Sequential hiyaima coupling/narasaka acylation reaction of (e)-1,2-disilylethene: rapid assembly of α,β-unsaturated carbonyl motifs

Article abstract of DOI:10.1002/ejoc.200900288

The synthesis and application of (E)-1,2-disilylethene 5 as a central functional building block in a sequential Hiyama coupling/Narasaka acylation reaction are described, Its use in the rapid and versatile construction of α,β-unsaturated carbonyl motifs found in a number of polyunsaturated natural products has been demonstrated. It was observed that due to the differential intrinsic reactivity of the two carbon-silicon bonds, this bis-metallated lynchpin-type reagent is activated selectively and sequentially by Pd and Rh catalysis, negating the need for any protecting group, A number of (E)-α,β-unsaturated ketones were efficiently synthesized with complete chemoselectively in the presence of a variety of halides and anhydride acids. Conjugated polyunsaturated ketones and diversely α'-functionalized α,β-enones, such, as chalcones, a heterocyclic dienone and the highly conjugated ethyl (2Z,4E)-6-oxo-6-(2-thienyl)hexa-2,4-dienoate, were obtained in good overall yields. Thus, this coupling sequence provides a high degree of modularity, that is, a single template is likely to produce a large number of synthetic targets.

Full text of DOI:10.1002/ejoc.200900288

FULL PAPER
DOI: 10.1002/ejoc.200900288
Sequential Hiyama Coupling/Narasaka Acylation Reaction of
(E)-1,2-Disilylethene: Rapid Assembly of α,β-Unsaturated Carbonyl Motifs
Carine Thiot,[a] Charles Mioskowski,[a][†] and Alain Wagner*[b]
Keywords: Acylation / Cross-coupling / Rhodium / Palladium / Ketones
The synthesis and application of (E)-1,2-disilylethene 5 as a
central functional building block in a sequential Hiyama cou-
pling/Narasaka acylation reaction are described. Its use in
the rapid and versatile construction of α,β-unsaturated car-
bonyl motifs found in a number of polyunsaturated natural
products has been demonstrated. It was observed that due to
the differential intrinsic reactivity of the two carbon–silicon
bonds, this bis-metallated lynchpin-type reagent is activated
selectively and sequentially by Pd and Rh catalysis, negating
the need for any protecting group. A number of (E)-α,β-un-
chemoselectively in the presence of a variety of halides and
anhydride acids. Conjugated polyunsaturated ketones and
diversely αЈ-functionalized α,β-enones, such as chalcones, a
heterocyclic dienone and the highly conjugated ethyl
(2Z,4E)-6-oxo-6-(2-thienyl)hexa-2,4-dienoate, were obtained
in good overall yields. Thus, this coupling sequence provides
a high degree of modularity, that is, a single template is likely
to produce a large number of synthetic targets.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
saturated ketones were efficiently synthesized with complete Germany, 2009)
Introduction
Low molecular weight and multifunctional molecules are
highly valuable building blocks (templates) because they
enable the construction of a variety of structurally diverse
motifs by selective and sequential catalytic coupling reac-
tions of their functional groups. In a synthetic strategy, this
building block approach is considered to be a versatile and
economic alternative to classic multistep syntheses. It allows
benefits, such as the facility to carry out the reactions one
Scheme 1. Assembly of polyene systems from 1,3,5-hexatriene 1.
after another without isolating the intermediate product
using a single catalyst or a combination of catalysts.
Straightforward modular access to key structural function-
alities is thus provided. In this regard, “olefin templates”
suitably functionalized for cross-coupling reactions have
been among the most successfully exploited for olefin motif
elaboration.[1] As examples, homo-bis-metallated olefins are
well-known coupling partners, particularly those of
tin,[1a,1b] silicon[1c,1d] and boron.[1e] Hetero-bis-metallated
lynchpin-type reagents,[1f] including a tin/silicon vinylic sys-
tem[1g] and a boron/tin alkene[1h] and triene 1 have also been
reported (Scheme 1).[1i,1j]
As an elegant demonstration of this assembly strategy,
Burghart and Bruckner very recently used a heptatrienyldi-
stannane building block 2 in the total synthesis of the natu-
rally configured pyrrhoxanthin (marine carotenoid product)
by iterative Stille coupling reactions (Figure 1).[2]
The design of differentially functionalized building
blocks and the development of reaction sequences that al-
low other key structural units are of intense ongoing syn-
thetic interest. In contrast to olefin templates, very few ex-
amples of molecules that give access to α,β-unsaturated car-
bonyl motifs have been reported in the literature, despite
their key role in organic synthesis. Their great synthetic
value derives from the fact that the positions α, β and γ to
the carbonyl groups can be activated and functionalized by
various means. However, it is noteworthy that Suzuki and
co-workers have described the regio- and stereoselective
synthesis of α,β-unsaturated ketones by a sequential cross-
[a] Laboratoire de Synthèse Bio-Organique, Université Louis
Pasteur, Faculté de Pharmacie,
74 route du Rhin, 67401 Illkirch-Graffenstaden, France
Fax: +33-3-90244306
[b] Novalyst Discovery, BioPark Boulevard Sébastien Brandt,
67400 Illkirch-Graffenstaden, France
Fax: +33-3-88107226
E-mail: aw@novalyst.com
[†] Deceased June 2, 2007.
Eur. J. Org. Chem. 2009, 3219–3227
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3219

C. Thiot, A. Wagner, C. Mioskowski
FULL PAPER
Figure 1. Natural pyrrhoxanthin from bifunctional heptatrenyldi-
stannane 2.
coupling reaction of (E)-(2-bromoethenyl)diisopropoxybor-
ane (3) with α-alkoxyalkenylzinc chlorides and organic ha-
lides (Scheme 2).[3]
Scheme 3. Stereodefined α,β-unsaturated ketones from 1,2-disilyl-
ethenes.
(E)-Ethylene synthons 4 and 5 were efficiently prepared
by the hydrosilylation[4] of the commercially available tri-
methyl- and dimethyl(phenyl)silylacetylene (6 and 7) with
diethoxy(methyl)silane using our previously reported meth-
odology based on metal soaking (Scheme 4).[5,6]
Scheme 2. Synthesis of (E)-α,β-enones from 3.
Results and Discussion
Herein, we report the regio- and stereoselective synthesis
of (E)-1,2-disilylethenes 4 and 5 (Figure 2), and efficient se-
quential cross-coupling/acylation reactions of 5 to give (E)-
α,β-unsaturated ketones in good yields.
Scheme 4. Preparation of 1,2-bis-silylethenes 4 and 5.
Based upon earlier work,[5c] the reaction of 6 and di-
ethoxy(methyl)silane was carried out in the presence of po-
lyionic gel-soaked rhodium complex 8[5c] (0.04% mol Rh)
Figure 2. Homo-1,2-bis-silylethenes 4 and 5.
In this strategy, the silyl functional groups have a defined in dioxane at 60 °C for 24 h to give the thermodynamically
stereochemistry and are differentiated from each other by more stable (E)-1,2-disilylethene 4 after rhodium-promoted
their intrinsic reactivity. We assumed that the two carbon isomerization of the initially formed (Z)-1,2-disilylethene
silicon bonds (both dialkoxyalkyl- and trialkylsilyl bearing 4.[7] Dimethyl(phenyl)silylacetylene (7) similarly underwent
moieties) would react orthogonally under transition-metal this reaction with diethoxy(methyl)silane to give the E ad-
catalysis and allow the aforementioned Pd- and Rh-cata- duct 5 regio- and stereoselectively.[8] The pure hydro-
lyzed sequence, the Hiyama coupling/Narasaka acylation silylation products 4[9] and 5 were obtained in 70 and 75%
(Scheme 3).
yields, respectively, by simple bulb-to-bulb distillation. The
3220
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3219–3227

Rapid Assembly of α,β-Unsaturated Carbonyl Motifs
stereochemistry of 5 was unambiguously confirmed by the acid anhydrides.[15] Thus, the introduction of the acyl motif
coupling constants (3J = 15.8 Hz for Z; 22.7 Hz for E) of was attempted by subjecting the 1,2-bis-silylethenes 4 and
1
the two vicinal vinylic protons in the H NMR spectrum.
