Efficient acylation and transesterification catalyzed by dilithium tetra-tert-butylzincate at low temperatures

Article abstract of DOI:10.1016/j.tetlet.2016.03.096

The acylation and transesterification of alcohols with vinyl acetate and carboxylic esters were investigated in the presence of a catalytic amount (1-10 mol %) of dilithium tetra-tert-butylzincate (TBZL) as a catalyst. The acylation proceeded quantitatively at 0 °C within 1 h. The transesterification occurred for a wide range of combinations of esters and alcohols at 0 to -40 °C. To the best of our knowledge, this is the first successful transesterification at such low temperatures. The time-conversion plots for the transesterification show that the reaction reached equilibrium within 5 min at 0 °C. The reaction proceeded quantitatively by addition of molecular sieves 4A. In addition, the transesterification proceeded even in the presence of H₂O and amines.

Full text of DOI:10.1016/j.tetlet.2016.03.096

Tetrahedron Letters xxx (2016) xxx–xxx
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Tetrahedron Letters
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Efficient acylation and transesterification catalyzed by dilithium
tetra-tert-butylzincate at low temperatures
⇑
Miyuki Oshimura , Yuki Oda, Keita Kondoh, Tomohiro Hirano, Koichi Ute
Department of Chemical Science and Technology, Institute of Technology and Science, Tokushima University, 2-1 Minami-josanjima, Tokushima 770-8506, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The acylation and transesterification of alcohols with vinyl acetate and carboxylic esters were investi-
gated in the presence of a catalytic amount (1–10 mol %) of dilithium tetra-tert-butylzincate (TBZL) as
a catalyst. The acylation proceeded quantitatively at 0 °C within 1 h. The transesterification occurred
for a wide range of combinations of esters and alcohols at 0 to À40 °C. To the best of our knowledge, this
is the first successful transesterification at such low temperatures. The time–conversion plots for the
transesterification show that the reaction reached equilibrium within 5 min at 0 °C. The reaction pro-
ceeded quantitatively by addition of molecular sieves 4A. In addition, the transesterification proceeded
even in the presence of H2O and amines.
Received 28 January 2016
Revised 25 March 2016
Accepted 29 March 2016
Available online xxxx
Keywords:
Acylation
Transesterification
Zinc catalyst
Chemoselectivity
Ó 2016 Elsevier Ltd. All rights reserved.
Introduction
Recently, we reported that TBZL catalyzed ring-opening poly-
merization of e-caprolactone.11g In a subsequent study of the
Transesterification is a useful method for preparing various
esters.1 Acids2 and bases3 are commonly used as catalysts to pro-
mote these reactions. However, severe conditions are generally
required, that is, a high reaction temperature, long reaction time,
and large amount of catalyst. Consequently, thermally sensitive
functional groups undergo undesirable side reactions during the
transesterification.
copolymerization of e-caprolactone with 2-hydroxylethyl
methacrylate (HEMA), TBZL was found to act not only as an
anionic initiator but also as a transesterification catalyst.12 This
finding led us to investigate the acylation and transesterification
of alcohols with vinyl acetate and carboxylic esters in the presence
of a catalytic amount (1–10 mol %) of TBZL (Scheme 1).
Effective catalysts for promoting transesterification at room
temperature have been developed;4–9 for example, nitrogen–
heterocyclic carbenes catalyze transesterification of carboxylic
esters and acylation with vinyl acetate.4 The reactions are complete
within a few hours, using catalytic amounts (0.5–5.0 mol %) of the
carbenes. Et2Zn (10 mol %) catalyzes transesterification (acylation)
of benzyl alcohol (BnOH) with vinyl acetate at room temperature
in the presence of N-phenyldiethanolamine (N-PDEA, 5 mol %).7
Results and discussion
Homopolymerization of HEMA with TBZL in MeOH gave a
copolymer composed of two monomeric units, HEMA and methyl
methacrylate (Fig. S1). This result indicates that polymerization
accompanies transesterification of HEMA with MeOH at 30 °C
(Scheme 2). It is interesting to note that the reaction proceeded
at a moderate temperature.
