Structure, theoretical studies, and coupling reactions of some new cyclic boronic esters

Article abstract of DOI:10.1002/hc.21102

The present report describes the X-ray structural and theoretical studies of some new pinacolboronate esters, and it also outlines the use of the target structures in Suzuki coupling reactions to produce new aromatic or heteroaromatic esters and amides. X

Full text of DOI:10.1002/hc.21102

Heteroatom Chemistry
Volume 24, Number 5, 2013
Structure, Theoretical Studies, and Coupling
Reactions of Some New Cyclic Boronic Esters
Andrew Kuttler,1 Sravanthi Durganala,2,3 Albert Fratini,1
Alexander B. Morgan,2 and Vladimir Benin1
1Department of Chemistry, University of Dayton, Dayton, Ohio 45469-2357
2Applied Combustion and Energy Group, University of Dayton Research Institute, Dayton, Ohio
45469-0170
3Chemtura/Great Lakes Solutions, West Lafayette, Indiana 47906
Received 21 December 2012; revised 7 May 2013
INTRODUCTION
ABSTRACT: The present report describes the X-ray
structural and theoretical studies of some new pina-
colboronate esters, and it also outlines the use of
the target structures in Suzuki coupling reactions to
produce new aromatic or heteroaromatic esters and
amides. X-ray structural analysis of the studied com-
pounds revealed that the pinacolborane ring’s position
with respect to the benzene ring varies, depending on
the particular environment. An ortho-positioned car-
boxylic ester (methyl ester) causes a nearly perpen-
dicular orientation of the pinacolborane unit with re-
spect to the benzene ring, whereas an ortho-positioned
amide (N,N-dimethylamide) causes the pinacolbo-
rane unit to orient itself nearly coplanar. A plausi-
ble explanation has been provided, based on both
While modern polymeric materials bring many ben-
efits by their use in society, they typically suffer
from flammability/fire risk issues, and so they need
to be flame retarded to provide fire protection in
a variety of fire-risk scenarios. When a polymeric
material requires a flame retardant to be used/sold
in a particular application, one can use a nonre-
active flame-retardant molecule/polymer, which is
blended into the polymer, or one can use a reac-
tive flame-retardant molecule, which bonds directly
to the polymer during polymerization or via side-
chain/grafting reactions [1, 2]. With concerns about
environmental persistence of some flame-retardant
additives that are not bound to the polymer and
may leach out over time [3–8], the use of reactive
flame retardants has become more attractive. Fur-
ther, there is a desire to develop condensed-phase
(char-forming) reactive flame retardants, so that
more of the polymer fuel can be converted into low-
flammability carbon char (graphite/glassy carbon)
rather than the polymer mass being pyrolyzed as
high heat release decomposition products [1, 9]. To
that end, we have proposed the synthesis of boron-
and phosphorus-functionalized reactive structures,
which could copolymerize with thermoset-type poly-
mers such as epoxy and polyurethane.
ꢀC
steric and electronic factors.
2013 Wiley Periodi-
cals, Inc. Heteroatom Chem. 24:361–371, 2013; View
this article online at wileyonlinelibrary.com. DOI
10.1002/hc.21102
Correspondence to: V. Benin; e-mail: vbenin1@udayton.edu.
Contract grant sponsor: National Institute of Standards and
Technology, Building and Fire Research Laboratory (NIST-
BFRL).
Contract grant number: Fire Research Grant # 70NANB9H9183.
Contract grant sponsor: Chemistry Department at the University
of Dayton.
Boron has shown some interesting condensed-
phase flame-retardant activity, when available as a
boronic acid/boroxine structure [10, 11]. We have
Supporting Information is available in the online issue at
wileyonlinelibrary.com.
ꢀC
2013 Wiley Periodicals, Inc.
361

362 Kuttler et al.
SCHEME 1
therefore focused on the preparation of specific tar-
gets containing one or two boronic acids or es-
ter groups, using transition metal catalyzed cou-
pling reactions [12]. The outcome of the studies
on the flame-retardant properties of those struc-
tures, both in a stand-alone fashion and incor-
porated into polyurethane samples, is described
elsewhere [12,13]. The current report is focused ex-
clusively on the structural and theoretical analysis of
the cyclic boronic ester structures, which were gen-
erated as precursors to the corresponding boronic
acids. By understanding the chemical structure of
these compounds, we may gain more insight into
what boron-based flame retardants can be practi-
cally made for future use. Cyclic boronic esters, con-
taining the pinacolborane unit, have been the subject
of X-ray crystallographic analysis [14–17], nuclear
magnetic resonance (NMR)-based structural inves-
tigation [18], and some limited theoretical studies
[19]. Careful analysis of our target structures and
the examples available from literature provoked us,
however, to conduct further investigation, in an at-
tempt to address the following issues:
RESULTS AND DISCUSSION
Synthesis of Boronic Esters
All of the target structures were prepared using io-
dinated aromatic compounds as precursors. Pre-
liminary studies using the corresponding bromi-
nated derivatives showed them to be unreactive
under the reaction conditions. No attempts were
made for direct introduction of the boronate es-
ter functionality via C H bond activation, as de-
scribed by Hartwig and co-workers [20]. The cyclic
boronic ester 3 was prepared in good yield from
dimethyl iodoterephthalate and pinacolborane, us-
ing (dppp)2NiCl2 as a catalyst (Scheme 1) [12, 21].
