Structural effects in the Pd-induced enantioselective deprotection-decarboxylation of β-ketoesters

Article abstract of DOI:10.1016/j.tetasy.2007.11.017

Structural effects in the chiral base and the influence of some key reaction parameters (catalyst type and solvent) in the Pd-induced enantioselective decarboxylation (cascade reaction) of three different α,α-disubstituted benzyl β-ketoesters were explored. The reaction intermediate after debenzylation (β-keto-carboxylic acid) was synthesized and its decarboxylation studied independently. The highest ee (up to 60%) in the cascade reaction was achieved with those substrates that contained an aromatic ring system and with chiral amino alcohols that possessed an extended aromatic ring (quinine and quinidine). Polar solvents with weak H-bond donor and acceptor properties favor enantioselection.

Full text of DOI:10.1016/j.tetasy.2007.11.017

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 18 (2007) 2859–2868
Structural effects in the Pd-induced enantioselective
deprotection–decarboxylation of b-ketoesters
*
´
ˇ
Pavel Kukula, Vaclav Matousek, Tamas Mallat and Alfons Baiker
Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Ho¨nggerberg,
HCI, CH-8093 Zurich, Switzerland
Received 24 August 2007; accepted 15 November 2007
Abstract—Structural effects in the chiral base and the influence of some key reaction parameters (catalyst type and solvent) in the Pd-
induced enantioselective decarboxylation (cascade reaction) of three different a,a-disubstituted benzyl b-ketoesters were explored. The
reaction intermediate after debenzylation (b-keto-carboxylic acid) was synthesized and its decarboxylation studied independently. The
highest ee (up to 60%) in the cascade reaction was achieved with those substrates that contained an aromatic ring system and with chiral
amino alcohols that possessed an extended aromatic ring (quinine and quinidine). Polar solvents with weak H-bond donor and acceptor
properties favor enantioselection.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
alcohols and amines are suitable as a part of the catalyst
system,2,7,9 but the ee rarely exceeds 80%. In the case of
chiral amino alcohols, the absolute configuration of the
ketone depends upon the configuration of the carbon
carrying the amino group, not the OH group, of the
modifier.2 It has been found that the type of the supported
Pd catalyst significantly influences the reaction rate and the
enantioselectivity, which might indicate the key role of Pd
in the cascade reaction.6,7,9,10
The application of one-pot domino, or cascade, reactions is
a highly attractive route to the synthesis of complex chiral
molecules.1 An interesting example, the deprotection,
enantioselective decarboxylation reaction series leading to
optically active carbonyl compounds, has been intensively
investigated by Henin, Muzart, et al.2–7 The key intermedi-
ate, a b-ketoacid, can be produced in situ by a Pd-catalyzed
deprotection of a benzyl (or allyl) b-ketoester (Scheme 1)
and the enantioselective decarboxylation is assisted by a
chiral amino alcohol or amine. The amount of chiral base
varies between stoichiometric and catalytic (0.15–0.3
equiv);4–6,8 the latter ratio requires the proper choice of
catalyst and reaction conditions. Various chiral amino
In a mechanistic study, Detalle et al.2–7 concluded that the
cascade reactions afforded the chiral ketone via
Pd-catalyzed decarboxylation and enol isomerization. In
the reinvestigation of some of these cascade reactions, we
found strong indications that the role of Pd is probably
O
O
O
O
O
CH2Ph
Pd/support, H2
chiral base
O
OH
*
*
*
-CO2
3
2
1
Scheme 1. Domino reaction of 1 to 3 catalyzed by supported Pd and a chiral amine or amino alcohol (see Figs. 1 and 2).
*
Corresponding author. E-mail: baiker@chem.ethz.ch
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.11.017

2860
P. Kukula et al. / Tetrahedron: Asymmetry 18 (2007) 2859–2868
limited to the first step, the debenzylation of the benzyl (or
allyl) b-ketoester. Herein, we report the first part of our
study, focusing on the key structural effects that control
the stereochemical outcome of the reaction: the structure
of the substrate and the chiral base, and also the properties
of the solvent. To support these conclusions, we have in-
cluded in this study a broad range of chiral amines and amino
alcohols, which have already been applied in these types of
cascade reactions, although mainly not in the transforma-
tion of the substrates used in this work.
2. Results and discussion
2.1. The role of the chiral base
Various chiral amines and amino alcohols were tested in
the cascade reaction of 1 to find a relationship between
their molecular structure and the enantioselectivity (Figs.
1 and 2). It has been shown in the cascade reactions of benz-
yl b-ketoesters,8 that amino alcohols afford far better
enantioselectivities than amines; this conclusion is fully
Figure 1. Chiral amines and amino alcohols tested in the transformation of 1 (Scheme 1). The number in brackets after the ee indicates the conversion.
Reaction conditions: 20 mg 1, 0.025 equiv Pd, 0.3 equiv alkaloid, 2 mL MeCN, room temperature, 1 bar, H2, 2 h.

P. Kukula et al. / Tetrahedron: Asymmetry 18 (2007) 2859–2868
2861
Figure 2. Derivatives of cinchona alkaloids and their performance in the debenzylation–decarboxylation of 1 (Scheme 1). The number in brackets after the
ee indicates the conversion. Reaction conditions: 20 mg 1, 0.025 equiv Pd, 0.3 equiv alkaloid, 2 mL MeCN, room temperature, 1 bar, H2, 2 h.
confirmed by our results. The highest ee was obtained with
amino alcohols with a defined configuration at both stereo-
genic centers. A comparison of the primary, secondary,
and tertiary amino groups showed that the enantioselectiv-
ity decreased in this order (see norephedrine, ephedrine,
and N-methyl-ephedrine in the first row of Fig. 1). Further-
more, the larger the nitrogen substituent, the lower was the
enantioselectivity, cf. N-methyl-ephedrine with N,N-dibut-
yl-norephedrine. This relationship was, however, only valid
for ephedrine derivatives; cinchona alkaloids containing an
isoquinoline ring and a rigid tertiary amino group provided
higher enantioselectivity (Fig. 2). Substitution of the aro-
matic ring with a methoxy group (cinchonine!quinidine,
cinchonidine!quinine) almost tripled the ee (Fig. 2).
Replacement of the hydroxyl group of cinchonidine with
methoxy, phenoxy, and naphthoxy substituents diminished
the enantioselectivity, independent of the steric bulkiness of
the ether function. N-Alkylation of cinchonidine led to
(almost) complete loss of ee.
