Palladium Nanoparticles in Water: A Reusable Catalytic System for the Cycloetherification or Benzannulation of α-Allenols

Article abstract of DOI:10.1002/adsc.201501132

A convenient ligand-free catalytic system has been developed for the chemoselective cyclization reaction of various α-allenol derivatives by palladium nanoparticles (PdNPs) in an aqueous reaction medium. (Figure presented.) .

Full text of DOI:10.1002/adsc.201501132

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DOI: 10.1002/adsc.201501132
Palladium Nanoparticles in Water: A Reusable Catalytic System
for the Cycloetherification or Benzannulation of a-Allenols
Benito Alcaide,a,* Pedro Almendros,b,* Ana M. Gonzµlez,a Amparo Luna,a
and Sagrario Martínez-Ramírezc
a
Grupo de Lactamas y Heterociclos Bioactivos, Departamento de Química Orgµnica I, Unidad Asociada al CSIC, Facultad
de Química, Universidad Complutense de Madrid, 28040 Madrid, Spain
Fax: (+34)-91-394-4103; e-mail: alcaideb@quim.ucm.es
Instituto de Química Orgµnica General, Consejo Superior de Investigaciones Científicas, IQOG-CSIC, Juan de la Cierva
b
3, 28006 Madrid, Spain
Fax: (+34)-91-564-4853; e-mail: Palmendros@iqog.csic.es
Instituto de Estructura de la Materia, Consejo Superior de Investigaciones Científicas, IEM-CSIC, Serrano 121, 28006
c
Madrid, Spain
Received: December 11, 2015; Revised: March 29, 2016; Published online: May 24, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201501132.
Abstract: A convenient ligand-free catalytic system
has been developed for the chemoselective cycliza-
tion reaction of various a-allenol derivatives by pal-
ladium nanoparticles (PdNPs) in an aqueous reac-
tion medium.
The dihydrofuran motif has attracted much interest
because of both the biological activity of naturally oc-
curring representatives as well as its synthetic versatil-
ity as a building block.[5] Transition metal-catalyzed
cycloetherification of allenols is one of the most rapid
and convenient methods for the preparation of oxacy-
cles.[6] The synthesis of the relevant carbazole nu-
cleus[7] has also been accomplished through precious
metal-catalyzed carbocyclization/dehydration of alle-
nols.[8] However, the expensiveness of gold and plati-
num catalysts makes their use often impractical in
larger scale synthesis. Besides, the previously reported
Keywords: allenes; cyclization; environmental
chemistry; heterogeneous catalysis; palladium
Allenes, a class of compounds with two cumulative methods are homogeneous which circumvents the
carbon-carbon double bonds, are versatile synthetic noble metal catalyst recycling, thus diminishing their
intermediates in organic synthesis.[1] Metal nanoparti- applications. It has been reported for classical C C
À
cles (NPs) have recently received considerable atten- bond-forming reactions that the use of water instead
tion in organic synthesis because of their efficient cat- of organic solvents improved the catalytic activity of
alytic activity.[2] In contrast, there is lack of informa- PdNPs, because palladium clusters which could be
tion about the reactivity of the allene moiety in the stabilized in water were found to be the catalytically
presence of metal NPs. Among the different metallic active species for ligand-free palladium-catalyzed
nanocatalysts, palladium nanoparticles (PdNPs) have cross-coupling reactions.[9] We envisioned that the
generated a huge interest.[3] Traditional Pd-catalyzed oxycyclization or benzannulation of the allenol
reactions often require the use of expensive and un- moiety might be achieved utilizing a reusable metal
stable ligands. Thus, the use of ligand-free heteroge- catalyst in water. Herein, we present a convenient
neous Pd catalysts is highly desirable. Besides, the use cyclization of allenols towards the preparation of di-
of heterogeneous catalysts considerably reduces the hydrofurans and carbazoles catalyzed by PdNPs.[10]
residual metal impurities in the products. The solvent
To test the reactivity of the a-allenol moiety, sever-
used for the catalytic reaction is very important from al sets of conditions were screened. Allene 1a was
the perspective of preservation of the integrity of the chosen as a model substrate for the PdNPs-catalyzed
nanocatalytic species. Water has gained a lot of atten- oxycyclization reaction. There are several key experi-
tion in the recent times because of the appealing mental parameters that determine the formation of
properties of organic reactions in aqueous media PdNPs including reducing agent, solvent, surfactant,
from both the economical and “green chemistry” and temperature. There are also two different ap-
points of view.[4]
proaches for the preparation of PdNPs, namely, in situ
and precatalytic generation. In our typical optimized
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entry 1). Among the different phenol derivatives
tested, 4-bromophenol was encountered as the better
performance, rendering 2a in an 80% yield (Table 1,
entry 4). 4-Bromophenol was recovered unaltered as
stoichiometric product at the end of the reaction. No
phenol derivative was identified as a side reaction
product. The palladium source PdCl2 was used in
1.0 mol%. The conversion of a-allenol 1a to oxacycle
2a at 208C is less than 5%, but it can reach up to
80% at 608C (reaction time 1 h, additive: 4-bromo-
phenol). Consequently, it may be inferred that higher
temperature is beneficial to the catalytic activity of
the PdNPs.
