Allene substitution-controlled switching of dimerization to cycloisomerization in the PdII-catalyzed reaction of terminal α-allenones

Article abstract of DOI:10.1002/ejoc.200700128

In this contribution, we describe the role of steric interactions in Pd^II-catalyzed reactions of terminal α-allenones, which has not previously been invoked in discussions of these versatile compounds. By adopting [PdCl₂(MeCN)_2<

Full text of DOI:10.1002/ejoc.200700128

FULL PAPER
DOI: 10.1002/ejoc.200700128
Allene Substitution-Controlled Switching of Dimerization to
Cycloisomerization in the PdII-Catalyzed Reaction of Terminal α-Allenones
Benito Alcaide,*[a] Pedro Almendros,*[b] and Teresa Martínez del Campo[a]
Keywords: Allenes / Cyclization / Heterocycles / Palladium / Substituent effects
In this contribution, we describe the role of steric interactions
in PdII-catalyzed reactions of terminal α-allenones, which has
not previously been invoked in discussions of these versatile
lenones bearing an internal substituent favor the formation
of cycloisomerization products. Thus, for the first time the
mode of reaction (cycloisomerization vs. dimerization) of α-
compounds. By adopting [PdCl2(MeCN)2] as catalyst, the cy- allenones is substrate-directable.
cloisomerization/dimerization ratio of α-allenones is con-
trolled by the substitution of the allene compound: unsubsti-
tuted allenones mainly afford dimerization, whereas al-
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
reported.[7] Thus, it appears that the only known efficient
method for controlling the mode of reaction (cycloisomeri-
zation vs. dimerization) of α-allenones is the case of choice
of catalyst. However, substrate-directable reactions are an
important class of selective organic transformations, and
understanding their mechanism of direction is paramount
to their utility.[8] Following our commitment in heterocyclic
and allene chemistry,[9] we report herein that by adopting
PdII-catalyzed conditions, the cycloisomerization/dimeriza-
tion ratio of α-allenones is controlled by the substitution of
the allene compound: unsubstituted allenones mainly afford
dimerization, whereas allenones bearing an internal substit-
uent favor the formation of cycloisomerization products.
Introduction
Of the various heterocyclic structures, polysubstituted fu-
rans are among the most important, because of their pres-
ence in natural and synthetic substances, pharmaceuticals,
and fragances.[1] A second feature of furans receiving in-
creasing attention stems from the realisation that they rep-
resent readily accessible and highly flexible building blocks
for the construction of a wide-range of other compounds
including natural products.[2] On the other hand, during the
past decades the allene moiety has developed from almost
a rarity to an established member of the weaponry utilized
in modern organic synthetic chemistry, by taking advantage
of its inherent chirality and high reactivity in such diverse
transformations as addition, cyclization/cycloaddition, cy-
cloisomerization, and cross-coupling reactions.[3] Allenones
are of particular interest since they undergo selective cyclo-
isomerization or dimerization reactions to afford furans.
Marshall and co-workers discovered the RhI- or AgI-cata-
lyzed selective cycloisomerization of α-allenones to substi-
tuted furans,[4] while Hashmi and co-workers reported the
PdII-catalyzed dimerization of terminal α-allenones to af-
ford 2,4-disubstituted furans.[5] More recently, the cyclo-
Results and Discussion
The starting substrates, unsubstituted α-allenones 2a–f
and substituted α-allenones 3a–l, were obtained from the
appropriate carbaldehyde 1a–f following sequential coup-
ling/oxidation protocols. α-Allenones 2 were obtained from
carbaldehydes 1 by zinc-mediated carbonyl–propargylation
followed by Dess–Martin oxidation with concomitant pro-
pargyl to allene rearrangement (Scheme 1, Table 1). α-Al-
lenones 3 were readily prepared in good overall yield begin-
ning from the appropriate carbaldehyde 1 (Scheme 2,
isomerization of α-allenones catalyzed by AuIII [6]
palladatricyclo[4.1.0.0(2,4)]heptane catalyst have also been
,
or by a
[a] Departamento de Química Orgánica I, Facultad de Química, Table 2) via regiocontrolled indium-mediated Barbier-type
carbonyl–allenylation reaction in aqueous media,[10] fol-
Universidad Complutense de Madrid,
28040 Madrid, Spain
lowed by Dess–Martin oxidation.
