Boron trifluoride facilitated transesterification of dioxaborolanes

Article abstract of DOI:10.1016/j.tetlet.2017.08.052

The direct transesterification of dioxaborolanes (alkane-1,2-diol based boronate esters) was explored. Using BF₃·OEt₂, alkane-1,2-diol based mono- and bis-boronate esters (i.e., pinacol and ethylene glycol) have been converted quantitatively to either benzene-1,2-diol or alkane-1,3-diol based boronate esters. In the case of pinacol esters, esterification is facilitated by the accompanying pinacol rearrangement, thus shifting the reaction equilibrium.

Full text of DOI:10.1016/j.tetlet.2017.08.052

Accepted Manuscript
Boron Trifluoride Facilitated Transesterification of Dioxaborolanes
Chathuri J. Kombala, Dulamini I. Ekanayake, Dustin E. Gross
PII:
S0040-4039(17)31059-6
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.08.052
TETL 49242
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
26 July 2017
19 August 2017
21 August 2017
Please cite this article as: Kombala, C.J., Ekanayake, D.I., Gross, D.E., Boron Trifluoride Facilitated
Transesterification of Dioxaborolanes, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.
2017.08.052
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Boron Trifluoride Facilitated Transesterification of Dioxaborolanes
Chathuri J. Kombala, Dulamini I. Ekanayake, and Dustin E. Gross*
Department of Chemistry, Sam Houston State University, Huntsville, TX 77341
*E-mail: degross@shsu.edu
Abstract
The direct transesterification of dioxaborolanes (alkane-1,2-diol based boronate
esters) was explored. Using BF3⋅OEt2, alkane-1,2-diol based mono- and bis-boronate
esters (i.e., pinacol and ethylene glycol) have been converted quantitatively to either
benzene-1,2-diol or alkane-1,3-diol based boronate esters. In the case of pinacol esters,
esterification is facilitated by the accompanying pinacol rearrangement, thus shifting the
reaction equilibrium.
Graphical Abstract
O
O
B
HO
OH
O
+
t
E
O
O
O
·
B
F
B
+
HO
OH
Keywords: boronic acids • dioxaborolanes • boronate esterification • boron trifluoride •
pinacol rearrangement
Introduction
Boronic acids have the ability to react with diols to give cyclic boronate esters.1
This reversible transformation is driven by the removal of water from the medium. The
dynamic covalent nature of this reaction has led to its application in a number of
areas.2–4 It has also enabled the synthesis of large and complex compounds such as
boronate ester based linear oligomers/polymers,5–7 macrocycles,8–14 and covalent
organic frameworks.15–17 Much of this work has involved the use of commercially
available bis-boronic acids as one of the monomer components. For the design and
1

synthesis of new boronic acid based monomers, pinacol boronate esters, have been the
ideal choice due to their stability and ease of isolation.1 Subsequent
deprotection/hydrolysis, such as NaIO4 oxidation,18,19 diethanolamine exchange,20
transesterification with polystyrene supported boronic acid,21 and via intermediate
potassium trifluoroborates22–24 has allowed the isolation of the free boronic acid
species. Despite these advances, purification of free boronic acids remains
challenging1 and the seemingly superfluous hydrolysis step may be eliminated if
appropriate conditions for direct transesterification are available. Therefore, we have
initiated experiments to investigate the viability of a direct transesterification method.
Results and Discussion
The transesterification of pinacol ester 1 was studied with catechol (2, a model
for an aromatic 1,2-diol), ethylene glycol (3, as a model of a less sterically encumbering
aliphatic 1,2-diol), neopentyl glycol (4, as a model of an aliphatic 1,3-diol) (Scheme 1).
Equimolar amounts of ester 1 and diols 2-4 were mixed in CDCl3 and the samples were
monitored over time by 1H NMR spectroscopy. Among the model diols studied,
neopentyl glycol (4) showed the highest transesterification (32%) whereas catechol (2)
exhibited the lowest transesterification (5%) (Table 1 and Fig. 1, hollow markers). In
addition to the low conversion, the transesterification is a slow process that takes >100
h to reach equilibrium.
2

Scheme 1. Transesterification of pinacolyl boronate ester 1.
Table 1. Transesterification of 1 with diols 2-4 in the absence and presence of
BF3·OEt2.
Entry Diol BF3·OEt2 Conversion Time
(equiv)[a]
(h)
>100
N/A
>10
>40
>40
>40
<24
>100
<17
>100
<6
2
1
0
<5%
<5%
23%
67%
83%
94%
100%
10%
24%
32%
100%
2
3
4
5
6
7
1[b]
2[b]
5[b]
1
2
5
0
5
0
5
3
4
8
9
10
11
[a] BF3·OEt2 equiv was determined by
integration of the appropriate 1H NMR
signals [b] BF3·OEt2 was freshly distilled
from CaH2
3

