Highly enantioselective alkylation of allyl acetates using tartrate-derived bioxazoline ligands

Article abstract of DOI:10.1002/ejoc.201301208

Tartrate-derived bioxazoline ligands, which form a five-membered chelate ring with metals, were evaluated for use in the asymmetric allylic alkylation (AAA) reactions of various symmetrical and unsymmetrical allyl acetates. Excellent enantioselectivities

Full text of DOI:10.1002/ejoc.201301208

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FULL PAPER
DOI: 10.1002/ejoc.201301208
Highly Enantioselective Alkylation of Allyl Acetates Using Tartrate-Derived
Bioxazoline Ligands
Samydurai Jayakumar,[a] Muthuraj Prakash,[a] Kaluvu Balaraman,[a] and
Venkitasamy Kesavan*[a]
Keywords: Asymmetric synthesis / Enantioselectivity / Palladium / Alkylation / Allylic compounds
Tartrate-derived bioxazoline ligands, which form a five-
membered chelate ring with metals, were evaluated for use
in the asymmetric allylic alkylation (AAA) reactions of vari-
ous symmetrical and unsymmetrical allyl acetates. Excellent
enantioselectivities were achieved by using both symmetri-
cal and unsymmetrical allyl acetates.
Introduction
Pd-catalyzed allylic substitution by a carbon nucleophile
is a versatile method for C–C bond formation. Because of
its wide applicability, enantioselective versions of the same
reaction have been carried out by using chiral ligands.[1]
Phosphorous-containing ligands are well known for their
efficiency in asymmetric allylic substitution reactions, but
they are sensitive to oxygen.[2] Oxazoline-containing li-
gands, which are stable and easy to handle, have received
significant attention in many asymmetric transformations.[3]
In particular bis(oxazoline)s 1, a class of privileged chiral
ligands, have been successfully employed in various mech-
anistically different asymmetric transformations, including
asymmetric allylic alkylation (AAA) reactions (see Fig-
ure 1). It is evident from the literature that the most efficient
chiral bis(oxazoline)s 1 are derived from either unnatural
tert-leucinol or expensive amino indanol.[4] Hence, there is
a need to explore and identify new ligands from an inexpen-
sive chiral source for use with various mechanistically dif-
ferent asymmetric reactions, including AAA reactions.
Our research has focused on developing new chiral li-
gands that are derived from readily available, inexpensive
chiral sources and exploring their applications to various
asymmetric transformations. We chose l-tartaric acid as a
chiral source to develop new bioxazoline ligands. Sang-gi
Lee and co-workers developed bioxazoline ligands 2 from
l-tartaric acid.[5] However, applications of these ligands to
the field of asymmetric catalysis are rather limited, as the
metal coordination sphere is oriented away from the chiral
center. Hence, we hypothesized that the introduction of an
Figure 1. Schematic representation of bis(oxazoline) and bioxazol-
ine ligands.
additional stereogenic center near the metal coordinating
nitrogen atom would mitigate the drawbacks that are exhib-
ited by the simple bioxazoline ligands 2. We have already
proved this hypothesis. Through a five-membered chelate
ring with a metal, ligand 3 has effectively catalyzed an
asymmetric Henry reaction,[6] an enantioselective alkyne
addition to an imine,[7] and the enantioselective fluorination
of β-keto esters.[8] Herein, we wish to report the scope of
ligand 3 with regard to the catalysis of AAA reactions.
Results and Discussion
First, rac-1,3-diphenyl-2-propenyl acetate (4) was sub-
jected to alkylation with dimethyl malonate in dichloro-
methane (DCM) at ambient temperature in the presence of
2.5 mol-% of [Pd(η3-C3H5)Cl]2 and 10 mol-% of the appro-
priate ligand (i.e., 2 or 3, see Figure 2). The results are sum-
marized in Table 1. Because there was no literature pre-
cedent for utilizing ligand 2 in an AAA reaction, we also
evaluated its use under the standard AAA reaction condi-
tions. Our observed results indicate that ligand 2 failed to
induce good asymmetric induction in this reaction. Bioxaz-
[a] Chemical Biology Laboratory, Department of Biotechnology,
Bhupat and Jyothi Metha School of Bioscience Building, Indian
Institute of Technology Madras,
Chennai 600036, India
E-mail: vkesan@iitm.ac.in
http://www.biotech.iitm.ac.in/faculty/kesavan/index.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301208.
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S. Jayakumar, M. Prakash, K. Balaraman, V. Kesavan
FULL PAPER
Figure 2. Schematic representations of ligands.
oline ligand 2a, which contained a sterically bulky ada- Table 1. Ligand and temperature effect on AAA reaction[a]; BSA =
N,O-bis(trimethylsilyl)acetamide.
mantyl group, afforded a trace amount of alkylated product
5 with poor enantioselectivity. When 2b was employed as
the ligand, only moderate enantioselectivity was observed
(see Table 1, Entries 1 and 2). The reaction with ligand 3a,
which contained a chiral appendage, yielded product 5 in
good yield and with good enantioselectivity (see Table 1,
Entry 3). This result clearly indicates that the chiral append-
age near the coordinating nitrogen atoms is responsible for
the observed enhancement in enantioselectivity. A marginal
increase in enantioselectivity was observed when the reac-
tion was performed at 5 °C, but this change resulted in a
lower reaction rate and yield (see Table 1, Entry 4).
Attempts to increase the enantioselectivity further with bi-
oxazoline 3b, which was obtained from a menthol-derived
acid, were not fruitful (see Table 1, Entry 5). This implies
that the enantioselectivity depended not only on the chiral
appendage but also on the presence of an aromatic ring at
the additional stereogenic center.
Entry
Ligand
% Yield[b]
% ee[c]
1
2
3
4
5
6
7
8
2a
2b
3a
3a
3b
3c
3d
3e
trace
80
90
50
50
58
92
71
14 (R)
68 (R)
90 (R)
92 (R)[d]
47 (R)
70 (R)
91 (S)
70 (S)
[a] The reaction was conducted with rac-1,3-diphenyl-2-propenyl
acetate (4) (0.12 mmol) and CH2(COOMe)2 (0.36 mmol) in di-
chloromethane with [Pd(η3-C3H5)Cl]2 (2.5 mol-%) and ligand
(10 mol-%) at 25 °C. [b] Isolated yield. [c] Enantiomeric excess
values were determined by using HPLC analysis with a chiral AD-
Because ligand 3a contained two chiral centers, it was
necessary to identify the most suitable diastereomeric pair
for the AAA to achieve the optimal enantioselectivity. The
possible diastereomeric ligands (i.e., 3c–3e) were synthe- H column. [d] Reaction was performed at 5 °C.
sized by choosing the appropriate stereoisomers of tartaric
acid and naproxen. It was identified that ligand 3a [from
two (S)-naproxens and (S,S)-bioxazoline (BOX)] and its diethyl ether was used as a solvent, the reaction proceeded
enantiomer 3d [from two (R)-naproxens and (R,R)-BOX] smoothly to afford a quantitative yield of alkylated product
were the most suitable bioxazolines for the AAA reaction 5, but there was a marginal decrease in the enantio-
(see Table 1, Entries 3 and 7). Diastereomers 3c and 3e were selectivity (see Table 2, Entry 1). In solvents such as N,N-
found to be less effective at inducing asymmetric induction dimethylformamide (DMF) and dichloroethane (DCE), the
in the AAA reaction (see Table 1, Entries 6 and 8). The ab- efficiency of the reaction was very low, which had an effect
solute configuration of the product depended on the abso- on the yield (see Table 2, Entries 2 and 3). When toluene or
lute configuration of the bioxazoline backbone, that is, the benzene was used as the solvent, the yield of the product
bioxazoline from l-tartaric acid yielded the product with was slightly diminished, but the outcome with regard to
the (R) configuration and vice versa. Thus, we demon- stereoselectivity remained unaffected (see Table 2, Entries 4
strated that tartrate-derived bioxazolines with an additional and 5). A trace amount of the product was formed when
chiral appendage are capable of mediating AAA reactions the reaction was carried out in dimethoxyethane (DME, see
with very good efficiency.
Table 2, Entry 6). Thus, it was concluded that DCM was
Efforts to identify a suitable reaction medium were car- the better choice for the reaction medium of an AAA reac-
ried out by using the standard reaction conditions. When tion that employed bioxazoline 3a.
2
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Enantioselective Alkylation of Allyl Acetates
Table 2. Solvent and additive optimization.[a]
or para position of the aryl ring (see Table 3, Entries 9 and
10). However, ortho-chloro-substituted substrate 6h failed
to undergo alkylation under the standard reaction condi-
tions (see Table 3, Entry 8). Hence, only substrates with a
bromo substituent at the meta and para positions were
studied. It is clear from the results that those substrates are
also ideal reactants, as they underwent alkylation with great
efficiency (see Table 3, Entries 11 and 12). The more steri-
cally hindered rac-1,3-di(naphthalen-2-yl)propenyl acetate
6m yielded the corresponding alkylated product 7m in an
admirable yield and enantioselectivity. It is noteworthy that
effects of ortho and meta-substituted diaryl allylic acetates
(i.e., 6c, 6e, 6f, 6i, 6k, and 6m) are being evaluated and re-
ported for the first time.
