Study of the lanthanide-catalyzed, aqueous, asymmetric Mukaiyama aldol reaction

Article abstract of DOI:10.1021/jo300800b

The development of efficient methods for the asymmetric Mukaiyama aldol reaction in aqueous solution has received great attention. We have developed a new series of chiral lanthanide-containing complexes that produce Mukaiyama aldol products with outstanding enantioselectivities. In this paper, we describe an optimized ligand synthesis, trends in stereoselectivity that result from changing lanthanide ions, and an exploration of substrate scope that includes aromatic and aliphatic aldehydes and silyl enol ethers derived from aromatic and aliphatic ketones.

Full text of DOI:10.1021/jo300800b

Article
pubs.acs.org/joc
Study of the Lanthanide-Catalyzed, Aqueous, Asymmetric
Mukaiyama Aldol Reaction
Yujiang Mei, Derek J. Averill, and Matthew J. Allen*
Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States
S
* Supporting Information
ABSTRACT: The development of efficient methods for the
asymmetric Mukaiyama aldol reaction in aqueous solution has
received great attention. We have developed a new series of
chiral lanthanide-containing complexes that produce Mukaiyama
aldol products with outstanding enantioselectivities. In this
paper, we describe an optimized ligand synthesis, trends in
stereoselectivity that result from changing lanthanide ions, and
an exploration of substrate scope that includes aromatic and
aliphatic aldehydes and silyl enol ethers derived from aromatic and aliphatic ketones.
(92:8 er). However, in our initial reports, the ligand synthesis
yielded only moderate syn:anti ratios (4:1 and 5:1), and we only
used Eu3+ to enable study of the system by luminescence-decay
measurements.14,29−31 We hypothesized that the choice of
solvent led to the lower than desired syn:anti ratios in our
ligand synthesis. Furthermore, because of the changes in size
and Lewis acidity across the lanthanide series, we hypothesized
that Eu3+ might not be the best metal to use with our best
ligand I. We have tested both of these hypotheses, and here, we
report (1) the optimization of the synthesis of chiral ligand I;
(2) the influence of lanthanide ion on stereoselectivity; and (3)
the exploration of the substrate scope.
INTRODUCTION
■
Compounds that contain optically active β-hydroxy carbonyl
moieties have received great attention from chemists and
biologists because these molecules are building blocks for
pharmaceuticals and natural products,1−7 and the Mukaiyama
aldol reaction is commonly used to synthesize the carbon−
carbon bonds in β-hydroxy carbonyls.2−27 To be stereo-
selective, this reaction requires a catalyst to induce stereo-
chemistry. Various Lewis-acid-catalyzed12−15 and organocata-
lyst-catalyzed16 Mukaiyama aldol reactions have been reported
for the enantioselective synthesis of β-hydroxy carbonyl
compounds; however, the majority of these reactions require
the use of aprotic anhydrous solvents because of the instability
of precatalysts and reaction intermediates in the presence of
water. In recent years, efforts have focused on the asymmetric
Mukaiyama aldol reaction in aqueous media because of the
environmental and financial benefits associated with water-
tolerant reactants.17 Examples of enantioselective catalysts that
work in the presence of water include Cu(OTf)2, Pb(OTf)2,
and Ln(OTf)3 with chiral crown ethers;18−22 Ga(OTf)3 with
Trost-type semicrowns;23,24 and Zn(OTf)2 and FeCl2 with
pybox-type ligands.25−27 These systems produce a wide range
of enantiometric ratios (er) that depend on the substrate
identity.
Recently, two reports of outstanding stereoselectivities for a
wide range of substrates in the presence of water were reported:
Fe(ClO4)2 with Bolm’s ligand15 and our C2-symmetric ligand
set (I−VI, Figure 1) with Eu(OTf)3.14 The Fe(ClO4)2 system
produced outstanding enantioselectivities (95:5−99:1 er),15 but
the ligand was synthesized in a moderate (54%) yield.28 Our
recent report of a new class of C2-symmetric ligands (I−VI)
with Eu(OTf)3 described efficient precatalysts for lanthanide-
catalyzed, enantioselective Mukaiyama aldol reactions in
aqueous solution (Figure 1). This catalytic system works for
aromatic aldehydes (95:5−97:3 er), aliphatic aldehydes (97:3−
99:1 er), and a silyl enol ether derived from an aliphatic ketone
RESULTS AND DISCUSSION
■
The moderate syn:anti ratios of ligands I−VI (Figure 1)
obtained during our ligand synthesis suggested that the (S)-
methyl 2-bromopropanoate was undergoing racemization
during the reaction with 1,7-diaza-12-crown-4 (Table 1). This
moderate syn:anti ratio presents a problem because the
undesirable anti ligands produce racemic aldol products. A
possible mechanism for this racemization is solvolysis of the
(S)-methyl 2-bromopropanoate; consequently, we hypothe-
sized that screening a variety of solvents would lead to a
minimization of racemization because solvolysis is faster in
polar, protic solvents. To test our hypothesis, we prepared
chiral ligand I from commercially available (S)-2-bromopropa-
noic acid (97.5:2.5 er) (Table 1). After esterification of (S)-2-
bromopropanoic acid, the resulting (S)-methyl 2-bromopropa-
noate was used directly in the next step. Our previously
reported synthesis in CH3CN provided ligand I with a 4:1
syn:anti ratio and >99:1 er at ambient temperature.14 To
increase the syn:anti ratio, we screened solvents and monitored
the syn:anti ratios of the resulting ligands for the reaction
Received: April 19, 2012
Published: June 14, 2012
© 2012 American Chemical Society
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Figure 1. C2-symmetric and racemic precatalysts (anti ligands form as a result of racemization of the bromide starting material during the ligand
syntheses).14
not as high as with ligand in a syn:anti ratio of >99:1 that was
achieved by purification by high-performance liquid chroma-
tography (HPLC). However, if HPLC purification is needed, a
starting point of 16:1 allows for much more pure syn isomer to
be obtained relative to a starting point of 5:1. These
experiments demonstrated that enantioselectivity is imparted
to products by syn ligands but not anti ligands and supports our
previously proposed mechanism for these precatalysts.14
Table 1. Solvent Effect on Synthesis of Chiral Ligand I
b
b
solvent
yield (%)
syn:anti
er (syn)
With our improved ligand synthesis, we studied the effect of
the choice of lanthanide ion on the stereoselectivity in the
Mukaiyama aldol reaction. The screening of lanthanide ions
was carried out using (Z)-trimethyl(1-phenylprop-1-enyloxy)-
silane and benzaldehyde catalyzed by 24 mol % ligand I
(syn:anti > 99:1) and 20 mol % lanthanide triflate (Table 3).