Fax: +34-91-3944103
E-mail: alcaideb@quim.ucm.es
[b] Instituto de Química Orgánica General, Consejo Superior de
Investigaciones Científicas, CSIC,
First, the general reactivity of α-allenones toward the
bond reorganization was tested with aromatic substrates 2a,
3a, and 3b by the use of [PdCl2(MeCN)2] as catalyst
(Scheme 3). As expected, the PdII-catalyzed reaction of un-
substituted α-allenone 2a yielded the dimer 4a bearing a
furan ring, which is the result of a cycloisomerization fol-
Juan de la Cierva 3, 28006 Madrid, Spain
Fax: +34-91-5644853
E-mail: iqoa392@iqog.csic.es
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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PdII-Catalyzed Reaction of Terminal α-Allenones
FULL PAPER
Table 2. Regioselective preparation of substituted α-allenic ketones
3.[a]
Scheme 1. Regioselective preparation of α-allenic ketones 2. Rea-
gents and conditions: a) (i) Zn, THF, NH4Cl (aq. satd.), room
temp.; (ii) Dess–Martin periodinane, CH2Cl2, room temp.
Table 1. Regioselective preparation of unsubstituted α-allenic
ketones 2.[a]
[a] Yield of pure, isolated product with correct analytical and spec-
troscopic data. PMP = 4-MeOC6H4.
Scheme 2. Regioselective preparation of α-allenic ketones 3. Rea-
gents and conditions: a) (i) In, THF, NH4Cl (aq. satd.), room
temp.; (ii) Dess–Martin periodinane, CH2Cl2, room temp.
lowed by allenone coupling. Interestingly, the reaction of α-
allenone 3b bearing an internal methyl substituent gave in
reasonable yield and very high selectivity the monomer 5a
which bears a furan ring, which is just the result of a cyclo-
isomerization. Gratifyingly, the reaction of phenyl-substi-
tuted α-allenone 3c afforded in good yield the furan 5b as
the sole product. On the basis of the markedly different
[a] Yield of pure, isolated product with correct analytical and spec-
behavior observed for the above systems, we suggest that troscopic data. PMP = 4-MeOC6H4.
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B. Alcaide, P. Almendros, T. Martínez del Campo
FULL PAPER
the allene substituents play an important role in the process,
such as preventing the dimerizacion reaction by steric inter-
actions. Thus, for the first time the mode of reaction (cyclo-
isomerization vs. dimerization) of α-allenones is substrate-
directable.
Scheme 3. Substrate controlled switching of dimerization to cyclo-
isomerization in aromatic α-allenic ketones. Reagents and condi-
tions: a) 5 mol-% [PdCl2(MeCN)2], MeCN, room temp., 4a: 8 h;
5a: 3 h; 5b: 3 h. Ar = p-tolyl.
Because total control is observed for the dimerization
and cycloisomerization reactions of aromatic α-allenones in
the presence of catalytic amounts of [PdCl2(MeCN)2], it
was decided to test the effect of the nature of the α-allenone
on the PdII-catalyzed process. To study whether or not the
switching of dimerization to cycloisomerization could be
applied to aliphatic derivatives, unsubstituted α-allenones
2b–f and substituted α-allenones 3c–l were treated under
similar conditions. In fact, useful control was observed, be-
cause internally substituted α-allenones gave good or total
selectivities in favor of cycloisomerization products
(Scheme 4 and Scheme 5). The role of the bulky β-lactam
ring is noticeable for the unsubstituted α-allenones 2c–f, be-
cause considerable amounts of the unexpected cycloisomeri-
zation products are normally obtained. On the other hand,
the stereochemical integrity at the proximal stereocenters
was retained in the course of the process. Enantiopure 2-
azetidinone-tethered furans 4e–j and 5e–o are of special
interest, because they can be regarded as hybrids of two
different pharmacophoric subunits, β-lactam and furan
ring. The E configuration of the tri- or tetrasubstituted
double bond in dimers 4 was assigned by NMR spectro-
scopic methods, on the basis of qualitative homonuclear
NOE difference spectra.
