Studies of the Electronic Effects of Zinc Cluster Catalysts and Their Application to the Transesterification of β-Keto Esters

Article abstract of DOI:10.1002/asia.201600062

The electronic effects of tetranuclear zinc cluster catalysts on transesterification were investigated by changing the carboxylate ligands in the clusters. High catalyst activity crucially depended on the balance between Lewis acidity and Br?nsted basicity of the catalyst; this was consistent with the dual activation of both the electrophile and nucleophile by the cooperative zinc centers. In addition, tetranuclear zinc cluster catalysts achieved the transesterification of β-keto esters with unprecedented levels of broad substrate generality, in which a newly developed pentafluoropropionate-bridged zinc cluster and 4-dimethylaminopyridine additive greatly improved the reactivity of sterically congested α- and α,α-disubstituted β-keto esters. Lewis versus Br?nsted: High catalyst activity of zinc clusters on transesterification crucially depend on a balance between Lewis acidity and Br?nsted basicity of the catalyst. Zinc clusters, including a newly developed pentafluoropropionate-bridged zinc cluster, achieved the transesterification of β-keto esters with unprecedented levels of broad substrate generality (see figure).

Full text of DOI:10.1002/asia.201600062

DOI: 10.1002/asia.201600062
Full Paper
Reaction Mechanisms
Studies of the Electronic Effects of Zinc Cluster Catalysts and
Their Application to the Transesterification of b-Keto Esters
Kazushi Agura,[a] Yukiko Hayashi,[b] Mari Wada,[a] Daiki Nakatake,[a] Kazushi Mashima,*[b] and
Takashi Ohshima*[a]
Abstract: The electronic effects of tetranuclear zinc cluster
catalysts on transesterification were investigated by chang-
ing the carboxylate ligands in the clusters. High catalyst ac-
tivity crucially depended on the balance between Lewis
acidity and Brønsted basicity of the catalyst; this was consis-
tent with the dual activation of both the electrophile and
nucleophile by the cooperative zinc centers. In addition, tet-
ranuclear zinc cluster catalysts achieved the transesterifica-
tion of b-keto esters with unprecedented levels of broad
substrate generality, in which a newly developed pentafluor-
opropionate-bridged zinc cluster and 4-dimethylaminopyri-
dine additive greatly improved the reactivity of sterically
congested a- and a,a-disubstituted b-keto esters.
tion metals, such as iron,[11] nickel,[12] copper,[13] palladium,[14]
zinc;[15] and organocatalysts, such as N-heterocyclic carbenes
(NHCs),[16] 4-dimethylaminopyridine (DMAP),[17] 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU),[18] and others,[19] have been report-
ed. Despite these successes, however, there remains a high
demand for the development of a green catalytic transesterifi-
cation with high catalytic activity and high functional group
compatibility.
Introduction
Transesterification is a fundamental organic transformation.[1]
Because transesterification can convert a simple ester into
a structurally more complicated and/or more functionalized
ester in a single step, it is often used for the preparation of
high-class esters. In classical methods, simple acids (both or-
ganic and inorganic) or bases (typically alkali-metal alkoxides)
are used as a catalyst, but such harsh reaction conditions
sometimes lead to the decomposition of functional group(s)
on substrates, which limits the substrate generality. In this con-
text, many efficient catalyses were developed to promote
transesterification under milder conditions. Alkoxides of hard
metals, such as aluminum[2] and Group IV metals,[3] are good
catalysts for transesterification. Tin complexes are also an im-
portant class of transesterification catalysts.[4,5] Otera et al. re-
ported that distannoxane complexes were excellent catalysts
for transesterification,[4] and a practical and green catalytic
system was developed by applying fluorous biphase technolo-
gy.[4f] GagnØ et al. reported that alkali-metal alkoxide clusters
catalyzed ester metathesis reactions of methyl esters with tert-
butyl acetate to afford the corresponding tert-butyl esters.[6]
Furthermore, reactions with indium;[7] lanthanoids;[8–10] transi-
We previously reported m-oxo-tetranuclear zinc cluster 1b as
an efficient catalyst for the direct formation of oxazolines from
esters, carboxylic acids, lactones, and nitriles;[20a] transesterifica-
tion of various methyl esters;[20b,c,h] acetylation of alcohols in
EtOAc;[20d] deacylation of esters in MeOH;[20e] and cyclic carbon-
ate synthesis from epoxides and CO2[20i] (Figure 1). A unique hy-
[a] Dr. K. Agura, M. Wada, D. Nakatake, Prof. Dr. T. Ohshima
Graduate School of Pharmaceutical Sciences
Kyushu University, CREST
Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)
E-mail: ohshima@phar.kyushu-u.ac.jp
[b] Dr. Y. Hayashi, Prof. Dr. K. Mashima
Department of Chemistry, Graduate School of Engineering Science
Osaka University, CREST, Toyonaka
Osaka 560-8631 (Japan)
E-mail: mashima@chem.es.osaka-u.ac.jp
Supporting information for this article can be found under http://
dx.doi.org/10.1002/asia.201600062.
