132.5 (CH), 128.7 (CH), 127.3 (CH), 126.8 (CH),
51.9 ppm (CH3); IR (KBr): n˜ =1594, 1624, 1653, 1709 cmꢀ1; UV/Vis
(CHCl3): lmax (e)=290 nm (25500 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV): m/z
(%): 222 (83) [M+]; elemental analysis (%) calcd for C11H10O2S (222.3):
C 59.44, H 4.53, S 14.42; found: C 59.89, H 4.78, S 13.56.
3-(4-Cyanophenyl)-1-(4-fluorophenyl)prop-2-en-1-one (3r): This com-
pound was prepared according to the general procedure; purification by
recrystallization from ethanol gave light beige crystals. M.p. 151–1528C;
1H NMR (CDCl3, 300 MHz): d=8.07 (dd, J=8.8, 5.4 Hz, 2H), 7.78 (d,
J=15.7 Hz, 1H), 7.72 (m, 4H), 7.58 (d, J=15.6 Hz, 1H), 7.20 ppm (m,
2H); 13C NMR (CDCl3, 75 MHz): d=188.4 (Cquat), 166.3 (d, 1J
254.0 Hz, Cquat), 142.7 (CH), 139.5 (Cquat), 134.4 (d, 4J
(C,F)=2.9 Hz,
quat), 133.1 (CH), 131.6 (d, 3J
(C,F)=9.3 Hz, CH), 129.1 (CH), 125.0
(CH), 118.7 (Cquat), 116.4 (d, 2J
(C,F)=21.6 Hz, CH), 114.0 ppm (Cquat);
ACHTRE(UNG C,F)=
AHCTREUNG
C
ACHTREUNG
AHCTREUNG
19F NMR (CDCl3, 282 MHz): d=ꢀ130.4 ppm; IR (KBr): n˜ =1610, 1663,
2230 cmꢀ1; UV/Vis (CHCl3): lmax (e)=305 nm (23200 molꢀ1 dm3 cmꢀ1);
MS (EI, 70 eV): m/z (%): 251 (100) [M+], 222 (15), 156 (12) [M+
ꢀFC6H4+], 128 (10) [M+ꢀFC6H4CO], 123 (28) [FC6H4CO+], 95 (21)
[C6H4F+]; elemental analysis (%) calcd for C16H10FNO (251.3): C 76.49,
H 4.01, N 5.57; found: C 76.43, H 3.64, N 5.62.
1-(2-Furyl)-3-(4-nitrophenyl)prop-2-en-1-one (3x): This compound was
prepared according to the general procedure; purification by recrystalli-
[49]
zation from ethanol/THF gave a beige powder. M.p. 2328C (lit.
1
2388C); H NMR (CDCl3, 300 MHz): d=8.27 (d, J=8.8 Hz, 2H), 7.88 (d,
J=15.9 Hz, 1H), 7.79 (d, J=8.8 Hz, 2H), 7.69 (d, J=1,1 Hz, 1H), 7.56
(d, J=15.8 Hz, 1H), 7.39 (d, J=3.6 Hz, 1H), 6.63 ppm (dd, J=1.7,
3.6 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=186.0 (Cquat), 147.0 (CH),
140.9 (Cquat), 140.8 (CH), 129.0 (CH), 128.6 (Cquat), 124.9 (CH), 124.2
(CH), 123.7 (Cquat), 118.3 (CH), 112.9 ppm (CH).
1-(4-Bromophenyl)-3-(4-cyanophenyl)prop-2-en-1-one (3s): This com-
pound was prepared according to the general procedure; purification by
[48]
recrystallization from ethanol gave a beige solid. M.p. 1688C (lit.
1678C); 1H NMR (CDCl3, 300 MHz): d=7.87–7.90 (m, 2H), 7.78 (d, J=
15.7 Hz, 1H), 7.70–7.72 (m, 4H), 7.64–7.67 (m, 2H), 7.54 ppm (d, J=
15.7 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=188.4 (Cquat), 142.4 (CH),
138.8 (Cquat), 136.1 (Cquat), 132.5 (CH), 131.9 (CH), 129.8 (CH), 128.5
(CH), 128.3 (Cquat), 124.3 (CH), 118.1 (Cquat), 113.5 ppm (Cquat).
3-(4-Cyanophenyl)-1-(10-hexyl-10H-phenothazin-3-yl)prop-2-en-1-one
(3y): This compound was prepared according to the general procedure;
purification by chromatography on silica gel (petroleum ether/ethyl ace-
tate 3:1) and recrystallization from ethanol gave an orange-red solid.