Under the present study it appears that the K2CO3
should act as the reducing agent to form the PdNPs
from the pre-catalyst PdCl2.[11] To prove this, the cycli-
zation reaction of a-allenol 1a was performed in the
Figure 1. TEM image (JEOL-JEM-2100) of the pre-generat-
ed PdNPs (magnification=600000).
generation of PdNPs, PdCl2 was used as the Pd pre- absence of K2CO3 under otherwise identical condi-
cursor, K2CO3 was selected as the reducing agent, tions. In the event, just 5% yield of the desired prod-
water was used as the solvent, and TBAB (tetrabutyl- uct 2a was isolated after 3 h of reaction. The PdNPs
ammonium bromide) as the surfactant. The solution were not formed in the absence of K2CO3 as in this
of PdCl2 turns into a black heterogeneous mixture case no visual formation (non-existence of blackening
due the presence of both K2CO3 and TBAB, which at the reaction mixture) was observed and little reac-
implied the formation of PdNPs as checked by using tion took place.
transmission electron microscopy (TEM) as analytical
In the absence of 4-bromophenol the reaction of al-
technique (Figure 1). Disappointingly, the reaction of lenol 1a in the presence of PdNPs did not occur, thus
allenol 1a in the presence of PdNPs did not occur, re- highlighting the crucial role of this additive in our cat-
covering unaltered the starting material. Happily, the alytic system. This result suggests that the phenol acts
addition of a stoichiometric amount of phenol to the as a ligand to the palladium active species. The pro-
reaction system, results in an unanticipated benefit posed charge transfer interaction between PdNPs and
for the cycloetherification reaction. While PdNPs gen- the aromatic ring of 4-bromophenol has been invoked
erated in situ in the presence of phenol could catalyze based on previous literature reports on cation-p inter-
the cycloetherification reaction of 1a to 2,5-dihydro- action.[12]
furan 2a in a very poor 3% yield, the pre-generated
It is well known that the use of a stabilizer is essen-
PdNPs in the presence of phenol gave the desired tial to prevent agglomeration of the metal NPs.[13] Tet-
product 2a in a more promising 10% yield (Table 1, raalkylammonium stabilizers act through electrostatic
and steric interactions. Taking into account the poor
results in the absence of TBAB, it should impart elec-
trosteric (combination of steric and electrostatic) sta-
bilization.
Table 1. PdNPs-catalyzed oxycyclization reaction of a-alle-
nol 1a.[a]
With the optimized reaction conditions in hand we
then examined the scope and generality of the
PdNPs-catalyzed method. Various alkyl- and aryl-sub-
stituted a-allenols 1b–j were reacted to give a range
of 2,5-dihydrofurans 2b–j, serving the above process
as
a
general approach to 2,5-dihydrofurans
(Scheme 1). Both electron-donating (OMe) and elec-
tron-withdrawing substituents (Cl, Br, COOMe, CN)
on the aromatic rings were tolerated. The above ob-
servation points to the great activity under mild con-
ditions of nanosized palladium particles as heteroge-
neous catalyst in aqueous environment.