Figure 1. Structure of tetranuclear zinc clusters 1, octanuclear cobalt clusters
2, and alkoxide-bridged dinuclear cobalt complex 3.
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droxy-group-selective acylation in the presence of inherently
much more nucleophilic amino groups was also achieved by
1b.[20b] We recently revealed that octanuclear cobalt cluster 2,
which is a kind of dimer of a tetranuclear cobalt cluster such
as zinc cluster 1 and in equilibrium with the tetranuclear clus-
ter in solution, has similar catalytic activity and chemoselectivi-
ty for transesterification as that of zinc cluster 1b.[20j] In the
presence of 2,2’-bipyridine, octanuclear cobalt cluster 2 reacted
with alcohol to generate an alkoxide-bridged dinuclear cobalt
complex 3, and isolated complex 3 exhibited excellent catalytic
activity (turnover number (TON)=1120 and turnover frequency
(TOF)=224 hÀ1); this suggested that alkoxide cobalt complex 3
was the active species in this catalytic cycle. In addition, kinetic
studies and DFT calculations revealed the Michaelis–Menten
behavior of complex 3 through an ordered ternary complex
mechanism similar to that of dinuclear metalloenzymes. The
zinc-cluster-catalyzed transesterification was drastically acceler-
ated by the addition of alkyl amine and N-heteroaromatic li-
gands,[20f] which coordinate to the metals, stabilize the clusters
with lower nuclearities, and enhance catalytic activity for trans-
esterification.[20f,j] On the other hand, the ligand effects of car-
boxylate ligands have not been studied. To gain further insight
into these unique catalyst systems and to develop more effi-
cient catalysts, we intensively studied the electronic effects of
zinc cluster catalysts by changing the carboxylate ligands. We
also describe the successful application of the optimized zinc
catalyst systems to the transesterification of b-keto esters with
broad substrate generality.[21]
Table 1. Synthesis of tetranuclear zinc clusters 1a–e.
Entry[a]
R
T
Yield[b]
[%]
[8C]
1
2
3
4
5
CH3 (1a)
CF3 (1b)
CF2CF3 (1c)
CF2CF2CF3 (1d)
CF2CH2CH3 (1e)
250
320
320
200
200
79
84
84
80
70
[a] Reactions performed on a 1.0 g scale. Products 1a–e were isolated by
vacuum distillation. [b] Calculated as the number of crystal water x=2.
Table 2. Comparison of the catalytic activities of 1a–e for transesterifica-
tion.
