Organogold(I) phosphanes in palladium-catalyzed cross-coupling reactions in aqueous media

Article abstract of DOI:10.1002/ejoc.201201720

Cross-coupling reaction of organogold(I) phosphanes with organic electrophiles in aqueous media has been investigated. Reactions between isolated aryl-, alkenyl-, or alkynylgold(I) phosphanes and aryl halides or triflates, alkenyl halides, and allyl acetates proceed under palladium catalysis conditions at room temperature or 80 °C in water with THF as a co-solvent. The coupling reactions give good yields and are highly versatile and chemoselective, allowing the presence of free amino or hydroxy groups in the electrophile. This methodology was applied to the preparation of substituted phenylalanine esters in a demonstration that gold(I) organometallics are suitable reagents for metal-catalyzed cross-coupling reactions under protic conditions. Organogold(I) phosphanes react with organic electrophiles in aqueous media under palladium catalysis conditions. The reactions take place at room temperature or 80 °C in water with THF as co-solvent. The coupling is versatile and chemoselective and allows the presence of free amino and hydroxy groups in the electrophile. Copyright

Full text of DOI:10.1002/ejoc.201201720

FULL PAPER
DOI: 10.1002/ejoc.201201720
Organogold(I) Phosphanes in Palladium-Catalyzed Cross-Coupling Reactions
in Aqueous Media
Miguel Peña-López,[a] Luis A. Sarandeses,*[a] and José Pérez Sestelo*[a]
Dedicated to Professor Julio Delgado Martín on the occasion of his 70th birthday
Keywords: Homogeneous catalysis / Gold / Palladium / Cross-coupling / Water chemistry
Cross-coupling reaction of organogold(I) phosphanes with
organic electrophiles in aqueous media has been investi-
gated. Reactions between isolated aryl-, alkenyl-, or alk-
ynylgold(I) phosphanes and aryl halides or triflates, alkenyl
halides, and allyl acetates proceed under palladium catalysis
conditions at room temperature or 80 °C in water with THF
as a co-solvent. The coupling reactions give good yields and
are highly versatile and chemoselective, allowing the pres-
ence of free amino or hydroxy groups in the electrophile. This
methodologywasappliedtothepreparationofsubstitutedphenyl-
alanine esters in a demonstration that gold(I) organometallics
are suitable reagents for metal-catalyzed cross-coupling re-
actions under protic conditions.
In recent years, the use of gold(I) complexes in organic
synthesis has increased considerably, due to their particular
Lewis acid character and their ability to catalyze nucleo-
philic additions to unsaturated carbon-carbon bonds.[8]
Carbon–gold(I) species have been postulated as intermedi-
ates in these transformations, and in some cases they have
even been isolated.[9] These findings have stimulated re-
search into gold(I) organometallics in metal-catalyzed reac-
tions, and cross-coupling reactions under palladium and
nickel catalysis conditions have been developed.[10] In this
research area, we have reported that organogold(I) phos-
phanes (RAuPPh3) react efficiently with aryl, benzyl, benz-
oyl, alkenyl, and allyl electrophiles under palladium cataly-
sis conditions.[11] The main features of gold(I) organometal-
lics in palladium-catalyzed cross-coupling reactions are
their high reactivity and efficiency under mild conditions,
as well as their versatility and stability in air. Although the
mechanisms of palladium-catalyzed cross-coupling reac-
tions with organogold reagents have not been fully estab-
lished, transmetallation from the AuI reagent to a PdII com-
plex (formed by oxidative addition of the electrophile to
Pd0) followed by reductive elimination has been pro-
posed.[12] On the other hand, the preparation of water-solu-
ble gold(I) complexes and organometallics has allowed their
use in catalysis.[13] Here we report palladium-catalyzed
cross-coupling reactions between organogold(I) phos-
phanes and organic electrophiles in aqueous media.
Introduction
Water is a unique green solvent because it is inexpensive,
safe, and environmentally friendly.[1] Research into organic
reactions in (or on) water is important for understanding
and reproduction of the chemical transformations that oc-
cur in biological systems. However, the development of syn-
thetic methodologies under aqueous conditions has signifi-
cant limitations associated either with the low solubilities
of organic compounds or with their hydrolysis. A key strat-
egy for overcoming these problems involves the use of solu-
bilizing agents, phase-transfer catalysts, or water-tolerant
reagents, in what is a research area of current interest.[2]
Transition-metal-catalyzed cross-coupling reactions are
among the most important chemical reactions in contempo-
rary chemistry,[3] a fact recognized with the 2010 Nobel
Prize in Chemistry.[4] However, despite their high selectivity
and functional group compatibility, most cross-coupling re-
actions are performed in organic solvents; this is mainly due
to better solubilities of the organometallic reagents or to
prevent their hydrolysis.[5] In this field, the higher stabilities
of organoboron reagents have allowed the establishment of
a protocol for Suzuki–Miyaura coupling in aqueous me-
dia,[6] but the use of other organometallics is limited to par-
ticular reaction conditions.[7]
[a] Departamento de Química Fundamental, Universidade da
Coruña,
15071 A Coruña, Spain
Fax: +34-981-167-065
Results and Discussion
Our study started with the preparation of a variety of
gold(I) organometallics from the corresponding organo-
E-mail: sestelo@udc.es; qfsarand@udc.es
Homepage: ciencias.udc.es/investigacion-qf
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201720.
Eur. J. Org. Chem. 2013, 2545–2554
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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M. Peña-López, L. A. Sarandeses, J. Pérez Sestelo
FULL PAPER
lithium compounds, Grignard reagents, or boronic acids coupling product 3a in high yield (Table 1, Entries 7–9). It
and the commercially available (triphenylphosphane)gold(I) should be noted that these conditions avoid the use of phos-
chloride (Ph3PAuCl).[14] In the light of our previous results, phane ligands and that this makes the reaction environmen-
the feasibility of palladium-catalyzed cross-coupling reac- tally desirable.[16] These successful coupling reactions with
tions in aqueous media was assessed in the reaction be- either PdII or Pd0 complexes seem to indicate that the cata-
tween phenyl(triphenylphosphane)gold(I) (PhAuPPh3, 1a, lytic cycle starts with a oxidative addition to Pd0, followed
Table 1) and 4-iodotoluene (2) in the presence of different by transmetallation (AuI/PdII) and reductive elimination.
palladium catalysts and under different reaction conditions. The high reactivities and stabilities of gold(I) organometal-
Organogold(I) reagents are insoluble in alcohols and water lics in aqueous media are remarkable, which gives further
but are generally soluble in most common organic solvents, evidence of the potential for performing tandem gold-cata-
so we envisaged carrying out the coupling reactions in water lyzed transformations/cross-coupling reactions under aque-
with THF as co-solvent to dissolve the organogold phos- ous conditions.[17]
phane. Interestingly, the addition of PdCl2(PPh3)2 (5 mol-
Encouraged by these results, we studied the aqueous cou-
%) to a homogeneous H2O/THF (9 mL, 2:1) solution of pling with a variety of organogold(I) phosphanes and func-
previously isolated PhAuPPh3 (110 mol-%) and 4-iodotol- tionalized organic electrophiles. Gold(I) reagents bearing
uene (100 mol-%), afforded the cross-coupling product 3a aryl, heteroaryl, alkynyl, and alkenyl groups (1a–g, Table 2)
in 91% yield in 1 h at room temperature (Table 1, Entry 1). were employed, whereas the electrophiles were aryl halides
This result is identical to that obtained with pure THF as functionalized with amino or hydroxy groups, such as 4-
solvent (Table 1, Entry 2)[11a] and shows the high stability iodoaniline (4) and 4-iodophenol (5). As in our first screen-
of the organogold(I) phosphane in aqueous media (proto- ing, the reactions were performed in water with THF as co-
deauration was not detected). It is interesting to note that solvent in order to obtain homogeneous reaction mix-
is not necessary to use degassed solvents and that the reac- tures.[18] For practical reasons we also decided to use the
tion can be carried out with water taken directly from the commercially available PdCl2(PPh3)2 as catalyst.
tap.
Table 2. Cross-coupling reaction of organogold(I) phosphanes with
aryl iodides in aqueous media.
Table 1. Cross-coupling reaction between phenyl(triphenylphos-
phane)gold(I) (1a) and 4-iodotoluene (2).
Entry
Catalyst
Solvent
H2O/THF[c]
THF
Yield [%][a,b]
Entry
R
Electrophile Product Yield [%][a]
1
2
3
4
5
6
7
8
9
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd2dba3
Pd(PPh3)4
Pd/C
91
92
92
70
93
90
84
90
88
1
2
3
4
5
6
7
8
Ph (1a)
2
4
5
3a
3b
3c
3d
3e
91
95
89
93
89
98
96
91
91
99
94
92
88
89
93
o-MeOC6H4 (1b)
m-O2NC6H4 (1c)
p-F3CC6H4 (1d)
2-furyl (1e)
H2O
neat
H2O/THF[c]
H2O/THF[c]
H2O/THF[c]
H2O/THF[c]
H2O/THF[c]
PhCϵC (1f)
3f
(E)-hept-1-enyl (1g)[b]
Ph (1a)
3g[c]
6a
6b
6c
PdCl2
Pd(OAc)2
9
o-MeOC6H4 (1b)
m-O2NC6H4 (1c)
p-F3CC6H4 (1d)
2-furyl (1e)
10
11
12
13
14
15
[a] Isolated yields. [b] All the reactions were performed with iso-
lated PhAuPPh3. [c] H2O/THF (2:1).
6d
6e
PhCϵC (1f)
6f
The observed high reactivity led us to try the reaction in
neat water. In this case, even though the reagents are insolu-
ble in water, the reaction proceeded smoothly over 12 h at
room temperature and the coupling product 3a was isolated
in 92% yield (Table 1, Entry 3). To our delight, simple mix-
ing of the reaction components in air at room temperature,
in the absence of solvent, provided 3a in good yield after
(E)-hept-1-enyl (1g)[b]
Ph (1a)
6g[d]
7a
[a] Isolated yields. [b] As an E/Z (82:18) mixture by 1H NMR spec-
troscopy. [c] As an E/Z (82:18) mixture by H NMR spectroscopy.