5 to the Narasaka reaction conditions in the presence of
In the second step, the templates 4 and 5 were submitted acetic anhydride (3 equiv.) and catalytic [RhCl(CO)2]2
to both palladium-catalyzed coupling and rhodium-cata- (5mol-%) in dioxane at 90 °C for 24 h.[16] We expected that
lyzed acylation conditions. Silicon-based cross-coupling re- the reaction would occur chemoselectively at the trialkyl-
actions[10] (Hiyama coupling) of aryl- and vinylsilanes with silyl moiety. Unfortunately, a complex mixture of products
various halide partners has been widely studied. This Pd- was obtained with no acylation product formed at all. We
catalyzed C–C bond-forming reaction has gained promi- assumed that reaction with the dialkoxymethyl terminus led
nence in synthetic organic chemistry as a reliable alternative to the formation of oligomers, precluding the Narasaka re-
to Suzuki, Stille and Negishi couplings, which may have action. These results revealed that the Hiyama coupling re-
drawbacks, such as the involvement of toxic reagents and action has to be first performed in a one-pot sequential
byproducts, as well as oxygen and moisture sensitivity is- strategy.
sues. In particular, Hiyama and co-workers reported the use
We then tested (E)-(2-arylvinyl)silanes 10 and 11 under
of alkenylsilanes bearing 2-thienyl-,[11] dicholoro-[12] and di- the same acylation conditions. Both reactions afforded the
fluoro-functionalized[13] silicons. In this coupling reaction, expected (E)-benzylideneacetone (12a) in 64 and 85% yields
a pentacoordinated silicon intermediate is reported to be a respectively. In agreement with the literature, (E)-(2-aryl-
prerequisite to successful cross-coupling. TBAF is usually vinyl)dimethyl(phenyl)silane 11 appears to be more reactive
used as a nucleophilic activator to generate the activated than vinylsilane 10 with a trimethylsilyl group.[15b] Efforts
species and promote Pd transmetallation. Denmark et al. were made to further improve the procedure by examining
showed that under these conditions, dialkoxy-, chloro- or two other rhodium precursors ([RhCl(PPh3)3] and
alternatively 2-pyridyl derivatives and siletanes are the most [RhCl(cod)2]2) as well as their corresponding poly-ionic gel-
reactive silanes towards Pd transmetallation, whereas trialk- soaked complexes, prepared according to our reported pro-
ylsilanes failed to react or afforded poor yields.[14]
cedure.[5a] Only the reaction with the heterogeneous ionic
Hiyama coupling of bifunctional 4 and 5 with iodo- [RhCl(CO)2]2-based catalyst was successful, which enabled
benzene and n-tetrabutylammonium fluoride using our re- the formation of α,β-unsaturated ketone 12a from 11 in a
ported ionic gel palladium catalyst 9[5a] provided the (E)-(2- modest 41% isolated yield. As the best catalyst for this reac-
arylvinyl)silanes 10 and 11 in 88 and 92% yields, respec- tion, homogeneous [RhCl(CO)2]2 was used in further stud-
tively (Scheme 5). Note that the reactions proceeded quanti- ies.
tatively with no evidence of the competing reactions of the
Interestingly, in the reaction of 10 with benzoic anhy-
trimethyl- and dimethyl(phenyl)silyl-bearing termini. The dride as the acylating agent, the desired phenyl vinyl ketone
reason for the observed chemoselectivity was that selective 12b was obtained in a 71% yield together with 13% of the
fluoride-based activation of the diethoxy(methyl)silyl moi- phenylated product 13, which arises from a decarbonylative
ety occurred to effect transmetallation. The corresponding side-reaction.[17] With dimethyl(phenyl)vinylsilane 11, this
homogeneous catalyst, Pd(OAc)2, also provided the desired undesired reaction was suppressed (Scheme 5).
products 10 and 11, but in slightly lower yields (62 and
86%, respectively).
These results prompted us to further develop the one-pot
version of this bimetallic catalyzed-sequence from bifunc-
tional building block 5. Further control experiments vali-
dated the cross-selectivity of the two catalytic systems.[18]
As was previously observed, the incompatibility of 5 with
acid anhydrides was confirmed, which led us to perform the
oriented Hiyama coupling/Narasaka acylation sequence.
Interestingly, the first attempt to perform the one-pot re-
action by adding all the reagents together was unsuccessful,
resulting only in the isolation of the coupling intermediate
(E)-11 with no trace of the target compound 12a. The same
result was observed with the sequential addition of the
coupling and acylation partners. To overcome this diffi-
culty, we proposed to deactivate the rhodium catalyst by
using fluoride anions, required to generate the activated
pentacoordinate silicon species for the Hiyama coupling re-
action. Consequently, we refined the reaction conditions of
the first step. When various bases were screened (DBU,
K2CO3, Cs2CO3, Ag2O and BaO·H2O), no acylated prod-
uct was detected. Only BaO·H2O quantitatively provided
Scheme 5. Rhodium(I)-catalyzed acylation of vinylsilanes with ben-
zoic anhydride.
With regard to the activation of the second C–Si bond, the coupling intermediate 11, whereas no reaction was ob-
Narasaka and co-workers recently developed a rhodium(I)- served with other activators. As this alternative did not suc-
catalyzed acylation of trialkylvinylsilanes using carboxylic ceed, we revisited the fluoride strategy. Simple filtration
Eur. J. Org. Chem. 2009, 3219–3227
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3221

C. Thiot, A. Wagner, C. Mioskowski
FULL PAPER
Scheme 6. One-pot sequential Hiyama/Narasaka coupling reactions with bis-silylated 5.
through Celite followed by work-up of the intermediate to the competitive conjugate addition reaction[23,24] limit its
eliminate fluoride scavengers resulted in the expected sub- use. In addition, a survey of the literature revealed that ex-
strate (E)-12, but in a low overall yield of 27%. Ultimately, amples of reactions using aryl vinyl ketones are extremely
both replacement of the TBAF solution with polymer-sup- rare.[25] Note that in the new methodology involving oxy-
ported ammonium fluoride 14[19] and rapid filtration of the gen-promoted PdII cross-coupling in the absence of bases,
intermediate allowed the coupling sequence to proceed the reaction with methyl vinyl ketone and phenylboronic
smoothly to yield the desired (E)-benzylideneacetone (12a) acid afforded (E)-4-phenyl-3-buten-2-one (12a) without the
in an overall yield of 83% (Scheme 6). Note that under undesired homo-coupled product but in a lower yield
homogeneous conditions (Pd(OAc)2 and [RhCl(CO)2]2), the (71%).[26]
expected product 12a was formed in a satisfactory overall
yield of 73%.