Entry[a]
4
5
t[b]
[h]
1
Yield[b]
[%]
Results and Discussion
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4b
4b
4b
4b
4b
4b
4b
4b
4b
4b
4b
5a
5a
5a
5a
5a
5b
5b
5b
5b
5c
5c
5c
5c
5a
5a
5a
5a
5b
5b
5b
5b
5c
5c
5c
5c
10
10
10
10
10
8
8
8
8
25
25
25
25
10
10
10
10
8
1a
1e
1b
1c
1d
1a
1b
1c
1d
1a
1b
1c
1d
1a
1b
1c
1d
1a
1b
1c
1d
1a
1b
1c
1d
7
38
65
69
29
34
62
68
28
10
46
60
12
8
20
20
6
18
38
27
14
3
Synthesis of a Series of Tetranuclear Zinc Clusters
To explore the mechanism of transesterification catalyzed by
zinc cluster 1 in more detail, we initially examined the effects
of the Lewis acidity of zinc clusters by changing the carboxyl-
ate ligands on 1.[22] First, we synthesized a series of tetranu-
clear zinc clusters, Zn4(OCOR)6O (1a: R=CH3, 1b: R=CF3, 1c:
R=CF2CF3, 1d: R=CF2CF2CF3, 1e: R=CF2CH2CH3), as white
solids in good yield (70–84%) by pyrolysis of the correspond-
ing zinc carboxylates and purification by vacuum distillation
(<0.02 mmHg; Table 1).[20a,g]
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
Effects of Carboxylate Ligands
8
8
8
25
25
25
25
Zinc clusters 1a–e were then applied to the catalytic transes-
terification of several combinations of methyl esters 4 and al-
cohols 5 (Table 2). In the presence of catalytic amounts of zinc
clusters 1 (1.25 mol%), methyl 3-phenylpropanoate (4a) or
methyl 4-chlorobenzoate (4b), and 1.2 equivalents of primary
or secondary alcohols, such as benzyl alcohol (5a), n-hexanol
(5b), and cyclohexanol (5c), in diisopropyl ether[23] were
heated at reflux for a period of time. Depending on the pKa
values of the corresponding carboxylic acids, the Lewis acidi-
ties of zinc clusters 1 should increase in the following order:
1a<1e<1b<1c<1d. The results of all examined substrate
combinations revealed that the Lewis acidity of zinc ions se-
10
5
1
[a] Reactions performed on a 1.0 mmol scale; 1.7 mL of iPr2O was used.
[b] Determined by GC analysis.
verely affected the catalytic activity of the zinc clusters in the
transesterifications, and the yields of products 6 tended to fast
increase and then decrease with an increase in the Lewis acidi-
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ty of 1, and moderately Lewis acidic 1b (for aromatic ester 4b)
and/or 1c (for aliphatic ester 4a) afforded the best results. In-
terestingly, Lewis acidic cluster 1d had only limited catalytic
activity, which significantly decreased the product yield in all
combinations. For example, in the reactions of ester 4a with
alcohols 5a, acetate-bridged zinc cluster 1a gave product 6aa
in only 7% yield (Table 2, entry 1). The use of more Lewis
acidic zinc clusters 1b and 1c greatly improved the yield to 65
and 69% yield, respectively (Table 2, entries 3 and 4), whereas
Lewis acidic zinc cluster 1d gave product 6aa in only 29%
yield (Table 2, entry 5). Because 1d has longer alkyl chains than
the others, the steric effects were a concern. Thus, zinc cluster
1e, the carboxylate ligands of which have alkyl chains the
same length as those of 1d, but different electron-withdrawing
ability, was prepared and applied to the transesterification of
4a with 5a (Table 2, entry 2). The difference in catalytic activi-
ties between 1e (Table 2, entry 2, 38% yield) and 1d (Table 2,
entry 5, 29% yield) rules out the possibility that the lower cata-
lytic activity of 1d is due to steric effects.
In general, an increase in Lewis acidity improves the catalytic
activity of Lewis acid catalysts. In the zinc cluster system, how-
ever, either an increase or decrease in Lewis acidity from 1b
and 1c decreased the catalytic activity. These findings suggest-
ed that a balance between Lewis acidity and Brønsted basicity
of the catalyst was very important to achieve high catalyst ac-
tivity, consistent with the dual activation of the electrophile
(ester) and nucleophile (alcohol) by the cooperative zinc cen-
ters, similar to the alkoxide-bridged dinuclear cobalt complex
3[20j] and dinuclear metalloenzymes[24] (Scheme 1). Higher Lewis
Transesterification of b-Keto Esters
Based on our in-depth studies of the ligand effects, we next
examined the transesterification of b-keto esters.[1] Because of
their electrophilic and nucleophilic nature, b-keto esters are
highly useful for various transformations, such as condensation
reactions and alkylation,[21] and are thus used as organic build-
ing blocks for the synthesis of complex bioactive natural prod-
ucts, such as paclitaxel[26] and podophyllotoxin.[27] For the syn-
thesis of a wide variety of b-keto esters, the transesterification
of various combinations of b-keto esters (especially methyl and
ethyl esters) with alcohols has received considerable attention.