M.p. 1238C; 1H NMR (CDCl3, 300 MHz): d=7.86 (dd, J=2.3, 8.5 Hz,
1H), 7.78 (d, J=1.7 Hz, 1H), 7.68–7.74 (m, 5H), 7.57 (d, J=15.7 Hz,
1H), 7.11–7.21 (m, 2H), 6.95–6.99 (m, 1H), 6.89 (d, J=8.3 Hz, 2H), 3.89
(t, J=6.9 Hz, 2H), 1.78–1.88 (m, 2H), 1.41–1.48 (m, 2H), 1.28–1.37 (m,
4H), 0.89 ppm (t, J=7.0 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d=186.7
(Cquat), 149.6 (Cquat), 143.3 (Cquat), 141.0 (CH), 139.2 (Cquat), 132.4 (CH),
131.5 (Cquat), 128.5 (CH), 128.4 (CH), 127.6 (CH), 127.6 (CH), 127.3
(CH), 124.5 (CH), 124.4 (Cquat), 123.5 (Cquat), 123.2 (CH), 118.2 (Cquat),
115.6 (CH), 114.4 (CH), 113.1 (Cquat), 47.7 (CH2), 31.2 (CH2), 26.5 (CH2),
(E)-3-(4-Nitrophenyl)-1-thiophen-3-ylpropenone (3t): This compound
was prepared according to the general procedure; purification by chro-
matography on silica gel (pentane/diethyl ether) and crystallization from
ethanol gave a pale yellow solid. M.p. 182–1858C; 1H NMR (CDCl3,
300 MHz): d=8.25 (d, J=8.7 Hz, 2H), 8.21 (dd, J=1.1, 2.8 Hz, 1H), 7.76
(d, J=8.8 Hz, 2H), 7.67 (dd, J 1.1, 5.2 Hz, 1H), 7.50 (d, J=15.6 Hz, 1H),
7.39 ppm (dd, J=2.8, 5.1 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=183.0
(Cquat), 148.5 (Cquat), 142.6 (Cquat), 140.9 (Cquat), 140.8 (CH), 132.8 (CH),
9090
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 9081 – 9094

Synthesis of Chalcones
FULL PAPER
26.3 (CH2), 22.3 (CH2), 13.7 ppm (CH3); IR (KBr): n˜ =1570, 1605, 1656,
2227 cmꢀ1; UV/Vis (CHCl3): lmax (e)=438 (9800), 306 (37800), 258 nm
(25200 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV): m/z (%): 438 (100) [M+], 367
(79) [M+ꢀC5H11], 353 (91) [M+ꢀC6H13]; elemental analysis (%) calcd
for C28H26N2OS (438.6): C 76.68, H 5.98, N 6.39, S 7.31; found: C 76.87,
H 5.98, N 6.54, S 7.28.
elemental analysis (%) calcd for C16H10NOF (251.3): C 76.49, H 4.01,
N 5.57; found: C 76.17, H 4.40, N 5.51.
Kinetic studies: All reactions were carried out in NMR tubes. Compound
4r (30 mg, 0.12 mmol) was dissolved in a total volume of 0.6 mL of sol-
(4r)=0.20 molLꢀ1). The reaction was then monitored by record-
vents (c0CAHTREUNG
ing 19F NMR spectra. The 19F NMR signals were observed at d=
ꢀ139.1 ppm (4r) and d=ꢀ130.4 ppm (3r). The obtained data were pro-
1-(4-Cyanophenyl)-4-methylene-hex-1-en-3-one (3z): This compound was
prepared according to the general procedure; purification by recrystalli-
AHCTREcGNU essed by logarithmic and linear regression analyses furnishing time–con-
1
zation from ethanol gave a colorless solid. M.p. 1118C; H NMR (CDCl3,
version plots, slopes, and axis intercepts (Tables 6–18).
300 MHz): d=7.63–7.68 (m, 4H), 7.59 (d, J=15.8 Hz, 1H), 7.31 (d, J=
15.8 Hz, 1H), 6.05 (s, 1H), 5.84 (t, J=1.4 Hz, 1H), 2.41 (q, J=7.4 Hz,
2H), 1.08 ppm (t, J=7.4 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d=191.0
(Cquat), 151.0 (Cquat), 140.6 (CH), 139.1 (Cquat), 132.4 (CH), 128.3 (CH),
124.9 (CH), 123.1 (CH2), 118.2 (Cquat), 113.1 (Cquat), 24.0 (CH2), 12.3 ppm
(CH3); IR (KBr): n˜ =1559, 1602, 1656, 2225 cmꢀ1; UV/Vis (CHCl3): lmax
(e)=300 nm (18800 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV): m/z (%): 211 (65)
Table 6. Kinetics in triethylamine as a solvent, c0ACHTREUNG
(4r)=0.20 molLꢀ1, T=
348 K.[a]
t [s]
Percentage 4r Percentage 3r
A
]
ln([4r]t/A[4r]0)
A
CHTREUNG
+
+
+
ꢀ
[M ], 196 (34) [M ꢀCH3], 156 (100) [M ꢀCH2=C C2H5], 154 (14), 128
(51) [M+ꢀCH2=C(CO)C2H5], 101 (15); elemental analysis (%) calcd for
C14H13NO (211.3): C 79.59, H 6.20, N 6.63; found: C 79.37, H 6.23,
N 6.61.