Entry
Solvent
Additive
% Yield[b]
% ee[c]
1
2
3
4
5
6
7
8
9
10
Et2O
DMF
DCE
toluene
benzene
DME
DCM
DCM
DCM
DCM
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
NaOAc
LiOAc
AgOAc
AgOAc
95
30
30
80
70
trace
78
80
30
50
88
93
90
92
92
–
85
92
Ͼ99
96
Table 3. Scope of symmetrical substrates of AAA.[a]
[a] The reaction was conducted with rac-1,3-diphenyl-2-propenyl
acetate (4) (0.12 mmol) and CH2(COOMe)2 (0.36 mmol) in di-
chloromethane with [Pd(η3-C3H5)Cl]2 (2.5 mol-%) and ligand
(10 mol-%) at 25 °C. [b] Isolated yield. [c] Enantiomeric excess
values were determined by using HPLC analysis with a chiral AD-
H column.
Entry Ar
Substrate 6
% Yield[b]
% ee[c]
To identify a suitable additive, the reaction was per-
formed in DCM. Using NaOAc as an additive resulted in a
diminished enantiomeric excess value and yield (see Table 2,
Entry 7). Although the asymmetric induction was unaffec-
ted when LiOAc was used, the lower yield of 80% was no-
ticeable (see Table 2, Entry 8). Using AgOAc as an additive
improved the enantiopurity of the product up to 99%ee,
but the yield was lowered to 30%. Efforts to increase this
conversion using AgOAc at 40 °C resulted in only a mar-
ginal increase of the yield to 50%, even after 3 d (see
Table 1, Entries 9 and 10). Hence, KOAc was chosen as the
additive in combination with BSA to evaluate the scope of
the substrate diversity.
1
2
3
4
5
6
7
8
4-OMeC6H4
6a
6b
6c
6d
6e
6f
50
95
96
92
99
71
91
92
94
95
94
93
–
90
91
93
92
91
4-MeC6H4
3-NO2C6H4
4-NO2C6H4
2-FC6H4
3-FC6H4
4-FC6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
3-BrC6H4
4-BrC6H4
2-naphthyl
95
6g
6h
6i
96
n.r.[d]
95
9
10
11
12
13
6j
90
89
85
98
6k
6l
6m
[a] The reaction was conducted with rac-1,3-diphenyl-2-propenyl
acetate (4) (0.12 mmol) and CH2(COOMe)2 (0.36 mmol) in di-
chloromethane with [Pd(η3-C3H5)Cl]2 (2.5 mol-%) and ligand
(10 mol-%) at 25 °C. [b] Isolated yield. [c] Enantiomeric excess
values were determined by using HPLC analysis with a chiral AD-
H column. [d] n.r.: no reaction
Various symmetrically substituted diaryl acetates[9] were
subjected to the AAA reaction under the optimized condi-
tions. It is clear from the results in Table 3 that the presence
of the mesomerically electron-releasing OMe group (at the
para position) on the aryl ring retarded both the yield and
enantioselectivity of the reaction (see Table 3, Entry 1).
The efficiency of our catalytic system for the AAA reac-
There was no change in either the yield or asymmetric in- tion encouraged us to expand the substrate scope to unsym-
duction when rac-1,3-di(p-tolyl)2-propenyl acetate 6b was metrical allyl acetates. To study these substituent effects, we
used as a substrate (see Table 3, Entry 2). The presence of systematically varied the unsymmetrical substrates. Allyl
the electron-withdrawing nitro group at either the meta or acetates 8a–8c contained an aromatic ring at the C-1 carbon
para positions did not affect the yield or the enantio- that was substituted by either an electron-releasing OMe
selectivity (see Table 3, Entries 3 and 4). After examining group or an electron-withdrawing halogen atom as well as
the effects of electron-releasing and electron-withdrawing an unsubstituted aromatic ring at the C-3 carbon.[10] To
substituents, we proceeded to evaluate the effect of halogen study the effect of the aromatic ring at C-1, unsymmetrical
substituents on the aryl ring. Diaryl allyl acetates that con- allyl acetates 8a–8f were subjected to the AAA reaction.
tained a fluoro substituent at the ortho, meta, or para posi- The reactions proceeded smoothly to afford the corre-
tions underwent allylic alkylations in quantitative yields sponding alkylated products 9 and 10 (regioisomers) in
and with very good enantioselectivities (see Table 3, En- quantitative yields in an almost equal ratio. Our earlier ob-
tries 5–7). There was no change in the outcome of the AAA servation (see Table 3, Entry 1) that the presence of the
reaction when a chloro substituent was located at the meta OMe group affected the enantioselectivity of the reaction
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S. Jayakumar, M. Prakash, K. Balaraman, V. Kesavan
FULL PAPER
was vindicated by the observed enantioselectivity of prod- effect of their presence at the ortho position of the phenyl
uct 9a. The other regioisomer that resulted from nucleo- ring at C-3 was studied. The presence of a bulky ortho-
philic attack at the C-3 carbon was also obtained with very bromo substituent enabled nucleophilic attack at the C-3
good enantioselectivity (see Table 4, Entry 1). For sub- position with a preference for one face.[11] This resulted in
strates 8b and 8c, the reaction proceeded smoothly in good enhanced enantioselectivity for regioisomer 10d. As no
yield and with good enantioselectivity (see Table 4, En- bromo group was present at the C-1 aryl ring, a slightly
tries 2 and 3). Although electron-withdrawing groups on diminished enantioselectivity was noticed with 9d (see
the aryl moiety at C-1 of the unsymmetrical substrates did Table 4, Entry 4). A similar effect was observed with sub-
not affect the outcome with regard to enantioselectivity, the strate 8e, which also contained a bromo group at the ortho
position of the aryl group at C-3 (see Table 4, Entry 5). Al-
though symmetrically substituted ortho-chloro-substituted
substrate 6h did not undergo allylic substitution (see
Table 3, Entry 8), the similar chloro substituents in unsym-
metrical substrate 8f did not pose any difficulty to the con-
version into the corresponding alkylated products 9f and
10f, which occurred in quantitative yield and with high
enantioselectivity (see Table 4, Entry 6).
Table 4. Substrate scope for unsymmetrical allyl acetates.[a]
Finally, we examined the adaptability of a combination
of aromatic and aliphatic unsymmetrical acetates under our
protocol. The results are summarized in Figure 3. When we
employed rac-(E)-4-phenylbut-3-en-2-yl acetate (11) as a
substrate, almost a single regioisomeric product (i.e., 12a)
was obtained with 53% enantioselectivity. Similarly, the use
of rac-1-phenylallyl acetate (13) as a substrate resulted in
the formation of the linear alkylated product 14a over the
branched alkylated product 14b in a ratio of 13:1 and with
an ee value of 46% for 14b. This result indicates that the
nucleophic attack preferred the less hindered side of the
allyl cation.
From all of these results, we were able to rationalize that
the electronic nature of the aromatic substituents had a pro-
found effect on rate, regioselectivity, enantioselectivity, and
yield. The presence of strong electron-releasing group con-
siderably affected the yield as well as the enantioselectivity.
The ortho effect played a major role in the case of symmetri-
cal substrates. Here, substitutents that were placed at the
ortho position of the aryl group impeded the nucleophilic
attack, but in the case of unsymmetrical substrates, the
enantioselectivity increased up to 99%.
Entry Substituents
Substrate 9/10[b]
%
% ee 9,
8
Yield[c]
10[d]
1
2
3
4
5
6
R = OMe, X = H
8a
8b
8c
8d
8e
8f
1:1
2:1
1:1
1:1
1:1
1:1
85
98
96
95
98
98
73, 91
91, 91
95, 92
84, 97
82, 99
94, 97
R = F, X = H
R = Cl, X = H
R = H, X = Br
R = F, X = Br
R = Cl, X = Cl
[a] The reaction was conducted with substrate 8 (0.12 mmol) and
CH2(COOMe)2 (0.36 mmol) in dichloromethane with [Pd(η3-
C3H5)Cl]2 (2.5 mol-%) and ligand 3a (10 mol-%) at 25 °C. [b] Ratio
of the regioisomers was determined by using HPLC analysis with
a chiral AD-H column. [c] Isolated yield. [d] Enantiomeric excess
values were determined by using HPLC analysis with a chiral AD-
H column.
Figure 3. Allylic alkylation of mixed allyl acetates. [a] Enantiomeric excess value was determined by using HPLC analysis with a chiral
OD-H column. [b] Enantiomeric excess value was determined by using HPLC analysis with a chiral OJ-H column.
4
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Enantioselective Alkylation of Allyl Acetates
with 10% aqueous HCl solution, saturated aqueous NaHCO3, and
brine solution and then dried with anhydrous Na2SO4 and concen-
trated by a rotary evaporator. The residue was purified by column
chromatography (silica gel, 40% ethyl acetate/hexane) to give the
O-benzyl bis(amide) (2.7 g, 80% yield) as a colorless solid; m.p.