Screening of various amino alcohols indicates that the
rigidity of the C–C bond between C-atoms bearing the
amino and hydroxyl groups and the presence of an
extended aromatic system seem to play an important role
in the enantioselection.
2.2. The effect of Pd catalyst
A comparison of various commercial catalysts with differ-
ent Pd loadings and supports in the cascade reaction of 1
to 3 is presented in Figure 3. The most active Pd catalysts
were those supported on C, TiO2, and Al2O3. Apparently,
higher enantioselectivities were obtained on the less active
Pd catalysts supported on CaCO3, SiO2, or BaSO4, which
did not provide full conversion within 2 h.
We can speculate that a fast debenzylation of the substrate,
relative to the rate of decarboxylation, leads to high actual
concentration of the intermediate ketoacid 2. The resulting
low actual chiral amino alcohol/2 ratio in the reaction
mixture is detrimental to the enantioselection, although it
can be compensated for with a higher (not catalytic) initial
amino alcohol/1 ratio. It should be noted that the influence
of the type and source of supported Pd, observed in former
studies6,7,9,10 may be used as indirect evidence for the
critical role of Pd as the catalyst in the whole cascade reac-
tion series. In contrast, our opinion is that Pd controls, via
the deprotection step, only the actual concentration of the
ketoacid and thus the chiral base/ketoacid ratio; the latter
has a strong influence on the enantioselectivity.
From all the chiral bases tested, the highest enantioselectiv-
ities were achieved with the rigid structures of cinchona
alkaloids (almost 60% using quinine and quinidine); ephed-
rine derivatives were less efficient (14–30%). Another
important difference between ephedra and cinchona deriv-
atives is the opposite effect of the amino alcohol configura-
tion on the stereochemistry of the product: while the
(1R,2S)-configuration of ephedrine gives the (R)-ketone,
the same configuration of cinchona alkaloid (e.g., quinine
and cinchonidine) gives the (S)-product. This may be a
valuable observation for future mechanistic studies.

2862
P. Kukula et al. / Tetrahedron: Asymmetry 18 (2007) 2859–2868
100
80
60
40
20
0
70
60
50
40
30
20
10
0
Figure 3. Effect of catalyst composition on conversion (r) and ee (columns) of debenzylation–decarboxylation of 1. Reaction conditions: 20 mg 1,
0.025 equiv Pd, 0.3 equiv quinine, 2 mL MeCN, room temperature, 1 bar, H2, 2 h. Ee achieved with C-supported Pd catalysts is represented by black
columns.
2.3. Solvent effect
supported Pd usually contains 5–10 (sometimes up to 50)
mass% water, which can contribute to the large differences
observed among different Pd/C catalysts (Fig. 3).
Preliminary experiments on the cascade reaction of 1 to 3
revealed a dramatic influence of the solvent, including its
purity, on the enantioselectivity. In the case of acetonitrile,
the ee strongly depended on the water content. The addi-
tion of one drop of water to our standard reaction mixture
prepared with dry acetonitrile resulted in a drop of ee from
58% to 27% ee. It should be noted that commercial carbon-
The enantioselectivities, ordered according to decreasing
reaction rates, are shown in Figure 4 for a broad range
of solvents. The highest conversion and lowest enantio-
selectivity were achieved in protic polar solvents. Appar-
ently, these solvents are suitable for the debenzylation
100
90
65
55
ee [%]
80
conversion [%]
45
70
60
50
40
30
20
10
0
35
25
15
5 (S)
5 (R)
Figure 4. Solvent effect on the conversion and enantioselectivity in the cascade reaction of 1 to 3. Reaction conditions: 20 mg 1, 0.025 equiv Pd (5 wt % Pd/
C, Fluka), 0.3 equiv quinine, 2 mL MeCN, room temperature, 1 bar, H2, 2 h.

P. Kukula et al. / Tetrahedron: Asymmetry 18 (2007) 2859–2868
2863
reaction and rapidly provide the key intermediate 2,
100
90
80
70
60
50
40
30
20
10
0
a
although they are less appropriate for the enantioselective
decarboxylation step. In some cases, even the major enan-
tiomer was inverted. An example is the transformation of 1
with Pd/C and cinchonidine: the ketone (S)-3 was formed
in acetonitrile, while (R)-3 was the major product in t-buta-
nol, both with the same ee of 12%. Inversion was also ob-
served in these experiments when cinchonidine was
replaced by cinchonine.
The solvent effect is less clear on the ‘right side’ of Figure 4,
because the conversion varies in this region and the solvent
effect may be substantially different in the debenzylation
and decarboxylation steps.
2.4. Solvent effect in the decarboxylation of 2
0
20
40
60
80
100
120
min (%)
To find a more reliable correlation between the solvent
properties and the enantioselection, the reaction intermedi-
ate 2 was synthesized and the solvent effect studied inde-
pendently of the deprotection step of the cascade
reaction. It should be noted that 2 is unstable at room tem-
perature and has to be stored at ꢀ20 ꢁC. Its decomposition
is, however, orders of magnitude slower in the absence of a
chiral base or solvent (diluent) than under reaction
conditions. For example, under reaction conditions, in
acetonitrile, only 5% of 2 decomposed in 2.5 h while the
reaction was complete in about 1 h in the presence of
1 equiv quinine (see Fig. 5).
50
45
40
35
30
25
20
15
10
b
Preliminary experiments in acetonitrile revealed that a
much higher concentration of amino alcohol (P1 equiv rel-
ative to 2) is required to obtain reasonable enantioselectiv-
ity. For example, the enantioselective decarboxylation of 2
with 1 equiv of quinine in acetonitrile gave 35% ee of (R)-4
at almost complete conversion (98%) and high yield (95%).
When the reaction was repeated with only 0.3 or 0.1 equiv
of quinine, the ee dropped to 19.5% and 9.5%, respectively.
The probable explanation is that in the cascade reaction,
intermediate 2 is produced slowly by deprotection of 1
while the actual molar ratio of the chiral base to 2 is much
higher than the initial chiral base/1 ratio.