9600 90.89
9.11
18.46
30.61
33.63
34.81
38.66
0.1808
0.1623
0.1381
0.1321
0.1297
0.1221
0.0956
0.2041
0.3654
0.4099
0.4279
0.4887
12600 81.54
16500 69.39
20100 66.37
22740 65.19
26520 61.34
1-(4-Cyanophenyl)hexa-1,4-dien-3-one (3aa): This compound was pre-
pared according to the general procedure; purification by chromatogra-
phy on silica gel (petroleum ether/ethyl acetate 4:1) gave a yellow solid.
M.p. 112–1138C; 1H NMR (CDCl3, 300 MHz): d=7.68 (d, J=8.7 Hz,
2H), 7.64 (d, J=8.7 Hz, 2H), 7.59 (d, J=15.9 Hz, 1H), 7.03 (d, J=
15.9 Hz, 1H), 7.05 (dq, J=15.5, 6.9 Hz, 1H), 6.44 (dq, J=15.5, 1.5 Hz,
1H), 1.98 ppm (dd, J=1.5, 6.8 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d=
188.1 (Cquat), 144.3 (CH), 140.1 (CH), 139.0 (Cquat), 132.4 (CH), 130.7
(CH), 128.3 (CH), 127.3 (CH), 118.1 (Cquat), 113.1 (Cquat), 18.3 ppm
(CH3); IR (KBr): n˜ =1559, 1594, 1633, 1661, 1675, 2226 cmꢀ1; UV/Vis
(CHCl3): lmax (e)=300 nm (31300 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV): m/z
(%): 197 (7) [M+], 69 (23) [CH3CH=CHCO+], 41 (37) [CH3CH=CH+],
39 (100) [CH3C=C+]; elemental analysis (%) calcd for C13H11NO (197.2):
C 79.17, H 5.62, N 7.10; found: C 78.93, H 5.71, N 7.10.
[a] Evaluation from 9 to 40% conversion, since 3r started to precipitate.
Slope: kobs’ =2.27”10ꢀ5 mol2 Lꢀ2 sꢀ1. r2 =0.92.
Table 7. Kinetics in toluene/triethylamine (1:1), c0ACHTREUNG
(4r)=0.20 molLꢀ1, T=
348 K.[a]
t [s]
Percentage 4r Percentage 3r
A
]
ln([4r]t/A[4r]0)
A
CHTREUNG
13500 84.49
18300 80.38
21000 76.30
24780 64.14
27300 61.10
29100 55.94
33600 55.86
34800 51.37
39000 50.59
42600 44.18
46200 36.67
48900 37.30
15.51
19.62
23.71
35.86
38.90
44.06
44.14
48.63
49.41
55.82
63.32
62.70
0.1681
0.1600
0.1518
0.1276
0.1216
0.1113
0.1112
0.1022
0.1007
0.08792
0.07297
0.07422
0.1685
0.2184
0.2706
0.4441
0.4926
0.5809
0.5823
0.6662
0.6814
0.8168
1.003
TricarbonylACHTREUNG
(h6-{(E)-3-[(E)-2-phenylethenyl)}prop-1-en-3-onyl]benzene)-
chromium(0) (3ab): This compound was prepared according to the gener-
al procedure; purification by chromatography on silica gel (pentane/di-
ethyl ether) and crystallization from pentane/diethyl ether gave an
orange-red solid. M.p. 688C; 1H NMR ([D6]DMSO, 300 MHz): d=5.80–
6.30 (m, 5H), 7.18–7.83 ppm (m, 9H); 13C NMR ([D6]DMSO, 75 MHz):
d=233.5 (Cquat), 188.1 (Cquat), 143.7 (CH), 140.3 (CH), 134.7 (Cquat), 130.9
(CH), 129.2 (CH), 128.7 (CH), 126.5 (CH), 125.7 (CH), 101.8 (Cquat), 95.8
(CH), 95.5 (CH), 94.2 ppm (CH); IR (KBr): n˜ =1618, 1651, 1886,
0.9862
[a] Evaluation from 15 to 63% conversion, since 3r started to precipitate.
Slope: kobs’ =2.42”10ꢀ5 mol2 Lꢀ2 sꢀ1. r2 =0.97.
1965 cmꢀ1
;
UV/Vis (DMSO): lmax (e)=445 (2800), 311 nm
(16600 molꢀ1 dm3 cmꢀ1); MS (EI): m/z (%): 370 (19) [M+], 314 (15) [M+
ꢀ2CO], 286 (100) [M+ꢀ3CO], 234 (17) [M+ꢀCr(CO)3], 52 (49) [Cr+];
HRMS calcd for C20H14CrO4: 370.0297; found: 370.0296.
Table 8. Kinetics in ethanol/triethylamine (1:1), c0ACHTREUNG
(4r)=0.20 molLꢀ1, T=
348 K.[a]
3-(4-Cyanophenyl)-1-(4-fluorophenyl)-prop-2-yn-1-ol (4r): [PdCl2ACHTRE(UNG PPh3)2]
(28.0 mg, 0.04 mmol) and CuI (3.8 mg, 0.02 mmol) were added to a de-
gassed solution of 1d (364 mg, 2.00 mmol) and 2e (315 mg, 2.10 mmol) in
triethylamine (5.0 mL) and THF (5.0 mL). The mixture was heated to
reflux for 20 min and then cooled to room temperature. Then diethyl
ether (15 mL) was added to precipitate the triethylammonium bromide.