175 °C. [α]2D6 = –6.00 (c = 0.25, CHCl3). 1H NMR (500 MHz,
CDCl3): δ = 7.36 (m, 5 H, Ar), 6.59 (d, J = 7 Hz, 1 H, NH), 4.51
(d, J = 11.5 Hz, 1 H, CH), 4.42 (d, J = 11.5 Hz, 1 H, CH), 4.23
(m, 1 H, CH), 3.64 (dd, J = 9.5 Hz, 4.5 Hz, 1 H, CH), 3.49 (dd, J
= 9.5 Hz, 6 Hz, 1 H, CH), 1.96 (td, J = 11.5 Hz, 3 Hz, 1 H, CH),
1.68 (m, 5 H, CH2), 1.38 (tt, J = 11.5 Hz, 3 Hz, 1 H, CH), 1.31 (m,
1 H, CH), 1.1 (q, J = 12 Hz, 1 H, CH), 0.96 (m, 2 H, CH2), 0.88
(d, J = 5 Hz, 3 H, CH3), 0.87 (d, J = 5.5 Hz, 3 H, CH3), 0.75 (d,
J = 7 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 172.6,
137.7, 128.4, 127.9, 127.8, 73.4, 68.9, 50.4, 49.9, 44.3, 39.6, 34.5,
Conclusions
In this study, we demonstrated the necessity of a second
chiral center in the bioxazoline ligand to mitigate the draw-
back that occurred by using simple bioxazoline 2, which
was derived from tartaric acid. Ligand 3a was extensively
employed in the Pd-catalyzed AAA reactions of symmetri-
cal and unsymmetrical allyl acetates. In the case of symmet-
rical allyl acetates 6, an enantioselectivity of up 95% was
achieved. The investigation of unsymmetrical allyl acetates
8 revealed that excellent enantioselectivities were obtained
for both possible regioisomeric products. With unsymmetri-
cal substrates, the bulky ortho-bromo substituent affected
the enantioselectivity of the regioisomer that resulted from
attack at the C-3 carbon. Further efforts by our group will
explore the potential of ligand 3a in the synthesis of spiro-
oxindoles.
32.3, 28.6, 23.7, 22.3, 21.4, 16.0 ppm. FTIR (KBr): ν = 3433, 3300,
˜
2952, 2914, 2868, 1636, 1540, 1453, 1386, 1366, 1294, 1243, 1095,
734, 696 cm–1. MS (ESI): m/z = 633 [M]+. HRMS (ESI): calcd. for
[C40H61N2O4] 633.4631; found 633.4650.
(1R,1ЈR,2S,2ЈS,5R,5ЈR)-N,NЈ-[(2S,3S)-1,4-Dihydroxybutane-2,3-di-
yl]bis(2-isopropyl-5-methylcyclohexanecarboxamide): To 10% Pd-C
(250 mg) was added a stirred solution of the O-benzyl bis(amide)
(2.5 g, 4 mmol) in methanol (25 ml) under argon. Then, argon was
replaced by a hydrogen balloon (1 atm). The reaction mixture was
stirred until completion (monitored by TLC) and then filtered
through a Celite 545 pad by using an excess amount of methanol
and CHCl3. The organic fraction was concentrated. The crude ma-
terial was purified over column chromatography (100–200 mesh sil-
ica gel, 5 % methanol/DCM) to give the bis(amido)diol (1.52 g,
85% yield); m.p. 233 °C. [α]2D6 = –20.00 (c = 0.25, CHCl3) 1H NMR
(500 MHz, CDCl3): δ = 6.83 (br. s, 1 H, NH), 4.23 (m, 1 H, CH),
4.03 (br. s, 1 H, OH), 3.87 (dd, J = 12.5 Hz, 2 Hz, 1 H, CH), 3.64
(m, 2 H, CH2), 3.57(dd, J = 12 Hz, 5 Hz, 1 H, CH), 2.19 (t, J =
10 Hz, 1 H, CH), 1.82 (m, 1 H, CH), 1.76 (m, 1 H, CH2), 1.68 (m,
2 H, CH2), 1.55 (t, 11.5 Hz, 1 H, CH2), 1.4 (m, 1 H, CH2), 1.18
(q, 12.5 Hz, 1 H, CH), 1.03 (qd, J = 13 Hz, 3 Hz, 2 H, CH2), 0.94
(d, J = 7 Hz, 3 H, CH3), 0.91 (d, J = 6.5 Hz, 3 H, CH3), 0.82 (d,
J = 7 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 178.5,
63.6, 52.9, 49.7, 44.1, 39.7, 34.4, 32.3, 28.9, 23.6, 22.2, 21.4,
Experimental Section
General Methods: All reactions were carried out in a flame-dried
flask. Solvents, which were used for the reactions and column
chromatography, were commercial grade and distilled prior to use.
Toluene and tetrahydrofuran (THF) were dried with sodium/benzo-
phenone, and CH2Cl2 and CHCl3 were dried with CaH2. Solvents
for HPLC analysis were purchased as analytical grade and used
without further purification. TLC was performed on precoated
Merck silica gel aluminium plates with 60F254 indicator and visu-
alized by irradiation with UV light. Column chromatography was
performed with silica gel (Merck 100–200 and 230–400 mesh). The
1H and 13C NMR spectroscopic data were recorded with a Bruker
AV 500 MHz. CDCl3 was used as the solvent, and the multiplicity
was reported as s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet), dd (doublet of doublet), dt (doublet of triplet), br. s
(broad singlet), and td (triplet of doublet). Coupling constants (J)
are reported in Hz. High resolution mass spectra were obtained by
ESI with a Waters/Micromass QTOF mass spectrometer. IR spec-
tra were recorded with a Perkin–Elmer FT/IR-420 spectrometer,
and the data are reported in terms of frequency of absorption
(cm–1). The enantiomeric excess values were obtained by HPLC
analysis with a chiral stationary phase column (CHIRALPAK AD-
H, AS-H, CHIRAL CEL OD-H, OJ-H, and Phenominex Lux-3
cellulose-5) Optical rotations were recorded with a Jasco DIP pola-
rimeter at a wavelength of 589 nm.
16.2 ppm. FTIR (KBr): ν = 3434, 3317, 2953, 2915, 2872, 1637,
˜
1624, 1465, 1456, 1387, 1242, 1216, 1065, 684 cm–1. MS (ESI): m/z
= 453 [M]+. HRMS (ESI): calcd. for [C26H49N2O4]+ 453.3692;
found 453.3698.
(4S,4ЈS)-2,2Ј-Bis[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]-
4,4Ј,5,5Ј-tetrahydro-4,4Ј-bioxazole (3b): Anhydrous NEt3 (1.6 ml,
12 mmol) and MsCl (methanesulfonyl chloride, 0.53ml, 7 mmol)
were added to a stirred solution of the bis(amido)diol (1.4 g,
3 mmol) in dry THF (15 mL) at 0 °C, and the reaction mixture
gradually warmed to room temperature. The stirring was continued
until the completion of the reaction (2 d). The volatile components
Syntheses of Ligands: Ligands 2a, 2b, 3a, and 3c–3e were synthe-
sized according to a published procedure.[6]
Synthesis of Ligand 3b
(1R,1ЈR,2S,2ЈS,5R,5ЈR)-N,NЈ-[(2S,3S)-1,4-Bis(benzyloxy)butane- were removed under vacuum, and the resulting yellow oil was dis-
2,3-diyl]bis(2-isopropyl-5-methylcyclohexanecarboxamide): HPTU
[O-(1,2-dihydro-2-oxo-pyridyl)-N,N,NЈ,NЈ-tetramethyluronium
hexafluorophosphate, 2.1 g, 5.7 mmol] was added to a stirred solu-
tion of the menthyl-derived acid (1R,2S,5R)-2-isopropyl-5-methyl-
cyclohexanecarboxylic acid (1 g, 5.4 mmol) and DIPEA (N,N-di-
isopropylethylamine, 1.35 mL, 8.1 mmol) in dry DCM (15ml) at
0 °C under argon. The stirring was continued for an additional
15 min followed by the addition of (2S,3S)-1,4-bis(benzyloxy)bu-
tane-2,3-diamine (0.8 g, 2.7 mmol). The stirring was continued un-
til the reaction was complete (monitored by TLC). The reaction
mixture was quenched by the addition of H2O and then diluted
with DCM (40 ml). The organic phase was washed successively
solved with DCM. The solution was washed with H2O followed by
brine solution, and then the organic layer was dried with anhydrous
Na2SO4 and concentrated. The crude material was purified by col-
umn chromatography (30% ethyl acetate/hexane) to give 3b (1.1 g,
86% yield) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 4.5
(m, 1 H, CH), 4.13 (t, J = 10 Hz, 1 H, CH2), 3.90 (dd, J = 9 Hz,
6.5 Hz, 1 H, CH2), 2.36 (td, J = 0.5 Hz, 3 Hz, 2 H, CH2), 1.74 (m,
2 H, CH2), 1.65 (m, 2 H, CH2), 1.43 (tt, J = 11.5 Hz, 3 Hz, 3 H,
CH3), 1.36 (m, 1 H, CH), 1.21 (q, J = 7 Hz, 1 H, CH), 1.01 (qd, J
= 13 Hz, 3 Hz, 3 H, CH3), 0.93 (td, J = 12.5 Hz, 2.5 Hz, 1 H, CH),
0.89 (d, J = 5 Hz, 3 H, CH3), 0.87 (d, J = 5 Hz, 3 H, CH3), 0.77
(d, J = 7 Hz, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ =
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O31208
/KAP1
Date: 13-11-13 18:55:25
Pages: 11
S. Jayakumar, M. Prakash, K. Balaraman, V. Kesavan
172.1, 67.7, 67.6, 44.5, 41.5, 39.8, 34.6, 32.2, 28.9, 24.1, 22.2, 21.1, obtained as colorless oil. The ee value was determined by HPLC
FULL PAPER
15.9 ppm. FTIR (KBr): ν = 3215, 2954, 2927, 2871, 2720, 1737,
analysis (Chiralpak AD-H column; hexanes/2-propanol, 80:20;
0.8 mL/min; 254 nm): tR = 9.2 (major enantiomer) and 11.9 min
(minor enantiomer); 91 % ee. 1H NMR (500 MHz, CDCl3): δ =
7.23–7.18 (m, 4 H, Ar), 7.14–7.08 (m, 4 H, Ar), 6.50 (d, J =
15.5 Hz, 1 H, CH), 6.27 (dd, J = 16.0 Hz, 8.5 Hz, 1 H, CH), 4.23
(dd, J = 11.0 Hz, 8.5 Hz, 1 H, CH), 3.94 (d, J = 11.0 Hz, 1 H,
CH), 3.71 (s, 3 H, CH3), 3.55 (s, 3 H, CH3), 2.33 (s, 6 H, CH3) ppm.