The reaction was carried out in the presence of tri-
ethylamine or dicyclohexylmethylamine, as a base,
leading to the product in similar yields. Boronate
ester 3 was subsequently used as a starting ma-
terial in a number of Suzuki coupling reactions,
leading to the generation of several new, multifunc-
tional aromatic or heteroaromatic strustures (vide
infra).
The cyclic boronic ester 7, based on a terephtha-
lamide core, was also prepared using Pd-catalyzed
coupling, of the iododiamide 6 (Scheme 2). The lat-
ter was prepared in two steps from the iodoester 1,
including alkaline hydrolysis to the diacid 5 [22], fol-
lowed by conversion, in a single step, to the diamide
6 [23].
The diboronic ester 10 was prepared using
dimethyl 2,5-diiodoterephthalate 9 as a precursor
(Scheme 3) [12, 24]. It involved diiodination of
p-xylene, followed by oxidation and Fischer es-
terification of the resultant dicarboxylic acid. The
diiodo ester 9 was converted to the target us-
ing pinacolborane, with (Ph3P)2PdCl2 as a catalyst.
The generation of 10 was associated with the for-
mation of noticeable amounts of hydrodeborona-
tion bi-products, namely compound 3 and dimethyl
terephthalate.
1. Potential influence of Lewis acid-base interac-
tions at the boron center on the overall geometry.
2. Role of the steric factor on the geometry of the
target boronic esters.
3. Comparison of the studied structures with pre-
viously published structural accounts of com-
pounds containing a pinacolborane or similar
boronic ester unit.
To answer these questions, we have (1) intro-
duced appropriate chemical modifications, in an
attempt to enhance potential Lewis acid—base in-
teractions, and (2) conducted detailed density func-
tional theory (DFT) calculations, to determine the
inherent steric preferences of the available sub-
stituents, and thus rationalize the observed struc-
tures.
Heteroatom Chemistry DOI 10.1002/hc

Structure, Theoretical Studies, and Coupling Reactions of Some New Cyclic Boronic Esters 363
SCHEME 2
ular to the benzene core, while the same substruc-
ture is nearly coplanar in 7. The boron atom in com-
pound 3 (or 10) is in the center of a trigonal planar
environment, with values slightly larger than 120◦
for the O(2)-B(1)-C(2) and O(1)-B(1)-C(2) angles,
while the O(2)-B(1)-O(1) angle has a value of about
113◦. Structure 10 has a center of symmetry, so the
structural parameters for it listed in Table 1 use
the crystallographic designation and numbering of
compound 3.
Suzuki Coupling Reactions of Boronic Ester 3
The cyclic boronic ester 3 was successfully used
to conduct a number of Suzuki coupling reactions
(Scheme 1). Those were carried out in typical con-
ditions, employing (Ph3P)4Pd as a catalyst, in a mix-
ture of toluene and aqueous K2CO3. It should be
noted that original attempts were done using small
amounts of ethanol as well, as recommended by a
number of literature references. However, we found
out that under such conditions, trans-esterification
occurred, leading to a mixture of products con-
taining methyl and/or ethyl ester functionalities.
Consequently, reactions were performed without
any alcohol. Several new aromatic and heteroaro-
matic targets were prepared, using both bromo- and
iodoarenes as starting materials.
One of the most interesting structural features
of compounds 3 and 10 is the apparent proximity
of the boron and carbonyl oxygen centers, rais-
ing the question about potential Lewis acid–base
interaction. In structure 3, the two centers are at
˚
a distance of 2.59 A, which is rather large to be
qualified as a B O dative bond. On the other hand,
the dihedral angle O(1)-O(2)-C(2)-B(1) has a value
of 6.1◦, that is, there is some degree of deviation
from the ideal trigonal planar geometry, and a
pyramidalization towards the carbonyl oxygen.
We did extensive literature research, to provide
an in-depth structural analysis and comparison of
our target compounds with previously published
X-ray data. Some of the literature structures are
shown in Fig. 2. Four of them, 11–14, contain a
pinacolborane unit connected to a benzene ring,
and the two substructures are nearly coplanar.
