Palladium-catalyzed asymmetric allylic alkylation using phosphine-amide derived from chiral trans-2-aminocyclohexanol

Article abstract of DOI:10.1080/10426500902737372

A novel phosphine-amide derived from resolved trans-2-aminocyclohexanol has been synthesized and studied in palladium-catalyzed asymmetric allylic alkylation of racemic (E)-1,3-diphenyl-2-propenyl acetate with various nucleophiles.

Full text of DOI:10.1080/10426500902737372

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Palladium-Catalyzed
Asymmetric Allylic Alkylation
Using Phosphine-Amide
Derived from Chiral trans-2-
Aminocyclohexanol
Katarzyna Glegoła a b , Camille Midrier a , Eric
Framery a & K. Michał Pietrusiewicz b
a ICBMS, UMR CNRS 5246, Equipe Synthèse
Asymétrique, Université de Lyon, Villeurbanne
Cedex, France
b Maria Curie-Skłodowska University, Department of
Organic Chemistry, Lublin, Poland
Version of record first published: 26 Mar 2009.
To cite this article: Katarzyna Glegoła , Camille Midrier , Eric Framery & K. Michał
Pietrusiewicz (2009): Palladium-Catalyzed Asymmetric Allylic Alkylation Using
Phosphine-Amide Derived from Chiral trans-2-Aminocyclohexanol, Phosphorus, Sulfur,
and Silicon and the Related Elements, 184:4, 1065-1075
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Phosphorus, Sulfur, and Silicon, 184:1065–1075, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902737372
Palladium-Catalyzed Asymmetric Allylic Alkylation Using
Phosphine-Amide Derived from Chiral
trans-2-Aminocyclohexanol
Katarzyna Glegolꢀa,1,2 Camille Midrier,1 Eric Framery,1
and K. Michalꢀ Pietrusiewicz2
1ICBMS, UMR CNRS 5246, Equipe Synthe`se Asyme´trique, Universite´
de Lyon, Villeurbanne Cedex, France
2Maria Curie-Sklꢀodowska University, Department of Organic
Chemistry, Lublin, Poland
A novel phosphine-amide derived from resolved trans-2-aminocyclohexanol has
been synthesized and studied in palladium-catalyzed asymmetric allylic alkylation
of racemic (E)-1,3-diphenyl-2-propenyl acetate with various nucleophiles.
Keywords Asymmetric allylic alkylation; 1H-15
N HMBC NMR; Pd-complexes;
phosphine-amide ligand; resolved trans-2-aminocyclohexanol
INTRODUCTION
Palladium-catalyzed asymmetric allylic alkylation is certainly one of
the most useful processes for asymmetric carbon-carbon or carbon-
heteroatom bond formation.1 Since the first example described by Trost
and Strege in 1977,2 a large variety of chiral ligands have been stud-
ied. Among them, for example, the bidentate Trost’s P,P-ligand based
on trans-1,2-diaminocyclohexane3 and a phosphine-oxazoline known as
Pfaltz’s P,N-ligand,4 rank among the best and afford enantioselectivi-
ties up to 99%.
Received 14 January 2008; accepted 31 January 2008.
Dedicated to Professor Marian Mikolꢀajczyk, CBMiM PAN in Ło´dz´, Poland, on the
occasion of his 70th birthday.
We thank Polonium program for support of the exchange, and K.G. thanks the MENSR
for the fellowship.
Address correspondence to Eric Framery, ICBMS, UMR CNRS 5246, Equipe Synthe`se
Asyme´trique, Universite´ de Lyon, Universite´ Lyon 1, 43 Bd du 11 Novembre 1918,
F-69622 Villeurbanne Cedex, France. E-mail: framery@univ-lyon1.fr or K. Michalꢀ
Pietrusiewicz, Maria Curie-Sklodowska University, Department of Organic Chemistry,
Gliniana 33, PL-20 615 Lublin, Poland. E-mail: michal@hermes.umcs.lublin.pl
1065

1066
K. Glegolꢀa et al.
FIGURE 1 Ligands used in the studied Pd-catalyzed allylic alkylation.
High catalyst performance requires careful choice of the activating
metal but also of the chiral ligands. During the last 10 years, carbo-
hydrates including xylose, glucose, D-glucosamine, galactose, manni-
tol, and trehalose backbones have appeared as good sources of chi-
ral ligands for asymmetric catalysis.5 For example, Ruffo et al.6 have
prepared bis(phosphine-amides) based on 2,3-glucodiamine, closely re-
sembling (1S, 2S)-cyclohexanediamine. In 2003, our group reported on
the potential of the monophosphine-amide ligand 1 derived from D-
glucosamine (Figure 1).7 Using this ligand, enantioselectivities up to
97% have been obtained in the allylic alkylation of racemic (E)-1,3-
diphenyl-2-propenyl acetate with various nucleophiles, despite the fact
that the chiral information of the auxiliary was considerably distant
from the ligating achiral phosphorus center. We have also studied the
infuence of the stereochemistry of the D-glucosamine moiety on the
enantioselectivity of allylic alkylation by modifying the configuration
and the nature of the substituent at the anomeric position in the lig-
and in order to reveal its potential modes of interactions with the metal
center.8
In this article, we present the synthesis of structurally simplified
phosphine-amide ligands 2 (Figure 1) derived from chiral trans-2-
aminocyclohexanol and the evaluation of these ligands in the model
palladium-catalyzed asymmetric allylic substitution reactions. By com-
paring the results obtained with the both types of phosphine-amides 1
and 2, we can demonstrate that the presence of the structurally rich
carbohydrate framework in the ligand is crucial for the achievement of
a high level of enantioselectivity in the studied reaction.
RESULTS AND DISCUSSION
The new phosphine-amide ligands 2 were obtained from resolved trans-
2-aminocyclohexanol (Scheme 1). The latter compound can be easily
obtained by several methods: resolution of the racemic compound as
salts of tartaric acid,9 ring-opening reaction of cyclohexene oxide by

Palladium-Catalyzed Asymmetric Allylic Alkylation
1067
SCHEME 1 Synthesis of ligands (R,R)-2 and (S,S)-2: (i) 2-(diphenyl-
phiosphino)benzoic acid, EDC, HOBT, DMF, rt, 18 h; (ii) Ac2O, DMAP, Py, rt,
5 h.
chiral methylbenzylamine resulting in diastereomers, which can be
separated and debenzylated (Overman’s method),10 or the same ring-
opening reaction by TMS-azide in the presence of chiral chromium com-
plex followed by reduction.11 As Nishida et al.12 have described, Over-
man’s protocol was the best one to obtain both enantiomers of trans-
2-aminocyclohexanol in enantiomerically pure form, and we repeated
this protocol also in our study. In order to obtain the corresponding
phosphine-amide derivatives, a condensation reaction between (1R,2R)-
or (1S,2S)-2-aminocyclohexanol and 2-(diphenylphosphino)benzoic acid
in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide
(EDC) and 1-hydroxybenzotriazole (HOBT) as coupling reagents was
performed in DMF at room temperature for 18 h. After purifica-
tion by flash chromatography, the chiral 2-(diphenylphosphino)-N-(2-
hydroxycyclohexyl)-benzamides (R,R)-3 and (S,S)-3 were isolated in
80% yield. Then, the intermediates (R,R)-3 and (S,S)-3 were acety-
lated to give the chiral 2-[2-(diphenylphosphino)benzoyl]amino cyclo-
hexyl acetates (R,R)-2 and (S,S)-2 in 75% and 79% yield, respectively.
The new ligands 2 were examined in the palladium-catalyzed asym-
metric allylic alkylation of racemic (E)-1,3-diphenyl-2-propenyl ac-
etate with several nucleophiles, using [(η3-C3H5)PdCl]2 as the pal-
ladium source (Scheme 2). The obtained results were compared to
SCHEME 2 Allylic alkylation of racemic 1,3-diphenylprop-2-enyl acetate.

1068
K. Glegolꢀa et al.
TABLE I Palladium-Catalyzed Asymmetric Allylic Alkylation
of Racemic 1,3-Diphenylprop-2-enyl Acetate with Several
Nucleophiles at 60◦C and Using (R,R)-2 as Liganda
Pd/L
NuH
Time
Yield (%)b
e.e. (%)c (config)d
1/1
1/2
1/1
1/2
1/1
1/2
1/1
1/2
1/1
1/2
CH2(CO2Me)2
CH2(CO2Me)2
CH3CH(CO2Me)2
CH3CH(CO2Me)2
AcNHCH(CO2Me)2
AcNHCH(CO2Me)2
Benzylamine
Benzylamine
Morpholine
Morpholine
24 h
24 h
96 h
96 h
96 h
96 h
96 h
96 h
96 h
96 h
30
97
92
95
15
50
35
10
30
50
57 (S)
80 (S)
37 (R)
67 (R)
63 (R)
54 (R)
31 (R)
57 (R)
33 (R)
48 (R)
a[substrate]/[NuH]/[Base]/[Pd] = 25/75/75/1.
bYields of isolated pure product after column chromatography.
cEnantiomeric excess determined by HPLC analysis (column Chiralpak
AD 0.46 × 25 cm).
dThe absolute configuration was determined by comparison with an
authentic sample.
eK2CO3 used as base.
those observed previously using ligand 1 derived from D-glucosamine7
(Table I). The reactions were performed in THF (0.125 M) at 60◦C, using
2 mol % of [(η3-C3H5)PdCl]2, 4 or 8 mol % of ligand 2, 3 equiv. of nucle-
ophile (NuH), a mixture of N, O-bis(trimethylsilyl)acetamide (BSA) (3
equiv.), and KOAc (2 mol %) as the base.
In Table I, we have reported only the results obtained with ligand
(R,R)-2. However, the allylic alkylations were also performed using
ligand (S,S)-2 under the same reaction conditions as reported above
and using the same nucleophile. The allylic products showed almost
the same level of enantioselectivity as for the other enantiomer, as
could have been predicted.
Compared with phosphine-amide 1 based on D-glucosamine,7 the
efficacy of ligands (R,R)-2 and (S,S)-2 in the studied reaction was gen-
erally lower. In fact, high yields were obtained with difficulty and the
reactions required higher temperature (Table I). At room temperature,
independently of which ligands and nucleophiles were used, no conver-
sion was observed. The best yields (97% and 95%) were obtained for
the CH2(CO2Me)2 and CH3CH(CO2Me)2 with the Pd/ligand ratio of 1/2
(Table I) at 60◦C during 24 and 96 h, respectively. The enantiomeric
excesses were moderate to good (31% to 80%) and were lower than
those measured for the same allylic product obtained using derivative

Palladium-Catalyzed Asymmetric Allylic Alkylation
1069
1 as ligand with a Pd/ligand ratio of 1:1. In contrast, with the ligand
based on D-glucosamine, in all cases except when AcNHCH(CO2Me)2
was used as nucleophile (Table I), the enantioselectivity was higher
when the Pd/ligand 2 ratio of 1:2 was applied.
In order to obtain an insight into the possible mode of chelation
of ligand 2 to palladium, we performed a NMR study of (R,R)-2 and
its Pd-complexes with a Pd/ligand ratio of 1:1 and 1:2. We focused
our NMR study on the chemical shifts of the carbon atoms of the two
carbonyl groups of the ligand before and after the complexation, as well
as on the chemical shifts of the phosphorus and nitrogen atoms. Before
complexation of the ligand (R,R)-2, the two signals corresponding to
carbonyl groups linked to NH and an oxygen atom were detected at
168.8 and 172.3 ppm, respectively. The chemical shift of the phosphorus
atom was at –8.9 ppm. Using a 1H-15N HMBC NMR sequence, the
chemical shift of the nitrogen atom was found at 128.1 ppm (Figure 2a).
FIGURE 2 1H-15N HMBC NMR (CDCl3) spectra for (R,R)-2 (a) and for the
corresponding Pd-complexes: Pd/L ratio of 1:1 (b) and of 1:2 (c). (Continued)

1070
K. Glegolꢀa et al.
FIGURE 2 (Continued)

Palladium-Catalyzed Asymmetric Allylic Alkylation
1071
After complexation with palladium, in the case of a Pd/ (R,R)-2 ratio
of 1:1, no change was observed for the chemical shifts of the carbonyl
groups. Two signals were detected in the 31P NMR spectrum at 26.9 and
27.6 ppm, indicating two types of chelation to palladium (the chemical
shift of the corresponding phosphine oxide is at 35 ppm). In addition,
1
no signal was observed in the H-15N HMBC NMR spectrum (Figure
2b), indicating a possible chelation to the metal. Recently, Amatore
et al.13 reported on the basis of X-ray analysis that, in the case of
Trost’s ligand, the bidentate P, P-complex can generate a P, O-chelate
1
as well as a P, N-chelate after intramolecular deprotonation. The H-
15N HMBC NMR sequence uses a polarization transfer between the two
nuclei, so the absence of a signal seems to indicate that the nitrogen
atom is deprotonated in favor of the coordination to palladium. In the
spectrum of Pd/ (R,R)-2 with a ratio of 1:2, in the region typical for
carbonyl groups, two new signals for the carbonyl group linked to NH
at 166.5 and 167.4 ppm, as well as two signals for the carbonyl group
linked to the oxygen atom at 170.8 and 172.1 ppm, were detected,
in addition to the two signals appearing at 168.8 and 172.3 ppm. In
the 31P NMR spectra, we observed four signals at 20.4, 24.4, 26.9,
and 27.6 ppm, with the first two displaying a high intensity. In the
1H-15N HMBC NMR spectrum (Figure 2c) one signal at 129.8 ppm
was detected, indicating no chelation between the palladium and the
nitrogen atoms. This NMR study shows that various complexes were
obtained from the studied ligand and the palladium. It seems that
there is equilibrium between mono- and bidentate chelates. In the case
of Pd/ (R,R)-2 ratio of 1:1, the bidentate P, N-complex and monodendate
P, P-complexes are probably in equilibrium. In the case of Pd/ (R,R)-2
ratio of 1:2, the monodentate P, P-complex seems to be in equilibrium
with two bidentate P, O-complexes involving the oxygen atoms of the
carbonyl groups of the acetamido function and acetoxy function.
CONCLUSION
To summarize, in our previous study using derivative 1 as ligand, we
proposed in the case of Pd:1 ratio of 1:1 the existence of bidentate
complexes in equilibrium, in which the palladium was chelated to the
phosphorus atom and also to the oxygen atom of the carbonyl groups
linked to C-1, C-3, and NH of the carbohydrate skeleton.8 No com-
plexation of the palladium atom to the nitrogen atom was observed.
By comparing the results on allylic alkylation using ligand 1 with the
results obtained with ligand (R,R)-2, we have demonstrated that the
presence of an acetoxy group at the β-position at the anomeric center

1072
K. Glegolꢀa et al.
of the D-glucosamine residue is crucial but not sufficient for obtaining
allylic products with high enantioselectivity. The other carbonyl groups
linked to carbohydrate moiety, most probably those linked to C-3 and
NH, seem thus to play a very important role in stabilizing and rigid-
ifying the formed complexes with palladium and in effecting higher
induction in the allylic substitutions studied.
EXPERIMENTAL
Solvents were purified by standard methods and dried if necessary. All
commercially available reagents were used as received. All reactions
were monitored by TLC (TLC plates GF254 Merck). Air- and moisture-
sensitive reactions were performed using the usual inert atmosphere
techniques. Reactions involving organometallic catalysis were carried
out in a Schlenk tube under an inert atmosphere. Column chromatog-
raphy was performed on silica gel 60 (230–240 mesh, Merck). Optical
rotations were recorded using a Perkin-Elmer 241 polarimeter. NMR
spectra were recorded with a Bruker AMX 300 spectrometer and ref-
1
erenced as follows: H (300 MHz) internal SiMe4 at δ 0.00 ppm, 13C
(75 MHz) internal CDCl3 at δ 77.2 ppm, and 31P (121 MHz) external
85% H3PO4 at δ 0.0 ppm. Conversion was determined by GC using a
Quadrex OV1 column (30 m × 0.25 mm), and enantiomeric excess was
determined by HPLC with a ChiralpakAD column (25 cm × 4.6 mm)
using a ratio of hexane:i-propanol as eluent.
Synthesis of (R,R)- and (S,S)-3: General Procedure
In a Schlenk tube under nitrogen 2-(diphenylphosphino)benzoic acid
(0.34 g, 1.11 mmol), (1R,2R)- or (1S,2S)-2-aminocyclohexanol (0.18 g,
1.56 mmol), EDC · HCl (0.25 g, 1.33 mmol), HOBT (0.18 g, 1.33 mmol),
and NaHCO3 (0.11 g, 1.33 mmol) were stirred in DMF (10 mL) for 18
h at rt. After evaporation of the solvent, the product was purified by
flash chromatography (CH2Cl2:MeOH 10:1) to afford (R,R)- or (S,S)-3.
2-(Diphenylphosphino)-N-[(1R,2R)-2-hydroxy-cyclohexyl]-
benzamide (R,R)-3
Yield: 80%; white solid; mp = 140–142◦C; Rf = 0.30 (CH2Cl2/MeOH
10 : 1); [α]2D5 -9.0 (c 0.5, CH2Cl2). H NMR (CDCl3): δ = 7.65–7.60 (m,
1
1H, arom-H), 7.42–7.22 (m, 12H, arom-H), 6.99–6.92 (m, 1H, arom-H),
5.84 (d, J = 6.8 Hz, 1H, NH), 3.78–3.66 (m, 1H, CHNH), 3.19 (ddd, J =
10.0, 9.8, 4.3 Hz, 1H, CHOH), 2.03–1.99 (m, 1H, CH2), 1.89–1.82 (m,

Palladium-Catalyzed Asymmetric Allylic Alkylation
1073
1H, CH2), 1.71–1.60 (m, 2H, CH2), 1.42–1.07 (m, 3H, CH2), 1.00–0.86
(m, 1H, CH2). 13C NMR (CDCl3): δ = 174.3, 142.1 (d, J = 27.9 Hz), 136.3
(d, J = 9.3 Hz), 136.2 (d, J = 8.7 Hz), 134.5 (d, J = 16.1 Hz), 134.3, 134.1
(d, J = 7.5 Hz), 133.8 (d, J = 7.5 Hz), 130.4, 129.3 (d, J = 5.5 Hz), 129.2,
129.0 (d, J = 6.8 Hz), 128.8 (d, J = 6.8 Hz), 128.5 (d, J = 5.6 Hz), 74.9,
56.3, 33.8, 31.2, 24.7, 24.1. 31P NMR (CDCl3): δ = -10.3. Anal. Calcd for
C25H26NO2P: C 74.42, H 6.50; found C 74.02, H 6.56%.
2-(Diphenylphosphino)-N-[(1S,2S)-2-hydroxy-cyclohexyl]
benzamide (S,S)-3
Yield: 80%; white solid; mp = 135–137◦C; Rf = 0.30 (CH2Cl2/MeOH
25
1
10 : 1); [α]D +9.7 (c 0.5, CH2Cl2). H NMR (CDCl3): δ = 7.65–7.62 (m,
1H, arom-H), 7.42–7.24 (m, 12H, arom-H), 6.99–6.95 (m, 1H, arom-H),
5.76 (d, J = 6.8 Hz, 1H, NH), 3.79–3.67 (m, 1H, CHNH), 3.21 (ddd, J =
9.9, 9.9, 4.3 Hz, 1H, CHOH), 2.03–2.00 (m, 1H, CH2), 1.85–1.82 (m, 1H,
CH2), 1.71–1.60 (m, 2H, CH2), 1.39–0.98 (m, 3H, CH2), 0.95–0.86 (m,
1H, CH2). 13C NMR (CDCl3): δ = 170.6, 142.3 (d, J = 27.7 Hz), 136.6 (d,
J = 8.7 Hz), 136.5 (d, J = 8.7 Hz), 134.7 (d, J = 18.8 Hz), 134.6, 134.4
(d, J = 7.5 Hz), 134.1 (d, J = 7.5 Hz), 130.7, 129.6, 129.5 (d, J = 5.6 Hz),
129.3 (d, J = 8.7 Hz), 129.1 (d, J = 9.3 Hz), 128.5 (d, J = 5.6 Hz), 75.1,
56.6, 34.1, 31.5, 25.0, 24.4; 31P NMR (CDCl3): δ = -10.3. Anal. Calcd for
C25H26NO2P: C 74.42, H 6.50; found C 74.10, H 6.49%.
Synthesis of (R,R)- and (S,S)-2: General Procedure
In a Schlenk tube under nitrogen, (R,R)- or (S,S-3 (0.20 g, 0.49 mmol)
and a few crystals of DMAP were dissolved in pyridine (5 mL). At
0◦C, Ac2O (0.06 g, 0.58 mmol) was added dropwise, and the mixture
was stirred at rt for 5 h. After evaporation of the pyridine, the residue
was dissolved in CH2Cl2 (10 mL), washed with cold water (2 × 5 mL),
dried over Na2SO4, concentrated, and purified by flash chromatography
(CH2Cl2:MeOH 30:1) to afford (R,R)-2 or (S,S)-2.
(1R,2R)-2-[2-(Diphenylphosphino)benzoyl]amino Cyclohexyl
Acetate (R,R)-2
Yield: 75%; white solid; mp = 69–70◦C; Rf = 0.60 (CH2Cl2/MeOH
30 : 1); [α]2D5 -28.8 (c 0.5, CH2Cl2). 1H NMR (CDCl3): δ = 7.49–7.45 (m,
1H, arom-H), 7.38–7.21 (m, 12H, arom-H), 6.95–6.90 (m, 1H, arom-H),
5.94 (d, J = 9.1 Hz, 1H, NH), 4.61 (ddd, J = 10.5, 10.5, 4.3 Hz, 1H,
CHOAc), 4.05–3.94 (m, 1H, CHNH), 2.06 (s, 3H, CH3), 1.96–1.91 (m,
2H, CH2), 1.76–1.60 (m, 2H, CH2), 1.50–1.40 (m, 1H, CH2), 1.30–1.20

1074
K. Glegolꢀa et al.
(m, 2H, CH2), 1.05–0.90 (m, 1H, CH2). 13C NMR (CDCl3): δ = 172.3,
168.8, 141.8 (d, J = 25.4 Hz), 137.9 (d, J = 11.8 Hz), 137.8 (d, J = 11.8
Hz), 136.7 (d, J = 21.1 Hz), 134.8, 134.4 (d, J = 4.5 Hz), 134.2 (d, J =
4.5 Hz), 130.6, 129.1 (d, J = 9.9 Hz), 129.0 (d, J = 5.0 Hz), 128.9 (d, J =
9.8 Hz), 128.8, 127.6 (d, J = 4.9 Hz), 75.0, 53.4, 32.1, 31.1, 24.5, 24.4,
21.8. 31P NMR (CDCl3): δ = -8.9. HRMS (ESI) [M].+ C27H28NO3P: calcd
445.1806, found 445.1790.
(1R,2R)-2-[2-(Diphenylphosphino)benzoyl]amino Cyclohexyl
Acetate (S,S)-2
Yield: 79%; white solid; mp = 60–62◦C; Rf = 0.60 (CH2Cl2/MeOH
30 : 1); [α]25+30.0 (c 0.5, CH2Cl2). 1H NMR (CDCl3): δ = 7.41–7.38 (m,
1H, arom-DH), 7.29–7.17 (m, 12H, arom-H), 6.87–6.84 (m, 1H, arom-H),
5.92 (d, J = 8.6 Hz, 1H, NH), 4.53 (ddd, J = 10.4, 10.4, 4.5 Hz, 1H,
CHOAc), 3.98–3.86 (m, 1H, CHNH), 2.08 (s, 3H, CH3), 1.88–1.83 (m,
2H, CH2), 1.67–1.64 (m, 1H, CH2), 1.55–1.52 (m, 1H, CH2), 1.45–1.33
(m, 1H, CH2), 1.27–1.08 (m, 2H, CH2), 0.97–0.85 (m, 1H CH2). 13C NMR
(CDCl3): δ = 172.4, 168.8, 141.7 (d, J = 26.0 Hz), 137.9 (d, J = 11.0 Hz),
137.8 (d, J = 11.8 Hz), 136.7 (d, J = 21.0 Hz), 134.8, 134.3 (d, J = 19.8
Hz), 134.1 (d, J = 20.4 Hz), 130.6, 129.1, 129.0 (d, J = 6.2 Hz), 128.9
(d, J = 5.0 Hz), 128.8 (d, J = 4.9 Hz), 127.6 (d, J = 4.9 Hz), 75.0, 53.3,
32.0, 31.4, 24.5, 24.4, 21.8. 31P NMR (CDCl3): δ = −8.9. HRMS (ESI)
[M].+ C27H28NO3P: calcd 445.1806, found 445.1794.
Allylic Alkylation: General Procedure
In a Schlenk tube, [Pd(η3-C3H5)Cl]2 (8.8 mg, 24 µmol) and the ligand
(21.3 mg, 48 µmol, or 42.7 mg, 96 µmol) were dissolved in THF (1
mL). After stirring for 1 h at rt, a solution of racemic 1,3-diphenyl-
2-propenyl acetate (302 mg, 1.2 mmol) in THF (1 mL) was added.
After 30 min, this solution was transferred to a Schlenk tube con-
taining dimethyl malonate (475 mg, 3.6 mmol), BSA (732 mg, 3.6
mmol), and KOAc (2.3 mg, 24 µmol) in THF (2 mL). The reaction
mixture was stirred at 60◦C for the desired time. The conversion was
determined by GC analysis. The mixture was then diluted with di-
ethyl ether (15 mL) and water (5 mL). The organic phase was washed
with brine and dried over MgSO4. Evaporation of the solvent gave a
residue, which was purified by chromatography (petroleum ether:ethyl
acetate 10:1). The enantiomeric excesses were determined by HPLC
analysis.

Palladium-Catalyzed Asymmetric Allylic Alkylation
1075
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