However, the transesterification reaction of b-keto esters was
sluggish and required a large excess of b-keto ester and high-
boiling alcohols.[1] In addition, unlike simple esters, the chela-
tion nature of b-keto esters suppresses the activity of metal
catalysts through the formation of a coordinate bond to metal
ions, and the acidic nature of b-keto esters (pKa ꢀ14 in DMSO)
suppresses the activity of the base catalyst. To date, several
acidic and basic catalysts, such as DMAP,[17,28] zeolites,[29] super
acid,[30] montmorillonite,[31] Zn/I2,[15a] amberlyst-15,[32] Nb2O5,[33]
N-bromosuccinimide (NBS),[34] Al(H2PO4)3,[35] and BiCl3,[36] have
been used for the transesterification of b-keto esters. The sub-
strate generality of b-keto esters, however, has much room for
improvement. Almost all of the substrates used for the reac-
tions were a-unsubstituted simple b-keto esters, and reactions
of sterically more congested a-substituted b-keto esters have
not been well studied.
First, under the optimized conditions for simple esters, the
reactions of methyl benzoacetate (7a) with representative al-
cohols 5a–c were performed (Table 3). As expected, transes-
terification of 7a with 5a and 5b proceeded efficiently in dii-
sopropyl ether at reflux without decomposition of 7a or side
reactions. Because the reaction with sterically congested alco-
hol 5c did not go to completion, even after 42 h (Table 3,
entry 3), higher temperature conditions in toluene as the sol-
vent were examined, and the yield of 8ac was greatly im-
proved to 95% (Table 3, entry 6).
Table 3. Transesterification of b-keto ester 7a in iPr2O and toluene at
reflux.
Scheme 1. Dual activation of ester and alcohol by zinc cluster 1.
acidity increases the electrophilicity of the coordinated carbon-
yl group of esters, thereby facilitating transesterification,
whereas the nucleophilicity of the zinc alkoxide moieties is re-
duced. In contrast to transesterification, the catalytic activity of
zinc cluster 1 in ester–amide exchange reactions had a some-
what opposite tendency; moderately Lewis acidic zinc clusters
1b and 1c afforded a lower yield, and less acidic 1a and more
acidic 1d afforded a higher yield;[25] this indicated that amida-
tion catalyzed by zinc cluster 1 proceeded through a reaction
mechanism that differed from the cooperative mechanism of
transesterification catalyzed by 1.
Entry[a]
Solvent
Alcohol 5
t
[h]
Yield[b]
[%]
1
2
3
4
5
6
iPr2O
iPr2O
iPr2O
toluene
toluene
toluene
5a (R2 =Bn)
42
48
42
45
48
45
88
88
65
89
86
95
5b (R2 =nHex)
5c (R2 =cHex)
5a (R2 =Bn)
5b (R2 =nHex)
5c (R2 =cHex)
[a] Reactions were performed on a 3.0 mmol scale. [b] Yield of product
isolated.
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Table 5. Transesterification of various b-dicarbonyl compounds 7 with
5b.
Table 4. Transesterification of b-keto ester 7a with various alcohols 5.
Entry[a]
Alcohol 5
t
[h]
Yield[b]
[%]
Entry[a]
b-Dicarbonyl compound 7
t
[h]
Yield[b]
[%]
1
(5d)
(5e)
(5 f)
44
65
48
89
86
82
1
2
(7b)
48
48
81
81
2[c]
3
(7c)
(7d)
(7e)
4
(5g)
(5h)
(5i)
60
48
48
89
86
94
5
3
4
48
42
60
87
6[d]
7
8
(5j)
44
87
5
(7 f)
(7g)
(7h)
48
68
68
97
98
73
(5k)
44
93
6[c]
9[e]
(5l)
44
72
97
85
7[c]
10[f]
(5m)
8
(7i)
(7j)
60
48
77
87
11[g]
12
tBuOH
PhOH
(5n)
(5o)
72
45
82
N.R.[h]
9[d]
[a] Reactions were performed on a 3.0 mmol scale; 5.0 mL of toluene was
used [b] Yield of product isolated. [c] iPr2O was used as the solvent.
[d] 10 mol% of DMAP was added. [e] 1.5 equivalents of 5l were used.
[f] 2.0 equivalents of 5m were used. [g] 5.0 equivalents of 5n were used.
[h] N.R.=not recorded.
[a] Reactions were performed on a 3.0 mmol scale; 5.0 mL of toluene was
used [b] Yield of product isolated. [c] 2.6 equivalents of alcohol were
used. [d] Benzyl alcohol (5a) was used instead of 5b.
