Functionalization of dihalophenylboronic acids by deprotonation of their N-butyldiethanolamine esters

Article abstract of DOI:10.1002/ejoc.200900526

Deprotonative lithiation of various 6-butyl-2-(dihalophenyl)-(N-B)-1,3,6,2- dioxazaborocanes (N-butyldiethanolamine esters of dihalophenylboronic acids) was investigated. It was found that selective transformations can be best achieved by use of LDA as the lithiating reagent. The reactivities of these compounds vary significantly, depending on the natures and positions of the halogen atoms. The resultant boron-lithium bimetallic intermediates were subjected to reactions with electrophiles to afford functionalized halogenated arylboronic acids.

Full text of DOI:10.1002/ejoc.200900526

FULL PAPER
DOI: 10.1002/ejoc.200900526
Functionalization of Dihalophenylboronic Acids by Deprotonation of Their
N-Butyldiethanolamine Esters
Krzysztof Durka,[a] Paweł Kurach,[a] Sergiusz Lulin´ski,*[a] and Janusz Serwatowski[a]
Keywords: Lithiation / Boron / Substituent effects
Deprotonative lithiation of various 6-butyl-2-(dihalophenyl)-
(N–B)-1,3,6,2-dioxazaborocanes (N-butyldiethanolamine es-
ters of dihalophenylboronic acids) was investigated. It was
found that selective transformations can be best achieved by
use of LDA as the lithiating reagent. The reactivities of these
compounds vary significantly, depending on the natures and
positions of the halogen atoms. The resultant boron-lithium
bimetallic intermediates were subjected to reactions with
electrophiles to afford functionalized halogenated aryl-
boronic acids.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
work we report for the first time on the application of de-
protonative metallation for the functionalization of related
arylboron derivatives.
Introduction
Arylboronic acids and esters have recently become very
important reagents in modern organic synthesis; they have
also found applications in other fields.[1] Ongoing interest in
novel functionalized arylboronic acid derivatives stimulates
work on the development of new simple general synthetic
routes to these compounds. Classically, they can be ob-
tained by transmetallation of aryllithium[2] or arylmagne-
sium[3] compounds with trialkylborates, although aryl de-
rivatives of silicon, mercury, tin or thallium have also been
used in combination with borane or tribromoborane.[4]
More recent approaches involve Pd-[5] and CuI-catalysed[6]
coupling of aryl halides with diboron derivatives or hydro-
boranes.
Alternative strategies based on the structural modifica-
tion of protected arylboronic acids have also been devel-
oped.[7] One of these is based on the generation of bimetal-
lic boron-metal intermediates. Besides magnesiated aryl-
boronic pinacol esters,[8] the syntheses and reactivities of a
few types of boron-lithium bimetallic reagents have been
reported. Examples include potassium (3- and 4-lithio-
phenyl)trifluoroborates,[9] as well as closely related lithium
(lithiophenyl)triisopropoxyborates.[10] The conversion of ar-
ylboronic acids into 6-alkyl-2-aryl-(N–B)-1,3,6,2-dioxaza-
borocanes (for simplicity designated throughout this paper
by the ad hoc term “arylboronic azaesters”) has also been
used for the introduction of lithium into the boronated aro-
matic ring.[11] All of these bimetallic reagents were gener-
ated by means of halogen-lithium exchange from the corre-
sponding bromine- or iodine-containing precursors. In this
Results and Discussion
Protection of Dihalophenylboronic Acids
In
a modification of previously reported proce-
dures[11a–11c] and by our reported protocol[11d] we used N-
butyldiethanolamine (BDEA) instead of N-methyldietha-
nolamine, because we assumed that the longer alkyl chain
should increase the solubilities of arylboronic azaesters and
(at least to some extent) the resistance of the boronic moiety
to nucleophilic attack, due to the better steric protection.