0
20
40
60
80
100
120
time (min)
Figure 5. The effect of solvent on the rate (a) and enantioselectivity (b) in
the decarboxylation of 2; r—acetonitrile, j—chloroform, n—ethyl
acetate, s—dichloromethane. Reaction conditions: 40 mg 2, 63.5 mg
(1.0 equiv) quinine, 5 mL solvent.
dehalogenation with the Pd/H system leads to HCl forma-
tion and catalyst deactivation. Acetonitrile and acetone
were also good solvents for the decarboxylation of 2: they
are sufficiently polar but are weak H-bond donors and
acceptors. The ee was significantly lower in protic polar
solvents (t-butanol) and in weak polar solvents (toluene).
A feasible explanation for the solvent effect is that a polar
solvent could stabilize the substrate-chiral base interaction
but not distort it with additional H-bonding interactions.
The effect of solvent on the conversion and enantioselectiv-
ity in the decarboxylation of 2 is shown in Table 1. To com-
pare the reaction rates in different solvents, in one series of
experiments the reaction was stopped after 15 min. Conver-
sions higher than 70% were reached with the majority of
the solvents. The enantioselectivities measured after
15 min (ex) varied remarkably, and in toluene even the
opposite enantiomer of 3 was obtained. At complete con-
version there was a reasonably good correlation between
the enantioselectivity (ee100) and solvent properties charac-
terized by the empirical solvent parameter ðENT Þ for polar-
ity, and the Kamlet–Taft solvent parameters a and b for
the H-bond donor and acceptor strength, respectively.
The highest enantioselectivity was obtained in those polar
solvents, which are poor H-bond donors and acceptors.
Chloroform and dichloromethane were the best solvents:
their polarity is moderate but they are poor H-bond donors
and acceptors. Unfortunately, chlorinated solvents are not
appropriate for the cascade reaction, since their slow
As it can be seen in Table 1, the enantioselectivity varies
with conversion and the solvent has a big influence on this
correlation. A more detailed analysis is shown in Figure 5
for four different solvents. The samples were withdrawn
from the reaction mixture and quenched with diazometh-
ane to stop the conversion of 2 while the amount of 2
was determined as its methyl ester. The rate of decarboxyl-
ation decreased in the order: ethyl acetate > acetonitrile >
dichloromethane > chloroform. The enantioselectivity
changed significantly with time; it reached a minimum at

2864
P. Kukula et al. / Tetrahedron: Asymmetry 18 (2007) 2859–2868
Table 1. Influence of solvent properties on the conversion of 2 and the
enantioselectivity to (S)-3
ee). The transformation of cinchonine to the rigid b-iso-cin-
chonine resulted in some loss of ee. The efficiency of ephed-
rine derivatives changed significantly: the highest ee (38%)
was obtained with ephedrine, not with norephedrine. In
general, the results in Figures 1, 2 and 6 show that although
the effect of the chiral base is substrate dependent, for the
similar substrates 1 and 4 the differences are not big.
Solvent
Polarity a (Taft) b (Taft) X (%) eex (%) ee100
ðENT Þ
(%)
MeCN
t-BuOH 0.389
Acetone 0.355
CH2Cl2
CHCl3
EtOAc
THF
Dioxane 0.164
Et2O 0.117
Toluene 0.099
0.460
0.19
0.42
0.08
0.13
0.20
0.00
0.00
0.00
0.00
0.00
0.40
0.93
0.48
0.10
0.10
0.45
0.55
0.37
0.47
0.11
56
14
93
34
17
93
100
82
90
71
30
24
35
14
24
23
18
14
12
10a
34
16
36
38
44
23
20
12
16
4
0.309
0.259
0.228
0.207
Finally, another a-disubstituted b-ketoester (substrate 6 in
Fig. 7) that possesses no aromatic functionality was
chosen. The structural differences between 1 and 6 are
reflected by the results in Figures 1, 2, and 7: in most cases,
the reaction rates are somewhat higher while the enantio-
selectivities are considerably lower in the cascade reaction
6 to 7. An exception was the reaction in the presence of
b-iso-cinchonine, which was the most efficient chiral base
in this series. We assume that the generally poor enantio-
selectivities are mainly due to the missing aromatic func-
tion in 6.
X—conversion after 15 min, eex—ee after 15 min, ee100—ee at 100%
conversion. Reaction conditions: 5 mg 2, 8 mg (1.0 equiv) quinine, 2 mL
solvent.
a Product with (R)-configuration.
the beginning of the reaction, and then increased until com-
plete conversion.
2.5. Effect of substrate structure
3. Conclusions
The debenzylation–decarboxylation of 4 was studied using
the most promising chiral amino alcohols (Fig. 6). The
same reaction conditions were applied as in the trans-
formation of 1 (Figs. 1 and 2) to allow comparison of the
results. When using cinchona alkaloids as chiral bases,
the reactivity of 4 was lower than that of 1 but the enantio-
selectivities were similar or slightly better. The best chiral
bases were again quinine (58% ee) and quinidine (60%
The enantioselective one-pot debenzylation–decarboxyl-
ation of a-disubstituted b-ketoesters 1, 4, and 6 was
(re)investigated on supported Pd catalysts, in the presence
of a broad range of chiral amines and amino alcohols.
The best enantioselectivities up to 60% were achieved with
quinine and quinidine. Efficient enantioselection required
at least equimolar amount of the chiral base related to
the ketoacid intermediate and a polar solvent that does
Figure 6. Various chiral amino alcohols tested in the enantioselective debenzylation–decarboxylation of 4. The number in brackets after the ee indicates
the conversion. Reaction conditions: 20 mg 4, 0.025 equiv Pd (5 wt % Pd/C, Fluka), 0.3 equiv quinine, 2 mL MeCN, 1 bar H2, room temperature, 2 h.