[15, 17, 25, 26] However, compounds 3 and 10,
with a carbonyl oxygen as a potential electron
donor, bear more resemblance to the remaining
two structures in Fig. 2, namely catechol [2-
(diisopropylamino)carbonyl]phenylboronate (15)
X-ray Structural Studies
X-ray crystallographic analysis was conducted on
compounds 3, 7, and 10. Inspection of the Oak Ridge
Thermal-Ellipsoid Plot Program (ORTEP) drawings
(Fig. 1) and selected structural parameters
(Table 1) reveals some significant differences, par-
ticularly between structures 3 and 10 on one hand,
and structure 7 on the other. Thus, the methyl ester
units in 3 and 10 are virtually coplanar with the ben-
zene ring core, while the N,N-dimethylamide units
in 7 are considerably twisted. Equally different is
the relative positioning of the pinacolborane unit(s).
In structures 3 and 10, the five-membered ring (or
rings) is/are slightly puckered and nearly perpendic-
SCHEME 3
Heteroatom Chemistry DOI 10.1002/hc

364 Kuttler et al.
FIGURE
1
ORTEP drawings of dimethyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)terephthalate (3), N,N,Nꢁ,Nꢁ-
tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)terephthalamide (7), and dimethyl 2,5-bis(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)terephthalate (10). Thermal ellipsoids are drawn at 50% probability. Hydrogen atoms are given arbitrary
radii.
[27] and ethylene glycol [([1]R)-1-acetamido-3-
methylthio)propyl]boronate (16) [28], both of
which contain an amide group, ortho-positioned
to the boronate ester unit. Several structures have
also been described in a recent work of Kawashima
and co-workers, all having an amino or a diazo
group serving as the electron donor [18]. In both
structures 15 and 16, X-ray analysis supports a
true dative B O bond, with distance values of 1.56
been used to explain these experimental findings.
On one hand, the B O distance and degree of
bonding probably depend on the electron-donating
ability of the Lewis donor center, and it is expected
to be greater in amides (such as 15 and 16), as
compared with esters (such as 3 and 10). On the
other hand, the Lewis acidity of the boron center
is also thought to play a crucial role. In the same
work ([18]), a clear distinction is made between
a catecholborane ester and a pinacolborane ester
unit. In the former, the oxygen atoms bonded to
boron experience strong interactions with the fused
˚
and 1.64 A, respectively, which are only slightly
longer than the typical B O covalent bond distance
˚
values of 1.43–1.44 A. Two different effects have
˚
TABLE 1 Selected Experimental (Regular Text) Bond Lengths (A) and Angles (Degrees) for Dimethyl 2-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)terephthalate (3), N,N,N ꢁ,N ꢁ-Tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)terephthalamide (7), and Dimethyl 2,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)terephthalate (10). Theoretical Values
(Italicized Text) are from B3LYP/6–31+G(d) Calculations, using Gaussian03/GaussView4 [29] on a Linux-operated 16-CPU
quad-core 64-bit Xeon QuantumCubeTM [45]
Parameter
3
7
10a
B(1)-O(1)
B(1)-O(2)
1.362(5), 1.37
1.360(5), 1.37
1.578(5), 1.58
2.59, 2.61
1.369(2), 1.37
1.369(2), 1.37
1.559(2), 1.56
3.83, 3.52
1.348(3), 1.37
1.362(3), 1.37
1.573(3), 1.58
2.60, 2.61
B(1)-C(2)
B(1)-O(3)b
O(1)-B(1)-O(2)
O(1)-B(1)-C(2)
O(2)-B(1)-C(2)
O(1)-B(1)-O(2)-C(8)
C(2)-B(1)-O(2)-C(8)
O(1)-B(1)-C(2)-C(3)
C(2)-C(1)-C(13)-O(3)
C(5)-C(4)-C(15)-O(5)–ester 3
C(5)-C(4)-C(16)-O(4)– amide 7
113.1(3), 113.5
122.3(3), 122.7
123.9(3), 123.0
11.6(4), 11.5
− 178.5(3), 178.8
90.9(4), 84.6
− 2.9(5), −1.1
10.4(5), 0.1
113.72(11), 113.0
126.13(11), 124.6
120.10(11), 122.4
8.1(1), 8.1
− 174.30(10), −170.2
165.49(11), 157.1
106.53(13), 81.4
–
114.3(2), 113.4
121.7(2), 122.9
123.5(2), 122.8
4.5(3), 11.6
− 167.1(2), −178.5
− 97.8(3), 87.9
− 13.6(3), −1.5
–
–
− 108.34(13), −127.3
–
aCompound 10 has a center of symmetry. For consistency, structural parameters were defined in accordance with the crystallographic
designation and numbering for compound 3, as shown in Figure 1.
bB(1)–O(3) is a distance, not an actual bond.