Scheme 5. Substrate controlled switching of dimerization to cyclo-
isomerization in 2-azetidinone-tethered α-allenic ketones. Reagents
and conditions: a) 5 mol-% [PdCl2(MeCN)2], MeCN, room temp.,
4e: 4.5 h; 4g: 5 h; 4h: 5.5 h; 4j: 6.5 h; 5f: 3 h; 5g: 6 h; 5i: 4.5 h; 5j:
6 h; 5k: 6 h; 5l: 5 h; 5n: 5 h; 5o: 5 h.
2a–f that are lacking a group gave dimerization, while the
allenones 3b, 3d, 3f, 3h, 3j, and 3l, which bear a phenyl
group at the internal allenic carbon exclusively underwent
a cycloisomerization reaction. Allenones 3a, 3c, 3e, 3g, 3i,
and 3k, bearing an internal methyl substituent yielded cy-
cloisomerization adducts as the sole or major products. The
pathway proposed in Scheme 6 looks valid for the forma-
tion of products 4 and 5. This pathway resembles Hashmi’s
proposal.[5] It could be presumed that the initially formed
allene-palladium complex 6 undergoes an intramolecular
attack by the ketone group (oxypalladation), giving rise to
the furan intermediate 7, which after H-migrations affords
the aromatic palladium species 8. Palladafuran 8 may suffer
Scheme 4. Substrate controlled switching of dimerization to cyclo-
isomerization in aliphatic enantiopure α-allenic ketones. Reagents
and conditions: a) 5 mol-% [PdCl2(MeCN)2], MeCN, room temp.,
4c: 6 h; 5c: 6 h; 5d: 4 h.
It seems that the reactivity in this type of PdII-catalyzed a reductive elimination to yield furans 5. Alternatively, in-
reactions is determined by the presence or absence of a sub- termediate 8 is trapped by another allenone molecule in a
stituent at the internal allene carbon atom, as the allenones subsequent coupling process leading to dimers 4 via 9. The
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PdII-Catalyzed Reaction of Terminal α-Allenones
FULL PAPER
NMR spectra were recorded in CDCl3 solutions, except otherwise
stated. Chemical shifts are given in ppm relative to TMS (1H,
0.0 ppm), or CDCl3 (13C, 76.9 ppm). Low and high resolution mass
spectra were taken on a HP5989A spectrometer using the electronic
impact (EI) or electrospray modes (ES) unless otherwise stated.
Specific rotation [α]D is given in 10–1 deg cm2 g–1 at 20 °C, and the
concentration (c) is expressed in grams per 100 mL. All commer-
cially available compounds were used without further purification.
formation of the E isomer in alkene derivatives 4 is the con-
sequence of an addition of the organometallic species to the
allene side remote from the acyl group. It may be inferred
that different steric effects in the organometallic species 8
may be responsible for the different reactivity preference,
stabilizing one of the intermediates rather than the other.
Dimerization falters in the presence of sterically encumber-
ing allenones. Probably, dimerization via 9 is restricted by
the steric hindrance of the R2 substituent (R2 = Me or Ph)
when a second molecule of allenone 3 is trying to approach
to the palladafuran 8.
General Procedure for the Preparation of Unsubstituted Terminal α-
Allenic Ketones 2a–f: Propargyl bromide (3.0 mmol) was added to
a
well stirred suspension of the corresponding aldehyde 1
(1.0 mmol) and zinc dust (6.0 mmol) in THF/NH4Cl (aq. satd.)
(1:5, 5 mL) at 0 °C. Then, the mixture was stirred at room temp.