P. Kukula et al. / Tetrahedron: Asymmetry 18 (2007) 2859–2868
2865
O
O
O
CH2Ph
1. Pd/C, H2
O
*
*
2. chiral base
6
7
H
N
H
H
R'O
OH
HO
N
N
O
R
R
NH2
N
N
N
β-iCN
(1S,2R)-(+)-2-amino-
1,2-diphenylethanol
ee 7% (S) (100)
CN ee 3% (S) (95)
CD ee 4% (R) (92)
ee 32% (R) (86)
QD ee 20% (R) (100)
QN ee 23% (S) (100)
PhOCD ee 7% (R) (100)
OH
HN
OH
OH
N
NH2
OH
NH2
(1R,2R)-(+)-amino-2-indanol
ee 1% (S) (100)
(-)-ephedrine
(-)-norephedrine
(-)-N-methyo-ephedrine
ee 3% (R) (100)
ee 1% (R) (100)
ee 7% (R) (100)
Figure 7. Various chiral amino alcohols tested in enantioselective debenzylation–decarboxylation of 6. The number in brackets after the ee indicates the
conversion. Reaction conditions: 20 mg 6, 0.025 equiv Pd (5 wt % Pd/C, Fluka), 0.3 equiv quinine, 2 mL MeCN, room temperature, 1 bar H2, 2 h.
not promote H-bonding interactions. The enantioselectivi-
ty was considerably higher when an aromatic ring was pres-
ent in the substrates 1 and 4 and an extended aromatic ring
in the chiral base (cinchona alkaloids). The observation
may indicate that the cascade reaction is triggered by deb-
enzylation on the Pd surface, but the subsequent decarbox-
ylation occurs in solution by the interaction of the chiral
base (being present in at least stoichiometric amounts)
and the ketoacid. The structural effects in the substrate
and chiral base, the high base/ketoacid ratio, and the sol-
vent effect suggest that the chiral base–ketoacid interac-
tions involve a p-bonding interaction and also H-bonds.
It is also known that quinine and quinidine adsorb more
weakly on Pd than cinchonidine and cinchonine.11 Hence,
doubling the enantioselectivity when replacing cinchoni-
dine or cinchonine by the aryl-substituted alkaloids quinine
or quinidine (Figs. 2 and 6) supports the assumption that
decarboxylation does not occur on the Pd surface (involv-
ing Pd as the active species and the chiral base as a chiral
surface ‘modifier’), but rather the origin of enantioselection
is the decarboxylation in solution catalyzed by the chiral
base being present in at least equimolar amounts.8,12 More
evidence in this direction, based on catalytic and spectro-
scopic studies, will be reported in the second part of our
work.13
equipped with Agilent capillary column HP-5 (30 m ·
0.32 mm · 0.25 lm). The intermediates and products of
the reactions were analyzed by an Agilent GC–MS (HP
6890 MSD) equipped with an HP-5MS column
(30 m · 0.25 mm · 0.25 lm). Separations were carried out
by column chromatography (Fluka Silica Gel 60 (0.04–
0.063 mm); solvent: 8:2 hexane/ethyl acetate) and the prod-
ucts were analyzed by TLC (Merck TLC plates pre-coated
with Silica Gel 60 F254; visualization by treatment with
Mostain solution). After separation and isolation of the
pure compounds, elementary analysis (automatic analyzers
1
Leco CHN-900 and Leco RO-478) and H and 13C NMR
spectroscopy (DPX 300 and AVANCE 500 from Bruker
AG) were used to characterize all compounds prepared.
The enantiomeric excess (ee) was determined by GC and
HPLC using a Trace GC (Thermo Finnigan) and a Merck
LaChrom system, respectively. The analysis was carried
out on a GC Chrompack capillary column CP-Chirasil-
Dex CB (25 m · 0.25 mm · 0.25 lm) and HPLC chiral col-
umn Chiracel OD (240 mm · 4.6 mm i.d., 10 lm particle
size).
4.2. Chemicals
The majority of chiral amines and amino alcohols tested
are commercially available. The methoxy-, phenoxy-, and
naphthoxy-cinchonidine,14 as well as N-methyl cinchonidi-
nium chloride and iodide,15 and b-isocinchonine16,17 were
prepared as described elsewhere. All other chiral amines
were commercial products and used as received. Palladium
catalysts were supplied by various catalyst producers:
5 wt % Pd/C (Fluka: F75992, Rohner: E101 O/W);
10 wt % Pd/C (Fluka: F75990, Acros: A020058801);
4. Experimental
4.1. General
All samples were analyzed by gas chromatography using a
Trace GC (Thermo Finnigan) gas chromatograph

2866
P. Kukula et al. / Tetrahedron: Asymmetry 18 (2007) 2859–2868
5 wt % Pd/SiO2 (Strem: 46-2090); 5 wt % Pd/TiO2 (Engel-
hard: 44057); 5 wt % Pd/Al2O3 (Engelhard: 40692);
5 wt % Pd/CaCO3 (Engelhard: 737); 5 wt % Pd/BaSO4
(Engelhard: 2190); 4 wt % Pd/1 wt % Pt/5 wt % Bi/C (De-
gussa: 1319). The solvents used for the synthesis and catal-
ysis were dried by standard procedures. The preparation of
starting materials was carried out under argon. Hydrogen
(99.999%) and argon (99.999%) were purchased from
Pangas.
was added dropwise under vigorous mechanical stirring.
After stirring for 1 h, three portions of tetrabutylammo-
nium bromide (1 g each, ca. 0.1 equiv) were added at inter-
vals of 30 min. Then, methyl iodide (75 mL, 171 g,
13 equiv) was added dropwise within 1 h and the mixture
was stirred overnight. The mixture was cooled to 0 ꢁC
and quenched with 2 M aqueous HCl (440 mL). The
organic phase was separated and the aqueous phase ex-
tracted three times with diethyl ether (3 · 200 mL). The
combined organic extracts were washed with brine, dried
over MgSO4, and evaporated to dryness to give crude
2-methyl-2-carboethoxy-1-tetralone (19.5 g, 92% yield).
GC (80 ꢁC, 2 min, 20 ꢁC/min, 300 ꢁC, 4 min, inj. 260 ꢁC,
det. 260ꢁ, flow 1.5 mL/min): rt 9.9 min. GC–MS (80 ꢁC,
2 min, 20 ꢁC/min, 280 ꢁC, 8 min, inj. 250 ꢁC, flow 1 mL/
min): rt 9.2 min. EI-MS: 232 (39, M+), 217 (7, M+ꢀMe),
187 (5, M+ꢀOEt), 158 (100, M+ꢀCOOEt), 131 (19), 118
(46), 90 (29). 1H NMR (500 MHz, CDCl 3):1.15 (t,
4.3. Synthesis of the starting materials
Compounds 1, 2, 4, and 6 were prepared by slightly
modified methods described elsewhere.3,8 Diazomethane
solution in diethyl ether, used for quenching the decarbox-
ylation of 2, was prepared from Diazald 214 using the stan-
dard procedure.18
4.3.1. 1-Tetralone-2-carboxylic acid ethyl ester 8. 1-Tetra-
lone (21.8 g, 149 mmol) was added dropwise to a stirred
suspension of NaH (60% dispersion in oil, 1.3 equiv,
8.0 g, 0.2 mol) in dry diethyl carbonate (5.0 equiv, 97.5 g,
100 mL, 825 mmol) under Ar. The reaction mixture was
heated at reflux and a white-violet solid was formed. After
1 h at reflux, the mixture was cooled down to 5 ꢁC and
200 mL of 2 M HCl was added dropwise while stirring.