Heteroatom Chemistry DOI 10.1002/hc

Structure, Theoretical Studies, and Coupling Reactions of Some New Cyclic Boronic Esters 365
FIGURE 2 Some examples of structures containing a cyclic boronic ester unit, previously studied by X-ray crystallography.
benzene ring, leading to reduced electron-donating
ability of those oxygens and a concomitant increase
of the Lewis acidity of the boron center. The
ability of boron in catecholborane esters to strongly
coordinate to an electron-donor center, oxygen or
nitrogen, is clearly demonstrated both in structure
15 and the several structures listed in Kawashima’s
work. In the latter work, using 11B NMR studies,
the pinacolborane ester unit was concluded to be
incapable of coordination to a Lewis donor center,
because of the inherently greater electron-donating
ability of the five-membered ring oxygens, which
makes the boron center less Lewis acidic. At the
same time, structure 16 seems to suggest that
the boron center in a cyclic ester, which is very
similar to pinacolborane, is clearly capable of strong
interaction with a Lewis electron donor center.
To gain further insight, we undertook the prepa-
ration of the corresponding terephthalamide 7,
which would closely mimic the environment present
in structure 15. However, X-ray analysis on crystals
role of method/level on the structure and geome-
try of the studied compounds. All stationary points
were validated by subsequent frequency calcula-
tions at the same level of theory. All minimum
structures had sets of only positive second deriva-
tives, while TS structures all had one imaginary fre-
quency. TS searches were conducted employing the
Transit-Guided Quasi-Newton method (opt = qst2),
or the Berny algorithm (opt = TS) [38, 39]. Values
of Gibbs free energy and enthalpy changes were ob-
tained after frequency calculations and zero-point
energy (ZPE) corrections, which were not scaled.
Scaling factors for the ZPE values are available for
related levels of theory, such as B3LYP/6–31G(d) and
B3LYP/6–31+G(d,p), and are 0.9863 and 0.9988, re-
spectively, that is, very close to unity [40]. In addi-
tion, since this work was interested in differences of
Gibbs free energies (i.e., ꢀG= and ꢀG values), we an-
ticipated that such values would be largely invariant
towards the introduction of the same small correc-
tion in the constituent G values. Based on this, we
considered scaling ZPE values unnecessary.
of 7 does not lend any support to a possible B
O
dative bond. In fact, as seen from Fig. 1 and the data
in Table 1, structure 7 has the amide units consider-
ably twisted with respect to the benzene ring, while
the pinacolborane unit is nearly coplanar.
Experimental data suggest that the inherent op-
timal positioning of a pinacolborane ester unit, at-
tached to a benzene ring, is approximately copla-
nar in absence of interfering factors, such as steric
bulk or electron donors. This is evident in the case
of reported sulfonamide derivatives, such as 12 and
the para-substituted analog of 11 [41]. It has also
been demonstrated in some recently published X-ray
structures, such as the germafluorene derivatives 13,
and modified Tro¨ger’s bases containing the pinacolb-
orane unit, such as 14 [14,17]. Theoretical analysis,
available in published works, is in agreement. Ex-
tensive calculations conducted by Bock and cowork-
ers, employing DFT or MP2, indicate that for (1,3,2-
dioxaborolan-2-yl)benzene the coplanar structure is
a minimum, while the perpendicular arrangement
Theoretical Studies
All calculations were performed using the Gaus-
sian03/GaussView software package [29], on a
Linux-operated QuantumCube QS16–2500C-X64Q
by Parallel Quantum Solutions [30]. Calculations,
both of the actual structures and of model com-
pounds, were conducted using DFT at the B3LYP
level with 6–31+G(d) basis set [31–33]. In addi-
tion, the target structures were also calculated at
the MP2/6–31+G(d) level [34–37], to investigate the
Heteroatom Chemistry DOI 10.1002/hc

366 Kuttler et al.
FIGURE 3 (a) Stationary points for compounds 3, 7 and 10, calculated using B3LYP/6–31+G(d); (b) Stationary points for
compounds 3 and 7, calculated using MP2/6–31+G(d).
corresponds to a transition state, which is roughly
5.5 kcal mol higher in energy [19].
an incremental approach. Each group was studied
individually, using the model systems 17–20, as pre-
sented in Fig. 4. Rotation around the indicated bonds
was investigated in an attempt to find out: (1) the
ground state orientation of each moiety, and (2)
the energy cost associated with deviation from the
minimum orientation. The results from the analy-
sis, in terms of enthalpies and Gibbs free energies
of activation, are also shown in Fig. 4. Data clearly
support the conclusion that both the pinacolborane
and methyl ester substructures are coplanar with
the benzene ring in their ground states, while the
dimethylamide group is twisted at about 45◦ tor-
sion angle. In the corresponding transition states,
the first two are nearly perpendicular to the benzene
ring, while the dimethylamide group is coplanar. The
rotational energy profiles for all three moieties are
almost isoenergetic.