[d] As an E/Z (86:14) mixture by H NMR spectroscopy.
1
1
The reactions between 4-iodotoluene and the isolated
24 h stirring (70%, Table 1, Entry 4). This is a good exam- arylgold(I) phosphanes bearing either electron-donating
ple of a sustainable transformation and suggests that the groups (such as o-methoxy, 1b) or electron-withdrawing
coupling takes place on water.[15] Other palladium com- groups (such as m-nitro, 1c), under palladium catalysis con-
plexes such as Pd(PPh3)4 or Pd2dba3 also proved to be ef- ditions at room temperature, gave the corresponding cross-
ficient (Table 1, Entries 5 and 6) and the reaction also pro- coupling products (such as 3b and 3c) in excellent yields
ceeded under ligand-free conditions [Pd/C, PdCl2, or (89–95%, Table 2, Entries 2 and 3). Analogously, the reac-
Pd(OAc)2, 5 mol-%] at room temperature, to give the cross- tion with 4-trifluoromethylphenylgold(I) reagent 1d at room
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Aqueous Pd-Catalyzed Cross-Coupling Reactions
temperature afforded the biaryl compound 3d in 93% yield, Table 3. Cross-coupling reaction of organogold(I) phosphanes with
aryl bromides and triflates in aqueous media.
whereas the coupling reaction with the 2-furylgold(I) rea-
gent 1e gave the coupling product 3e in high yield (89%,
Table 2, Entries 4 and 5). The reactivity of alkynyl and alk-
enylgold(I) phosphanes in cross-coupling reactions in aque-
ous media was also investigated. Under the previously de-
veloped conditions, the reaction between the isolated phen-
ylethynyl(triphenylphosphane)gold(I) (1f) and 4-iodotol-
uene in the presence of PdCl2(PPh3)2 (5 mol-%) at room
temperature in H2O/THF (2:1) solution gave the arylalkyne
3f in quantitative yield (98%, Table 2, Entry 6). Similarly,
the reaction with the stereodefined (E)-hept-1-enyl(triphen-
ylphosphane)gold(I) (1g) afforded the coupling product 3g
in 96% yield with retention of the double bond configura-
tion (Table 2, Entry 7). In comparison with other organo-
metallic reagents, it is interesting to highlight that all reac-
tions proceed at room temperature without any additive or
base, attractive features for the development of tandem and
stereoselective transformations.
Entry
R
R–X
Product Yield [%][a]
1
2
3
4
5
6
7
Ph (1a)
p-F3CC6H4 (1d)
2-furyl (1e)
8
10a
10d
10e
10f
90
80
92
93
PhCϵC (1f)
(E)-hept-1-enyl (1g)[b]
Ph (1a)
10g[c]
10a
10f
81
9
80 (99)[d,e]
PhCϵC (1f)
77 (97)[d,e]
[a] Isolated yields. [b] As an E/Z (82:18) mixture by 1H NMR spec-
troscopy. [c] As an E/Z (80:20) mixture by H NMR spectroscopy.
[d] Reactions performed with isolated RAuPPh3 and LiCl
(100 mol-%). [e] Yields based on recovered starting material in pa-
rentheses.
1
Once we had demonstrated the efficiency of this process
with functionalized aryl-, heteroaryl-, alkynyl-, and alkenyl-
gold(I) phosphanes, our next step was to test the functional
group tolerance by using 4-iodoaniline (4) as the electro-
With the aim of assessing the influence of the leaving
phile. Gratifyingly, we found that the reactions between ar- group, the aqueous cross-coupling reaction was studied
ylgold(I) reagents 1a–e and 4 gave the corresponding cou- with aryl triflate 9. In this case, treatment of the isolated
pling products 6a–e in excellent yields at room temperature phenylgold(I) reagent 1a with 9 in H2O/THF (2:1) in the
(91–99%, Table 2, Entries 8–12). Analogously, the reaction presence of PdCl2(PPh3)2 (5 mol-%) as catalyst at 80 °C
with the alkynylgold(I) reagent 1f provided 6f in 88% yield gave the coupling product 10a in only 23% yield, along with
and the reaction with the (E)-alkenylgold(I) 1g gave the significant amounts of biphenyl from dimerization of the
coupling product 6g in 89% yield without isomerization of gold organometallic and recovery of some starting material.
the double bond (Table 2, Entries 13 and 14).
Interestingly, a similar result was also reported by Gagné
Furthermore, this protocol was also assessed with 4- for the palladium-catalyzed cross-coupling reactions be-
iodophenol (5) as electrophile. In this case, the reaction with tween isolated vinyl- or arylgold(I) reagents and tolyl tri-
phenyl(triphenylphosphane)gold(I) (1a) proceeded at room flate.[19] In our previous work,[11a] we reported that when
temperature, affording 1,1Ј-biphenyl-4-ol (7a) in 93% yield the organogold reagent was generated in situ, the cross-cou-
(Table 2, Entry 15). From these results it can be concluded pling reaction between 1a and 9 produced 10a in 93% yield,
that the cross-coupling reaction of organogold(I) phos- which suggests that the lithium chloride generated during
phanes with aryl iodides in aqueous media at room tem- the formation of the organogold(I) phosphane could play a
perature shows high reactivity, versatility, and chemoselec- crucial role in the coupling. The LiCl effect in palladium-
tivity, tolerating organogold(I) reagents of different natures catalyzed cross-coupling reactions was discovered by Stille
and electrophiles substituted with amino and hydroxy when using organotin reagents,[20] and can be attributed to
groups without any observed protodeauration. stabilization of the palladium species after the oxidative ad-
As a continuation of this work, and to demonstrate that dition.
the aqueous palladium-catalyzed cross-coupling reaction of
To confirm the above hypothesis, we carried out the reac-
gold(I) organometallics is not limited to aryl iodides, other tion between isolated organogold 1a and the aryl triflate 9
electrophiles were also tested. In this research, the coupling in the presence of lithium chloride (100 mol-%). Under
of arylgold(I) phosphanes 1a and 1d with 4-bromoaceto- these conditions, the cross-coupling product 10a was ob-
phenone (8) under PdCl2(PPh3)2 (5 mol-%) catalysis condi- tained in 80% yield after 12 h at 80 °C [99% yield based on
tions in the homogeneous H2O/THF mixture at room tem- recovered starting material (brsm), Table 3, Entry 6]. In this
perature afforded the coupling products only in low yields. study, we also performed the reaction with the isolated
However, when the mixtures were heated at 80 °C for 12 h phenylethynyl(triphenylphosphane)gold(I) (1f) in the ab-
the coupling products 10a and 10d were obtained in 90% sence of LiCl, which gave rise to the coupling product 10f in
and 80% yields, respectively (Table 3, Entries 1 and 2). 25% yield. The corresponding reaction with the organogold
Analogously, cross-coupling reaction with the 2-furyl- (rea- prepared in situ gave a 72% yield, and with the isolated 1f
gent 1e), alkynyl- (reagent 1f), and alkenylgold(I) (reagent and 100 mol-% of lithium chloride the coupling product
1g) phosphanes at 80 °C provided the cross-coupling prod- was obtained in 77% yield (97% brsm, Table 3, Entry 7).
ucts 10e–10g in high yields (81–93%, Table 3, Entries 3–5). These results confirm the key role of lithium chloride in the
cross-coupling reactions with aryl triflates.
Eur. J. Org. Chem. 2013, 2545–2554
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M. Peña-López, L. A. Sarandeses, J. Pérez Sestelo
FULL PAPER
Scheme 1. Cross-coupling reaction of organogold(I) phosphanes with β-(E)-bromostyrene and (E)-cinnamyl acetate in aqueous media.
To expand the scope of this methodology, we studied the 14a in 51% yield with recovery of some of the starting iod-
reactivity of the gold(I) organometallics with alkenyl and ide and organometallic reagent. Alternatively, when the re-
allylic electrophiles. The cross-coupling reaction of phen- action was performed at 80 °C the coupling product was
yl-, p-trifluoromethylphenyl-, furyl-, alkynyl-, and heptenyl- isolated in higher yield (62%). Analogously, the reaction
gold(I) phosphanes (1a–g) with the stereodefined alkenyl between phenylethynyl(triphenylphosphane)gold(I) (1f) and
halide β-bromostyrene (E/Z = 90:10) in the presence of 13 at 80 °C provided the coupling product 14f in 60% yield.
PdCl2(PPh3)2 (5 mol-%) as catalyst in H2O/THF (2:1) mix- These examples show the utility of organogold(I) phos-
tures took place effectively at 80 °C to produce the corre- phanes in the synthesis of phenylalanine analogues.
sponding alkenes 11a–11g in excellent yields (81–96%,
Scheme 1). It is worth noting that the aqueous cross-cou-
pling reaction proceeds stereospecifically without isomer-
ization of the double bonds either in the electrophile or in
the gold(I) reagent.
The suitability of allylic substrates in the aqueous cross-
coupling reaction was also analyzed. Recently, we reported
Scheme 2. Synthesis of 4-substituted phenylalanines.
that aryl- and alkenylgold(I) organometallics react regiose-
lectively with allylic electrophiles such as cinnamyl and ger-
anyl halides (bromide, chloride) and acetates under palla-
Conclusions
dium catalysis conditions in dry THF at 80 °C to afford the
α-substitution products with moderate to high yields.[11b]
Here, we found that the palladium-catalyzed reactions be-
tween the phenylgold(I) phosphane 1a and cinnamyl brom-
ide or chloride in H2O/THF (2:1) as solvent at 80 °C only
led to hydrolysis of the allyl halides. However, when the
corresponding reaction was performed with cinnamyl acet-
ate, the α-substituted coupling product 12a was obtained in
85% yield with retention of the double bond configuration
(Scheme 1). Analogously, treatment of cinnamyl acetate
(100 mol-%) with p-trifluoromethylphenylgold(I) (reagent
1d) and 2-furylgold(I) (reagent 1e) phosphanes (110 mol-%)
under palladium catalysis conditions also provided the α-
substituted products 12d and 12e stereoselectively in high
yields (Scheme 1). The cross-coupling reaction with the
stereodefined hept-1-enylgold(I) phosphane 1g (E/Z =
82:18) proceeded effectively to give the (1E,4E)-diene 12g
in 90% yield with retention of configuration in both rea-
gents (4E/4Z 83:17, Scheme 1).
In summary, we have shown that isolated aryl-, het-
eroaryl-, alkynyl- and alkenylgold(I) organometallics react
with aryl and alkenyl halides, aryl triflates, and allyl acet-
ates in aqueous media under palladium catalysis conditions.
The reactions take place under mild conditions and in short
reaction times to afford the corresponding cross-coupling
products in excellent yields. The stability of the organogold
reagents under aqueous conditions is remarkable, as is their
versatility and chemoselectivity, with amino and hydroxy
groups being tolerated in the electrophile. Our reactions
support the classical mechanism for palladium-catalyzed
cross-coupling reactions and suggest the use of the transient
gold(I) organometallics in aqueous gold-catalyzed pro-
cesses. Further studies to confirm the mechanism and to
develop dual gold/palladium-catalyzed cross-coupling reac-
tions are currently underway in our laboratories.
The high chemoselectivity exhibited by the organogold(I)
phosphanes led us to apply our methodology to the synthe-
sis of functionalized α-amino acids. Metal-catalyzed cross-
coupling reactions have been used to prepare non-natural
aromatic α-amino acids, but most procedures require the
use of protecting groups at the amino and the carboxylic
acid functionalities.[21] By our methodology, the coupling of
PhAuPPh3 (1a) with the methyl ester of p-iodophenylalan-
ine (13, Scheme 2) in the presence of PdCl2(PPh3)2 in H2O/
Experimental Section
General Methods: Reaction temperatures refer to external bath
temperatures. Anhydrous THF was obtained by distillation from
sodium/benzophenone. All other commercially available reagents
were used as received. Organic extracts were dried with anhydrous
MgSO4, filtered, and concentrated with a rotary evaporator at aspi-
rator pressure (20–30 Torr). TLC was carried out on silica gel
60 F254 (layer thickness 0.2 mm) and components were located by
observation under UV light and/or by treating the plates with a
THF at room temperature afforded the coupling product phosphomolybdic acid or p-anisaldehyde reagent followed by heat-
2548 Eur. J. Org. Chem. 2013, 2545–2554
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Aqueous Pd-Catalyzed Cross-Coupling Reactions
ing. Column chromatography was performed on silica gel (230–
400 mesh).[22] NMR spectra were obtained with a Bruker Av-
ance 300 spectrometer with use of the residual solvent signal as
internal standard. DEPT was used to assign carbon types. The low-
resolution electron-impact mass spectra were measured with a
Thermo Finnigan Trace MS spectrometer at 70 eV. The high-reso-
lution mass spectra were measured with a Thermo Finnigan
MAT 95XP spectrometer. Infrared spectra were obtained with a
Bruker Vector 22 instrument and with ATR (“attenuated total re-
flectance”).
7.64 (m, 15 H), 7.87–7.94 (m, 2 H), 8.45 (br. s, 1 H) ppm. 13C NMR
(75 MHz, CDCl3, 25 °C): δ = 120.5 (s, CH), 127.5 (s, CH), 129.2
[d, J(C,P) = 10.8 Hz, 6ϫ CH], 130.2 (s, C), 130.9 (s, C), 131.3 [d,
J(C,P) = 2.2 Hz, CH], 133.5 (s, CH), 134.3 [d, J(C,P) = 13.8 Hz,
6ϫ CH], 146.0 (s, 3ϫ CH), 147.5 (s, 3ϫ C) ppm. 31P NMR
(121.5 MHz, CDCl ): δ = 43.36 (s) ppm. IR (ATR): ν = 3052, 2923,
˜
3
2852, 1509, 1479, 1435 cm–1. MS (EI): m/z (%) = 581 (3) [M]+, 459
(12) [M – C6H4NO2]+, 262 (100) [M – C7H4F3Au]+. HRMS (EI):
calcd. for C24H19NO2PAu [M]+ 581.0813; found 581.0823.
[4-(Trifluoromethyl)phenyl](triphenylphosphane)gold (1d):[10c] The
General Procedure afforded 1d as a brown powder (72.6 mg,
0.120 mmol, 79%), m.p. 155–157 °C. 1H NMR (300 MHz, C6D6,
25 °C): δ = 6.91–6.99 (m, 9 H), 7.33–7.41 (m, 6 H), 7.66 (d, J =
7.7 Hz, 2 H), 7.95 (t, J = 6.3 Hz, 2 H) ppm. 13C NMR (75 MHz,
C6D6, 25 °C): δ = 123.6 (m, 2ϫ CH), 127.6 (s, 3ϫ C), 128.9 [d,
J(C,P) = 10.9 Hz, 6ϫ CH], 130.5 (s, C), 130.8 [d, J(C,P) = 2.1 Hz,
2ϫ CH], 131.2 (s, C), 134.2 [d, J(C,P) = 13.7 Hz, 6ϫ CH], 139.9
(s, 3ϫ CH), 178.3 [d, J(C,P) = 116.8 Hz, C] ppm. 31P NMR
General Procedure for the Preparation of Organogold Com-
pounds:[11a] A 25 mL round-bottomed flask containing a stirrer bar
was charged with Ph3PAuCl (75 mg, 0.152 mmol) and a positive
argon pressure was established. Dry THF (3 mL) was added, and
the resulting solution was cooled to –20 °C. A solution of RLi or
RMgBr (0.182 mmol) was added dropwise, the mixture was stirred
for 20 min, the cooling bath was removed, and the reaction mixture
was stirred for 1 h at room temp. The solvent was evaporated under
reduced pressure and toluene (5 mL) was added. The mixture was
filtered through Celite, concentrated to dryness in vacuo, washed
with pentane, and dried. The solid was re-extracted with the mini-
mum possible quantity of toluene, filtered, washed with pentane,
and dried under high vacuum.
(121.5 MHz, C D ): δ = 43.62 (s) ppm. IR (ATR): ν = 3057, 1591,
˜
6
6
1556, 1479, 1322 cm–1. MS (EI): m/z (%) = 604 (1) [M]+, 459 (3)
[M – C7H4F3]+, 262 (100) [M – C7H4F3Au]+. HRMS (EI): calcd.
for C25H19F3PAu [M]+ 604.0837; found 604.0808.
2-Furyl(triphenylphosphane)gold (1e):[23] The General Procedure af-
forded 1e as a white powder (74.2 mg, 0.141 mmol, 93%), m.p.
Phenyl(triphenylphosphane)gold (1a):[10c] The General Procedure af-
forded 1a as a white powder (74.8 mg, 0.139 mmol, 92%), m.p.
1
157–159 °C. H NMR (300 MHz, C6D6, 25 °C): δ = 6.68 (dd, J =
1
160–161 °C. H NMR (300 MHz, C6D6, 25 °C): δ = 6.88–6.97 (m,
1.6, 3.0 Hz, 1 H), 6.83–7.00 (m, 10 H), 7.25–7.33 (m, 6 H), 7.90 (d,
9 H), 7.26 (t, J = 7.4 Hz, 1 H), 7.37–7.44 (m, 6 H), 7.52 (t, J = J = 1.5 Hz, 1 H) ppm. 13C NMR (75 MHz, C6D6, 25 °C): δ = 108.4
7.5 Hz, 2 H), 8.11 (d, J = 7.0 Hz, 2 H) ppm. 13C NMR (75 MHz,
C6D6, 25 °C): δ = 125.9 (s, 2ϫ CH), 127.5 (s, 3ϫ C), 127.7 (s, C), 10.8 Hz, 6ϫ CH], 130.6 [d, J(C,P) = 2.3, 51.5 Hz, C], 130.8 [d,
(s, CH), 118.9 (br. s, CH), 127.6 (s, 3ϫ C), 128.8 [d, J(C,P) =
127.7 (br. s, 2ϫ CH), 128.7 [d, J(C,P) = 10.5 Hz, 6ϫ CH], 130.6
(br. s, CH), 134.2 [d, J(C,P) = 13.9 Hz, 6ϫ CH], 140.0 (s, 3ϫ
CH) ppm. 31P NMR (121.5 MHz, C6D6): δ = 43.99 (s) ppm. IR
J(C,P) = 2.3 Hz, CH], 134.2 [d, J(C,P) = 13.8 Hz, 6ϫ CH], 144.2
(s, 3ϫ CH) ppm. 31P NMR (121.5 MHz, C6D6): δ = 43.90 (s) ppm.
IR (ATR): ν = 3062, 1478, 1433, 1350 cm–1. MS (EI): m/z (%) =
˜
(ATR): ν = 3051, 3006, 2922, 2851, 1571, 1478, 1434 cm–1. MS
526 (1) [M]+, 459 (2) [M – C4H3O]+, 262 (100) [M – C4H3OAu]+.
HRMS (EI): calcd. for C22H18OPAu [M]+ 526.0755; found
526.0740.
˜
(EI): m/z (%) = 536 (71) [M]+, 459 (100) [M – C6H5]+. HRMS (EI):
calcd. for C24H20PAu [M]+ 536.0963; found 536.0944.
2-Methoxyphenyl(triphenylphosphane)gold (1b):[11b] The General
Procedure afforded 1b as a white powder (69.3 mg, 0.122 mmol,
81%), m.p. 140–142 °C. 1H NMR (300 MHz, C6D6, 25 °C): δ =
3.65 (s, 3 H), 6.89–7.00 (m, 10 H), 7.22–7.33 (m, 2 H), 7.44–7.51
2-Phenylethynyl(triphenylphosphane)gold (1f):[24] The General Pro-
cedure afforded 1f as a white powder (84.3 mg, 0.150 mmol, 99%),
m.p. 161–162 °C. 1H NMR (300 MHz, C6D6, 25 °C): δ = 6.84–6.98
(m, 9 H), 7.02–7.08 (m, 3 H), 7.19–7.26 (m, 6 H), 7.84 (d, J =
(m, 6 H), 8.09 [dt, J(C,P) = 1.9, 6.5 Hz, 1 H] ppm. 13C NMR 7.9 Hz, 2 H) ppm. 13C NMR (75 MHz, C6D6, 25 °C): δ = 126.1 (s,
(75 MHz, C6D6, 25 °C): δ = 55.0 (s, CH3), 110.0 [d, J(C,P) = CH), 127.5 (s, C), 127.8 (s, C), 128.1 [d, J(C,P) = 12.2 Hz, CH],
4.3 Hz, CH], 120.9 [d, J(C,P) = 6.0 Hz, CH], 126.6 (s, CH), 128.7 128.8 [d, J(C,P) = 11.2 Hz, CH], 129.9 (s, C), 130.6 (s, C), 130.8
[d, J(C,P) = 10.6 Hz, 6ϫ CH], 130.5 [d, J(C,P) = 2.1 Hz, 3ϫ CH], [d, J(C,P) = 2.2 Hz, CH], 132.4 (s, CH), 134.1 [d, J(C,P) = 13.9 Hz,
131.6 [d, J(C,P) = 48.8 Hz, 3ϫ C], 134.3 [d, J(C,P) = 13.8 Hz, 6ϫ
CH], 140.2 (s, CH), 160.5 [d, J(C,P) = 112.8 Hz, C], 166.1 [d, J(C,P)
CH] ppm. 31P NMR (121.5 MHz, C6D6): δ = 41.98 (s) ppm. IR
(ATR): ν = 3053, 2923, 2357, 1595, 1483, 1435, 1331 cm–1. MS
˜
= 0.9 Hz, C] ppm. 31P NMR (121.5 MHz, C6D6, 25 °C): δ = 44.25 (EI): m/z (%) = 560 (18) [M]+, 459 (1) [M – C8H5]+, 404 (100).
(s) ppm. IR (ATR): ν = 3054, 2944, 2828, 1566, 1479 cm–1. MS
HRMS (EI): calcd. for C26H20PAu [M]+ 560.0963; found 560.0985.
˜
(EI): m/z (%) = 566 (1) [M]+, 459 (2) [M – C7H7O]+, 262 (100) [M –
C7H7OAu]+. HRMS (EI): calcd. for C25H22OPAu [M]+ 566.1068;
found 566.1063.
(E)-Hept-1-enyl(triphenylphosphane)gold (1g):[11a] A solution of (E)-
hept-1-enyllithium, prepared from (E)-1-iodohept-1-ene (40.8 mg,
0.182 mmol, E/Z = 82:18) and tBuLi (0.215 mL, 1.7 m in pentane,
3-Nitrophenyl(triphenylphosphane)gold (1c):[14] Cs2CO3 (236.9 mg, 0.364 mmol), was added to a solution of Ph3PAuCl (90 mg,
0.727 mmol) and Ph3PAuCl (180 mg, 0.363 mmol) were added suc-
cessively to a solution of 3-nitrophenylboronic acid (121.4 mg,
0.727 mmol) in dry isopropyl alcohol (5 mL). The resulting white
suspension was stirred at 50 °C for 24 h and taken to dryness by
rotary evaporation. The solid was extracted with benzene, filtered
through Celite, concentrated to dryness in vacuo, washed with
pentane, and dried. The solid was re-extracted with a minimum of
benzene, filtered, washed with pentane, and dried under high vac-
uum, to give the organogold phosphane 1c as a white powder
(192.5 mg, 0.331 mmol, 91%), m.p. 170–171 °C. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.41 (dd, J = 7.3, 8.1 Hz, 1 H), 7.46–
0.182 mmol) in THF (3 mL) as described in the General Procedure,
and the resulting organogold phosphane 1g was used directly in
the palladium-catalyzed cross-coupling reaction. Alternatively, 1g
can be prepared from (E)-hept-1-enylboronic acid: Cs2CO3
(105.4 mg, 0.323 mmol) and Ph3PAuCl (80 mg, 0.161 mmol) were
added successively to a solution of (E)-hept-1-enylboronic acid
(45.9 mg, 0.323 mmol) in dry isopropyl alcohol (5 mL). The result-
ant white suspension was stirred at 50 °C for 24 h and taken to
dryness by rotary evaporation. The solid was extracted with benz-
ene, filtered through Celite, concentrated in vacuo to dryness,
washed with pentane, and dried. The solid was re-extracted with a
Eur. J. Org. Chem. 2013, 2545–2554
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2549

M. Peña-López, L. A. Sarandeses, J. Pérez Sestelo
FULL PAPER
minimum of benzene, filtered, washed with pentane, and dried un-
der high vacuum, to give the organogold phosphane 1g as a pale
brown solid (80.7 mg, 0.145 mmol, 90%), m.p. 91–93 °C. 1H NMR
(300 MHz, C6D6, 25 °C): δ = 0.87 (t, J = 7.2 Hz, 3 H), 1.26–1.49
7.77 (m, 4 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 21.1
(CH3), 125.6 (q, J = 3.8 Hz, CH), 127.1 (2ϫ CH), 127.2 (2ϫ CH),
127.6 (CH), 128.8 (C), 129.2 (C), 129.7 (2ϫ CH), 136.9 (C), 138.1
(C), 144.6 (C) ppm. IR (ATR): ν = 2922, 2852, 2361, 2340, 1615,
˜
(m, 4 H), 1.61–1.71 (m, 2 H), 2.56 (q, J = 6.9 Hz, 2 H), 6.43–6.56 1329 cm–1. MS (EI): m/z (%) = 236 (100) [M]+, 235 (21) [M – 1]+,
(m, 1 H), 6.85–6.97 (m, 9 H), 7.35–7.43 (m, 6 H), 7.53 (dd, J = 167 (25) [M – CF3]+. HRMS (EI): calcd. for C14H11F3 [M]+
18.4, 5.1 Hz, 1 H) ppm. 13C NMR (75 MHz, C6D6, 25 °C): δ = 14.0
(s, CH3), 22.8 (s, 2ϫ CH2), 30.2 (s, CH2), 31.7 (s, CH2), 128.7 [d,
J(C,P) = 10.5 Hz, 6ϫ CH], 130.5 (s, CH), 131.7 [d, J(C,P) =
47.2 Hz, 3ϫ C], 134.2 [d, J(C,P) = 13.8 Hz, 6ϫ CH], 144.4 (s, CH),
146.4 (s, 3ϫ CH) ppm. 31P NMR (121.5 MHz, C6D6, 25 °C): δ =
236.0807; found 236.0808.
2-(p-Tolyl)furan (3e):[29] The General Procedure afforded 3e as a
yellow oil (19.4 mg, 0.123 mmol, 89%). 1H NMR (500 MHz,
CDCl3, 25 °C): δ = 2.37 (s, 3 H), 6.46 (dd, J = 1.8, 3.3 Hz, 1 H),
6.60 (dd, J = 0.6, 3.3 Hz, 1 H), 7.19 (d, J = 7.9 Hz, 2 H), 7.45 (dd,
J = 0.8, 1.8 Hz, 1 H), 7.57 (d, J = 8.2 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 20.0 (CH3), 103.0 (CH), 110.3 (CH),
122.6 (2ϫ CH), 127.0 (C), 128.1 (2ϫ CH), 135.9 (C), 140.5 (CH),
45.41 (s) ppm. IR (ATR): ν = 3053, 2952, 2916, 2849, 1583,
˜
1479 cm–1. MS (EI): m/z (%) = 556 (1) [M]+, 459 (2) [M –
C7H13]+, 262 (100) [M – C7H13Au]+.
153.0 (C) ppm. IR (ATR): ν = 3115, 3029, 2923, 2855, 1517,
˜
General Procedure for the Palladium-Catalyzed Cross-Coupling Re-
actions: A solution of isolated RAuPPh3 (1.1 equiv.) in H2O/THF
(2:1, 9 mL) was added to a mixture of the electrophile (1.0 equiv.)
and palladium catalyst (5 mol-%). The resulting homogeneous
solution was stirred either at room temp. or at 80 °C until the start-
ing material had been consumed (TLC). The reaction mixture was
diluted with Et2O (20 mL), and the ethereal phase was washed with
brine (10 mL), dried with MgSO4, filtered, and concentrated to a
reduced volume under vacuum. The residue was purified by flash
chromatography to afford, after concentration and high-vacuum
drying, the corresponding cross-coupling product in the reported
yield.
1485 cm–1. MS (EI): m/z (%) = 158 (100) [M]+, 129 (51). HRMS
(EI): calcd. for C11H10O [M]+ 158.0726; found 158.0727.
1-Methyl-4-(2-phenylethynyl)benzene (3f):[30] The General Pro-
cedure afforded 3f as a colorless oil (22.4 mg, 0.116 mmol, 98%).
1H NMR (300 MHz, CDCl3, 25 °C): δ = 2.39 (s, 3 H), 7.17 (d, J
= 7.7 Hz, 2 H), 7.33–7.39 (m, 3 H), 7.45 (d, J = 8.1 Hz, 2 H), 7.52–
7.57 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.5 (CH3),
88.7 (C), 89.5 (C), 120.2 (C), 123.5 (C), 128.1 (CH), 128.3 (2ϫ
CH), 129.1 (2ϫ CH), 131.5 (2ϫ CH), 131.6 (2ϫ CH), 138.4
(C) ppm. IR (ATR): ν = 3030, 2919, 2852, 2216, 1661, 1595, 1509,
˜
1485 cm–1. MS (EI): m/z (%) = 192 (100) [M]+, 191 (46) [M – 1]+.
HRMS (EI): calcd. for C15H12 [M]+ 192.0934; found 192.0930.
4-Methylbiphenyl (3a):[25] The General Procedure afforded 3a as a
1
(E)-1-(Hept-1-enyl)-4-methylbenzene (3g):[31] The General Pro-
cedure afforded 3g as a colorless oil (24.0 mg, 0.127 mmol, 96%,
white solid (22.9 mg, 0.136 mmol, 91%), m.p. 46–48 °C. H NMR
(300 MHz, CDCl3, 25 °C): δ = 2.42 (s, 3 H), 7.24–7.63 (m, 9
H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 21.1 (CH3), 126.9
(2ϫ CH), 127.0 (2ϫ CH), 127.2 (CH), 128.7 (2ϫ CH), 129.5 (2ϫ
1
E/Z = 82:18). H NMR (300 MHz, CDCl3, 25 °C): δ = 0.91 (t, J
= 6.9 Hz, 3 H), 1.27–1.52 (m, 6 H), 2.20 (q, J = 6.8 Hz, 2 H), 2.33
(s, 3 H), 6.18 (dt, J = 6.8, 15.8 Hz, 1 H), 6.35 (d, J = 15.8 Hz, 1
H), 7.11 (d, J = 8.0 Hz, 2 H), 7.25 (d, J = 8.0 Hz, 2 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 14.0 (CH3), 21.1 (CH3), 22.5 (CH2),
29.1 (CH2), 31.4 (CH2), 33.0 (CH2), 125.8 (2ϫ CH), 129.1 (2ϫ
CH), 129.5 (CH), 130.2 (CH), 135.2 (C), 136.4 (C) ppm. IR (ATR):
CH), 137.0 (C), 138.4 (C), 140.2 (C) ppm. IR (ATR): ν = 3027,
˜
2922, 2857, 2360, 1739, 1601, 1518, 1486 cm–1. MS (EI): m/z (%)
= 168 (100) [M]+, 167 (76) [M – 1]+, 153 (19) [M – CH3]+. HRMS
(EI): calcd. for C13H12 [M]+ 168.0934; found 168.0935.
2-Methoxy-4Ј-methylbiphenyl (3b):[26] The General Procedure af-
forded 3b as a white solid (20.7 mg, 0.104 mmol, 95%), m.p. 77–
ν = 3021, 2955, 2923, 2855, 1512, 1458 cm–1. MS (EI): m/z (%) =
˜
188 (44) [M]+, 131 (100) [M – C4H9]+, 91 (13) [M – C7H13]+.
HRMS (EI): calcd. for C14H20 [M]+ 188.1560; found 188.1553.
1
79 °C. H NMR (300 MHz, CDCl3, 25 °C): δ = 2.41 (s, 3 H), 3.83
(s, 3 H), 7.02 (dd, J = 7.4 Hz, 2 H), 7.25 (d, J = 7.9 Hz, 2 H), 7.30–
7.36 (m, 2 H), 7.45 (d, J = 8.1 Hz, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 21.2 (CH3), 55.5 (CH3), 111.2 (CH), 120.8 (CH), 128.4
(CH), 128.7 (2ϫ CH), 129.4 (2ϫ CH), 130.7 (C), 130.8 (C), 135.6
Biphenyl-4-amine (6a):[32] The General Procedure afforded 6a as a
yellow solid (18.3 mg, 0.108 mmol, 91%), m.p. 52–54 °C. 1H NMR
(300 MHz, CDCl3): δ = 3.73 (br. s, 2 H), 6.75–6.80 (m, 2 H), 7.25–
7.32 (m, 1 H), 7.38–7.46 (m, 4 H), 7.53–7.58 (m, 2 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 115.4 (2ϫ CH), 126.2 (CH), 126.4
(2ϫ CH), 128.0 (2ϫ CH), 128.7 (2ϫ CH), 131.6 (C), 141.2 (C),
(C), 136.6 (C), 156.5 (C) ppm. IR (ATR): ν = 3025, 2922, 2835,
˜
1904, 1598, 1584 cm–1. MS (EI): m/z (%) = 198 (100) [M]+, 183 (37)
[M – CH3]+. HRMS (EI): calcd. for C14H14O [M]+ 198.1039; found
198.1046.
145.8 (C) ppm. IR (ATR): ν = 3426, 3393, 3309, 3207, 3059, 3032,
˜
2925, 2854, 2359 cm–1. MS (EI): m/z (%) = 169 (100) [M]+, 168 (10)
[M – 1]+. HRMS (EI): calcd. for C12H11N [M]+ 169.0886; found
169.0879.
4-Methyl-3-nitrobiphenyl (3c):[27] The General Procedure afforded
3c as a colorless oil (28.0 mg, 0.131 mmol, 89%). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 2.42 (s, 3 H), 7.30 (d, J = 7.9 Hz, 2
H), 7.53 (d, J = 8.1 Hz, 2 H), 7.59 (t, J = 7.9 Hz, 1 H), 7.90 (dq,
J = 1.0, 7.9 Hz, 1 H), 8.17 (dq, J = 1.0, 8.1 Hz, 1 H), 8.44 (t, J =
2.0 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 21.1
(CH3), 121.6 (CH), 121.7 (CH), 126.9 (2ϫ CH), 129.6 (CH), 129.8
(2ϫ CH), 132.8 (CH), 135.7 (C), 138.6 (C), 142.8 (C), 148.7
2Ј-Methoxybiphenyl-4-amine (6b):[33] The General Procedure af-
forded 6b as a brown oil (19.1 mg, 0.096 mmol, 91%). 1H NMR
(300 MHz, CDCl3): δ = 3.71 (br. s, 2 H), 3.82 (s, 3 H), 6.75 (d, J
= 8.6 Hz, 2 H), 6.96–7.04 (m, 2 H), 7.25–7.32 (m, 2 H), 7.37 (d, J
= 8.6 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 55.5 (CH3),
111.2 (CH), 114.8 (CH), 120.8 (CH), 127.8 (CH), 128.7 (C), 130.4
(2ϫ CH), 130.5 (2ϫ CH), 130.7 (C), 145.4 (C), 156.5 (C) ppm. IR
(C) ppm. IR (ATR): ν = 3089, 3027, 2921, 2852, 2361, 1914, 1614,
˜
1529 cm–1. MS (EI): m/z (%) = 213 (100) [M]+, 167 (24) [M –
NO2]+, 152 (43) [M
–
CH3NO2]+. HRMS (EI): calcd. for
(ATR): ν = 3445, 3372, 3218, 3026, 2925, 2851, 2834, 1728,
˜
C13H11O2N [M]+ 213.0784; found 213.0787.
1620 cm–1. MS (EI): m/z (%) = 199 (100) [M]+, 183 (48) [M –
NH2]+. HRMS (EI): calcd. for C13H13ON [M]+ 199.0992; found
199.0983.
4-Methyl-4Ј-(trifluoromethyl)biphenyl (3d):[28] The General Pro-
cedure afforded 3d as a white solid (32.5 mg, 0.137 mmol, 93%),
1
m.p. 131–132 °C. H NMR (300 MHz, CDCl3, 25 °C): δ = 2.43 (s,
3Ј-Nitrobiphenyl-4-amine (6c): The General Procedure afforded 6c
3 H), 7.30 (d, J = 7.9 Hz, 2 H), 7.52 (d, J = 8.1 Hz, 2 H), 7.68–
as an orange solid (23.2 mg, 0.109 mmol, 99%), m.p. 128–130 °C.
2550
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2545–2554

Aqueous Pd-Catalyzed Cross-Coupling Reactions
1H NMR (300 MHz, CDCl3): δ = 3.84 (br. s, 2 H), 6.80 (d, J = 4Ј-Phenylacetophenone (10a):[38] The General Procedure afforded
8.6 Hz, 2 H), 7.47 (d, J = 8.6 Hz, 2 H), 7.55 (t, J = 8.0 Hz, 1 H),
7.85 (dq, J = 1.0, 7.7 Hz, 1 H), 8.11 (dq, J = 1.0, 8.2 Hz, 1 H),
8.40 (t, J = 2.0 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
115.4 (2ϫ CH), 120.8 (CH), 120.9 (CH), 128.1 (2ϫ CH), 128.7
(C), 129.5 (CH), 132.1 (CH), 142.8 (C), 146.9 (C), 148.8 (C) ppm.
10a as a white solid (21.1 mg, 0.107 mmol, 90% from 4-bromo-
acetophenone and 21.9 mg, 0.111 mmol, 80% from aryl triflate),
1
m.p. 118–120 °C. H NMR (300 MHz, CDCl3): δ = 2.65 (s, 3 H),
7.38–7.51 (m, 3 H), 7.63–7.72 (m, 4 H), 8.05 (d, J = 8.5 Hz, 2
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 26.7 (CH3), 127.2 (2ϫ
CH), 127.3 (2ϫ CH), 128.2 (CH), 128.9 (2ϫ CH), 129.0 (2ϫ CH),
IR (ATR): ν = 3482, 3382, 2922, 2852, 2361, 2341, 1620, 1606 cm–1.
˜
MS (EI): m/z (%) = 214 (100) [M]+, 168 (46) [M – NO2]+. HRMS
135.9 (C), 139.9 (C), 145.8 (C), 197.8 (C) ppm. IR (ATR): ν = 3076,
˜
(EI): calcd. for C12H10O2N2 [M]+ 214.0737; found 214.0736.
3000, 2920, 1677, 1602, 1561, 1519 cm–1. MS (EI): m/z (%) = 196
(69) [M]+, 181 (100) [M – CH3]+, 152 (49) [M – C2H3O]+. HRMS
(EI): calcd. for C14H12O [M]+ 196.0883; found 196.0882.
4Ј-(Trifluoromethyl)biphenyl-4-amine (6d):[34] The General Pro-
cedure afforded 6d as a pale brown solid (26.5 mg, 0.112 mmol,
94%), m.p. 149–151 °C. 1H NMR (300 MHz, CDCl3): δ = 3.81 (br.
s, 2 H), 6.78 (d, J = 8.4 Hz, 2 H), 7.44 (d, J = 8.6 Hz, 2 H), 7.64
(s, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 115.4 (2ϫ CH),
119.0 (C), 122.6 (C), 125.6 (q, J = 3.8 Hz, 2ϫ CH), 126.4 (2ϫ CH),
1-[4Ј-(Trifluoromethyl)biphenyl-4-yl]ethanone (10d):[39] The General
Procedure afforded 10d as a white solid (27.0 mg, 0.102 mmol,
1
80%), m.p. 124–126 °C. H NMR (300 MHz, CDCl3): δ = 2.66 (s,
3 H), 7.70 (d, J = 8.5 Hz, 2 H), 7.72–7.74 (m, 4 H), 8.07 (d, J =
8.3 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 26.7 (CH3),
125.9 (q, J = 3.8 Hz, 2ϫ CH), 127.4 (2ϫ CH), 127.6 (2ϫ CH),
129.0 (2ϫ CH), 130.0 (C), 130.4 (C), 136.6 (C), 143.4 (C), 144.2
128.2 (2ϫ CH), 129.8 (C), 144.6 (C), 146.7 (C) ppm. IR (ATR): ν
˜
= 3436, 3310, 3212, 3041, 2921, 2852, 1637, 1594 cm–1. MS (EI):
m/z (%) = 237 (100) [M]+, 236 (5) [M – 1]+. HRMS (EI): calcd. for
C13H10NF3 [M]+ 237.0760; found 237.0763.
(C), 197.5 (C) ppm. IR (ATR): ν = 2359, 1684, 1605, 1420,
˜
1355 cm–1. MS (EI): m/z (%) = 264 (49) [M]+, 249 (100) [M –
CH3]+, 221 (8) [M – C2H3O]+. HRMS (EI): calcd. for C15H11OF3
[M]+ 264.0757; found 264.0747.
4-(Furan-2-yl)aniline (6e):[35] The General Procedure afforded 6e as
a pale brown solid (20.3 mg, 0.127 mmol, 92%), m.p. 57–59 °C. 1H
NMR (300 MHz, CDCl3): δ = 3.74 (br. s, 2 H), 6.42–6.46 (m, 2
H), 6.71 (d, J = 8.6 Hz, 2 H), 7.40 (t, J = 1.2 Hz, 1 H), 7.49 (d, J
= 8.5 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 102.4 (CH),
11.4 (CH), 115.1 (2ϫ CH), 122.0 (C), 125.2 (2ϫ CH), 140.9 (CH),
1-[4-(Furan-2-yl)phenyl]ethanone (10e):[40] The General Procedure
afforded 10e as a white solid (23.3 mg, 0.125 mmol, 92%), m.p.
1
105–107 °C. H NMR (300 MHz, CDCl3): δ = 2.62 (s, 3 H), 6.52
(dd, J = 1.8, 3.5 Hz, 1 H), 6.80 (dd, J = 0.6, 3.5 Hz, 1 H), 7.54 (dd,
J = 0.6, 1.8 Hz, 1 H), 7.75 (d, J = 8.7 Hz, 2 H), 7.98 (d, J = 8.7 Hz,
2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 26.5 (CH3), 107.5
(CH), 112.0 (CH), 123.5 (2ϫ CH), 128.9 (2ϫ CH), 134.8 (C), 135.5
145.6 (C), 154.6 (C) ppm. IR (ATR): ν = 3460, 3371, 3204, 3140,
˜
3115, 3038, 2923, 2852, 1618, 1518 cm–1. MS (EI): m/z (%) = 159
(100) [M]+, 130 (83) [M – CHO]+. HRMS (EI): calcd. for C10H9ON
[M]+ 159.0679; found 159.0681.
(C), 143.3 (CH), 152.8 (C), 197.4 (C) ppm. IR (ATR): ν = 2956,
˜
4-(Phenylethynyl)aniline (6f):[36] The General Procedure afforded 6f
as a yellow solid (20.2 mg, 0.104 mmol, 88%), m.p. 127–129 °C. 1H
NMR (300 MHz, CDCl3): δ = 3.82 (br. s, 2 H), 6.62–6.67 (m, 2 H),
7.29–7.37 (m, 5 H), 7.48–7.52 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 87.3 (C), 90.1 (C), 112.7 (C), 114.7 (2ϫ CH), 123.9
(C), 127.6 (CH), 128.2 (2ϫ CH), 131.3 (2ϫ CH), 132.9 (2ϫ CH),
2920, 2851, 2357, 1714, 1667 cm–1. MS (EI): m/z (%) = 186 (62)
[M]+, 171 (100) [M – CH3]+, 143 (23) [M – C2H3O]+. HRMS (EI):
calcd. for C12H10O2 [M]+ 186.0675; found 186.0676.
4Ј-(2-Phenylethynyl)acetophenone (10f):[41] The General Procedure
afforded 10f as a white solid (30.0 mg, 0.136 mmol, 93% from 4-
bromoacetophenone and 22.0 mg, 0.099 mmol, 77% from aryl
triflate), m.p. 84–86 °C. 1H NMR (300 MHz, CDCl3, 25 °C): δ =
2.63 (s, 3 H), 7.36–7.40 (m, 3 H), 7.55–7.58 (m, 2 H), 7.62 (d, J =
8.6 Hz, 2 H), 7.95 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR (75 MHz,
CDCl3, 25 °C): δ = 26.6 (CH3), 88.6 (C), 92.7 (C), 122.6 (C), 128.2
(C), 128.3 (2ϫ CH), 128.4 (2ϫ CH), 128.8 (CH), 131.7 (2ϫ CH),
146.6 (C) ppm. IR (ATR): ν = 3476, 3381, 3200, 3037, 2923, 2853,
˜
2212, 1617, 1592, 1515 cm–1. MS (EI): m/z (%) = 193 (100) [M]+,
165 (13). HRMS (EI): calcd. for C14H11N [M]+ 193.0886; found
193.0890.
(E)-4-(Hept-1-en-1-yl)aniline (6g): The General Procedure afforded
6g as a brown oil (22.6 mg, 0.120 mmol, 89%, E/Z = 86:14). 1H
NMR (300 MHz, CDCl3): δ = 0.91 (t, J = 6.9 Hz, 3 H), 1.27–1.51
(m, 6 H), 2.17 (dq, J = 1.3, 6.9 Hz, 2 H), 3.75 (br. s, 2 H), 6.05 (dt,
J = 6.9, 15.8 Hz, 1 H), 6.29 (d, J = 15.8 Hz, 1 H), 6.68 (d, J =
8.4 Hz, 2 H), 7.18 (d, J = 8.4 Hz, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 14.1 (CH3), 22.6 (CH2), 29.3 (CH2), 31.5 (CH2), 33.0
(CH2), 115.6 (2ϫ CH), 126.9 (2ϫ CH), 128.0 (CH), 129.3 (CH),
131.7 (2ϫ CH), 136.2 (C), 197.3 (C) ppm. IR (ATR): ν = 3339,
˜
3064, 2999, 2919, 2850, 2219, 1896, 1676, 1601 cm–1. MS (EI): m/z
(%) = 220 (73) [M]+, 205 (100) [M – CH3]+, 177 (14) [M –
C2H3O]+. HRMS (EI): calcd. for C16H12O [M]+ 220.0883; found
220.0885.
(E)-1-[(4-Acetyl)phenyl]hept-1-ene (10g):[42] The General Procedure
afforded 10g as a colorless oil (23.5 mg, 0.109 mmol, 81%, E/Z =
80:20). 1H NMR (300 MHz, CDCl3): δ = 0.92 (t, J = 6.9 Hz, 3 H),
1.27–1.53 (m, 6 H), 2.21–2.28 (m, 2 H), 2.59 (s, 3 H), 6.33–6.46 (m,
2 H), 7.41 (d, J = 8.3 Hz, 2 H), 7.89 (d, J = 8.3 Hz, 2 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 14.0 (CH3), 22.5 (CH2), 26.5 (CH3),
28.8 (CH2), 31.4 (CH2), 33.1 (CH2), 125.9 (2ϫ CH), 128.7 (2ϫ
CH), 128.9 (CH), 134.6 (CH), 135.4 (C), 142.7 (C), 197.6 (C) ppm.
129.4 (C), 144.2 (C) ppm. IR (ATR): ν = 3362, 3025, 2956, 2924,
˜
2854, 2361, 1619 cm–1. MS (EI): m/z (%) = 189 (38) [M]+, 132 (100)
[M – C4H9]+. HRMS (EI): calcd. for C13H19N [M]+ 189.1512;
found 189.1511.
Biphenyl-4-ol (7a):[37] The General Procedure afforded 7a as a white
solid (23.3 mg, 0.137 mmol, 93%), m.p. 158–160 °C. 1H NMR
(300 MHz, CDCl3): δ = 4.89 (br. s, 1 H), 6.90–6.93 (m, 2 H), 7.31
(tt, J = 1.7, 7.3 Hz, 1 H), 7.42 (tt, J = 1.7, 7.6 Hz, 2 H), 7.47–7.50
(m, 2 H), 7.53–7.56 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 115.6 (2ϫ CH), 126.7 (CH), 126.7 (2ϫ CH), 128.4 (2ϫ CH),
IR (ATR): ν = 2956, 2925, 2855, 1679, 1648, 1601 cm–1. MS (EI):
˜
m/z (%) = 216 (100) [M]+, 201 (99) [M – CH3]+, 131 (73) [M –
C4H9]+. HRMS (EI): calcd. for C15H20O [M]+ 216.1509; found
216.1509.
128.7 (2ϫ CH), 134.0 (C), 140.7 (C), 155.0 (C) ppm. IR (ATR): ν (E)-Stilbene (11a): The General Procedure afforded 11a as a white
˜
= 3413, 3061, 3036, 2921, 2851, 1608, 1596 cm–1. MS (EI): m/z (%)
solid (24.3 mg, 0.135 mmol, 95%), m.p. 120–122 °C. 1H NMR
= 170 (100) [M]+, 141 (19). HRMS (EI): calcd. for C12H10O [M]+ (300 MHz, CDCl3, 25 °C): δ = 7.14 (s, 2 H), 7.26–7.31 (m, 2 H),
170.0726; found 170.0726.
7.38 (t, J = 7.7 Hz, 4 H), 7.53–7.56 (m, 4 H) ppm. 13C NMR
Eur. J. Org. Chem. 2013, 2545–2554
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2551

M. Peña-López, L. A. Sarandeses, J. Pérez Sestelo
FULL PAPER
(75 MHz, CDCl3, 25 °C): δ = 126.5 (4ϫ CH), 127.6 (2ϫ CH), (%) = 194 (64) [M]+, 117 (50) [M – C6H5]+. HRMS (EI): calcd. for
128.6 (4ϫ CH), 128.7 (2ϫ CH), 137.3 (2ϫ C) ppm. IR (ATR): ν
C15H14 [M]+ 194.1090; found 194.1092.
(E)-1-Phenyl-3-(4-trifluoromethylphenyl)propene (12d):[48] The Ge-
˜
= 3077, 3058, 3021, 2925, 1598, 1577, 1495, 1451 cm–1. MS (EI):
m/z (%) = 180 (100) [M]+, 103 (33) [M – C6H5]+. HRMS (EI):
calcd. for C14H12 [M]+ 180.0937; found 180.0933.
neral Procedure afforded 12d as
a colorless oil (30.7 mg,
1
0.117 mmol, 78%). H NMR (300 MHz, CDCl3, 25 °C): δ = 3.62
(d, J = 6.7 Hz, 2 H), 6.34 (dt, J = 6.7, 15.8 Hz, 1 H), 6.50 (d, J =
15.8 Hz, 1 H), 7.21–7.40 (m, 7 H), 7.59 (d, J = 8.0 Hz, 2 H) ppm.
13C NMR (75 MHz, CDCl3, 25 °C): δ = 39.1 (CH2), 125.4 (q, J =
3.8 Hz, CF3), 125.4 (C), 126.2 (4ϫ CH), 127.4 (CH), 127.9 (CH),
128.6 (2ϫ CH), 128.9 (2ϫ CH), 131.9 (CH), 137.1 (C), 144.3 (d,
(E)-1-Styryl-4-(trifluoromethyl)benzene (11d):[43] The General Pro-
cedure afforded 11d as a white solid (30.1 mg, 0.121 mmol, 81%,
E/Z = 92:8), m.p. 134–136 °C. 1H NMR (300 MHz, CDCl3, 25 °C):
δ = 7.13 (d, J = 16.3 Hz, 1 H), 7.21 (d, J = 16.3 Hz, 1 H), 7.28–
7.34 (m, 1 H), 7.36–7.43 (m, 2 H), 7.55 (d, J = 7.1 Hz, 2 H), 7.61–
7.63 (m, 4 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 125.6
(q, J = 3.8 Hz, 2ϫ CH), 126.6 (2ϫ CH), 126.8 (2ϫ CH), 127.1
(CH), 128.3 (CH), 128.8 (2ϫ CH), 129.0 (C), 129.5 (C), 131.2
J = 1.3 Hz, C) ppm. IR (ATR): ν = 3029, 1620, 1601, 1497,
˜
1323 cm–1. MS (EI): m/z (%) = 262 (100) [M]+, 193 (25) [M – CF3]+.
HRMS (EI): calcd. for C16H13F3 [M]+ 262.0964; found 262.0957.
(E)-1-Phenyl-3-(furan-2-yl)propene (12e):[49] The General Procedure
afforded 12e as a colorless oil (21.7 mg, 0.117 mmol, 91%). 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 3.57 (d, J = 6.7 Hz, 2 H),
6.09 (dd, J = 0.8, 3.2 Hz, 1 H), 6.27–6.38 (m, 2 H), 6.51 (d, J =
15.8 Hz, 1 H), 7.20–7.40 (m, 6 H) ppm. 13C NMR (75 MHz,
CDCl3, 25 °C): δ = 31.8 (CH2), 105.6 (CH), 110.3 (CH), 125.6
(CH), 126.2 (2ϫ CH), 127.3 (CH), 128.5 (2ϫ CH), 132.0 (CH),
(CH), 136.6 (C), 140.8 (C) ppm. IR (ATR): ν = 3025, 2928, 1615,
˜
1580, 1323 cm–1. MS (EI): m/z (%) = 248 (100) [M]+, 179 (44) [M –
CF3]+. HRMS (EI): calcd. for C15H11F3 [M]+ 248.0807; found
248.0800.
(E)-2-Styrylfuran (11e):[44] The General Procedure afforded 11e as
a white solid (21.9 mg, 0.129 mmol, 96%, E/Z = 93:7), m.p. 51–
53 °C. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 6.37 (d, J = 3.3 Hz,
1 H), 6.44 (dd, J = 1.6, 3.3 Hz, 1 H), 6.91 (d, J = 16.3 Hz, 1 H),
7.06 (d, J = 16.3 Hz, 1 H), 7.25–7.28 (m, 1 H), 7.33–7.39 (m, 2 H),
7.42 (d, J = 1.8 Hz, 1 H), 7.45–7.50 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3, 25 °C): δ = 108.5 (CH), 111.6 (CH), 116.5 (CH),
126.3 (2ϫ CH), 127.1 (CH), 127.6 (CH), 128.7 (2ϫ CH), 137.0
137.2 (C), 141.4 (CH), 153.9 (C) ppm. IR (ATR): ν = 3082, 3059,
˜
3027, 1596, 1504, 1448 cm–1. MS (EI): m/z (%) = 184 (100) [M]+,
155 (31) [M – CHO]+. HRMS (EI): calcd. for C13H12O [M]+
184.0883; found 184.0874.
(1E,4E)-1-Phenyldeca-1,4-diene (12g): The General Procedure af-
forded 12g as a colorless oil (25.9 mg, 0.121 mmol, 90%, 4E/4Z
83:17). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 0.91 (t, J = 6.8 Hz,
3 H), 1.25–1.44 (m, 6 H), 2.00–2.07 (m, 2 H), 2.90–2.94 (m, 2 H),
5.44–5.59 (m, 2 H), 6.24 (dt, J = 6.5, 15.8 Hz, 1 H), 6.41 (d, J =
15.8 Hz, 1 H), 7.18–7.39 (m, 5 H) ppm. 13C NMR (75 MHz,
CDCl3, 25 °C): δ = 14.1 (CH3), 22.6 (CH2), 29.2 (CH2), 31.4 (CH2),
32.6 (CH2), 35.9 (CH2), 126.0 (2ϫ CH), 126.9 (CH), 127.5 (CH),
128.5 (2ϫ CH), 129.4 (CH), 130.2 (CH), 132.1 (CH), 137.8
(C), 142.1 (CH), 153.3 (C) ppm. IR (ATR): ν = 3025, 2922, 2850,
˜
2361, 1597, 1498, 1483, 1446 cm–1. MS (EI): m/z (%) = 170 (100)
[M]+, 169 (26) [M – 1]+. HRMS (EI): calcd. for C12H10O [M]+
170.0726; found 170.0729.
(E)-1,4-Diphenylbut-1-en-3-yne (11f):[45] The General Procedure af-
forded 11f as a white solid (24.2 mg, 0.118 mmol, 92%, E/Z =
90:10), m.p. 92–94 °C. 1H NMR (300 MHz, CDCl3, 25 °C): δ =
6.40 (d, J = 16.2 Hz, 1 H), 7.06 (d, J = 16.2 Hz, 1 H), 7.30–7.56
(m, 10 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 88.9 (C),
91.7 (C), 108.1 (CH), 123.4 (C), 126.3 (2ϫ CH), 128.2 (CH), 128.3
(2ϫ CH), 128.6 (CH), 128.7 (2ϫ CH), 131.5 (2ϫ CH), 136.3 (C),
(C) ppm. IR (ATR): ν = 3025, 2955, 2923, 2871, 2854, 1494,
˜
1448 cm–1. MS (EI): m/z (%) = 214 (47) [M]+ , 143 (100) [M –
C5H11]+, 130 (43) [M – C6H12]+. HRMS (EI): calcd. for C16H22
[M]+ 214.1716; found 214.1711.
141.2 (CH) ppm. IR (ATR): ν = 3080, 3032, 2923, 1973, 1900,
˜
1810, 1748, 1678 cm–1. MS (EI): m/z (%) = 204 (100) [M]+, 101 (22)
[M – C8H7]+. HRMS (EI): calcd. for C16H12 [M]+ 204.0939; found
204.0943.
Methyl (S)-2-Amino-3-(4-iodophenyl)propanoate (13): Et3N (2 mL)
was added at room temp. to a stirred suspension of 4-iodo-l-phen-
ylalanine methyl ester hydrochloride[50] (0.839 g, 2.45 mmol) in
CH2Cl2 (15 mL), and the mixture was stirred for a further 30 min.