The acylation of BnOH with vinyl acetate was examined to inves-
tigate the transesterification catalytic ability of TBZL13 (Table 1).14
Irreversible transesterification proceeded quantitatively with
A
l-oxo-tetranuclear zinc cluster catalyzes acylation of
alcohols under reflux conditions even in the presence of amine
compounds, which could impede the reaction.10
Uchiyama and coworkers11 reported that dilithium tetra-tert-
butylzincate (TBZL) catalyzed allylations of haloaromatics via
halogen–zinc exchange reactions. No protection is required for
haloaromatics containing a broad range of functional groups,
because of the unusually low basicity of TBZL.11b,c The high
chemoselectivity of TBZL enables direct polymerization of
N-isopropylacrylamide in aqueous media.11a,b
2-
tBu
2Li+
Zn
tBu
tBu
tBu
O
O
1 –10 mol% TBZL
0 to –40 °C
R3OH
R2OH
R2
R3
+
+
R1
O
R1
O
Scheme 1. Acylation and transesterification of alcohols with vinyl acetate and
carboxylic esters in the presence of TBZL.
⇑
Corresponding author.
http://dx.doi.org/10.1016/j.tetlet.2016.03.096
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Oshimura, M.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.03.096

2
M. Oshimura et al. / Tetrahedron Letters xxx (2016) xxx–xxx
polymerization
in MeOH
H
tBu
n
O
O
O
O
×
H
tBu
n
copolymerization
transesterification
with MeOH
OH
OH
O
O
O
O
OH
O
O
Scheme 2. Anionic polymerization of HEMA with TBZL in MeOH at 30 °C for 1 h, giving copolymer of HEMA and methyl methacrylate.
Table 1
Table 2
Acylation of alcohols with vinyl acetate in Presence of TBZL or Et2Zn with N-
Acylation of alcohols with vinyl acetate catalyzed by TBZL in Toluenea
phenyldiethanolamine (PDEA) as a catalysta
O
TBZL
O
O
+
R OH
+
O
R
in toluene
0 oC, 1h
O
Catalyst
Solvent
O
O
O
H
HO
+
+
O
O
H
b
Run
1
ROH
Product (isolated yield)
Run
Catalyst (mol %)
Solvent
Temp.
(°C)
Time
(h)
Conv.
(%)b
O
O
HO
1
2
3
4
5
6
7
8
TBZL (10)
TBZL (10)
TBZL (10)
TBZL (10)
TBZL (10)
TBZL (10)
TBZL (1)
TBZL (1)
Toluene
THF
Toluene
THF
n-Hexane
Bulk
Toluene
Toluene
Toluene
Toluene
THF
Toluene
THF
Bulk
25
25
0
0
0
0
0
0
0
25
25
0
0
0
1
1
1
1
1
1
0.5
1
1.5
1
>99
>99
>99
>99
>99
>99
58
BnOH
>99 %
O
HO
HO
1-hexanol
O
2
3
>99 %
87
O
O
9
TBZL (1)
>99
>99
35
67
6
10
11
12
13
14c
Et2Zn (10) + N-PDEA (5)
Et2Zn (10) + N-PDEA (5)
Et2Zn (10) + N-PDEA (5)
Et2Zn (10) + N-PDEA (5)
TBZL (2)
O
O
2-ethoxyethanol
1
1
1
1
>99 %
OH
O
HO
>99
O
a
4c
O
1,4-butanediol
Vinyl acetate (5.0 mmol), benzyl alcohol (1.0 mmol), solvent (2.0 mL).
Conversion was determined by intensities of Ph–CH2–O– proton signals of
O
b
>99 %
benzyl alcohol and that of benzyl acetate.
Cl
Cl
O
c
iPrOH was used as an alcohol instead of benzyl alcohol.
HO
Cl
Cl
Cl
O
5
Cl
2,2,2-trichloroethanol
10 mol % TBZL in toluene or THF at 25 °C within 1 h (Runs 1 and 2).