It seems, therefore, that in structures 3 and 10,
the methyl ester groups are oriented in a manner
corresponding to their energy-minimum position
(coplanar with the ring), while the pinacolborane
unit is twisted in a manner resembling the transition
state of its rotational profile. Assuming that twist-
ing one of the groups minimizes steric interactions
between them, the arrangement observed in 3 and
10 is optimal, that is, since both groups cannot be
As stated above, one of the main issues, arising
from our X-ray structural analysis was the possibility
for a Lewis acid–base interaction between the pina-
colborane unit and a carbonyl oxygen center from
an ortho-positioned ester or amide group. To address
this issue and provide comprehensive explanation of
the observed geometries of structures 3, 7, and 10,
we undertook a series of theoretical studies. Images
of the stationary points of all studied compounds are
shown in Fig. 3, and selected structural parameters
are listed in Table 1 (italicized values). If compared
with the X-ray data, it is immediately evident that the
DFT calculations reproduce the experimental struc-
tures rather accurately, properly predicting the rel-
ative orientations of the pinacolborane unit and the
ester (or amide, in the case of 7) group, with values
of the relevant geometry parameters being very close
to the experimental.
Based on the fact that DFT calculations repro-
duced the experimental structures much better, we
employed them in our further, model compound
studies. To computationally analyze the interactions
of the groups attached to the benzene ring (pina-
colborane ester, carboxylic ester, or amide) and ra-
tionalize the structures of 3, 7, and 10, we adopted
Heteroatom Chemistry DOI 10.1002/hc

Structure, Theoretical Studies, and Coupling Reactions of Some New Cyclic Boronic Esters 367
FIGURE 4 Ground- and transition-state structures for model compounds 17–20 and their rotational barriers. Results from
B3LYP/6–31+G(d) calculations. Dihedral angle definitions are based on the crystallographic designation and numbering from
Fig. 1.
coplanar at the same time, the group that requires
less energy to rotate (the pinacolborane) is twisted
out of planarity. In structure 7, the situation is differ-
ent: Both the amide and the pinacolborane units are
oriented in a manner that is close to or coincident
with their ground-state orientations (coplanar pina-
colborane, twisted amide). At the same time, with
one of them twisted out of coplanarity to the ben-
zene ring, it is also the arrangement with minimum
steric repulsion. Structure 7 therefore presents an
arrangement that is ideal from both electronic and
steric standpoint.
Overall, for all of the analyzed structures, orien-
tations of the substituents attached to the benzene
core are dictated by the relative energy costs for de-
viation from their respective ground-state positions,
while at the same time trying to achieve relative posi-
tioning that would minimize steric interactions. The
only other factor, which could additionally affect the
orientation, is a stabilizing B (carbonyl) O coor-
dination. Experimental results and the incremental
group analysis both seem to suggest that such inter-
action is either nonexistent or very weak and there-
fore incapable of compensating for the energy cost
associated with rotating the individual groups out of
their ground state orientations (as would be the case
if a B—O interaction were to take place in structure
7). Thus, our studies are in line with the findings of
Kawashima and co-workers, who concluded, on the
basis of their 11B NMR studies, that the pinacolbo-
rane unit was incapable of coordination to a Lewis
donor center. Although structures 3 and 10 do dis-
play some apparent coordination, it is probably just
fortuitous, as the optimal orientations of the methyl
ester and pinacolborane units, from the standpoint
of minimized steric interactions, place the boron and
oxygen atoms in close spatial proximity.
The lack of coordination, exhibited by the pina-
colborane unit, is to be related to the strong elec-
tronic interactions of the oxygen atoms in the five-
membered ring with the boron center. It results in
significant increase of electron density at the other-
wise inherently deficient boron, reducing its affin-
ity for additional interaction with Lewis basis. In
stark contrast, a catecholborane unit behaves quite
differently, due to the conjugation of the same oxy-
gen centers with the fused benzene ring. Previous
experimental studies have clearly shown the cate-
cholborane unit to be capable of donor–acceptor in-
teraction with an amide, as in the case of structure
15. At the same time, our theoretical studies show
that the interaction of a catecholborane unit with the
benzene ring is identical to that of a pinacolborane
(Structures 19 and 20, Fig. 4). Efforts to prepare and
Heteroatom Chemistry DOI 10.1002/hc

368 Kuttler et al.
study the catecholborane analogs of structures 3 and
7 are currently under way in our laboratory.
was conducted at 140 K using the phi and omega
scans technique. Final cell constants were deter-
mined based on the full data set, leading to a triclinic
˚
cell (P–1) with these dimensions: a = 7.3513(8) A, b =
CONCLUSIONS
◦
3
˚
˚
9.9505(11) A, c = 11.6181(13) A, α = 76.927(10) , β =
◦
◦
˚
New cyclic boronic esters have been successfully
prepared, structurally characterized, and utilized in
Suzuki coupling reactions. The differences between
the structures, in relative orientation of the sub-
stituents with respect to the benzene ring, have been
considered and rationalized, based on (1) minimiza-
tion of steric repulsion between ortho-substituents,
and (2) optimal orientation of each substituent,
based on theoretical results from calculations on
monosubstituted model compounds. The existence
of a Lewis donor–acceptor interaction between the
boron center and the carbonyl oxygen from the adja-
cent C O bond cannot be ruled out, but our analysis
seems to suggest that, at best, it is a minor effect,
in good agreement with previous studies of systems
containing the pinacolborane unit.
81.665(9) , γ = 79.487(10) , V = 809.15(15) A . For
Z = 2 and formula weight (F.W.) = 320.14, the cal-
culated density is 1.314 g/cm3. Non-hydrogen atoms
were refined anisotropically; hydrogen atoms were
assigned based on geometry. The final structure has
values for the unweighted agreement factor R1 =
0.0768 based on 1650 strong reflections (I > 2σ) and
R1 = 0.0963 based on all 2201 reflections.
X-ray crystallography of N,N,Nꢁ,Nꢁ-tetramethyl-
2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)
terephthalamide (7)
A crystal (colorless plate) of 7 (C18H27BN2O4) having
approximate dimensions 0.116 × 0.236 × 0.265 mm
was mounted on a glass fiber. Data acquisition was
conducted at 110 K using the phi and omega scans
technique. Final cell constants were determined
based on the full data set, leading to a orthorhom-
The cyclic boronic ester 3 has been successfully
utilized in a number of Suzuki coupling reactions,
which has led to the preparation of several previously
unknown aromatic and heteroaromatic structures.
˚
bic (Pbca) with these dimensions: a = 12.9993(4) A,
˚
˚
b = 11.9270(4) A, c = 24.2822(8) A, V = 3764.8(2)
EXPERIMENTAL
3
˚
A . For Z = 8 and F.W. = 346.23, the calculated den-
1H and 13C spectra were recorded at 300 MHz and
75 MHz, respectively, and referenced to the sol-
vent (CDCl3: 7.27 ppm and 77.0 ppm). X-ray struc-
tures were obtained using an Oxford Diffraction
Xcalibur3 diffractometer with graphite monochro-
matic Cu Kα radiation. Structure solution and
refinement were performed using the SHELXTL
6.10 software package [42]. Elemental analysis was
provided by Atlantic Microlab, Norcross, GA. High
resolution mass spectrometry (HRMS) data was pro-
vided by the Mass Spectrometry and Proteomics fa-
cility at the Ohio State University. The preparation
of iodoterephthalic acid (5) has been reported in lit-
erature [43, 44], but the method used in this study
is entirely different and the experimental protocol
is therefore provided. Full experimental details on
the preparation and spectroscopic characterization
of compounds 1, 3, and 10 are reported in a recent
publication [12].
sity is 1.222 Mg/m3. Non-hydrogen atoms were re-
fined anisotropically; hydrogen atoms were assigned
based on geometry. The final structure has values for
the unweighted agreement factor R1 = 0.0395 based
on 3278 strong reflections (I > 2σ) and R1 = 0.0442
based on all 3692 reflections.
X-ray crystallography of dimethyl 2,5-bis
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)
terephthalate (10)
A crystal (colorless plate) of 10 (C22H32B2O8) having
approximate dimensions 0.110 × 0.206 × 0.268 mm
was mounted on a glass fiber. Data acquisition was
conducted at 110 K using the phi and omega scans
technique. Final cell constants were determined
based on the full data set, leading to a monoclinic
˚
cell (P21/n) with these dimensions: a = 10.2195(5) A,
˚
˚
b = 11.9099(6) A, c = 10.3627(5) A, β = 108.448(6)³,
3
˚
V = 1196.45(11) A . For Z = 2 and F.W. = 446.09,
X-ray Crystallography of Dimethyl 2-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)
terephthalate (3)
the calculated density is 1.234 g/cm3. Non-hydrogen
atoms were refined anisotropically; hydrogen atoms
were assigned based on geometry. The final struc-
ture has values for the unweighted agreement factor
R1 = 0.0649 based on 1925 strong reflections (I >
2σ) and R1 = 0.0697 based on all 2110 reflections.
A crystal (colorless plate) of 3 (C16H21BO6) having
approximate dimensions 0.031 × 0.161 × 0.349 mm
was mounted on a glass fiber. Data acquisition
Heteroatom Chemistry DOI 10.1002/hc

Structure, Theoretical Studies, and Coupling Reactions of Some New Cyclic Boronic Esters 369
(CDCl3) δ 3.82 (s, 3H), 3.96 (s, 3H), 7.46 (d, J = 3.3 Hz,
Generalized protocol for Suzuki coupling
reactions of dimethyl 2-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)terephthalate (3)
1H), 7.78 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 3.2 Hz, 1H),
8.15 (dd, J1 = 8.0 Hz, J2 = 1.7 Hz, 1H), 8.36 (d, J =
1.6 Hz, 2H). 13C NMR (CDCl3) δ 52.8, 52.9, 120.7,
129.6, 130.6, 131.2, 132.5, 133.1, 135.8, 143.9, 165.3,
165.8, 168.7; Anal. Calcd. for C13H11NO4S: C, 56.31;
H, 4.00; N, 5.05. Found: C, 56.29; H, 3.97; N, 4.88.
A mixture of compound 3 (1.0 eqv.), an aromatic
halide (1.0 eqv.), aqueous K2CO3 (6.0 eqv. K2CO3, in
0.15 mL H2O per mmol K2CO3) and (Ph3P)4Pd (0.05
eqv.), in toluene (10 mL per mmol of 3), was stirred
at reflux for 18 h, under nitrogen atmosphere. Af-
ter cooling the mixture was washed with water, the
organic layer separated, dried (MgSO4) and the sol-
vent removed under reduced pressure. The residue
was purified by silica gel chromatography.
2-Iodoterephthalic acid (5)
Dimethyl iodoterephthalate 1 (3.00 g, 9.37 mmol)
was dissolved in 15 mL of methanol, and KOH
(2.10 g, 13.75 mmol) was added to the solution. The
reaction was continued for 30 min at 35◦C. Water
(30 mL) was added, the aqueous layer was extracted
with ether (2 × 25 mL), and then acidified to pH
2 using concentrated HCl. The mixture was kept in
the refrigerator for about 2 h and the white solid was
vacuum-filtered and air-dried to yield 2.68 g (98%) of
the target. Mp 296–299◦C (lit. Mp 299–300◦C [43]).
1H NMR (DMSO-d6) δ 7.74 (d, J = 8.0 Hz, 1H), 7.96
(dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 8.39 (d, J = 1.5 Hz,
1H), 13.57 (bs, 2H).
Dimethyl 2-phenylterephthalate (4a)
Purified by silica gel chromatography (CH2Cl2:
Hexanes = 2:1). Yields: 83% (with iodobenzene as
the aromatic halide), 45% (with bromobenzene as
the aromatic halide). Colorless oil. 1H NMR (CDCl3)
δ 3.66 (s, 3H), 3.95 (s, 3H), 7.32–7.43 (m, 5H), 7.86
(d, J = 8.7 Hz, 1H), 8.07 (dd, J1 = 1.7 Hz, J2 = 7.1 Hz,
1H), 8.08 (s, 1H).
N,N,Nꢁ,Nꢁ-tetramethyl-2-
Dimethyl 2-(4-nitrophenyl)terephthalate (4b)
iodoterephthalamide (6)
Purified by silica gel chromatography (CH2Cl2:
hexanes = 1:1), followed by recrysatallization from
methanol. Yield: 71%. White solid. Melting point
(Mp) 174–176◦C. 1H NMR (CDCl3) δ 3.72 (s, 3H),
3.97 (s, 3H), 7.49 (d, J = 8.8 Hz, 2H), 8.01 (d, J =
8.4 Hz, 1H), 8.03 (d, J = 2.0 Hz, 1H), 8.16 (dd, J1 =
Iodoterephthalic acid 5 (2.00 g, 6.85 mmol) was
dissolved in DMF (20 mL), in a 50 mL round bot-
tom flask, under nitrogen atmosphere. Thionyl chlo-
ride (2.04 g, 10.02 mmol, 1.25 mL) was added and
the solution was stirred at 150◦C for 5 h. Saturated
aqueous sodium bicarbonate (2 mL) was added and
the solution was stirred for 0.5 h. Solvents were re-
moved under reduced pressure, the resultant solid
was suspended in acetonitrile and vacuum filtered.
Further purification via column chromatography on
silica gel (acetone:hexane = 3:1), yielding the prod-
uct as a white solid (1.00 g, 42% yield). Mp 179–
183◦C. 1H NMR (CDCl3) δ 2.85 (s, 3H), 2.97 (bs,
3H), 3.10 (bs, 3H), 3.14 (s, 3H), 7.24 (d, J = 7.7 Hz,
1H), 7.43 (dd, J1 = 7.7 Hz, J2 = 1.5 Hz, 1H), 7.87
(d, J = 1.5 Hz, 1H). 13C NMR (DMSO-d6) δ 34.0, 34.7,
37.8, 38.9, 92.9, 126.81, 126.84, 136.7, 138.0, 143.5,
167.8, 169.1; Anal. Calcd. for C12H15IN2O2: C, 41.64;
H, 4.37; N, 8.09. Found: C, 41.69; H, 4.25; N, 8.11.
8.1 Hz, J2 = 1.7 Hz, 1H), 8.30 (d, J = 8.8 Hz, 2H). 13
C
NMR (CDCl3) δ 52.5, 52.6, 123.4, 129.3, 130.6, 131.5,
133.0, 134.0, 140.7, 147.2, 165.7, 167.2; Anal. Calcd.
for C16H13NO6: C, 60.95; H, 4.16; N, 4.44. Found: C,
61.03; H, 4.15; N, 4.40.
Dimethyl 2-(2-thiophenyl)terephthalate (4c)
Purified by passing through a short silica gel column
(CH2Cl2:hexanes = 1:1). Yield: 42%. Colorless oil. 1H
NMR (CDCl3) δ 3.77 (s, 3H), 3.96 (s, 3H), 7.08–7.10
(m, 2H), 7.39 (dd, J1 = 3.9 Hz, J2 = 2.4 Hz, 1H), 7.76
(dd, J1 = 8.0 Hz, J2 = 0.3 Hz, 1H), 8.05 (dd, J1 =
8.1 Hz, J2 = 1.7 Hz, 1H), 8.17 (dd, J1 = 1.7 Hz, J2 =
0.3 Hz, 1H). 13C NMR (CDCl3) δ 52.5, 126.5, 126.8,
127.4, 128.5, 129.4, 132.0, 132.2, 134.2, 135.5, 140.8,
165.9, 168.6; Anal. Calcd. for C14H12O4S: C, 60.86;
H, 4.38. Found: C, 60.78; H, 4.35.
N,N,Nꢁ,Nꢁ-tetramethyl-2-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)terephthalamide (7)
Compound 6 (0.57 g, 1.73 mmol), bis(pinacolato)
diboron (0.91 g, 36.00 mmol), (dppf)2PdCl2 (0.035 g,
0.04 mmol), potassium acetate (0.34 g, 3.47 mmol),
and DMF (10 mL) were introduced into a 50 mL
round bottom flask, under nitrogen atmosphere. The
Dimethyl 2-(2-thiazolyl)terephthalate (4d)
Purified by silica gel chromatography (hexanes:
acetone = 7:1). Yield: 58%. Yellow oil. 1H NMR
Heteroatom Chemistry DOI 10.1002/hc

370 Kuttler et al.
resultant mixture was stirred at 125◦C for 19 h. The
solvent was removed under reduced pressure and the
resultant solid was dissolved in benzene (40 mL).
The organic layer was washed with water (2 × 50
mL), dried (MgSO4), and the solvent evaporated un-
der reduced pressure. The solid material was washed
with a small quantity of cold pentane to yield the
product as a white solid (0.10 g, 17% yield). Further
purification via recrystallization from methanol. Mp
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1
183–185◦C. H NMR (CDCl3) δ 1.28 (s, 12H), 2.79
(bs, 3H), 2.93 (s, 3H), 3.06 (bs, 3H), 3.08 (s, 3H),
7.29 (d, J = 7.8 Hz, 1H), 7.47 (dd, J1 = 7.8 Hz,
J2 = 1.8 Hz, 1H), 7.83 (d, J = 1.4 Hz, 1H). 13C NMR
(DMSO-d6) δ 24.9,35.0, 35.3, 39.0, 39.5, 83.9, 125.6,
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SUPPORTING INFORMATION
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2008, 64, 7774–7781.
Supporting Information Available. Crystallogra-
phic data (excluding structure factors) for the struc-
tures in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supple-
mentary publication numbers CCDC 795279, CCDC
916569, and CCDC 916570. Copy of the data can be
obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK (fax: +44-
1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
Calculated energies and thermodynamic param-
eters for all target boronic esters (3, 7, and 10) can
be found in Table S1. Calculated energies and ther-
modynamic parameters for model structures 17–20
are listed in Table S2.
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