In our protocol, a mixture of a dihalophenylboronic acid
(50–100 mmol), BDEA (50–100 mmol) and anhydrous
MgSO4 in acetone was stirred for ca. 1 h at 35–40 °C. The
resulting mixture was filtered and subjected to concentra-
tion to remove acetone. Upon addition of diethyl ether the
precipitated material was filtered off. In all cases well-de-
fined, air-stable and crystalline 6-butyl-2-haloaryl-(N–B)-
1,3,6,2-dioxazaborocanes 1–12 were obtained in high yields,
in general exceeding 90% (Table 1). In addition, 6-tert-but-
yl-2-(3Ј,5Ј-difluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane
(13) was also prepared from 3,5-difluorophenylboronic acid
and N-tert-butyldiethanolamine. The tetrahedral boron en-
vironment with the B–N dative bond was established di-
rectly by 11B NMR analyses, which in all cases showed sin-
gle resonances at δ ≈ 7–8 ppm. Compounds 1–12 are insolu-
ble in hexane and diethyl ether but very soluble in THF. On
the other hand, compound 13 is only sparingly soluble in
THF and exhibits fluxional behaviour in CDCl3 solution at
room temperature, manifested in the strong broadening of
the resonances of the methylene protons bonded to the ni-
trogen atom.
[a] Physical Chemistry Department, Faculty of Chemistry, Warsaw
University of Technology,
Noakowskiego 3, 00-664 Warsaw, Poland
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K. Durka, P. Kurach, S. Lulin´ski, J. Serwatowski
FULL PAPER
Table 1. Preparation of 6-butyl-2-(dihalophenyl)-(N–B)-1,3,6,2-di-
oxazaborocanes.
Scheme 1.
Product
X, Y
% Yield
1
4-F, H
98
97
98
94
92
96
97
97
96
96
96
96
99
2
3-F, 5-F
2-F, 4-F
2-F, 3-F
3-F, 4-F
2-F, 5-F
3-Cl, 5-Cl
3-Cl, 4-Cl
2-Cl, 3-Cl
3-Br, 5-Br
3-Br, 5-F
2-F, 5-CF3
3-F, 5-F
susceptibility of the boron atom to nucleophilic attack is
due to the fluxional behaviour of the azaester moiety in 13.
In addition, a competition experiment was performed to
assess the impact of boronation on the reactivity of the 1,3-
difluorobenzene system towards lithiation. For this pur-
pose, a mixture of 1,3-difluorobenzene (1 equiv.) and 2
(1 equiv.) was treated with LDA (1 equiv.). Subsequent
trapping with Me3SiCl (1 equiv.), followed by hydrolysis,
gave a mixture of 1,3-difluoro-2-(trimethylsilyl)benzene and
3,5-difluorophenylboronic acid, which indicates that the
proton abstraction from the boronated 1,3-difluorobenzene
derivative is strongly retarded relative to that from the par-
ent compound.
3
4
5
6
7
8
9
10
11
12
13
Lithiation of Dihalophenylboronic Azaesters
We started our work with an attempted metallation of 6-
An approach similar to that optimized for 2 also proved
butyl-2-(4Ј-fluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (1). useful in the lithiation of the closely related 6-butyl-2-(2Ј,4Ј-
Unfortunately, this compound proved essentially resistant difluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (3, Scheme
against deprotonation with LDA and LDA/tBuOK. Even 1). Again, lithiation proceeded effectively at low tempera-
the stronger alkyllithium bases nBuLi, nBuLi/PMDTA and ture, and subsequent treatment with electrophiles gave 3-
sBuLi were not effective. It should be noted that simple substituted 2,4-difluorophenylboronic acids in good yields.
fluorobenzene is readily lithiated with sBuLi,[12] whereas
These results encouraged us to investigate the metallation
nBuLi/PMDTA has been successfully used for deproton- of azaesters of other isomeric difluorophenylboronic acids.
ation of fluoroanisoles ortho to fluorine.[13] It seems that However, we observed that the lithiation of 6-butyl-2-(3Ј,4Ј-
the reduced reactivity of 1 is the result of the electronic difluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (4) does
influence of the borocanyl group on the fluorophenyl ring. not occur under the conditions successfully applied for sub-
This group acts as a σ-donor, and hence the increased elec- strates 2 and 3. Treatment of the reaction mixture with
tron density in the aromatic ring makes the ortho-fluoro DMF, followed by the hydrolytic workup, simply afforded
hydrogen atoms much less susceptible to abstraction.
recovered 3,4-difluorophenylboronic acid, and no incorpo-
We next turned our attention to more acidic substrates ration of the formyl group onto the aromatic ring was ob-
containing two halogen atoms in the aromatic ring. The served.