The solid was dissolved and the phases separated. The
aqueous phase was extracted (2·) with toluene. The com-
bined extracts were dried over MgSO4 and evaporated in
vacuum to give a brown oil (30.2 g). The crude product
was purified by flash chromatography (petrol ether/ethyl
acetate, 9:1) to give 24.0 g (73% yield) of 2-carboethoxy-
1-tetralone. The keto/enol ratio was approximately 1:2.
The spectroscopic data were in agreement with those pub-
lished elsewhere.1 1H NMR (500 MHz, CDCl3): 1.28 (t,
J = 7.1 Hz, Me, 3H, ketone), 1.32 (t, J = 7.1 Hz, Me, 3H,
enol), 2.30–2.35 (m, H–C(3), 1H, ketone), 2.40–2.50 (m,
H–C(3), 1H, ketone), 2.53–2.57 (m, H–C(3), 2H, enol),
2.77–2.80 (m, H–C(4), 2H, enol), 2.93–3.06 (m, H–C(4),
2H, ketone), 3.57 (dd, J = 4.7, 10.5 Hz, H–C(2), 1H, ke-
tone), 4.12–4.31 (m, OCH2, 2H, ketone), 4.26 (q,
J = 7.1 Hz, OCH2, 2H, enol), 7.14 (dd, J = 0.8, 7.2 Hz,
H–C(5), 1H, enol), 7.21 (d, J = 7.7 Hz, H–C(5), 1H, ke-
tone), 7.23–7.31 (m, H–C(6,7), 3H, ketone and enol), 7.45
(td, J = 1.5, 7.9, H–C(7), 1H, ketone), 7.78 (dd, J = 1.4,
7.5 Hz, H–C(8), 1H, enol), 8.03 (dd, J = 1.1, 7.9 Hz, H–
C(8), 1H, ketone), 12.50 (s, OH, 1H, enol). 13C NMR
(125 MHz, CDCl3): 14.2 (q, Me, ketone), 14.3 (q, Me,
enol), 20.6 (t, C(3), enol), 26.4 (t, C(3), ketone), 27.6 (t,
C(4), keto), 27.8 (t, C(4), enol), 54.6 (d, C(2), keto), 60.5
(t, OCH2, enol), 61.2 (t, OCH2, keto), 97.0 (s, C(2), enol),
124.3 (d, C(8), enol), 126.5 (d, C(6), enol), 126.9 (d, C(6),
ketone), 127.4 (d, C(5), enol), 127.7 (d, C(8), ketone),
128.8 (d, C(5), ketone), 130.1 (s, C(4a), enol), 130.5 (d,
C(7), enol), 131.8 (s, C(4a), ketone), 133.8 (d, C(7), ketone),
139.4 (s, C(8a), enol), 143.7 (s, C(8a), ketone), 165.0 (s,
C(1), enol), 170.2 (s, OC@O, ketone), 172.7 (s, OC@O,
enol), 193.2 (s, C(1), ketone).
J = 7.1 Hz, CH3CH , 3H), 1.49 (s, Me–C(2), 3H), 2.00–
2
2.06 (m, H–C(3), 1H), 2.54–2.62 (m, H–C(3), 1H), 2.90–
3.06 (m, H–C(4), 2H), 4.12 (qd, J = 1.9, 7.1 Hz, OCH2,
2H), 7.20 (d, 7.7 Hz, H–C(5), 1H), 7.29 (dd, J = 7.5,
7.7 Hz, H–C(6), 1H), 7.45 (dd, J = 1.4, 7.5 Hz, H–C(7),
1H), 8.05 (dd, J = 1.4, 7.9 Hz, H–C(8), 1 H). 13C NMR
(125 MHz, CDCl3): 14.0 (q, CH3CH2), 20.6 (q, Me–C(2)),
26.0 (t, C(3)), 33.9 (t, C(4)), 53.8 (s, C(2)), 61.2 (t,
CH2CH3), 126.7 (d, C(6)), 128.0 (d, C(8)), 128.7 (d,
C(5)), 131.8 (s, C(4a)), 133.4 (d, C(7)), 143.1 (s, C(8a)),
172.8 (s, COOEt), 196.1 (s, C(1)).