13C NMR (125 MHz, CDCl3): δ = 168.3, 167.8, 137.3, 137.2, 136.6,
134.1, 131.4, 129.3, 129.1, 128.2, 127.7, 126.2, 57.7, 52.5, 52.4, 48.8,
˜
1659, 1557, 1456, 1387, 1370, 1348, 1286, 1242, 1223, 1167, 1135,
1086, 1044, 988, 736 cm–1. MS (ESI): m/z = 417 [M + H]+. HRMS
(ESI): calcd. for [C26H45N2O2] 417.3481; found 417.3468.
General Experimental Procedure for Catalytic Reaction: All allyl
acetates were prepared according to the reported procedure.[9] To
a stirred solution of [Pd(η3-C3H5)Cl]2 (0.9 mg, 0.0025 mmol) in
CH2Cl2 (2 mL) was added ligand 3a (5.8 mg, 0.010 mmol) under
argon. After 2 h, rac-allyl acetate (0.1 mmol) was added followed
by N,O-bis(trimethylsilyl)acetamide (0.072 mL, 0.3 mmol), di-
methyl malonate (0.042 mL, 0.3 mmol), and KOAc (0.01 mmol) at
25 °C. The mixture was stirred continuously until the reaction was
complete (monitored by TLC). The solvent was then evaporated,
and the crude material was purified over column chromatography
using silica gel (230–400 mesh, petroleum ether/ethyl acetate, 10:1)
to afford the alkylated product.
21.1, 21.0 ppm. FTIR (KBr): ν = 3463, 3024, 2952, 1759, 1513,
˜
1434, 1312, 1256, 1159, 1021, 968, 818, 781 cm–1.
(E)-Dimethyl 2-[1,3-Bis(3-nitrophenyl)allyl]malonate (7c): The prep-
aration was carried out according to the general procedure by using
rac-(E)-1,3-bis(3-nitrophenyl)allyl acetate (35 mg, 0.1 mmol) and
dimethyl malonate (0.042 mL, 0.3 mmol) with a reaction time of
2 d. The desired product 7c (39.7 mg, 96% yield) was obtained as
a yellow solid. The ee value was determined by HPLC analysis
(Chiralpak AD-H column; hexanes/2-propanol, 80:20; 0.8 mL/min;
254 nm): tR = 21.2 (major enantiomer) and 37.9 min (minor
Racemic Standard: All racemic allylic alkylated products were pre-
pared by using the general experimental procedure. PPh3 was used
instead of ligand 3a.
1
enantiomer); 92%ee. H NMR (500 MHz, CDCl3): δ = 8.22–7.64
(E)-Dimethyl 2-(1,3-Diphenylallyl)malonate (5): The preparation
was carried out according to the general procedure by using (E)-
1,3-diphenyl-2-propen-1-yl acetate (4, 26 mg, 0.1 mmol) and di-
methyl malonate (0.042 mL, 0.3 mmol) with a reaction time of 2 d.
The desired product 5 (30 mg, 90% yield) was obtained as a color-
less oil. The ee value was determined by HPLC analysis (Chiralpak
AD-H column; hexanes/2-propanol, 80:20; 0.8 mL/min; 254 nm):
tR = 8.5 (major enantiomer) and 11 min (minor enantiomer);
90%ee. The absolute stereochemistry was assigned as R by com-
(m, 6 H, Ar), 7.56 (t, d = 8 Hz, 1 H, Ar), 7.50 (t, J = 8 Hz, 1 H,
Ar), 6.61–6.48 (m, 2 H, CH), 4.46 (dd, J = 10.5 Hz, 8.5 Hz, 1 H,
CH), 4.03 (d, J = 10.5 Hz, 1 H, CH), 3.76 (s, 1 H, CH3), 3.60 (s, 3
H, CH3) ppm. 13C NMR (125 Hz, CDCl3): δ = 167.5, 167.1, 148.6,
148.5, 141.8, 137.9, 134.2, 132.3, 131.0, 130.8, 129.9, 129.6, 122.8,
122.63, 122.61, 121.0, 56.8, 52.9, 52.8, 48.4 ppm. FTIR (KBr): ν =
˜
3652, 3413, 3054, 2952, 2925, 2850, 1967, 1896, 1818, 1738, 1585,
1529, 1479, 1350, 1310, 1235, 1192, 1119, 1094, 1027, 998, 807,
743, 699 cm–1.
paring the retention times with those of reported HPLC data.[3] 1
H
NMR (500 MHz, CDCl3): δ = 7.35–7.21 (m, 10 H, Ar), 6.50 (d, J
= 15.7 Hz, 1 H, CH), 6.35 (dd, J = 15.7 Hz, 8.1 Hz, 1 H, CH), 4.29
(dd, J = 10.7 Hz, 8.5 Hz, 1 H, CH), 3.98 (d, J = 10.8 Hz, 1 H,
CH), 3.73 (s, 3 H, CH3), 3.54 (s, 3 H, CH3) ppm. 13C NMR
(500 MHz, CDCl3): δ = 168.2, 167.7, 140.1, 136.8, 131.8, 129.1,
128.7, 128.4, 127.8, 127.5, 127.1, 126.3, 57.6, 52.6, 52.4, 49.2 ppm.
(E)-Dimethyl 2-[1,3-Bis(4-nitrophenyl)allyl]malonate (7d): The prep-
aration was carried out according to the general procedure by using
rac-(E)-1,3-bis(4-nitrophenyl)allyl acetate (35 mg, 0.1 mmol) and
dimethyl malonate (0.042 mL, 0.3 mmol) with a reaction time of
2 d. The desired product 7d (38 mg, 92% yield) was obtained as a
yellow solid. The ee value was determined by HPLC analysis (Chi-
ralpak AD-H column; hexanes/2-propanol, 80:20; 0.8 mL/min;
254 nm): tR = 18.6 (major enantiomer) and 26.6 min (minor
FTIR (KBr): ν = 3654, 3473, 3028, 2952, 1953, 1739, 1599, 1494,
˜
1452, 1435, 1027, 967, 766, 699 cm–1.
1
enantiomer); 94%ee. H NMR (500 MHz, CDCl3): δ = 8.20–8.23
(E)-Dimethyl 2-[1,3-Bis(4-methoxyphenyl)allyl]malonate (7a): The
preparation was carried out according to the general procedure by
using rac-(E)-1,3-bis(4-methoxylphenyl)-2-propen-1-yl acetate
(40 mg, 0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol)