After disappearance of the starting material (TLC) the mixture was
extracted with ethyl acetate (3ϫ5 mL). The organic extract was
washed with brine, dried (MgSO4) and concentrated under reduced
pressure. Then, a solution of the above prepared homopropargylic
alcohol (0.64 mmol) in dichloromethane (1 mL) was added to a
solution of Dess–Martin periodinane (DMP) (329 mg, 0.77 mmol)
in dichloromethane (4 mL) with stirring. After disappearance of
the starting material (TLC), the homogeneous reaction mixture was
diluted with 5 mL of ethyl acetate and the resulting suspension was
added to 2 mL of 1  sodium hydroxide. The organic extract was
washed with brine, dried (MgSO4) and concentrated under reduced
pressure. Chromatography of the residue eluting with ethyl acetate/
hexanes or dichloromethane/ethyl acetate mixtures gave analyti-
cally pure compounds 2. Spectroscopic and analytical data for
some representative forms of compounds 2 follow.[11]
α-Allenic Ketone (+)-2e: From 355 mg (1.0 mmol) of aldehyde (+)-
1e, and after chromatography of the residue using dichlorometh-
ane/ethyl acetate (36:1) as eluent gave compound (+)-2e (224 mg,
57%) as a colorless oil. [α]D = +59.1 (c = 0.5 in CHCl3). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.95 and 6.90 (d, J = 9.0 Hz, each
2 H), 7.27 and 6.87 (d, J = 9.0 Hz, each 2 H), 6.43 (d, J = 5.4 Hz,
1 H), 5.87 (t, J = 6.5 Hz, 1 H), 5.41 (d, J = 5.4 Hz, 1 H), 5.39 (d,
J = 6.6 Hz, 2 H), 3.86 (s, 3 H), 3.78 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3, 25 °C): δ = 217.3, 191.9, 164.4, 164.2, 160.4,
156.8, 132.2, 118.5, 118.3, 114.4, 114.0, 113.9, 94.8, 81.1, 74.3, 61.6,
Scheme 6. Mechanistic explanation for the substrate controlled
switching of dimerization to cycloisomerization in α-allenic
ketones.
55.5, 55.4 ppm. IR (CHCl ): ν = 3030, 1937, 1744, 1732, 1684 cm–1.
˜
3
MS (ES): m/z (%) = 394 (100) [M + H]+, 393 (11) [M]. C22H19NO6
(393.4): calcd. C 67.17, H 4.87, N 3.56; found C 67.30, H 4.83, N
3.59.
General Procedure for the Preparation of Substituted Terminal α-
Allenic Ketones 3a–l: 1-Bromo-2-butyne or 1-bromo-3-phenyl-2-
propyne (3.0 mmol) was added to a well stirred suspension of the
Conclusions
In conclusion, the presence of a substituent at the α-posi-
tion in a terminal allenone has a profound influence on the
reactivity, inducing a switching of dimerization to cyclo-
isomerization in the PdII-catalyzed reaction. For instance,
the presence of a phenyl group at the α-position of the al-
lenone makes inert the substrate to the dimerization. These
transformations are relevant from a synthetic standpoint,
since for the first time the mode of reaction (cycloisomeriza-
tion vs. dimerization) of α-allenones is substrate-directable,
and from a biological perspective, since hybrid natural
products have emerged as a promising approach to diversity
oriented synthesis.
corresponding aldehyde
1 (1.0 mmol) and indium powder
(6.0 mmol) in THF/NH4Cl (aq. satd.) (1:5, 5 mL) at 0 °C. Then,
the mixture was stirred at room temp. After disappearance of the
starting material (TLC) the mixture was extracted with ethyl ace-
tate (3ϫ5 mL). The organic extract was washed with brine, dried
(MgSO4) and concentrated under reduced pressure. Then, a solu-
tion of the above prepared allenic alcohol (0.64 mmol) in dichloro-
methane (1 mL) was added to a solution of DMP (329 mg,
0.77 mmol) in dichloromethane (4 mL) with stirring. After disap-
pearance of the starting material (TLC), the homogeneous reaction
mixture was diluted with 5 mL of ethyl acetate and the resulting
suspension was added to 2 mL of 1  sodium hydroxide. The or-
ganic extract was washed with brine, dried (MgSO4) and concen-
trated under reduced pressure. Chromatography of the residue elut-
ing with ethyl acetate/hexanes or dichloromethane/ethyl acetate
mixtures gave analytically pure compounds 3. Spectroscopic and
analytical data for some representative forms of compounds 3 fol-
low.[11]
Experimental Section
General Methods: H NMR and 13C NMR spectra were recorded
1
on a Bruker Avance-300, Varian VRX-300S or Bruker AC-200.