The solvent was removed under reduced pressure, EtOAc (15 mL)
was added, and the mixture was filtered. The filtrate was washed
with a saturated solution of NaHCO3 (3ϫ 15 mL) and water (3ϫ
15 mL), dried with anhydrous MgSO4, and filtered. The solution
was concentrated under reduced pressure and the residue was puri-
fied by column chromatography (10% MeOH/CH2Cl2) to afford 13
(1E,3E)-Nona-1,3-dienylbenzene (11g):[46] The General Procedure
afforded 11g as a colorless oil (21.8 mg, 0.109 mmol, 84%, 1E,3E/
1
1E,3Z 85:15). H NMR (300 MHz, CDCl3, 25 °C): δ = 0.91 (t, J
= 6.9 Hz, 3 H), 1.27–1.49 (m, 6 H), 2.15 (q, J = 6.9 Hz, 2 H), 5.85
(dt, J = 15.1, 7.0 Hz, 1 H), 6.22 (dd, J = 15.1, 10.4 Hz, 1 H), 6.45
(d, J = 15.7 Hz, 1 H), 6.77 (dd, J = 15.7, 10.4 Hz, 1 H), 7.17–7.44
(m, 5 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 14.0 (CH3),
22.5 (CH2), 29.0 (CH2), 31.4 (CH2), 32.8 (CH2), 126.1 (2ϫ CH),
127.0 (CH), 128.5 (2ϫ CH), 129.5 (CH), 129.9 (CH), 130.4 (CH),
1
(0.440 g, 1.44 mmol) as a slightly brown oil. H NMR [500 MHz,
(CD3)2SO, 25 °C]: δ = 1.75 (br. s, 2 H), 2.72 (dd, J = 7.5, 13.4 Hz,
1 H), 2.82 (dd, J = 6.1, 13.4 Hz, 1 H), 3.54 (t, J = 6.2 Hz, 1 H),
3.57 (s, 3 H), 7.00 (d, J = 8.3 Hz, 2 H), 7.62 (d, J = 8.3 Hz, 2
H) ppm. 13C NMR [125 MHz, (CD3)2SO, 25 °C]: δ = 40.0 (CH2),
51.4 (CH3), 55.5 (CH), 92.1 (C), 131.7 (2ϫ CH), 136.8 (2ϫ CH),
136.0 (CH), 137.7 (C) ppm. IR (ATR): ν = 3079, 3059, 3021, 2955,
˜
2924, 2854, 1643, 1596 cm–1. MS (EI): m/z (%) = 200 (100) [M]+,
199 (37) [M – 1]+. HRMS (EI): calcd. for C15H20 [M]+ 200.1565;
found 200.1560.
137.9 (C), 175.3 (C) ppm. IR (ATR): ν = 3379, 3312, 2948, 2925,
˜
2853, 1732 cm–1. MS (EI): m/z (%) = 305 (10) [M]+, 246 (38) [M –
C2H3O2]+, 88 (100). HRMS (EI) calcd. for C10H12O2NI [M]+
304.9907; found 304.9911.
(E)-1,3-Diphenylpropene (12a):[47] The General Procedure afforded
12a as a colorless oil (24.2 mg, 0.124 mmol, 85%). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 3.58 (d, J = 6.3 Hz, 2 H), 6.39 (dt,
J = 6.3, 15.7 Hz, 1 H), 6.49 (d, J = 15.8 Hz, 1 H), 7.20–7.41 (m,
10 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 39.4 (CH2),
126.1 (2ϫ CH), 126.2 (CH), 127.1 (CH), 128.5 (4ϫ CH), 128.7
(2ϫ CH), 129.2 (CH), 131.1 (CH), 137.5 (C), 140.2 (C) ppm. IR
Methyl (S)-2-Amino-3-(biphenyl-4-yl)propanoate (14a): The Gene-
ral Procedure afforded 14a as a white solid (19.1 mg, 0.075 mmol,
1
62%), m.p. 47–49 °C. H NMR [500 MHz, (CD3)2SO, 25 °C]: δ =
1.80 (br. s, 2 H), 2.80 (dd, J = 7.3, 13.4 Hz, 1 H), 2.91 (dd, J = 6.1,
13.4 Hz, 1 H), 3.58–3.62 (m, 4 H), 7.27 (d, J = 8.1 Hz, 2 H), 7.34
(ATR): ν = 3059, 3025, 2897, 1600, 1494, 1451 cm–1. MS (EI): m/z
˜
2552
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2545–2554

Aqueous Pd-Catalyzed Cross-Coupling Reactions
[7] Stille coupling: a) W. Susanto, C.-Y. Chu, W. J. Ang, T.-C.
Chou, L.-C. Lo, Y. Lam, Green Chem. 2012, 14, 77–80; b) J. C.
García-Martínez, R. Lezutekong, R. M. Crooks, J. Am. Chem.
Soc. 2005, 127, 5097–5103. Sonogashira reaction: c) B. H. Lip-
shutz, D. W. Chung, B. Rich, Org. Lett. 2008, 10, 3793–3796;
d) B. Inés, R. SanMartin, F. Churruca, E. Domínguez, M. K.
Urtiaga, M. I. Arriortua, Organometallics 2008, 27, 2833–2839;
e) R. J. Brea, M. P. López-Deber, L. Castedo, J. R. Granja, J.
Org. Chem. 2006, 71, 7870–7873. Hiyama coupling: f) E. Ala-
cid, C. Nájera, Adv. Synth. Catal. 2006, 348, 945–952; g) A.
Gordillo, E. de Jesús, C. López-Mardomingo, Org. Lett. 2006,
8, 3517–3520.
(t, J = 7.4 Hz, 1 H), 7.45 (t, J = 7.4 Hz, 2 H), 7.57 (d, J = 8.2 Hz,
2 H), 7.61–7.65 (m, 2 H) ppm. 13C NMR [125 MHz, (CD3)2SO,
25 °C]: δ = 40.2 (CH2), 51.3 (CH3), 55.6 (CH), 126.3 (2ϫ CH),
126.4 (2ϫ CH), 127.1 (CH), 128.6 (2ϫ CH), 129.7 (2ϫ CH), 137.2
(C), 138.0 (C), 139.9 (C), 175.3 (C) ppm. IR (ATR): ν = 3378, 3027,
˜
2950, 2924, 2853, 1736 cm–1. MS (EI): m/z (%) = 255 (7) [M]+, 196
(24) [M – C2H3O2]+, 167 (100). HRMS (EI) calcd. for C16H17O2N
[M]+ 255.1254; found 255.1257.
(S)-Methyl 2-Amino-3-[4-(phenylethynyl)phenyl]propanoate (14f):
The General Procedure afforded 14f as a white solid (20.3 mg,
1
0.073 mmol, 60%). Mp 103–105 °C. H NMR [500 MHz, (CD3)2-
[8] For recent reviews, see: a) L.-P. Liu, G. B. Hammond, Chem.
Soc. Rev. 2012, 41, 3129; b) T. C. Boorman, I. Larrosa, Chem.
Soc. Rev. 2011, 40, 1910; c) A. Corma, A. Leyva-Pérez, M. J.
Sabater, Chem. Rev. 2011, 111, 1657–1712.
SO, 25 °C]: δ = 1.79 (br. s, 2 H), 2.80 (dd, J = 7.4, 13.4 Hz, 1 H),
2.89 (dd, J = 6.2, 13.4 Hz, 1 H), 3.57–3.60 (m, 4 H), 7.24 (d, J =
8.1 Hz, 2 H), 7.41–7.44 (m, 2 H), 7.46 (d, J = 8.0 Hz, 2 H), 7.52–
7.65 (m, 3 H) ppm. 13C NMR [125 MHz, (CD3)2SO, 25 °C]: δ =
40.4 (CH2), 51.3 (CH3), 55.5 (CH), 88.9 (C), 89.3 (C), 120.0 (C),
122.3 (C), 128.6 (CH), 128.7 (2ϫ CH), 129.6 (2ϫ CH), 131.0 (2ϫ
[9] a) L.-P. Liu, B. Xu, M. S. Mashuta, G. B. Hammond, J. Am.
Chem. Soc. 2008, 130, 17642–17643; b) D. Weber, M. A. Tar-
selli, M. R. Gagné, Angew. Chem. 2009, 121, 5843; Angew.
Chem. Int. Ed. 2009, 48, 5733–5736; c) A. S. K. Hashmi, A. M.
Schuster, F. Rominger, Angew. Chem. 2009, 121, 8396; Angew.
Chem. Int. Ed. 2009, 48, 8247–8249; d) R. L. LaLonde, W. E.
Brenzovich Jr., D. Benitez, E. Tkatchouk, K. Kelley, W. A.
Goddard III, F. D. Toste, Chem. Sci. 2010, 1, 226–233; e)
A. S. K. Hashmi, Angew. Chem. 2010, 122, 5360; Angew. Chem.
Int. Ed. 2010, 49, 5232–5241; f) W. E. Brenzovich Jr., D. Beni-
tez, A. D. Lackner, H. P. Shunatona, E. Tkatchouk, W. A.
Goddard III, F. D. Toste, Angew. Chem. 2010, 122, 5651; An-
gew. Chem. Int. Ed. 2010, 49, 5519–5522; g) N. P. Mankad,
F. D. Toste, J. Am. Chem. Soc. 2010, 132, 12859–12861.
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CH), 131.2 (2ϫ CH), 138.9 (C), 175.2 (C) ppm. IR (ATR): ν =
˜
3381, 3058, 3030, 2923, 2853, 1736 cm–1. MS (EI): m/z (%) = 279
(50) [M]+, 220 (15) [M – C2H3O2]+, 191 (100). HRMS (EI) calcd.
for C18H17O2N [M]+ 279.1254; found 279.1249.
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 1H and 13C NMR spectra for all compounds
prepared.
Acknowledgments
The authors are grateful to the Xunta de Galicia (IN-
CITE08PXIB103167PR) and the Ministerio de Ciencia e Innova-
ción (MICINN) (CTQ2009-07180) for financial support. M. P. L.
thanks the MICINN for an FPU predoctoral fellowship. Mr.
Miguel Ayán-Varela is thanked for preliminary experiments.
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Published Online: March 15, 2013
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