acidities of isomeric dihalobenzenes depend on the posi-
In the next attempt we added Me3SiCl as an electrophile
tions of the two halogens atoms with respect to each other, and the reaction mixture was allowed to warm up slowly to
1,3-dihalobenzene being more acidic than the 1,2- and 1,4- 0 °C. Me3SiCl is known to co-exist with bulky lithium
isomers because of the cooperating effects of two ortho-hal- amides such as LTMP and LDA in solution but reacts quite
ogens.[14] We hence expected that 6-butyl-2-(3Ј,5Ј-difluoro- rapidly even with some sterically hindered aryllithiums,[15]
phenyl)-(N–B)-1,3,6,2-dioxazaborocane (2) should be suffi- so we assumed that this electrophile should effectively trap
ciently reactive. Indeed, the lithiation of 2 with LDA in the lithiated azaester, thus preventing its plausible degrada-
THF at ca –75 °C (Scheme 1) proved feasible. The forma- tion at higher temperature (e.g., by an aryne mechanism).
tion of the resultant 4Ј-lithio intermediate 2-Li was indi- Indeed, the workup of the resulting mixture cleanly gave
cated by its precipitation from the solution.
3,4-difluoro-5-(trimethylsilyl)phenylboronic
acid
(4a),
Subsequent derivatization of 2-Li with selected electro- which indicates that of the two potential metallation sites
philes afforded 3,5-difluorophenylboronic acids function- ortho to fluorine, lithium goes selectively to the less hin-
alized at their 4-positions (Table 2), including the interest- dered one (Scheme 2).
ing fluorinated 1,4-phenylenediboronic acid 2c. For com-
In a similar way, the boronation of 4 was performed with
parison, the isomeric tert-butyl azaester 13 gave a mixture LTMP/B(OiPr)3. It had previously been demonstrated that
of products; these contained some borinic derivatives, B(OiPr)3 is compatible with bulky lithium amides in the in
which suggested that the boron atom in 13 is protected less situ quench technique.[16] Unfortunately, an attempted stan-
effectively than in 2. It is plausible that the increased nylation with LTMP/Bu3SnCl did not proceed cleanly. Be-
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Functionalization of Dihalophenylboronic Acids by Deprotonation
Table 2. The preparation of functionalized dihaloarylboronic acids
through deprotonation of dihalophenylboronic BDEA azaesters
with LDA.
Scheme 2.
cause the low-temperature metallation of 6-butyl-2-(2Ј,3Ј-
difluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (5) was
also unsuccessful, we also employed the lithiation/silylation
and lithiation/boronation protocols described above for 4
for this substrate. Again, we succeeded in the isolation of
the silylated boronic acid 5a, as well as the diboronic acid
5b. In a similar approach, treatment of 6 with LDA/Me3-
SiCl gave an almost equimolar mixture of 2,5-difluoro-3-
(trimethylsilyl)phenylboronic acid (6a) and 2,5-difluoro-4-
(trimethylsilyl)phenylboronic acid (6b). In this case lithi-
ation at the position between fluorine and the borocanyl
function is apparently hampered by steric congestion. On
the other hand, this function does not exhibit any appreci-
able long-range electronic effects, which should result in
some preference in the formation of acids 6a or 6b.
The lower reactivities of azaesters 4–6 with respect to 2–
3 correlate with different relative reactivities of the parent
difluorobenzenes. 1,3-Difluorobenzene is more reactive
than both 1,2- and 1,4-difluorobenzene, although all these
compounds are readily deprotonated with LDA at –75 °C.
Boronation significantly decreases the reactivities of all di-
fluorobenzenes, but nevertheless, azaesters 2 and 3 derived
from 1,3-difluorobenzene can be lithiated at –75 °C. This is
no longer the case, however, for 4–6, derived from less
acidic difluorobenzenes, because they require higher tem-
peratures for effective proton abstraction. One interpret-
ation, assuming the operation of a CIPE-based mecha-
nism,[17] would involve better precoordination of the base
close to the metallation site flanked by two heteroatoms.
However, this alternative seems to be less likely, because
fluorine (in fluoroarenes) is recognized as a weak donor for
lithium, in sharp contrast with the oxygen in the solvent
(THF). There is indeed no spectroscopic evidence, for in-
stance, for Li···F interaction between fluorobenzene and
nBuLi in toluene.[18] The ortho-directing ability of fluorine
is hence due only to its inductive effect, resulting in the
enhancement of both thermodynamic and kinetic acidities.