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B. Alcaide, P. Almendros, T. Martínez del Campo
FULL PAPER
α-Allenic Ketone (+)-3i: From 178 mg (0.5 mmol) of aldehyde (+)-
1e, and after chromatography of the residue using hexanes/ethyl
acetate (3:1) as eluent gave compound (+)-3i (130 mg, 64%) as a
colorless oil. [α]D = +125.9 (c = 0.6 in CHCl3). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.74 and 6.72 (d, J = 9.0 Hz, each
2 H), 7.08 and 6.68 (d, J = 9.0 Hz, each 2 H), 6.25 (d, J = 5.5 Hz,
1 H), 5.38 (d, J = 5.5 Hz, 1 H), 5.15 (m, 2 H), 3.67 (s, 3 H), 3.60
3-Furanyl-2-butenone (+)-4i: Colorless oil. [α]D = +86.5 (c = 0.5 in
CHCl3). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.92 and 7.28 (d,
J = 9.0 Hz, each 2 H), 7.81 and 7.27 (d, J = 9.0 Hz, each 2 H),
6.86 (m, 8 H), 6.71 (br. s, 1 H), 6.39 (d, J = 5.5 Hz, 1 H), 6.11 (d,
J = 5.0 Hz, 1 H), 5.39 (d, J = 5.0 Hz, 1 H), 5.28 (d, J = 5.5 Hz, 1
H), 3.87 (s, 3 H), 3.86 (s, 3 H), 3.80 (s, 3 H), 3.79 (s, 3 H), 1.71 (d,
J = 1.5 Hz, 3 H), 1.64 (s, 3 H), 1.45 (d, J = 1.7 Hz, 3 H) ppm. 13C
(s, 3 H), 1.47 (t, J = 2.9 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3, NMR (75 MHz, CDCl3, 25 °C): δ = 195.0, 164.3, 164.0, 161.3,
25 °C): δ = 216.5, 192.5, 164.3, 164.1, 160.5, 156.7, 132.1, 130.4,
161.2, 156.8, 142.2, 140.5, 132.3, 131.9, 131.8, 130.5, 130.3, 129.1,
121.0, 120.4, 119.7, 118.8, 118.4, 114.6, 114.5, 114.4, 113.9, 113.7,
113.6, 76.5, 67.4, 62.7, 55.6, 55.5, 55.4, 55.3, 54.9, 23.4, 23.3, 16.4
120.3, 118.6, 114.3, 113.8, 102.5, 80.8, 74.3, 61.4, 55.4, 12.6 ppm.
IR (CHCl ): ν = 3028, 1935, 1747, 1730, 1686 cm–1. MS (ES): m/z
˜
3
(%) = 408 (100) [M + H]+, 407 (7) [M]+. C23H21NO6 (407.4): calcd.
ppm. IR (CHCl ): ν = 1746, 1731, 1670 cm–1. MS (ES): m/z (%) =
˜
3
C 67.80, H 5.20, N 3.44; found C 67.93, H 5.16, N 3.41.
815 (100) [M + H]+, 814 (17) [M]+; C46H42N2O12 (814.8): calcd. C
67.80, H 5.20, N 3.44; found C 67.94, H 5.15, N 3.40.