In our strategy, we observed that Narasaka reactions
with poorly reactive aliphatic anhydrides were sluggish (en-
The reaction of 5 was carried out sequentially, per- try 2). Rhodium catalyst loading and reaction time were in-
forming the Hiyama coupling with iodobenzene and the creased to obtain enones in acceptable yields (entries 3–6).
supported TBAF activator 14 followed after 2 h by fil- Compounds 12e and 12f by aldol condensation of benzal-
tration through a pad of Celite and the addition of acetic dehyde with 3-methylbutan-2-one and pinacolone have been
anhydride and the rhodium catalyst to promote the acety- prepared previously in lower yields (58 and 50%, respec-
lation. With the use of a heterogeneous fluoride source and tively, compared with 72 and 64%, entries 5 and 6).[27] In
polyionic gel-soaked palladium, the sequence is essentially the reactions involving conjugated anhydrides, no decar-
quantitative and clean, and the purification is largely sim- bonylative coupling was detected (entries 7–10). Also, de-
1
plified. The H NMR spectrum of the crude after filtration spite the sensitivity of the acylation catalyst towards halide
revealed that only the desired product 11 was present, with anions, no deactivation of the rhodium species was ob-
no byproduct. The sensitivity of the rhodium catalyst served by introducing various functional and heteroaryl
towards halide anions might account for the previously ob- groups (free hydroxy, thiophene, isoxazole, pyrazine and es-
served low activity of the ionic gel-soaked rhodium.
ter functions). The isomerisation of secondary propargylic
To probe the versatility of this procedure, the homo-bis- alcohols to α,β-enones was recently developed by Tanaka
metallated olefin 5 was used as a precursor of various stere- and co-workers using a cationic rhodium(I)/BINAP com-
odefined and conjugated α,β-unsaturated ketones. A variety plex, which gave good yields and selectivity.[28] However,
of iodide partners and carboxylic anhydrides were tested substrate limitation was reported with phenyl- and the
under the above-optimized reaction conditions (Table 1). highly coordinating 2-pyridyl-substituted alcohols, which
No difficulty was encountered in obtaining isolated prod- led, respectively, to a complex mixture of products and no
ucts in Ն98% isomeric purity after simple and single silica reaction. Satisfyingly, 12b and 12o could be prepared by
gel chromatographic purification.
our coupling sequence in 86 and 70% yields, respectively
Satisfyingly, in all cases, the sequential Hiyama/Narasaka (entries 7 and 16). Note that derivatives 12g,h,j,l with sub-
reactions proceeded with complete stereocontrol, that is, stituted chalcone skeletons are intermediates in the biosyn-
with retention of configuration, and the E stereoisomers thesis of flavonoids, which are associated with various phar-
were formed exclusively. Good isolated overall yields, rang- macological activities (anti-malarial, anti-inflammatory,
ing from 40 to 87%, of the final polyunsaturated α,β-enones cytotoxic, anti-cancer, diuretic, choleretic), and were pre-
were obtained from the starting bifunctional 5. The most pared from a unique chalcone template[29] (entries 8, 9, 11
common access to this structural unit is by the Claisen– and 13). The scope of the Narasaka acylation was extended
Schmidt condensation of aldehydes and ketones, a reaction to previously unexplored functionalized anhydrides, leading
that is amply documented and described.[20,21] However, to enones 12d and 12g–i (entries 4 and 8–10). In addition,
this method suffers from the drawbacks of narrow substrate dienone 12n with an isoxazole moiety was obtained selec-
diversity, the reversibility of the aldol addition and several tively in a moderate yield (entry 15). Interestingly, reaction
side-reactions under relatively strong basic conditions (Z with ethyl (Z)-3-iodoacrylate produced the highly conju-
isomer,[22] ketone self-condensation, Michael addition and gated (E,Z)-12p as a pure regio- and stereoisomeric adduct
Cannizzaro byproducts). The Heck-type coupling of vinyl without affecting the Z configuration of the remote double
ketone derivatives is also a valuable C–C bond-forming re- bond (entry 17). No Heck coupling side-reaction was ob-
action, which allows the formation of α,β-unsaturated served. Its polyunsaturated nature made the synthesis par-
ketones, but the poor stability of alkenone substrates and ticularly challenging due to its sensitivity to light, oxygen,
3222
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3219–3227

Rapid Assembly of α,β-Unsaturated Carbonyl Motifs
Table 1. Access to stereodefined and conjugated α,β-unsaturated ketones 12a–p.[a,b]
[a] Method A: 1) 5 (0.50 mmol), R1I (0.39 mmol), 14 (0.54 mmol), 9 (9.0 mol-% Pd), dioxane (2 mL), 60 °C for 2 h; 2) (R2CO)2O
(1.17 mmol), [RhCl(CO)2]2 (5.0 mol-%), 90 °C for 24 h. [b] Method B: the reaction was carried out with 10.0 mol-% of [RhCl(CO)2]2 for
48 h. [c] Isolated yields.
Eur. J. Org. Chem. 2009, 3219–3227
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3223

C. Thiot, A. Wagner, C. Mioskowski
FULL PAPER
NaI (397 mg, 2.65 mmol, 3.9 equiv. in 15 mL of a 1:1 mixture of
DMF/H2O) was introduced into the syringe in three steps
(3ϫ5 mL). Between each anionic exchange, the syringe was shaken
at room temperature for 1 h. Finally, the beads were drained and
successively washed with DMF/H2O (2ϫ5 mL), DMF (3ϫ5 mL),
EtOH/CH2Cl2 (3ϫ5 mL) and Et2O (2ϫ5 mL). Air was used to
dry the beads before they were transferred into a vial and dried
under vacuum to afford the polyammonium iodide gel (450 mg).
Elemental analysis (mmolg–1): N 1.23, I 0.99.
and many common synthetic reagents. This material has
been recently utilized in the Julià–Colonna asymmetric pro-
cedure to furnish a valuable optically active epoxide.[30]
Conclusions
The development of a suitably functionalized reagent 5
as a central building block for the rapid and versatile con-
struction of α,β-unsaturated ketone motifs has been de-
scribed. The intrinsic differential reactivity of the two car-
bon–silicon bonds of 1,2-bis-silylethene 5 has been ex-
ploited to enable the catalytic stepwise elaboration of α,β-
unsaturated ketones by sequential Hiyama coupling/Nara-
saka acylation reactions. The valuable synthetic targets ef-
ficiently obtained include stereodefined polyunsaturated
ketones and diversely αЈ-functionalized α,β-enones. Thus,
this modular assembly strategy illustrates the potential of
bifunctional templates as synthetic tools to rapidly synthe-
sise a variety of structurally related molecules and it is a
worthwhile valuable alternative to known methods. Exten-
sion of the scope of this strategy and further investigations
into the utility of this functional building block are un-
derway.
Polyionic Gel Rh Catalyst 8: The previously prepared polyam-
monium iodide gel (500 mg, 0.615 mmol, 1.23 mmol N per g) and
CH2Cl2 (5 mL) were introduced into a 100 mL scintillation vial.
The vial was shaken for 10 min before the addition of a solution
of [RhCl(PPh3)3] (569 mg, 0.615 mmol, 1 equiv.) in CH2Cl2
(10 mL). The resulting mixture was then mixed for 6 h at 45 °C.
The solution was drained and the orange-coloured beads were
thoroughly washed with CH2Cl2 (4ϫ5 mL) and Et2O (2ϫ5 mL).
The resin was transferred into a vial and dried under vacuum to
give catalyst 8 (422 mg). The loading was determined to be
0.08 mmol Rh per g by elemental analysis.
Polyionic Gel Pd Catalyst 9: The previously prepared polyam-
monium chloride gel (500 mg, 0.681 mmol, 1.37 mmolg–1) and
DMF (4 mL) were added to a 10 mL reaction vessel containing a
stirring bar. The resin was mixed for 10 min (mixed every 3.5 s,
upstroke 2.2 s, upward = 65%), before adding a solution of
Pd(OAc)2 (15.3 mg, 0.068 mmol, 0.1 equiv.) in DMF (8 mL). The
resulting mixture was then mixed for 20 h at 30 °C. After this time,
the solution was drained and the orange-coloured beads were suc-
cessively washed with DMF (2ϫ4 mL), EtOH/CH2Cl2 (3ϫ4 mL)
and Et2O (2ϫ4 mL). Air was used to dry the beads before they
were transferred into a vial and dried under vacuum to afford ionic
gel palladium catalyst 9 (390 mg, 0.15 mmol Pd per g by elemental
analysis).
