A concise synthesis of substituted stilbenes and styrenes from propargylic phosphonium salts by a cobalt-catalyzed Diels-Alder/wittig olefination reaction sequence

Article abstract of DOI:10.1021/jo701406d

(Chemical Equation Presented) The cobalt(I)-catalyzed Diels-Alder reaction of propargylic phosphonium salts and longer chained alkyne-functionalized phosphonium salts with 1,3-dienes led to dihydroaromatic phosphonium salt intermediates which were directl

Full text of DOI:10.1021/jo701406d

A Concise Synthesis of Substituted Stilbenes and Styrenes from
Propargylic Phosphonium Salts by a Cobalt-Catalyzed Diels-Alder/
Wittig Olefination Reaction Sequence
Gerhard Hilt* and Christoph Hengst
Fachbereich Chemie, Philipps-UniVersita¨t Marburg, Hans-Meerwein-Strasse, 35043 Marburg, Germany
hilt@chemie.uni-marburg.de
ReceiVed July 4, 2007
The cobalt(I)-catalyzed Diels-Alder reaction of propargylic phosphonium salts and longer chained alkyne-
functionalized phosphonium salts with 1,3-dienes led to dihydroaromatic phosphonium salt intermediates
which were directly used in a one-pot Wittig-type olefination reaction with aldehydes. Subsequent oxidation
led to styrene- and stilbene-type products under formation of three new carbon-carbon bonds in a single
synthetical step starting from three variable starting materials. The E/Z stereoselectivities of the products
revealed that the dihydroaromatic phosphonium ylides behave as semistabilized ylides giving predominantly
the E-configured products. The application of unsymmetrical 1,3-dienes as well as internal phosphonium
functionalized alkynes is also described.
Introduction
with a consequent Diels-Alder cyclization reaction.2 An inverse
reaction sequence where an unsaturated phosphonium salt
undergoes a thermally induced or transition metal catalyzed
cycloaddition process to produce an in situ generated Wittig
reagent has not been described thus far to the best of our
knowledge.
Under these circumstances, the generation of functionalized
dihydroaromatic compounds by means of a cobalt-catalyzed
Diels-Alder reaction of nonactivated 1,3-dienes and nonacti-
vated alkynyl type dienophiles has long been a focus of our
research. Several functionalized building blocks could be used
in this transition metal catalyzed process containing boron-,
silicon-, nitrogen-, phosphorus-, oxygen-, and sulfur-function-
alized 1,3-dienes or accordingly functionalized alkynes.3 In
addition, several valuable follow-up functionalizations and
modifications of the primarily formed dihydroaromatic com-
pounds could be carried out for the synthesis of numerous highly
functionalized products.3d,4
The combination of powerful synthetic methods in subsequent
one-pot reaction sequences provides a variable access toward a
broad variety of products with greatly increased complexity,
which incorporate at least three starting materials in a single
synthetic transformation. Such processes belong to the classes
of intermolecular domino, tandem, and cascade reactions which
find broad applications in organic synthesis of complex struc-
tures.1 Among such very well-established reactions are the
Diels-Alder cyclooaddition as well as the Wittig olefination.
Under these circumstances, some examples are described where
an electron-deficient dienophile is generated via a Wittig reaction
(1) For selected recent reviews, see: (a) Tietze, L. F.; Brasche, G.;
Gericke, K. M. Domino Reactions in Organic Synthesis; Wiley-VCH:
Weinheim, 2006. (b) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew.
Chem. 2006, 118, 7292; Angew. Chem., Int. Ed. 2006, 45, 7134. (c) Enders,
D.; Grondal, C.; Huttl, H. R. M. Angew. Chem. 2007, 119, 1590; Angew.
Chem., Int. Ed. 2007, 46, 1570. (d) Chapman, C. J.; Frost, C. G. Synthesis
2007, 1. (e) Malacria, M. Chem. ReV. 1996, 96, 289. (f) Tietze, L. F. Chem.
