Phosphinocyclodextrins as confining units for catalytic metal centres. applications to carbon-carbon bond forming reactions

Article abstract of DOI:10.3762/bjoc.10.249

The capacity of two cavity-shaped ligands, HUGPHOS-1 and HUGPHOS-2, to generate exclusively singly phosphorus-ligated complexes, in which the cyclodextrin cavity tightly wraps around the metal centre, was explored with a number of late transition metal cations. Both cyclodextrin-derived ligands were assessed in palladium-catalysed Mizoroki-Heck coupling reactions between aryl bromides and styrene on one hand, and the rhodium-catalysed asymmetric hydroformylation of styrene on the other hand. The inability of both chiral ligands to form standard bis(phosphine) complexes under catalytic conditions was established by high-pressure NMR studies and shown to have a deep impact on the two carbon-carbon bond forming reactions both in terms of activity and selectivity. For example, when used as ligands in the rhodium-catalysed hydroformylation of styrene, they lead to both high isoselectivity and high enantioselectivity. In the study dealing with the Mizoroki-Heck reactions, comparative tests were carried out with WIDEPHOS, a diphosphine analogue of HUGPHOS-2.

Full text of DOI:10.3762/bjoc.10.249

Phosphinocyclodextrins as confining units for catalytic
metal centres. Applications to carbon–carbon bond
forming reactions
Matthieu Jouffroy1, Rafael Gramage-Doria1, David Sémeril1, Dominique Armspach*1,
Dominique Matt*1, Werner Oberhauser2 and Loïc Toupet3
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 2388–2405.
1Laboratoire de Chimie Inorganique Moléculaire et Catalyse, Institut
de Chimie UMR 7177 CNRS, Université de Strasbourg, 1, rue Blaise
Pascal, 67008 Strasbourg Cedex, France, 2Istituto di Chimica dei
Composti OrganoMetallici CNR, via Madonna del Piano, 10, 50019
Sesto Fiorentino, Firenze, Italy and 3Groupe Matière Condensée et
Matériaux, UMR 6626 CNRS, Université de Rennes 1, 263, avenue
du Général Leclerc, 35042 Rennes Cedex, France
doi:10.3762/bjoc.10.249
Received: 11 July 2014
Accepted: 09 September 2014
Published: 15 October 2014
This article is part of the Thematic Series "Superstructures with
cyclodextrins: Chemistry and applications II".
Email:
Dominique Armspach* - d.armspach@unistra.fr; Dominique Matt* -
dmatt@unistra.fr
Guest Editor: G. Wenz
© 2014 Jouffroy et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
asymmetric hydroformylation; cyclodextrin; Heck reaction;
homogeneous catalysis; palladium; phosphine; rhodium
Abstract
The capacity of two cavity-shaped ligands, HUGPHOS-1 and HUGPHOS-2, to generate exclusively singly phosphorus-ligated
complexes, in which the cyclodextrin cavity tightly wraps around the metal centre, was explored with a number of late transition
metal cations. Both cyclodextrin-derived ligands were assessed in palladium-catalysed Mizoroki–Heck coupling reactions between
aryl bromides and styrene on one hand, and the rhodium-catalysed asymmetric hydroformylation of styrene on the other hand. The
inability of both chiral ligands to form standard bis(phosphine) complexes under catalytic conditions was established by high-pres-
sure NMR studies and shown to have a deep impact on the two carbon–carbon bond forming reactions both in terms of activity and
selectivity. For example, when used as ligands in the rhodium-catalysed hydroformylation of styrene, they lead to both high
isoselectivity and high enantioselectivity. In the study dealing with the Mizoroki–Heck reactions, comparative tests were carried out
with WIDEPHOS, a diphosphine analogue of HUGPHOS-2.
Introduction
Since the studies of Fu, Buchwald and Hartwig on the use of Suzuki–Miyaura reactions [4-6], there is a renewed interest for
monophosphine ligands in cross-coupling reactions, notably tertiary phosphines that favour the formation of singly phos-
carbon–carbon ones such as the Mizoroki–Heck [1-3] and phorus-ligated complexes when opposed to transition metal
2388

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
Results and Discussion
ions. Such a behaviour, which was shown to have a deep impact
on the catalyst performance, is classically observed with very Metal coordination
bulky monophosphines [1,7-10], including dendrimeric ones As shown previously, HUGPHOS-1 and HUGPHOS-2 are able
[11,12], and is also found with hybrid ligands displaying hemi- to accommodate small organometallic moieties, for example the
lability so as to prevent the coordination of a second phos- PdCl(dmba) moiety (dmba = Me2NCH2C6H4), as in complexes
phorus atom [13,14] or cavity-shaped phosphines [15]. The use 1 [38] and 2 [45] (Scheme 1). In view of the embracing nature
of sterically-hindered P(III)-derivatives, notably phosphites [16- of these cavity-shaped ligands, we wondered whether it would
21], has also proven beneficial in yet another carbon–carbon be possible to promote the selective formation of monophos-
forming reaction, namely the rhodium-catalysed hydroformyla- phine complexes with MX2 (M = Pd, Pt) fragments that
tion [22] of α-olefins [23-29]. By favouring the formation of normally form [ML2X2] complexes with tertiary phosphines.
singly phosphorus-ligated complexes, these ligands not only
improve the catalyst activity, but also its regioselectivity, the When reacted with HUGPHOS-1 in CH2Cl2, both
branched regioisomer(s) being formed at the expense of the [PdCl2(PhCN)2] and [PtCl2(PhCN)2] afforded a mixture of
linear one. However, when it comes to enantioselectivity, only complexes (Scheme 2). The presence of a unique broad signal
one chiral mono-P(III) ligand [30-32] has so far shown some in each 31P{1H} NMR spectrum is consistent with the presence
potential in the notoriously challenging, but industrially rele- of several species in equilibrium. This may reflect exchange
vant asymmetric hydroformylation [33-37]. Recently, we have processes involving methoxy groups of the primary face and/or
synthesised a new type of chiral phosphine ligand (HUGPHOS- free benzonitrile. Mass spectrometric measurements carried out
1 [38] and HUGPHOS-2 [39], see Figure 1), which consists of on the crude reaction mixtures showed a peak corresponding to
methylated cyclodextrins (CD) equipped with an embedded MCl2(HUGPHOS-1) fragments. There was no indication for the
phosphorus atom. In contrast to previously reported monophos- formation of complexes with a molecular weight higher than
phines [40-43] based on methylated CDs [41-44], our ligands that of [MCl2(HUGPHOS-1)], this suggesting that no stable
have confining properties because of the presence of an inward- bis(phosphine) complexes had formed.
pointing P(III) atom [44,45]. The present study is concerned
with the ability of HUGPHOS-1 and HUGPHOS-2 to generate A similar study was carried out with the larger HUGPHOS-2.
exclusively singly P(III)-ligated complexes with a number of d6 Its reaction with [PtCl2(PhCN)2] in CH2Cl2 resulted in the for-
and d8 metal cations and the evaluation of the catalytic prop- mation of the monophosphine complex [PtCl2(HUGPHOS-
erties of palladium and rhodium complexes of this type in the 2)(PhCN)] (3) in 95% yield, but this complex could not be sep-
Mizoroki–Heck and asymmetric hydroformylation reactions. arated from a minor product, probably the benzonitrile-free
The related trans-chelating diphosphine WIDEPHOS (Figure 1) complex [PtCl2(HUGPHOS-2)]. The 31P{1H} NMR spectrum
was also tested for comparison purposes in the case of the of 3 showed a sharp signal at 3.2 ppm, with Pt satellites
Mizoroki–Heck coupling studies.
(1JP,Pt = 3433 Hz). The mass spectrum of the mixture of prod-
Figure 1: CD-based mono- and diphosphines with inward-pointing phosphorus atoms.
2389

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
Scheme 1: Complexation of a "PdCl(dmba)" unit by HUGPHOS ligands.
Scheme 2: Reaction of HUGPHOS-1 with [MCl2(PhCN)2] complexes (M = Pd, Pt). Only one isomer with a given MeO–M bond has been drawn.
ucts showed an intense peak at m/z = 1866.61 (100%), corres- It should be reminded that monophosphine complexes of the
ponding to the [M + Na]+ cation, as well as a peak resulting general formula [MX2(phosphine)(pyridine)] usually undergo
from the loss of PhCN (m/z = 1763.57 (11) [M – PhCN + Na]+). facile ligand dissociation in solution [48]. This is, however, not
No peaks corresponding to compounds with two phosphine the case for complex 4. Owing to the protecting role played by
ligands were detected in the spectrum. Addition of 1 equiv of the cavity, this complex proved to be particularly robust, to such
pyridine to the mixture containing 3 gave quantitatively com- an extent that it could be purified by column chromatography
plex 4 (Scheme 3). The 1H NMR spectrum of 4 shows that (this being necessary for removing PhCN) without noticeable
some H-5 signals are significantly low-field shifted with respect decomposition. Attempts to produce a palladium analogue of 3
to their counterparts in the free ligand, an observation which is starting from [PdCl2(PhCN)2] failed, the corresponding reac-
indicative of an entrapped chlorido ligand. Note that the marked tion leading to a mixture of equilibrating species that could not
affinity of CDs for metal halide bonds is well documented be separated. However, when the reaction mixture was
[46,47]. The trans P,N configuration was deduced from a subjected to column chromatography on wet SiO2, a single aqua
ROESY experiment which showed strong correlations between palladium complex (5) was recovered in high yield (90%). The
the pyridinic H-4 proton and some inner cavity H-5 protons. P-monoligated nature of this complex was inferred from its
Also, a 1JP,Pt coupling constant typical of this particular geom- mass spectrum, which displays a strong peak at m/z = 1675.52
etry (1JP,Pt = 3542 Hz) unequivocally established the configur- corresponding to the [M + Li]+ ion. The 31P{1H} NMR spec-
ation of the complex [48].
trum of 5 revealed a single, slightly broad singlet at
2390