Experimental Section
1
General: All reactions were carried out under argon. H, 13C and
31P NMR were recorded with Bruker 200 and 300 MHz spectrome-
ters with CDCl3 as solvent. Chemical shifts are denoted in ppm (δ)
relative to TMS (1H, 13C) or external H3PO4 (31P). The gel-phase
samples were prepared in CDCl3. IR spectra of chloroform solu-
tions were recorded using KRS-5 disks by using a Perkin–Elmer
2000 FTIR spectrometer. Solvents were dried and distilled under
argon from sodium and benzophenone before use. Merrifield resins
were purchased from Senn Chemicals (1% cross-linked with divi-
nylbenzene, 200–400 mesh, 1.58 mmolg–1). (Trimethylsilyl)- and di-
methyl(phenyl)silylacetylenes, aryl, alkenyl and N-heteroaryl
iodides and the anhydride acids were obtained from Aldrich or
Lancaster and used as received. 4-Iodo-3,5-dimethylisoxazole was
obtained from Maybridge. Diethoxy(methyl)silane, TBAF (1 
solution in THF), NaI, [RhCl(CO)2]2, [RhCl(cod)]2 and Wilkin-
son’s catalyst were from Alfa Aesar and were used directly.
Pd(OAc)2 was obtained from Aldrich. Elemental analyses were car-
ried out by the Service Central dЈAnalyse du CNRS in Vernaison
(France).
Supported TBAF 14: Merrifield-type resin (1 g, 1.58 mmol,
1.58 mmol Cl per g) was introduced into a 25 mL scintillation vial
followed by a 1:1 mixture of toluene/acetonitrile (10 mL). The vial
was shaken for 15 min and then tributylamine (4 mL, 15.80 mmol,
10 equiv.) was added and stirred at 80 °C for 3 d. The mixture was
poured into a fritted funnel and the resin was washed successively
with MeOH/CH2Cl2 (3ϫ10 mL) and Et2O (2ϫ10 mL). The resin
was transferred into a vial and dried under vacuum to give polyam-
monium chloride gel (980 mg); elemental analysis (mmolg–1): N
1.21. The resulting resin was swollen in DMF (10 mL) for 10 min
and a solution of NaF (194 mg, 4.62 mmol, 3.9 equiv. in 15 mL of
a 1:1 mixture of DMF/H2O) was introduced into the syringe in
three steps (3ϫ5 mL). Between each anionic exchange, the syringe
was shaken at room temperature for 1 h. Finally, the beads were
drained and successively washed with DMF/H2O (2ϫ10 mL),
DMF (3ϫ10 mL), EtOH/CH2Cl2 (3ϫ10 mL) and Et2O
(2ϫ10 mL). Air was used to dry the beads before they were trans-
ferred into a vial and dried under vacuum to afford the supported
ammonium fluoride gel (923 mg). Elemental analysis (mmolg–1):
N 1.14, F 1.02.
Polyammonium Chloride Gel: Merrifield-type resin (5 g, 7.91 mmol,
1.58 mmol Cl per g) was introduced into a 100 mL scintillation vial
followed by a 1:1 mixture of toluene/acetonitrile (50 mL). The vial
was shaken for 15 min and then triethylamine (11 mL, 79.82 mmol,
10 equiv.) was added and stirred at 80 °C for 3 d. The mixture was
poured into a fritted funnel and the resin was washed successively
with MeOH/CH2Cl2 (3ϫ50 mL) and Et2O (2ϫ50 mL). The resin
was transferred into a vial and dried under vacuum to give polyam-
monium chloride gel (5.47 g); elemental analysis (mmolg–1): N
1.37.
General Procedure for the Hydrosilylation of Trimethylsilylacetylene
(6) with Catalyst 8: Diethoxy(methyl)silane (17 mL, 105.7 mmol)
was added to a suspension of trimethylsilylacetylene (6) (10 mL,
70.5 mmol) and polyionic gel catalyst 8 (35 mg, Rh = 0.04 mol-%)
in dry dioxane (100 mL) under argon. The mixture was stirred at
60 °C for 24 h. After this time, the mixture was filtered through a
Celite pad, washed with CH2Cl2 and concentrated in vacuo. The
filtrate was then subjected to bulb-to-bulb distillation (66–67 °C,
Polyammonium Iodide Gel: The previously prepared ammonium
chloride gel (500 mg, 0.681 mmol, 1.37 mmol N per g) was intro-
duced into a 20 mL Supelco syringe together with a 1:1 mixture of
DMF/H2O (5 mL). The resin was then drained and a solution of
3224
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3219–3227

Rapid Assembly of α,β-Unsaturated Carbonyl Motifs
1
0.065 Torr) under reduced pressure to give pure (E)-4 (11.4 g, 70%
mercial sample. m.p. 39–41 °C. H NMR (300 MHz, CDCl3): δ =
yield).
2.28 (s, 3 H), 6.63 (d, J = 16.2 Hz, 1 H), 7.29–7.31 (m, 3 H), 7.40–
7.46 (m, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 27.3, 127.0,
(E)-1-[Diethoxy(methyl)silyl]-2-(trimethylsilyl)ethylene
(4):[9]
128.1, 128.8, 130.3, 134.3, 143.2, 198.1 ppm. IR (KRS5): ν = 1257,
˜
Colourless oil. 1H NMR (300 MHz, CDCl3): δ = 0.06 (s, 9 H), 0.19
(s, 3 H), 1.21 (t, J = 7.1 Hz, 6 H), 3.75 (q, J = 7.1 Hz, 4 H), 6.42
(d, J = 22.9 Hz, 1 H), 6.85 (d, J = 22.9 Hz, 1 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = –5.1, –2.0, 18.1, 57.8, 143.5, 155.1 ppm. IR
1610, 16669, 1692 cm–1. MS: m/z = 147 [M + 1]+.
(E)-Benzylideneacetophenone [(E)-Chalcone, 12b): Prepared from 11
by method A (silica gel, cyclohexane/ethyl acetate, 9:1). Yield
36 mg, 83%; yellow needles. Rf = 0.51 (silica gel, cyclohexane/ethyl
acetate, 8:2); m.p. 55–57 °C. 1H NMR (300 MHz, CDCl3): δ =
7.39–7.41 (m, 3 H), 7.46–7.65 (m, 6 H), 7.83 (d, J = 15.7 Hz, 1 H),
8.04 (dd, J = 1.5, J = 8.4 Hz, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 122.0, 128.5, 128.6, 128.7, 129.0, 130.5, 132.8, 134.9,
(KRS5): ν = 839, 1081, 1106, 1249, 2973, 1495 cm–1. MS: m/z =
˜
233 [M + 1]+.
(E)-1-[Diethoxy(methyl)silyl]-2-dimethyl(phenyl)silylethylene
(5):
Yield 15.6 g, 75%; colourless oil (b.p. = 84–85 °C/0.015 Torr). 1H
NMR (300 MHz, CDCl3): δ = 0.19 (s, 3 H), 0.36 (s, 3 H), 0.44 (s,
3 H), 1.21 (t, J = 7.1 Hz, 6 H), 3.82 (q, J = 7.1 Hz, 4 H), 6.54 (d,
J = 22.7 Hz, 1 H), 6.93 (d, J = 22.7 Hz, 1 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = –2.8, –0.8, 18.4, 58.3, 58.5, 127.9, 129.2,
138.2, 144.8, 190.4 ppm. IR (KRS5): ν = 747, 1215, 1336, 1606,
˜
1664 cm–1. MS: m/z = 209 [M + 1]+.
