A chiral bis(arsine) ligand: Synthesis and applications in palladium-catalyzed asymmetric allylic alkylations

Article abstract of DOI:10.1021/om400144s

The new chiral bis(arsine) ligand N,N′-bis[2′-(diphenylarsino) benzoyl]-(1R,2R)-cyclohexanediamine (BiAsBA, 3), based on the backbone of the Trost modular ligand (TML), was synthesized in three steps. A useful approach to introduce the -AsPh₂ g

Full text of DOI:10.1021/om400144s

Article
pubs.acs.org/Organometallics
A Chiral Bis(arsine) Ligand: Synthesis and Applications in Palladium-
Catalyzed Asymmetric Allylic Alkylations
†
,‡
,†
́
Paula M. Uberman, Mino R. Caira,* and Sandra E. Martın*
†
́
́
INFIQC-CONICET, Departamento de Quımica Organ
́
ica, Facultad de Ciencias Quımicas, Universidad Nacional de Cor
́
doba,
Medina Allende y Haya de la Torre, X5000HUA Cor
́
doba, Argentina
‡Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
S
* Supporting Information
ABSTRACT: The new chiral bis(arsine) ligand N,N′-bis[2′-
(diphenylarsino)benzoyl]-(1R,2R)-cyclohexanediamine (BiAsBA,
3), based on the backbone of the Trost modular ligand (TML),
was synthesized in three steps. A useful approach to introduce
the −AsPh2 group on arsine ligands by Pd-catalyzed arsination
was used. The molecular structure and configuration of the
BiAsBA ligand was determined by single-crystal X-ray crystallog-
raphy. In the asymmetric allylic alkylation of 1,3-diphenyl-2-
propenyl acetate with dimethyl malonate very high to complete
conversion and modest enantioselectivity were achieved. Despite the low enantioselectivity obtained, the bis(arsine) ligand
BiAsBA showed significant potential, since it provided a higher ee value than the phosphorus-containing homologous “Trost
standard ligand” (TSL) with the same substrate.
ransition-metal-catalyzed asymmetric allylic substitutions
Thave become some of the most powerful tools for
asymmetric C−C and C−heteroatom bond formation,1,2
finding wide application in the synthesis of valuable molecules
and complex natural products.3 In the past few decades, a large
number of chiral ligands have been designed and applied to Pd-
catalyzed asymmetric allylic substitutions, affording excellent
enantioselectivity.1,2 Chiral diphosphine ligands have been one
of the largest classes of ligands used in asymmetric
substitutions.2c
Trost and co-workers have reported the development and
application of the ligand (R,R)-1, normally referred to as the
“Trost standard ligand” (TSL) (Figure 1). This ligand was
especially successful with the previously challenging cyclic
allylic substrates and played a crucial role in the improvement
of Pd-catalyzed asymmetric allylic substitutions.4 Following this
initial report, this ligand has been effectively applied to a large
number and range of asymmetric allylic alkylation reactions.
Moreover, the Trost modular ligand (TML) system 2 (Figure
1) has been expanded and developed, resulting in a class of
ligands broadly applied in asymmetric transition-metal-
catalyzed C−C bond formation reactions.5 However, to our
knowledge there have been no reports of arsine ligands derived
from the TML system.