We chose this metal-to-ligand ratio because higher ligand
loadings led to outstanding stereoselectivities with many of the
larger lanthanides, making it impossible to differentiate the
influence of lanthanide ion selection on stereoselectivity. From
these reactions, we found that diastereoselectivity and
enantioselectivity are related to the ionic radius of the
MeOH
77
98
98
40
98
98
98
1:1
4:1
6:1
7:1
8:1
8:1
59:41
>99:1
>99:1
>99:1
>99:1
>99:1
CH3CN
a
THF
hexanes
EtOAc
CHCl3
CH2Cl2
c
c
16:1
>99:1
a
b
Tetrahydrofuran. Determined by chiral high-performance liquid
chromatography (HPLC) analysis. HPLC chromatogram in the
Supporting Information.
c
between (S)-methyl 2-bromopropanoate and 1,7-diaza-12-
crown-4 (Table 1). We found that the choice of solvent has
a substantial influence on the selectivity and efficiency of this
reaction: the protic solvent MeOH afforded ligand I with low
yield, low syn:anti ratio (1:1), and poor er (59:41) of the syn
product. This observation is expected because protic solvents
promote solvolysis of α-bromo esters. Aprotic solvents afforded
moderate to excellent syn:anti ratios (4:1−16:1) and excellent
er (>99:1). Among these aprotic solvents, the reaction went to
completion in CH2Cl2 providing I in the highest syn:anti ratio
(syn:anti = 16:1).
Table 3. Influence of Lanthanide Ion on the Mukaiyama
Aldol Reaction of (Z)-Trimethyl(1-phenylprop-1-
a
enyloxy)silane with Benzaldehyde
c
def
, ,
deg
, ,
lanthanide ion
Ln3+ radius (pm)
syn:anti
er (syn)
Using our newly synthesized ligand I with Eu(OTf)3, we
established the relationship between enantioselectivity of
catalysis and the syn:anti ratio of the ligand I (Table 2).14
Ligand I with 16:1 syn:anti ratio was used to produce syn
product 3a with a 95:5 er. This value of er is higher than the
value obtained with ligand I in a 4:1 or 5:1 syn:anti ratio, but
La3+
Ce3+
Pr3+
103.2
102
1.7:1
1.8:1
2.2:1
3.0:1
2.1:1
2.4:1
2.7:1
2.5:1
2.0:1
1.9:1
1.8:1
1.5:1
1.3:1
1.4:1
52:48
60:40
74:26
82:18
58:42
75:25
74:26
72:28
64:36
59:41
58:42
53:47
50:50
51:49
99
Nd3+
Sm3+
Eu3+
Gd3+
Tb3+
Dy3+
Ho3+
Er3+
98.3
95.8
94.7
93.8
92.3
91.2
90.1
89.0
88.0
86.8
86.1
a
Table 2. Purification Improves Stereoselectivity
Tm3+
Yb3+
Lu3+
e
e
e
e
syn:anti
f
syn:anti
f
syn:anti
syn:anti
f
ligand I
= 4:1
= 5:1
= 16:1
> 99:1
a
Reaction conditions: To a mixture of ligand I (24 mol %) and
b
yield (%)
85
88
89
92
Ln(OTf)3 (20 mol %), which was stirred at 50 °C for 2 h and then
cooled to −25 °C, were added (Z)-trimethyl(1-phenylprop-1-
enyloxy)silane (48.8 μmol, 1.5 equiv) and benzaldehyde (32.5 μmol,
1.0 equiv); All isolated yields were 99%. Ligand syn:anti > 99:1.
From ref 33. Determined by chiral HPLC analysis. Reactions were
product
26:1
26:1
28:1
32:1
cd
,
syn:anti
c
b
er (syn)
93:7
94:6
95:5
97:3
a
c
d
e
Reaction conditions: To a mixture of ligand I (48 mol %) and
Eu(OTf)3 (20 mol %), which was stirred at 50 °C for 2 h and then
cooled to −25 °C, were added (Z)-trimethyl(1-phenylprop-1-
enyloxy)silane (48.8 μmol, 1.5 equiv) and benzaldehyde (32.5 μmol,
repeated three times and listed values represent the mean values of
f
between 2 and 5 independent trials. Standard error of the mean for all
g
reactions was between 0 and 0.8 of the normalized syn value. Standard
b
c
1.0 equiv). Isolated yield. Determined by chiral HPLC analysis.
error of the mean for the numerator of er (syn) was between 0.3 and
6.4.
d
e
f
syn:anti of 3a. syn:anti for ligand I. From ref 14.
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lanthanide ion. From La3+ through Nd3+ (Pm3+ was skipped
because it is radioactive), the decrease in ionic radius
corresponded to an increase in the stereoselectivity of our
system: the syn:anti ratio of product 3a did not change with
metal ion (Student’s t-test, 95% confidence level), but the er
values increased from 52:48 to 82:18. However, the continued
decrease in ionic radius (from Nd3+ through Lu3+)
corresponded to a decrease in er values from 82:18 to 51:49
with no change in the syn:anti ratio of 3a (Student’s t-test, 95%
confidence level). Under the nonoptimal conditions used for
this comparison study, the most effective metal (Nd3+) yielded
product with a syn:anti ratio of 3.0:1 and an er of the syn isomer
of 82:18. We hypothesize that coordination of Nd3+ by ligand I
allows the most favorable steric environment for substrates
during catalysis and, consequently, the best stereoselectivity.
Because Nd3+ afforded a higher er than the other lanthanide
ions (Student’s t-test, 95% confidence), we selected this ion to
examine the influence of ligand I loading on enantioselectivity.