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
Scheme 3: Synthesis of complexes 3–5.
δ = 34.4 ppm. Although not visible at room temperature, the co- less distorted 5 (Δδ = 0.18 ppm). Note that complex 5 is readily
ordinated water molecule appeared as a broad singlet at reformed in the presence of water.
δ = 5.64 ppm in the 1H NMR spectrum recorded at −80 °C [45].
This chemical shift value is typical for aqua palladium
complexes [49-51]. A single crystal X-ray diffraction study
(Figure 2) confirmed the coordination of a {PdCl2(H2O)} frag-
ment, which lies inside the β-CD cavity. To date, only one other
example of [MCl2(phosphine)(H2O)] aqua complex has been
reported [52].
Complex 5 could be dehydrated using a Dean–Stark apparatus
to give the corresponding methoxy-bonded complex 6
(Scheme 4). The mass spectrum of 6 shows a strong peak at
m/z = 1673.52 having the isotopic profile expected for the
[M + Na]+ ion. The 1H NMR spectra of 5 and 6 are very
similar, however small differences could be detected, in particu-
Scheme 4: Dehydration of Pd(II) complex 5.
lar in the chemical shift range where methoxy protons resonate.
Although it was not possible to determine which methoxy group
was bonded to the metal centre because of overlapping signals, HUGPHOS-2 was further opposed to [RuCl2(p-cymene)]2. This
coordination of the one belonging to glucose unit G seems to be reaction gave a 57:43 mixture of the two rotamers 7 and 8,
the most likely according to CPK models. Also, the anomeric which could be separated by column chromatography
protons of 6 lie in a wider range (Δδ = 0.36 ppm) than those of (Figure 3). Careful examination of the ROESY spectrum of 7
2391

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
Figure 3: Ruthenium complexes 7 and 8 in Newman projection along
the Ru–P bond.
and A, but not with protons from the PPh ring or glucose units
B and C. In keeping with these findings, the only cross peaks
associated with the CHMe2 proton of 7 involved protons from
the PPh ring. Similar observations, which establish the same
blocked rotations about the P–Ru and the Ru–arene bonds were
made for 8. It should be emphasised that prolonged heating of 7
in refluxing toluene did not result in the formation of 8.
Restricted rotation about the Ru–P bond in 7 is possibly caused
by the entrapment of one of the chlorido ligands inside the
cavity.
Further proof for the capacity of HUGPHOS-1 to prevent the
formation of bis(phosphine) complexes came from the reaction
of [RhCl(CO)2]2 with excess ligand, which only produced cis-
[RhCl(HUGPHOS-1)(CO)2] (9) together with free phosphine,
rather than the expected complex trans-[RhCl(HUGPHOS-
1)2(CO)] (Figure 4, Scheme 5). The corresponding IR spectrum
Figure 2: X-ray structure of aqua palladium complex 5 [44] (top: side
view; bottom: view from the primary face). The cavity contains two
non-coordinated water molecules. Ow stands for water molecules.
indicates that the rotations about the P–Ru bond and the is typical of CO ligands in relative cis positions (strong CO
Ru–arene bond are both restricted. Thus, the ROESY spectrum bands at 2009 and 2082 cm−1). Further, with some CD H-5
of this complex showed correlations between the Me group of protons belonging to non-bridged glucose units strongly upfield
the p-cymene ligand and protons belonging to glucose units G shifted upon metal complexation (Δδ up to 0.7 ppm), the
Figure 4: Titration of HUGPHOS-1 with [Rh(CO)2Cl]2 at 25 °C.
2392

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
Scheme 5: Synthesis of rhodium carbonyl complexes 9–11.
1H NMR spectrum of 9 is fully consistent with a CD-encapsu- rhodium complex 13 (see Scheme 6) was treated with LiCl
lated chlorido ligand [53], which can only mean that two cis under CO (1 atm). When the reaction between HUGPHOS-2
configured CO ligands are present [22].
and [RhCl(CO)2]2 was repeated, but applying a 1:1 instead of
1:0.5 stoichiometry, the dinuclear complex [Rh2(μ-
In the case of HUGPHOS-2, the reaction with 0.5 equiv of Cl)2(HUGPHOS-2)(CO)3] (11) formed (see Experimental part).
[RhCl(CO)2]2 resulted in the formation of an 85:15 mixture of Clearly, the cavity of HUGPHOS-2 is capable of accommo-
the inseparable, mononuclear stereoisomeric complexes 10a dating up to two metal centres, whereas the smaller
and 10b (Scheme 5), in which the two CO ligands are respect- HUGPHOS-1 ligand is unable to do so.
ively cis (strong CO IR bands at 2009 and 2082 cm−1 [54]) and
trans (strong CO IR band at 1985 cm−1 [55,56]) configured. The HUGPHOS ligands were further reacted with
Remarkably, the same ratio of stereoisomers was obtained when [Rh(acac)(CO)2] (acac = acetylacetonate), this producing
quantitatively the singly P-ligated rhodium complexes 12 and
13 (Scheme 6). While in 13 the large β-CD cavity hosts the acac
ligand, the same ligand is located outside the α-CD cavity in 12
according to ROESY experiments. On the other hand, the
smaller CO rod is nested in the α-CD cavity of 12, and located
outside the β-CD cavity in 13. Clearly, size selectivity is at
work in these metal complexes. As already observed for com-
plex 4, both 12 and 13 are remarkably stable and can be puri-
fied by column chromatography on SiO2. This makes them, a
priori, good candidates for hydroformylation studies.
High-pressure NMR studies
Upon subjecting complex 13 to a syngas (1:1 CO/H2 mixture)
pressure of 40 bar at 80 °C in toluene-d8 (Scheme 7), the only
species that was detected by high-pressure NMR and IR spec-
troscopy [44] was complex trans-[RhH(HUGPHOS-2)(CO)3]
(14). Confirmation of a 5-coordinate rhodium centre in 14 came
from MS measurements carried out from the toluene-d8 solu-
Scheme 6: Synthesis of rhodium complexes 12 and 13.
tion, which showed the presence of a peak at 1663.53 (1%,
2393

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
Scheme 7: Selective formation of complex 14 under 40 bar CO/H2 at 80 °C.
exact isotopic profile) corresponding to the expected [M + H]+ trans to the P atom was inferred from the 1H NMR spectrum of
ion.
14 (25 °C, 40 bar), which displays a signal at –8.8 ppm
(1JH,Rh = 6.2 Hz) with a large 2J(H,P) coupling constant
The 31P{1H} NMR spectrum of 14 consisted of a doublet at (2JH,P = 103 Hz) (Figure 5). The three close together carbonyl
28.1 ppm (1JP,Rh = 95 Hz). The presence of a hydride ligand bands at 1982 (vs), 1989 (vs), and 1992 (sh, vs) cm–1 and the
Figure 5: High pressure NMR spectra of 13 under CO/H2 (1:1) recorded in toluene-d8 (at various temperatures and pressures), showing its conver-
sion into trans-[RhH(CO)3(HUGPHOS-2)] (14). The asterisk and double cross denote traces of oxidized and free HUGPHOS-2, respectively.
2394

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
Figure 6: IR spectra of 14 recorded in CH2Cl2 at 50 °C under 40 bar of CO/H2 1:1.
additional Rh–H broad band of low intensity at 2084 cm−1
(Figure 6) in the IR spectrum of 14 measured at 50 °C under
40 bar of CO/H2 are consistent with a trigonal bipyramidal
complex having C1 symmetry.
The carbonyl region of the IR spectrum of 13 markedly differs
from that of the only other reported trans-[RhH(CO)3L] com-
plex (where L is a bulky phosphoramidite), the observed three
carbonyl bands (2055 (sh), 2022 (w) and 1998 (s) cm−1) being
here spread over a larger frequency range [31]. Note that the
related cobalt complex trans-[CoH(CO)3(PCy3)] displays a
higher symmetry (D3h), and accordingly, its IR spectrum shows
only one carbonyl band [57-60].
The phosphorus atom in 14 probably binds the rhodium centre
specifically in an apical fashion because of the confining prop-
erties of the phosphine. In fact, the trigonal bipyramidal com-
plex has no other option, but to adopt a linear P–Rh–H arrange-
ment (Figure 7), so that steric interactions between the carbon-
yl ligands and the cavity inner wall are reduced to the
maximum.
Hydroformylation of styrene
The results of the above HP-NMR studies prompted us to
investigate the properties of HUGPHOS ligands in an asym-
metric hydroformylation [33-37]. Styrene was chosen as this
substrate is compatible in terms of size with both CD cavities.
Figure 7: Calculated structures (Spartan 10) of trigonal bipyramidal
[RhH(CO)3(HUGPHOS-2)] with the phosphorus being either in apical
(top) or equatorial (bottom) position.
Five different parameters, namely temperature, pressure, CO/H2
and L/Rh ratios as well as pre-catalyst loadings were varied
2395