pure arsine ligands in asymmetric catalysis remains at a
primitive stage. Likewise, the use of chiral arsine ligands still
remains unexplored in Pd-catalyzed allylic alkylation. Only
8
diastereoselective allylic alkylation with azlactones using AsPh3
and the influence of the ligands, including AsPh3, in (η3-3-
methylbutenyl)palladium (L2) complexes have been described.9
Arsine ligands, to a large extent, have not yet been developed,
probably mainly due to the lack of readily available As-
containing precursor compounds.10 The development of new
methods to obtain arsines is thus increasingly recognized as
central in the synthesis of new ligands. We have developed a
versatile methodology that allows for C−As bond formation
through a cross-coupling Pd-catalyzed reaction with the arsine−
stannane n-Bu3SnAsPh2 (4) in a one-pot, two-step reaction.11,12
This methodology allowed the synthesis of functionalized
arsines and arsine ligands.6,11b
Herein, we describe the synthesis and application of the
novel chiral bis(arsine) ligand BiAsBA (3; Figure 1). This ligand
was developed on the basis of the successful backbone of TSL,
having in mind that the steric and electronic properties of the
ligands could be tuned by changing the heteroatom. The
BiAsBA ligand structure and configuration have been confirmed
by single-crystal X-ray crystallography. The chiral bis(arsine)
ligand 3 was evaluated in the Pd-catalyzed asymmetric allylic
alkylation using the benchmarking reaction with 1,3-diphenyl-2-
propenyl acetate and dimethyl malonate.
Arsines have been shown to be excellent supporting ligands,
and there are several examples where arsine complexes give
catalysts more active or selective than phosphines in transition-
metal-catalyzed reactions.6 In contrast to the many chiral
phosphine-based ligands that have been synthesized, relatively
few arsine ligands have been prepared and applied in
asymmetric catalysis.7 The application of enantiomerically
Received: February 19, 2013
© XXXX American Chemical Society
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Figure 1. Phosphine and arsine Trost modular ligands.
Scheme 1. Synthetic Strategies for the Chiral Bis(arsine) Ligand BiAsBA (3)
a
Scheme 2. Synthesis of Bis(arsine) Ligand 3 by Strategy 1
a
Reagents and conditions: (a) H2SO4, MeOH, reflux, overnight; (b) n-Bu3SnAsPh2 (4), (Ph3P)2PdCl2, toluene, 100 °C, 24 h; (c) t-BuOK, Et2O,
H2O, 25 °C, 96 h; (d) 5, DCC, HOBt, CH2Cl2/H2O, 24 h; (e) n-Bu3SnAsPh2 (4), (Ph3P)2PdCl2, PPh3, LiCl, DMF, 120 °C, 24 h. All yields
correspond to isolated yields.
providing examples of the synthesis of Ph2AsAr from sterically
hindered and ortho-substituted arenes.11b By this approach the
arsination reaction was carried out to obtain the new
bis(arsine) chiral ligand 3. In Scheme 2 are summarized the
results achieved by strategy 1.
Direct arsination of carboxylic acid 3 was not successful
(Scheme 2).15 After a Fischer sterification, 7 was obtained.
When the ester 7 was allowed to react with stannane 4 in
toluene with (PPh3)2PdCl2, methyl 2-(diphenylarsino)benzoate
(8) was obtained (75%). As an alternative, methyl 2-
(trifluoromethylsulfonyloxy)benzoate (10) was evaluated. The
use of triflates in Pd-catalyzed arsination with the arsine−
stannane 4 was previously reported.12b The arsination was
carried out under conventional conditions with triflate 10 and
stannane 4 catalyzed by (PPh3)2PdCl2 in DMF. However, the
yield of the reaction was lower than that with iodide ester 7 (8,
35%).
RESULTS AND DISCUSSION
■
Synthesis and Characterization of the Chiral Bis-
(arsine) Ligand BiAsBA (3). For the synthesis of the new
bis(arsine) ligand BiAsBA (3), two synthetic strategies were
proposed, which are shown in Scheme 1. The key step in the
proposed methodologies was to achieve the introduction of the
diphenylarsine group. The main difference between them was
the stage at which the introduction of the diphenylarsine group
(−AsPh2) took place.