Therefore, transesterification of 7a with various alcohols was
performed in toluene at reflux (Table 4). The reaction of steri-
cally congested neopentyl alcohol (5d) gave the desired prod-
uct 8ad in high yield (Table 4, entry 1). b-Keto esters of allylic
alcohols such as 8ae are difficult to prepare because they
readily proceed to Carroll rearrangement.[37] Indeed, in toluene
at reflux, the reaction of cinnamyl alcohol (5e) led to the for-
mation of the desired allylic ester 8ae in moderate yield, along
with 1,3-diphenyl-1-oxo-4-pentene, which was generated
through Carroll rearrangement and subsequent decarboxyla-
tion.[25] Fortunately, such a side reaction was efficiently pre-
vented by lowering the reaction temperature to that of iPr2O
at reflux to give 8ae in 86% yield (Table 4, entry 2). Propargylic
alcohol (5 f) and alcohols with pivaloyl ester and silylether
groups 5g and 5h have not been used for the transesterifica-
tion of b-keto esters, but they were compatible with this zinc
catalysis, affording the products in high yield (Table 4, en-
tries 3–5). The highly acid-sensitive tetrahydropyranyl (THP)
ether group was partially decomposed owing to the acidity of
b-keto ester 7a, but the addition of 10 mol% of DMAP[20f] effi-
ciently suppressed the decomposition of THP ether to provide
8ai in 94% yield (Table 4, entry 6). Reactions of sterically more
congested secondary alcohols, menthol (5k) and (+)-borneol
(5l), and tertiary alcohol adamantanol (5m) also proceeded
smoothly (Table 4, entries 7–10). Transesterification of tert-buta-
nol (5n) is a difficult task, not only because of its steric bulki-
ness, but also because it is prone to undesired elimination. Al-
though the reaction was sluggish under standard reaction con-
ditions,[24] the use of 5 equivalents of 5n greatly improved the
yield of 8an to 82% yield (Table 4, entry 11). In contrast, acidic
alcohol, phenol (5o), resulted in almost no reaction because
5o may cause the formation of inactive zinc phenoxide species
(Table 4, entry 12).[20j]
Next, the substrate scope of b-keto esters 7 was examined
(Table 5). b-Alkyl substituted b-keto esters, such as methyl ace-
toacetate (7b) and sterically demanding methyl pivaloylacetate
(7c), were also good substrates (Table 5, entries 1 and 2).
Whereas a-methyl-substituted b-keto ester 7d gave product
8 db in only moderate yield, even after 48 h (Table 5, entry 3,
see below), b-keto esters derived from 5- and 6-membered
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cyclic ketones were efficiently transesterified to form 8eb and
8 fb, respectively, in high yield (Table 5, entries 4 and 5). This
zinc catalysis was highly effective for b-keto esters and other
active b-dicarbonyl derivatives. In the case of b-diesters di-
methyl malonate (7g) and Meldrum’s acid (7h), both ester
groups were transesterified with 2.6 equivalents of alcohol 5b
to give dihexyl malonate (8gb) in good yield (Table 5, entries 6
and 7). When methyl-N-hexyl malonamide (7i) and trimethyl
phosphonoacetate (7j) were used, only the ester groups were
reacted, leaving the remaining amide and phosphate groups
intact (Table 5, entries 8 and 9).
acidic a-proton, such as 7d, because a basic additive/catalyst
is not effective for these substrates.