With 20 mol % Nd3+ and 42 mol % I, the syn product was
observed with 96:4 er (Table 4, entry 3). However, the er
Table 5. Influence of Solvent on the Mukaiyama Aldol
Reaction of (Z)-Trimethyl(1-phenylprop-1-enyloxy)silane
a
with Benzaldehyde
c
d
d
entry
solvent
yield (%)
syn:anti
er (syn)
1
2
3
4
5
6
7
8
9
90:10 DMF/H2O
90:10 THF/H2O
90:10 CH3CN/H2O
90:10 i-PrOH/H2O
90:10 EtOH/H2O
85:15 EtOH/H2O
70:30 EtOH/H2O
60:40 EtOH/H2O
50:50 EtOH/H2O
7
11
12
80
93
90
81
62
5
3:1
11:1
7:1
55:45
74:26
86:14
94:6
13:1
36:1
15:1
5:1
96:4
95:5
88:12
87:13
85:15
4:1
1:1
a
Reaction conditions: To a mixture of ligand I (42 mol %) and
Nd(OTf)3 (20 mol %), which was stirred at 50 °C for 2 h and then
cooled to −25 °C, were added (Z)-trimethyl(1-phenylprop-1-
enyloxy)silane (48.8 μmol, 1.5 equiv) and benzaldehyde (32.5 μmol,
Table 4. Influence of Ligand Loading on the Mukaiyama
Aldol Reaction of (Z)-Trimethyl(1-phenylprop-1-
b
c
d
1.0 equiv). Ligand syn:anti > 99:1. Isolated yield. Determined by
chiral HPLC analysis.
a
enyloxy)silane with Benzaldehyde
to the poor aqueous solubility of (Z)-trimethyl(1-phenylprop-
1-enyloxy)silane and the competing hydrolysis reaction of (Z)-
trimethyl(1-phenylprop-1-enyloxy)silane, as others have ob-
served.22
c
d
d
entry
X
reaction time (h)
yield (%)
syn:anti
er (syn)
Having established optimized reaction conditions, we probed
the generality of ligand I and Nd(OTf)3 in the Mukaiyama
aldol reaction of (Z)-trimethyl(1-phenylprop-1-enyloxy)silane
with a variety of aromatic and aliphatic aldehydes in EtOH/
H2O (Table 6). Notably, a broad substrate scope was observed.
Aromatic aldehydes with electron-withdrawing (Table 6, entry
2) or -donating (Table 6, entry 3) substituents were
investigated, and the effect of these substituents on the
enantioselectivity of products was found to be negligible.
However, diastereoselectivity was lower (12:1) with electron-
withdrawing substituents relative to electron-donating sub-
stituents or unsubstituted aromatic aldehydes (Table 6, entries
1−3). Heteroaromatic aldehydes also effectively engaged in the
Mukaiyama aldol reaction (Table 6, entries 4 and 5), affording
excellent er (94:6 and 89:11) and high diastereoselectivities
(>99:1). The reactions of the α,β-unsaturated and aliphatic
aldehydes also gave excellent stereoselectivities (Table 6,
entries 6−9); however, bulky aldehydes (Table 6, entries 9
and 10) afforded little or no product (percent yields of 10 and
0) likely because of steric hindrance preventing the aldehyde
from binding with Nd3+ resulting in unreacted starting material.
At higher temperatures (>−20 °C), we see a drop in selectivity;
this loss in selectivity may be due to changes in the relative
rates of syn and anti product formation or due to uncomplexed
metal catalyzing the formation of racemic product. Finally,
when the (S,S)-enantiomer of ligand I was used in place of the
(R,R)-enantiomer, the er of the product (Table 6, entry 1)
switched from 96:4 with the (R,R) isomer to 7:93 with the
(S,S) isomer. These examples illustrate that different aldehydes
affect yields, but the enantioselectivity of catalysis is minimally
affected by aldehyde selection when the silyl enol ether is
derived from an aromatic ketone.
1
2
3
24
36
42
24
72
99
97
93
3.0:1
22:1
36:1
82:18
95:5
96:4
168
a
Reaction conditions: To a mixture of ligand I (X mol %) and
Nd(OTf)3 (20 mol %), which was stirred at 50 °C for 2 h and then
cooled to −25 °C, were added (Z)-trimethyl(1-phenylprop-1-
enyloxy)silane (48.8 μmol, 1.5 equiv) and benzaldehyde (32.5 μmol,
1.0 equiv). Ligand syn:anti > 99:1. Isolated yield. Determined by
chiral HPLC analysis.
b
c
d
decreased to 95:5 when 36 mol % ligand I was used (Table 4,
entry 2) and 82:18 when 24 mol % of ligand I was used (Table
4, entry 1). These results suggest that 42 mol % of ligand I
corresponds to the amount of ligand required for Nd3+−ligand
complexes to predominate over free Nd3+. The minimization of
unchelated Nd3+ is important because unchelated Nd3+ can
catalyze racemic Mukaiyama aldol reactions. Using the xylenol
orange test for free metal, we determined that increasing
concentrations of ligand I correspond to lower concentrations
of free Nd3+,32 which supports our hypothesis for the need of
larger amounts of ligand relative to Nd3+.
To further optimize the reaction conditions, we examined the
effect of solvent composition on the yield and stereoselectivity
of the Mukaiyama aldol reaction using Nd(OTf)3 and ligand I.
Similar to previous studies, low yields, diastereoselectivities, and
enantioselectivities were observed when the Mukaiyama aldol
reaction was carried out in aqueous aprotic solvents such as
dimethylformamide (DMF), CH3CN, or THF (Table 5, entries
1−3).17,21 Protic solvents such as i-PrOH and EtOH (Table 5,
entries 4 and 5) with 10% water resulted in improved yields and
stereoselectivities relative to aprotic solvents (Table 5, entries
1−3). However, larger amounts of water resulted in lower
yields and stereoselectivities (Table 5, entries 5−9) likely due
The variation of the substitution pattern on the phenyl ring
of silyl enol ethers was also investigated (Table 7). Electron-
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a
Table 6. Mukaiyama Aldol Reaction of (Z)-Trimethyl(1-phenylprop-1-enyloxy)silane with Different Aldehydes
a
Reaction conditions: To a mixture of ligand I (42 mol %) and Nd(OTf)3 (20 mol %), which was stirred at 50 °C for 2 h and then cooled to −25
b
°C, were added (Z)-trimethyl(1-phenylprop-1-enyloxy)silane (48.8 μmol, 1.5 equiv) and aldehyde (32.5 μmol, 1.0 equiv). Ligand syn:anti > 99:1.
c
d
e
f
g
h
Isolated yield. Determined by chiral HPLC analysis. er of syn product was 7:93 if (S,S) chiral ligand I was used. anti. No reaction. Not
determined.