Both methods used commercially available, inexpensive
starting materials. From ( )-trans-1,2-diaminocyclohexane
and L-tartaric acid as resolution agent the salt (1R,2R)-
(2R,3R)-5 was obtained in high yield and diastereomeric excess
(46% yield, 99% de).13 The tartrate salt 5 was directly
derivatized to afford the corresponding bis(amide), avoiding
the regeneration of enantiopure free 1,2-diaminocyclohexane,
which is troublesome due to its high solubility in water.14
In previous works,11,12 we described the Pd-catalyzed cross-
coupling arsination with the stannane n-Bu3SnAsPh2 (4),
For hydrolyses of arsine ester 8, the conventional methods
with inorganic bases in water or MeOH were not effective, due
to the low solubility of 8 in those media. Using the
B
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a
Scheme 3. Synthesis of Bis(arsine) Ligand 3 by Strategy 2
a
Reagents and conditions: (a) SOCl2, reflux, 4 h; (b) (1R,2R)-(2R,3R)-5, NaOH, H2O, Et2O, overnight; (c) Pd-catalyzed arsination with n-
Bu3SnAsPh2 (4) (see Table 1).
methodology developed for sterically hindered esters with t-
BuOK/H2O in ethyl ether, hydrolysis was successfully
accomplished (Scheme 2).16 Finally, the coupling of carboxylic
acid 9 with the salt (1R,2R)-(2R,3R)-5 to give the new chiral
bis(arsine) 3 was performed, and the BiAsBA ligand 3 was
obtained in modest yield (25%).
Table 1. Pd-Catalyzed Arsination of Bis(amide) 12 with n-
Bu3SnAsPh2 (4) Catalyzed by (PPh3)2PdCl2
a
In order to improve the overall yield of chiral bis(arsine)
ligand 3 synthesis, an alternative strategy was proposed
(strategy 2, Scheme 3). The approach involved in a first step
the formation of chiral bis(amide) 12, from the acid chloride 11
and the diastereomerically pure salt (1R,2R)-(2R,3R)-5,
followed by the introduction of the −AsPh2 group by Pd-
catalyzed arsination. Acid chloride 11 was quantitatively
obtained and allowed to react under basic conditions with
(1R,2R)-(2R,3R)-5. The novel bis(amide) iodide 12, which
precipitated from the reaction mixture, was obtained in 95%
isolated yield. As a final step, direct arsination of bis(amide) 12
was carried out following the methodology previously described
for a Pd-catalyzed coupling reaction with stannane 4 in a one-
pot, two-step procedure. Several experiments were performed
to establish the optimal reaction conditions for the
unprecedented disubstitution Pd-catalyzed arsination reaction.
The most relevant results are shown in Table 1.
Under the most efficient conditions obtained in the Pd-
catalyzed arsination with ester 8 (strategy 1), the reaction did
not occur, since bis(amide) 12 was not soluble in toluene
(entry 1, Table 1). Likewise, when the reaction was carried out
in DMF, bis(arsine) ligand 3 was not obtained. Instead, the
dehalogenated bis(amide) 13 was obtained in 70% yield (entry
2, Table 1). An important development in Pd-catalyzed cross-
coupling reactions involves the use of Cu(I) as cocatalyst,
which increases the rates and yields.17 When CuI and PPh3
were added to the reaction mixture, ligand 3 was obtained in
32% yield (entry 3, Table 1). Furthermore, when the reaction
was performed in DMF with PPh3 and CsF as an activator of
the organotin reagent,18 no desired coupling product was
obtained (entry 4, Table 1). An improvement in the coupling
reaction of 12 was observed by increasing the reaction time to
72 h, when the ligand BiAsBA (3) was obtained in 48% isolated
yield (entry 5, Table 1).
b
additive
conditions (time
(h))
CuI
CsF
product
c
entry
ligand (L:Pd) (Cu:Pd) (equiv)
(%)
d
1
2
toluene, 100 °C (24)
DMF, 120 °C (24)
3 (−)
3 (−)
13 (70)
3
4
PPh3 (4:1)
PPh3 (4:1)
2:1
3 (32)
13 (16)
3 (<5)
13 (28)
3
5
6
DMF, 120 °C (72)
PPh3 (4:1)
2:1
2:1
3 (48)
13 (23)
3 (13)
P(tBu)2Me
(4:1)
13 (28)
3 (17)
7
DMF, microwave
(10−11 W), 120
°C (0.33)
PPh3 (4:1)
2:1
13 (40)
a
Reaction conditions: the Ph2As− anion was prepared in liquid
ammonia (400 mL) from AsPh3 (1 mmol) and Na metal (2 mmol);
then n-Bu3SnCl (1 mmol) was added. The cross-coupling reaction was
carried out with bis(amide) 12 (0.35 mmol) and (PPh3)2PdCl2 (1.5
mol %), ligand (Pd:L 1:4), CsF (3 equiv), or CuI (Pd:Cu 1:2) Both
additives and catalyst were calculated considering that for every
b
c
millimole of substrate two reactions occur. Isolated yield. The yields
reported represent at least the average of two reactions. Bis(amide)
d
12 was not soluble in toluene.