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
during the catalytic study (Table 1 and Table 2). When stan- addition of free ligand to the reaction medium maintained at
dard hydroformylation conditions (Table 1, entry 1) were 80 °C (20 bar) was detrimental to the catalyst activity, this
applied, next to full conversion was observed after 24 h with 13. suggesting that at this temperature unreactive bis(phosphine)
As expected, the branched product was formed predominantly, complexes formed (Table 1, entries 4 and 5), although for
however with poor enantioselectivity. Surprisingly, raising the HUGPHOS ligands bis(phosphine) complexes have never been
CO/H2 from 1:1 to 1:2, which is known to speed up the reac- isolated so far.
tion, produced the opposite effect and was also detrimental to
enantioselectivity [22], but without significantly altering regio- Raising the temperature to 120 °C caused the catalyst activity to
selectivity (Table 1, entry 2). On the other hand, increasing the drop significantly and led predominantly to the (S)-enantiomer,
partial CO pressure led to a marked reaction rate increase, suggesting a profound transformation of the catalyst upon
however with neither enantioselectivity, nor regioselectivity heating (Table 2, entry 2). However, both regioselectivity and
increase (Table 1, entry 3). An unexpected observation was that enantioselectivity improved significantly upon lowering the
Table 1: Rhodium-catalysed hydroformylation of styrene using precatalyst 13 – variation of ligand/Rh and CO/H2 ratio.a
entry
equiv of
HUGPHOS-2b
CO/H2 ratio
convc
[%]
aldehydesc
b:ld
eee
[%]
l [%]
b [%]
1
2
3
4
5
0
0
0
1
4
1/1
1/2
2/1
1/1
1/1
96.8
71.5
99.3
75.1
12.9
37.1
32.0
32.6
38.2
20.3
62.9
68.0
67.4
61.8
79.7
1.7
2.2
2.1
1.6
3.9
27 (R)
17 (R)
26 (R)
19 (R)
36 (R)
aStyrene (5 mmol), styrene/complex = 2500, T = 80 °C, t = 24 h, P(CO/H2) = 20 bar, toluene/n-decane (15 mL/0.5 mL), incubation overnight at 80 °C
under P(CO/H2) = 20 bar. bEquiv of free ligand HUGPHOS-2 added to preformed rhodium complex 13 after overnight incubation. cDetermined by GC
using decane as internal standard. db:l (branched:linear) aldehyde ratio. eDetermined by chiral-phase GC after reduction with LiAlH4.
Table 2: Rhodium-catalysed hydroformylation of styrene using precatalysts 12 and 13 – variation of pressure and temperature.a
entry
complex
P(CO/H2)b
T
convc
[%]
aldehydesc
b/ld
eee
[%]
[bar]
[°C]
l [%]
b [%]
1
2
13
13
13
13
13
20
20
20
20
40
80
120
60
96.8
31.5
43.7
79.0
66.2
37.1
43.0
13.9
6.8
62.9
57.0
86.1
93.2
98.3
1.7
1.3
27 (R)
34 (S)
63 (R)
80 (R)
92 (R)
3
6.2
4f
5f
40
13.7
57.8
20
1.7
6
12
12
12
12
20
20
20
20
80
60
40
20
86.3
100
27.2
11.4
6.3
72.8
88.6
93.7
99.0
2.7
7.8
33 (R)
62 (R)
80 (R)
93 (R)
7f
8f
9f
99.8
30.6
14.9
99.0
1.0
10f
11f
12f
13f
12
12
12
12
5
40
40
20
4
19.8
99.2
60.7
34.0
21.4
3.9
78.6
96.1
98.3
100
3.7
24.6
41 (R)
90 (R)
95 (R)
93 (R)
40
40
40
1.7
57.8
traces
>100g
aStyrene (5 mmol), styrene/complex = 2500, t = 24 h, toluene/n-decane (15 mL/0.5 mL), incubation overnight at 80 °C under P(CO/H2) = 20 bar.
bCO/H2 1:1 v/v. cDetermined by GC using decane as internal standard. db:l aldehyde ratio. eDetermined by chiral-phase GC after reduction with
LiAlH4.fRun carried out with a ratio styrene/complex = 250. gExact value not determined because of a very low amount of linear aldehydes.
2396

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
temperature, reaching 63% ee at 60 °C (Table 2, entry 3). probably because the singly phosphine-ligated active species
Increasing the metal to substrate ratio by 10-fold and further behaves differently from the usual bis(phosphine) complexes
lowering the temperature allowed to maintain a reasonable (Scheme 8). The observed enantio- and isoregioselectivities are
activity while further increasing the ee value and b:l ratio amongst the highest reported for the asymmetric hydroformyla-
(Table 2, entry 4). Interestingly, complexes 12 and 13 led tion of styrene [61-63]. The presence of monophosphine inter-
roughly to the same results (Table 2, entries 5 and 12). This mediates (and not bis(phosphine) ones) in the catalytic cycle is
means that the reaction is insensitive to cavity size, this being likely to favour the formation of a [Rh(η3-(styrenyl))(CO)2]
indicative of a catalytic transformation taking place at the cavity intermediate [31,32,37], precursor of the branched aldehyde,
entrance, rather than inside. Pressure had also a dramatic effect over that of the electron poorer [Rh(σ-(phenylethyl))(CO)2]
on both regioselectivity and enantioselectivity as raising it from isomer, which leads to the linear aldehyde. The high enantio-
5 to 40 bar increased the ee value by a staggering 49% and the selectivities probably arise from the embracing properties of the
b:l ratio from 3.7 to 24.6 (Table 2, entries 10 and 11). Not HUGPHOS ligands, which facilitates chirality transfer.
surprisingly, the best result (Table 2, entry 12) was obtained at
room temperature and high pressure, the ee value and the Heck cross-coupling
proportion of branched aldehyde reaching then 95% and 98.3%, Phosphine-assisted Heck reactions strongly depend on the bulk-
respectively.
iness of the phosphine used [64]. To assess HUGPHOS-2 in
Heck coupling, we focused on the reaction between styrene and
Clearly, isoregioselectivity increases concomitantly with aryl bromides using [Pd(OAc)2] (OAc = acetate) as a palladium
enantioselectivity contrary to what is generally observed [37], source [65]. In a preliminary study, 4-bromoanisole was reacted
Scheme 8: Possible mechanism for the hydroformylation of styrene when using monophosphine complexes 12 or 13 as precatalysts.
2397

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
Table 3: Optimisation of conditions for the Heck cross-coupling of 4-bromoanisole with styrene using HUGPHOS-2 as ligand.a
entry
ligand:[Pd(OAc)2] ratio
T [°C]
conv [%]b
HUGPHOS-2
WIDEPHOS
1
2
3
4
5
6
0:1
1:2
1:2
2:1
1:1
1:1
110
110
130
110
110
130
4.3
5.6
10.4
20.7
/
17.6
22.4
45.7
46.5
45.5
<1
/
a[Pd(OAc)2] (5 × 10−3 mmol), 4-bromoanisole (0.5 mmol), styrene (1.0 mmol), Cs2CO3 (1.0 mmol), DMF (1.5 mL), decane (0.05 mL), 1 h.
bConversions were determined by GC using decane as internal standard.
for 1 h with styrene in N,N-dimethylformamide (DMF) in the for 4-bromotoluene, while the 3- and 2-substituted isomers led
presence of Cs2CO3 (Table 3). The runs were carried out at to conversions of 37.9% and 28.6%, respectively (Table 4,
different temperatures and L:M ratios. The highest yield entries 2–4). Not surprisingly, the activated 2-bromo-6-
(46.5%) was obtained when operating with 1 mol-% catalyst methoxynaphtalene afforded the corresponding coupling pro-
and one equivalent of HUGPHOS-2 per palladium (Table 3, duct in relatively high yield (71%; Table 4, entry 5). As already
entry 5). Higher phosphine:Pd ratios did not improve the observed in the hydroformylation experiments, HUGPHOS-1
catalytic outcome (Table 3, entry 4). These results clearly indi- generally gave slightly better results than the larger
cate that a single phosphine ligand is sufficient to stabilise the HUGPHOS-2, which points to a catalytic reaction taking place
active palladium species. We observed that by raising the outside the cavity. It is noteworthy that the activities obtained in
temperature to 130 °C, the conversions remained practically Mizoroki–Heck coupling with the above catalytic systems lie in
unchanged (Table 3, entry 6). For comparison purposes, we also the range obtained with other phosphines [69,70], these being,
assessed the catalytic behaviour of the related diphosphine however, always used in excess [2,71]. In fact, HUGPHOS-
WIDEPHOS [39,52]. When using a WIDEPHOS:Pd ratio of derived catalysts are much more active than previously reported
1:1, practically no reaction occurred (Table 3, entry 5). This is CD-based Heck coupling catalysts [72]. The relatively low
probably caused by the formation of a stable pseudo-trans- performance of WIDEPHOS, when operating as a
chelate complex with this ligand, which forbids completion of bis(monodentate) ligand, is probably the result of the severe
the catalytic cycle [66,67]. Clearly, decoordination of a phos- steric encumbrance generated within the cavity of the postu-
phine end cannot take place in this stable trans complex, which lated dinuclear complex.
seems vital for completion of the whole catalytic cycle [68].
However, when applying a WIDEPHOS:Pd ratio of 1:2, the According to a number of mechanistic studies, the structure of
reaction proceeded with 10.4% conversion (Table 3, entry 2). the catalytic intermediates of Mizoroki–Heck reactions is
With the same ratio and by raising the temperature to 130 °C, strongly dependent on the phosphine used [73-81]. With very
the conversion increased to 20.7% (Table 3, entry 3). These bulky monophosphines, active species having only one phosphi-
results suggest that in the presence of an excess palladium, ne coordinated to the metal have been proposed [80,82]. In view
WIDEPHOS operates as a ligand with two independent of the above complexation studies, such mono-ligated inter-
monophosphine arms, each of them binding a palladium atom. mediates are also likely to be operative with HUGPHOS ligands
(Scheme 9). The fact that the observed reaction rates are higher
We then applied the aforementioned optimal conditions in the with HUGPHOS ligands than with other bulky phosphines may
coupling of styrene with different aryl bromides (Table 4), be related to the presence of hemilabile methoxy groups [83]
using either HUGPHOS-(1 or 2) or WIDEPHOS as ligands. In able either to stabilise highly reactive intermediates or assist the
the case of HUGPHOS-2, a conversion of 61.0% was observed reduction–elimination step [80,82].
2398

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
Table 4: Palladium-catalysed Mizoroki–Heck cross-coupling of arylbromides with styrene using HUGPHOS-1, HUGPHOS-2 and WIDEPHOS.a
entry
ArBr
conv [%]b
HUGPHOS-1
58.3
HUGPHOS-2
WIDEPHOS
20.7
1
2
45.5
61.0
50.5
31.1
3
4
5
42.4
32.5
80.6
37.9
28.6
71.1
25.5
16.0
74.2
aGeneral conditions: Ligand (2.5 × 10−3 mmol for HUGPHOS-1,2; 1.25 × 10−3 mmol for WIDEPHOS), [Pd(OAc)2] (2.5 × 10−3 mmol), aryl bromide
(0.25 mmol), styrene (0.50 mmol), Cs2CO3 (0.50 mmol), DMF (0.750 mL), decane (0.025 mL), T = 130 °C, 1 h.
bConversions were determined by GC using decane as internal standard.
Scheme 9: Simplified Heck coupling mechanism when using HUGPHOS-1 or HUGPHOS-2 as ligands. Doted lines stand for labile Pd–O bonds.
2399

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
Conclusion
were synthesized according to literature procedures. The
In conclusion, we have shown that the cavity-shaped phos- synthesis and characterisation of compounds 5, 9, 12 and
phines HUGPHOS-1 and HUGPHOS-2 exclusively form 13, as well as the general procedure for rhodium catalysed
monophosphine complexes with Pd(II), Pt(II), Rh(I), and Ru(II) hydroformylation reactions have been reported in a preliminary
cations. In all these complexes, the CD cavity tightly embraces communication [44]. In the present full paper, the glucose
the metal centre. Such a feature has a strong influence on the units are ranged clockwise when looking at the primary
catalytic outcome of both olefin hydroformylation and Heck face. The numbering of the atoms within a glucose unit is as
coupling reactions. Despite being generally regarded as incom- follows:
patible, both high regio- and high enantioselectivity were
observed with HUGPHOS ligands in the Rh-catalysed hydro-
formylation of styrene. In these systems, the high isoselectivity
arises from the ligand ability to exclusively generate monophos-
phine complexes while the high enantioselectivity is a result of
the efficient chirality transfer imposed by the embracing char-
acter of the chiral CD cavity. To the best of our knowledge, the
chiral inductions obtained with these ligands are the highest 2: A solution of [(PdCl(dmba)]2 (0.170 g, 0.30 mmol) in
ever observed for a CD-derived catalyst operating in organic CH2Cl2 (20 mL) was added to a solution of HUGPHOS-2
media [46,84-88]. Future work is aimed at extending the appli- (0.900 g, 0.61 mmol) in CH2Cl2 (10 mL) under vigorous stir-
cations of HUGPHOS ligands to other metal-catalysed reac- ring at room temperature. After 15 min, the solvent was
tions.
removed in vacuo and the residue was subjected to column
chromatography (CH2Cl2/MeOH, 97:3, v/v) to afford pure 2
(0.900 g, 84%) as a pale yellow solid. Rf (SiO2, CH2Cl2/MeOH,
Experimental
All commercial reagents were used as supplied. All manipula- 94:6, v/v) = 0.35; mp dec. >250 °C; 1H NMR (300.1 MHz,
tions were performed in Schlenk-type flasks under N2. Solvents CDCl3, 25 °C) δ (assignment by COSY, ROESY and HMQC)
were dried by conventional methods and distilled immediately 1.73–1.86 (m, 1H, H-6aA), 2.51–2.59 (m, 1H, H-6aB), 2.66 (s,
prior to use. Column chromatography was performed on silica 3H, NMe), 2.88 (s, 3H, NMe), 3.03–3.31 (10H, H-2, H-4A,B,
gel 60 (particle size 40–63 μm, 230–240 mesh). CDCl3 was H-6), 3.12 (s, 3H, OMe), 3.36 (s, 3H, OMe), 3.41 (s, 3H, OMe),
passed down a 5 cm thick alumina column and stored under N2 3.43 (s, 6H, OMe), 3.44 (s, 3H, OMe), 3.45 (s, 3H, OMe), 3.47
over molecular sieves (3 Å). Routine 1H, 13C{1H} and 31P{1H} (s, 3H, OMe), 3.48 (s, 6H, OMe), 3.51 (s, 6H, OMe), 3.60 (s,
NMR spectra were recorded with Bruker FT instruments 3H, OMe), 3.62 (s, 6H, OMe), 3.63 (s, 3H, OMe), 3.66 (s, 3H,
(AVANCE 300, 400, 500, 600 spectrometers). 1H NMR spec- OMe), 3.70, (s, 3H, OMe), 3.71 (s, 3H, OMe), 3.40–3.91 (29H,
tral data were referenced to residual protiated solvents H-3, H-4, H-5, H-6, H-6bA,B, NCH2), 3.98 (d, 1H, 2JH-6b,H-6a =
(δ = 7.26 ppm for CDCl3), 13C chemical shifts are reported rela- 10.1 Hz, H-6), 4.17 (d, 1H, 2J = 12.9 Hz, NCH2), 4.49 (d, 1H,
tive to deuterated solvents (δ = 77.16 ppm for CDCl3) and the 3JH-5,H-6 = 9.3 Hz, H-5), 4.86 (d, 1H, 3JH-1,H-2 = 1.7 Hz, H-1),
31P NMR data are given relative to external H3PO4. Mass 4.87 (m, 1H, H-5B), 4.88 (d, 1H, 3JH-1,H-2 = 3.9 Hz, H-1), 5.00
spectra were recorded either on a Maldi TOF spectrometer (d, 1H, 3JH-1,H-2 = 3.3 Hz, H-1), 5.03 (d, 1H, 3JH-1,H-2 = 4.6 Hz,
(MALDI–TOF) using α-cyano-4-hydroxycinnamic acid as H-1), 5.04 (m, 1H, H-5A), 5.07 (d, 1H, 3JH-1,H-2 = 3.1 Hz, H-1),
matrix, or on a Bruker MicroTOF spectrometer (ESI–TOF) 5.09 (d, 1H, 3JH-1,H-2 = 4.0 Hz, H-1), 5.10 (d, 1H, 3JH-1,H-2 =
using CH2Cl2, MeCN or MeOH as the solvent. Elemental 3.8 Hz, H-1), 6.31 (t, 1H, J = 6.9 Hz, o-H of dmba), 6.46 (t, 1H,
analyses were performed by the Service de Microanalyse, J = 7.5 Hz, m-H of dmba), 6.78 (t, 1H, J = 7.3 Hz, p-H of
Institut de Chimie UMR 7177, Strasbourg. Melting points were dmba), 6.93 (d, 1H, J = 7.5 Hz, m-H of dmba), 7.23–7.31 (m,
determined with a Büchi 535 capillary melting point apparatus. 3H, m-H, p-H), 7.65–7.71 (m, 2H, o-H) ppm; 13C{1H} NMR
The catalytic solutions containing the aldehydes were analysed (75.5 MHz, CDCl3, 25 °C) δ (assignment by HMQC) 32.94 (d,
by using a Varian 3900 gas chromatograph equipped with a 1JC,P = 23.5 Hz, C-6A), 33.6 (d, 1JC,P = 29.4 Hz, C-6B), 49.63
WCOT fused-silica column (25 m × 0.25 mm). This allowed to (br s, NCH3), 50.44 (br s, NCH3), 57.81, 57.96, 58.04, 58.19
determine the b:l ratio. In order to determine the enantiomeric [×2], 58.65, 58.75, 58.85 [×2], 58.90 [×2], 59.09, 61.21, 61.30,
excess, a sample of the reaction mixture (toluene) was treated 61.56, 61.62, 61.70 [×2], 62.05 (OMe), 66.25 (d, 2JC,P = 5.8
with LiAlH4 for 0.5 h. After filtration, the toluene solution Hz, C-5A), 70.17 (d, 2JC,P = 7.8 Hz, C-5B), 70.90 [×2], 71.09
containing enantiomeric alcohols was analysed by GC with a [×2], 71.75 (C-5), 71.09, 71.32, 71.52, 71.64, 72.36 (C-6),
Chirasil-DEX CB column (25 m × 0.25 mm). HUGPHOS-1, 73.01 (NCH2), 79.91, 79.98, 80.58, 80.89 [×2], 80.98, 81.19,
HUGPHOS-2 [38], WIDEPHOS [39], and [PdCl(dmba)]2 [89], 81.74 [×3], 82.17, 82.36, 82.53, 82.68 [×2], 82.82, 82.94, 83.08,
2400

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
83.45 (C-2, C-3, C-4), 88.02 (d, 3JC,P = 9.5 Hz, C-4A), 88.65 (d, provide microanalytical data for this compound because of fast
3JC,P = 4.4 Hz, C-4B), 96.57, 97.94, 98.79, 100.20 [×2], 100.29, rehydration in air.
101.58 (C-1), 122.01 (d, 4JC,P = 2.3 Hz, dmba-Cmeta), 123.52
(dmba-Cpara), 125.36 (d, 4JC,P = 6.0 Hz, dmba-Cmeta), 128.15 7 and 8: A solution of HUGPHOS-2 (0.126 g, 0.09 mmol) in
(d, 3JC,P = 10.4 Hz, dmba-Cortho-H), 130.15 (Cpara), 132.38 (d, CH2Cl2 (5 mL) was added dropwise to a solution of [RuCl2(η6-
2JC,P = 10.8 Hz, Cortho), 134.91 (d, 1JC,P = 49.0 Hz, Cipso), p-cymene)]2 (0.052 g, 0.08 mmol) in CH2Cl2 (5 mL) under
136.47 (d, 3JC,P = 10.0 Hz, Cmeta), 147.67 (dmba-Cortho-C), vigorous stirring at room temperature. The solution was stirred
152.44 (dmba-Cipso) ppm; 31P{1H} NMR (121.5 MHz CDCl3, for 1 h before being evaporated to dryness. The crude product
25 °C) δ 25.5 (s) ppm; elemental analysis (%) calcd for was purified by column chromatography (SiO2, CH2Cl2/MeOH,
C76H123ClNO33PPd (1751.62): C, 52.11; H, 7.08; N, 0.80; 97:3 to 95:5, v/v) affording 7 (0.085 g, 56%) and 8 (0.065 g,
found: C, 52.34; H, 7.07;, N, 0.80; MS (ESI–TOF): m/z (%): 42%) as brown solids. 7: mp 210 °C; 1H NMR (500.1 MHz,
1714.67 (100) [M – Cl]+, 1774.64 (4) [M + Na]+, 1790.60 (8) CDCl3, 25 °C) δ (assignment by combined COSY, ROESY and
[M + K]+.
HSQC) 1.13 (d, 3H, 3JCH3,CH = 7.1 Hz, CH3iPr of p-cymene),
1.15 (d, 3H, 3JCH3,CH = 7.1 Hz, CH3iPr’ of p-cymene), 1.63 (s,
6: Water was removed over 12 h by azeotropic distillation of a 3H, CH3 of p-cymene), 2.57 (ddd, 1H, 2JH-6a,H-6b = 15.3 Hz,
toluene solution (100 mL) of compound 5 (0.100 g, 0.06 mmol) 2JH-6a,P = 11.4 Hz, 3JH-6a,H-5 = 2.5 Hz, H-6aA), 2.71 (sept, 1H,
using a Dean–Stark apparatus. After allowing the solution to 3JCH,CH3 = 7.1 Hz, CHiPr of p-cymene), 3.00 (dd, 1H, 3JH-2,H-1
reach room temperature, the solvent was removed in vacuo = 2.9 Hz, 3JH-2,H-3 = 9.8 Hz, H-2), 3.19 (s, 3H, OMe), 3.34 (s,
affording quantitatively compound 6 (0.098 g, 0.06 mmol) as a 3H, OMe), 3.35 (s, 3 H, OMe), 3.40 (s, 3H, OMe), 3.41 (s, 3H,
colourless solid. mp dec. >250 °C; 1H NMR (300.1 MHz, OMe), 3.45 (s, 3H, OMe), 3.46 (s, 3H, OMe), 3.47 (s, 3H,
CDCl3, 25 °C) δ (assignment by COSY and HMQC) 2.37 (m, OMe), 3.48 (s, 3H, OMe), 3.51 (s, 3H, OMe), 3.52 (s, 3H,
1H, H-6aA), 2.59 (m, 1H, H-6aB), 2.69 (dd, 1H, 3JH-2,H-3 = 9.9 OMe), 3.53 (s, 3H, OMe), 3.54 (s, 3H, OMe), 3.56 (s, 3H,
Hz, 3JH-2,H-1 = 2.8 Hz, H-2), 2.93–3.07 (2H, H-6bA,B), OMe), 3.58 (s, 3H, OMe), 3.62 (s, 3H, OMe), 3.63 (s, 3H,
3.12–3.26 (5H, H-2), 3.34 (m, 3H, OMe), 3.38 (s, 3H, OMe), OMe), 3.69 (s, 3H, OMe), 3.82 (s, 3H, OMe), 3.06–3.85 (36H,
3.39 (s, 3H, OMe), 3.40 (s, 3H, OMe), 3.43 (s, 3H, OMe), 3.48 H-2, H-3, H-4, H-5, H-6), 3.88 (dd, 1H, 2JH-6a,H-6b = 10.8 Hz,
(s, 6H, OMe), 3.51 (s, 12H, OMe), 3.56 (m, 3H, OMe), 3.60 (s, 3JH-6a,H-5 = 4.3 Hz, H-6), 3.91–3.95 (m, 1H, H-5), 4.02–4.10 (2
3H, OMe), 3.61 (s, 3H, OMe), 3.63 (s, 6H, OMe), 3.64 (s, 3H, H, H-5, H-5A), 4.82 (d, 1H, 3JH-1,H-2 = 2.8 Hz, H-1), 4.88 (dd,
OMe), 3.65 (s, 3H, OMe), 3.68 (m, 3H, OMe), 3.30–3.93 (27H, 1H, 3Jm-H,o-H = 5.6 Hz, 3Jm-H,m-H’ = 2.3 Hz, m-H of p-cymene),
H-2, H-3, H-4, H-5, H-6), 3.99 (dd, 1H, 2JH-6b,H-6a = 9.7 Hz, 4.95 (d, 1H, 3JH-1,H-2 = 4.1 Hz, H-1), 5.04 (d, 1H, 3JH-1,H-2 =
3JH-6b,H-5 = 2.7 Hz, H-6), 4.19 (dd, 1H, 2JH-6b,H-6a = 11.0 Hz, 3.9 Hz, H-1), 5.05 (d, 1H, 3JH-1,H-2 = 3.5 Hz, H-1), 5.06–5.09
3JH-6b,H-5 = 2.4 Hz, H-6), 4.25 (m, 1H, H-5), 4.42 (m, 1H, (2H, H-1, o-H of p-cymene), 5.14–5.18 (2H, H-1, o-H’ of
H-5A), 4.50 (m, 1H, H-5B), 4.85 (d, 1H, 3JH-1,H-2 = 4.7 Hz, p-cymene), 5.26–5.29 (m, 1H, m-H’ of p-cymene), 5.36 (d, 1H,
H-1), 4.98 (d, 1H, 3JH-1,H-2 = 2.6 Hz, H-1), 5.06 (d, 1H, 3JH-1,H-2 = 4.1 Hz, H-1), 7.45–7.56 (3H, m-H, p-H), 7.91–7.96
3JH-1,H-2 = 3.7 Hz, H-1), 5.08 (d, 1H, 3JH-1,H-2 = 3.6 Hz, H-1), (2 H, o-H) ppm; 13C{1H} NMR (125.8 MHz, CDCl3, 25 °C) δ
5.11 (d, 1H, 3JH-1,H-2 = 3.1 Hz, H-1), 5.15 (d, 1H, 3JH-1,H-2 = (assignment by HSQC) = 16.32 (CH3 of p-cymene), 21.04,
3.1 Hz, H-1), 5.21 (d, 1H, 3JH-1,H-2 = 3.1 Hz, H-1), 7.33–7.45 21.10 (CH3iPr of p-cymene), 27.26 (d, 1JC,P = 27.8 Hz, C-6A),
(3H, m-H, p-H), 7.97 (ddd, 2H, 3Jo-H,P = 12.1 Hz, 3Jo-H,m-H = 27.36 (d, 1JC,P = 23.8 Hz, C-6B), 29.50 (CH of p-cymene),
6.9 Hz, 3Jo-H,p-H = 1.0 Hz, o-H) ppm; 13C{1H} NMR (75.5 55.99, 56.99, 57.61, 57.74, 57.77, 57.83, 58.05, 58.13, 58.16,
MHz, CDCl3, 25 °C) δ (assignment by HMQC) 27.94–28.09 58.26, 58.33, 59.00, 59.69, 60.01, 60.24, 60.44, 60.61, 60.64,
(m, C-6A,B), 57.89, 58.29 [×2], 58.59 [×2], 58.62 [×2], 59.01, 60.81, 63.79 (d, 2JC,P = 9.4 Hz, C-5A), 68.48 (d, 2JC,P = 10.1
59.05, 59.11, 59.25 [×2], 60.77, 60.98, 61.04, 61.32, 61.36, Hz, C-5B), 69.88 [×2] (C-6), 69.94 [×2], 70.39 (C-5), 70.46,
61.65, 61.71 (OMe), 65.36 (d, 2JC,P = 8.6 Hz, C-5B), 69.30 (d, 70.55 (C-6), 70.70 (C-5), 70.82 (C-6), 71.76 (C-5), 76.84,
2JC,P = 3.9 Hz, C-5A), 70.80, 71.09 [×2], 71.26, 71.52 (C-5), 78.21, 79.16, 79.80 [×2], 79.93, 80.09, 80.34 [×2], 80.45, 80.61,
71.10, 71.36 [×2], 71.43, 71.61 (C-6), 79.15, 79.39, 79.91, 80.68, 81.01, 81.20, 81.32 [×2], 81.61 [×2], 81.93, 82.74, 84.46,
80.03, 80.12, 80.82, 80.87, 81.19, 81.32, 81.42, 81.49, 81.84 87.88 (C-2, C-3, C-4, Cortho of p-cymene), 88.64, 90.43 (Cmeta
[×2], 81.89 [×2], 82.10, 82.24, 82.35, 82.41, 83.53, 84.17 (C-2, of p-cymene), 91.55 (Cipso of p-cymene), 95.27, 96.29, 96.73,
C-3, C-4), 96.98, 97.26, 98.79, 98.97, 99.36, 99.47, 99.64 (C-1), 98.54, 98.74, 98.92 [×2] (C-1), 109.23 (Cipso of p-cymene),
128.57 (Cpara), 128.97 (d, 3JC,P = 5.8 Hz, Cmeta), 131.46 (d, 127.74, 127.81 (Cmeta), 129.17 (Cpara), 130.30, 130.35 (Cortho),
1JC,P = 50.6 Hz, Cipso), 132.53 (d, 2JC,P = 10.5 Hz, Cortho) ppm; 132.65 (d, 1JC,P = 38.3 Hz, Cipso) ppm; 31P{1H} NMR (161.9
31P{1H} NMR (121.5 MHz CDCl3, 25 °C) δ 19.8 (s) ppm; MS MHz, CDCl3, 25 °C) δ 20.4 (s) ppm; elemental analysis (%)
(ESI–TOF): m/z (%): 1673.52 (40) [M + Na]+. We do not calcd for C77H125Cl2O33PRu·CH2Cl2 (1781.75 + 84.93): C,
2401

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
50.19; H, 6.86; found: C, 50.05; H, 6.80; MS (ESI-TOF): m/z 10a and 10b: A solution of HUGPHOS-2 (0.100 g, 0.07 mmol)
(%): 1803.62 (100) [M + Na]+. 8: mp 210 °C; 1H NMR (500.1 in CH2Cl2 (5 mL) was added dropwise to a solution of
MHz, CDCl3, 25 °C) δ (assignment by combined COSY, [Rh(CO)2Cl]2 (0.016 g, 0.04 mmol) in CH2Cl2 (5 mL) under
ROESY and HSQC) 0.94 (d, 3H, 3JCH3,CH = 7.1 Hz, CH3iPr of vigorous stirring at room temperature. The reaction mixture was
p-cymene), 1.05 (d, 3H, 3JCH3,CH = 7.1 Hz, CH3iPr’ of stirred for 1 h before being evaporated to dryness in vacuo to
p-cymene), 1.73 (s, 3H, CH3 of p-cymene), 2.28 (sept, 1H, afford quantitatively a mixture of 10a and 10b (10a/10b, 85:15,
3JCH,CH3 = 7.1 Hz, CHiPr of p-cymene), 2.50 (dt, 1H, 0.114 g, 99%) as a brown solid. Rf (SiO2) = dec; mp > 250 °C;
2JH-6a,H-6b = 18.2 Hz, 2JH-6a,P = 3JH-6a,H-5 = 7.2 Hz, H-6aA), Selected spectroscopic data: 13C{1H} NMR (125.8 MHz,
2.59 (dd, 1H, 3JH-2,H-1 = 3.1 Hz, 3JH-2,H-3 = 9.9 Hz, H-2A), CDCl3, 25 °C) δ 181.12–182.82 (m, CO), 187.24–189.73 (m,
2.75 (ddd, 1H, 2JH-6a,H-6b = 14.3 Hz, 2JH-6a,P = 12.0 Hz, CO) ppm; 31P{1H} NMR (161.9 MHz, CDCl3, 25 °C) δ 13.9
3JH-6a,H-5 = 2.6 Hz, H-6aB), 2.88 (t, 1H, 3JH-4,H-3 = 3JH-4,H-5 = (10b, d, 1JP,Rh = 121 Hz), 20.1 (10a, d, 1JP,Rh = 124 Hz) ppm;
9.5 Hz, H-4A), 3.12–3.27 (7H, H-2, H-6bB), 3.35 (s, 3H, OMe), IR: 2090 (s, CO), 2005 (s, CO), 1985 (s, CO) cm−1; elemental
3.36 (s, 3H, OMe), 3.38 (s, 3H, OMe), 3.39 (s, 3H, OMe), 3.40 analysis (%) calcd for C69H111ClO35PRh·3CH2Cl2 (1669.93 +
(s, 3H, OMe), 3.41 (s, 3H, OMe), 3.45 (s, 3H, OMe), 3.46 (s, 254.80): C 44.99, H 6.31 found: C 45.01, H 6.99; MS
3H, OMe), 3.48 (s, 6H, OMe), 3.49 (s, 3H, OMe), 3.53 (s, 3H, (ESI–TOF): m/z (%): 1605.58 (100) [M – CO – Cl]+, 1663.54
OMe), 3.56 (s, 3H, OMe), 3.57 (s, 3H, OMe), 3.58 (s, 3H, (20) [M – CO + Na]+; MS (ESI–TOF): m/z (%): 1675.55 (100)
OMe), 3.61 (s, 3H, OMe), 3.62 (s, 3H, OMe), 3.63 (s, 3H, [M – CO + Cl]−; MS (MALDI–TOF): m/z (%): 1605.58 (100)
OMe), 3.64 (s, 3H, OMe), 3.33–3.87 (26H, H-3, H-4, H-5, [M – CO – Cl]+, 1719.69 (5) [M + CO + Na]+.
H-6), 3.92 (dd, 1H, 2JH-6a,H-6b = 10.3 Hz, 3JH-6a,H-5 = 2.5 Hz,
H-6), 4.10 (d, 1H, 2JH-6a,H-6b = 10.3 Hz, H-6), 4.21–4.32 (2H, 11: A solution of [Rh(CO)2Cl]2 (0.080 g, 0.20 mmol) in
H-5B, H-6), 4.35 (ddd, 1H, 2JH-5,H-6a = 7.2 Hz, 2JH-5,H-6b = CH2Cl2 (7 mL) was added dropwise to a solution of
26.1 Hz, 3JH-5,H-4 = 10.9 Hz, H-5A), 4.73 (d, 1H, 3JH-1,H-2 = HUGPHOS-2 (0.100 g, 0.07 mmol) in CH2Cl2 (5 mL) under
5.1 Hz, H-1), 4.74 (d, 1H, 3Jo-H,m-H = 5.9 Hz, o-H’ of vigorous stirring at room temperature. After 1 h, the volume of
p-cymene), 4.95 (d, 1H, 3Jm-H,o-H = 5.9 Hz, m-H’ of p-cymene), the reaction mixture was reduced to 5 mL and pentane (40 mL)
4.96 (d, 1H, 3JH-1,H-2 = 2.4 Hz, H-1), 4.98 (d, 1H, 3JH-1,H-2 = was added in order to precipitate unreacted [Rh(CO)2Cl]2,
2.7 Hz, H-1), 5.06 (d, 1H, 3JH-1,H-2 = 3.1 Hz, H-1), 5.10 (d, 1H, which was removed by filtration on a pad of Celite. The
3JH-1,H-2 = 3.2 Hz, H-1), 5.13 (d, 1H, 3Jm-H,o-H = 6.5 Hz, m-H resulting solution was evaporated to dryness in vacuo to afford
of p-cymene), 5.15 (d, 1H, 3JH-1,H-2 = 3.4 Hz, H-1), 5.16 (d, quantitatively 11 as a brown powder (0.103 g, 83%). mp dec
1H, 3JH-1,H-2 = 3.4 Hz, H-1), 5.25 (d, 1H, 3Jo-H,m-H = 6.5 Hz, >250 °C; 1H NMR (500.1 MHz, CDCl3, 25 °C) δ (assignment
o-H of p-cymene), 7.32–7.40 (3H, m-H, p-H), 8.03–8.11 (2H, by combined COSY and HSQC) = 1.91 (q, 1H, 2JH-6a,H-6b =
o-H) ppm; 13C{1H} NMR (125.8 MHz, CDCl3, 25 °C) δ 2JH-6a,P = 3JH-6a,H-5 = 15.4 Hz, H-6aB), 2.17 (t, 1H, 2JH-6a,H-6b
(assignment by HSQC) 16.77 (CH3 of p-cymene), 20.80, 21.24 = 2JH-6a,P = 14.2 Hz, H-6aA), 3.02 (m, 1H, H-6bB), 3.20 (s, 3H,
(CH3iPr of p-cymene), 23.46 (d, 1JC,P = 25.8 Hz, C-6A), 28.57 OMe), 3.30 (s, 3H, OMe), 3.32 (s, 3H, OMe), 3.36 (s, 3H,
(d, 1JC,P = 26.0 Hz, C-6B), 28.95 (CH of p-cymene), 56.36, OMe), 3.45 (s, 6H, OMe), 3.46 (s, 3H, OMe), 3.48 (s, 3H,
56.97, 57.09, 57.63, 57.68, 57.83 [×2], 57.99, 58.03, 58.12, OMe), 3.50 (s, 6H, OMe), 3.52 (s, 3H, OMe), 3.53 (s, 3H,
58.19, 58.61, 59.40, 60.19, 60.31, 60.42, 60.46, 60.93, 60.97 OMe), 3.59 (s, 6H, OMe), 3.62 (s, 3H, OMe), 3.64 (s, 3H,
(OMe), 65.82 (d, 2JC,P = 11.1 Hz, C-5B), 67.61 (d, 2JC,P = 9.3 OMe), 3.65 (s, 3H, OMe), 3.68 (s, 3H, OMe), 3.76 (s, 3H,
Hz, C-5A), 69.61 (C-5), 69.63 (C-6), 69.75, 69.93 (C-5), 69.99, OMe), 3.13–3.79 (26H, H-2, H-3, H-4, H-6), 3.80–3.92 (4H,
70.06 [×2], 70.13 (C-6), 70.34, 70.96 (C-5), 74.88 (d, 3JC,P = H-6), 3.93–4.01 (4H, H-5, H-6), 4.07–4.13 (3H, H-5, H-6), 4.36
4.4 Hz, C-4A), 79.29, 79.34, 79.40, 79.55, 80.06 [×2], 80.48, (dt, 1H, 3JH-5,H-4 = 3JH-5,H-6b = 10.5 Hz, 3JH-5,H-6a = 15.4 Hz,
80.53, 80.62 [×2], 80.67, 80.69, 80.81, 80.85, 80.95, 81.23, H-5B), 4.95 (d, 1H, 3JH-1,H-2 = 3.7 Hz, H-1), 5.00 (d, 1H,
81.26, 81.41, 82.89 (C-2, C-3, C-4), 83.45, 83.65 (Cortho of 3JH-1,H-2 = 4.6 Hz, H-1), 5.03 (d, 1H, 3JH-1,H-2 = 3.7 Hz, H-1),
p-cymene), 83.84 (Cmeta of p-cymene), 84.43 (C-4B), 88.01 5.08–5.11 (3H, H-1), 5.20 (d, 1H, 3JH-1,H-2 = 3.7 Hz, H-1),
(Cmeta of p-cymene), 95.54 (C-1), 95.62 (Cipso of p-cymene), 5.35–5.45 (m, 1H, H-5A), 7.42–7.46 (3H, m-H, p-H), 7.82–7.87
96.42, 97.94, 98.35, 98.76 [×2], 98.86 (C-1), 108.11 (Cipso of (2H, o-H) ppm; 13C{1H} NMR (125.8 MHz, CDCl3, 25 °C) δ
p-cymene), 126.06, 126.13 (Cmeta), 128.94 (Cpara), 130.68, (assignment by HSQC) = 32.32 (d, 1JC,P = 29.3 Hz, C-6A),
130.82 (Cortho), 134.91 (d, 1JC,P = 38.5 Hz, Cipso) ppm; 35.77 (d, 1JC,P = 29.3 Hz, C-6B), 56.74, 57.18, 57.26, 57.63
31P{1H} NMR (161.9 MHz, CDCl3, 25ºC) δ 22.8 (s) ppm; [×2], 57.78, 57.91, 57.96, 57.99, 58.06, 58.08, 58.29, 60.13,
elemental analysis (%) calcd for C77H125Cl2O33PRu·CH2Cl2 60.31, 60.54 [×2], 60.56, 60.70, 60.83 (OMe), 63.30 (C-5A),
(1781.75 + 84.93): C, 50.19; H, 6.86; found: C, 50.03; H, 6.78; 69.43, 69.50, 69.68, 69.90, 69.94 (C-5), 70.01, 70.24, 70.44,
MS (ESI–TOF): m/z (%): 1803.62 (100) [M + Na]+.
70.60, 70.76 (C-6), 71.31 (d, 2JC,P = 15.9 Hz, C-5B), 78.57,
2402