withdrawing (Table 7, entries 2 and 6) and electron-donating
(Table 7, entries 3 and 7) substituents on the silyl enol ether
have limited effects on yield and enantioselectivity, but as with
the aldehydes in Table 6, the electron-withdrawing chloro-
substituent lowered diastereoselectivity slightly. In general,
good yields (89−93%) were observed when the substrate was
benzaldehyde, and low yields (10−56%) were observed when
the substrate was heptanal. However, the enantioselectivities
remained excellent (er 96:4−98:2) whether the substrate was
an aromatic or an aliphatic aldehyde. With trimethyl(1-
phenylvinyloxy)silane (Table 7, entry 4), the yield was low
(73%) because trimethyl(1-phenylvinyloxy)silane is prone to
hydrolysis,24−26 and the poor enantioselectivity of this example
suggests that substitution on the double bond is helpful in the
control of product enantioselectivity. We were unable detect
product in the reaction between the aliphatic aldehyde 2h and
the aliphatic silyl enol ether 1e (Table 7, entry 8).
would give similar results to Eu3+. Surprisingly, we found Nd3+
gave a lower yield and stereoselectivity than Eu3+ (Table 8,
entries 1 and 2). These two results suggest that Nd3+ is not as
good as Eu3+ when the substrate is a silyl enol ether derived
from an aliphatic ketone, and these observations could be due
to the difference in Lewis acidity between the two metal ions.
Next, we increased the ratio of EtOH/H2O (Table 8, entries 3
and 4) and found that the increased EtOH/H2O ratio has
negligible influence on the enantioselectivity. Additionally,
dimethoxyethane (DME) was tested as the organic cosolvent in
this reaction because DME enabled high stereoselectivities with
other catalytic systems.15,26 However, while the use of DME
with our precatalyst led to high diastereoselectivity, this solvent
produced a poor yield and low er (Table 8, entry 5).
Because of the low selectivity of Nd3+-based precatalysts for
silyl enol ethers derived from aliphatic ketones, we used the
Eu3+-based version of our precatalyst to explore the scope of
these substrates. Two aromatic aldehydes bearing 4-Cl and 4-
CH3 were tested (Table 9, entries 2 and 3), and the reactions
We also examined our precatalyst with a silyl enol ether
derived from an aliphatic ketone. We suspected that Nd3+
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a
Table 7. Mukaiyama Aldol Reaction of Silyl Enol Ethers Derived from Aromatic Ketones with Benzaldehyde or Heptanal
a
Reaction conditions: To a mixture of ligand I (42 mol %) and Nd(OTf)3 (20 mol %), which was stirred at 50 °C for 2 h and then cooled to −25
b
c
d
°C, were added silyl enol ether (48.8 μmol, 1.5 equiv) and aldehyde (32.5 μmol, 1.0 equiv). Ligand syn:anti > 99:1. Isolated yield. Determined by
chiral HPLC analysis. No reaction. Not determined.
e
f
with these substituents afforded Mukaiyama-aldol products
with good enantioselectivities (er 93:7 and 92:8). However, the
yields were lower with substituted benzaldehyde (Table 9,
entries 1−3). These observations indicate that electronic
properties of substituents on the phenyl rings of the aldehydes
have negligible influence on the enantioselectivity of this
reaction. But the steric hindrance introduced by substituents on
the phenyl rings can affect the efficiency of this reaction.
Furthermore, thiophene-2-carboxaldehyde offered the product
in good er, suggesting that heteroatoms are compatible with our
system (Table 9, entry 4), and cyclohexenyloxytrimethylsilane
gave a low er (76:24) (Table 9, entry 5).
to 16:1. We found that the loading of ligand I can be decreased
when Nd3+ is used instead of Eu3+. Finally, a broad substrate
scope is compatible with the precatalysts described in this paper
that includes relatively challenging substrates like aliphatic
aldehydes and silyl enol ethers derived from aliphatic ketones.
This work highlights a new class of lanthanide-based chiral
precatalysts for aqueous carbon−carbon bond-forming reac-
tions that offers a broad substrate scope, high enantioselectivity,
and low cost.
EXPERIMENTAL SECTION
■
Materials. Commercial chemicals were of reagent-grade purity or
better and were used without further purification. The er (97.5:2.5) of
(S)-2-bromopropanoic acid was determined by high-performance
liquid chromatography (HPLC) analysis (Chiralpak AS-H, isocratic
9:1 hexanes/2-propanol, flow rate 1.0 mL/min, λ = 210 nm) tR = 5.69
min (minor, R), 6.63 min (major, S). Water was purified using a water
purification system. (Z)-Trimethyl(1-phenylprop-1-enyloxy)silane
(1a) (Z/E = 12:1),24 (Z)-(1-(4-chlorophenyl)prop-1-enyloxy)-
trimethylsilane (1b) (Z/E > 20:1),24 (Z)-trimethyl-(1-p-tolylprop-1-
CONCLUSIONS
■
We performed a detailed study of C2-symmetric ligands for
lanthanides as precatalysts for the Mukaiyama aldol reaction in
aqueous solution. The synthesis of chiral ligand I was improved
relative to our initial report by using CH2Cl2 instead of
CH3CN, resulting in an increase in the syn:anti ratio from 4:1
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were obtained using a 101 MHz spectrometer. DEPT spectra were
used to assign 13C NMR peaks. Data for 1H NMR spectra are reported
as follows: chemical shift (ppm) relative to residual CHCl3 in CDCl3
(7.27 ppm); multiplicity (“s” = singlet, “d” = doublet, “t” = triplet, “m”
= multiplet, and “brs” = broad singlet); coupling constant, J, (Hz); and
integration. Italicized elements are those that are responsible for the
shifts. Data for 13C NMR spectroscopy are reported as ppm relative to
CDCl3 (77.23 ppm). High-resolution electrospray ionization mass
spectra (HRESIMS) were obtained on an electrospray time-of-flight
high-resolution mass spectrometer. HPLC analyses were carried out
on a liquid chromatography−mass spectrometry (LC−MS) instru-
ment equipped with a Chiralpak AS-H, Chiralpak AD-H, Chiralcel
OD-H, Chiralcel OJ-H, or Chiralpak IC column (250 × 4.6 mm) using
a binary isocratic method (pump A: 2-propanol; pump B: hexanes or
n-heptane).