(E)-1,2-Diphenylethylene (trans-Stilbene, 13): Obtained as a side-
product from the reaction of 10 by method A (silica gel, cyclohex-
ane). Yield 5 mg, 13%; white crystals. Rf = 0.46 (silica gel, cyclo-
hexane). The spectroscopic data were identical to those of a com-
mercial sample. 1H NMR (300 MHz, CDCl3): δ = 7.18 (s, 2 H),
7.32 (tt, J = 1.5, 7.3 Hz, 2 H), 7.42 (tt, J = 1.5, 7.2 Hz, 4 H), 7.59
(dd, J = 1.1, 8.3 Hz, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
134.0, 138.2, 146.1, 153.2 ppm. IR (KRS5): ν = 839, 1081, 1106,
˜
1249, 1806, 1891, 1955, 2973, 3025, 3069 cm–1. MS: m/z = 295 [M
+ 1]+.
General Procedure for the Hiyama Coupling Reaction with Catalyst
9:
(E)-1-Diethoxy(methyl)silyl-2-trimethylsilylethylene
(4)
(0.14 mmol, 1.3 equiv.) and iodobenzene (0.11 mmol, 1 equiv.) were
successively added to a suspension of polyionic gel catalyst 9
(65 mg, 9.0 mol-% Pd) in dioxane (1.5 mL) under argon. After
dropwise addition of TBAF (1.0  in THF, 0.15 mmol, 1.4 equiv.),
the reaction was stirred at 60 °C for 2 h. The mixture was filtered
through a Celite pad and concentrated in vacuo. The crude product
was purified by silica gel chromatography to afford the product 10
(17.1 mg, 88% yield).
126.6, 127.7, 128.8, 137.4 ppm. IR (KRS5): ν = 963, 1452, 1495,
˜
3021 cm–1. MS: m/z = 180 [M]+.
General Procedure for the One-Pot Hiyama/Narasaka Coupling Pro-
tocol with Catalysts 9 and [RhCl(CO)2]2: See Table 1. Polyionic gel
catalyst 9 (230 mg, 0.035 mmol, 9.0 mol-% Pd) was added to a di-
oxane solution (2 mL) of iodobenzene (0.39 mmol, 1 equiv.),
(E)-1-[diethoxy(methyl)silyl]-2-[dimethyl(phenyl)silyl]ethylene (5;
0.50 mmol, 1.3 equiv.) and supported TBAF 14 (0.54 mmol,
1.4 equiv., 0.79 mmol Rh per g). The mixture was heated at 60 °C
for 2 h and filtered through a Celite pad. After the addition of
[RhCl(CO)2]2 (7.8 mg, 0.019 mmol, 5mol-%) and acetic anhydride
(1.17 mmol, 3 equiv.), the mixture was heated at 90 °C for 24 h and
concentrated in vacuo. The crude product was purified by thin-
layer chromatography to afford (E)-4-phenylbut-3-en-2-one (12a;
47.2 mg, 83%).
(E)-2-Phenyl-1-(trimethylsilyl)ethylene (10):[5c] Purified by silica gel
chromatography with cyclohexane as eluent. Yellow oil. Rf = 0.68
(silica gel, cyclohexane/ethyl acetate, 95:5). The spectroscopic data
are identical to those of a commercial sample. 1H NMR (300 MHz,
CDCl3): δ = 0.19 (s, 9 H), 6.51 (d, J = 19.0 Hz, 1 H), 6.91 (d, J =
19.0 Hz, 1 H), 7.27–7.48 (m, 5 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = –0.4, 127.1, 128.6, 129.2, 130.2, 139.0, 144.3 ppm. IR
(KRS5): ν = 755, 843, 867, 1247, 1606, 2956, 3023, 3067 cm–1. MS:
˜
m/z = 177 [M + 1]+.
(E)-1-Phenylpent-1-en-3-one (12c):[33] Prepared by method B (silica
gel, cyclohexane/ethyl acetate, 9:1). Yield 45 mg, 73%, pale-yellow
oil. Rf = 0.25 (silica gel, cyclohexane/ethyl acetate, 95:5). 1H NMR
(200 MHz, CDCl3): δ = 1.17 (t, J = 7.3 Hz, 3 H), 2.70 (q, J =
7.3 Hz, 2 H), 6.74 (d, J = 16.1 Hz, 1 H), 7.37–7.40 (m, 3 H), 7.52–
7.60 (m, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 8.4, 34.2,
(E)-1-[Dimethyl(phenyl)silyl]-2-phenylethylene (11):[31] Prepared by
following the above procedure for the synthesis of 10 and purified
by silica gel chromatography with cyclohexane as eluent. Yield
24.1 mg, 92%; yellow oil. Rf = 0.80 (silica gel, cyclohexane). The
spectroscopic data were identical to those of a commercial sample.
1H NMR (300 MHz, CDCl3): δ = 0.67 (s, 6 H), 6.82 (d, J =
19.3 Hz, 1 H), 7.19 (d, J = 19.3 Hz, 1 H), 7.40–7.68 (m, 8 H), 7.80–
7.85 (m, 2 H) ppm. 13C NMR (50 MHz, CDCl3): δ = –0.2, 126.7,
127.3, 128.0, 128.4, 128.7, 129.3, 134.1, 138.3, 138.7, 145.5 ppm.
126.2, 128.4, 129.1, 130.5, 134.7, 142.4, 201.1 ppm. IR (KRS5): ν
˜
= 1611, 1668, 1693, 2977 cm–1. MS: m/z = 161 [M + 1]+. HRMS
(EI): calcd. for C11H12O 160.0888 [M]+; found 160.0893.
(E)-1-Phenylhepta-1,6-dien-3-one (12d): Prepared by method B (sil-
ica gel, cyclohexane/ethyl acetate, 95:5). Yield 48 mg, 66%; yellow
oil. Rf = 0.39 (silica gel, cyclohexane/ethyl acetate, 95:5). 1H NMR
(300 MHz, CDCl3): δ = 2.39–2.48 (m, J = 1.2, J = 7.1 Hz, 2 H),
2.77 (t, J = 7.1 Hz, 2 H), 5.01 (dq, J = 1.2, J = 1.5, J = 10.3 Hz,
1 H), 5.08 (dq, J = 1.2, J = 1.5, J = 17.1 Hz, 1 H), 5.87 (m, J =
7.8, J = 10.3, J = 17.1 Hz, 1 H), 6.75 (d, J = 16.2 Hz, 1 H), 7.38–
7.40 (m, 3 H), 7.53–7.60 (m, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 28.4, 40.1, 115.4, 126.3, 128.4, 129.1, 130.6, 134.7,
IR (KRS5): ν = 755, 843, 867, 1247, 1606, 1806, 1890, 1955, 2956,
˜
3023, 3067 cm–1. MS: m/z = 239 [M + 1]+. HRMS (EI): calcd. for
C16H18Si 238.1121 [M]+; found 238.1116.
General Procedure for the Narasaka Acylation with [RhCl(CO)2]2:
[RhCl(CO)2]2 (4.1 mg, 0.01 mmol, 5 mol-%) and acetic anhydride
(0.63 mmol, 3 equiv.) were added to a dioxane solution (2 mL) of
(E)-1-dimethyl(phenyl)silyl-2-phenylethylene
(11;
0.21 mmol,
1 equiv.) and the mixture was heated at 90 °C for 24 h. After evapo-
ration of the solvent, the crude product was purified by silica gel
chromatography to afford (E)-4-phenylbut-3-en-2-one (12a; 26 mg,
85%).
137.4, 142.7, 199.7 ppm. IR (KRS5): ν = 1612, 1662, 1690,
˜
2920 cm–1. MS: m/z = 187 [M + 1]+. HRMS (EI): calcd. for
C13H14O 186.1045 [M]+; found 186.1049.