The mixture was filtered and the solvents were removed from the filtrate
in vacuo. The residue was subjected to chromatography on silica gel
(hexane/acetone 3:1) and after crystallization from diethyl ether/pentane
373 mg (74%) of 4r were obtained as intense yellow crystals. M.p. 68–
698C; 1H NMR (CDCl3, 300 MHz): d=7.51–7.61 (m, 6H), 7.04–7.12 (m,
2H), 5.68 (s, 1H), 2.51 ppm (br, 1H); 13C NMR (CDCl3, 75 MHz): d=
162.8 (d, J=246.0 Hz, Cquat), 135.9 (d, J=3.3 Hz, Cquat), 132.2 (CH), 132.0
(CH), 128.5 (d, J=8.4 Hz, CH), 127.1 (Cquat), 118.2 (Cquat), 115.6 (d, J=
21.8 Hz, CH), 112.1 (Cquat), 92.9 (Cquat), 85.0 (Cquat), 64.3 ppm (CH);
19F NMR (CDCl3, 282 MHz): d=ꢀ139.1 ppm; IR (KBr): n˜ =1604,
t [s]
Percentage 4r Percentage 3r
G
]
ln([4r]t/A[4r]0)
U
CHTREUNG
8100 72.98
27.02
34.05
42.62
47.42
56.06
61.92
66.11
66.14
65.71
72.80
72.86
79.80
83.00
83.35
88.89
0.3149
0.4163
0.5555
0.6429
0.8224
0.9655
1.082
1.083
1.070
1.302
1.304
1.600
1.772
1.793
2.197
11100 65.95
14400 57.38
15900 52.58
17580 43.94
19200 38.08
21900 33.89
23880 33.86
25620 34.29
28200 27.20
29880 27.14
32700 20.20
35700 17.00
38280 16.65
43380 11.11
2227 cmꢀ1
;
UV/Vis (CHCl3): lmax (e)=274 nm (25300), 262
(25800 molꢀ1 dm3 cmꢀ1); MS (EI, 70 eV): m/z (%): 251 (96) [M+], 250
(100) [M+ꢀH], 234 (34) [M+ꢀOH], 232 (23) [M+ꢀF], 149 (14) [C=
CCH(OH)C6H4F+], 127 (17) [NCC6H4C=CH+], 123 (27) [FC6H4CO+];
[a] Evaluation from 27 to 89% conversion. Slope:
k
obs’ =5.23”
10ꢀ5 mol2 Lꢀ2 sꢀ1. r2 =0.98.
Chem. Eur. J. 2006, 12, 9081 – 9094
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9091

T. J. J. Müller et al.
Table 9. Kinetics in acetonitrile/triethylamine (1:1), c
T=348 K.[a]
0A
,
Table 13. Kinetics in acetonitrile/triethylamine (14:1),
0.48 molLꢀ1, c (4r)=0.20 molLꢀ1, T=348 K.[a]
0A
cACHTREUNG
CTHREUNG
t [s]
960 86.55
2640 58.00
6780 31.96
7920 27.14
9120 18.62
9720 17.42
10860 11.54
11340 10.29
Percentage 4r Percentage 3r
G
]
ln([4r]t/A[4r]0)
U
E
t [s] Percentage 4r Percentage 3r
[4r]t [molLꢀ1
1920 75.50
2400 71.19
U
]
ln
A
CHTREUNG
13.45
42.00
68.04
72.86
81.38
82.58
88.46
89.71
91.90
0.1444
0.5447
1.141
1.304
1.681
1.747
2.159
2.274
2.513
24.50
28.81
29.66
37.38
39.60
49.79
60.70
67.56
70.32
73.68
78.24
75.58
0.2810
0.3398
0.3519
0.4680
0.5042
0.6889
0.9340
1.1259
1.2146
1.3350
1.5252
1.4098
3300 70.34
3840 62.62
5460 60.40
7140 50.21
11460 39.30
13740 32.44
15060 29.68
16200 26.32
17400 21.76
20700 24.42
12480
8.11
[a] Evaluation from 13 to 92% conversion. Slope:
kobs’ =2.01”
10ꢀ4 mol2 Lꢀ2 sꢀ1. r2 =0.98.
[a] Evaluation from 24 to 76% conversion. Slope:
kobs’ =6.86”
10ꢀ5 mol2 Lꢀ2 sꢀ1. r2 =0.97.