(2R,3R)-3-Hydroxy-2-methyl-1,3-diphenylpropan-1-one
(3a). Yield 8.0 mg, 93%: TLC Rf = 0.20 (10:1 hexanes/ethyl acetate);
HPLC (Chiralpak AS-H, isocratic 9:1 hexanes/2-propanol, flow rate
1.0 mL/min, λ = 254 nm) 96:4 er; 36:1 syn:anti; tR = 8.02 min (major,
syn), 12.34 min (minor, syn), 13.99 min (major, anti), 18.56 min
(minor, anti). The configuration of the product was determined as
2R,3R using a Chiralcel OJ-H column by comparison with the
retention order of authentic compounds on a Chiralcel OJ column.12
(syn)-3-(4-Chlorophenyl)-3-hydroxy-2-methyl-1-phenylpro-
pan-1-one (3b). Yield 8.1 mg, 90%: TLC Rf = 0.20 (10:1 hexanes/
ethyl acetate); HPLC (Chiralpak AD-H, isocratic 9:1 hexanes/2-
propanol, flow rate 1.0 mL/min, λ = 254 nm) 95:5 er; 12:1 syn:anti; tR
= 9.71 min (major, syn), 11.25 min (minor, syn), 14.07 min (major,
anti), 18.09 min (minor, anti). The configuration of the product was
determined as syn by comparison with the retention order of authentic
compounds on a Chiralpak AD-H column.26
Table 8. Solvent Effects in the Mukaiyama Aldol Reaction of
(Z)-Trimethyl(pent-2-en-3-yloxy)silane
a
yield
c
er
d
d
entry
1
X
ion
solvent
(%)
syn:anti
(syn)
42
48
48
48
48
Nd3+ 90:10 EtOH/H2O
17
61
46
14
8
5:1
11:1
12:1
14:1
45:1
84:16
92:8
e
2
Eu3+
Eu3+
Eu3+
Eu3+
90:10 EtOH/H2O
95:5 EtOH/H2O
99:1 EtOH/H2O
90:10 DME/H2O
3
4
5
92:8
90:10
85:15
a
Reaction conditions: To a mixture of ligand I (X mol %) and
Ln(OTf)3 (20 mol %), which was stirred at 50 °C for 2 h and then
cooled to −25 °C, were added (Z)-trimethyl(pent-2-en-3-yloxy)silane
(48.8 μmol, 1.5 equiv) and benzaldehyde (32.5 μmol, 1.0 equiv).
b
c
d
Ligand syn:anti > 99:1. Isolated yield. Determined by chiral HPLC
e
analysis. From ref 14.
enyloxy)silane (1c) (Z/E > 34:1),24 and (Z)-trimethyl(pent-2-en-3-
yloxy)silane (1e) (Z/E = 4.5:1)34 were synthesized using previously
published procedures.
Characterization. Flash chromatography was performed using
silica gel 60, 230−400 mesh.35 Analytical thin-layer chromatography
(TLC) was carried out on TLC plates precoated with silica gel 60 F254
(250 μm layer thickness). TLC visualization was accomplished using a
UV lamp or charring with phosphomolybdic acid stain (5 g
phosphomolybdic acid in 50 mL of absolute ethanol). 1H NMR
spectra were obtained using a 400 MHz spectrometer. 13C NMR and
distortionless enhancement by polarization transfer (DEPT) spectra
(syn)-3-Hydroxy-2-methyl-1-phenyl-3-(p-tolyl)propan-1-one
(3c). Yield 7.0 mg, 85%: TLC Rf = 0.20 (10:1 hexanes/ethyl acetate);
HPLC (Chiralpak AD-H, isocratic 9:1 hexanes/2-propanol, flow rate
a
Table 9. Mukaiyama Aldol Reaction of Silyl Enol Ethers Derivated from Aliphatic Ketones with Aromatic Aldehydes
a
Reaction conditions: To a mixture of ligand I (48 mol %) and Eu(OTf)3 (20 mol %), which was stirred at 50 °C for 2 h and then cooled to −25 °C,
b
c
d
were added silyl enol ether (48.8 μmol, 1.5 equiv) and aldehyde (32.5 μmol, 1.0 equiv). Ligand syn:anti > 99:1. From ref 14. Isolated yield.
e
f
1
Determined by chiral HPLC analysis. Determined by H NMR spectroscopy.
5629
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The Journal of Organic Chemistry
Article
1.0 mL/min, λ = 254 nm) 96:4 er; 36:1 syn:anti; tR = 9.25 min (major,
syn), 10.64 min (minor, syn), 14.93 min (anti). The configuration of
the product was determined as syn by comparison with the retention
order of authentic compounds on a Chiralpak AD-H column.26
(syn)-3-Hydroxy-2-methyl-1-phenyl-3-(thiophen-2-yl)-
propan-1-one (3d). Yield 6.6 mg, 82%: 1H NMR (400 MHz, CDCl3,
δ) 7.96−7.93 (m, 2H), 7.62−7.58 (m, 1H), 7.51−7.46 (m, 2H), 7.25−
7.22 (m, 1H), 7.00−6.96 (m, 2H), 5.49 (t, J = 3.2 Hz, 1H), 3.84−3.76
(m, 1H), 3.59 (d, J = 3.2 Hz, 1H), 1.32 (d, J = 7.2 Hz, 3H); 13C NMR
(101 MHz, CDCl3, δ) 205.2, 146.0, 135.7, 133.9 (CH), 129.0 (CH),
128.7 (CH), 126.9 (CH), 124.5 (CH), 123.7 (CH), 70.7 (CH), 47.9
(CH), 12.3 (CH3); TLC Rf = 0.20 (8:1 hexanes/ethyl acetate);
HRESIMS (m/z) [M + Na]+ calcd for C14H14O2SNa, 269.0612;
found, 269.0615; HPLC (Chiralpak AD-H, isocratic 98.5:1.5 n-
heptane/2-propanol, flow rate 0.8 mL/min, λ = 254 nm) 94:6 er;
>99:1 syn:anti; tR = 56.87 min (major, syn), 71.46 min (minor, syn).