α-Allenic Ketone (+)-3j: From 178 mg (0.5 mmol) of aldehyde (+)-
1e, and after chromatography of the residue using dichlorometh-
ane/ethyl acetate (40:1) as eluent gave compound (+)-3j (249 mg,
53%) as a colorless oil. [α]D = +28.3 (c = 0.3 in CHCl3). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.89 and 6.88 (d, J = 9.0 Hz, each
2 H), 7.33 and 6.82 (d, J = 9.0 Hz, each 2 H), 7.21 (m, 5 H), 6.53
1
Furan (+)-5k: Colorless oil. [α]D = +161.7 (c = 0.3 in CHCl3). H
NMR (300 MHz, CDCl3, 25 °C): δ = 7.87 and 6.86 (d, J = 8.8 Hz,
each 2 H), 7.29 and 6.84 (d, J = 8.8 Hz, each 2 H), 7.24 (d, J =
2.0 Hz, 1 H), 6.18 (d, J = 4.8 Hz, 1 H), 6.08 (d, J = 2.0 Hz, 1 H),
5.45 (d, J = 4.8 Hz, 1 H), 3.85 (s, 3 H), 3.78 (s, 3 H), 2.05 (s, 3 H)
(d, J = 5.4 Hz, 1 H), 5.70 (d, J = 5.4 Hz, 1 H), 5.68 (br. s, 2 H), 3.83 ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 164.7, 163.8, 161.5,
(s, 3 H), 3.80 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ 156.7, 142.7, 141.1, 132.0, 130.7, 121.1, 120.7, 118.5, 114.5, 113.6,
= 218.0, 190.8, 164.6, 164.1, 159.5, 156.9, 132.3, 130.4, 130.0, 128.6,
113.5, 76.6, 55.5, 55.4, 54.6, 9.7 ppm. IR (CHCl3): ν˜ = 1745, 1732
128.2, 128.0, 120.2, 118.8, 114.4, 113.8, 109.0, 82.8, 74.6, 62.2, 55.5 cm–1. MS (ES): m/z (%) = 408 (100) [M + H]+, 407 (19) [M]+;
ppm. IR (CHCl ): ν = 3033, 1937, 1745, 1732, 1685 cm–1. MS (ES):
C23H21NO6 (407.4): calcd. C 67.80, H 5.20, N 3.44; found C 67.78,
H 5.15, N 3.47.
˜
3
m/z (%) = 470 (100) [M + H]+, 469 (11) [M]+. C28H23NO6 (469.5):
calcd. C 71.63, H 4.94, N 2.98; found C 71.49, H 4.90, N 3.02.
Furan (+)-5l: From 55 mg (0.12 mmol) of α-allenone (+)-3j, and
after chromatography of the residue using hexanes/ethyl acetate
(1:1) as eluent gave compound (+)-5l (40 mg, 72%) as a colorless
oil. [α]D = +109.7 (c = 0.2 in CHCl3). 1H NMR (300 MHz, CDCl3,
25 °C): δ = 7.91 and 6.86 (d, J = 9.0 Hz, each 2 H), 7.47 (m, 5 H),
7.38 (d, J = 1.7 Hz, 1 H), 7.17 and 6.78 (d, J = 9.0 Hz, each 2 H),
6.45 (d, J = 1.7 Hz, 1 H), 6.34 (d, J = 4.9 Hz, 1 H), 5.58 (d, J =
4.9 Hz, 1 H), 3.84 (s, 3 H), 3.75 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3, 25 °C): δ = 164.8, 163.9, 161.4, 156.6, 155.4, 143.4, 141.5,
139.9, 132.1, 130.6, 128.9, 128.4, 128.3, 127.7, 118.5, 114.4, 113.6,
General procedure for the substrate-controlled switching of dimer-
ization to cycloisomerization in the PdII-catalyzed reaction of ter-
minal α-allenones. [PdCl2(MeCN)2] (0.005 mmol) and K2CO3
(0.10 mmol) were sequentially added to a stirred solution of the
corresponding α-allenone
2 or 3 (0.10 mmol) in acetonitrile
(1.0 mL). The reaction was stirred under argon atmosphere until
disappearance of the starting material (TLC). Water (0.5 mL) was
added before being extracted with ethyl acetate (3ϫ4 mL). The
organic phase was washed with water (2ϫ2 mL), dried (MgSO4)
and concentrated under reduced pressure. Chromatography of the
residue eluting with hexanes/ethyl acetate mixtures gave analytically
pure 3-furanyl-2-butenones 4 or furans 5. Spectroscopic and ana-
lytical data for some representative forms of compounds 4 and 5
follow.[11]
111.9, 76.7, 55.4, 54.4 ppm. IR (CHCl ): ν = 1747, 1734 cm–1. MS
˜
3
(ES): m/z (%) = 470 (100) [M + H]+, 469 (11) [M]+; C28H23NO6
(469.5): calcd. C 71.63, H 4.94, N 2.98; found C 71.76, H 4.90, N
2.90.