100%
80%
60%
40%
20%
0%
100%
80%
60%
40%
20%
0%
2 with BF3
3 with BF3
4 with BF3
2
3
4
2 with BF3
3 with BF3
4 with BF3
2
3
4
0
50
100
150
200
250
0
5
10
15
20
Time (h)
Time (h)
Fig. 1. Reaction progress of 1 and diols 2-4 with BF3·OEt2 (solid markers) and without
BF3·OEt2 (hollow markers) in CDCl3. Left: 0-250 min. Right: 0-20 min.
To increase the rate of the transesterification, alternative conditions were sought.
Increasing the temperature to 50 °C had little effect; therefore, the use of a Lewis acid
catalyst, specifically BF3·OEt2, was investigated. This catalyst has been shown to be
effective in COF synthesis with acetonide protected diols.25 Pinacolyl ester 1 was
mixed with neopentyl glycol (4, 1 equiv) in CDCl3 and BF3·OEt2 (5 equiv) was added
(Scheme 2). Soon after mixing, transesterification began and was essentially complete
within 6 h. In the presence of BF3·OEt2 there was not only an increase in rate, but
surprisingly 100% conversion to ester 7 was observed.
Scheme 2. Transesterification of 1 with diols 2-4 in the presence of BF3·OEt2.
Interestingly, the signals corresponding to free pinacol were not observed in the
1H-NMR spectrum, however two new signals were observed at δ = 2.3 and 1.2 ppm
(Fig. S2). In this reaction, the participation of BF3·OEt2 is not limited to catalyzing the
esterification; it also facilitates the pinacol rearrangement to pinacolone 9 (Scheme 3).
This concurrent consumption of pinacol shifts the transesterification equilibrium to the
right, which results in the quantitative formation of neopentyl glycol ester 7. In a
4

separate experiment under identical conditions, pinacol was mixed with BF3·OEt2 and
complete conversion to pinacolone was observed (Fig. S3).
Scheme 3. BF3·OEt2 facilitated rearrangement of pinacol 8.
In the absence of neopentyl glycol (Scheme 4), there was no appreciable
change, which means that the process relies in part on the transesterification step. This
unforeseen, yet justifiable, result prompted a more detailed look into the BF3·OEt2
promoted transesterification.
Scheme 4. BF3·OEt2 reaction with pinacol ester 1.
The BF3·OEt2 promoted transesterification of 1 was then carried out separately
with catechol (2) and then with ethylene glycol (3, discussed below). In both cases, the
rate and the percent conversion increased in the presence of BF3·OEt2 (Fig. 1). The
transesterification with catechol (2) reached 100% conversion within 30 hours (Fig. 2).
This was in stark contrast to the 5% conversion in the absence of BF3·OEt2. It should
also be noted that the presence of phenylboronic acid or triphenylboroxine could not be
detected (protons equivalent to Ha typically appear at 7.7 or 8.2 ppm, respectively),
which means that if these are intermediates they are short-lived under these conditions.
5

Fig. 2. Partial 1H NMR spectra for the reaction of ester 1 with catechol (2) in the
presence of BF3·OEt2 in CDCl3.
To determine the optimal amount of BF3·OEt2 needed for the transesterification,
BF3·OEt2 was freshly distilled from CaH2; however, this had an adverse effect on the
reaction (Table 1 entries 2-4). Therefore, straight from the bottle (“wet” BF3·OEt2) was
used.26 As seen in the original experiment (Fig. 1), the use of 5 equiv of BF3·OEt2
reached 100% transesterification in less than 24 h (Fig. 3). When using 2 and 1 equiv of
BF3·OEt2 the reactions took greater than 40 h to reach equilibrium with 94% and 83%
conversion, respectively. While these latter reactions did not achieve 100% conversion,
there was still a great improvement when compared to using freshly distilled BF3·OEt2.
6

100%
80%
60%
40%
20%
0%
1:1
1:2
1:5
0
10
20
30
40
50
Time (h)
Fig. 3. The effect of BF3·OEt2 (1, 2, and 5 equiv) on the 1:1 reaction of ester 1 and
catechol 2 in CDCl3.
With optimized conditions (5 equiv BF3·OEt2, 24 h, rt) various mono- and bis-
dioxaborolanes (10-16) were investigated (Scheme 5). All pinacolyl boronate esters
showed little esterification (<5%) in the absence of BF3·OEt2. Upon the addition
BF3·OEt2, transesterification began and quantitative formation of the catechol esters
(17-23) was observed. During the formation of esters 21 and 22 crystals appeared in
the NMR tube, which were isolated and analyzed separately. 1H NMR analysis of the
redissolved crystals in fresh CDCl3 confirmed their identity.
We then investigated the preparative scale reaction of 1 and 2 in chloroform with
BF3⋅OEt2. Only 2.5 equivalents of BF3⋅OEt2 were needed, and the complete formation of
catechol ester 5 and pinacolone 9 was observed after 24 h (Scheme 6). After removing
the volatiles (BF3⋅OEt2, CHCl3, and pinacolone) at 40 °C under high vacuum for 1 h,
only catechol ester 5 was observed upon NMR analysis. Toluene was also found to be
a suitable solvent for this transformation and similar results were obtained.
7