Considering that significant progress has been made based
on sterically demanding electron-rich phosphines as ligands for
Stille cross-coupling,19 the phosphine P(t-Bu)2Me20 was
examined as a ligand. When the reaction of 12 and 4 was
carried out with this ligand, a lower yield of ligand 3 was
obtained (entry 6, Table 1). By using other electron-rich
phosphine ligands the yield could not be improved. In an
attempt to reduce the reaction time, the effect of microwave
(MW) radiation on Pd-catalyzed arsination was evaluated
(entry 7, Table 1). MW-assisted heating has been proven as a
valuable technology for organic synthesis, and its application in
several cases has led to acceleration of reactions and
improvement of yields and selectivities.21 Pd-catalyzed coupling
reactions have been carried out under MW conditions;22
however, the use of MW irradiation in the Stille reaction has a
limited scope, and only a few examples have been reported.23
We started with the optimized reaction conditions and explored
different methods and systems for MW irradiation. To our
disappointment, it was not possible to achieve results better
than those obtained with conventional heating for the reaction
C
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of bis(amide) 12 and stannane 4. While the decrease in
reaction time was considerable under the best conditions found,
the ligand BiAsBA (3) was obtained in 17% isolated yield with a
large amount of product 13 (entry 5 vs 7, Table 1).
unsubstituted phenyl rings on the left-hand side adopt
significantly different spatial arrangements in the two
molecules, reflected in differences in all three corresponding
C−As−C−C dihedral angles. (For a graphical overlay of
molecules A and B and geometrical data for 3, see the
Supporting Information.) As expected, the As−C distances
(Figure 2) are significantly longer than the P−C distances
reported for the phosphorus analogue (range 1.828(3)−
1.847(3) Å).24
The supramolecular assembly of ligand 3 in the crystal
(Figure 3) is also interesting, involving the formation of
hydrogen-bonded motifs that comprise two molecules of A and
one molecule of B, as well as acetonitrile molecules. Two
distinct N−H···O hydrogen bonds (N72−H72···O31, with
N···O = 2.888(7) Å and bond angle 168°; and N22−
H22···O71i, with N···O = 2.910(5) Å and bond angle 165°)
link molecules A and B, creating a large ring motif. At the top
of the figure, a third hydrogen bond (N29−H29···N76, with
N···N = 2.81(1) Å and bond angle 164°) links the acetonitrile
molecule to the ligand molecule A. The complete supra-
molecular motif has C2 symmetry. The configurations at the
chiral centers of the BiAsBA ligand were assigned on the basis
of the known configuration of the starting material, the salt
(1R,2R)-(2R,3R)-5, and were confirmed as 1R,2R on the basis
of the value of the Flack parameter.
Catalytic Applications of the new Chiral Bis(arsine)
Ligand BiAsBA (3) in Pd-Catalyzed Asymmetric Allylic
Substitutions. The substrate 1,3-diphenyl-2-propenyl acetate
was often used to compare the activity of different ligands in
the so-called standard catalyzed reaction for the asymmetric Pd-
catalyzed nucleophilic allylic substitutions.2 In order to explore
the application of the new chiral ligand BiAsBA (3) in Pd-
catalyzed asymmetric allylic alkylation, we evaluated the
reaction of 1,3-diphenylpropenyl acetate (14) with dimethyl
malonate (15) under several reaction conditions. The reactions
were carried out at room temperature in the presence of the
catalyst formed in situ from [Pd(η3-C3H5)Cl]2 and ligand 3.