Decreasing the reaction temperature to 0 °C or changing the solvent
scarcely affected the reaction (Runs 3–6). These results are compara-
ble to those for reactions catalyzed by Et2Zn combined with a
N-PDEA (Runs 10–13).7a,7b A decrease in the amount of TBZL to
1 mol % gave quantitative conversion within 1.5 h (Runs 7–9).
>99 %
O
HO
O
6
7
geraniol
>99 % (>99 %)
O
O
HO
NH2
i
+
Acylation of secondary alcohols such as PrOH with vinyl acetate
N
H
OH
3-amino-1-propanol
HN
also proceeded smoothly in bulk at 0 °C and were complete within
1 h (Run 14 and Fig. S2). These results show that TBZL is a better
catalyst than those reported so far.
mixture (~ 1 : 1)
a
Vinyl acetate (5.0 mmol), alcohol (1.0 mmol), TBZL (0.1 mmol), Toluene
Irreversible transesterification proceeded quantitatively for the
acylation of a wide range of alcohols, except for 3-amino-1-propa-
nol, with vinyl acetate catalyzed by TBZL (Table 2). The acylation of
3-amino-1-propanol was failed because immediate amidation and
subsequent cyclization occurred before addition of TBZL due to
high reactivity of vinyl acetate with amino group (Run 7).
The transesterification occurred for a wide range of combina-
(2.0 mL); 0 °C, 1 h.
b
Conversion was determined by NMR.
Vinyl acetate (10.0 mmol).
c
knowledge, this is the first successful transesterification at such
low temperatures.
t
t
tions of esters and alcohols, except for BuOH, PhOH, and BuOAc
(Table 3).15 Half the amount of EtOAc was converted to MeOAc
in the transesterification of an equimolar mixture of EtOAc and
MeOH (Run 1). The time–conversion plots for the transesterifica-
tion show that the reaction reached equilibrium within 5 min at
0 °C or within 60 min at À20 °C (Fig. 1).16 The transesterification
proceeded at a practical rate even at À40 °C. To the best of our
Removal of the product alcohol should shift the equilibrium
toward complete transesterification; Molecular sieves 4A was
therefore added to the mixtures of MeOAc and BnOH at 0 °C to
adsorb the MeOH produced via transesterification.17 The reaction
proceeded quantitatively, regardless of the feed ratio of MeOAc
to BnOH (Fig. 2). Similar results were observed using MeOBz
instead of MeOAc.
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M. Oshimura et al. / Tetrahedron Letters xxx (2016) xxx–xxx
3
Table 3
Transesterification of equimolar mixtures of ester and alcohol catalyzed by TBZL
100
a
2 mol% TBZL
O
O
MeOAc / BnOH
R3OH
R2OH
R2
R3
+
+
80
60
40
20
0
oC, 1 h
R1
O
R1
O
0
Product b
Run
1
Ester
Alcohol
MeOBz / BnOH
O
O
+
EtOH
EtOH
EtOH
HO
O
O
EtOAc
MeOH
50 %
O
O
O
HO
TBZL
+
+
HO
R
O
HO
O
R
O
2
EtOAc
+
+
R=Me;
MeOAc
BnOH
R=Ph; BzOAc
41 %
O
0
10
20
30
Time (h)
40
50
3
4
5
6
7
EtOAc
O
HO
38 %
O
O
Figure 2. Time–conversion curves for transesterification of equimolar mixtures of
MeOAc or MeOBz, and BnOH catalyzed by 2 mol % TBZL in presence of molecular
sieves 4A.
EtOH
+
+
+
+
O
O
HO
26 %
O
O
HO
O
O
MeOH
MeOH
MeOH
2 mol% TBZL
oC, 1 h
O
O
+
+
HO
HO
0
MeOAc
61 %
O
O
in the presence of
(a) H2O,
(b) n-propylamine
(c) triethyl amine
O
47 %
MeOAc
51 % with amidation (6 %)
53 %
HO
55 %
O
Scheme 3. Transesterification of equimolar mixtures of EtOAc and MeOH with
2 mol % TBZL at 0 °C for 1 h in the presence of H2O or amines.