Scheme 5. Conversion of pinacol boronate esters (10-16) to catechol boronate esters
(17-23).
Scheme 6. Reaction of pinacol ester 1 with catechol (2) in the presence of BF3⋅OEt2.
followed by subsequent removal of the volatile components.
When the esterification of 1 was attempted with ethylene glycol (3, Scheme 2
and Fig. 1, triangles) in the presence of BF3·OEt2 only 24% percent conversion to
ethylene glycol ester 6 was achieved. While this was an increase from the 10%
observed in the uncatalyzed reaction, it was not clear why the conversion was not
reaching higher values as it did in the case of 5 and 7. Attempts to increase the
conversion, using drying agents (MgSO4 and molecular sieves) or increasing the
amount of BF3·OEt2, resulted in little change in reaction outcome. Due to the incomplete
conversion of pinacol ester 1 to ester 6 (Scheme 2 and Table 1 entry 9), we examined
8

the transesterification of 6 with diols 2, 4, and 8 without BF3·OEt2 (Scheme 7a). Similar
to the work of Roy and Brown27 catechol (2) displayed low percent transesterification
(26%, Fig. 4). Transesterification with neopentyl glycol (4) exhibited an equilibrium
mixture preferring the neopentyl glycol ester (7, 73%) within 1.5 h. Conversely, pinacol
(8) showed slow transesterification, taking >100 h, but eventually reaching >95%
conversion to pinacol ester 1. Steric hindrance of diol 8 may cause the slow
displacement of ethylene glycol from ester 6; this behavior was similar to what is
observed for the formation of pinacol ester 1 from the reaction of phenylboronic acid
and pinacol.
Scheme 7. Transesterification of ester 6 with diols 2, 4, and 8. a) without BF3·OEt2 and
b) with BF3·OEt2.
100%
80%
60%
catechol (2)
40%
neopentyl glycol (4)
pinacol (8)
20%
0%
0
20
40
60
80
100
120
Time (h)
Fig. 4. Reaction progress of ethylene glycol ester 6 with diols 2, 4, and 8 in CDCl3.
It is likely that the BF3·OEt2 is complexing with the ethylene glycol, thus hindering
the esterification of 1 to 6. Evidence of this complexation has been observed (Fig. S5).
Accordingly, we thought that this behavior might be advantageous for the
transesterification of 6. To test this idea, the reactions described above in Scheme 7a
(where catechol (2) and neopentyl glycol (4) had 26% and 73% conversion,
respectively) were repeated in the presence of BF3·OEt2 (Scheme 7b). This resulted in
rapid conversion of the ethylene glycol ester 6 to esters 5 and 7. The analysis of the
9

reaction of 6 with pinacol (8) was complicated due to the concurrent pinacol
rearrangement reaction. However, the reaction of 6 and neopentyl glycol (4) with
BF3·OEt2 (1.8 equiv) was rapid and quantitative (Fig. S6). The reaction of 6 with
catechol 2 requires a near ten-fold excess of BF3⋅OEt2; fewer equivalents resulted in
lower conversion (Figs. S7 and S8). In a separate experiment, the BF3⋅OEt2 addition
was delayed until after ester 6 and catechol (2) were allowed to reach equilibrium (27%
transesterification). Then, BF3⋅OEt2 (10 equiv) was added, which facilitated near
complete (~95%) conversion within 10 min.
Conclusions
In summary, by using BF3⋅OEt2 we have been able to achieve effective
transesterification of dioxaborolanes. Specifically, we found that in the presence of
BF3⋅OEt2, pinacolyl boronate esters (i.e., 1) were transesterified quantitatively to
aromatic 1,2-diol (i.e., catechol) and aliphatic 1,3-diol (i.e., neopentyl glycol) based
boronate esters at room temperature. This process involves the concomitant pinacol
rearrangement that helps to shift the reaction equilibrium toward the desired product
esters. In the absence of BF3⋅OEt2 the conversion was slow and only 5-32% conversion
could be obtained due to the greater stability of the pinacol esters. This methodology
also works with bis-esters (i.e., 21-23). The transesterification of ethylene glycol ester 6
was also improved in the presence of BF3⋅OEt2, which is likely due to the complexation
between ethylene glycol and BF3. In this case, conversions were increased from 26%
and 73% to 95% and 100% for the catechol and neopentyl glycol esters, respectively.
Ultimately, the described BF3⋅OEt2 facilitated transesterification of dioxaborolanes may
be a viable entry point for boronic based monomers in the construction of oligoboronate
materials. We are currently investigating this possibility.
Acknowledgements
This work was supported in part by the Welch Foundation [grant x-0011], and start-up
funding from Sam Houston State University. Acknowledgment is made to the Donors of
the American Chemical Society Petroleum Research Fund for support (or partial
support) of this research.
A. Supplementary data
Supplementary data associated with this article can be found in the online version.
10

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Catechol boronate esters can be synthesized from pinacolyl boronate esters.
The transesterification is facilitated by boron trifluoride.
The process is assisted by the concomitant pinacol rearrangement.
12