The results are summarized in Table 2.
It should be noted that, despite the moderate yield achieved
in the disubstitution arsination reaction (48%), the new chiral
bis(arsine) ligand 3 could be readily prepared in three steps
following strategy 2. The BiAsBA ligand was obtained as an air-
stable solid, and its structure was confirmed by X-ray
crystallography. Although ligand 3 was obtained via both
strategies, strategy 2 was simpler, involving fewer steps and
givng a higher yield. Synthetically, remarkable features that
extended the applications of Pd-catalyzed arsination were the
two simultaneous cross-coupling reactions, which allowed C−
As bond formation for the synthesis of structurally complex
arsines. One of the few examples where the introduction of aryl
heteroatom groups has been carried out by direct disubstitution
was the synthesis of the chiral arsine 2,2′-bis(diphenylarsino)-
1,1′-binaphthyl (BINAs).7g In this case, the arsination reaction
was performed from the corresponding triflate and Ph2AsH by
a Ni-catalyzed reaction, affording only 34% yield after 3 days.
X-ray Crystallographic Study of BiAsBA (3). The solid-
state structure of the ligand is isostructural with that of the
phosphine analogue.24 Both compounds crystallize in the
orthorhombic space group P21212 and contain acetonitrile as
the common solvent of crystallization. However, since the
emphasis of the report describing the P analogue was on the
catalytic activity of this species, several interesting features of
the X-ray structure were not discussed. Here, some of these
features, as they occur in the isostructural arsine analogue, are
highlighted for the first time. The unit cell contains six
molecules of the ligand 3, four in general positions (type A)
and two on crystallographic 2-fold axes (type B). Representa-
tive molecules A and B, shown in Figure 2, clearly adopt
different overall conformations. While the right-hand halves of
molecules A and B have similar conformations, the two
First, we examined the complex derived from ligand 3 under
the standard conditions reported by Trost et al.,25 which
involve NaH as base in THF (entry 1, Table 2). Under these
conditions the complex [Pd-BiAsBA] was found to be an
effective catalyst for allylic alkylation, since the alkylated
malonate 16 was obtained in 98% yield: however, with only
23% ee. Despite the low enantioselectivity obtained, this result
showed the significant potential of the bis(arsine) ligand
BiAsBA, since the TSL 1 gave allylic malonate 16 in only 29%
yield and 12% ee under the same reaction conditions (entry 2,
Table 2).25 It is very important to highlight the greater
reactivity of ligand 3 in comparison to that of TSL 1. The
remarkable improvement in catalytic activity with ligand 3 is an
example of a ligand-acceleration effect,26 which offers a
powerful approach to increasing reaction efficiency and
provides new opportunities to accelerate allylic alkylation
reactions with arsine ligands. Considering that the structure of
the BiAsBA ligand is isostructural with that of TSL, it seems
that the electronic changes of the chiral arsine ligand 3 achieved
by modifying the heteroatom are relevant for catalytic activity.
The general catalytic cycle involving oxidative addition to afford
a [Pd-allyl]+ intermediate, followed by nucleophilic attack, has
become firmly established in the literature. Considering the
general assumption that under catalytic conditions the [Pd-
allyl]+ intermediate is the “resting state” of the catalytic cycle,27
Figure 2. Perspective views of the two crystallographically
independent molecules of ligand 3 with displacement ellipsoids at
the 40% probability level. H atoms are omitted for clarity. Molecule A
is in a general equivalent position, while molecule B is located on a 2-
fold axis. (Symmetry transformation used to generate equivalent atoms
in B: (i) 1 − x, 1 − y, z.) The As−C bond distance ranges are As1−C
= 1.962(5)−1.972(5) Å, As38−C = 1.956(6)−1.975(6) Å, and As51−
C = 1.970(5)−1.984(5) Å.
