Synthesis of dihydroisobenzofurans via palladium-catalyzed sequential alkynylation/annulation of 2-bromobenzyl and 2-chlorobenzyl alcohols under microwave irradiation

Article abstract of DOI:10.1002/adsc.201400457

The palladium-catalyzed synthesis of dihydroisobenzofurans has been performed by sequential Sonogashira cross-coupling/cyclization reactions between terminal alkynes and 2-(hydroxymethyl)bromoand chlorobenzenes in methanol as solvent at 130 °C under microwave irradiation. A 4,4'-dichlorobenzophenone oxime-derived chloro-bridged palladacycle is an efficient pre-catalyst to perform this tandem process using 2-dicyclohexylphosphanyl-2',4',6'-triisopropylbiphenyl (Xphos) as ancillary ligand and potassium hydroxide as base in the absence of a copper cocatalyst. Under these conditions, functionalized 2-bromo- and 2-chlorobenzaldehydes are also suitable partners in the domino process affording phthalans in good yields. All the reactions can be performed under air and employing reagentgrade chemicals under low loading conditions (1 mol% Pd).

Full text of DOI:10.1002/adsc.201400457

FULL PAPERS
DOI: 10.1002/adsc.201400457
Synthesis of Dihydroisobenzofurans via Palladium-Catalyzed
Sequential Alkynylation/Annulation of 2-Bromobenzyl and
2-Chlorobenzyl Alcohols under Microwave Irradiation
Eduardo Buxaderas,a Diego A. Alonso,a,* and Carmen Nꢀjeraa,*
a
Departamento de Quꢁmica Orgꢀnica & Instituto de Sꢁntesis Orgꢀnica, Universidad de Alicante, Carretera de San Vicente
del Raspeig s/n, 03690 San Vicente del Raspeig, Alicante, Spain
Fax : (+34)-96-590-3549; e-mail: diego.alonso@ua.es or cnajera@ua.es
Received: May 6, 2014; Revised: July 8, 2014; Published online: October 16, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400457.
Abstract: The palladium-catalyzed synthesis of dihy- sence of a copper cocatalyst. Under these conditions,
droisobenzofurans has been performed by sequential functionalized 2-bromo- and 2-chlorobenzaldehydes
Sonogashira cross-coupling/cyclization reactions be- are also suitable partners in the domino process af-
tween terminal alkynes and 2-(hydroxymethyl)bro- fording phthalans in good yields. All the reactions
mo- and chlorobenzenes in methanol as solvent at can be performed under air and employing reagent-
1308C under microwave irradiation. A 4,4’-dichloro- grade chemicals under low loading conditions
benzophenone oxime-derived chloro-bridged palla- (1 mol% Pd).
dacycle is an efficient pre-catalyst to perform this
tandem process using 2-dicyclohexylphosphanyl- Keywords: alkynes; cycloisomerization; dihydroiso-
2’,4’,6’-triisopropylbiphenyl (Xphos) as ancillary benzofurans; microwaves; palladium; Sonogashira
ligand and potassium hydroxide as base in the ab- reaction
Introduction
(Scheme 1). In order to gain versatility and simplicity,
a tandem Sonogashira–Hagihara coupling/intramolec-
The transition metal-catalyzed addition of nucleo- ular hydroalkoxylation would be desirable, an ap-
philes to unactivated carbon-carbon multiple bonds[1] proach which has been barely studied using (2-iodo-
is of major importance in synthetic organic chemistry phenyl)methanol and (2-bromophenyl)methanol de-
due to its step- and atom-economic nature.[2] Palladi- rivatives under Pd[7] or Cu[8] catalysis (Scheme 1).[9] Fi-
um[3] is the most versatile and widely used metal for nally, a copper-free protocol to avoid the homocou-
this type of processes. Particularly, the intramolecular pling of alkynes (major limitation in the conventional
cyclization of palladium p-alkene and p-alkyne com- Sonogashira reaction involving less reactive aryl bro-
plexes bearing an internal nucleophile is a very effi- mides and chlorides) would be attractive as well.
cient method for the synthesis of a wide variety of
In recent years, we have demonstrated the high ac-
heterocycles,[4] compounds which have attracted ex- tivity of oxime palladacycles as source of palladium
tensive attention for a long time due to their remark- nanoparticles[10] in a wide variety of cross-coupling re-
able biological activities. The Pd(II)-catalyzed cycliza- actions using organic and aqueous solvents.[11] In par-
tion of alkynes bearing an oxygen nucleophile has
been employed for the regioselective synthesis of var-
ious oxygen-containing heterocycles such as 1,3-dihy-
droisobenzofurans, which are useful building blocks
and key structural units in numerous natural products
and drugs.[5] In general, these compounds have been
prepared from the corresponding 2-(alkynyl)benzyl
alcohols via an intramolecular hydroalkoxylation,[6]
reaction which might suffer from stereo- and regiose-
lectivity problems since both the 6-endo-dig and 5-
exo-dig cyclizations are allowed by Baldwinꢂs rules droalkoxylation towards 1,3-dihydroisobenzofurans.