Table 10. Kinetics in acetonitrile/triethylamine (1:1),
cACHTREUNG
0A
t [s]
960 86.55
2640 58.00
6780 31.96
7920 27.14
9120 18.62
9720 17.42
10860 11.54
11340 10.29
Percentage 4r Percentage 3r
G
]
ln
G
CHTREUNG
Table 14. Kinetics
in
acetonitrile/triethylamine
(1:1),
ln
c0ACHTREUNG
(4r)=
0.20 molLꢀ1, T=328 K.[a
13.45
42.00
68.04
72.86
81.38
82.58
88.46
89.71
91.89
0.1444
0.5447
1.141
1.304
1.681
1.747
2.159
2.274
2.513
t [s] Percentage 4r Percentage 3r
5640 82.84
[4r]t [molLꢀ1
]
C
CHTREUNG
17.16
34.59
40.56
52.60
55.90
67.20
72.14
77.46
75.68
77.33
80.25
0.1649
0.1302
0.1183
0.1882
0.4245
0.5203
0.7465
0.8187
1.115
1.278
1.490
1.414
1.484
10260 65.41
14820 59.44
19440 47.40
22020 44.10
25740 32.80
29340 27.86
30780 22.54
32640 24.32
34380 22.67
36060 19.75
0.09433
0.08776
0.06527
0.05543
0.04485
0.04841
0.04511
0.03930
12480
8.105
[a] Evaluation from 13 to 92% conversion. Slope:
kobs’ =2.01”
10ꢀ4 mol2 Lꢀ2 sꢀ1. r2 =0.98.
1.622
Table 11. Kinetics in acetonitrile/triethylamine (5:1),
cACHTREUNG
[a] Evaluation from 17 to 80% conversion. Slope:
kobs’ =4.80”
0A
10ꢀ5 mol2 Lꢀ2 sꢀ1. r2 =0.98.
t [s]
1980 64.92
2520 64.50
Percentage 4r Percentage 3r
ln
CHTREUNG
35.08
35.50
53.07
58.45
68.37
71.65
75.91
81.22
84.78
87.59
0.4321
0.4385
0.7564
0.8782
1.1512
1.2604
1.4233
1.6724
1.8828
2.0863
Table 15. Kinetics
in
acetonitrile/triethylamine
(1:1),
ln
c0ACHTREUNG(4r)=
0.20 molLꢀ1, T=338 K.[a]
3600 46.93
4140 41.55
5760 31.63
6300 28.35
7380 24.09
8520 18.78
9600 15.22
10680 12.41
t [s] Percentage 4r Percentage 3r
4740 63.54
[4r]t [molLꢀ1
]
CHTREUNG
36.46
46.17
54.59
71.55
73.58
80.48
78.21
81.82
80.64
89.45
94.50
0.1264
0.1071
0.4535
0.6194
0.7894
1.257
1.331
1.634
1.524
1.705
1.642
2.249
2.901
6540 53.83
8460 45.41
12840 28.45
14160 26.42
16860 19.52
18600 21.79
20340 18.18
21240 19.36
27180 10.55
0.09037
0.05661
0.05257
0.03885
0.04335
0.03618
0.03854
0.02099
0.01094
[a] Evaluation from 35 to 88% conversion. Slope:
kobs’ =1.97”
10ꢀ4 mol2 Lꢀ2 sꢀ1. r2 =0.996.
27720
5.50
Table 12. Kinetics in acetonitrile/triethylamine (10:1),
cACHTREUNG
0A
[a] Evaluation from 36 to 95% conversion. Slope:
kobs’ =8.85”
10ꢀ5 mol2 Lꢀ2 sꢀ1. r2 =0.93.
t [s]
1380 83.77
2940 68.15
Percentage 4r Percentage 3r
[4r]t [molLꢀ1
]
ln
G
CHTREUNG
16.23
31.85
41.31
54.40
62.35
64.75
70.22
77.17
76.08
85.09
0.1667
0.1356
0.1168
0.0907
0.0749
0.0702
0.0593
0.0454
0.0476
0.0297
0.1771
0.3835
0.5329
0.7853
0.9767
1.0426
1.2113
1.4773
1.4306
1.9030
Acknowledgements
4080 58.69
6240 45.60
7980 37.65
9360 35.25
10620 29.78
11700 22.83
12780 23.92
15000 14.91
This work was supported by the Deutsche Forschungsgemeinschaft
(Graduate College 850). Financial support by the Fonds der Chemischen
Industrie and the Dr.-Otto-Rçhm Gedächtnisstiftung is gratefully ac-
knowledged. The authors also cordially thank Daniel Aktah, Ulrike
Troppmann, Serif Kalkan, Peter Speer, Michael Miserok, and Christoph
Busche for experimental assistance, Dr. Nasser A. M. Yehia, Oana G.
Schramm, and Daniel M. DꢁSouza for valuable discussions, and the
BASF AG for the generous donation of chemicals.
[a] Evaluation from 16 to 85% conversion. Slope:
kobs’ =1.20”
10ꢀ4 mol2 Lꢀ2 sꢀ1. r2 =0.98.
9092
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 9081 – 9094

Synthesis of Chalcones
FULL PAPER
Table 16. Kinetics
in
acetonitrile/triethylamine
[4r]t [molLꢀ1
(1:1),
ln
c
G
[8] Q.-B. Song, X.-N. Li, T.-H. Shen, S.-D. Yang, G.-R. Qiang, X.-L. Wu,
Y.-X. Ma, Synth. Commun. 2003, 33, 3935–3941.
[9] a) J.-C. Ribierre, G. Cheval, F. Huber, L. Mager, A. Fort, R. Muller,
S. Mery, J. F. Nicoud, J. Appl. Phys. 2002, 91, 1710–1712; b) C.
Melzer, M. Barzoukas, A. Fort, S. Mery, J.-F. Nicoud, Appl. Phys.
Lett. 1997, 71, 2248–2250.
0.20 molLꢀ1, T=348 K.[a]
t [s] Percentage 4r Percentage 3r
E
]
N
960 86.55
2640 58.00
6780 31.96
7920 27.14
9120 18.62
9720 17.42
10860 11.54
11340 10.29
13.45
42.00
68.04
72.86
81.38
82.58
88.46
89.71
91.89
0.1722
0.1154
0.1444
0.5447
1.141
1.304
1.681
1.747
2.159
2.274
2.513
0.06360
0.05402
0.03705
0.03467
0.02297
0.02048
0.01613
[10] D. H. Choi, J. H. Park, J. H. Lee, S. D. Lee, Thin Solid Films 2000,
360, 213–221.
[11] General reviews on 1,3-dipolar cycloadditions: a) L. Raimondi, M.
Benaglia, Eur. J. Org. Chem. 2001, 1033–1043; b) J. Mulzer, Nachr.
Chem. Tech. Lab. 1984, 32, 961–965; c) R. Carrie, Heterocycles
1980, 14, 1529–1545; d) P. K. Kadaba, Synthesis 1973, 71–84.
[12] Reviews: a) B. Stanovnik, B. Jelen, C. Turk, M. Zlicar, J. Svete, J.
Heterocycl. Chem. 1998, 35, 1187–1204; b) B. Stanovnik, Tetrahe-
dron 1991, 47, 2925–2945.
12480
8.105
[a] Evaluation from 13 to 92% conversion. Slope:
kobs’ =1.90”
10ꢀ4 mol2 Lꢀ2 sꢀ1. r2 =0.976.
[13] Reviews: A. Katritzky, Y. Zhang, S. Yuming, K. Sandeep, Heterocy-
cles 2003, 60, 1225–1239.
[14] Reviews: H. M. I. Osborn, N. Gemmell, L. M. Harwood, J. Chem.
Soc. Perkin Trans. 1 2002, 2419–2438.
[15] Review: S. Lçber, P. Rodriguez-Loaiza, P. Gmeiner, Org. Lett. 2003,
5, 1753–1755.
[16] Review: C. Grundmann, Synthesis 1970, 344–359.
[17] C. Thebtaranonth, Y. Thebtaranonth in The Chemistry of Enones,
Vol. 29 (Eds.: S. Patai, Z. Rappoport), Wiley, Chichester, New York,
Brisbane, Toronto, Singapore, 1989, pp. 199–280.
[18] a) S. A. May, P. A. Grieco, Chem. Commun. 1998, 15, 1597–1598;
b) M. B. Cid, G. Pattenden, Synlett 1998, 540–542.
[19] A. Liguori, G. Sindona, N. Uccella, Tetrahedron 1984, 40, 1901–
1906.
[20] T. Hirao, D. Misu, T. Agawa, J. Am. Chem. Soc. 1985, 107, 7179–
7181.
Table 17. Kinetics
in
acetonitrile/triethylamine
(1:1),
ln
c0ACHTREUNG
(4r)=
0.20 molLꢀ1, T=358 K.[a]
t [s]
Percentage 4r
Percentage 3r
A
]
A
CHTREUNG
1440
2040
2640
3120
3660
4200
4740
63.54
45.24
34.23
32.80
18.49
11.54
12.23
36.46
54.76
65.77
67.20
81.51
88.46
87.77
0.1264
0.4535
0.7932
1.072
1.115
1.688
2.159
2.102
0.09003
0.06813
0.06527
0.03680
0.02297
0.02433
[a] Evaluation from 36 to 88% conversion. Slope:
kobs’ =5.44”
10ꢀ4 mol2 Lꢀ2 sꢀ1. r2 =0.952.
[21] a) S. Swaminathan, K. V. Narayan, Chem. Rev. 1971, 71, 429–438;
b) M. Edens, D. Boerner, C. R. Chase, D. Nass, M. D. Schiavelli, J.
Org. Chem. 1977, 42, 3403.
Table 18. Temperature-dependent kinetics in acetonitrile/triethylamine
(1:1), c0A
(4r)=0.20 molLꢀ1
C
.
[a]
T
[K]
1/T kobs’
[Kꢀ1 [mol2 Lꢀ2 sꢀ1
lnkobs’
kobs’/T
(kobs’/T)[b]
lnACHTREUNG
[22] Recent reviews on transition metal assisted sequential transforma-
tions and domino processes: a) G. Balme, E. Bossharth, N. Mon-
teiro, Eur. J. Org. Chem. 2003, 3403–3408; b) G. Battistuzzi, S.