D
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Figure 3. Stereoview of the supramolecular hydrogen-bonded motif in the crystal structure of ligand 3. The view direction is parallel to the C2 axis in
molecule B.
of catalyst deactivation by formation of the inactive Pd(II)
complex may be occurring with the arsine ligand.
Table 2. Pd-Catalyzed Allylic Alkylation of 1,3-Diphenyl-2-
propenyl Acetate (14) with Dimethyl Malonate (15)
Catalyzed by [Pd-BiAsBA]
a
In an effort to optimize the performance of the [Pd-BiAsBA]
catalyst with diphenylpropenyl acetate 14, the effect of the
solvent was investigated. When the reaction was performed in
CH2Cl2, the yield of product 16 was practically the same,
without improvement of the enantioselectivity (entry 3, Table
2). When the solvent was changed to toluene, practically no
reaction was observed, and the allylic substrate 14 was
recovered in 90% yield (entry 4, Table 2).
It is well-known that the structure of the nucleophile affects
the enantioselectivity of these reactions.5 Consequently, N,O-
bis(trimethylsilyl)acetamide (BSA)30 and catalytic amounts of
MAcO as base were employed to facilitate the deprotonation of
dimethyl malonate 15 and produced the nucleophile in situ
(entries 5−10, Table 2). When NaAcO/BSA was employed in
THF as solvent, the substrate 14 was recovered unreacted
(entry 5, Table 2). The best results in CH3CN were achieved
using LiAcO/BSA as base, and the product 16 was obtained in
only 61% yield and low ee value (entry 6, Table 2). In this
solvent the conversion was complete and the reduced substrate
was obtained. Changing the solvent to CH2Cl2 led to improved
results: total conversion and modest enantioselectivity were
accomplished (entry 7, Table 2).
b
c
d
entry
1
base
solvent
yield (%)
confign
ee (%)
e
NaH
NaH
NaH
NaH
THF
98
29
95
<5
<5
61
95
94
93
90
R
R
S
23
12
6
f
e
2
THF
3
CH2Cl2
toluene
THF
4
g
5
NaAcO/BSA
g
6
LiAcO/BSA
LiAcO/BSA
CH3CN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
S
S
S
S
S
22
49
30
rac
9
g
7
g
8
NaAcO/BSA
g
9
KAcO/BSA
g
10
CsAcO/BSA
a
Reaction conditions: reactions were carried out with [Pd] (2.5 mol
%) and the chiral ligand BiAsBA 3 (7.5 mol %), in 1 mL of solvent at
b
room temperature for 24 h under a nitrogen atmosphere. Determined
c
by GC with an internal standard method. The assignment is based on
the sign of the optical rotation and comparison with literature.29
d
1
Enantiomeric excesses were determined by H NMR using Eu(hfc)3
e
as the chiral shift reagent. The reactions were carried out with 3 equiv
The change of the acetate countercation provided a slight
decrease in the yield and decreased the ee value (entries 8−10,
Table 2). In general, as the basicity of the acetate increased, the
ee value decreased. The dependence of ee values on metal
cations reveals that the structure of the ion pair that forms the
nucleophile is critical for the molecular recognition.
f
of base. The reaction was carried out under the standard conditions
reported by Trost with 1.25 The reactions were carried out with 1 mol
g
% of MAcO and 3 equiv of BSA.
To explain the asymmetric induction produced by TSL, an
empirically derived C2-symmetric “wall-flap” cartoon model was
developed by Trost,31 and the newly developed Lloyd−Jones−
Norrby model32 involves two regiochemically distinct NH
positions for hydrogen bonding of the ligand with the incoming
nucleophile. Taking into account that the structure of the
BiAsBA ligand is isostructural with that of TSL and that the
TSL bound to Pd catalyst exhibits optimal catalytic and
asymmetric efficiency when the allylic substrate is of a smaller
size,25 the modest asymmetric induction observed with ligand
3, although slightly better than that with TSL 1, could be
attributed to structural dynamics associated with the steric
strain being induced in [Pd-allyl]+ by a clash of the Ph-As
a weaker σ-donor arsine ligand could increase the electro-
philicity of the [Pd-allyl]+ intermediate and promote the
nucleophilic attack by malonate 15.