4.3.3. 2-Methyl-1-tetralone-2-carboxylic acid benzyl ester 1
(from 9). Benzyl ester 1 was prepared by transesterifica-
tion with benzyl alcohol in the presence of tetraisopropyl
titanate, as described by Seebach et al.19 To a mixture of
8 (10 g, 43 mmol) and benzyl alcohol (37 mL, 357 mmol)
was added titanium isopropoxide (12.8 mL, 43.3 mmol)
and the mixture heated at 120 ꢁC for 3 h. The cooled mix-
ture (<20 ꢁC) was quenched with 1 M HCl and extracted
with ether/hexane (1:1). The organic extract was washed
with saturated aqueous solution of NaHCO3 and saturated
NaCl solution, and dried with MgSO4. The solvent was dis-
tilled off (65–75 ꢁC/0.05–0.1 torr) and the residue was puri-
fied by flash chromatography (petrol ether/acetone, 9:1) to
give 7.1 g (56% yield) racemic benzyl 2-methyl-1-tetralone-
2-carboxylate. GC (80 ꢁC, 2 min, 20 ꢁC/min, 300 ꢁC, 4 min,
inj. 260 ꢁC, det. 260ꢁ, flow 1.5 mL/min): rt 12.9 min. GC–
MS (80 ꢁC, 2 min, 20 ꢁC/min, 280 ꢁC, 8 min, inj. 250 ꢁC,
flow 1 mL/min): rt 13.1 min. EI-MS: 294 (14, M+), 203
(10, M+ꢀBn), 159 (51, M+ꢀCOOBn), 145 (7), 141 (9),
131 (16), 118 (31), 91 (100), 65 (11). HPLC (9:1 n-hex-
ane/2-propanol, flow 0.9 mL/min): rt 13.3 and 14.5 min,
(R)- and (S)-enantiomers of 1 (1:1, not assigned). 1H
NMR (500 MHz, CDCl3): 1.52 (s, Me–C(2), 3H), 2.02–
2.08 (m, H–C(3), 1H), 2.57–2.62 (m, H–C(3), 1H), 2.78–
2.99 (m, H–C(4), 2H), 5.05 (d, 12.5 Hz, OCH2, 1H), 5.17
(d, 12.5 Hz, OCH2, 1H), 7.10–7.14 (m, 2H), 7.17 (d,
J = 7.7 Hz, 1H), 7.23–7.25 (m, 3H), 7.29–7.32 (m, 1H),
7.43–7.47 (dd, J = 1.4, 6.5 Hz, H–C(7), 1H), 8.06 (dd,
J = 1.1, 7.9 Hz, H–C(8), 1 H). 13C NMR (125 MHz,
CDCl3): 20.5 (q, Me), 25.9 (t, C(3)), 33.9 (t, C(4)), 53.9
(s, C(2)), 66.7 (t, CH2Ph), 126.8 (d, Ph), 127.6 (2d, Ph),
128.0 (d, C(5)), 128.0 (d, C(6)), 128.4 (2d, Ph), 128.7 (d,
4.3.2. 2-Methyl-1-tetralone-2-carboxylic acid ethyl ester
9. Ethyl ester 8 (20 g, 92 mmol) was dissolved in toluene
(500 mL) and an aqueous 50% NaOH solution (250 mL)

P. Kukula et al. / Tetrahedron: Asymmetry 18 (2007) 2859–2868
2867
C(7)), 131.9 (s, Ph), 133.4 (d, C(8)), 135.6 (s, C(4a)), 143.1
(s, C(8a)), 172.8 (s, COO), 196.1 (s, C(1)). Anal. Calcd for
C19H18O3 (294.35): C, 77.53; H, 6.16; O, 16.31. Found: C,
77.44; H, 6.26; O, 16.39.
4.3.6. 2-Methyl-1-indanone-2-carboxylic acid benzyl ester
4. Benzyl ester 4 was prepared from 1-indanone by the
same procedure as benzyl ester 1. The total yield of acyla-
tion, methylation, and transesterification was 36%. GC
(80 ꢁC, 2 min, 20 ꢁC/min, 300 ꢁC, 4 min, inj. 260 ꢁC, det.
260ꢁ, flow 1.5 mL/min): rt 12.1 min. GC–MS (80 ꢁC,
2 min, 20 ꢁC/min, 280 ꢁC, 8 min, inj. 250 ꢁC, flow 1 mL/
min): rt 12.5 min. EI-MS: 280 (4, M+), 189 (7, M+ꢀBn),
146 (75, M+ꢀCOOBn), 133 (14), 115 (31), 105 (3), 91
(100), 77 (8), 65 (14), 51 (5). HPLC (9:1 n-hexane/2-propa-
nol, flow 0.9 mL/min): rt 18.1 and 21.4 min, (R)- and (S)-
4.3.4. 2-Methyl-1-tetralone-2-carboxylic acid 2. 2-Methyl-
2-carbomethoxy-1-tetralone (17.4 g, 80 mmol), prepared
by acylation of 1-tetralone with dimethyl carbonate and
methylation with MeI in the presence of t-BuOK by the
methods described above, was dissolved in methanol
(250 mL) and cooled down to 0 ꢁC on an ice-water bath.
A pre-cooled aqueous solution of KOH (13.5 g in
110 mL water) was slowly poured into the methanolic solu-
tion of 2-methyl-2-carbomethoxy-1-tetralone and the mix-
ture was led to warm up to room temperature and stirred
for 2 h. Methanol was evaporated under reduced pressure
at 0 ꢁC. The aqueous-methanolic phase was extracted with
dichloromethane (5 · 40 mL), acidified with diluted HCl to
enantiomers of
4
(1:1, not assigned). 1H NMR
(500 MHz, CDCl3): 1.54 (s, Me–C(2), 3H), 2.99 (d,
J = 17.1 Hz, H–C(3), 1H), 3.69 (d, J = 17.1 Hz, H–C(3),
1H), 5.10 (d, 12.6 Hz, OCH2, 1H), 5.15 (d, 12.6 Hz,
OCH2, 1H), 7.13–7.33 (m, 5H), 7.39 (t, J = 7.5 Hz, 1H),
7.45 (d, J = 7.7 Hz, 1H), 7.60 (dd, J = 1.1, 7.5 Hz, H–
C(7), 1H), 7.78 (dd, J = 1.1, 7.7 Hz, H–C(8), 1H). 13C
NMR (125 MHz, CDCl3): 21.0 (q, Me), 39.9 (t, C(3)),
56.1 (s, C(2)), 66.9 (t, CH2Ph), 126.5 (d, Ph), 127.7 (2d,
Ph), 128.0 (d, C(5)), 128.2 (d, C(6)), 128.5 (2d, Ph), 129.0
(d, C(7)), 134.7 (s, Ph), 135.3 (d, C(8)), 135.7 (s, C(4a)),
152.5 (s, C(8a)), 171.8 (s, COO), 203.2 (s, C(1)). Anal.
Calcd for C18H16O3 (280.33): C, 77.12; H, 5.75; O, 17.12.
Found: C, 77.33; H, 6.21; O, 16.89.
pH
2
and again extracted with dichloromethane
(5 · 50 mL). The organic extracts were washed with brine
and dried over MgSO4. The solvent was evaporated to
1/3 and the product was then crystallized by adding a
portion of hexane. The mother liquor was concentrated
in vacuum and the pure white crystals of 2-carboxy-2-
methyl-1-tetralone (11.6 g, 71% yield) were separated by
filtration. The acid was unstable at room temperature
and decomposed readily to the 2-methyl-1-tetralone and
carbon dioxide (see also Ref. 8). Therefore, it was stored
in the freezer at ꢀ20 ꢁC, where it remained stable for a
period of weeks. TLC: Rf 0. 1H NMR (500 MHz,
CDCl3):1.41 (s, Me–C(2), 3H), 1.98–2.03 (m, H–C(3),
1H), 2.45–2.49 (m, H–C(3), 1H), 2.82–2.88 (m, H–C(4),
1H), 2.95–3.01 (m, H–C(4), 1H), 7.12 (d, J = 7.7 Hz,
H–C(5), 1H), 7.20 (dd, J = 7.4, 7.7 Hz, H–C(7), 1H), 7.37
(ddd, J = 1.1, 7.4, 7.8 Hz, H–C(6), 1H), 7.94 (d,
J = 7.8 Hz, H–C(8), 1H), 12.75 (br s, OH, 1H). 13C
NMR (125 MHz, CDCl3): 20.4 (q, Me–C(2)), 25.6 (t,
C(3)), 33.2 (t, C(4)), 53.4 (s, C(2)), 126.8 (d, C(6)), 128.0
(d, C(8)), 128.7 (d, C(5)), 131.8 (s, C(4a)), 133.7 (d, C(7)),
143.2 (s, C(8a)), 178.7 (s, COOH), 196.2 (s, C(1)).