Scheme 1. Sonogashira coupling and/or intramolecular hy-
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Eduardo Buxaderas et al.
Table 1. Sonogashira/hydroalkoxylation reaction of 2-bromo-
benzyl alcohol with phenylacetylene in water. Reaction con-
ditions optimization.[a]
Entry Ligand[b] Additive[c] Base
Yield
[%][d]
2/3/4/5[e]
1
2
3
4
5
6
7
8
Xphos
Xphos
Xphos
Xphos
Xphos
Xphos
Xphos
Xphos
–
SDBS
SDBS
SDBS
SDBS
TBAB
CTAB
PTS
KOH[f] 99
KOH 99
K2CO3 81
NaOH 99
27/62/4/7
12/85/3/0
26/42/9/23
35/40/5/20
2/93/2/3
Scheme 2. Sonogashira coupling catalyzed by oxime palada-
cycles.[12]
KOH
KOH
KOH
KOH
KOH
KOH
KOH
53
50
78
84
24
99
70
3/95/1/1
ticular, palladacycles derived from 4,4’-dichlorobenzo-
phenone oxime 1a and 4-(hydroxy)acetophenone
oxime 1b have been shown as very active precatalysts
in the copper-free Sonogashira–Hagihara coupling of
aryl halides and aryl imidazolylsulfonates with termi-
nal alkynes (Scheme 2).[12] In continuation of our ex-
ploration on the application of oxime palladacycles in
À
57/40/2/1
36/61/2/1
9/91/0/0
18/78/2/2
19/72/2/7
–
9
SDBS
SDBS
SDBS
SDBS
TBAB
SDBS
SDBS
[g]
10
11
12
13
14
15
–
Cy3P
Xphos
Xphos
Xphos
Xphos
KOH[h] 93 (65) 2/93/5/0
KOH[h] 49
KOH[i] 90
KOH[j] 91
2/96/3/0
27/67/3/3
10/68/5/17
C(sp) CACHTUNGTRENNUNG
(sp2) cross-couplings, herein we describe the
stereo- and regioselective synthesis of 3-alkylidene-
1,3-dihydroisobenzofurans[13] via Cu-free Pd-catalyzed
sequential Sonogashira alkynylation/hydroalkoxyla-
tion of functionalized aryl bromides and aryl chlorides
under microwave irradiation conditions.
[a]
[b]
[c]
Reaction conditions: 1a (1 mol% Pd), ligand (2 mol%),
additive (1 equiv.), base (4 equiv.), H2O, MW, 1308C,
30 min.
Xphos=2-dicyclohexylphosphino-2’,4’,6’-triisopropylbi-
phenyl; Davephos=2-dicyclohexylphosphino-2’-(N,N-di-
methylamino)biphenyl.
SDBS=sodium dodecyl benzenesulfonate; TBAB=
tetra-n-butylammonium bromide; CTAB=hexadecyltri-
methylammonium bromide; PTS=polyoxyethanyl-a-to-
copheryl sebacate.
Results and Discussion
Initially, the reaction between 2-bromobenzyl alcohol
and phenylacetylene was studied under conditions
similar to those previously employed in our group for
the Sonogashira alkynylation of aryl bromides and
chlorides using water as solvent and microwave irradi-
ation.[12c] Thus, 2-bromobenzyl alcohol reacted with
phenylacetylene in the presence of oxime palladacycle
1a (1 mol% Pd), sodium dodecyl benzenesulfonate
(SDBS, 1 equiv.) as additive, 2-dicyclohexylphosphan-
yl-2’,4’,6’-triisopropylbiphenyl (Xphos, 2 mol%)[14] as
ancillary ligand, and pyrrolidine (2 equiv.) as base
(Scheme 3). With an initial microwave irradiation of
[d]
Conversion determined by 1H NMR analysis. In paren-
thesis, isolated yield after silica-gel preparative chroma-
tography.
[e]
[f]
[g]
[h]
[i]
1
Determined by H NMR of the crude reaction mixture.
2 equiv. of base were used.
Davephos was used as ligand.
Reaction time 1 h.
Catalyst 1b (1 mol% Pd) was used.
The reaction was performed under conventional thermal
conditions (1308C, 15 h).
[j]
40 W, the reaction temperature was maintained at reomers. Also, trace amounts of isobenzofuran-1(3H)-
1308C for 30 min. Under these conditions, the Sono- one (5) and benzaldehyde were detected in the crude
gashira coupling product 2 was obtained in a 76% reaction mixture. Then, an optimization of the reac-
1
yield (CG and H NMR analysis) and only a 22% tion conditions was carried out in order to improve
yield of 1-benzylidene-1,3-dihydroisobenzofurans 3 the yield and selectivity of the process. Selected ex-
and 4 was observed as a 91/9 Z/E mixture of diaste- periments are reported in Table 1.[15]
Using similar reaction conditions as those shown in
Scheme 3, a base study was initially performed in
order to improve the yield and selectivity of the hy-
droalkoxylation process. As depicted in Table 1, en-
tries 1–4, the best result in terms of yield and selectiv-
ity was obtained using 4 equivalents of KOH as base
(entry 2). Clearly, shifting from pyrrolidine to KOH
as base promoted the cycloisomerization process.
With respect to the surfactant, even though cationic
tetra-n-butylammonium bromide (TBAB) and hexa-
Scheme 3. Sonogashira/hydroalkoxylation of 2-bromobenzyl
alcohol.
decyltrimethylammonium bromide (CTAB) improved
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Synthesis of Dihydroisobenzofurans via Palladium-Catalyzed Sequential
Scheme 4. Stability studies of 3.
the selectivity of the reaction towards 3 (Table 1, en-
tries 5 and 6), the conversion of the process decreased
significantly. On the other hand, the non-ionic surfac-
tant polyoxyethanyl-a-tocopheryl sebacate (PTS) af-
forded, as a major product, the Sonogashira com-
pound 2 (entry 7). The absence of surfactant led to
a decrease in the conversion to 3 (entry 8). Regarding
the ligand study, when the reaction was carried out
under ligand-free conditions, a low 24% conversion
Figure 1. Sonogashira/hydroalkoxylation of 2-bromobenzyl
alcohol. Solvent and surfactant study.
was obtained in the process (Table 1, entry 9). On the also carried out under the optimized reaction condi-
other hand, as shown in entries 10 and 11, other dicy- tions for the Sonogashira/annulation process but in
clohexylphosphine-derived ligands[15] such as tricyclo- the absence of phenylacetylene. As depicted in
hexylphosphine and 2-dicyclohexylphosphino-2’-(N,N- Scheme 4, good conversions of compound 3 to isoben-
dimethylamino)biphenyl (Davephos) did not improve zofuran-1(3H)-one (5) were observed using water
the result obtained with Xphos as ancillary ligand.
(60% conversion, 1H NMR analysis) as solvent as
The reaction time for the best two experiments well as under solvent-free conditions (70% conver-
using water as solvent (Table 1, entries 2 and 5) was sion).[17,18]
increased to 1 h, affording, in the case of SDBS the
At this point, we decided to perform a solvent
best result obtained in the study so far furnishing study in order to improve the isolated yield of 3. This
compound 3 in a 65% isolated yield (Table 1, solvent should also allow to use a straightforward
entry 12). Also, the activity of catalyst 1b under the method to isolate (Z)-1-benzylidene-1,3-dihydroiso-
optimized reaction conditions was tested in the model benzofuran (3) avoiding additional decomposition
reaction. As depicted in Table 1, entry 14, 1b afforded processes. From the above-mentioned stability studies
lower conversion towards compound 3 than pallada- (Scheme 4), MeOH was chosen to perform a study
cycle 1a. Finally, the efficiency of the microwave irra- where the amount of water as cosolvent and surfac-
diation in this process was demonstrated since a very tant (SDBS) were varied. The study was carried out
low selectivity was observed when the reaction be- using the most challenging conventional thermal heat-
tween 2-bromobenzyl alcohol and phenylacetylene ing conditions as previously demonstrated using water
was performed under conventional thermal conditions as solvent (Table 1, entry 15). As depicted in Figure 1,
(1308C, 15 h, Table 1, entry 15).