The configuration of the product was determined as syn by
δ) 204.6, 141.9, 140.3, 134.2, 130.1 (CH), 129.3 (CH), 128.5 (CH),
127.7 (CH), 126.2 (CH), 73.4 (CH), 47.4 (CH), 11.6 (CH3); TLC Rf
= 0.20 (10:1 hexanes/ethyl acetate); HRESIMS (m/z) [M + Na]+
calcd for C16H15O2ClNa, 297.0658; found, 297.0660; HPLC
(Chiralpak AD-H, isocratic 90:10 n-heptane/2-propanol, flow rate
0.8 mL/min, λ = 254 nm) 96:4 er; 15:1 syn:anti; tR = 14.59 min
(major, syn), 19.60 min (minor, syn), 18.03 min (minor, anti), 32.93
min (major, anti). The configuration of the product was determined as
syn by comparison with the 1H NMR spectra of authentic
compounds.24
(syn)-3-Hydroxy-2-methyl-3-phenyl-1-(p-tolyl)propan-1-one
1
(3l). Yield 7.4 mg, 89%: H NMR (400 MHz, CDCl3, δ) 7.87−7.84
(m, 2H), 7.43−7.34 (m, 4H), 7.29−7.25 (m, 3H), 5.25 (t, J = 2.4 Hz,
1H), 3.77 (d, J = 1.6 Hz, 1H), 3.72−3.64 (m, 1H), 2.43 (s, 3H), 1.18
(d, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3, δ) 205.8, 144.8,
142.1, 133.3, 129.7 (CH), 128.9 (CH), 128.4 (CH), 127.5 (CH), 126.3
(CH), 73.2 (CH), 47.0 (CH), 21.9 (CH3), 11.3 (CH3); TLC Rf = 0.20
(10:1 hexanes/ethyl acetate); HRESIMS (m/z) [M + Na]+ calcd for
C17H18O2Na, 277.1204; found, 277.1196; HPLC (Chiralpak AD-H,
isocratic 90:10 n-heptane/2-propanol, flow rate 0.8 mL/min, λ = 254
nm) 96:4 er; 30:1 syn:anti; tR = 12.36 min (major, syn), 15.95 min
(minor, syn), 23.69 min (minor, anti), 30.30 min (major, anti). The
configuration of the product was determined as syn by comparison
22
1
comparison with the H NMR spectra of authentic compounds.
(syn)-3-Hydroxy-2-methyl-1-phenyl-3-(pyridin-2-yl)propan-
1
1-one (3e). Yield 4.3 mg, 55%: H NMR (400 MHz, CDCl3, δ) 8.56
(d, J = 4.6 Hz, 1H), 7.99−7.95 (m, 2H), 7.71−7.66 (m, 1H), 7.60−
7.55 (m, 1H), 7.52−7.44 (m, 3H), 7.20−7.16 (m, 1H), 5.24 (t, J = 4.0
Hz, 1H), 4.18 (d, J = 3.2 Hz, 1H), 4.11−4.04 (m, 1H), 1.16 (d, J = 7.2
Hz, 3H); 13C NMR (101 MHz, CDCl3, δ) 205.2, 160.8, 148.9 (CH),
136.8 (CH), 136.0, 133.6 (CH), 128.9 (CH), 128.8 (CH), 122.6
(CH), 121.5 (CH), 73.9 (CH), 46.4 (CH), 11.9 (CH3); TLC Rf = 0.20
(2:1 hexanes/ethyl acetate); HRESIMS (m/z) [M + H]+ calcd for
C15H16NO2, 242.1181; found, 242.1184; HPLC (Chiralpak AS-H,
isocratic 90:10 n-heptane/2-propanol, flow rate 0.3 mL/min, λ = 254
nm) 89:11 er; >99:1 syn:anti; tR = 30.73 min (major, syn), 44.91 min
(minor, syn). The configuration of the product was determined as syn
24
1
with the H NMR spectra of authentic compounds.
(S)-3-Hydroxy-1,3-diphenylpropan-1-one (3m). Yield 5.4 mg,
1
73%: H NMR (400 MHz, CDCl3, δ) 8.04−7.96 (m, 2H), 7.63−7.58
(m, 1H), 7.58−7.44 (m, 4H), 7.42−7.37 (m, 2H), 7.34−7.29 (m, 1H),
5.39−5.34 (m, 1H), 3.60 (d, J = 3.2 Hz, 1H), 3.39 (d, J = 5.6 Hz, 2H);
13C NMR (101 MHz, CDCl3, δ) 200.5, 143.1, 136.8, 133.9 (CH),
128.9 (CH), 128.8 (CH), 128.4 (CH), 127.9 (CH), 126.0 (CH), 70.2
(CH), 47.6 (CH2); TLC Rf = 0.20 (10:1 hexanes/ethyl acetate);
HRESIMS (m/z) [M + Na]+ calcd for C15H14O2Na, 249.0891; found,
249.0890; HPLC (Chiralcel OD−H, isocratic 90:10 hexanes/2-
propanol, flow rate 1.0 mL/min, λ = 254 nm) 68:32 er; tR = 12.47
min (S, major), 13.96 min (R, minor). The configuration of the
product was determined as S by comparison with the retention order
of authentic compounds on a Chiralcel OD−H column.38
1
by comparison with the H NMR spectra and the retention order of
authentic compounds.27
(2R,3S)-3-Hydroxy-2-methyl-1-phenylhex-4-en-1-one (3f).
Yield 4.2 mg, 63%: TLC Rf = 0.20 (10:1 hexanes/ethyl acetate);
HPLC analysis (Chiralcel OD−H, isocratic 99:1 n-heptane/2-
propanol, flow rate 0.8 mL/min, λ = 254 nm) 95:5 er; 8:1 syn:anti;
tR = 21.37 min (major, syn), 28.32 min (minor, syn), 41.35 min
(minor, anti), 44.44 min (major, anti). The configuration of the
product was determined as 2R,3S on a Chiralcel OD-H column by
comparison with the retention order of authentic compounds on a
Chiralcel OD-H column.36
(syn)-1-(4-Chlorophenyl)-3-hydroxy-2-methylnonan-1-one
1
(3n). Yield 1.8 mg, 19%: H NMR (400 MHz, CDCl3, δ) 7.91−7.87
(m, 2H), 7.48−7.45 (m, 2H), 4.05−3.99 (m, 1H), 3.45−3.37 (m, 1H),
2.94 (d, J = 3.2 Hz, 1H), 1.62−1.23 (m, 13H), 0.89 (t, J = 7.2 Hz,
3H); 13C NMR (101 MHz, CDCl3, δ) 204.8, 140.2, 134.5, 130.1
(CH), 129.3 (CH), 71.5 (CH), 44.8 (CH), 34.6 (CH2), 32.0 (CH2),
29.5 (CH2), 26.3 (CH2), 22.8 (CH2), 14.3 (CH3), 11.3 (CH3); TLC Rf
= 0.30 (10:1 hexanes/ethyl acetate); HRESIMS (m/z) [M + Na]+
calcd for C16H23O2NaCl, 305.1284; found, 305.1291; HPLC
(Chiralpak AS-H, isocratic 95:5 n-Heptane/2-propanol, flow rate 0.3
mL/min, λ = 254 nm) 97:3 er; 5:1 syn:anti; tR = 20.23 min (major,
syn), 29.75 min (minor, syn), 22.23 min (major, anti), 44.37 min
(minor, anti). The configuration of the product was determined as syn
(anti)-3-Hydroxy-2-methyl-1-phenylbutan-1-one (3g). Yield
3.2 mg, 56%: TLC Rf = 0.20 (8:1 hexanes/ethyl acetate); HPLC
(Chiralpak AS-H, isocratic 95:5 n-heptane/2-propanol, flow rate 0.6
mL/min, λ = 254 nm) 97:3 er; 3:1 anti:syn; tR = 16.10 min (major,
anti), 23.24 min (minor, anti), 19.82 min (major, syn), 37.49 min
(minor, syn). The configuration of the product was determined as anti
37
1
by comparison with the H NMR spectra of authentic compounds.