with a reaction time of 2 d. The desired product 7a (25 mg, 50%
yield) was obtained as colorless oil. The ee value was determined
by HPLC analysis (Chiralpak AD-H column; hexanes/2-propanol,
80:20; 0.8 mL/min; 254 nm): tR = 18.2 (major enantiomer) and
29.5 min (minor enantiomer); 71 % ee. 1H NMR (500 MHz,
CDCl3): δ = 7.24–7.19 (m, 4 H, Ar), 6.85–6.78 (m, 4 H, Ar), 6.38
(d, J = 15.5 Hz, 1 H, CH), 6.16 (dd, J = 15.5 Hz, 8.5 Hz, 1 H,
CH), 4.19 (dd, J = 10.5 Hz, 8.5 Hz, 1 H, CH), 3.88 (d, J = 11.0 Hz,
1 H, CH), 3.78 (s, 3 H, CH3), 3.77 (s, 3 H, CH3), 3.69 (s, 3 H,
CH3), 3.52 (s, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ =
168.3, 167.9, 159.1, 158.5, 132.4, 130.9, 129.7, 128.8, 127.5, 127.1,
(m, 2 H, Ar), 8.15–8.17 (m, 2 H, Ar), 7.45–7.50 (m, 4 H, Ar), 6.57
(d, J = 15.8 Hz, 1 H, CH), 6.50 (dd, J = 15.8 Hz, 8.1 Hz, 1 H,
CH), 4.44 (dd, J = 10.4 Hz, 8.1 Hz, 1 H, CH), 3.99 (d, J = 10.5 Hz,
1 H, CH), 3.74 (s, 3 H, CH3), 3.58 (s, 3 H, CH3) ppm.
(E)-Dimethyl 2-[1,3-Bis(2-fluorophenyl)allyl]malonate (7e): The
preparation was carried out according to the general reaction pro-
cedure by using rac-(E)-1,3-bis(4-fluorophenyl)-2-propen-1-yl acet-
ate (30 mg, 0.1 mmol) and dimethyl malonate (0.042 mL,
0.3 mmol) with a reaction time of 1 d. The desired product 7e
(36 mg, 99% yield) was obtained as colorless oil. The ee value was
determined by HPLC analysis (Chiralpak AD-H column; hexanes/
2-propanol, 80:20; 0.8 mL/min; 254 nm): tR = 7.8 (major enantio-
mer) and 8.6 min (minor enantiomer); 95 % ee. 1 H NMR
(500 MHz, CDCl3): δ = 7.41 (td, J = 8 Hz, 2 Hz, 1 H, Ar), 7.33
(td, J = 7.5 Hz, 2 Hz, 1 H, Ar), 7.18–7.26 (m, 2 H, Ar), 7.12 (td, J
= 7.5 Hz, 1.5 Hz, 1 H, Ar), 7.08 (m, 2 H, Ar), 7.01(ddd, J = 11 Hz,
8.5 Hz, 1 Hz, 1 H, Ar), 6.7 (d, J = 16 Hz, 1 H, CH), 6.49 (ddd, J
= 16 Hz, 9 Hz, 1 Hz, 1 H, CH), 4.51 (dd, J = 10.5 Hz, 9 Hz, 1 H,
CH), 4.14 (d, J = 11 Hz, 1 H, CH), 3.74 (s, 3 H, CH3), 3.56 (s, 3
H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 168.05, 167.68,
114.0, 113.8, 57.9, 55.3, 55.2, 52.5, 52.4, 48.4 ppm. FTIR (KBr): ν
˜
= 3491, 2954, 2837, 1755, 1738, 1608, 1512, 1463, 1302, 1250, 1176,
1033, 968, 832, 813 cm–1. MS (ESI): m/z = 407 [M + Na]+. HRMS
(ESI): calcd. for [C22H24O6Na]+ 407.1471; found 407.1466.
(E)-Dimethyl 2-(1,3-Di-p-tolylallyl)malonate (7b): The preparation
was carried out according to the general procedure by using rac-
(E)-1,3-bis(4-methylphenyl)-2-propen-1-yl acetate (30 mg, 161.70, 161.15, 157.7, 159.1, 129.97, 129.96, 129.93, 129.92, 129.87,
0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol) with a re-
action time of 2 d. The desired product 7b (33 mg, 95% yield) was
129.83, 129.01, 128.94, 127.56, 127.53, 127.00, 126.89, 125.28,
125.25, 124.56, 124.46, 124.43, 124.40, 124.05, 124.02, 116.06,
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O31208
/KAP1
Date: 13-11-13 18:55:25
Pages: 11
Enantioselective Alkylation of Allyl Acetates
115.89, 115.74, 115.57, 56.06, 56.05, 52.67, 52.53, 44.79 ppm. FTIR NMR (125 MHz, CDCl3): δ = 167.9, 167.5, 141.9, 138.4, 134.6,
(KBr): ν = 3644, 3545, 3464, 3004, 2955, 2847, 1746, 1613, 1584, 134.5, 131.2, 130.1, 129.8, 128.1, 127.7, 126.3, 126.1, 124.7, 57.2,
˜
1488, 1455, 1436, 1337, 1231, 1154, 1119, 1025, 970, 848, 803, 759, 52.8, 52.6, 48.7 ppm. FTIR (KBr): ν = 3464, 3062, 3004, 2953,
˜
722, 696, 543 cm–1. MS (ESI): m/z = 383 [M + Na]+. HRMS (ESI):
2844, 1738, 1594, 1573, 1475, 1434, 1297, 1253, 1192, 1164, 1081,
calcd. for [C20H18O4F2Na]+ 383.1071; found 383.1074.
967, 879, 782, 696 cm–1.
(E)-Dimethyl 2-[1,3-Bis(4-chlorophenyl)allyl]malonate (7j): The
preparation was carried out according to the general procedure by
using rac-(E)-1,3-bis(4-chlorophenyl)-2-propen-1-yl acetate (32 mg,
0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol) with a re-
action time of 2 d. The desired product 7j (35 mg, 90% yield) was
obtained as a colorless oil. The ee value was determined by HPLC
analysis (Chiralpak AD-H column; hexanes/2-propanol, 80:20;
0.8 mL/min; 254 nm): tR = 13.6 (major enantiomer) and 21.0 min
(minor enantiomer); 91 % ee. 1H NMR (500 MHz, CDCl3): δ =
7.30–7.27 (m, 2 H, Ar), 7.25–7.20 (m, 6 H, Ar), 6.39 (d, J =
16.0 Hz, 1 H, CH), 6.25 (dd, J = 16.0 Hz, 9.0 Hz, 1 H, CH), 4.23
(dd, J = 11.0 Hz, 9.0 Hz, 1 H, CH), 3.89 (d, J = 10.5 Hz, 1 H,
CH), 3.70 (s, 3 H, CH3), 3.54 (s, 3 H, CH3) ppm. 13C NMR
(125 MHz, CDCl3): δ = 167.9, 167.5, 138.5, 135.0, 133.4, 133.1,
131.0, 129.3, 129.2, 128.9, 128.7, 127.6, 57.3, 52.7, 52.6, 48.4 ppm.
(E)-Dimethyl 2-[1,3-Bis(3-fluorophenyl)allyl]malonate (7f): The
preparation was carried out according to the general reaction pro-
cedure by using rac-(E)-1,3-bis(4-fluorophenyl)-2-propen-1-yl acet-
ate (30 mg, 0.1 mmol) and dimethyl malonate (0.042 mL,
0.3 mmol) with a reaction time of 2 d. The desired product 7f
(34 mg, 94% yield) was obtained as a white solid; m.p. 54 °C. The
ee value was determined by HPLC analysis (Chiralpak AD-H col-
umn; hexanes/2-propanol, 80:20; 0.8 mL/min; 254 nm): tR = 8.1
1
(major enantiomer) and 10.4 min (minor enantiomer); 94%ee. H
NMR (500 MHz, CDCl3): δ = 7.31 (m, 1 H, Ar), 7.26 (m, 1 H,
Ar), 7.09 (d, J = 8 Hz, 2 H, Ar), 7.03 (tt, J = 10 Hz, 2.5 Hz, 2 H,
Ar), 6.95 (m, 2 H, Ar), 6.47 (d, J = 16 Hz, 1 H, CH), 6.32 (dd, J
= 15.5 Hz, 8.5 Hz, 1 H, CH), 4.29 (dd, J = 10.5 Hz, 9 Hz, 1 H,
CH), 3.94 (d, J = 10.5 Hz, 1 H, CH), 3.73 (s, 3 H, CH3), 3.58 (s, 3
H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 167.9, 167.5,
163.04 (d, J = 245 Hz), 162.90 (d, J = 246 Hz), 142.46 (d, J =
6.25 Hz), 138.91 (d, J = 7.5 Hz), 131.32, 131.30, 130.31 (d, J =
8.75 Hz), 130.0 (d, J = 8.75 Hz), 129.97, 123.52 (d, J = 2.5 Hz),
122.36 (d, J = 2.5 Hz), 114.88 (d, J = 21.25 Hz), 114.59 (d, J =
21.25 Hz), 114.28 (d, J = 21.25 Hz), 112.85 (d, J = 21.25 Hz), 57.28,
FTIR (KBr): ν = 3665, 3462, 2953, 1899, 1754, 1594, 1488, 1159,
˜
1013, 827 cm–1.
(E)-Dimethyl 2-[1,3-Bis(3-bromophenyl)allyl]malonate (7k): The
preparation was carried out according to the general procedure by
using rac-(E)-1,3-bis(3-bromophenyl)-2-propen-1-yl acetate (42 mg,
0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol) with a re-
action time of 2 d. The desired product 7k (44 mg, 89% yield) was
obtained as a colorless oil. The ee value was determined by HPLC
analysis (Chiralpak AD-H column; hexanes/2-propanol, 80:20;
0.8 mL/min; 254 nm): tR = 7.4 (major enantiomer) and 9.5 min
(minor enantiomer); 93 % ee. 1H NMR (500 MHz, CDCl3): δ =
7.49–7.45 (m, 2 H, Ar), 7.41–7.35 (m, 2 H, Ar), 7.25–7.20 (m, 3 H,
Ar), 7.18–7.15 (m, 1 H, Ar), 6.42 (d, J = 16.0 Hz, 1 H, CH), 6.31
(dd, J = 15.5 Hz, 8.5 Hz, 1 H, CH), 4.24 (dd, J = 10.5 Hz, 8.5 Hz,
1 H, CH), 3.93 (d, J = 10.5 Hz, 1 H, CH), 3.74 (s, 3 H, CH3), 3.59
(s, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 167.8, 167.4,
142.2, 138.7, 131.1, 131.0, 130.7, 130.5, 130.4, 130.1, 129.9, 129.2,
126.5, 125.2, 122.8, 122.7, 57.2, 52.8, 52.6, 48.6 ppm. FTIR (KBr):
52.75, 52.62, 48.64 ppm. FTIR (KBr): ν = 3031, 3004, 2954, 1738,
˜
1611, 1585, 1487, 1447, 1435, 1257, 1146, 1022, 969, 875, 783,
698 cm–1. MS (ESI): m/z = 383 [M + Na]+. HRMS (ESI): calcd.
for [C20H18O4F2Na]+ 383.1071; found 383.1060.