3-Furanyl-2-butenone (–)-4h: From 68 mg (0.17 mmol) of α-al-
lenone (+)-2e, and after chromatography of the residue using hex-
anes/ethyl acetate (1:1) as eluent gave compound (–)-4h (42 mg,
64%) as a colorless oil. [α]D = –290.0 (c = 0.6 in CHCl3). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.97 and 7.65 (d, J = 9.0 Hz, each
2 H), 7.54 and 7.32 (d, J = 8.8 Hz, each 2 H), 7.45 (br. s, 1 H),
6.87 (m, 4 H), 6.72 and 6.63 (d, J = 9.0 Hz, each 2 H), 6.46 (br. s,
1 H), 6.28 (d, J = 5.0 Hz, 1 H), 6.21 (d, J = 5.5 Hz, 1 H), 5.43 (d,
J = 5.0 Hz, 1 H), 5.41 (d, J = 5.5 Hz, 1 H), 5.21 (br. s, 1 H), 3.82
(s, 3 H), 3.77 (s, 3 H), 3.72 (s, 3 H), 3.45 (s, 3 H), 1.58 (s, 3 H)
ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 195.6, 164.8, 164.7,
164.5, 164.1, 157.0, 156.9, 153.7, 144.7, 133.1, 132.4, 131.8, 130.0,
129.9, 120.0, 118.7, 118.3, 117.3, 114.2, 122.8, 118.6, 118.5, 114.7,
114.6, 114.0, 77.6, 76.9, 63.9, 55.6, 55.5, 55.4, 55.3, 51.2, 23.0 ppm.
Acknowledgments
Support for this work by the Dirección General de Investigación,
Ministerio de Educación
BQU2003-07793-C02-01, CTQ2006-10292) and Comunidad Autó-
noma de Madrid – Universidad Complutense de Madrid (CAM-
UCM) (Grant GR45/05) are gratefully acknowledged. T. M. C.
thanks the MEC for a predoctoral grant.
y Ciencia (DGI-MEC) (Projects
[1] For selected reviews, see: a) X.-L. Hou, Z. Yang, K.-S. Yeung,
H. N. C. Wong, in Progress in Heterocyclic Chemistry (Eds.:
G. W. Gribble, J. A. Joule), Elsevier: Oxford, 2005, vol. 17, pp.
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IR (CHCl ): ν = 1766, 1720, 1672 cm–1. MS (ES): m/z (%) = 787
˜
3
(100) [M + H]+, 786 (25) [M]+; C44H38N2O12 (786.8): calcd. C
67.17, H 4.87, N 3.56; found C 67.30, H 4.83, N 3.59.
Preparation of 3-Furanyl-2-butenone (+)-4i and Furan (+)-5k: From
40 mg (0.098 mmol) of α-allenone (+)-3i, and after chromatography
of the residue using hexanes/ethyl acetate (1:1) as eluent, 20 mg
(50%) of the less polar compound (+)-5k and 13 mg (32%) of the
more polar compound (+)-4i were obtained.
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Eur. J. Org. Chem. 2007, 2844–2849

PdII-Catalyzed Reaction of Terminal α-Allenones
FULL PAPER
Compounds in Flavours and Aromas (Ed.: G. Vernin.), Ellis
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[11] Full spectroscopic and analytical data for compounds not in-
cluded in this Experimental Section are described in the Sup-
porting Information. It contains compound characterization
data and experimental procedures for compounds 2a–d, (+)-2f,
3a–h, (+)-3k, (+)-3l, 4a–g, (+)-4j, 5a–j, and 5m–o.
Received: February 13, 2007
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Published Online: April 17, 2007
Eur. J. Org. Chem. 2007, 2844–2849
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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