(syn)-3-Hydroxy-2-methyl-1-phenylnonan-1-one (3h). Yield
1.5 mg, 19%: TLC Rf = 0.30 (10:1 hexanes/ethyl acetate); HPLC
(Chiralpak AS-H, isocratic 95:5 n-heptane/2-propanol, flow rate 0.3
mL/min, λ = 254 nm) 97:3 er; 8:1 syn:anti; tR = 20.25 min (major,
syn), 26.87 min (minor, syn), 21.27 min (major, anti), 50.15 min
(minor, anti). The configuration of the product was determined as syn
by comparison with the retention order of authentic compounds on a
Chiralpak AS-H column.26
3
by the comparation of JHH of the syn and anti isomers (3JHH (syn) =
2.4 Hz, JHH (anti) = 7.0 Hz).39
3
3-Hydroxy-2-methyl-1-(p-tolyl)nonan-1-one (3o). Yield 1.5
1
mg, 18%: H NMR (400 MHz, CDCl3, δ) 7.86 (d, J = 8.0 Hz, 2H),
7.29 (d, J = 8.0 Hz, 2H), 4.05−4.00 (m, 1H), 3.49−3.40 (m, 1H), 2.44
(s, 3H), 1.62−1.24 (m, 13H), 0.89 (t, J = 5.6 Hz, 3H); 13C NMR (101
MHz, CDCl3, δ) 205.9, 144.6, 133.6, 129.7 (CH), 128.8 (CH), 71.5
(CH), 44.4 (CH), 34.5 (CH2), 32.0 (CH2), 29.5 (CH2), 26.3 (CH2),
22.9 (CH2), 21.9 (CH3), 14.3 (CH3), 11.3 (CH3); TLC Rf = 0.30
(10:1 hexanes/ethyl acetate); HRESIMS (m/z) [M + Na]+ calcd for
C17H26O2Na, 285.1831; found, 285.1823; HPLC (Chiralpak AS-H,
isocratic 95:5 n-Heptane/2-propanol, flow rate 0.3 mL/min, λ = 254
nm) 98:2 er; 22:1 syn:anti; tR = 19.58 min (major, syn), 30.93 min
(minor, syn), 21.87 min (major, anti), 59.31 min (minor, anti). The
configuration of the product was determined as syn by the
(anti)-3-Cyclohexyl-3-hydroxy-2-methyl-1-phenylpropan-1-
one (3i). Yield 0.8 mg, 10%: TLC Rf = 0.25 (10:1 hexanes/ethyl
acetate); HPLC (Chiralpak AS-H, isocratic 95:5 n-heptane/2-
propanol, flow rate 0.6 mL/min, λ = 254 nm) 97:3 er; 15:1 anti:syn;
tR = 12.25 min (major, anti), 21.45 min (minor, anti), 11.38 min
(major, syn), 29.02 min (minor, syn). The configuration of the product
1
was determined as anti by comparison with the H NMR spectra of
authentic compounds.21
3
comparation of JHH of the syn and anti isomers (3JHH (syn) = 2.4
(syn)-1-(4-Chlorophenyl)-3-hydroxy-2-methyl-3-phenylpro-
pan-1-one (3k). Yield 8.1 mg, 90%: 1H NMR (400 MHz, CDCl3, δ)
7.88−7.85 (m, 2H), 7.46−7.44 (m, 2H), 7.41−7.33 (m, 4H), 7.30−
7.25 (m, 1H), 5.23 (t, J = 2.4 Hz, 1H), 3.69−3.62 (m, 1H), 3.48 (d, J =
2.4 Hz, 1H), 1.21 (d, J = 7.6 Hz, 3H); 13C NMR (101 MHz, CDCl3,
Hz, JHH (anti) = 6.4 Hz).39
3
(syn)-1-(4-Chlorophenyl)-1-hydroxy-2-methylpentan-3-one
1
(3r). Yield 2.5 mg, 39%: H NMR (400 MHz, CDCl3, δ) 7.34−7.30
(m, 2H), 7.29−2.25 (m, 2H), 5.08 (d, J = 3.2 Hz, 1H), 3.25 (brs, 1H),
5630
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The Journal of Organic Chemistry
Article
2.84−2.77 (m, 1H), 2.61−2.51 (m, 1H), 2.45−2.34 (m, 1H), 1.07−
1.02 (m, 6H). 13C NMR (101 MHz, CDCl3, δ) 216.6, 140.5, 133.2,
128.7 (CH), 127.5 (CH), 72.6 (CH), 52.1 (CH), 35.6 (CH2), 10.5
(CH3), 7.7 (CH3); TLC Rf = 0.20 (10:1 hexanes/ethyl acetate);
HRESIMS (m/z) [M + Na]+ calcd for C12H15O2NaCl, 249.0658;
found, 249.0651; HPLC (Chiralpak IC, isocratic 95:5 n-heptane/2-
propanol, flow rate 1.0 mL/min, λ = 210 nm) 93:7 er; tR = 8.32 min
(minor, syn), 9.03 min (major, syn). The configuration of the product
ACKNOWLEDGMENTS
■
This research was supported by startup funds from Wayne State
University, a Schaap Faculty Scholar Award, and a CAREER
Award from the National Science Foundation (CHE-0955000).
REFERENCES
■
(1) Xuan, R.; Oh, H.-S.; Lee, Y.; Kang, H.-Y. J. Org. Chem. 2008, 73,
1456−1461.