(E)-4-Phenylbut-3-en-2-one (Benzylideneacetone, 12a):[32] Purified
by silica gel chromatography with cyclohexane/ethyl acetate (8:2)
as eluent. White crystals. Rf = 0.46 (silica gel, cyclohexane/ethyl
acetate, 8:2). The spectroscopic data are identical to those of a com-
(E)-4-Methyl-1-phenylpent-1-en-3-one (12e):[34] Prepared by method
B (silica gel, cyclohexane). Yield 49 mg, 72%; pale-yellow oil. Rf =
0.60 (silica gel, cyclohexane/ethyl acetate, 9:1). 1H NMR
(200 MHz, CDCl3): δ = 1.18 (d, J = 6.8 Hz, 6 H), 2.94 (sept, J =
Eur. J. Org. Chem. 2009, 3219–3227
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3225

C. Thiot, A. Wagner, C. Mioskowski
FULL PAPER
6.8 Hz, 1 H), 6.82 (d, J = 15.9 Hz, 1 H), 7.36–7.40 (m, 3 H), 7.54–
(E)-4-[2-(Hydroxymethyl)phenyl]but-3-en-2-one (12k): Prepared by
7.65 (m, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 18.7, 39.5, method A (silica gel, cyclohexane/ethyl acetate, 95:5). Yield 49 mg,
124.7, 128.5, 129.1, 130.5, 133.2, 142.6, 204.0 ppm. IR (KRS5): ν
72%; yellow oil. Rf = 0.48 (silica gel, cyclohexane/ethyl acetate,
˜
1
= 1056, 1613, 1664, 1689, 2969 cm–1. MS: m/z = 175 [M + 1]+. 8:2). H NMR (200 MHz, CDCl3): δ = 2.38 (s, 3 H), 5.24 (s, 2 H),
HRMS (EI): calcd. for C12H14O 174.1044 [M]+; found 174.1045.
6.64 (d, J = 16.1 Hz, 1 H), 7.33–7.50 (m, 3 H), 7.58–7.64 (m, 1 H),
7.82 (d, J = 16.1 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
27.7, 64.0, 127.0, 129.3, 129.7, 130.4, 130.6, 134.2, 135.1, 139.9,
(E)-4,4-Dimethyl-1-phenylpent-1-en-3-one (12f):[35] Prepared by
method B (silica gel, cyclohexane). Yield 47 mg, 64%; pale-yellow
oil. Rf = 0.84 (silica gel, cyclohexane/ethyl acetate, 95:5). 1H NMR
(300 MHz, CDCl3): δ = 1.23 (s, 9 H), 7.13 (d, J = 15.4 Hz, 1 H),
7.37–7.39 (m, 3 H), 7.55–7.57 (m, 2 H), 7.68 (d, J = 15.4 Hz, 1
H) ppm. 13C NMR (50 MHz, CDCl3): δ = 26.5, 43.4, 121.0, 128.4,
198.3 ppm. IR (KRS5): ν = 757, 1227, 1255, 1672, 1740, 3495 cm–1.
˜
MS: m/z = 177 [M + 1]+. HRMS (EI): calcd. for C11H12O2
176.0837 [M]+; found 176.0832.
(E)-3-[2-(Hydroxymethyl)phenyl]-1-(2-thienyl)prop-2-en-1-one (12l):
Prepared by method A (silica gel, cyclohexane/ethyl acetate, 8:2).
Yield 67 mg, 70%; yellow oil. Rf = 0.22 (silica gel, cyclohexane/
129.0, 130.3, 135.3, 143.1, 204.3 ppm. IR (KRS5): ν = 1077, 1611,
˜
1684, 2969 cm–1. MS: m/z = 189 [M + 1]+. HRMS (EI): calcd. for
C13H16O 188.1201 [M]+; found 188.1208.
ethyl acetate, 8:2). H NMR (300 MHz, CDCl3): δ = 1.63 (s, 1 H),
1
4.89 (s, 2 H), 7.18 (dd, J = 3.8, 5.0 Hz, 1 H), 7.34–7.42 (m, J = 1.5,
7.1 Hz, 2 H), 7.39 (d, J = 15.2 Hz, 1 H), 7.47 (td, J = 1.5, 7.1 Hz,
1 H), 7.69 (dd, J = 1.2, 5.0 Hz, 1 H), 7.73 (dd, J = 1.5, 7.1 Hz, 1
H), 7.87 (dd, J = 1.2, 3.8 Hz, 1 H), 8.17 (d, J = 15.2 Hz, 1 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 63.2, 124.3, 127.3, 128.5, 129.1,
130.6, 132.2, 132.7, 133.8, 134.2, 141.0, 145.6, 182.3 ppm. IR
(E)-1-(4-Methoxyphenyl)-3-phenylprop-2-en-1-one (12g):[36] Pre-
pared by method A (silica gel, cyclohexane/ethyl acetate, 95:5).
Yield 81 mg, 87%; yellow solid; m.p. 105–106 °C. Rf = 0.46 (silica
1
gel, cyclohexane/ethyl acetate, 8:2). H NMR (300 MHz, CDCl3):
δ = 3.90 (s, 3 H), 7.00 (d, J = 9.1 Hz, 2 H), 7.41–7.43 (m, 3 H),
7.56 (d, J = 15.8 Hz, 1 H), 7.64–7.67 (m, 2 H), 7.81 (d, J = 15.8 Hz,
1 H), 8.06 (d, J = 9.1 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 55.6, 114.0, 122.0, 128.5, 129.0, 130.4, 130.9, 131.2, 135.2,
(KRS5): ν = 728, 755, 1415, 1592, 1649, 3467 cm–1. MS: m/z = 245
˜
[M + 1]+. HRMS (EI): calcd. for C14H12O2S 244.0558 [M]+; found
244.0553.
144.1, 163.5, 188.8 ppm. IR (KRS5): ν = 763, 1600, 1655,
˜
2938 cm–1. MS: m/z = 239 [M + 1]+. HRMS (EI): calcd. for
(E)-1-(3,5-Dimethylisoxazol-4-yl)-4-methylpent-1-en-3-one (12m):
Prepared by method B (silica gel, cyclohexane/ethyl acetate, 95:5).
Yield 45 mg, 60%; pale-yellow oil. Rf = 0.59 (silica gel, cyclohex-
C16H14O2 238.0994 [M]+; found 238.0990.
(E)-3-Phenyl-1-(2-thienyl)prop-2-en-1-one (12h): Prepared by
method A (silica gel, cyclohexane/ethyl acetate, 95:5). Yield 44 mg,
53%; yellow oil. Rf = 0.60 (silica gel, cyclohexane/ethyl acetate,
1
ane/ethyl acetate, 8:2). H NMR (200 MHz, CDCl3): δ = 1.15 (d,
J = 7.1 Hz, 2 H), 2.38 (s, 3 H), 2.49 (s, 3 H), 2.81 (sept, J = 6.8 Hz,
1 H), 6.53 (d, J = 16.4 Hz, 1 H), 7.39 (d, J = 16.4 Hz, 1 H) ppm.
13C NMR (50 MHz, CDCl3): δ = 11.9, 12.2, 18.5, 39.9, 111.9,
1
8:2). H NMR (300 MHz, CDCl3): δ = 7.20 (dd, J = 3.8, 5.0 Hz,
1 H), 7.42–7.44 (m, 3 H), 7.43 (d, J = 15.6 Hz, 1 H), 7.64–7.67 (m,
2 H), 7.69 (dd, J = 1.2, 5.0 Hz, 1 H), 7.88 (d, J = 15.6 Hz, 1 H),
7.87–7.89 (dd, J = 1.2, 3.8 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 121.7, 128.3, 128.6, 129.1, 130.7, 131.9, 134.0, 134.8,
124.1, 130.5, 158.6, 170.2, 203.2 ppm. IR (KRS5): ν = 1059, 1265,
˜
1624, 1692, 2971 cm–1. MS: m/z = 194 [M + 1]+. HRMS (EI): calcd.
for C11H15NO2 193.1103 [M]+; found 193.1108.