4.3.7. 2-Methyl-1-indanone 5. GC (80 ꢁC, 2 min, 20 ꢁC/
min, 300 ꢁC, 4 min, inj. 260 ꢁC, det. 260ꢁ, flow 1.5 mL/
min): rt 7.2 min. GC–MS (80 ꢁC, 2 min, 20 ꢁC/min,
280 ꢁC, 8 min, inj. 250 ꢁC, flow 1 mL/min): rt 6.9 min.
EI-MS: 146 (69), 131 (100), 117 (33), 103 (26), 91 (14), 77
(11), 63 (9), 51 (13), 39 (11). HPLC (9:1 n-hexane/2-propa-
nol, flow 0.9 mL/min): 8.5 min (R)-5 and 9.2 min (S)-5. The
absolute configuration was determined by comparison with
published data.20
4.3.8. 1,3,3-Trimethyl-2-oxo-cyclohexanecarboxylic acid
benzyl ester 6. The benzyl ester 6 was prepared by trans-
esterification with tetraisopropyl titanate as described by
Seebach et al.19 To a mixture of 1,3,3-trimethyl-2-oxo-
cyclohexanecarboxylic acid ethyl ester (1.16 g, 5.5 mmol)
and benzyl alcohol (8 mL, 77 mmol) was added titanium
isopropoxide (1.7 mL, 5.8 mmol) and the mixture was
heated at 120 ꢁC for 3 h. The cooled mixture (<20 ꢁC)
was quenched with 1 M HCl (20 mL) and extracted with
ether/hexane (1:1). The organic extract was washed with
a saturated aqueous solution of sodium hydrogen carbon-
ate and saturated sodium chloride solution, and dried over
magnesium sulfate. The solvent was distilled off (65–75 ꢁC/
0.05–0.1 torr) and the residue purified by flash chromato-
graphy (hexane/ethyl acetate, 9:1) to give 0.82 g (54% yield)
racemic 6. GC (80 ꢁC, 2 min, 10 ꢁC/min, 180 ꢁC, 20 min,
inj. 200 ꢁC, det. 200 ꢁC, flow 1.5 mL/min, CP-Chirasil-
Dex CB (25 m · 0.25 mm · 0.25 lm)): rt 19.1 min and
19.3 min, (R)- and (S)-enantiomers of 6 (1:1, not assigned).
GC–MS (80 ꢁC, 2 min, 20 ꢁC/min, 280 ꢁC, 8 min, inj.
250 ꢁC, flow 1 mL/min, HP-5MS (30 m, 0.25 mm,
0.25 lm)): rt 11.7 min. EI-MS: 274 (5, M+), 177 (6), 155
(11), 140 (42), 125 (5), 109 (17), 91 (100), 69 (19), 55 (8).
1H NMR (500 MHz, CDCl3): 0.97 (s, CH3, 3H), 1.07 (s,
CH3, 3H), 1.31 (s, CH3, 3H), 1.39–1.46 (m, CH2, 1H),
1.56–1.62 (m, CH2, 2H), 1.66–1.70 (m, CH2, 1H), 1.95–
4.3.5. 2-Methyl-1-tetralone 3. TLC: Rf 0.50. GC (80 ꢁC,
2 min, 20 ꢁC/min, 300 ꢁC, 4 min, inj. 260 ꢁC, det. 260ꢁ, flow
1.5 mL/min): rt 8.2 min. GC–MS (80 ꢁC, 2 min, 20 ꢁC/min,
280 ꢁC, 8 min, inj. 250 ꢁC, flow 1 mL/min): rt 7.5 min. EI-
MS: 160 (72), 145 (28), 131 (22), 118 (100), 90 (50), 77 (10),
63 (8), 51 (7), 39 (6). HPLC (9:1 n-hexane/2-propanol, flow
0.9 mL/min): 7.2 min (R)-4 and 7.8 min (S)-4. The absolute
configuration was determined by comparison with pub-
lished data.20 1H NMR (500 MHz, CDCl3):1.25 (d,
J = 6.8 Hz, Me–C(2), 3H), 1.82–1.90 (m, H–C(2), 1H),
2.15–2.20 (m, H–C(3), 1H), 2.55–2.59 (m, H–C(3), 1H),
2.92–3.05 (m, H–C(4), 2H), 7.21 (d, J = 7.7 Hz, H–C(5),
1H), 7.27 (dd, J = 7.4, 7.7 Hz, H–C(7), 1H), 7.43 (dd,
J = 7.4, 7.8 Hz, H–C(6), 1H), 8.01 (d, 7.8 Hz, H–C(8),
1H). 13C NMR (125 MHz, CDCl3): 15.2 (q, Me–C(2)),
28.6 (t, C(3)), 31.1 (t, C(4)), 42.4 (d, C(2)), 126.3 (d,
C(6)), 127.0 (d, C(8)), 128.5 (d, C(5)), 132.1 (s, C(4a)),
133.9 (d, C(7)), 144.0 (s, C(8a)), 200.5 (s, C(1)). Anal. Calcd
for C11H12O (160.22): C, 82.46; H, 7.55; O, 9.99. Found: C,
82.44; H, 7.47; O, 10.03.