the study showed straight MeOH in the absence of
Next step in our study was to analyze the reasons surfactant as the best conditions to carry out the So-
behind the low isolated yield obtained for compound nogashira/hydroalkoxylation reaction between 2-bro-
3 under the optimized reaction conditions using water mobenzyl alcohol and phenylacetylene with high yield
as solvent. As mentioned above, different amounts of and complete selectivity towards the formation of 3.
isobenzofuran-1(3H)-one (5) and benzaldehyde were
The absence of by-products when using straight
detected in many of the crude reactions (CG and MeOH as solvent allowed an easy and straightfor-
1H NMR analysis). The oxidation of the benzylidene ward purification of dihydroisobenzofuran 3 from the
moiety[16] of the dihydroisobenzofuran by molecular crude reaction mixture by recrystallization. Thus,
oxygen would explain the formation of the observed after only 3 h reaction time, pure 3 was obtained in
by-products. In fact, when stirring pure compound 3 a 95% isolated yield (Scheme 5). On the other hand,
in water under aerobic conditions for 18 h, the forma- under similar reaction conditions but using microwave
tion of isobenzofuran-1(3H)-one (5) (8% conversion, heating (40 W initial irradiation), (Z)-1-benzylidene-
1H NMR analysis) was observed (Scheme 4). Similar- 1,3-dihydroisobenzofuran (3) was obtained in an 89%
ly, a 38% conversion towards 5 was detected when isolated yield only after 15 min (Scheme 5).
stirring 3 under aerobic solvent-free conditions, and
Finally, a loading and catalyst study was carried out
a 3% conversion when stirring for 18 h in MeOH under the optimized reaction conditions using micro-
(Scheme 4). The stability experiments with 3 were wave heating (Table 2). The reaction did not work in
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Eduardo Buxaderas et al.
Table 3. Sonogashira/hydroalkoxylation of 2-bromobenzyl
alcohols with terminal alkynes. Substrate study.
Scheme 5. Optimized conditions for the synthesis of (Z)-1-
benzylidene-1,3-dihydroisobenzofuran (3) in MeOH.
Table 2. Sonogashira/hydroalkoxylation of 2-bromobenzyl
alcohol with phenylacetylene in MeOH. Catalyst study.
Entry
Pd Catalyst (mol% Pd)
Yield [%][a]
1
2
3
4
5
6
7
8
1a (1)
89 (0/100/0/0)
<5
<5
82 (5/94/0/1)
<5
90 (0/100/0/0)
81 (3/95/1/1)
71 (0/99/0/1)
<5
–
1a (1)[b]
1a (0.1)
1a (0.01)
1b (1)
1b (0.1)
PdCl2 (1)
PdCl2 (0.1)
9
10
11
12
Pd
Pd
G
76 (0/99/0/1)
<5
84[e] (7/93/0/0)
[a]
Isolated yield of 3 after purification by crystallization in
MeOH. In parenthesis, selectivity 2/3/4/5 determined by
1H NMR analysis of the crude reaction mixture.
Reaction carried out in the absence of Xphos.
Reaction performed under conventional thermal heating
conditions (1308C, 3 h).
[b]
[c]
[a]
Isolated yield after purification by crystallization in
MeOH.
Compound
[b]
8 was obtained as (Z)-4-(isobenzofuran-
[d]
[e]
A drop of Hg was added after 5 min and the reaction
was run for 3 h.
1(3H)-ylidenemethyl)benzoic acid as a consequence of
the ester hydrolysis under the reaction conditions.
1
Conversion determined by H NMR analysis of the crude
reaction after 3 h.
To test the effectiveness of the optimized catalytic
the absence of catalyst, or without ligand (Table 2, en- system in the Pd-catalyzed Sonogashira coupling in
tries 2 and 3). In general, under the optimized condi- MeOH, various terminal alkynes were examined in
tions, all the tested Pd(II) and Pd(0) catalysts showed the reaction with different 2-bromobenzylic alcohols
good isolated yields of (Z)-1-benzylidene-1,3-dihy- (Table 3). As previously described for phenylacety-
droisobenzofuran (3) when using 1 mol% Pd as cata- lene, 2-bromobenzyl alcohol afforded 1,3-dihydroiso-
lyst loading (Table 2, entries 1, 6, 8, and 10). However, benzofurans 6–9 with isolated yields ranging from 75
when the catalyst loading was significantly reduced to to 94% after reaction with different electron-rich and
0.1 mol% of Pd (Table 2, entries 4, 7, 9, and 11) only electron-poor phenylacetylene derivatives under the
palladacycle 1b showed comparable activity to 1a (en- optimized reaction conditions (Table 3, entries 2–5).