Next, the challenging a-hydroxyallenyl-tethered in-
doles 1k–n were selected as systems to explore the
catalytic activity of PdNPs. a-Hydroxyallenyl C-3
tethered indoles 1k and 1l reacted to afford cyclo-
etherification products 2k and 2l in reasonable yields
Entry
Additive
Time [h]
Yield [%][b]
1
2
3
4
phenol
3.5
24
4
10
11
39
80
4-nitrophenol
4-methoxyphenol
4-bromophenol
3
[a]
A precatalytic approach was used for the generation of
the palladium nanoparticles.
Yield of pure, isolated product 2a after silica gel chroma-
tography with correct analytical and spectral data.
[b]
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Figure 2. Histogram of the pre-generated PdNPs.
doles 1m and 1n were employed as substrates, the re-
action failed to afford 2,5-dihydrofuran products, and
carbazoles 3m and 3n were obtained instead
(Scheme 2). For thoses cases, C-cyclization was fav-
oured over O-cyclization. Besides, the PdNPs-cata-
lyzed oxy- or carbocyclization reactions of indole pre-
cursors 1 occurred without harming the sensitive
indole ring. As a consequence of the high surface
area of nanoparticles, the required catalyst concentra-
tion is lower. Thus, the cyclization of a-allenols 1 can
be achieved using just 1.0 mol% of one of the most
economical sources of palladium, PdCl2.
The characterization of PdNPs was carried out by
Scheme 1. Synthesis of 2,5-dihydrofurans 2b–i through
PdNPs-catalyzed oxycyclization reaction of a-allenols 1b–i, using transmission electron microscopy (TEM) as an-
2b: 1.5 h; 2c: 3 h; 2d: 2 h; 2e: 3.5 h; 2f: 4 h; 2g: 6 h; 2h: 8 h;
2i: 2 h; 2j: 3 h.
alytical technique. Thus, it was shown that the ob-
tained Pd(0) particles are in the nano region with an
average size of 2.2 nm (Figure 1 and Figure 2).[14] The
electron dispersive X-ray (EDX) spectrum confirmed
(Scheme 2). The above transformation (Scheme 1 and that the metal component of our nanoparticles is pal-
Scheme 2) tolerates precursors that contain Cl- and ladium (Figure S1, Supporting Information).
Br-substituted aryl rings (1b–e and 1l), which could
To study the recyclability of the PdNPs, when the
suffer a Heck-type reaction with the allene moiety. In- reaction of a-allenols 1a and 1b has gone to comple-
terestingly, when a-hydroxyallenyl C-2 tethered in- tion, the mixture was allowed to cool to room temper-
ature and the catalyst was recovered by centrifuga-
tion. Then, the solid was washed with water and ace-
tone, dried under reduced pressure and reused for fur-
ther oxycyclization reactions. A high level of catalytic
activity was retained in the PdNPs at least after four
cycles, because 2,5-dihydrofurans 2a and 2b were ob-
tained in similar yields even in the fourth recycling as
shown in Table 2.
The above results point to a good retention factor
of palladium in the cyclization reactions, because cat-
alyst leaching should be accompanied by diminished
catalytic activity after recycling. The experiments
using 1a and 1b proved the ability of the PdNPs to be
recycled because the cyclization reaction was itera-
tively repeated using the same batch of catalyst. TEM
studies of fresh and reused catalysts after the fourth
cycle point to the unchanged nanoparticle size before
and after the cyclization reaction (Figures S2–S7, Sup-
porting Information).
Micro-Raman spectroscopy was used to analyze the
possible presence of embedded TBAB in the PdNPs.
Scheme 2. Synthesis of 2,5-dihydrofurans 2k, l and carba-
zoles 3m, n through PdNPs-catalyzed cyclization reaction of
a-allenols 1k–n, 2k: 24 h; 2l: 24 h; 3m: 3.5 h; 3n: 5 h; py=2-
pyridyl.
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Table 2. Catalyst recovery from the PdNPs-catalyzed oxy-
cyclization reaction of a-allenols 1.[a]
acetone (green line). In the light regions, no TBAB
was detected in the spectra of the PdNP samples, indi-
cating the absence of TBAB in the metallic catalyst.
For the oxycyclization reaction of allenol 1a, we de-
tected that the dihydrofuran formation catalyzed by
PdNPs was faster than that catalyzed by homogene-
ous PdCl2. Thus, the turnover frequency (TOF) of the
À
catalyst for the heterogeneous C O bond formation
was 155-fold higher than that for the homogeneous
catalyst.[15] These results demonstrate improved effi-
ciency of PdNPs over homogeneous catalysis in this
particular reaction. By contrast, it was observed that
cyclization/coupling reaction sequences of allenols
1 with unsaturated halides were not feasible. The mix-
ture of allenol 1a either with allyl bromide or iodo-
benzene under PdNPs-catalyzed conditions was non-
productive for the oxycyclization/cross-coupling
adduct formation.
In conclusion, the activity of palladium nanoparti-
cles (PdNPs) as a convenient catalyst for the chemo-
selective cyclization reaction of various a-allenol de-
rivatives in water under ligandless conditions has
been disclosed. The heterogeneous catalyst also offers
the advantages of recyclability, ease of removal, and
high turnover frequency than the homogeneous cata-
Cycle
Product
Yield [%][b]
Catalyst Recovery [%]
native[a]
1
2a
2a
2a
2a
2b
2b
2b
2b
80
78
75
71
59
58
56
53
96
91[c]
88[c]
80[c]
95
2
3
native[a]
1
2
3
90[c]
86[c]
80[c]
[a]
PdNPs were generated through a precatalytic approach.
Yield of pure, isolated product 2 after silica gel chroma-
tography with correct analytical and spectral data.
With recovered catalyst.
[b]
[c]
Raman spectra were obtained using two excitation lyst.
wavelengths (532 and 633 nm) and making power
scans of 2.5 mW and 25 mW, respectively, to select the
best conditions of register for each wavelength.
Experimental Section
Figure 3 shows Raman spectra of TBAB (red line), al-
lenol 1a (black line), precatalytic generated PdNPs
(sky blue line), recycled (one cycle) PdNPs washed
with water and acetone (cobalt blue line), recycled
(one cycle) PdNPs without washing with water and
General Methods
1H NMR and 13C NMR spectra were recorded on a Bruker
AMX-500, Bruker Avance-300, or Varian VRX-300S. NMR
spectra were recorded in CDCl3 solutions, except where oth-
erwise stated. Chemical shifts are given in ppm relative to
TMS (1H, 0.0 ppm), or CDCl3 (13C, 77.0 ppm). Low and high
resolution mass spectra were taken on an AGILENT 6520
Accurate-Mass QTOF LC/MS spectrometer using the elec-
trospray mode (ES) unless otherwise stated. IR spectra
were recorded on a Bruker Tensor 27 spectrometer. The
transmission electron microscopy (TEM) analysis was per-
formed on a JEOL-JEM-2010 microscope using a 200 kV
voltage. Dispersive Raman spectra at 633 and 532 nm were
recorded in a RM 1000 Renishaw Raman Microscope
System. The Raman spectrometer is equipped with a Leica
microscope and an electrically refrigerated CCD camera.
The spectra were obtained with ”50 magnification objective
lenses. The final spectra were the result of 10 accumulations
to improve the signal-to-noise ratio and the integration time
was 10 s. The software employed for data acquisition and
analysis was Wire for Windows and Galactic Industries
GRAMS/32TM. Five scans were recorded to improve the
signal-to-noise ratio. The Raman shift was calibrated before
the measurements according to the silicon peak at 520 cmÀ1.
The 633 nm line had a laser power from 0.25 to 25 mW and
finally, the 532 nm line had a laser power from 0.0005 to
5 mW. The measurements were done directly in the sample
(in situ), the sample preparation is not necessary. All com-
Figure 3. Raman spectra recorded using a wavelength of
532 nm (except for allenol 1a which required 633 nm). All
the Raman spectra were normalized to the maximun intensi-
ty.
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1
mercially available compounds were used without further
purification.
yield: 55 mg (75%); H NMR (300 MHz, CDCl3, 258C): d=
7.44 (dd, J=8.3, 1.8 Hz, 1H), 7.30 (d, J=1.8 Hz, 1H), 6.70
(d, J=8.3 Hz, 1H), 5.97 (d, J=1.3 Hz, 1H), 4.99 and 4.89
(m, each 1H), 3.17 (s, 3H), 1.43 (m, 3H); 13C NMR
(75 MHz, CDCl3, 258C): d=175.0, 142.9, 135.2, 132.8, 130.3,
127.6, 125.3, 115.8, 109.7, 92.2, 76.5, 26.3, 11.1; IR (CHCl3):
n=1730, 1468 cmÀ1; HR-MS (ES): m/z=293.0053, calcd. for
C13H12BrNO2 [M]+: 293.0051.
Typical Procedure for Cyclization of Allenols using in
situ Generated PdNPs
To a magnetically stirred solution of tetrabutylammonium
bromide (TBAB) (0.25 mmol), PdCl2 (0.01 mmol) and
K2CO3 (0.25 mmol) in H2O (4 mL) were added the corre-
sponding allenol 1 (1 mmol) and 4-bromophenol (1 mmol)
at 608C. Upon completion of the reaction (monitored by
TLC), the reaction mixture was allowed to cool to room
temperature, was diluted with ethyl acetate (3”5 mL), and
the ethyl acetate layer was separated from the aqueous
layer. The organic extract was dried over anhydrous MgSO4
and concentrated under reduced pressure. Chromatography
of the residue using hexanes/ethyl acetate mixtures gave an-
alytically pure compounds.
Dihydrofuran (2d): From 40 mg (0.16 mmol) of allenol 1d,
and after chromatography of the residue using hexanes/ethyl
acetate (4:1) as eluent, gave compound 2d as a yellow solid;
yield: 32 mg (80%); mp 81–838C; 1H NMR (300 MHz,
CDCl3, 258C): d=7.24 (dd, J=8.1, 1.2 Hz, 1H), 7.08 (dd,
J=7.3, 1.2 Hz, 1H), 6.98 (t, J=7.7 Hz, 1H), 5.97 (m, 1H),
4.99 and 4.89 (dt, J=12.4, 1.9 Hz, each 1H), 3.56 (s, 3H),
1.44 (m, 1H); 13C NMR (75 MHz, CDCl3, 258C): d=175.9,
139.7, 135.5, 132.2, 131.2, 125.1, 123.9, 123.0, 115.7, 91.8,
76.5, 29.7, 11.1; IR (CHCl3): n=1734, 1461 cmÀ1; HR-MS
(ES): m/z=249.0551, calcd. for C13H12ClNO2 [M]+: 249.0557.
Dihydrofuran (2e): From 43 mg (0.22 mmol) of allenol 1e,
and after chromatography of the residue using hexanes/ethyl
acetate (9:1) as eluent, gave compound 2e as a colorless oil;
Typical Procedure for Cyclization of Allenols using
Precatalytic Generation of PdNPs
1
yield: 26 mg (60%); H NMR (300 MHz, CDCl3, 258C): d=
A
solution of tetrabutylammonium bromide (TBAB)
7.32 (d, J=8.5 Hz, 2H), 7.21 (d, J=8.5 Hz, 2H), 5.65 (m,
1H), 5.46 (m, 1H), 4.84 and 4.71 (m, each 1H), 1.55 (m,
3H); 13C NMR (75 MHz, CDCl3, 258C): d=140.0, 138.1,
133.5, 128.6 (2C), 128.2 (2C), 121.0, 89.8, 75.5, 12.4; IR
(CHCl3): n=1730, 1684, 1091 cmÀ1; HR-MS (ES): m/z=
194.0506, calcd. for C11H11ClO [M]+: 194.0498.
(0.25 mmol), PdCl2 (0.01 mmol) and K2CO3 (0.25 mmol,) in
H2O (4 mL) was stirred for fifteen minutes at 608C. Then,
the corresponding allenol 1 (1 mmol) and 4-bromophenol
(1 mmol) were added. The reaction mixture was stirred at
608C until the starting material disappeared as indicated by
TLC. The reaction mixture was allowed to cool to room
temperature, was diluted with ethyl acetate (3”5 mL), and
the ethyl acetate layer was separated from the aqueous
layer. The organic extract was dried over anhydrous MgSO4
and concentrated under reduced pressure. Chromatography
of the residue using hexanes/ethyl acetate mixtures gave an-
alytically pure compounds. Spectroscopic and analytical data
for pure forms of compounds 2 and 3 follow.
Dihydrofuran (2f): From 47 mg (0.25 mmol) of allenol 1f,
and after chromatography of the residue using hexanes/ethyl
acetate (7:1) as eluent, gave compound 2f as a yellow oil;
1
yield: 22 mg (46%); H NMR (300 MHz, CDCl3, 258C): d=
7.30 (d, J=8.6 Hz, 2H), 6.89 (d, J=8.8 Hz, 2H), 5.05 (t, J=
2.5 Hz, 1H), 4.92 (m, 2H), 3.81 (s, 3H), 1.55 (t, J=3.1 Hz,
3H); 13C NMR (75 MHz, CDCl3, 258C): d=159.3, 138.5,
133.5, 128.2 (2C), 120.6, 113.8 (2C), 90.1, 75.1, 55.2, 12.5; IR
(CHCl3): n=1609, 1511, 1248 cmÀ1; HR-MS (ES): m/z=
191.1067, calcd. for C12H15O2 [M+H]+: 191.1072.
Dihydrofuran (2a): From 40 mg (0.18 mmol) of allenol 1a,
and after chromatography of the residue using hexanes/ethyl
acetate (1:1) as eluent, gave compound 2a as a colorless oil;
1
Dihydrofuran (2g): From 47 mg (0.21 mmol) of allenol 1g,
and after chromatography of the residue using hexanes/ethyl
acetate (6:1) as eluent, gave compound 2g as a colorless oil;
yield: 31 mg (80%); H NMR (300 MHz, CDCl3, 258C): d=
7.32 (td, J=7.7, 1.2 Hz, 1H), 7.20 (d, J=6.3 Hz, 1H), 7.07
(t, J=7.5 Hz, 1H), 6.82 (d, J=7.7 Hz, 1H), 5.96 (q, J=
1.5 Hz, 1H), 5.01 and 4.90 (dt, J=12.4, 1.9 Hz, each 1H),
3.20 (s, 3H), 1.42 (m, 3H), 13C NMR (75 MHz, CDCl3,
258C): d=175.6, 144.0, 135.8, 130.0, 128.3, 124.9, 124.4,
1
yield: 38 mg (83%); H NMR (300 MHz, CDCl3, 258C): d=
6.44 (d, J=2.2 Hz, 2H), 6.40 (m, 1H), 5.63 (m, 1H), 5.41
(m, 1H), 4.84 and 4.70 (m, each 1H), 3.79 (s, 6H), 1.58 (m,
3H); 13C NMR (75 MHz, CDCl3, 258C): d=160.9 (2C),
143.9, 138.4, 120.8, 104.7 (2C), 99.8, 90.5, 75.4, 55.3 (2C),
12.5; IR (CHCl3): n=1596, 1153 cmÀ1; HR-MS (ES): m/z=
221.1175, calcd. for C13H17O3 [M+H]+: 221.1178.
123.1, 108.2, 92.4,76.3, 26.3, 11.1; IR (CHCl3): n=1715 cmÀ1
;
HR-MS (ES): m/z=215.0956, calcd. for C13H13NO2 [M]+:
215.0946.
Dihydrofuran (2b): From 57 mg (0.23 mmol) of allenol 1b,
and after chromatography of the residue using hexanes/ethyl
acetate (1:1) as eluent, gave compound 2b as a yellow oil;
Dihydrofuran (2h): From 45 mg (0.20 mmol) of allenol 1h,
and after chromatography of the residue using hexanes/ethyl
acetate (3:1) as eluent, gave compound 2h as a colorless oil;
1
yield: 34 mg (59%); H NMR (300 MHz, CDCl3, 258C): d=
1
yield: 26 mg (60%); H NMR (300 MHz, CDCl3, 258C): d=
7.30 (dd, J=8.3, 2.1 Hz, 1H), 7.18 (d, J=2.1 Hz, 1H), 6.75
(d, J=8.3 Hz, 1H), 5.98 (m, 1H), 5.00 and 4.90 (dt, J=12.4,
2.0 Hz, each 1H), 3.18 (s, 3H), 1.44 (q, J=2.0 Hz, 1H);
13C NMR (75 MHz, CDCl3, 258C): d=175.1, 142.5, 135.2,
130.0, 129.9, 128.6, 125.3, 124.9, 109.2, 92.3, 76.5, 26.4, 11.1;
8.16 (d, J=8.4 Hz, 2H), 7.17 (m, 2H), 5.38 (m, 1H), 5.13 (q,
J=1.6 Hz, 1H), 4.61 (m, 2H) 3.50 (s, 3H), 1.23 (t, J=
1.3 Hz, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=137.0,
147.9, 138.8, 130.7, 130.5, 127.3, 121.7, 90.5, 76.1, 51.9, 12.6;
IR (CHCl3): n=1723, 1281, 1112 cmÀ1; HR-MS (ES): m/z=
218.0938, calcd. for C13H14O3 [M]+: 218.0943.
Dihydrofuran (2i): From 40 mg (0.16 mmol) of allenol 1i,
and after chromatography of the residue using hexanes/ethyl
acetate (7:1) as eluent, gave compound 2i as a colorless oil;
IR (CHCl3): n=1729, 1487 cmÀ1
; HR-MS (ES): m/z=
250.0612, calcd. for C13H13ClNO2 [M+H]+: 250.0635.
Dihydrofuran (2c): From 75 mg (0.25 mmol) of allenol 1c,
and after chromatography of the residue using hexanes/ethyl
acetate (2:1) as eluent, gave compound 2c as a yellow oil;
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yield: 28 mg (71%); H NMR (300 MHz, CDCl3, 258C): d=
7.35 (s, 4H), 7.14 (m, 3H), 7.09 (d, J=3.0 Hz, 2H), 6.05 (td,
J=4.6, 1.8 Hz, 1H), 5.98 (q, J=1.9 Hz, 1H), 4.76 (d, J=
1.9 Hz, 1H), 4.74 (m, 1H); 13C NMR (75 MHz, CDCl3,
258C): d=146.7, 141.3, 133.0, 132.7, 129.0, 128.6, 128.5,
127.2, 124.2, 119.0, 112.8, 87.9, 76.1; IR (CHCl3): n=2230,
1758, 843 cmÀ1; HR-MS (ES): m/z=247.1005, calcd. for
C17H13NO [M]+: 247.0997.
(d, J=2.4 Hz, 1H), 7.29 (s, 1H), 7.16 (s, 1H), 7.08 (dd, J=
8.8, 2.5 Hz, 1H), 7.03 (d, J=7.9 Hz, 1H), 3.93 (s, 3H), 3.80
(s, 3H), 2.57 (s, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=
153.5, 141.9, 136.0, 135.8, 123.0, 120.2, 119.8 (2C), 114.0,
108.9, 108.7, 103.2, 56.1, 29.0, 22.2; IR (CHCl3): n=1486,
1287 cmÀ1
;
HR-MS (ES): m/z=225.1153, calcd. for
C15H15NO [M]+: 225.1154.
Dihydrofuran (2j): From 47 mg (0.27 mmol) of allenol 1j,
and after chromatography of the residue using hexanes/ethyl
acetate (9:1) as eluent, gave compound 2j as a colorless oil;
Typical Procedure for the Recovery and Recyclability
of PdNPs
1
Upon completion of the reaction (monitored by TLC) of
the appropriate allenol (1 mmol), the reaction mixture was
allowed to cool to room temperature and was diluted with
ethyl acetate (2”5 mL). The aqueous layer which contains
the Pd nanoparticles, was separated from the organic layer.