(E)-Dimethyl 2-[1,3-Bis(4-fluorophenyl)allyl]malonate (7g): The
preparation was carried out according to the general procedure by
using rac-(E)-1,3-bis(4-fluorophenyl)-2-propen-1-yl acetate (30 mg,
0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol) with a re-
action time of 2 d. The desired product 7g (35 mg, 96% yield) was
obtained as a colorless oil. The ee value was determined by HPLC
analysis (Chiralpak AD-H column; hexanes/2-propanol, 80:20;
0.8 mL/min; 254 nm): tR = 10.04 (major enantiomer) and 15.01 min
(minor enantiomer); 93 % ee. 1H NMR (500 MHz, CDCl3): δ =
7.29–7.23 (m, 4 H, Ar), 7.03–6.94 (m, 4 H, Ar), 6.41 (d, J =
15.6 Hz, 1 H, CH), 6.21 (dd, J = 15.5 Hz, 8.5 Hz, 1 H, CH), 4.26–
4.22 (m, 1 H, CH), 3.88 (d, J = 11.0 Hz, 1 H, CH) 3.70 (s, 3 H,
CH3), 3.53 (s, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ =
168.0, 167.3, 163.0 (d, J = 64.1 Hz), 161.1 (d, J = 64.1 Hz), 135.8
(d, J = 3.7 Hz), 132.8 (d, J = 3.7 Hz), 130.8, 129.4 (d, J = 8.7 Hz),
128.5, 127.8 (d, J = 7.5 Hz), 115.6 (d, J = 21.3 Hz), 115.4 (d, J =
ν = 3425, 2951, 2924, 1737, 1591, 1566, 1473, 1433, 1298, 1254,
˜
1164, 1072, 966, 781, 692 cm–1.
(E)-Dimethyl 2-[1,3-Bis(4-bromophenyl)allyl]malonate (7l): The
preparation was carried out according to the general procedure by
using rac-(E)-1,3-bis(3-bromophenyl)-2-propen-1-yl acetate (42 mg,
0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol) with a re-
action time of 2 d. The desired product 7l (41 mg, 85% yield) was
obtained as a colorless oil. The ee value was determined by HPLC
analysis (Chiralpak AD-H column; hexanes/2-propanol, 80:20;
0.8 mL/min; 254 nm): tR = 16.5 (major enantiomer) and 24.5 min
(minor enantiomer); 92 % ee. 1H NMR (500 MHz, CDCl3): δ =
7.48–7.45 (m, 2 H, Ar), 7.43–7.40 (m, 2 H, Ar), 7.20–7.17 (m, 4 H,
Ar), 6.41 (d, J = 15.5 Hz, 1 H, CH), 6.29 (dd, J = 16.0 Hz, 8.5 Hz,
1 H, CH), 4.24 (dd, J = 11.0 Hz, 8.5 Hz, 1 H, CH), 3.91 (d, J =
21.3 Hz), 57.6, 52.6, 52.5, 48.2 ppm. FTIR (KBr): ν = 3440, 3004,
˜
2954, 2923, 2850, 1738, 1601, 1508, 1435, 1311, 1229, 1159, 1103,
1021, 968, 836 cm–1. MS (ESI): m/z = 383 [M + Na]+. HRMS
(ESI): calcd. for [C20H18O4F2Na]+ 383.1071; found 383.1074.
(E)-Dimethyl 2-[1,3-Bis(3-chlorophenyl)allyl]malonate (7i): The
preparation was carried out according to the general procedure by
using (E)-1,3-bis(3-chlorophenyl)-2-propen-1-yl acetate (32 mg,
0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol) with a re-
action time of 2 d. The desired product 7i (37 mg, 95% yield) was
obtained as a colorless oil. The ee value was determined by HPLC
analysis (Chiralpak AD-H column; hexanes/2-propanol, 80:20;
0.8 mL/min; 254 nm): tR = 7.2 (major enantiomer) and 9.2 min
(minor enantiomer); 90 % ee. 1H NMR (500 MHz, CDCl3): δ =
7.33–7.29 (m, 2 H, Ar), 7.28–7.27 (m, 1 H, Ar), 7.25–7.18 (m, 5 H,
Ar), 6.44 (d, J = 15.5 Hz, 1 H, CH), 6.32 (dd, J = 15.5 Hz, 9.0 Hz,
1 H, CH), 4.26 (dd, J = 11.0 Hz, 9.0 Hz, 1 H, CH), 3.94 (d, J =
10.5 Hz, 1 H, CH), 3.72 (s, 3 H, CH3), 3.57 (s, 3 H, CH3) ppm. 13
C
NMR (125 MHz, CDCl3): δ = 167.9, 167.5, 138.9, 135.5, 131.9,
131.6, 131.1, 129.6, 129.2, 127.9, 121.5, 121.2, 57.2, 52.7, 52.6,
48.4 ppm. FTIR (KBr): ν = 3462, 3026, 2952, 1738, 1487, 1434,
˜
1312, 1254, 1160, 1072, 968, 824 cm–1.
(E)-Dimethyl 2-[1,3-Di(naphthalen-2-yl)allyl]malonate (7m): The
preparation was carried out according to the general procedure by
using rac-(E)-1,3-bis(naphthalene-2-yl)-2-propen-1-yl acetate
(35 mg, 0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol)
with a reaction time of 2 d. The desired product 7m (41 mg, 98%
10.5 Hz, 1 H, CH), 3.73 (s, 3 H, CH3), 3.58 (s, 3 H, CH3) ppm. 13
C
Eur. J. Org. Chem. 0000, 0–0
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S. Jayakumar, M. Prakash, K. Balaraman, V. Kesavan
FULL PAPER
yield) was obtained as a white solid; m.p. 106 °C. The ee value was
determined by HPLC analysis (Chiralpak AD-H column; hexanes/
2-propanol, 80:20; 0.8 mL/min; 254 nm): tR = 19.2 (major enantio-
mer) and 25.3 min (minor enantiomer); 91 % ee. 1H NMR
(500 MHz, CDCl3): δ = 7.86–7.75 (m, 7 H, Ar), 7.70 (s, 1 H, Ar),
7.57–7.55 (m, 1 H, Ar), 7.52–7.43 (m, 5 H, Ar), 6.71 (d, J =
15.5 Hz, 1 H, CH), 6.57 (dd, J = 15.5 Hz, 8.5 Hz, 1 H, CH), 4.56–
4.52 (m, 1 H, CH), 4.16 (d, J = 10.5 Hz, 1 H, CH), 3.76 (s, 3 H,
CH3), 3.52 (s, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ =
168.2, 167.8, 137.6, 134.2, 133.6, 133.5, 132.9, 132.6, 132.2, 129.3,
128.5, 128.1, 127.9, 127.8, 127.7, 127.6, 126.5, 126.3, 126.2, 126.1,
2954, 2844, 1890, 1755, 1648, 1601, 1505, 1451, 1434, 1285, 1160,
1102, 1026, 968, 939, 913, 836, 744, 699 cm–1.
(E)-Dimethyl 2-[1-(4-Chlorophenyl)-3-phenylallyl]malonate (9c) and
(E)-Dimethyl 2-[3-(4-Chlorophenyl)-1-phenylallyl]malonate (10c):
The preparation was carried out according to the general procedure
by using rac-(E)-1-(4-chlorophenyl)-3-phenylallyl acetate (30 mg,
0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol) with a re-
action time of 2 d. The desired product (i.e., 9c and 10c, 34 mg,
96% yield) was obtained as colorless oil with equal ratio of 9c and
10c. The ee values were determined by HPLC analysis, and the
HPLC sample was prepared by preparative TLC. HPLC (Chi-
ralpak AD-H column; hexanes/2-propanol, 80:20; 0.8 mL/min;
254 nm): tR = 15.2 (major enantiomer of 9c) and 18.0 min (minor
enantiomer of 9c); 95%ee; tR = 18.7 (major enantiomer of 10c) and
126.1, 125.8, 123.5, 57.6, 53.4, 52.6, 49.3 ppm. FTIR (KBr): ν =
˜
3453, 3055, 3020, 2951, 2923, 2849, 1756, 1737, 1598, 1508, 1434,
1259, 1154, 1020, 966, 816, 749 cm–1.
1
31.2 min (minor enantiomer of 10c); 92%ee. H NMR (500 MHz,
(E)-Dimethyl 2-[1-(4-Methoxyphenyl)-3-phenylallyl]malonate (9a)
and (E)-Dimethyl 2-[3-(4-Methoxyphenyl)-1-phenylallyl]malonate
(10a): The preparation was carried out according to the general
procedure by using rac-(E)-1-(4-methoxyphenyl)-3-phenylallyl acet-
ate (30 mg, 0.1 mmol) and dimethyl malonate (0.042 mL,
0.3 mmol) with a reaction time of 2 d. The desired product (i.e., 9a
and 10a, 29 mg, 85% yield) was obtained as colorless oil with an
equal ratio of 9a and 10a. The ee values were determined by HPLC
analysis, and the HPLC sample was prepared by preparative TLC.