144.2, 145.6, 182.1 ppm. IR (KRS5): ν = 761, 1217, 1415, 1596,
(E)-1-(3,5-Dimethylisoxazol-4-yl)-4-methylpent-1,4-dien-3-one (12n):
Prepared by method A (silica gel, cyclohexane/ethyl acetate, 9:1).
Yield 30 mg, 40%; yellow oil. Rf = 0.73 (silica gel, cyclohexane/
˜
1652 cm–1. MS: m/z = 215 [M + 1]+. HRMS (EI): calcd. for
C13H10OS 214.0452 [M]+; found 214.0450.
1
ethyl acetate, 7:3). H NMR (300 MHz, CDCl3): δ = 1.99 (s, 3 H),
(E)-4-Methyl-1-phenylpenta-1,4-dien-3-one (12i): Prepared by
method A (silica gel, cyclohexane). Yield 42 mg, 63%; pale-yellow
oil. Rf = 0.50 (silica gel, cyclohexane/ethyl acetate, 95:5). 1H NMR
(300 MHz, CDCl3): δ = 2.01 (s, 3 H), 5.85 (d, J = 0.6 Hz, 1 H),
6.05 (s, 1 H), 7.30 (d, J = 15.9 Hz, 1 H), 7.39–7.41 (m, 3 H), 7.58–
7.61 (m, 2 H), 7.66 (d, J = 15.9 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 26.5, 43.4, 121.0, 128.4, 129.0, 130.3, 135.3, 143.1,
2.42 (s, 3 H), 2.52 (s, 3 H), 5.38 (d, J = 1.2 Hz, 1 H), 5.83 (d, J =
1.2 Hz, 1 H), 5.96 (s, 1 H), 7.01 (d, J = 15.9 Hz, 1 H), 7.44 (d, J =
15.9 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.0, 12.2,
18.3, 112.2, 121.2, 124.5, 131.6, 145.7, 158.6, 170.2, 191.3 ppm. IR
(KRS5): ν = 1087, 1346, 1611, 1669 cm–1. MS: m/z = 192 [M + 1]+.
˜
HRMS (EI): calcd. for C11H13NO2 191.0946 [M]+; found 191.0951.
204.3 ppm. IR (KRS5): ν = 1084, 1350, 1607, 1661 cm–1. MS: m/z
(E)-4,4-Dimethyl-1-(pyrazin-2-yl)pent-1-en-3-one (12o): Prepared by
method B (silica gel, cyclohexane/ethyl acetate, 9:1). Yield 52 mg,
70%; orange oil. Rf = 0.50 (silica gel, cyclohexane/ethyl acetate,
˜
= 173 [M + 1]+. HRMS (EI): calcd. for C12H12O 172.0883 [M]+;
found 172.0888.
1
8:2). H NMR (200 MHz, CDCl3): δ = 1.24 (s, 9 H), 7.63 (d, J =
(E)-3-(2-Hydroxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (12j):
Prepared by method A (silica gel, cyclohexane/ethyl acetate, 95:5).
A mixture of the expected product and p-anisic anhydride was ob-
tained and dissolved in CH2Cl2. The solution was quenched with
saturated NaHCO3. The organic layer was extracted with CH2Cl2
and the combined extracts were washed with H2O and dried with
Na2SO4. After evaporation, the product was obtained as a yellow
oil. Yield 54 mg, 55%. Rf = 0.60 (silica gel, cyclohexane/ethyl ace-
15.1 Hz, 1 H), 7.75 (d, J = 15.1 Hz, 1 H), 8.53 (d, J = 2.4 Hz, 1
H), 8.60 (t, J = 1.2, 2.4 Hz, 1 H), 8.66 (d, J = 1.2 Hz, 1 H) ppm.
13C NMR (50 MHz, CDCl3): δ = 26.2, 43.7, 127.0, 137.4, 145.0,
145.3, 146.0, 149.2, 204.3 ppm. IR (KRS5): ν = 1077, 1398, 1619,
˜
1687, 2969 cm–1. MS: m/z = 191 [M + 1]+. HRMS (EI): calcd. for
C11H14N2O 190.1106 [M]+; found 190.1102.
Ethyl (2Z,4E)-6-Oxo-6-(2-thienyl)hexa-2,4-dienoate (12p): Prepared
tate, 8:2). 1H NMR (300 MHz, CDCl3): δ = 7.20 (dd, J = 3.8, by method A (silica gel, cyclohexane). Yield 37 mg, 40%; pale-yel-
5.0 Hz, 1 H), 7.42–7.44 (m, 3 H), 7.43 (d, J = 15.6 Hz, 1 H), 7.64–
7.67 (m, 2 H), 7.69 (dd, J = 1.2, 5.0 Hz, 1 H), 7.88 (d, J = 15.6 Hz, 1
H), 7.87–7.89 (dd, J = 1.2, 3.8 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 121.7, 128.3, 128.6, 129.1, 130.7, 131.9, 134.0, 134.8,
low oil. Rf = 0.56 (silica gel, cyclohexane/ethyl acetate, 98:2). 1H
NMR (200 MHz, CDCl3): δ = 1.32 (t, J = 7.1 Hz, 3 H), 4.23 (q, J
= 7.2 Hz, 2 H), 6.22 (dd, J = 1.0, 11.2 Hz, 1 H), 6.84–6.88 (m, 2
H), 7.14 (dd, J = 4.1, 5.0 Hz, 1 H), 7.69 (dd, J = 1.2, 5.0 Hz, 1 H),
7.75 (dd, J = 1.2, 4.2 Hz, 1 H), 8.41 (qd, J = 1.0, 11.1, 15.3 Hz, 1
H) ppm. 13C NMR (50 MHz, CDCl3): δ = 14.1, 60.6, 124.5, 127.8,
129.4, 130.2, 131.7, 139.6, 140.5, 149.9, 165.8, 179.6 ppm. MS: m/z
144.2, 145.6, 182.1 ppm. IR (KRS5): ν = 761, 1217, 1415, 1596,
˜
1652 cm–1. MS: m/z = 255 [M + 1]+. HRMS (EI): calcd. for
C16H14O3 254.0452 [M]+; found 254.0450.
3226
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3219–3227

Rapid Assembly of α,β-Unsaturated Carbonyl Motifs
= 237 [M + 1]+. HRMS (EI): calcd. for C12H12O3S 236.0507
[M]+; found 236.0512.
[13] Y. Hatanaka, T. Hiyama, Tetrahedron Lett. 1990, 31, 2719.
[14] S. E. Denmark, R. F. Sweis, Acc.Chem. Res. 2002, 35, 835.
[15] a) M. Yamame, K. Uera, K. Narasaka, Chem. Lett. 2004, 33,
424; b) M. Yamame, K. Uera, K. Narasaka, Bull. Chem. Soc.
Jpn. 2005, 78, 477.
Acknowledgments
[16] See the Supporting Information.
[17] a) K. Kokubo, M. Matsumasa, M. Miura, M. Nomura, J. Org.
Chem. 1996, 61, 6941; b) K. Kokubo, M. Matsumasa, M. Mi-
ura, M. Nomura, J. Organomet. Chem. 1998, 560, 217; c) T.
Sugihara, T. Satoh, M. Miura, M. Nomura, Angew. Chem. Int.
Ed. 2003, 42, 4672.
[18] Under rhodium catalysis conditions, no coupling reaction oc-
curred with 5 and iodobenzene in the presence of TBAF,
whereas only degradation was observed when 1,2-bis-silyl-
ethene 5 and acetic anhydride were subjected to palladium
acylation catalysis.