1
was determined as syn by comparison with the H NMR spectra of
authentic compounds.40
(2) Park, J. W.; Oh, H.-S.; Jung, W. S.; Park, S. R.; Han, A. R.; Ban,
Y.-H.; Kim, E. J.; Kang, H.-Y.; Yoon, Y. J. Chem. Commun. 2008,
5782−5784.
(syn)-1-Hydroxy-2-methyl-1-(p-tolyl)pentan-3-one (3s). Yield
1.9 mg, 33%: 1H NMR (400 MHz, CDCl3, δ) 7.21 (d, J = 8.0 Hz, 2H),
7.15 (d, J = 8.0 Hz, 2H), 5.03 (d, J = 4.0 Hz, 1H), 2.89−2.80 (m, 1H),
2.54−2.46 (m, 1H), 2.40−2.30 (m, 1H), 2.34 (s, 3H), 1.10 (d, J = 7.2
Hz, 3H), 1.01 (t, J = 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3, δ)
216.6, 139.0, 137.2, 129.2 (CH), 126.1 (CH), 73.4 (CH), 52.5 (CH),
35.7 (CH2), 21.3 (CH3), 10.9 (CH3), 7.7 (CH3); TLC Rf = 0.20 (10:1
hexanes/ethyl acetate); HRESIMS (m/z) [M + Na]+ calcd for
C13H18O2Na, 229.1204; found, 229.1201; HPLC (Chiralpak AS-H,
isocratic 90:10 n-heptane/2-propanol, flow rate 0.6 mL/min, λ = 210
nm) 92:8 er; 24:1 syn:anti; tR = 11.99 min (major, syn), 15.14 min
(minor, syn), 13.61 min (minor, anti), 18.73 min (major, anti). The
configuration of the product was determined as syn by comparison
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3056.
41
1
with the H NMR spectra of authentic compounds.
(syn)-1-Hydroxy-2-methyl-1-(thiophen-2-yl)pentan-3-one
1
(3t). Yield 1.7 mg, 30%: H NMR (400 MHz, CDCl3, δ) 7.26−7.23
(11) Inamoto, Y.; Nishimoto, Y.; Yasuda, M.; Baba, A. Org. Lett.
(m, 1H), 7.03−6.95 (m, 1H), 6.95−6.92 (m, 1H), 5.32−5.29 (m, 1H),
3.18 (d, J = 3.2 Hz, 1H), 2.98−2.91 (m, 1H), 2.61−2.51 (m, 1H),
2.45−2.34 (m, 1H), 1.21 (d, J = 6.8 Hz, 3H), 1.03 (t, J = 6.8 Hz, 3H);
13C NMR (101 MHz, CDCl3, δ) 215.9, 145.9, 126.9 (CH), 124.6
(CH), 123.8 (CH), 70.7 (CH), 52.8 (CH), 35.6 (CH2), 11.5 (CH3),
7.7 (CH3); TLC Rf = 0.20 (8:1 hexanes/ethyl acetate); HRESIMS (m/
z) [M + Na]+ calcd for C10H14O2NaS, 221.0612; found, 221.0607;
HPLC (Chiralpak AD-H, isocratic 90:10 n-heptane/2-propanol, flow
rate 0.3 mL/min, λ = 210 nm) 91:9 er; >20:1 syn:anti; tR = 24.58 min
(major, syn), 26.60 min (minor, syn). The configuration of the product
2012, 14, 1168−1171.
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(13) Denmark, S. E.; Heemstra, J. R., Jr. Org. Lett. 2003, 5, 2303−
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Chem., Int. Ed. 2011, 50, 754−758.
1
was determined as syn by comparison with the H NMR spectra of
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authentic compounds.21
(syn)-2-(Hydroxy(phenyl)methyl)cyclohexanone (3u). Yield
1
(19) Nagayama, S.; Kobayashi, S. J. Am. Chem. Soc. 2000, 122,
11531−11532.
3.0 mg, 52%: H NMR (400 MHz, CDCl3, δ) 7.37−7.24 (m, 5H),
5.40 (s, 1H), 3.04 (brs, 1H), 2.64−2.58 (m, 1H), 2.49−2.34 (m, 2H),
2.11−2.07 (m, 1H), 1.88−1.84 (m, 1H), 1.78−1.62 (m, 3H), 1.58−
1.49 (m, 1H); 13C NMR (101 MHz, CDCl3, δ) 215.2, 141.6, 128.4
(CH), 127.2 (CH), 126.0 (CH), 70.8 (CH), 57.4 (CH), 42.9 (CH2),
28.2 (CH2), 26.2 (CH2), 25.1 (CH2); TLC Rf = 0.20 (10:1 hexanes/
ethyl acetate); HRESIMS (m/z) [M + Na]+ calcd for C13H16O2Na,
227.1048; found, 227.1048; HPLC (Chiralpak AS-H, isocratic 95:5 n-
heptane/2-propanol, flow rate 0.5 mL/min, λ = 210 nm) 76:24 er; 9:1
syn:anti; tR = 30.27 min (minor, syn), 37.38 min (major, syn), 41.26
min (minor, anti), 45.25 min (major, anti). The configuration of the
product was determined as syn by comparison with the retention order
of authentic compounds on a Chiralpak AS-H column.26
(20) Kobayashi, S.; Hamada, T.; Nagayama, S.; Manabe, K. Org. Lett.
2001, 3, 165−167.
(21) Kobayashi, S.; Nagayama, S.; Busujima, T. Tetrahedron 1999, 55,
8739−8746.
(22) Hamada, T.; Manabe, K.; Ishikawa, S.; Nagayama, S.; Shiro, M.;
Kobayashi, S. J. Am. Chem. Soc. 2003, 125, 2989−2996.
(23) Li, H.-J.; Tian, H.-Y.; Chen, Y.-J.; Wang, D.; Li, C.-J. Chem.
Commun. 2002, 2994−2995.
(24) Li, H.-J.; Tian, H.-Y.; Wu, Y.-C.; Chen, Y.-J.; Liu, L.; Wang, D.;
Li, C.-J. Adv. Synth. Catal. 2005, 347, 1247−1256.
(25) Mlynarski, J.; Jankowska, J. Adv. Synth. Catal. 2005, 347, 521−
525.
(26) Jankowska, J.; Mlynarski, J. J. Org. Chem. 2006, 71, 1317−1321.
(27) Jankowska, J.; Paradowska, J.; Rakiel, B.; Mlynarski, J. J. Org.
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ASSOCIATED CONTENT
■
S
* Supporting Information
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Notes
The authors declare no competing financial interest.
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