The obtained transesterified product 8kp, which was previ-
ously prepared from diallyl pimelate through Dieckmann con-
densation and subsequent a-methylation, was a highly useful
substrate for the enantioselective decarboxylative allylation de-
veloped by Stoltz et al. and the obtained enantioenriched a-
allyl ketones were successfully converted into various natural
products (Scheme 2).[38]
The results shown in Table 5, as well as those reported previ-
ously, highlight the issues of the low reactivity of sterically con-
gested a- and a,a-disubstituted b-keto esters in transesterifica-
tions. To address this issue, we further optimized the reaction
conditions based on the nitrogen[20f,j] and carboxylate ligand
effects (Table 6). Although several primary and secondary alkyl
amines accelerated the transesterification of simple esters cata-
lyzed by 1b,[20f] those alkyl amines reacted with b-keto esters
to form the corresponding imines/enamines. Therefore, we
evaluated the effects of adding DMAP to the reactions of 7d
and 7k. The addition of 20 mol% of DMAP had only a small
effect on the reaction of 7d and the yield of 8db was slightly
improved from 60 (Table 6, entry 1) to 65% (Table 6, entry 2),
probably owing to the existence of a rather acidic a-proton in
b-keto ester 7d. In contrast, the addition of DMAP was highly
effective for the reaction of 7k, which has no acidic a-proton,
and the yield of 8kp was greatly improved from 19 (Table 6,
entry 4) to 78% (Table 6, entry 5). Next, we examined the use
of zinc cluster 1c, which gave the best results for aliphatic
esters (Table 2). Slightly more Lewis acidic catalyst 1c afforded
better results for both b-keto esters 7d (Table 6, entry 3) and
7k (Table 6, entry 6) than those with 1b. This new zinc catalyst
1c is especially useful for the reaction of b-keto esters with an
Scheme 2. Utility of the transesterified product 8kp. (S)-tBuPHOX=(S)-4-tert-
butyl-2-[2-(diphenylphosphino)phenyl]-2-oxazoline, dba=dibenzylideneace-
tone.
Conclusion
A series of perfluoroalkyl carboxylate-bridged zinc clusters 1a–
e were synthesized and their use for transesterification eluci-
dated the electronic effects on the zinc-cluster-catalyzed trans-
esterification. The Lewis acidity of zinc ions severely affected
the catalytic activity of the zinc cluster and the yields of the
products tended to increase rapidly and then decrease with an
increase in the Lewis acidity of 1; moderately Lewis acidic clus-
ters 1b and 1c afforded the best results. Although an increase
in Lewis acidity generally improves the catalytic activity of
Lewis acid catalysts, a balance between Lewis acidity and
Brønsted basicity of the catalyst was very important to achieve
high catalyst activity in the zinc cluster system. These results
clearly indicated that the cooperative zinc centers simultane-
ously activated both the electrophile (ester) and nucleophile
(alcohol) similarly to the alkoxide-bridged dinuclear cobalt
complex 3 and dinuclear metalloenzymes.
Table 6. Transesterification of less reactive b-keto esters 7d and 7k.
We also examined the transesterification of b-keto esters,
which are highly useful building blocks for complex bioactive
natural-product synthesis. Although almost all of the sub-
strates previously used for the reactions were limited to a-un-
substituted simple b-keto esters, zinc cluster 1b efficiently cat-
alyzed the reactions of various sterically congested a-substitut-
ed b-keto esters. In addition, our intensive studies on carboxyl-
ate and nitrogen ligand effects allowed us to develop more ef-
ficient reaction systems; pentafluoropropionate-bridged zinc
cluster 1c and DMAP additive for sterically congested a- and
a,a-disubstituted b-keto esters. This new zinc catalyst 1c was
the best catalyst so far for the reaction of b-keto esters with an
acidic a-proton. Moreover, broad functional group tolerance,
such as pivaloyl ester, silylether, and THP ether groups, was
achieved for the first time, and reactions of other active b-di-
carbonyl derivatives, such as b-diesters, malonamide, and
phosphonoacetate, were also accomplished.
Entry[a] b-Keto ester 7 Alcohol 5
DMAP
(x)
Catalyst Yield
1
[%][b]
1
0
1b
60
nHexOH (5b)
2
3
(7d)
(7k)
20
0
1b
1c
65
82
4
0
1b
19
allyl alcohol
(5p)
5
6
20
0
1b
1c
78
50
[a] Reactions were performed on a 3.0 mmol scale; 5.0 mL of toluene was
used. [b] Yield of product isolated.
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Experimental Section
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General Procedure for Transesterification of b-Keto Esters Cat-
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Acknowledgements
This work was supported by the Core Research for Evolutional
Science and Technology (CREST) program of the Japan Science
and Technology Agency (JST), Japan and The Grant-in-Aid for
Scientific Research on Innovative Areas 2707 Middle Molecular
Strategy from the Ministry of Education, Culture, Sports, Sci-
ence and Technology (MEXT). Y.H. is the grateful recipient of
a scholarship from JSPS.
Keywords: beta-keto esters · electronic effects · synthesis
design · transesterification · zinc
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Manuscript received: January 15, 2016
Accepted Article published: February 25, 2016
Final Article published: April 14, 2016
Chem. Asian J. 2016, 11, 1548 – 1554
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim