Stability of boronic esters - Structural effects on the relative rates of transesterification of 2-(phenyl)-1,3,2-dioxaborolane

Article abstract of DOI:10.1016/j.jorganchem.2006.10.013

Relative rates of reaction of the achiral cyclic phenylboronic ester 2-(phenyl)-1,3,2-dioxaborolane with a wide variety of structurally modified diols, have been studied to understand the factors influencing the relative stabilities of boronic esters. It is found that the alkyl substituents on the α-carbons of diols slow down the transesterification, but produce thermodynamically more stable boronic ester. Six-membered boronic esters are thermodynamically more stable than their corresponding five-membered analogs. Amongst cyclic 1,2-diols, cis-1,2-cyclopentanediol displaces ethylene glycol instantaneously whereas trans-1,2-cyclopentanediol is totally unreactive, which suggests that the cis-stereochemistry of the 1,2-diol is a prerequisite for transesterification. Among the 1,5-diols, diethanolamine displaces ethylene glycol quite rapidly forming a more stable bicyclic chelate in which nitrogen is attached to boron by a coordinating bond (as evident by ¹¹B NMR spectroscopy). The oxygen atom of di(ethylene glycol) and the sulfur atom of 2,2′-thiodiethanol do not assist in displacing the ethylene glycol from their boronic esters.

Full text of DOI:10.1016/j.jorganchem.2006.10.013

Journal of Organometallic Chemistry 692 (2007) 784–790
www.elsevier.com/locate/jorganchem
Stability of boronic esters – Structural effects on the relative rates of
q
transesterification of 2-(phenyl)-1,3,2-dioxaborolane
*
Chandra D. Roy , Herbert C. Brown
Department of Chemistry, H.C. Brown Center for Borane Research, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA
Received 9 July 2006; received in revised form 7 October 2006; accepted 7 October 2006
Available online 14 October 2006
This paper is dedicated to the memory of my mentor, the late Professor Herbert C. Brown (1912–2004).
Abstract
Relative rates of reaction of the achiral cyclic phenylboronic ester 2-(phenyl)-1,3,2-dioxaborolane with a wide variety of structurally
modified diols, have been studied to understand the factors influencing the relative stabilities of boronic esters. It is found that the alkyl
substituents on the a-carbons of diols slow down the transesterification, but produce thermodynamically more stable boronic ester. Six-
membered boronic esters are thermodynamically more stable than their corresponding five-membered analogs. Amongst cyclic 1,2-diols,
cis-1,2-cyclopentanediol displaces ethylene glycol instantaneously whereas trans-1,2-cyclopentanediol is totally unreactive, which sug-
gests that the cis-stereochemistry of the 1,2-diol is a prerequisite for transesterification. Among the 1,5-diols, diethanolamine displaces
ethylene glycol quite rapidly forming a more stable bicyclic chelate in which nitrogen is attached to boron by a coordinating bond (as
11
evident by B NMR spectroscopy). The oxygen atom of di(ethylene glycol) and the sulfur atom of 2,20-thiodiethanol do not assist in
displacing the ethylene glycol from their boronic esters.
Ó 2006 Elsevier B.V. All rights reserved.
Keywords: Boronic esters; Diols; Transesterification; Stability; Chiral auxiliaries
1. Introduction
omerically pure compounds of chemical and biological rel-
evances. The discovery of asymmetric hydroboration in
1961 using diisopinocampheylborane (Ipc2BH) marked
the beginning of an effective asymmetric synthesis [2,3].
Since then, tremendous interest has developed to make
the asymmetric synthesis methodically rich and efficient.
Matteson and co-workers [4] achieved a very high degree
of stereo- and enantio-selectivities (>99% ee) during the
successive one-carbon homologation of cyclic boronic
esters derived from pinanediol with preformed (dichlorom-
ethyl)lithium (Scheme 1). This elegant successive asymmet-
ric homologation not only predicts the chirality at each
chiral center, but also introduces additional chiral centers
without limit. But due to the unusual resistance of pinane-
diol boronic esters toward hydrolysis, transesterification or
ligand exchange, remarkable difficulties were experienced
in recovering the costly chiral auxiliary, pinanediol. In
1988, we developed convenient procedures for the recovery
Boronic acids and their esters are highly valuable com-
pounds which have found extensive applications in organic
and medicinal chemistry [1a,1b,1c,1d,1e,1f]. Some of their
uses include, protecting groups in carbohydrate chemistry,
[1g] general substrates in the Suzuki coupling [1h] and the
Petasis reactions, [1i] chiral derivatizing agents, [1j,1k]
redox-sensitive protecting group [1l] and glucose-selective
fluorescence sensor [1m]. Asymmetric synthesis has proven
to be a very effective method for the preparation of enanti-
q
The work described herein was performed at Purdue University (1997–
2001). Preliminary results were presented at the H.C. Brown Lectures in
Organic Chemistry, Purdue University, April 4,1998.
*
Corresponding author. Present address: EMD Biosciences, Inc., 10394
Pacific Center Court, San Diego, CA 92121, USA. Tel.: +1 858 450 5618;
fax: +1 858 453 3552.
E-mail address: chandra61804@yahoo.com (C.D. Roy).
0022-328X/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2006.10.013

C.D. Roy, H.C. Brown / Journal of Organometallic Chemistry 692 (2007) 784–790
785
Cl
R C
O
O
O
O
O
O
LiCHCl2
-100 oC
ZnCl2
-100 o
Cl2HC
R
Li
R
B
B
B
C
H
R'MgX or R'Li
-78 o
C
H H
H
R C
R'
O
O
O
R
C C
R' R"
B
B
O
Scheme 1. Matteson’s asymmetric homologation.
of pinanediol from pinanediol boronic esters [5]. Recently,
Hutton et al. [6] reported a mild alternate method for the
deprotection of pinacol boronic ester utilizing polysty-
rene-boronic acid (competing boronic acid instead of a
diol) via transesterification.
OH
OH
OsO4, Me3NO, Pyridine
tert-BuOH, H2O, 85 oC, 24 h
Scheme 3. Dihydroxylation of 1-methylcyclopentene with OsO4.
Boronic esters have proven to be of great importance in
asymmetric synthesis [7]. The easy introduction and recov-
ery of chiral auxiliaries is the key factor in a chiral auxiliary
directed multistep stereo- and enantio-selective synthesis.
Transesterification is the one of the simplest, convenient,
gentle procedures which can introduce and also recover
the chiral auxiliaries to or from boronic esters, provided
the former boronic ester is thermodynamically less stable
than the latter. This persuaded us to undertake a systematic
study of the relative rates of transesterification of five-
membered boronic ester, 2-(phenyl)-1,3,2-dioxaborolane
with various structurally modified diols to understand the
factors influencing the stabilities of boronic esters and the
results of such study are described in this publication.
sequently characterized by 1H and 13C NMR spectroscopy
(Scheme 3).
2.3. Types of diols examined
In order to compare the electronic and steric effects on
transesterification of boronic ester with various diols, we
examined a wide variety of acyclic and cyclic diols which
are categorized below (Chart 1). Transesterifications
(0.05 mmol scale) were carried out in CDCl3 solvent in
NMR tubes under inert atmosphere and the progress of
1
the reactions were monitored by H NMR spectroscopy.
2.4. Transesterification of 2-(phenyl)-1,3,2-dioxaborolane
with representative acyclic 1,2-diols: substituent effects
2. Results and discussion
2.1. Preparation of 2-(phenyl)-1,3,2-dioxaborolane
Transesterification of 2-(phenyl)-1,3,2-dioxaborolane
with 1,2-propanediol 1 gives an equilibrium mixture favor-
ing 1,2-propanediol phenylboronic ester (68.6%) in less
than 0.1 h, which suggests that monosubstituted ethylene
glycol boronic ester is thermodynamically more stable than
its unsubstituted analog (Scheme 4, Table 1). Introduction
of a second methyl substituent further increases the ther-
modynamic stability of the boronic ester, as evident from
the equilibrium composition obtained in the case of
meso-2,3-butanediol 2 (74.7%). Pinacol 3, being a sterically
hindered diol, displaces ethylene glycol very slowly, but
produces a thermodynamically more stable boronic ester
than those of 1,2-propanediol and meso-2,3-butanediol,
shifting the equilibrium towards the pinacolboronic ester
(87.8%). (+)-Diisopropyl tartrate (DIPT) 4 gave no appre-
ciable amounts of DIPT boronic ester (<5%) suggesting
that the DIPT boronic ester is thermodynamically the least
stable boronic ester in this series. To test this unfavorable
equilibrium with DIPT, DIPT phenylboronic ester was pre-
pared and subjected to transesterification with ethylene gly-
col under identical conditions. There was an instantaneous
quantitative displacement of DIPT from its boronic ester
2-(Phenyl)-1,3,2-dioxaborolane was prepared in excel-
lent yield by treating phenylboronic acid (5.0 mmol) with
ethylene glycol (5.0 mmol) in n-pentane (15 mL) for 4–6 h
at room temperature. The product was characterized by
spectroscopic means (Scheme 2) [8–10].
2.2. Preparation of 1-methyl-cis-1,2-cyclopentanediol
Following the procedure reported by Ray and Matteson
[11], substituted cis-1,2-cyclopentanediols, cis-acenaphthyl-
enediol and exo,exo-2,3-norbornanediol were prepared in
excellent chemical yields (>90%) by OsO4-catalysed cis-
dihydroxylation of the corresponding olefins and were sub-
OH
B
OH
HO
HO
O
O
n-Pentane
RT, 4-6 h
H2O
+
+
B
Scheme 2. Reaction of phenylboronic acid with ethylene glycol in n-
pentane.

786
C.D. Roy, H.C. Brown / Journal of Organometallic Chemistry 692 (2007) 784–790
OH
OH
OH
OH
OH
OH
PriO2C
PriO2C
OH
OH
2
3
1
4
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
O
OH
5
6
7
8
9
10
11
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
12
13
14
OH
15
16
OH
OH
OH
OH
OH
OH
18
OH
17
19
20
OH
OH
OH
OH
OH
OH
OH
OH
OH
H3C
N
But
N
N
O
S
H
N
OH
22
OH
26
OH
21
23
24
25
Chart 1. Diols of diverse structural types.
by ethylene glycol which confirms our conclusion. This
observation clearly indicates that the chiral auxiliary diiso-
propyl tartrate can be very easily retrieved and recycled
from its boronic ester with a very cheap diol like ethylene
glycol or pinacol. The reaction profiles are depicted in
Fig. 1.
over instantaneously (<5 min), forming the more stable
cis-1,2-cyclopentanediol phenylboronic ester in >99%
chemical yield, whereas trans-1,2-cyclopentanediol
7
showed no appreciable transesterification even after 47 h.
In order to compare the effect of ring strain on rates and
2.5. Transesterification of 2-(phenyl)-1,3,2-dioxaborolane
with cyclic 1,2-diols: ring strain and conformational effects
100
80
Next we became interested in examining cyclic 1,2-diols,
5–11 which might differ in reactivity due to both ring strain
and conformational factors. The experimental results are
presented in Table 2 and the reaction profiles in Fig. 2.
The poor reactivity of catechol 5 during transesterification
may be attributed to the lower nucleophilicity of the
hydroxyl oxygen due to the presence of the phenyl ring.
In the case of cis-1,2-cyclopentanediol 6, the exchange is
60
Pinacol
meso-2,3-Butanediol
O
O
HO
HO
HO
HO
O
O
CDCl3
RT
1,2-Propanediol
40
B
B
+
+
(+)-Diisopropyl Tartrate
Scheme 4. General scheme for transesterification of 2-(phenyl)-1,3,2-
dioxaborolane with various diols 1–4.
20
Table 1
Transesterification of 2-(phenyl)-1,3,2-dioxaborolane with representative
substituted 1,2-ethanediols 1–4 at ambient temperature
0
Entry
1,2-Diol
Time (h)
% Transesterification
0
20
40
60
80
100
1
2
3
4
1,2-Propanediol 1
meso-2,3-Butanediol 2
Pinacol 3
0.1
0.1
94
68.6
74.7
87.8
4.5
Time (h)
Fig. 1. Transesterification of ethylene glycol phenylboronic ester (0.05 M)
with various 1,2-diols 1–4 (0.05 M) in CDCl3 at 25 °C.
(+)-Diisopropyl Tartrate 4
0.1

C.D. Roy, H.C. Brown / Journal of Organometallic Chemistry 692 (2007) 784–790
787
Table 2
molecular transesterification. The ring strain on the diol
accelerates the reaction rate and also favors the equilibrium
towards thermodynamically more stable cyclic boronic
ester. This study also reveals that stereoisomeric diols, such
as cyclic cis- and trans-1,2-diols could be very easily resolved
using transesterification methodology.
Transesterification of 2-(phenyl)-1,3,2-dioxaborolane with cyclic 1,2-diols
5–11 at ambient temperature
Entry 1,2-Diol
Time
(h)
%
Transesterification
1
2
3
4
5
6
7
Catechol 5
5
0.1
47
0.1
44
0.75
0.1
28
99
0
47
0
cis-1,2-Cyclopentanediol 6
trans-1,2-Cyclopentanediol 7
cis-1,2-Cyclohexanediol 8
trans-1,2-Cyclohexanediol 9
1,4-Anhydroerythritol 10
exo,exo--2,3-Norbornanediol
11
2.6. Transesterification of 2-(phenyl)-1,3,2-dioxaborolane
with representative cis-1,2-cyclopentanediols: substituent
effects
97
99.5
Encouraged by the results obtained from cis-1,2-cyclop-
entanediols 12–16, we decided to examine the steric effects
on the rates and equilibria of boronic esters during transe-
sterification. It is quite clear from the experimental results
that an introduction of alkyl group on the diol certainly
slows down the reaction rate, but yields thermodynami-
cally more stable substituted cyclopentanediol boronic
esters (Table 3). cis-1,2-Dimethyl-1,2-cyclopentanediol 15
appears to be most hindered diol in the cyclopentanediol
series. In order to test the thermodynamic stability of cis-
1,2-dimethyl-1,2-cyclopentanediol boronic ester, it was
treated with (+)-a-pinanediol.
a-Pinanediol which normally displaces cyclopentanedi-
ols and other diols relatively rapidly from boronic esters,
could displace only 5–6% of cis-1,2-dimethyl-1,2-cyclopen-
tanediol after 15 days which proves that cis-1,2-dimethyl-
1,2-cyclopentanediol boronic ester is thermodynamically
most stable in the cyclopentanediol series. The relative
slowness of the reaction is directly related to the substituent
bulk on the diol. It is hoped that cis-1,2-acenaphthylene-
diol 16, being a rigid system, might show improved results,
but only comparable results were obtained. These results
are represented graphically in Fig. 3.
equilibria, we carried out the transesterification with both
cis- and trans-1,2-cyclohexanediols.
cis-1,2-Cyclohexanediol 8 produces an equilibrium mix-
ture favoring cis-1,2-cyclohexanediol phenylboronic ester
by only 47% which suggests that the starting ethylene glycol
phenylboronic ester is slightly more stable than the product.
Like trans-1,2-cyclopentanediol, trans-1,2-cyclohexanediol
9 was also found to be an inert. The replacement of a CH2
group with an oxygen heteroatom slightly decreases the
product ratio (1,4-anhydroerythritol 10 showed only 97%
transesterification). exo,exo-2,3-Norbornanediol 11, being
a 3,5-disubstituted 1,2-cyclopentanediol, displays similar
reactivity as observed in the case of cis-1,2-cyclopentanediol.
These results unambiguously suggest that both ring strain
and the stereochemistry of the reacting diol influence the
rates and equilibria during transesterification. The
cis-stereochemistry of the diol is a prerequisite for an intra-
100
2.7. Transesterification of 2-(phenyl)-1,3,2-dioxaborolane
with acyclic 1,3-diols: ring size and substituent effects
Catechol
cis-1,2-Cyclopentanediol
trans-1,2-Cyclopentanediol
cis-1,2-Cyclohexanediol
trans-1,2-Cyclohexanediol
1,4-Anhydroerythritol
80
The correlation between the relative stability of a cyclic
compound and the ring size is well studied and understood.
In order to compare the stabilities of five-membered
boronic esters with six-membered boronic esters, we
exo,exo-2,3-Norbornanediol
60
40
20
0
Table 3
Transesterification of 2-(phenyl)-1,3,2-dioxaborolane with representative
substituted cis-1,2-cyclopentanediols 12–16 at ambient temperature
Entry 1,2-Diol
Time
(h)
%
Transesterification
1
2
3
4
5
cis-1-Methyl-1,
2-cyclopentanediol 12
cis-1-Ethyl-1,
2-cyclopentanediol 13
cis-1-Isopropyl-1,2-
cyclopentanediol 14
cis-1,2-Dimethyl-1,2-
cyclopentanediol 15
cis-1,2-Acenaphthylenediol 16
0.75 99
1.5
99
1.75 99
0
10
20
30
40
50
60
70
80
Time (h)
258
2.5
99
97
Fig. 2. Transesterification of ethylene glycol phenylboronic ester (0.05 M)
with various 1,2-diols 5–11 (0.05 M) in CDCl3 at 25 °C.

788
C.D. Roy, H.C. Brown / Journal of Organometallic Chemistry 692 (2007) 784–790
100
100
80
60
40
20
0
80
60
2,4-Pentanediol
cis-1,2-Dimethyl-1,2-cyclopentanediol
cis-1,2-Acenaphthylenediol
2,4-Dimethyl-2,4-pentanediol
1,3-Propanediol
cis-1-Isopropyl-1,2-cyclopentanediol
cis-1-Ethyl-1,2-cyclopentanediol
cis-1-Methyl-1,2-cyclopentanediol
cis-1,2-Cyclopentanediol
40
20
0
2,2-Dimethyl-1,3-propanediol
0
50
100
150
Time (h)
0
50
100
150
200
250
300
Time (h)
Fig. 4. Transesterification of ethylene glycol phenylboronic ester (0.05 M)
with various 1,2-diols 17–20 (0.05 M) in CDCl3 at 25 °C.
Fig. 3. Transesterification of ethylene glycol phenylboronic ester (0.05 M)
with various 1,2-diols 12–16 (0.05 M) in CDCl3 at 25 °C.
at C-2 position has no significant effects on the equilibrium
composition as seen with neopentyl glycol 19. These results
are represented graphically in Fig. 4.
decided to examine the relative rates of 2-(phenyl)-1,3,
2-dioxaborolane with four representative 1,3-diols 17–20.
1,3-Propanediol 17 gives an equilibrium mixture which
has 88.5% six-membered boronic ester. This clearly sug-
gests that six-membered boronic ester is thermodynami-
cally more stable than five-membered boronic ester. In
order to examine the steric effects on rates and equilibria
during transesterification, three substituted 1,3-diols are
treated with 2-(phenyl)-1,3,2-dioxaborolane under identical
conditions. It is clear from Table 4 that an introduction of
two methyl groups at 1,3-position shifts the equilibrium
(from 88.5% to 98%) towards more stable 2,4-pentanediol
phenylboronic ester. Further substitution at C-2 and C-4
positions of 2,4-pentanediol, e.g., 2,4-dimethyl-2,4-pen-
tanediol 20 not only slows down the exchange process,
but also produces boronic ester of lower stability (as
reflected by the equilibrium composition) in comparison
with 2,4-pentanediol 18. The substitution of methyl groups
2.8. Transesterification of 2-(phenyl)-1,3,2-dioxaborolane
with representative 1,5-diols: Effects of chelation by
heteroatoms
It is well known that diethanolamine forms stable che-
lated complexes with boronic acids. Persuaded by this fact,
we studied the rates and equilibria of few amino-1,5-diols
21–26 with boronic ester (Scheme 5). Diethanolamine 21
undergoes transesterification quantitatively in <5 min as
1
seen by 11B and H NMR spectroscopy (Table 5). Jung
et al. [12] and Iovine et al. [13] have independently utilized
diethanolamine/HCl to deprotect pinacol from their boro-
nic esters to get free boronic acids. N-methyldiethanol-
amine 22 was observed to be slightly less effective (70%
displacement) than the diethanolamine. Surprisingly, N-
tert-butyldiethanolamine 23, which was hoped to show
more effective chelation due to increased basicity of the
nitrogen due to the presence of the highly electron releasing
Table 4
Transesterification of 2-(phenyl)-1,3,2-dioxaborolane with representative
1,3-diols 17–20 at ambient temperature
Entry
1,2-Diol
Time (h)
Transesterification (%)
1
2
3
1,3-Propanediol 17
2,4-Pentanediol 18
2,2-Dimethyl-1,
3-propanediol 19
2,4-Dimethyl-2,
4-pentanediol 20
0.1
0.1
0.1
88.5
98
85
HO
HO
O
O
O
HO
HO
CDCl3
RT
+
N H
B
B
N H
+
O
4
67
91
Scheme 5. Transesterification of 2-(phenyl)-1,3,2-dioxaborolane with 1,5-
diols 21–26.

C.D. Roy, H.C. Brown / Journal of Organometallic Chemistry 692 (2007) 784–790
789
Table 5
borolane, and facilitate the transesterification. Unfortu-
nately, neither coordination between oxygen and boron
or sulphur and boron atoms nor any chelated boronic ester
Transesterification of 2-(phenyl)-1,3,2-dioxaborolane with representative
1,5-diols 21–26 at ambient temperature
1
formation is observed (as seen by 11B and H NMR spec-
Entry 1,2-Diol
Time (h) Transesterification
(%)
troscopy). These results are depicted in Fig. 5.
1
2
3
Diethanolamine 21
0.1
0.5
99
70
0
N-methyldiethanolamine 22
N-tert-butyldiethanolamine
23
72
3. Conclusions
4
5
6
2,6-Pyridinedimethanol 24
Di(ethylene glycol) 25
2,20-Thiodiethanol 26
129
70
69
9
0
0
Relative rates and equilibrium compositions resulting
from the reactions of an achiral cyclic phenylboronic
ester, 2-(phenyl)-1,3,2-dioxaborolane, with a wide variety
of diols of varied structural types, have been examined
to understand the factors influencing the relative stabili-
ties of boronic esters. Experimental results have shown
that the alkyl substituents on a-carbons of diols slow
down the transesterification, but produce the thermody-
namically more stable boronic ester. Six-membered boro-
nic esters have been observed to be thermodynamically
more stable than their corresponding five-membered ana-
logs. Amongst cyclic 1,2-diols, cis-1,2-cyclopentanediol
displaced ethylene glycol instantaneously whereas trans-
1,2-cyclopentanediol was found to be totally inert. Inter-
estingly, cis-1,2-cyclohexanediol could displace ethylene
glycol only up to 48% (again, the trans-isomer was found
to be inactive), which indicates that the higher reactivity
of cis-1,2-cyclopentanediol may be due to ring strain. A
systematic study of the steric effects of alkyl substituents
on cis-1,2-cyclopentanediols during transesterification
revealed that the isopropyl group was the best substituent
among the alkyl groups studied in driving the equilibrium
towards right-hand side, yielding thermodynamically
more stable boronic ester. cis-1,2-Dimethyl-1,2-cyclopen-
tanediol has been found to be the most sterically hindered
diol in the cyclopentanediol series. Among the 1,5-diols,
diethanolamine displaces ethylene glycol quite rapidly
forming a more stable bicyclic chelate in which nitrogen
is linked to boron by a coordinating bond (as evidenced
by 11B NMR spectroscopy). N-Methyldiethanolamine
was comparatively a less effective (70%) chelating agent
than the diethanolamine (99%) in the case of ethylene gly-
col phenylboronic ester. Surprisingly, N-tert-butyldietha-
nolamine failed to displace ethylene glycol, suggesting
that such an equilibrium was unfavorable due to the pres-
ence of the tert-butyl group on nitrogen. The oxygen
atom of di(ethylene glycol) and the sulfur atom of 2,20-
thiodiethanol also did not facilitate the displacement of
ethylene glycol from its boronic ester. In conclusion, this
study not only provided useful insights about the factors
influencing the thermodynamic stability of various boro-
nic esters, but also led us to resolve structural and stereo-
isomeric diols in a very practical and efficient way which
will be reported in due course. Also, many expensive C2-
symmetric chiral diol auxiliaries, such as (+)-2,3-butane-
diol, (+)-2,4-propanediol and (ꢀ)-diisopropyl tartrate
(DIPT), can be retrieved from the boronic esters using
cheap diols.
tert-butyl group, did not furnish any appreciable amount
of chelated boronic ester. Earlier, N-methyldiethanolamine
and the sodium salt of bicine were tested in the recovery of
pinanediol from pinanediol boronic esters, but without any
success. 2,6-Pyridinedimethanol 24 shows only small
amount of chelated boronic ester (<10%).
The oxygen and the sulphur atoms of diethyl ether (EE),
tetrahydrofuran (THF) and dimethylsulfide (DMS) are
known to coordinate with boron atoms to form stable
adducts. The strength of these coordinated X–B bonds
depends upon the nature of the substituents present on
both species. Therefore, it was interesting to examine
how the oxygen atom of di(ethylene glycol) 25 and the sul-
phur atom of 2,20-thiodiethanol 26 coordinate with the
boron atom of the boronic ester, 2-(phenyl)-1,3,2-dioxa-
100
80
60
2,2'-Thiodiethanol
Di(ethylene glycol)
2,6-Pyridinedimethanol
N-(tert-Butyl)diethanolamine
N-Methyldiethanolamine
Diethanolamine
40
20
0
0
20
40
60
80
Time (h)
Fig. 5. Transesterification of ethylene glycol phenylboronic ester (0.05 M)
with various 3-heteroatom substituted 1,5-diols 21–26 (0.05 M) in CDCl3
at 25 °C.

790
C.D. Roy, H.C. Brown / Journal of Organometallic Chemistry 692 (2007) 784–790
(f) W. Wang, X. Gao, B. Wang, Med. Res. Rev. 23 (2003) 346, and
4. Experimental
4.1. General
references cited therein;
(g) T.D. James, S. Sandanayake, S. Shinkai, Angew. Chem., Int. Ed.
Engl. 35 (1996) 1911;
(h) R. Miyaura, A. Suzuki, Chem. Rev. 95 (1995) 2457;
(i) N.A. Petasis, Z.D. Patel, Tetrahedron Lett. 41 (2000) 9607;
(j) K. Burgess, A.M. Porte, Angew. Chem., Int. Ed. Engl. 33 (1994)
1182;
All of the diols were commercially available (Aldrich)
except exo,exo-2,3-norbornanediol 11, cis-1-methyl-1,2-
cyclopentanediol 12, cis-1-ethyl-1,2-cyclopentanediol 13,
cis-1-isopropyl-1,2-cyclopentanediol 14, cis-1,2-dimethyl-
1,2-cyclopentanediol 15 and cis-1,2-acenaphthylenediol
16, which were prepared by OsO4-catalysed cis-dihydroxy-
lation of their corresponding olefins. The starting material,
2-(phenyl)-1,3,2-dioxaborolane was prepared in excellent
yield by esterifying phenylboronic acid (5.0 mmol) with
ethylene glycol (5.0 mmol) in n-pentane (15 mL) for 4–6 h
at room temperature. Water formed during the reaction
can very easily be removed by adding molcular sieves or
drying agents (anhydrous Na2SO4 or MgSO4). The product
was characterized by spectroscopic means (11B and 1H
NMR, Varian-Gemini, 300 MHz). All transesterification
reactions were carried out in CDCl3 solutions (0.05 mmol)
of both boronic ester and the desired diol in 1.0 mL CDCl3
in NMR tubes under an inert atmosphere. The progress of
(k) S. Morandi, E. Caselli, A. Forni, M. Bucciarelli, G. Torre, F.
Prati, Tetrahedron: Asymmetr. 16 (2005) 2918;
(l) J. Yan, S. Jin, B. Wang, Tetrahedron Lett. 46 (2005) 8503;
(m) V.V. Karnati, X. Gao, S. Gao, W. Wang, S. Ni, S. Sankar, B.
Wang, Bioorg. Med. Chem. Lett. 12 (2002) 3373.
[2] J.D. Morrison (Ed.), Asymmetric Synthesis, vols. 1–5, Academic
Press, New York, 1983.
[3] H.C. Brown, G. Zweifel, J. Am. Chem. Soc. 83 (1961) 486.
[4] (a) D.S. Matteson, Stereodirected Synthesis with Organoboranes,
Springer, Berlin, 1995, Chapter. 5;
(b) D.S. Matteson, K.M. Sadhu, M.L. Peterson, J. Am. Chem. Soc.
108 (1986) 810;
(c) L. Carmes, F. Carreaux, B. Carboni, J. Org. Chem. 65 (2000)
5403;
(d) D.S. Matteson, H.W. Man, O.C. Ho, J. Am. Chem. Soc. 118
(1996) 4560;
(e) H.C. Brown, P.V. Ramachandran, Pure Appl. Chem. 66 (1994)
201;
(f) D.S. Matteson, Pure Appl. Chem. 63 (1991) 339;
(g) D.S. Matteson, Chem. Rev. 89 (1989) 1535;
(h) M.M. Midland, J. Org. Chem. 63 (1998) 914.
[5] H.C. Brown, M.V. Rangaishenvi, J. Organomet. Chem. 358 (1988)
15.
1
the reactions was followed by H NMR spectroscopy.
Acknowledgements
[6] T.E. Pennington, C. Kardiman, C.A. Hutton, Tetrahedron Lett. 45
(2004) 6657.
[7] D.S. Matteson, Acc. Chem. Res. 21 (1988) 294.
[8] H.C. Brown, N.G. Bhat, V. Somayaji, Organometallics 2 (1983)
1311.
Financial support from the Purdue Borane Research
Fund is gratefully acknowledged. We also thank Professor
Donald S. Matteson for his interest and encouragement.
[9] H.C. Brown, T.E. Cole, Organometallics 2 (1983) 1316.
[10] (a) H.C. Brown, S.M. Singh, Organometallics 5 (1986) 994;
(b) P.R. Blakemore, S.P. Marsden, H.D. Vater, Organic Lett. 8
(2006) 773;
(c) H.C. Brown, A.S. Phadke, Synlett (1993) 927.
[11] R. Ray, D.S. Matteson, Tetrahedron Lett. 21 (1980) 449.
[12] M.E. Jung, T.I. Lazarova, J. Org. Chem. 64 (1999) 2976.
[13] E.K. Perttu, M. Arnold, P.M. Iovine, Tetrahedron Lett. 46 (2005)
8753.
References
[1] (a) D.G. Hall (Ed.), Boronic Acids: Preparations and Applications in
Organic Synthesis and Medicine, Wiley–VCH, Weinheim, 2005;
(b) D.S. Matteson, Tetrahedron 45 (1989) 1859;
(c) D.S. Matteson, Chemtech 29 (1999) 6;
(d) D.S. Matteson, J. Organomet. Chem. 581 (1999) 51;
(e) S. Kotha, K. Lahiri, D. Kashinath, Tetrahedron 58 (2002) 9633;