HPLC (Chiralpak AD-H column; hexanes/2-propanol, 90:10;
0.5 mL/min; 254 nm): tR = 28.4 (major enantiomer of 9a) and
40.2 min (minor enantiomer of 9a); 73 % ee; tR = 27.2 (major
enantiomer of 10a) and 41.7 min (minor enantiomer of 10a);
CDCl3): δ = 7.36–7.22 (m, 20 H, Ar), 6.46 (m, 2 H, CH) 6.32 (m,
2 H, CH), 4.27 (m, 2 H, CH), 3.96 (d, J = 11 Hz, 1 H, CH), 3.93
(d, J = 10.5 Hz, 2 H, CH), 3.73 (s, 3 H, CH3), 3.72 (s, 3 H, CH3),
3.57 (s, 3 H, CH3), 3.54 (s, 3 H, CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 168.16, 167.9, 167.7, 167.6, 139.9, 138.7, 136.6, 135.3,
133.2, 132.9, 132.2, 130.6, 129.8, 129.2, 128.8, 128.7, 128.6, 128.5,
127.8, 127.7, 127.5, 127.2, 126.4, 57.5, 57.4, 52.7, 52.6, 52.58, 52.4,
49.1, 48.4 ppm. FTIR (KBr): ν = 3647, 3478, 3083, 3060, 3004,
˜
2953, 2843, 1952, 1897, 1755, 1598, 1511, 1461, 1407, 1091, 940,
914, 828, 799, 748, 700, 676 cm–1.
(E)-Dimethyl 2-[3-(2-Bromophenyl)-1-phenylallyl]malonate (9d) and
(E)-Dimethyl 2-[1-(2-Bromophenyl)-3-phenylallyl]malonate (10d):
The preparation was carried out according to the general procedure
by using rac-(E)-3-(2-bromophenyl)-1-phenylallyl acetate (33 mg,
0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol) with a re-
action time of 2 d. The desired product (i.e., 9d and 10d, 38 mg,
95% yield) was obtained as colorless oil with equal ratio of 9d and
10d. The ee values were determined by HPLC analysis, and the
HPLC sample was prepared by preparative TLC. HPLC (Chiralcel
OD-H column; hexanes/2-propanol, 99:1; 0.5 mL/min; 254 nm): tR
= 25.0 (major enantiomer of 9d) and 27.4 min (minor enantiomer
of 9d); 84%ee; tR = 22.4 (major enantiomer of 10d) and 29.5 min
1
91%ee. H NMR (500 MHz, CDCl3): δ = 7.86–7.75 (m, 7 H, Ar),
7.70 (s, 1 H, Ar), 7.57–7.55 (m, 1 H, Ar), 7.52–7.43 (m, 5 H, Ar),
6.71 (d, J = 15.5 Hz, 1 H, CH), 6.57 (dd, J = 15.5 Hz, 8.5 Hz, 1
H, CH), 4.56–4.52 (m, 1 H, CH), 4.16 (d, J = 10.5 Hz, 1 H, CH),
3.76 (s, 3 H, CH3), 3.52 (s, 3 H, CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 168.2, 167.8, 137.6, 134.2, 133.6, 133.5, 132.9, 132.6,
132.2, 129.3, 128.5, 128.1, 127.9, 127.8, 127.7, 127.6, 126.5, 126.3,
126.2, 126.1, 126.1, 125.8, 123.5, 57.6, 53.4, 52.6, 49.3 ppm. FTIR
(KBr): ν = 3653, 3462, 3029, 3005, 2954, 2844, 1952, 1890, 1738,
˜
1602, 1507, 1495, 1450, 1435, 1226, 1104, 1023, 968, 939, 913, 834,
745, 700 cm–1.
1
(minor enantiomer of 10d); 97%ee. H NMR (500 MHz, CDCl3):
δ = 7.60 (dd, J = 8 Hz, 1 Hz, 1 H, Ar), 7.53 (dd, J = 8 Hz, 1.5 Hz,
1 H, Ar), 7.44 (dd, J = 8 Hz, 1.5 Hz, 1 H, Ar), 7.33 (m, 10 H, Ar),
7.24 (m, 3 H, Ar), 7.11 (m, 2 H, CH), 6.84 (d, J = 16 Hz 1 H, CH),
6.55 (d, J = 15.5 Hz, 1 H, CH), 6.31 (m, 2 H, CH), 4.85 (m, 1 H,
CH), 4.35 (dd, J = 10.5 Hz, 9 Hz, 1 H, CH), 4.13 (d, J = 10.5 Hz,
1 H, CH), 4.0 (d, J = 11 Hz, 1 H, CH), 3.77 (s, 3 H, CH3), 3.73 (s,
3 H, CH3), 3.59 (m, 3 H, CH3), 3.56 (s, 3 H, CH3) ppm. 13C NMR
(125 MHz, CDCl3): δ = 168.09, 168.03, 167.7, 167.61, 139.7, 139.4,
136.8, 136.7, 133.5, 132.8, 132.1, 130.5, 128.9, 128.8, 128.57,
128.50, 127.9, 127.75, 127.70, 127.48, 127.44, 127.3, 127.2, 126.4,
(E)-Dimethyl 2-[1-(4-Fluorophenyl)-3-phenylallyl]malonate (9b) and
(E)-Dimethyl 2-[3-(4-Fluorophenyl)-1-phenylallyl]malonate (10b):
The preparation was carried out according to the general procedure
by using rac-(E)-1-(4-fluorophenyl)-3-phenylallyl acetate (27 mg,
0.1 mmol) and dimethyl malonate (0.042 mL, 0.3 mmol) with a re-
action time of 2 d. The desired product (i.e., 9b and 10b, 33 mg,
98% yield) was obtained as a white solid with a 2:1 ratio of 9b and
10b; m.p. 95 °C The ee values were determined by HPLC analysis,
and the HPLC sample was prepared by preparative TLC. HPLC
(Chiralcel OJ-H column; hexanes/2-propanol, 90:10; 0.5 mL/min;
254 nm): tR = 40.0 (minor enantiomer of 9b) and 47.6 min (major
enantiomer of 9b); 91%ee; tR = 41.9 (major enantiomer of 10b)
and 48.6 min (minor enantiomer of 10b); 91 % ee. 1H NMR
(500 MHz, CDCl3): δ = 7.35–7.22 (m, 8 H, Ar), 7.031 (t, J =
8.5 Hz, 1 H, Ar), 6.98 (t, J = 8.5 Hz, 1 H, Ar), 6.47 (dd, J = 16 Hz,
57.5, 56.4, 52.8, 52.6, 52.5, 49.1, 47.4 ppm. FTIR (KBr): ν = 3058,
˜
3028, 3004, 2952, 1951, 1739, 1494, 1466, 1435, 1316, 1255, 1193,
1159, 1024, 966, 750, 699 cm–1. MS (ESI): m/z = 425 [M + Na]+.
HRMS (ESI): calcd. for [C20H19O4BrNa]+ 425.0364; found
425.0358.
1 H, CH), 6.30 (m, 1 H, CH), 4.28 (m, 1 H, CH), 3.95 (m, 1 H, (E)-Dimethyl 2-[3-(2-Bromophenyl)-1-(4-fluorophenyl)allyl]malonate
CH), 3.77 (s, 3 H, CH3), 3.73 (s, 3 H, CH3), 3.55 and 3.54 (s, 3 H, (9e) and (E)-Dimethyl 2-[1-(2-Bromophenyl)-3-(4-fluorophenyl)allyl-
CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 168.19, 168.03, ]malonate (10e): The preparation was carried out according to the
167.73, 167.69, 162.3 (d, J = 245 Hz), 161.84 (d, J = 243.7 Hz),
140.09, 136.67, 135.92 (d, J = 2.5 Hz), 132.97 (d, J = 2.5 Hz), 132.0,
general procedure by using rac-(E)-3-(2-bromophenyl)-1-(4-
fluorophenyl)allyl acetate (35 mg, 0.1 mmol) and dimethyl malon-
130.68, 129.47 (d, J = 8.75 Hz), 128.83, 128.76, 128.53,127.93, ate (0.042 mL, 0.3 mmol) with a reaction time of 2 d. The desired
127.86, 127.84, 127.70, 127.22, 126.39, 115.59 (d, J = 20 Hz),
115.38 (d, J = 21.25 Hz), 57.72, 57.62, 52.68, 52.63, 52.52, 52.47,
product (i.e., 9e and 10e, 41 mg, 98% yield) was obtained as as
white solid with an equal ratio of 9e and 10e; m.p. 89 °C. The ee
values were determined by HPLC analysis; and the HPLC sample
49.14, 48.35 ppm. FTIR (KBr): ν = 3655, 3462, 3055, 3029, 3005,
˜
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

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Pages: 11
Enantioselective Alkylation of Allyl Acetates
was prepared by preparative TLC. HPLC (Chiralcel OD-H column;
hexanes/2-propanol, 99:1; 0.5 mL/min; 254 nm): tR = 26.4 (major
enantiomer of 9e) and 30.0 min (minor enantiomer of 9e); 82%ee;
tR = 23.8 (major enantiomer of 10e) and 31.9 min (minor enantio-
mer of 10e); 99%ee. H NMR (500 MHz, CDCl3): δ = 7.58 (m, 2
H, Ar), 7.52 (td, J = 9.5 Hz, 1 Hz, 1 H, Ar), 7.44 (m, 2 H, Ar),
the general procedure by using rac-1-phenylallyl acetate (13, 20 mg,
0.11 mmol) and dimethyl malonate (0.045 mL, 0.33 mmol) with a
reaction time of 3d. The desired product (i.e., 14a and 14b, 18 mg,
65% combined yield) was obtained as a colorless oil as a mixture
of regioisomers (14a/14b, 13:1). The ee value was determined by
HPLC analysis (Chiralcel OJ-H column; hexanes/2-propanol, 99:1;
1
7.38 (m, 1 H, Ar), 7.30 (m, 6 H, Ar), 7.23 (m, 2 H, Ar), 7.11 (m, 0.5 mL/min; 240 nm): tR = 40.0 (major enantiomer) and 36.0 min
4 H, Ar), 7.01 (m, 5 H, Ar), 6.27 (m, 3 H, CH), 6.82 (d, J =
15.5 Hz, 1 H, CH), 6.50 (d, J = 16 Hz, 1 H, CH), 4.83 (m, 1 H,
CH), 4.34 (dd, J = 10.5 Hz, 8.5 Hz, 1 H, CH), 4.11 (d, J = 10.5 Hz,
1 H, CH), 3.95 (d, J = 11 Hz, 1 H, CH), 3.77 (s, 3 H, CH3), 3.73
(s, 3 H, CH3), 3.59 (s, 3 H, CH3), 3.57 (s, 3 H, CH3) ppm. 13C
NMR (125 MHz, CDCl3): δ = 168.3, 167.9, 167.6, 167.5, 166.9,
139.2, 136.6, 134.2, 133.5, 132.9, 132.8, 131.9, 131.6, 130.7, 129.58,
129.52, 129.4, 129.2, 129.1, 128.5, 128.2, 128.1, 128.06, 128.02,
127.9, 127.7, 127.5, 127.4, 127.2, 127.1, 124.7, 123.8, 123.5, 115.7,
115.6, 115.49, 115.42, 115.3, 57.6, 56.3, 52.8, 52.7, 52.64, 52.61,
(minor enantiomer); 46 % ee. 1H NMR (500 MHz, CDCl3): δ =
7.38–7.21 (m, 5 H, Ar), 6.20 (m, 1 H, CH), 5.13 (m, 2 H, CH2),
4.13 (dd, J = 8.5 Hz, 8 Hz, 1 H, CH), 3.78 (s, 6 H, CH3) ppm.
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 1H and 13C NMR spectra of all new compounds
and HPLC data for all substrates are provided.
Acknowledgments
This work was supported by the Department of Science & Technol-
ogy, Government of India, New Delhi (grant number SR/S1/OC-
60/2006), the Department of Biotechnology IIT-Madras for the in-
frastructure, the SAIF IIT-Madras for the spectral analysis, and
the Department of Chemistry for the HRMS analysis.
52.59, 48.2, 47.4 ppm. FTIR (KBr): ν = 3465, 3004, 2953, 2849,
˜
1738, 1645, 1603, 1509, 1466, 1435, 1231, 1161, 1021, 967, 835,
754 cm–1. MS (ESI): m/z = 443 [M + Na]+. HRMS (ESI): calcd.
for [C20H18O4NaFBr]+ 443.0270; found 443.0280.
(E)-Dimethyl 2-[3-(2-Chlorophenyl)-1-(4-chlorophenyl)allyl]malon-
ate (9f) and (E)-Dimethyl 2-[1-(2-Chlorophenyl)-3-(4-chlorophenyl)-
allyl]malonate (10f): The preparation was carried out according to
the general procedure by using rac-(E)-3-(2-chlorophenyl)-1-(4-
chlorophenyl)allyl acetate (32 mg, 0.1 mmol) and dimethyl malon-
ate (0.042 mL, 0.3 mmol) with a reaction time of 2 d. The desired
product (i.e., 9f and 10f, 38 mg, 98% yield) was obtained as a color-
less oil with an equal ratio of 9f and 10f. The ee values were deter-
mined by HPLC analysis, and the HPLC sample was prepared by
preparative TLC. HPLC (Phenominex Lux-3 cellulose-5 column;
hexanes/2-propanol, 90:10; 0.8 mL/min; 254 nm): tR = 9.9 (major
enantiomer of 9f) and 11.1 min (minor enantiomer of 9f); 94%ee;
tR = 13.4 min (major enantiomer of 10f) and 32.8 min (minor
enantiomer of 10f); 97%ee. 1H NMR (500 MHz, CDCl3): δ = 7.86–
7.75 (m, 7 H, Ar), 7.70 (s, 1 H, Ar), 7.57–7.55 (m, 1 H, Ar), 7.52–
7.43 (m, 5 H, Ar), 6.71 (d, J = 15.5 Hz, 1 H, CH), 6.57 (dd, J =
15.5 Hz, 8.5 Hz, 1 H, CH), 4.56–4.52 (m, 1 H, CH), 4.16 (d, J =
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i) G. V. Albano, M. Bandini, M. Monari, E. Marcucci, F. Picci-
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dron: Asymmetry 2010, 21, 2275–2280; m) X. Du, H. Liu, D.
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NMR (125 MHz, CDCl3): δ = 168.2, 167.8, 137.6, 134.2, 133.6,
133.5, 132.9, 132.6, 132.2, 129.3, 128.5, 128.1, 127.9, 127.8, 127.7,
127.6, 126.5, 126.3, 126.2, 126.1, 126.1, 125.8, 123.5, 57.6, 53.4,
52.6, 49.3 ppm. FTIR (KBr): ν = 3465, 3029, 3004, 2953, 2846,
˜
1906, 1738, 1593, 1491, 1471, 1455, 1435, 1406, 1311, 1257, 1161,
1092, 1035, 1014, 968, 826, 799, 754 cm–1. MS (ESI): m/z = 415 [M
+ Na]+. HRMS (ESI): calcd. for [C20H18O4Cl2Na]+ 415.0480;
found 415.0499.
(E)-Dimethyl 2-(4-Phenylbut-3-en-2-yl)malonate (12a): The prepa-
ration was carried out according to the general procedure by using
rac-(E)-4-phenylbut-3-en-2-yl acetate (20 mg, 0.1 mmol) and di-
methyl malonate (0.042 mL, 0.3 mmol) with a reaction time of 3d.
The desired product 12a (20 mg, 80% yield) was obtained as a col-
orless oil. The ee value was determined by HPLC analysis (Chi-
ralcel OD-H column; hexanes/2-propanol, 99:1; 0.5 mL/min;
240 nm): tR = 21.5 (major enantiomer) and 19.6 min (minor
1
enantiomer); 53%ee. H NMR (500 MHz, CDCl3): δ = 7.34–7.19
(m, 5 H, Ar), 6.45 (d, J = 15.5, 1 H, CH), 6.12 (dd, J = 16.0 Hz,
8.5 Hz, 1 H, CH), 3.75 (s, 3 H, CH3), 3.67 (s, 3 H, CH3), 3.40 (d,
J = 9.0 Hz, 1 H, CH), 3.16–3.09 (m, 1 H, CH), 1.19 (d, J = 6.5 Hz,
[5] a) S. G. Lee, C. W. Lim, C. M. Song, I. O. Kim, C. H. Jun,
Tetrahedron: Asymmetry 1997, 8, 2927–2932; b) S. G. Lee, C. V.
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C. W. Lim, Bull. Korean Chem. Soc. 2001, 22, 231–233; e) S. G.
3 H, CH ) ppm. FTIR (KBr): ν = 3463, 2954, 1754, 1738, 1435,
˜
3
1246, 1158, 1022, 968, 748, 694 cm–1.
Dimethyl 2-Cinnamylmalonate (14a) and Dimethyl 2-(1-Phenyl-
allyl)malonate (14b): The preparation was carried out according to
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O31208
/KAP1
Date: 13-11-13 18:55:25
Pages: 11
S. Jayakumar, M. Prakash, K. Balaraman, V. Kesavan
FULL PAPER
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Chem. 1999, 64, 4445–4451; f) S. G. Lee, H. R. Jung, K. M.
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Published Online: ᭿
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O31208
/KAP1
Date: 13-11-13 18:55:25
Pages: 11
Enantioselective Alkylation of Allyl Acetates
Asymmetric Allylic Alkylation
S. Jayakumar, M. Prakash, K. Balaraman,
V. Kesavan* ..................................... 1–11
Highly Enantioselective Alkylation of Allyl
Acetates Using Tartrate-Derived Bioxaz-
oline Ligands
Keywords: Asymmetric synthesis / Enantio-
selectivity / Palladium / Alkylation / Allylic
compounds
Palladium(II)-catalyzed asymmetric allylic
alkylation reactions of various symmetrical
and unsymmetrical allyl acetates were
achieved by using bioxazoline ligands,
which were derived from tartaric acid, to
give products with excellent enantioselec-
tivity.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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