The particles were collected by centrifugation and redis-
persed again in water. Then, the corresponding allenol
1 (1 mmol) and 4-bromophenol (1 mmol) were added. The
reaction mixture was stirred at 608C until the starting mate-
rial disappeared as indicated by TLC. The mixture was dilut-
ed with ethyl acetate (3”5 mL) and the ethyl acetate layer
was separated from the aqueous layer. The organic extract
was dried over anhydrous MgSO4 and concentrated under
reduced pressure. Chromatography of the residue using hex-
anes/ethyl acetate mixtures gave analytically pure com-
pounds. The process was repeated for four consecutive
times.
yield: 24 mg (50%); H NMR (300 MHz, CDCl3, 258C): d=
7.25 (m, 5H), 5.44 (q, J=1.6 Hz, 1H), 4.88 (m, 1H), 4.46
(m, 2H), 3.01 (dd, J=14.1, 3.9 Hz, 1H), 2.72 (dd, J=14.1,
6.8 Hz, 1H), 1.74 (m, 3H); 13C NMR (75 MHz, CDCl3,
258C): d=138.2, 137.5, 129.4 (2C), 128.0 (2C), 126.0, 121.3,
88.1, 74.4, 40.4, 12.7; IR (CHCl3): n=1759, 1081, 1027 cmÀ1
;
HR-MS (ES): m/z=174.1041, calcd. for C12H14O [M]+:
174.1045.
Dihydrofuran (2k): From 40 mg (0.12 mmol) of allene 1k,
and after chromatography of the residue using hexanes/ethyl
acetate (3:1) as eluent gave compound 2k as a pale yellow
1
oil; yield: 26 mg (64%); H NMR (300 MHz, CDCl3, 258C):
d=8.50 (m, 1H), 8.02 (d, J=7.9 Hz, 1H), 7.92 (d, J=8.2 Hz,
1H), 7.78 (td, J=7.7, 1.7 Hz, 1H), 7.57 (s, 1H), 7.45 (d, J=
7.6 Hz, 1H), 7.36 (ddd, J=7.7, 4.7, 1.0 Hz, 1H), 7.18 (m,
2H), 5.66 (m, 2H), 4.76 and 4.71 (m, each 1H), 1.52 (s,
3H); 13C NMR (75 MHz, CDCl3, 258C): d=155.3, 150.5,
138.1, 137.1, 136.0, 129.1, 127.6, 125.8, 124.8, 123.5, 122.3,
121.8, 121.6, 120.2, 113.9, 83.5, 75.2, 15.5; IR (CHCl3): n=
2850, 1377, 1188 cmÀ1; HR-MS (ES): m/z=341.0954, calcd.
for C18H17N2O3S [M+H]+: 341.0960.
Acknowledgements
Dihydrofuran (2l): From 40 mg (0.09 mmol) of allene 1l,
and after chromatography of the residue using hexanes/ethyl
acetate (3:1) as eluent gave compound 2l as a pale yellow
Support for this work by MINECO and FEDER (Projects
CTQ2012-33664-C02-01, CTQ2012-33664-C02-02, CTQ2015-
65060-C2-1-P, and CTQ2015-65060-C2-2-P), and CAM (Pro-
gram GEOMATERIALS-2-2013/MIT-2914). We thank M.
Elena de Orbe for preliminary studies.
1
oil; yield: 21 mg (56%); H NMR (300 MHz, CDCl3, 258C):
d=8.58 (m, 1H), 8.09 (dt, J=7.9, 0.9 Hz, 1H), 7.89 (m,
2H), 7.63 (s, 1H), 7.62 (d, J=1.7 Hz, 1H), 7.47 (ddd, J=7.7,
4.7, 1.1 Hz, 1H), 7.38 (dd, J=8.8, 1.9 Hz, 1H), 5.74 (m, 2H),
4.85 and 4.75 (m, each 1H), 1.59 (t, J=1.3 Hz, 3H);
13C NMR (75 MHz, CDCl3, 258C): d=155.0, 150.5, 138.2,
136.6, 134.7, 130.7, 127.7, 127.6, 126.8, 122.9, 122.2, 121.8,
121.0, 117.1, 115.4, 83.2, 75.2, 12.4; IR (CHCl3): n=2992,
1381, 1188 cmÀ1; HR-MS (ES): m/z=417.9971, calcd. for
C18H15BrN2O3S [M]+: 417.9986.
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