O
MeOAc
HO
51 %
O
a Ester (5.0 mmol), alcohol (5.0 mmol), TBZL (0.1 mmol); 0 °C, 1 h.
The mechanism of the TBZL-catalyzed transesterification is
unclear at this stage. A mechanistic study is therefore in progress.
In addition, a study of polymer synthesis using this chemoselective
transesterification is now under way.
b Conversion was determined by NMR.
Acknowledgments
60
0 oC
The authors are indebted to Dr. Eiichi Kaji and Tosoh Finechem
Corporation for kindly providing them with the THF solution of
TBZL. The authors are also grateful to Professor Yasushi Imada of
Tokushima University for valuable advice and discussions. This
work was supported in part by the Kyoto Technoscience Center.
-20 oC
40
-40 oC
Supplementary data
20
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.03.
096.
O
O
TBZL
+
+
HO
HO
O
O
0
References and notes
0
50
100
150
200
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Time (min)
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The transesterification proceeded even in the presence of H2O
and amines, although slight (about 6%) amidation accompanied
transesterification on addition of n-propylamine due to lower reac-
tivity of ethyl acetate compared with vinyl acetate (Scheme 3 and
Fig. S3, cf. Run 7 in Table 2).18 The conversions were comparable to
that in the absence of additives (cf. Run 1 in Table 3). These
results indicate that TBZL catalyzes the transesterification
chemoselectively.
Please cite this article in press as: Oshimura, M.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.03.096

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14. A typical procedure was as follows. Vinyl acetate (5.0 mmol), benzyl alcohol
(1.0 mmol), and solvent (2.0 mL) were added to a glass ampoule which had
been degassed and filled with nitrogen. A solution of TBZL (0.1 mmol) in THF
was added under a nitrogen atmosphere to the ampoule placed in a constant-
temperature bath. Then the mixture was kept at 25 or 0 °C and stirred. After a
prescribed period, the mixture was diluted with CDCl3 and transformed in a
NMR tube. Conversion of the reaction was determined by 1H NMR at 400 MHz.
15. A typical procedure was as described in Ref. 14. Carboxylic ester (5.0 mmol),
alcohol (5.0 mmol), and a solution of TBZL (0.1 mmol) in THF were used.
Solvent was not added.
16. The initial feeds of EtOAc, MeOH, and TBZL were 50, 50, and 1 mmol,
respectively. After initiation for 5 min, an aliquot was removed from the
reaction mixture using a syringe by flushing with N2 gas; the aliquot was
mixed with CDCl3 for NMR spectroscopy. Similar procedures were performed
after 10, 20, 30, 60, 120, and 240 min. The conversion was determined from the
integral intensities of the NMR signals of the CH3–CO–O– methyl protons of
EtOAc and MeOAc.
17. A typical procedure was as describe in Ref. 14. Molecular sieves 4A (2.5 g)
flame-dried in an ampoule were used to adsorb MeOH formed as by-products.
Carboxylic ester (5.0 mmol), alcohol (5.0 mmol), and
a solution of TBZL
(0.1 mmol) in THF were used. THF (2.3 mL) was used as a solvent.
18. A typical procedure was as described in Ref. 14. EtOAc (5.0 mmol), MeOH
(5.0 mmol), a solution of TBZL (0.1 mmol) in THF, and H2O (5.0 mmol) or
amines (5.0 mmol) were used. Solvent was not added.
12. Oshimura, M.; Hirano, T.; Ute, K. In Presented at the 9th SPSJ International
Polymer Conference, Kobe, Japan, December 11–14, 2012.
13. Titration and inductively coupled plasma optical emission spectroscopy
showed that the THF solution of TBZL (base: 0.626 mol LÀ1) contained 3.6 wt
% zinc and 1.4 wt% lithium.
Please cite this article in press as: Oshimura, M.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.03.096