ReV. 1996, 96, 115. (g) Winkler, J. D. Chem. ReV. 1996, 96, 167. (h) Parsons,
P. J.; Penkett, C. S.; Shell, A. J. Chem. ReV. 1996, 96, 195. (i) Denmark,
S. E.; Thorarensen, A. Chem. ReV. 1996, 96, 137. (j) Wasilke, J.-C.; Obrey,
S. J.; Baker, R. T.; Bazan, G. C. Chem. ReV. 2005, 105, 1001. (k) Posner,
G. H. Chem. ReV. 1986, 86, 831. (l) Ho, T.-L. Tandem Organic Reactions;
Wiley-Interscience: New York ,1992. (m) Hall, N. Science 1994, 266, 32.
(n) Tietze, L. F.; Beifuss, U. Angew. Chem. 1993, 105, 137; Angew. Chem.,
Int. Ed. 1993, 32, 131.
(2) Ramachary, D. B.; Barbas, C. F., III. Chem. Eur. J. 2004, 10,
5323.
(3) For functionalized building blocks, see the following. Boron: (a)
Hilt, G.; Smolko, K. I. Angew. Chem. 2003, 115, 2901; Angew. Chem., Int.
Ed. 2003, 42, 2795. Silicon: (b) Hilt, G.; Smolko, K. I. Synthesis 2002,
686. Nitrogen: (c) Hilt, G.; Galbiati, F. Synlett 2005, 829. Phosphorus:
(d) Hilt, G.; Hengst, C. Synlett 2006, 3247. Oxygen: (e) Hilt, G.; Smolko,
K. I.; Lotsch, B. V. Synlett 2002, 1081. Sulfur: (f) Hilt, G.; Lu¨ers, S.; Harms,
K. J. Org. Chem. 2004, 69, 624.
10.1021/jo701406d CCC: $37.00 © 2007 American Chemical Society
Published on Web 08/23/2007
J. Org. Chem. 2007, 72, 7337-7342
7337

Hilt and Hengst
SCHEME 1
SCHEME 2
Results and Discussion
In an attempt to apply phosphorus-containing starting materi-
als to the arsenal of building blocks suitable for cobalt-catalyzed
Diels-Alder reactions, we investigated alkynylphosphines5 and
propargylic phosphonium salts as well as longer chained alkyne-
functionalized phosphonium salts as dienophiles in the cobalt-
catalyzed cycloaddition process.
First, we investigated the use of an alkynylphosphine deriva-
tive (1) in the cobalt-catalyzed Diels-Alder reaction with a
simple symmetrical 1,3-diene such as 2,3-dimethyl-1,3-butadiene
(Scheme 1).
recrystallization, filtration, or precipitation. In addition, because
of the presence of paramagnetic cobalt catalyst components in
the reaction mixture the conversion could not be determined
by means of 31P NMR directly from the reaction mixture.
Therefore, all further investigations focused on the one-pot
cobalt-catalyzed Diels-Alder/Wittig olefination reaction se-
quence without any isolation of the air-sensitive dihydroaromatic
intermediates. The reaction products formed by this reaction
sequence were furthermore oxidized by the addition of DDQ
to generate the styrene (R ) aliphatic) or stilbene (R ) aromatic)
type products 6 which were then detectable and could be isolated
and characterized. Consequently, we report herein a sequential
three-step conversion which was performed without the iso-
lation of the dihydroaromatic intermediates of type 4 and 5 in
terms of a one-pot process. However, separation of the organic
intermediates of type 5 by simple filtration from the cobalt
catalyst mixture and its inorganic components was feasible
and led to the isolated dihydroaromatic styrene or stilbene
intermediates.
Unfortunately, we have not been able to identify an appropri-
ate cobalt catalyst system which is able to convert starting
materials of type 1 into a dihydroaromatic phosphine derivative
2. The low conversion of the alkynylphosphine 1 is most likely
based on a competitive complexation of the phosphorus donor
functionality versus the alkynyl moiety. The stronger Co-P
coordination of starting material 1 blocks free coordination sites
at the cobalt center so that the coordination of the alkyne or
the 1,3-diene is less favorable. These results are also in
accordance with previous observations namely that the addition
of excess phosphine ligand reduces the reactivity of the cobalt
catalyst system considerably. Therefore, the complexation of a
large excess of the starting material results in an efficient
retardation of activity of the cobalt catalyst. Even if the catalysts
were applied in up to 50 mol % the desired products will not
be obtained.6
Nevertheless, the use of propargylic phosphonium salts, such
as 3, was performed because in this type of starting material
the phosphorus does not behave as a donor ligand anymore. In
addition, this type of transformation seems to be of considerably
higher synthetic value in terms of the possibilities implied in
the allylic phosponium salt for further carbon-carbon bond
formation processes. While the follow-up chemistry of cycload-
ducts of type 2 is rather limited, the cycloadduct of type 4 should
allow a sequential Diels-Alder/Wittig reaction cascade. The
proposed cobalt-catalyzed Diels-Alder reaction of a propargylic
phosphonium salt such as 3 (Scheme 2) generates a new kind
of an allylic-type phosphonium salt 4 with a dihydroaromatic
subunit next to the acidic CH-protons suitable for an in situ
Wittig olefination with carbonyl compounds such as aldehydes.
If propargylic phosphonium salts such as 3 are brought to
reaction in a cobalt-catalyzed Diels-Alder reaction with 1,3-
dienes, a systematic problem arises. Not only the starting
materials but also the proposed dihydroaromatic intermediates
4 are saltlike intermediates. Therefore, the isolation of phos-
phonium salt 4 from all the other cobalt and zinc inorganic-
type ingredients in the reaction mixture is very tedious. In fact,
the phosphonium salt 4 could not be obtained in pure form by
The addition of a base and an aldehyde converted the
dihydroaromatic and allylic type phosphonium salts 4 into the
organic products 5 via the Wittig olefination reaction which
could then be detected by GC or GCMS analysis. Therefore, in
a series of experiments the reaction time and the cobalt catalyst
loading for the cobalt-catalyzed Diels-Alder reactions were
optimized using anisaldehyde for the Wittig olefination reaction.
The best results were obtained for a protocol in which 10-20
mol % of the catalyst was used in the cobalt-catalyzed Diels-
Alder reaction, and the mixture was stirred for 0.5 h at room
temperature after which the characteristic color change from
green toward a deep brown was observed. Then the base and
the aldehyde for the Wittig olefination reaction were added.
After further 1-2 h of stirring at ambient temperatures, the
dihydroaromatic product 5 could be detected and the conversion
estimated by GC and GCMS. The dihydroaromatic products
were obtained by simple filtration over a small amount of silica,
evaporation of the solvent before further oxidation by DDQ in
benzene or toluene to generate the corresponding aromatic
products 6. Without this simple filtration of the dihydroaromatic
intermediates from the cobalt-catalyst mixture the yields of
the desired products 6 were somewhat diminished if the DDQ
oxidation was performed in a straightforward one-pot reaction.
The results of the Diels-Alder-Wittig reaction-DDQ oxida-
tion sequences are summarized in Table 1.
(4) For leading references, see: (a) Hilt, G.; Galbiati, F. Org. Lett. 2006,
8, 2195. (b) Hilt, G.; Galbiati, F.; Harms, K. Synthesis 2006, 3575. (c) Hilt,
G.; Hess, W.; Schmidt, F. Eur. J. Org. Chem. 2005, 2526. (d) Hilt, G.;
Lu¨ers, S.; Smolko, K. I. Org. Lett. 2005, 7, 251. (e) Hilt, G.; Korn, T. J.;
Smolko, K. I. Synlett 2003, 241.
(5) (a) Ashburn, B. O.; Carter, R. G. Angew. Chem., Int. Ed. 2006, 45,
6737. (b) Ashburn, B. O.; Carter, R. G.; Lakharov, L. N. J. Am. Chem.
Soc. 2007, 129, 9109.
The variation of the base gave rather disappointing results.
If sodium hydride, sodium amide, or n-butyllithium was used
as a base, only traces of the product were formed whereas for
(6) In contrast, higher catalyst loadings in the case of sulfur-functionalized
alkynes led to the desired conversions. See ref 3f.
7338 J. Org. Chem., Vol. 72, No. 19, 2007

Cobalt-Catalyzed Diels-Alder/Wittig Olefination Reaction Sequence
TABLE 1. Results for the Cobalt-Catalyzed Diels-Alder/Wittig/
DDQ Oxidation Reaction Sequence
no obvious reason better results were obtained with sodium
hexamethyl disilazide (NaHMDS). Nevertheless, all of these
bases were inferior to potassium tert-butoxide, which was used
in all subsequent reactions. The variation of the temperature
for the Wittig reaction had no significant effect on the olefination
reaction in terms of reactivity or E/Z stereoselectivity. In general,
the conversion of the intermediate 4 with electron-rich as well
as electron-poor aromatic aldehydes led to the desired products
6 in acceptable to very good overall yields of up to 95%. The
substitution pattern and the nature of the substituents could be
varied covering a vast range. In the case of ortho-substituted
aldehydes, the steric hindrance by the substituents diminished
the yields somewhat (entries 5, 9, and 11). Nevertheless,
polyfunctionalized products could be obtained, and particularly
interesting were di- and trimethoxylated benzaldehyde deriva-
tives (entries 10-12) which led to products 6j-l, which exhibit
some structural similarities to the family of the combretastatine
natural products.7 Also the 1,4-diaryl-substituted 1,3-butadiene
6n could be obtained in a rather good yield of 64% (entry 14)
applying cinnamic aldehyde as starting material. It is noteworthy
to point out that for the 4-dimethylamino-functionalized ben-
zaldehyde the E-isomer was isolated exclusively. In all other
cases, mixtures of the newly formed double bond geometry were
observed with a moderate to good preference for the E-double
bond geometry. The nature of the carbonyl derivative, on the
other hand, could not be varied indefinitely, and the range was
limited toward aromatic aldehydes and a trifluoromethyl-
substituted ketone (entry 15) which could be applied in the
reaction sequence with reasonable success. The application of
other ketones such as acetone, acetophenone and cyclohexanone
gave the desired styrene type products in lower yields (25%
for acetophenone, otherwise <5% yield), indicating that the
semistabilized phosphonium ylide intermediate is not highly
reactive. Nevertheless, for the trifluoromethyl-functionalized
ketone (entry 15) only the E-isomer was detected. The trans-
formation with the sterically unhindered aliphatic aldehyde such
as propanal (entry 16) gave good results of up to 81% for the
crude dihydroaromatic derivative of type 5. Unexpectedly, the
following DDQ oxidation of this material led to decomposition
and/or polymerization side reactions so that the yield of the
desired aromatic product 6p in this case was considerably
diminished. The same behavior was observed for the other
aliphatic aldehyde with an allylic proton (entry 17), while the
tert-butyl-functionalized material 6r gave a reasonable yield of
44% after DDQ oxidation despite the steric hindrance. Alter-
natively, the oxidation could be performed with TCNE at
ambient temperature in dioxane solution. Under these conditions,
the rate of the thermal Diels-Alder reaction of the TCNE with
the congested 1,3-diene subunit in the dihydroaromatic deriva-
tive as side reaction is only moderate, and the electron-transfer
reaction dominates so that the desired aromatic products 6p and
6q were obtained in moderate yields of 40% and 45%,
respectively.8 Because the oxidation of the tert-butyl-substituted
dihydroaromatic intermediate (entry 18) could be performed with
DDQ to give the desired product 6r in 44% yield, a possible
(7) (a) Tron, G. C.; Pirali, T.; Sorba, G.; Pagliai, F.; Busacca, S.;
Genazzani, A. A. J. Med. Chem. 2006, 49, 3033. (b) Cirla, A.; Mann, J.
Nat. Prod. Rep. 2003, 20, 558. (c) Pettit, G. R.; Singh, S. B.; Niven, M. L.
J. Am. Chem. Soc. 1988, 110, 8539.
(8) Ramnial, T.; McKenzie, I.; Gorodetsky, B.; Tsang, E. M. W.;
Clyburne, J. A. C. Chem. Commun. 2004, 1054. Sterically hindered alkenyl
functionalized dihydroaromatic compounds bearing a 1,3-diene subunit led
to a fast redox reaction instead of the desired Diels-Alder reaction; see ref
4d.
a The compounds 6a,b,f,g,j,n,r were described previously; see ref 3d.
b For the optimization process, see the text. c Oxidation with TCNE as
oxidant. d The crude yields of the dihydroaromatic intermediates 5p and
5q were 81% and 84%, respectively.
J. Org. Chem, Vol. 72, No. 19, 2007 7339

Hilt and Hengst
SCHEME 3
SCHEME 4
SCHEME 5
side reaction of the aliphatic-substituted derivatives could be
attributed to allylic oxidation processes leading to unidentified
side products.
Based on the observation that the E/Z stereoselectivity of the
Wittig olefination of the dihydroaromatic phosphonium salts
of type 4 shows in most cases a moderate selectivity for the
E-configuration of the newly formed double bond of the styrene
derivatives, these phosphonium ylides exhibit selectivities
located between the stabilized ylides, such as the Wadsworth-
Horner-Emmons reagents, and the semistabilized ylides such
as the allylic-type phosphonium ylides as was outlined by
Berger.9 As could be shown, the stereoselectivity can be
controlled by the nature of the substituents on the phosphorus.
Within this study such modifications were not undertaken and
remain an option for the generation of enriched E or Z
stereoisomers.9,10
The separation of the E/Z stereoisomers of the products of
type 6 by means of column chromatography was accomplished
for most derivatives, and pure products could be obtained and
characterized. The situation became more complicated when
unsymmetrical 1,3-dienes, such as 2-methoxy-1,3-butadiene (7),
were used as starting materials in the cobalt-catalyzed Diels-
Alder reaction. In these cases, not only E/Z stereoisomers of
the newly formed olefinic double bond, as in the products of
type 9 and 10, were encountered but in addition regioisomers
(a and b) generated by the Diels-Alder reaction could be
observed (Scheme 3).
peaks. The situation became easier by the application of
trifluoromethyl acetophenone 11 where only the E-configured
products 12a and 12b were observed as could be determined
from GC, GCMS, and 19F and 13C NMR data (Scheme 4).
On the other hand, if 3,4,5-trimethoxybenzaldehyde 13 was
used in the reaction sequence the analysis of the product mixture
became more difficult because of the inherent impossibility of
a simple analysis by 19F NMR. In addition, as was found in
many other cases, the olefinic protons overlap with the aromatic
protons but fortunately the methoxy groups of all the four
In this case, the separation of the four isomers in pure form
could not be achieved by column chromatography. However,
from the 19F NMR data of the mixture the ratios of the isomers
1
isomers (14a,b and 15a,b) could be separated in an H NMR
spectrum (600 MHz) (Scheme 5). As expected, the Wittig
olefination also favors the E-stereochemistry of the olefinic
double bond, while the cobalt-catalyzed Diels-Alder reaction
gave predominantly the para-substituted products in moderate
selectivity.
1
could be determined while the corresponding GC, H NMR,
and 13C NMR gave partially overlapping or poorly separated
(9) (a) Ackermann, M.; Berger, S. Tetrahedron 2005, 61, 6764. (b) Appel,
M.; Blaurock, S.; Berger, S. Eur. J. Org. Chem. 2002, 1143. (c) Maryanoff,
B. E.; Reitz, A. B. Chem. ReV. 1989, 89, 863. (d) Tamura, R.; Saegusa, K.;
Kakihana, M.; Oda, D. J. Org. Chem. 1988, 53, 2723. (e) Vedejs, E.; Marth,
C. F.; Ruggeri, R. J. Am. Chem. Soc. 1988, 110, 3940. (f) Vedejs, E.; Marth,
C. F. J. Am. Chem. Soc. 1988, 110, 3948. (g) Robiette, R.; Richardson, J.;
Aggarwal, V. K.; Harvey, J. N. J. Am. Chem. Soc. 2006, 128, 2394.
(10) (a) Valentine, D. H.; Hillhouse, J. H. Synthesis 2003, 317. (b)
Celatka, C. A.; Liu, P.; Panek, J. S. Tetrahedron Lett. 1997, 38, 5449.
Terminal alkynylphosphonium salts are not the only reagents
which can be used in the reaction sequence. As could be shown
by the application of starting material 16 which bears a
phosphonium salt with an internal alkyne functionality, the
cobalt-catalyzed Diels-Alder reaction with 2,3-dimethyl-1,3-
butadiene led to a dihydroaromatic tetrasubstituted phosphonium
7340 J. Org. Chem., Vol. 72, No. 19, 2007

Cobalt-Catalyzed Diels-Alder/Wittig Olefination Reaction Sequence
SCHEME 6
SCHEME 7
salt intermediate which was then successfully applied in the
Wittig olefination for the synthesis of the styrene product 17
(Scheme 6).
Therefore, higher substituted and more complicated products
will be accessible applying phosphonium salts with internal
alkynyl functionalities.
Summary
The cobalt catalyst system [CoBr2(dppe)/ZnI2/Zn] represents
the first catalyst which is able to efficiently convert arylalky-
nylphosphonium salt dienophiles in a metal-catalyzed Diels-
Alder reaction with acyclic 1,3-dienes. The dihydroaromatic
intermediates can be converted in a Wittig olefination with
aldehydes to styrene- and stilbene-type products in acceptable
to very good yields. The newly formed double bond generated
by the olefination reaction exhibits predominantly E-geometry,
indicating that the phosphorus ylide intermediate can be assigned
as a semistabilized ylide. The regioselectivity of the cycload-
dition is controlled by steric factors to preferentially give the
para-substituted products when unsymmetrical starting materials
are used. When longer chained alkynylphosphonium salts are
applied, higher homologues are generated, and interestingly, in
the case of propene derivatives, side reactions during the DDQ
oxidation occur. The oxidation of dihydroaromatic butene
derivatives leads to a stereoselective oxidation by DDQ where
the E-double bond is oxidized to the 1E,3Z-isomer leaving the
Z-butene derivative untouched.
In a last set of experiments, longer chained alkynylphospho-
nium salts such as 18 and 20 were tested (Scheme 7). While
the cobalt-catalyzed Diels-Alder reaction and the Wittig
olefination could be performed in the same manner as before,
again problems were encountered in the DDQ oxidation step.
The DDQ oxidation to give the diarylpropene derivative 19
led to decreased yields by oxidative side reactions of the
allylic position and formation of unidentified side products.11
For the longer alkyl chain as shown in 20, the DDQ oxidation
led to side products which could be isolated and character-
ized. In this case, the DDQ oxidation led not only to the
oxidation of the dihydroaromatic substituent to yield product
21 but also to the partial introduction of another double bond
to generate product 22. It is notable that the DDQ oxidation
seems to be stereoselective since the Z-configured olefin 21
could be isolated in pure form while the E-isomer was oxidized
by DDQ to yield the diene 22. In addition, the newly formed
double bond in 22 is also formed with good stereoselectivity
and the NMR data indicate that 22 consists mainly (>95%) of
the 1E,3Z stereoisomer.
Experimental Section
General Methods. All reactions were carried out under an argon
atmosphere in flame-dried glassware. Dichloromethane was distilled
under nitrogen from P4O10, and ZnI2 was dried in vacuo at 150 °C
prior to use. Commercially available materials were used without
further purification.
Starting Materials. 2-Methoxy-1,3-butadiene12 as well as the
Wittig precursors13 were prepared according to adapted literature
procedures.
The presented protocol provides a very variable three
component access toward unsymmetrically polysubstituted
stilbene derivatives from simple and commercially available
starting materials. On the other hand, difficulties were encoun-
tered as the application of aliphatic aldehydes gave only
relatively poor results for propionic aldehyde and pivalyl
aldehyde (entries 20, 21).
(12) Marshall, K. S.; Dolby, L. J. Org. Prep. Proc. 1969, 1, 229.
(13) (a) Preparation of 3: Eiter, K.; Oedinger, H. Liebigs Ann. Chem.
1965, 682, 62. (b) Preparation of 16: Hann, M. M.; Sammes, P. G.;
Kennewell, P. D.; Taylor, J. B. J. Chem. Soc., Perkin Trans. 1 1982, 307.
(c) Preparation of 18: Hanko, R.; Hammond, M. D.; Fruchtmann, R.;
Pfitzner, J.; Place, G. A. J. Med. Chem. 1990, 33, 1163. (d) Preparation of
20: Sato, K.; Inoue, S.; Ota, S. J. Org. Chem. 1970, 35, 565.
(11) The reaction of 1,3-diphenylpropene with DDQ under otherwise
identical reaction conditions did not lead to any considerable transformation
of the starting material. Therefore, this behavior seems to be very limited
to the DDQ oxidation of the dihydroaromatic propene derivative. Further
investigations concerning this new type of reactivity are underway.
J. Org. Chem, Vol. 72, No. 19, 2007 7341

Hilt and Hengst
Representative Procedure for the Diels-Alder/Wittig Olefi-
nation Reaction Sequence. Synthesis of (E/Z)-5-(3,4-Dimethyl-
styryl)-1,2,3-trimethoxybenzene (6l). Under an argon atmosphere,
ZnI2 (319 mg, 1.0 mmol), zinc dust (39 mg, 0.6 mmol), and
CoBr2(dppe) (62 mg, 0.1 mmol) were suspended in anhydrous
CH2Cl2 (5 mL). After formation of the active catalytic species,
recognizable when the color of the suspension turned from green
to deep brown, triphenyl(prop-2-ynyl)phosphonium bromide (191
mg, 0.5 mmol) and 2,3-dimethyl-1,3-butadiene (62 mg, 0.75 mmol)
were added at room temperature. The resulting mixture was stirred
at rt for 30 min. After the solution was cooled with an ice bath,
KO-t-Bu (280 mg, 2.5 mmol) and 3,4,5-trimethoxybenzaldehyde
(147 mg, 0.75 mmol) were added at 0 °C. After additional stirring
at room temperature for 1 h, the solids were removed by filtration
over a short pad of silica gel (eluent: pentane/MTBE ) 1:1). After
the solvent was evaporated, the crude product was dissolved in
benzene (10 mL) and DDQ (136 mg, 0.6 mmol) was added. After
the resulting mixture was stirred at room temperature for 1 h, it
was washed twice with basic thiosulfate solution (10% NaOH/10%
Na2S2O3, 10 mL). The aqueous phases were combined and extracted
with MTBE (20 mL), and the combined organic phases were dried
(MgSO4). After the solvent was evaporated under reduced pressure,
the crude product was purified by column chromatography (elu-
ent: pentane/ethyl acetate ) 10:1). The product was obtained as a
white solid (141 mg, 95%).
(s, 2H), 3.94 (s, 6H), 3.90 (s, 3H), 2.31 (s, 3H), 2.30 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ ) 153.0, 136.3, 135.7, 134.9, 132.9,
130.2, 130.2, 129.6, 129.4, 126.4, 113.6, 106.3, 61.0, 56.0, 19.7,
19.6.
Z-isomer: 1H NMR (300 MHz, CDCl3) δ ) 7.09 (s, 1H), 7.05
(d, J ) 7.9 Hz, 1H), 7.01 (d, J ) 7.8 Hz, 1H), 6.53 (d, J ) 12.1
Hz, 1H), 6.52 (s, 2H), 6.43 (d, J ) 12.2 Hz, 1H), 3.84 (s, 3H),
3.67 (s, 6H), 2.22 (s, 3H), 2.19 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ ) 153.5, 137.9, 136.8, 136.3, 134.9, 133.5, 130.1, 128.3, 127.8,
127.5, 124.0, 103.6, 61.0, 56.2, 19.9, 19.6; MS (EI) m/z ) 298
(M+), 283, 223, 208, 195, 180, 165, 153, 133; HRMS m/z calcd
for C19H22O3 298.1569, found 298.1564; IR (KBr) 2917, 1582,
1506, 1449, 1420, 1339, 1260, 1239, 1127, 1009, 959, 852, 818,
631.
Acknowledgment. We thank the German Science Foun-
dation (Deutsche Forschungsgemeinschaft) for financial
support.
Supporting Information Available: Characterization data for
compounds 6a-r, 9a,b, 10a,b, 12a,b, 14a,b, 15a,b, 17, 19, and
21-22. This material is available free of charge via the Internet at
http://pubs.acs.org.
E-isomer: 1H NMR (300 MHz, CDCl3) δ ) 7.33 (s, 1H), 7.28
(d, J ) 7.7 Hz, 1H), 7.15 (d, J ) 7.8 Hz, 1H), 7.01 (s, 2H), 6.76
JO701406D
7342 J. Org. Chem., Vol. 72, No. 19, 2007