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
6. Walker, S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2004, 43, 1871–1876.
79.04, 79.79 [×2], 80.17, 80.23 [×2], 80.47, 80.51, 80.57, 80.90,
81.05, 81.12, 81.32, 81.40, 81.68, 81.76, 82.14, 83.09 (C-2,
C-3, C-4), 84.17 (d, 3JC,P = 10.7 Hz, C-4B), 88.02 (d, 3JC,P =
4.6 Hz, C-4A), 96.39, 97.66, 97.70, 98.52, 98.66, 99.37, 99.79
(C-1), 127.62, 127.70 (Cmeta), 130.08 (Cpara), 130.56, 130.64
(Cortho), 135.13 (d, 1JC,P = 57.5 Hz, Cipso), 176.16 [×2] (d,
1JC,Rh = 77.2 Hz, CO), 177.63 (dd, 1JC,Rh = 71.9 Hz, 2JC,P =
22.8 Hz, CO) ppm; 31P{1H} NMR (161.9 MHz, CDCl3, 25 °C)
δ 40.5 (d, 1JP,Rh = 172 Hz) ppm; IR: 2086 (vs, CO), 2026 (vs,
CO), 2004 (s, CO) cm−1; We do not provide microanalytical
data for this compound because of strong hydration; MS
(ESI–TOF): m/z (%): 1799.44 (70) [M – Cl]+, 1857.40 (100)
[M + Na]+.
doi:10.1002/anie.200353615
7. Ohzu, Y.; Goto, K.; Kawashima, T. Angew. Chem., Int. Ed. 2003, 42,
5714–5717. doi:10.1002/anie.200352616
8. Iwasawa, T.; Komano, T.; Tajima, A.; Tokunaga, M.; Obora, Y.;
Fujihara, T.; Tsuji, Y. Organometallics 2006, 25, 4665–4669.
doi:10.1021/om060615q
9. Ohta, H.; Tokunaga, M.; Obora, Y.; Iwai, T.; Iwasawa, T.; Fujihara, T.;
Tsuji, Y. Org. Lett. 2007, 9, 89–92. doi:10.1021/ol0626138
10.Dodds, D. L.; Boele, M. D. K.; van Strijdonck, G. P. F.; de Vries, J. G.;
van Leeuwen, P. W. N. M.; Kamer, P. C. J. Eur. J. Inorg. Chem. 2012,
1660–1671. doi:10.1002/Ejic.201101271
11.Fujihara, T.; Yoshida, S.; Ohta, H.; Tsuji, Y. Angew. Chem., Int. Ed.
2008, 47, 8310–8314. doi:10.1002/anie.200802683
12.Snelders, D. J. M.; van Koten, G.; Klein Gebbink, R. J. M.
J. Am. Chem. Soc. 2009, 131, 11407–11416. doi:10.1021/ja904042h
13.Kwong, F. Y.; Chan, A. S. C. Synlett 2008, 1440–1448.
doi:10.1055/s-2008-1078425
General procedure for palladium-catalysed Heck cross-
coupling reactions: In an oven-dried Schlenk tube, a solution
of [Pd(OAc)2] in DMF, a solution of HUGPHOS-1/2 or WIDE-
PHOS ligands in DMF, aryl bromide (1 equiv), styrene
(2 equiv), Cs2CO3 (2 equiv), decane (internal reference) and ad-
ditional DMF were introduced under an inert atmosphere. The
reaction mixture was heated for 1 h. After cooling to room
temperature, a small amount (0.5 mL) of the resulting solution
was passed through a Millipore filter and analyzed by GC. Each
experiment was repeated twice and the conversion values given
in Table 3 and Table 4 correspond to the mean value from two
catalytic tests.
14.Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47,
6338–6361. doi:10.1002/anie.200800497
15.Monnereau, L.; Sémeril, D.; Matt, D.; Toupet, L. Chem. – Eur. J. 2010,
16, 9237–9247. doi:10.1002/Chem.200903390
16.Pruett, R. L.; Smith, J. A. J. Org. Chem. 1969, 34, 327–330.
doi:10.1021/jo01254a015
17.Dabbawala, A. A.; Bajaj, H. C.; Jasra, R. V. J. Mol. Catal. A 2009, 302,
97–106. doi:10.1016/j.molcata.2008.12.002
18.Dabbawala, A. A.; Jasra, R. V.; Bajaj, H. C. Catal. Commun. 2010, 11,
616–619. doi:10.1016/j.catcom.2010.01.007
19.Kubis, C.; Ludwig, R.; Sawall, M.; Neymeyr, K.; Börner, A.;
Wiese, K.-D.; Hess, D.; Franke, R.; Selent, D. ChemCatChem 2010, 2,
287–295. doi:10.1002/cctc.200900292
20.Kubis, C.; Selent, D.; Sawall, M.; Ludwig, R.; Neymeyr, K.;
Baumann, W.; Franke, R.; Börner, A. Chem. – Eur. J. 2012, 18,
8780–8794. doi:10.1002/chem.201200603
Supporting Information
Supporting Information File 1
Copies of NMR spectra for compounds 2, 3, 6, 7, 8, 10a
and 10b and 11.
21.Tricas, H.; Diebolt, O.; van Leeuwen, P. W. N. M. J. Catal. 2013, 298,
198–205. doi:10.1016/j.jcat.2012.11.031
22.van Leeuwen, P. W. N. M.; Claver, C. Rhodium Catalyzed
Hydroformylation; Kluwer Academic Publishers: Dordrecht, 2002.
23.Selent, D.; Wiese, K.-D.; Röttger, D.; Börner, A. Angew. Chem., Int. Ed.
2000, 39, 1639–1641.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-10-249-S1.pdf]
doi:10.1002/(Sici)1521-3773(20000502)39:9<1639::Aid-Anie1639>3.0.
Co;2-C
Acknowledgements
This research was supported by the Région Alsace and the
Centre International pour la Recherche aux Frontières de la
Chimie (CIRFC).
24.Breit, B.; Winde, R.; Mackewitz, T.; Paciello, R.; Harms, K.
Chem. – Eur. J. 2001, 7, 3106–3121.
doi:10.1002/1521-3765(20010716)7:14<3106::Aid-Chem3106>3.0.Co;
2-Y
25.Baber, R. A.; Clarke, M. L.; Heslop, K. M.; Marr, A. C.; Orpen, A. G.;
Pringle, P. G.; Ward, A.; Zambrano-Williams, D. E. Dalton Trans. 2005,
1079–1085. doi:10.1039/b418259f
References
1. Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10–11.
26.Clarke, M. L. Curr. Org. Chem. 2005, 9, 701–718.
doi:10.2174/1385272053764980
doi:10.1021/jo9820059
2. Stambuli, J. P.; Stauffer, S. R.; Shaughnessy, K. H.; Hartwig, J. F.
J. Am. Chem. Soc. 2001, 123, 2677–2678. doi:10.1021/ja0058435
3. Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989–7000.
doi:10.1021/ja010988c
27.Rafter, E.; Gilheany, D. G.; Reek, J. N. H.; van Leeuwen, P. W. N. M.
ChemCatChem 2010, 2, 387–391. doi:10.1002/cctc.200900313
28.Dabbawala, A. A.; Jasra, R. V.; Bajaj, H. C. Catal. Commun. 2011, 12,
403–407. doi:10.1016/j.catcom.2010.10.026
4. Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L.
J. Am. Chem. Soc. 1999, 121, 9550–9561. doi:10.1021/ja992130h
5. Kataoka, N.; Shelby, Q.; Stambuli, J. P.; Hartwig, J. F. J. Org. Chem.
2002, 67, 5553–5566. doi:10.1021/jo025732j
29.Dabbawala, A. A.; Bajaj, H. C.; Rao, G. V. S.; Abdi, S. H. R.
Appl. Catal., A: Gen. 2012, 419–420, 185–193.
doi:10.1016/j.apcata.2012.01.027
2403

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
30.Bellini, R.; Reek, J. N. Chem. – Eur. J. 2012, 18, 7091–7099.
doi:10.1002/chem.201200225
53.Engeldinger, E.; Armspach, D.; Matt, D.; Jones, P. G. Chem. – Eur. J.
2003, 9, 3091–3105. doi:10.1002/chem.200304806
54.Li Wu, M.; Desmond, M. J.; Drago, R. S. Inorg. Chem. 1979, 18,
679–686. doi:10.1021/ic50193a030
31.Bellini, R.; Chikkali, S. H.; Berthon-Gelloz, G.; Reek, J. N. H.
Angew. Chem., Int. Ed. 2011, 50, 7342–7345.
doi:10.1002/Anie.201101653
55.Uguagliati, P.; Deganello, G.; Busetto, L.; Belluco, U. Inorg. Chem.
1969, 8, 1625–1630. doi:10.1021/ic50078a011
32.Bocokić, V.; Kalkan, A.; Lutz, M.; Spek, A. L.; Gryko, D. T.;
Reek, J. N. H. Nat. Commun. 2013, 4, No. 2670.
doi:10.1038/Ncomms3670
56.Deganello, G.; Uguagliati, P.; Crociani, B.; Belluco, U. J. Chem. Soc. A
1969, 2726–2729. doi:10.1039/J19690002726
33.Agbossou, F.; Carpentier, J.-F.; Mortreux, A. Chem. Rev. 1995, 95,
2485–2506. doi:10.1021/Cr00039a008
57.Wood, C. D.; Garrou, P. E. Organometallics 1984, 3, 170–174.
doi:10.1021/Om00079a030
34.Claver, C.; Diéguez, M.; Pàmies, O.; Castillón, S.
Top. Organomet. Chem. 2006, 18, 35–64. doi:10.1007/3418_016
35.Klosin, J.; Landis, C. R. Acc. Chem. Res. 2007, 40, 1251–1259.
doi:10.1021/Ar7001039
58.Leigh, J. S.; Whitmire, K. H. Acta Crystallogr., Sect. C 1989, 45,
210–212. doi:10.1107/S0108270188010960
59.Bartik, T.; Krümmung, T.; Happ, B.; Sieker, A.; Markó, L.; Boese, R.;
Ugo, R.; Zucchi, C.; Pályi, G. Catal. Lett. 1993, 19, 383–389.
doi:10.1007/Bf00767082
36.Gual, A.; Godard, C.; Castillón, S.; Claver, C. Tetrahedron: Asymmetry
2010, 21, 1135–1146. doi:10.1016/j.tetasy.2010.05.037
37.Franke, R.; Selent, D.; Börner, A. Chem. Rev. 2012, 112, 5675–5732.
doi:10.1021/cr3001803
60.Miessler, G. L.; Tarr, D. A. Inorganic Chemistry; Pearson Prentice Hall:
Upper Saddle River, NJ, 2011; pp 534–538.
61.Adint, T. T.; Wong, G. W.; Landis, C. R. J. Org. Chem. 2013, 78,
4231–4238. doi:10.1021/jo400525w
38.Engeldinger, E.; Poorters, L.; Armspach, D.; Matt, D.; Toupet, L.
Chem. Commun. 2004, 634–635. doi:10.1039/B315802K
39.Gramage-Doria, R.; Rodriguez-Lucena, D.; Armspach, D.; Egloff, C.;
Jouffroy, M.; Matt, D.; Toupet, L. Chem. – Eur. J. 2011, 17, 3911–3921.
doi:10.1002/chem.201002541
62.Nelsen, E. R.; Landis, C. R. J. Am. Chem. Soc. 2013, 135, 9636–9639.
doi:10.1021/Ja404799m
63.Noonan, G. M.; Cobley, C. J.; Mahoney, T.; Clarke, M. L.
Chem. Commun. 2014, 50, 1475–1477. doi:10.1039/C3cc48823c
64.Ziegler, C. B., Jr.; Heck, R. F. J. Org. Chem. 1978, 43, 2941–2946.
doi:10.1021/Jo00409a001
40.Machut-Binkowski, C.; Legrand, F.-X.; Azaroual, N.; Tilloy, S.;
Monflier, E. Chem. – Eur. J. 2010, 16, 10195–10201.
doi:10.1002/Chem.201000379
65.Heck, R. F.; Nolley, J. P. J. Org. Chem. 1972, 37, 2320–2322.
doi:10.1021/jo00979a024
41.Legrand, F.-X.; Six, N.; Slomianny, C.; Bricout, H.; Tilloy, S.;
Monflier, E. Adv. Synth. Catal. 2011, 353, 1325–1334.
doi:10.1002/Adsc.201000917
66.Gillie, A.; Stille, J. K. J. Am. Chem. Soc. 1980, 102, 4933–4941.
doi:10.1021/Ja00535a018
42.Tran, D. N.; Legrand, F.-X.; Menuel, S.; Bricout, H.; Tilloy, S.;
Monflier, E. Chem. Commun. 2012, 48, 753–755.
doi:10.1039/C1cc16326d
67.Sliger, M. D.; Broker, G. A.; Griffin, S. T.; Rogers, R. D.;
Shaughnessy, K. H. J. Organomet. Chem. 2005, 690, 1478–1486.
doi:10.1016/J.Jorganchem.2004.12.022
43.Takashima, Y.; Uramatsu, K.; Jomori, D.; Harima, A.; Otsubo, M.;
Yamaguchi, H.; Harada, A. ACS Macro Lett. 2013, 2, 384–387.
doi:10.1021/Mz4001942
68.Gramage-Doria, R.; Armspach, D.; Matt, D.; Toupet, L. Chem. – Eur. J.
2012, 18, 10813–10816. doi:10.1002/Chem.201201403
69.Sémeril, D.; Lejeune, M.; Jeunesse, C.; Matt, D. J. Mol. Catal. A 2005,
239, 257–262. doi:10.1016/j.molcata.2005.06.024
70.El Moll, H.; Sémeril, D.; Matt, D.; Youinou, M.-T.; Toupet, L.
Org. Biomol. Chem. 2009, 7, 495–501. doi:10.1039/B813373E
71.Shaughnessy, K. H.; Kim, P.; Hartwig, J. F. J. Am. Chem. Soc. 1999,
121, 2123–2132. doi:10.1021/ja983419m
44.Jouffroy, M.; Gramage-Doria, R.; Armspach, D.; Sémeril, D.;
Oberhauser, W.; Matt, D.; Toupet, L. Angew. Chem., Int. Ed. 2014, 53,
3937–3940. doi:10.1002/anie.201311291
45.Gramage-Doria, R. Large Cavity Cyclodextrin-Based Macrocyclic
Ligands: Synthesis, Coordination and Catalytic Properties. Ph.D.
Thesis, Université de Strasbourg , Strasbourg, 2012.
46.Engeldinger, E.; Armspach, D.; Matt, D.; Jones, P. G.; Welter, R.
Angew. Chem., Int. Ed. 2002, 41, 2593–2596.
72.Kanagaraj, K.; Pitchumani, K. Chem. – Eur. J. 2013, 19, 14425–14431.
doi:10.1002/Chem.201301863
73.Ben-David, Y.; Portnoy, M.; Gozin, M.; Milstein, D. Organometallics
1992, 11, 1995–1996. doi:10.1021/om00042a008
74.Crisp, G. T. Chem. Soc. Rev. 1998, 27, 427–436.
doi:10.1039/A827427Z
doi:10.1002/1521-3773(20020715)41:14<2593::Aid-Anie2593>3.0.Co;
2-M
47.Gramage-Doria, R.; Armspach, D.; Matt, D. Coord. Chem. Rev. 2013,
257, 776–816. doi:10.1016/J.Ccr.2012.10.006
75.Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009–3066.
doi:10.1021/Cr9903048
48.Kaufmann, W.; Venanzi, L. M.; Albinati, A. Inorg. Chem. 1988, 27,
1178–1187. doi:10.1021/Ic00280a018
76.Whitcombe, N. J.; Hii, K. K.; Gibson, S. E. Tetrahedron 2001, 57,
7449–7476. doi:10.1016/S0040-4020(01)00665-2
77.Surawatanawong, P.; Fan, Y.; Hall, M. B. J. Organomet. Chem. 2008,
693, 1552–1563. doi:10.1016/j.jorganchem.2008.01.034
78.Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314–321.
doi:10.1021/ar980063a
49.Espinet, P.; Martínez-Ilarduya, J. M.; Pérez-Briso, C.; Casado, A. L.;
Alonso, M. A. J. Organomet. Chem. 1998, 551, 9–20.
doi:10.1016/S0022-328X(97)00424-5
50.Bartolomé, C.; Espinet, P.; Vicente, L.; Villafañe, F.;
Charmant, J. P. H.; Orpen, A. G. Organometallics 2002, 21,
3536–3543. doi:10.1021/om020198r
79.Knowles, J. P.; Whiting, A. Org. Biomol. Chem. 2007, 5, 31–44.
doi:10.1039/B611547k
51.Vicente, J.; Arcas, A. Coord. Chem. Rev. 2005, 249, 1135–1154.
doi:10.1016/j.ccr.2004.11.005
80.Jutand, A. Mechanisms of the Mizoroki–Heck Reaction; John Wiley &
Sons, Ltd.: Chichester, United Kingdom, 2009.
52.Gramage-Doria, R.; Armspach, D.; Matt, D.; Toupet, L.
Angew. Chem., Int. Ed. 2011, 50, 1554–1559.
doi:10.1002/anie.201005169
2404

Beilstein J. Org. Chem. 2014, 10, 2388–2405.
81.Sumimoto, M.; Kuroda, T.; Yokogawa, D.; Yamamoto, H.; Hori, K.
J. Organomet. Chem. 2012, 710, 26–35.
doi:10.1016/J.Jorganchem.2012.03.008
82.van Strijdonck, G. P. F.; Boele, M. D. K.; Kamer, P. C. J.;
de Vries, J. G.; van Leeuwen, P. W. N. M. Eur. J. Inorg. Chem. 1999,
1073–1076.
doi:10.1002/(SICI)1099-0682(199907)1999:7<1073::AID-EJIC1073>3.
0.CO;2-T
83.Engeldinger, E.; Armspach, D.; Matt, D. Angew. Chem., Int. Ed. 2001,
40, 2526–2529.
doi:10.1002/1521-3773(20010702)40:13<2526::AID-ANIE2526>3.0.CO
;2-T
84.Wong, Y. T.; Yang, C.; Ying, K.-C.; Jia, G. Organometallics 2002, 21,
1782–1787. doi:10.1021/Om010995+
85.Schlatter, A.; Kundu, M. K.; Woggon, W.-D. Angew. Chem., Int. Ed.
2004, 43, 6731–6734. doi:10.1002/anie.200460102
86.Liu, K.; Häussinger, D.; Woggon, W.-D. Synlett 2007, 2298–2300.
doi:10.1055/s-2007-985569
87.Schlatter, A.; Woggon, W.-D. Adv. Synth. Catal. 2008, 350, 995–1000.
doi:10.1002/adsc.200700558
88.Guitet, M.; Zhang, P.; Marcelo, F.; Tugny, C.; Jiménez-Barbero, J.;
Buriez, O.; Amatore, C.; Mouriès-Mansuy, V.; Goddard, J.-P.;
Fensterbank, L.; Zhang, Y.; Roland, S.; Ménand, M.; Sollogoub, M.
Angew. Chem., Int. Ed. 2013, 52, 7213–7218.
doi:10.1002/anie.201301225
89.Hartley, F. R. The Chemistry of Platinum and Palladium; Wiley: New
York, 1973.
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.10.249
2405