[19] This reagent was prepared by quaternarisation of nBu3N from
Merrifield resin followed by anionic exchange with NaF.
[20] E. P. Kohler, H. M. Chadwel, Org. Synth. 1941, 1, 77.
[21] a) K. Mogilaiah, N. V. Reddy, Synth. Commun. 2003, 33, 73;
b) M. Hatsuda, T. Kuroda, M. Seki, Synth. Commun. 2003, 33,
427; c) U. Sensfuss, Tetrahedron Lett. 2003, 44, 2371; d) U. P.
Kreher, A. E. Rosamilia, C. L. Raston, J. L. Scott, C. R.
Strauss, Org. Lett. 2003, 5, 3107; e) S. D. Yang, L. Y. Wu, Z. Y.
Yan, Z. L. Pan, Y. M. Liang, J. Mol. Catal. A 2007, 268, 107.
[22] A. T. Nielsen, W. J. Houlihan, Org. React. 1968, 16, 1.
[23] G. Zou, J. Guo, Z. Wang, W. Huang, J. Tang, Dalton Trans.
2007, 28, 3055.
We are grateful for financial support from the French Ministère de
l’Education Nationale de la Recherche et de la Technologie
(MENRT), Polymer Laboratories, Ltd. and the European Commis-
ion (Integrated Biomimetic Approach to Asymmetric Catalysis
(IBAAC) network; MCRTN-CT-2003-5050201).
[1] For representative examples of bismetallated lynchpin-type rea-
gents for polyene synthesis, see: a) A. M. Echavarren, J. K.
Stille, J. Am. Chem. Soc. 1988, 110, 1557; b) A. F. Renaldo,
J. W. Labadie, J. K. Stille, Org. Synth. 1989, 67, 86; c) F. Babu-
dri, G. M. Farinola, V. Fiandanese, L. Mazzone, F. Naso, Tet-
rahedron 1998, 54, 1085; d) S. E. Denmark, S. A. Tymonko, J.
Am. Chem. Soc. 2005, 127, 8004; e) T. Ishiyama, N. Matsuda,
N. Miyaura, A. Suzuki, J. Am. Chem. Soc. 1993, 115, 11018;
f) J. Walkowiak, M. Jankkowska-Wajda, B. Marciniec, Chem.
Eur. J. 2008, 14, 6679; g) M. Murakami, T. Matsuda, K. Itami,
S. Ashida, M. Terayama, Synthesis 2004, 1522; h) F. Lhermitte,
B. Carboni, Synlett 1996, 377; i) R. S. Coleman, M. C. Wal-
czak, Org. Lett. 2005, 7, 2289; j) R. S. Coleman, X. Lu, I. Mo-
dolo, J. Am. Chem. Soc. 2007, 129, 3826.
[2] J. Burghart, R. Bruckner, Angew. Chem. Int. Ed. 2008, 47, 7664.
[3] a) S. Hyuga, N. Yamashina, S. Hara, A. Suzuki, Chem. Lett.
1988, 809; b) M. Ogima, S. Hyuga, S. Hara, A. Suzuki, Chem.
Lett. 1989, 1959.
[4] A. Mori, E. Takahiasa, H. Kajiro, K. Hirabayashi, Y. Nishih-
ara, T. Hiyama, Chem. Lett. 1998, 443.
[24] L. Botella, C. Najera, Tetrahedron Lett. 2004, 45, 1833.
[25] a) A. Bianco, C. Cavarischia, M. Guiso, C. Marra, Tetrahedron
Lett. 2003, 44, 9107; b) A. Bianco, C. Cavarischia, M. Guiso,
Eur. J. Org. Chem. 2004, 2894.
[26] K. S. You, C. H. Yoon, K. W. Jug, J. Am. Chem. Soc. 2006,
[5] a) C. Thiot, M. Schmutz, A. Wagner, C. Mioskowski, Angew.
Chem. Int. Ed. 2006, 45, 2868; b) C. Thiot, A. Wagner, C. Mios-
kowski, Org. Lett. 2006, 8, 5936; c) C. Thiot, M. Schmutz, A.
Wagner, C. Mioskowski, Chem. Eur. J. 2007, 13, 8971.
[6] See the Supporting Information for full details.
[7] A. Mori, E. Takahiasa, Y. Nishihara, T. Hiyama, Can. J. Chem.
2001, 79, 1522.
128, 16384.
[27] P. Peach, D. J. Cross, J. A. Kenny, I. Mann, I. Houson, L.
Campbell, T. Walsgrove, M. Wills, Tetrahedron 2006, 62, 1864.
[28] a) K. Tanaka, T. Shoji, M. Hirano, Eur. J. Org. Chem. 2007,
2687; b) K. Tanaka, T. Shoji, Org. Lett. 2005, 7, 3561.
[29] a) Z. Nowakowska, Eur. J. Med. Chem. 2007, 42, 125; b) J.
Tatsuzaki, K. F. Bastow, K. Nakagawa-Goto, S. Nakamura, H.
Itokawa, K. H. Lee, J. Nat. Prod. 2006, 69, 1445; c) D. N. Dhar,
The Chemistry of Chalcones and Related Compounds, Wiley,
New York, 1981.
[30] J. M. Lopez-Pedrosa, M. R. Pitts, S. M. Roberts, S. Samina-
than, J. Whittall, Tetrahedron Lett. 2004, 45, 5073.
[31] G. Berthon-Gelloz, J. M. Schumers, G. De Bo, I. Marko, J.
Org. Chem. 2008, 73, 4190.
[8] Interestingly, the reaction was completed after 2 h and gave a
70:30 mixture of (E)- and (Z)-1,2-bis-silylethene 5.
[9] Note that the formation of 4 was reported as a 29:71 mixture of
(E)-4 and the internal adduct formed by ruthenium-catalyzed
hydrosilylation; see: Y. Kawanami, Y. Sonoda, T. Mori, K. Ya-
mamoto, Org. Lett. 2002, 4, 2825.
[10] a) T. Hiyama, Y. Hatanaka, Pure Appl. Chem. 1994, 66, 1471;
b) T. Hiyama in Metal-Catalyzed, Cross–Coupling Reactions [32] S. Inaba, R. D. Rieke, J. Org. Chem. 1985, 50, 1373.
(Eds.: F. Diederich, P. J. Stang), Wiley-VCH, Weinheim, 1998,
chapter 10; c) T. Hiyama, E. Shirakawa, Top. Curr. Chem. 2002,
219, 61; d) S. E. Denmark, R. F. Sweis, Chem. Pharm. Bull.
2002, 50, 1531; e) S. E. Denmark, R. F. Sweis, Chem. Pharm.
[33] M. Arisawa, Y. Torisawa, M. Nagasawa, J. Org. Chem. 1997,
62, 4327.
[34] P. Wipf, L. T. Rahman, S. R. Rector, J. Org. Chem. 1998, 63,
7132.
Bull. 2002, 50, 1531; f) S. E. Denmark, J. M. Kallemeyn, J. Am. [35] T. Ooi, D. Ohara, M. Tamaru, K. Maruoka, J. Am. Chem. Soc.
Chem. Soc. 2006, 128, 15958.
2004, 126, 6844.
[36] R. J. Cox, S. Evitt, Org. Biomol. Chem. 2007, 5, 229.
[11] K. Hosoi, K. Nosaki, T. Hiyama, Chem. Lett. 2002, 31, 138.
[12] E. Hagiwara, K. I. Gouda, Y. Hatanaka, T. Hiyama, Tetrahe-
dron Lett. 1997, 38, 438.
Received: March 18, 2009
Published Online: May 27, 2009
Eur. J. Org. Chem. 2009, 3219–3227
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3227