2868
P. Kukula et al. / Tetrahedron: Asymmetry 18 (2007) 2859–2868
1.99 (m, CH2, 1H), 2.52–2.57 (m, CH2, 1H), 5.04 (d,
J = 12.39 Hz, CH2Ph, 1H), 5.17 (d, J = 12.39 Hz, CH2Ph,
1H), 7.28–7.41 (m, Ph, 5 H). 13C NMR (125 MHz, CDCl3):
18.4 (t), 23.5 (q), 25.3 (q), 26.7 (q), 36.8 (t), 40.5 (t), 46.0 (s),
55.2 (s), 66.7 (t, CH2Ph), 128.1 (2d), 128.2 (d), 128.5 (2d),
135.2 (s), 172.5 (s, C@O ester), 211.3 (s, C@O oxo). Anal.
Calcd for C17H22O3 (274.36): C, 74.42; H, 8.08; O, 17.49.
Found: C, 74.51; H, 8.12; O, 17.34.
Acknowledgment
Financial support by the Swiss National Foundation is
kindly acknowledged.
References
1. Walji, A. M.; MacMillan, D. W. C. Synlett 2007, 1477–1489.
2. Aboulhoda, S. J.; Reiners, I.; Wilken, J.; Henin, F.; Martens,
J.; Muzart, J. Tetrahedron: Asymmetry 1998, 9, 1847–1850.
3. Detalle, J. F.; Riahi, A.; Steinmetz, V.; Henin, F.; Muzart, J.
J. Org. Chem. 2004, 69, 6528–6532.
4. Roy, O.; Diekmann, M.; Riahi, A.; Henin, F.; Muzart, J.
Chem. Commun. 2001, 533–534.
5. Roy, O.; Riahi, A.; Henin, F.; Muzart, J. Eur. J. Org. Chem.
2002, 3986–3994.
6. Roy, O.; Loiseau, F.; Riahi, A.; Henin, F.; Muzart, J.
Tetrahedron 2003, 59, 9641–9648.
7. Aboulhoda, S. J.; Henin, F.; Muzart, J.; Thorey, C.; Behnen,
W.; Martens, J.; Mehler, T. Tetrahedron: Asymmetry 1994, 5,
1321–1326.
4.3.9. 2,2,6-Trimethylcyclohexanone 7. Product of decar-
boxylation of 6. GC (80 ꢁC, 2 min, 10 ꢁC/min, 180 ꢁC,
20 min, inj. 200 ꢁC, det. 200 ꢁC, flow 1.5 mL/min, CP-
Chirasil-Dex CB (25 m · 0.25 mm · 0.25 lm)): rt 6.6 min
(R)-7 and 6.8 min (S)-7. The absolute configuration was
determined by comparison with published data.21,22 GC–
MS (80 ꢁC, 2 min, 20 ꢁC/min, 280 ꢁC, 8 min, inj. 250 ꢁC,
flow 1 mL/min, HP-5MS (30 m, 0.25 mm, 0.25 lm)): rt
4.7 min. EI-MS: 140 (22, M+), 97 (10), 82 (100), 69 (48),
56 (49), 41 (40), 39 (20).
8. Henin, F.; Muzart, J.; Nedjma, M.; Rau, H. Monatsh. Chem.
1997, 128, 1181–1188.
4.4. Typical decarboxylation procedure
9. Aboulhoda, S. J.; Letinois, S.; Wilken, J.; Reiners, I.; Henin,
F.; Martens, J.; Muzart, J. Tetrahedron: Asymmetry 1995, 6,
1865–1868.
10. Baur, M. A.; Riahi, A.; Henin, F.; Muzart, J. Tetrahedron:
Asymmetry 2003, 14, 2755–2761.
11. Huck, W. R.; Mallat, T.; Baiker, A. Catal. Lett. 2003, 87,
241–247.
12. Brunner, H.; Muller, J.; Spitzer, J. Monatsh. Chem. 1996, 127,
845–858.
13. Kukula, P.; Matousek, V.; Mallat, T.; Baiker, A. Chem. Eur.
J., in press.
14. Diezi, S.; Mallat, T.; Szabo, A.; Baiker, A. J. Catal. 2004,
228, 162–173.
Starting from 1: the experiments were carried out in a
50-mL glass reactor equipped with heating and magnetic
stirring. The catalyst (5 wt % Pd/C, Fluka) and the chiral
amino alcohol (0.3 equiv to substrate) were brought into
the reactor together with the solvent (acetonitrile, 5 mL),
then the reactor was flushed with argon and hydrogen
and the mixture was stirred at the reaction temperature
under a flow of hydrogen for 10 min. The reaction was
started by the addition of 1 (100 mg, 0.34 mmol), dissolved
in acetonitrile (5 mL), via a syringe under hydrogen
atmosphere. The samples withdrawn during the reaction
were filtered and analyzed using GC, chiral HPLC, and
GC–MS.
15. Borszeky, K.; Burgi, T.; Zhaohui, Z.; Mallat, T.; Baiker, A. J.
¨
Catal. 1999, 187, 160–166.
´
16. Bartok, M.; Sutyinszki, M.; Felfo¨ldi, K. J. Catal. 2003, 220,
207–214.
Starting from 2: the chiral amino alcohol (1 equiv to sub-
strate) and the solvent (acetonitrile, 4 mL) were stirred
magnetically in a 25 mL round-bottomed flask under an
argon atmosphere at room temperature. The reaction was
started by the addition of acid 2 (40 mg, 0.2 mmol)
dissolved in 1 mL acetonitrile via a syringe under an argon
atmosphere. To the samples withdrawn during the reac-
tion, an excess of etheric diazomethane solution was added
to quench the reaction before chromatography. Thus, the
unreacted acid 2 was immediately and completely trans-
formed to its methyl ester.
17. Hoxha, F.; Mallat, T.; Baiker, A. J. Catal. 2007, 248, 11–19.
18. Vogel, A. I. Vogel’s Textbook of Practical Organic Chemistry,
5th ed.; Longman Scientific and Technical, 1989.
19. Seebach, D.; Hungerbuhler, E.; Naef, R.; Schnurrenberger,
¨
P.; Weidmann, B.; Zuger, M. Synthesis 1982, 138–141.
20. Mohr, J. T.; Nishimata, T.; Behenna, D. C.; Stoltz, B. M. J.
Am. Chem. Soc. 2006, 128, 11348–11349.
21. Yanagisawa, A.; Kikuchi, T.; Kuribayashi, T.; Yamamoto,
H. Tetrahedron 1998, 54, 10253–10264.
22. Yanagisawa, A.; Watanabe, T.; Kikuchi, T.; Yamamoto, H.
J. Org. Chem. 2000, 65, 2979–2983.