tries 4 and 7). These latter results could be an indica-
On the other hand, functionalized 2-bromobenzylic
tion of the existence of an induction period for the alcohols, such as (2-bromo-5-fluorophenyl)methanol,
nanoparticles formation. However, in this particular (2-bromo-5-methoxyphenyl)methanol, and (2-bromo-
tandem process, a mercury poisoning experiment per- 6-fluorophenyl)methanol reacted with phenylacety-
formed on the reaction under thermal conditions (see lene to yield dihydroisobenzofurans 10–12 with yields
the Supporting Information) pointed to the involve- of 73, 70 and 68%, respectively (entries 6–8). The se-
ment of other different catalytically active species quential Sonogashira cross-coupling/cyclization pro-
(Table 2, entry 12).
cess showed a certain degree of dependence with the
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Synthesis of Dihydroisobenzofurans via Palladium-Catalyzed Sequential
Table 4. Sonogashira/hydroalkoxylation of 2-chlorobenzyl al-
cohols with terminal alkynes in MeOH. Substrate study.
low reactivity shown by alkynes bearing electron-
withdrawing groups in the Sonogashira reaction
(entry 2). Functionalized aryl chlorides such as [2-
chloro-5-(trifluoromethyl)phenyl]methanol and (2-
chloro-6-fluorophenyl)methanol, yielded compounds
16 and 12 in 70 and 64% yields, respectively, on reac-
tion with phenylacetylene (Table 4, entries 6 and 7).
As commented above for aryl bromides, tertiary alco-
hols showed low reactivity in the studied process. In
the same way, dihydroisobenzofuran 13 was obtained
in a 31% yield by reaction of 1-(2-chlorophenyl)etha-
nol with phenylacetylene (entry 8). Finally, (Z)-7-ben-
zylidene-5,7-dihydrofuroACTHNUTRGENUGN[3,4-b]pyridine (15) was iso-
lated in a 73% yield from (2-chloropyrid-3-yl)metha-
nol and phenylacetylene (Table 4, entry 9).
2-Alkynylbenzaldehydes have been used as versa-
tile building blocks for the generation of a wide varie-
ty of cyclic compounds.[19] Dihydroisobenzofurans
have been synthesized by a palladium-catalyzed
domino addition/annulation process of ortho-alkynyl-
benzaldehydes in the presence of alcohols as nucleo-
philes.[6b,20,21] More recently, a variety of substituted di-
hydroisobenzofurans have been synthesized by a one-
pot three component Pd(0)/Cu(I)-catalyzed domino
reaction of o-bromobenzaldehydes, methanol and ter-
minal alkynes under microwave irradiation.[22] As de-
picted in Table 5, oxime palladacycle 1a in the pres-
[a]
Isolated yield after purification by crystallization in
MeOH.
Table 5. Sonogashira/hydroalkoxylation of 2-bromobenzyl
alcohols with terminal alkynes. Substrate study.
steric hinderance around the benzylic alcohol moiety
since low yields were observed when secondary and
tertiary alcohols where employed in the process. Thus,
as depicted in entries 9 and 10, the reaction of 1-(2-
bromophenyl)ethanol and 2-(2-bromophenyl)propan-
2-ol with phenylacetylene, afforded compounds 13
and 14 in 43 and 46% yields, respectively. Finally,
a good isolated yield was also obtained for the cou-
pling of (2-bromopyridin-3-yl)methanol with phenyla-
cetylene, a reaction which led to the formation of
(Z)-7-benzylidene-5,7-dihydrofuroACTHNUTRGNEUNG[3,4-b]pyridine (15)
in a 72% isolated yield (Table 3, entry 11).
The optimized reaction conditions for the Sonoga-
shira alkynylation/annulation process of aryl bromides
were also applied to the synthesis of functionalized di-
hydroisobenzofurans from aryl chlorides (Table 4). In
general, aryl chlorides afforded the corresponding
products with similar or slightly lower yields than aryl
bromides. As illustrated in Table 4 entries 1–5, (2-
chlorophenyl)methanol reacted with phenylacetylene,
4’-trifluoromethylphenylacetylene, 4’-methoxyphenyl-
ACHTUNGTRENNUNGacetylene, methyl 4-ethynylbenzoate, and 4’-tolylace-
tylene to give dihydroisobenzofurans 3, and 6–9 in
good isolated yields (75–85%) with the exception of
the reaction with the electron-poor 4’-trifluoromethyl-
phenylacetylene, which afforded compound 6 in
a 48% yield, a result which is in accordance with the
[a]
Isolated yield after purification by preparative thin layer
chromatography.