Additionally, catalytic reactions involving Pd complexes
bearing ligand 1 suffer from a competing reaction in which
the Pd(0) complex undergoes oxidation to generate a neutral
P,P,N,N-tetradentate-coordinated Pd(II) complex that is
catalytically inactive.28 A possible deactivation of catalyst Pd/
1 could occur through oxidation with dioxygen, although
reactions were achieved in degassed solvents under an inert
atmosphere.28b Consequently, to explain the higher conversion
with the bis(arsine) ligand 3 in comparison to TSL 1, we
should take into account the possibility that a reduced amount
E
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42, 2580−2584. (c) Trost, B. M.; Crawley, M. L. Top. Organomet.
Chem. 2012, 38, 321−340.
moiety with the allyl termini. Thus, it is presumed that the
palladium-bound ligand 3 should experience significant steric
hindrance when interacting with the 1,3-diphenylpropenyl
acetate substrate.
In summary, the new chiral bis(arsine) ligand BiAsBA derived
from TML was synthesized. The key step was the introduction
of the −AsPh2 group by Pd-catalyzed arsination. This reaction
proved to be a direct and simple synthetic methodology, which
could be employed effectively for the synthesis of arsine ligands.
The best results were obtained when two simultaneous
coupling arsination reactions were performed on bis(amide)
12.
The new chiral bis(arsine) ligand BiAsBA was found to be a
very good ligand for the asymmetric allylic alkylation of 1,3-
diphenyl-2-propenyl acetate with dimethyl malonate, where
very high to complete conversion was observed. Even though
the asymmetric alkylation reactions with the [Pd-BiAsBA]
complex proceed with modest enantioselectivity, the bis(arsine)
ligand BiAsBA provided a higher ee value than the phosphorus-
containing homologous TSL with 1,3-diphenyl acetate 14
under the same reaction conditions. On the basis of the results
obtained, the potential of chiral arsine ligands in asymmetric
allylic alkylation has been established. Further studies to explore
the scope of this ligand in asymmetric catalytic reactions are
currently in progress.
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ASSOCIATED CONTENT
■
S
* Supporting Information
A CIF file giving X-ray crystal structure data for 3·0.4-
(acetonitrile), a figure showing an overlay of molecules A and
B, text giving experimental procedures or details, and figures
giving full spectroscopic data for all new compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org. Crystallographic data are also available through
the Cambridge Crystallographic Database for compound 3
(CCDC 903122).
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́
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AUTHOR INFORMATION
■
(13) (a) Walsh, P. J.; Smith, D. K.; Castello, C. J. Chem. Educ. 1998,
75, 1459−1462. (b) Galsbøl, F.; Steenbøl, P.; SøndergaardSørensen, B.
Acta Chem. Scand. 1972, 26, 3605−3611.
Corresponding Author
*S.E.M.: tel, 54-351-4334170; fax, 54-351-4333030; e-mail,
martins@fcq.unc.edu.ar. M.R.C.: e-mail, Mino.Caira@uct.ac.za.
́
(14) Kaik, M.; Gawronski, J. Tetrahedron: Asymmetry 2003, 14,
1559−1563.
Notes
(15) Aryl iodide bearing a carboxylic acid group did not react at all,
which may be due to the fact that this substrate promoted the
formation of an inactive Pd complex and the catalysis was thus
inhibited. See: Garcia-Martinez, J. C.; Lezutekong, R.; Crooks, R. M. J.
Am. Chem. Soc. 2005, 127, 5097−5103.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
S.E.M. and P.M.U. thank the ACC, CONICET, FONCYT, and
SECYT, Universidad Nacional de Cor
tinuous support of our work. M.R.C. acknowledges research
support from the National Research Foundation (Pretoria) and
the University of Cape Town.
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920.
́
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