Cacchi, G. Fabrizi, Eur. J. Org. Chem. 2002, 2671–2681; c) E.-I. Ne-
gishi, C. Copꢂret, S. Ma, S.-Y. Liou, F. Liu, Chem. Rev. 1996, 96,
365–393; d) L. F. Tietze, Chem. Rev. 1996, 96, 115–136.
[23] Lead reviews on Sonogashira couplings: a) S. Takahashi, Y. Kuroya-
ma, K. Sonogashira, N. Hagihara, Synthesis 1980, 627–630; b) K. So-
nogashira in Metal Catalyzed Cross-coupling Reactions, Wiley-VCH,
Weinheim, 1998, 203–229; c) K. Sonogashira, J. Organomet. Chem.
2002, 653, 46–49; d) E.-I. Negishi, L. Anastasia, Chem. Rev. 2003,
103, 1979–2018.
G
]
]
[mol2 Lꢀ2 sꢀ1 Kꢀ1
]
358 0.00279 5.44”10ꢀ4
348 0.00287 1.90”10ꢀ4
338 0.00296 8.85”10ꢀ5
328 0.00305 4.80”10ꢀ5
ꢀ7.52
ꢀ8.57
ꢀ9.33
ꢀ9.95
1.52”10ꢀ6
5.45”10ꢀ7
2.62”10ꢀ7
1.46”10ꢀ7
ꢀ13.40
ꢀ14.42
ꢀ15.16
ꢀ15.74
[a] Arrhenius plot: r2 =0.978, x axis: lnA=18.04; A=0.69”108, slope:
ꢀEa/R=ꢀ9215.2 K; Ea =76.6 kJmolꢀ1. [b] Eyring plot: r2 =0.976, x axis:
ln
A
ꢀ8868.9; DHꢀ =73.7 kJmolꢀ1
.
[24] T. J. J. Müller, M. Ansorge, D. Aktah, Angew. Chem. 2000, 112,
1323–1326; Angew. Chem. Int. Ed. 2000, 39, 1253–1256.
[25] a) T. J. J. Müller, R. Braun, M. Ansorge, Org. Lett. 2000, 2, 1967–
1970; b) R. U. Braun, K. Zeitler, T. J. J. Müller, Org. Lett. 2000, 2,
4181–4184; c) R. U. Braun, K. Zeitler, T. J. J. Müller, Org. Lett.
2001, 3, 3297–3300; d) N. A. M. Yehia, K. Polborn, T. J. J. Müller,
Tetrahedron Lett. 2002, 43, 6907–6910; e) O. G. Dediu, N. A. M.
Yehia, Z. Naturforsch. B 2004, 59, 443–450; f) R. U. Braun, T. J. J.
Müller, Synthesis 2004, 2391–2406; g) R. U. Braun, T. J. J. Müller,
Tetrahedron 2004, 60, 9463–9469; h) D. M. DꢁSouza, F. Rominger,
T. J. J. Müller, Angew. Chem. 2005, 117, 156–161; Angew. Chem. Int.
Ed. 2005, 44, 153–158; i) O. G. Dediu, N. A. M. Yehia, T. Oeser, K.
Polborn, T. J. J. Müller, Eur. J. Org. Chem. 2005, 1834–1858.
[26] CCDC 607653 (3q) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
the Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
[1] Reviews on natural occurrence and biosynthetic pathways: a) M.
Iinuma, M. Mizuno, Phytochemistry 1989, 28, 681–694; b) B. Moore
C. Hertweck, J. N. Hopke, M. Izumikawa, J. A. Kalaitzis, G. Nilsen,
T. OꢁHare, J. Piel, P. R. Shipley, L. Xiang, M. B. Austin, J. P. Noel, J.
Nat. Prod. 2002, 65, 1956–1962.
[2] Reviews on bioactivity of chalcones: a) V. Opletalova, P. Ricicarova,
D. Sedivy, D. Meltrova, J. Krivakova, Folia Pharm. Univ. Carol.
2000, 25, 21–33; b) J. R. Dimmock, D. W. Elias, M. A. Beazely,
N. M. Kandepu, Curr. Med. Chem. 1999, 6, 1125–1149.
[3] M. Liu, P. Wilairat, M.-L. Go, J. Med. Chem. 2001, 44, 4443–4452.
[4] a) M. Artico, R. Di Santo, R. Costi, E. Novellino, G. Greco, S.
Massa, E. Tramontano, M. E. Marongiu, A. De Montis, P. La Colla,
J. Med. Chem. 1998, 41, 3948–3960; b) J. K. Buolamwini, H. Assefa,
J. Med. Chem. 2002, 45, 841–852.
[5] R. W. Ashford, P. Desjeux, P. de Raadt, Parasitol. Today 1992, 8,
104–105.
[6] L. Wattenberg, J. Cell. Biochem. 1995, (Suppl.22), 162–168.