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Eduardo Buxaderas et al.
ture of the reaction mixture inside the vessel was monitored
using a calibrated infrared temperature control under the re-
action vessel.
ence of Xphos as ligand, is an excellent catalytic
system for the synthesis of 3-methoxy-1,3-dihydroiso-
benzofurans from 2-bromobenzaldehydes via multi-
component reaction with the solvent and terminal al-
kynes. In this way, compounds 17–22 were prepared
in yields ranging from 52 to 79% in only 15 min
under microwave irradiation (Table 5, entries 1–6). Fi-
nally, the methodology was also applied to 2-chloro-
benzaldehyde which, after reaction with MeOH and
phenylacetylene, afforded (Z)-1-benzylidene-3-me-
thoxy-1,3-dihydroisobenzofuran (17) in a 50% isolat-
ed yield.
Typical Procedure for the Sonogashira Coupling
under MW Irradiation Conditions
A 10-mL MW vessel was charged with 2-bromobenzyl alco-
hol (0.056 g, 0.3 mmol, 1 equiv.), phenylacetylene (0.040 mL,
0.36 mmol, 1.2 equiv.), KOH (0.067 g, 1.2 mmol, 4 equiv.),
catalyst 1a (0.0012 g, 1 mol% Pd), Xphos (0.0029 g,
2 mol%) and MeOH (1 mL). The vessel was sealed with
a pressure lock, and the mixture was heated in air at 1308C
for 15 min with the aid of an initial 40 W MW irradiation in
a CEM Discover MW reactor. After this time, the reaction
mixture was extracted with EtOAc (3ꢄ10 mL), and the or-
ganic layers were washed with H2O (3ꢄ10 mL), dried over
MgSO4, filtered over Celite, and concentrated under re-
duced pressure. The crude residue was purified by simple
crystallization with cold MeOH to give the corresponding
dihydroisobenzofuran 3 as a yellow solid; yield: 89%; mp
92–948C (MeOH); IR: n=3049, 1650, 1466, 1293, 1036, 814,
Conclusions
We have disclosed a palladium-catalyzed copper-free
synthesis of dihydroisobenzofurans via sequential So-
nogashira alkynylation/annulation of functionalized 2-
bromo- and 2-chlorobenzylic alcohols as well as ben-
zaldehydes under microwave irradiation. This reaction
is carried out in the presence of Xphos as ligand
(2 mol%) and the bench stable oxime palladacycle 1a
as precatalyst under low loading conditions (1 mol%
Pd). The use of microwave heating and MeOH as sol-
vent are crucial for the tandem process.
758, 691 cmÀ1 1H NMR (CDCl3, 300 MHz): d=7.76–7.72
;
(2H, m), 7.60–7.55 (1H, m), 7.39–7.30 (5H, m), 7.17–7.11
(1H, m), 5.95 (1H, s), 5.52 (2H, s); 13C NMR (CDCl3,
101 MHz): d=156.3, 139.3, 136.4, 134.8, 128.7, 128.4, 128.1,
127.7, 125.3, 121.2, 120.0, 96.2, 74.9; MS: m/z=209 (M+ +1,
18), 208 (M+, 100), 207 (36), 193 (13), 179 (43), 178 (51),
165 (21), 89 (14).
Experimental Section
Acknowledgements
General Remarks
Financial support from the MINECO (Project CTQ2010–
20387), and Consolider INGENIO 2010 (CSD2007-00006),
FEDER, from the Generalitat Valenciana (Project PROME-
TEO/2009/038), and the University of Alicante is acknowl-
edged.
Unless otherwise noted all commercial reagents and solvents
were used without further purification. All the employed
surfactants tetra-n-butylammonium bromide, hexadecyltri-
methylammonium bromide, polyoxyethanyl-a-tocopheryl se-
bacate, and sodium dodecyl benzenesulfonate were commer-
cially available and were used without further purification.
All ligands and palladium catalysts were commercially avail-
able. Melting points were determined with a Reichert Ther- References
movar hot plate apparatus and were not corrected. IR spec-
tra were recorded on
a
Nicolet 510 P-FT apparatus.
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