[7] B. H. Lee, J. H. Kim, M. J. Cho, S. H. Lee, D. H. Choi, Dyes Pigm.
2004, 61, 235–242.
[27] K. Minn, Synlett 1991, 115–116.
[28] a) N. G. Kundu, P. Das, J. Chem. Soc. Chem. Commun. 1995, 99–
100; b) P. Das, N. G. Kundu, J. Chem. Res. (S) 1996, 298–299.
[29] In the HMBC spectrum the methine signal at d=7.78 ppm
(13C NMR at d=142 ppm) shows cross-peaks, that is, J couplings, to
3
Chem. Eur. J. 2006, 12, 9081 – 9094
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9093

T. J. J. Müller et al.
the carbonyl carbon nucleus at d=190 ppm and the methine carbon
atom in meta position to the cyano group appearing at d=129 ppm.
[30] The selectively deuterated propargyl alcohol [1-D]-2a was synthe-
sized by addition of lithium acetylide, generated from acetylene and
nBuLi, at ꢀ788C to 1-deuterobenzaldehyde, prepared according to
J. J. Gajewski, W. Bocian, N. J. Harris, L. P. Olson, J. P. Gajewski, J.
Am. Chem. Soc. 1999, 121, 326–334.
[37] H. G. O. Becker, R. Beckert, G. Domschke, E. Fanghänel, W. D.
Habicher, P. Metz, D. Pavel, K. Schwetlick, Organikum, 21 st ed.,
Wiley-VCH, Weinheim, 2001.
[38] a) L. Brandsma, Preparative Acetylenic Chemistry, Elsevier, Amster-
dam, Oxford, New York, Tokyo, 1988; b) N. Krause, D. Seebach,
Chem. Ber. 1987, 120, 1845–1851.
[39] H. Buu-Hoi, J. Chem. Soc. 1951, 1834–1836.
[40] I. Urasaki, Y. Ogata, J. Chem. Soc. Perkin Trans. 1, 1975, 1285–
1287.
[31] R. B. Woodward, R. Hoffmann, J. Am. Chem. Soc. 1965, 87, 2511–
2513.
[32] T. H. Lowry, K. Schueller Richardson, Mechanism and Theory in
Organic Chemistry, Harper Collins, New York, 1987, 197–199.
[41] G. Dannhardt, W. Kiefer, G. Krämer, S. Mährlein, U. Nowe, B. Fie-
bich, Eur. J. Med. Chem. 2000, 499–510.
[42] I. S. MacLean, S. T. Widdows, J. Chem. Soc. 1914, 105, 2169–2175.
[43] N. Singh, K. Krishan, Izv. Akad. Nauk SSSR Ser. Khim. 1974, 908–
910.
[44] H. Lendenfeld, Monatsh. Chem. 1906, 27, 970.
[45] A. L. Marzinzik, E. R. Felder, J. Org. Chem. 1998, 63, 723–727.
[46] G. Wagner, B. Voigt, D. Dänicke, T. Liebermann, Pharmazie 1976,
31, 528–532.
[47] A. M. Easton, M. J. A. Habib, J. Park, W. E. Watts, J. Chem. Soc.
Perkin Trans. 2 1972, 2290–2297.
[33] From the Arrhenius equation kobs’ =AeꢀDE /RT the linear logarithmic
a
Ea
expression lnkobs’ =lnAꢀRT is applied to establish a linear correla-
tion between lnkobs’ and reciprocal temperature. The slope of the
linear equation (r2 =0.978) is ꢀEa/R=ꢀ9215.2 K, and thus Ea =
76.6 kJmolꢀ1. The axis intercept is lnA, and thus the preexponential
factor calculates to A=0.69”108 mol2 Lꢀ2 sꢀ1
.
ꢀ
ꢀ
kB
[34] From the Eyring equation kobs’
mic expression ln(kobs’/T)=ln
=
TeꢀDH /RTeDS /R, the linear logarith-
h
A
(kB/h)+DSꢀ/RꢀDHꢀ/RT is applied to
establish a linear correlation between lnACHTREU(NG kobs’/T) and reciprocal tem-
perature. The slope of the linear equation (r2 =0.976) is ꢀDHꢀ/R=
[48] J. R. Merchant, A. S. U. Choughuley, Chem. Ber. 1962, 95, 1792–
1797.
[49] L. Greiner-Bechert, H.-H. Otto, Arch. Pharm. 1991, 324, 563–572.
ꢀ8868.9 K, and thus the activation enthalpy is DHꢀ =73.7 kJmolꢀ1
.
The axis intercept is ln
A
tion entropy calculates to DSꢀ =ꢀ104.5 JKꢀ1 molꢀ1
.
[35] X. Lu, X. Huang, S. Ma, Tetrahedron Lett. 1992, 33, 2535–2538.
[36] E. Piers, J. R. Grierson, C. K. Lau, I. Nagakura, Can. J. Chem. 1982,
60, 210–223.
Received: April 13, 2006
Published online: September 5, 2006
9094
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 9081 – 9094