Accordingly, the cumulative ortho-acidifying effect at the
position between two fluorines is responsible for the higher
reactivities of 2–3 with respect to 4–6.
We extended our research by using selected heavier halo-
gen analogues of 2–6. Azaesters of three isomeric dichlo-
rophenylboronic acids 7–9 were prepared and their behav-
iour towards LDA was studied. Compound 7 undergoes
lithiation readily at –75 °C (Scheme 3), as confirmed by the
high-yield formation of pinacol ester 7a and acid 7b. Azaes-
[a] In situ quenching. [b] Total yield, see Scheme 2. [c] Poor conver-
sion of the substrate.
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K. Durka, P. Kurach, S. Lulin´ski, J. Serwatowski
FULL PAPER
ters 8 and 9, however, proved to be less reactive than their of 3,5-difluorophenylboronic acid and traces of the acid 7b
fluorinated counterparts 4 and 5, because under similar li- (resulting from the lithiation/silylation of 7) were detected
thiation/silylation conditions they gave only small amounts in the reaction mixture. This result confirmed the observa-
of the corresponding silylated dichlorophenylboronic acids tions described above concerning the weaker reactivities of
8a and 9a, whereas simple dichlorophenylboronic acids re- chlorinated azaesters relative to their fluorinated analogues.
sulting from hydrolysis of the starting azaesters were found
It should be stressed that the route to arylboronic acids
as major products. The degree of conversion was higher described in this study, through the reversed approach in-
with LTMP as the lithiating agent in the case of 8, but it volving first the introduction of the functional group and
was still rather poor (ca 50%) from the point of view of then boronation, would not be trivial in most cases. The
preparative utility.
acid 2b could potentially be prepared from the commer-
cially available 1-bromo-3,5-fluorobenzene (14) by lithi-
ation/silylation with LDA/Me3SiCl,[20] followed by Br–Li
exchange and boronation (Scheme 5). However, the iso-
meric acid 4a is not easily accessible by the same route from
1-bromo-3,4-fluorobenzene (15), because this substrate de-
protonates between Br and F[21] rather than at the 5-posi-
tion. Another problematic example would be the synthesis
of 7a and 7b starting with deprotonation of 1-bromo-3,5-
dichlorobenzene (16), because this reaction would be ex-
pected to be unselective, due to the similar ortho-directing
abilities of chlorine and bromine.[22] On the other hand,
(2,4,6-tribromophenyl)trimethylsilane (17a) can be cleanly
obtained from 1,3,5-tribromobenzene (17),[23] but it cannot
serve as an optimal substrate for 10a because it preferen-
tially undergoes Br–Li interconversion ortho to the SiMe3
group.[24] Finally, the synthesis of the diboronic acids 2c,
4b, 5b, or 12a from the corresponding halogenated di-
lithiobenzenes by double boronation would seem to be the
simplest option. Unfortunately, such dilithiated intermedi-
ates are not easily accessible and so our protocol becomes
the only real alternative.
Scheme 3.
The lithiation of the two bromine-containing azaesters
10 and 11 was also accomplished (Scheme 3). Again, the
cumulated ortho-acidifying effects of two halogen atoms al-
lowed for the proton abstraction at –75 °C. Finally, metalla-
tion of the CF3-substituted azaester 12 was performed un-
der the conditions applied for 4–6, but with B(OiPr)3 as the
electrophile (Scheme 4). This approach resulted in the clean
formation of diboronic acid 12a, because lithiation occurs
only ortho to fluorine, whereas CF3 activates this position
through its potent long-range activating effect.[19]
Scheme 4.
In addition, we performed several competition experi-
ments to assess the relative reactivities of selected azaesters.
In the first of these, a mixture of 2 (1 equiv.) and 3 (1 equiv.)
was added at ca –75 °C to LDA (1 equiv.) in THF, followed
by quenching with Me3SiCl (1 equiv.). A mixture contain-
ing comparable amounts of acids 2b and 3b was formed
(together with the two difluorophenylboronic acids re-
sulting from the hydrolysis of unreacted azaesters). This in-
dicates that the position of the borocanyl moiety with re-
spect to the metallation site (meta vs. para) does not have a
significant influence on the reactivity.
Scheme 5.
Conclusions
In conclusion, the generation of bimetallic boron-lithium
reagents by deprotonation of halogenated arylboronic aza-
A different situation was observed when a mixture of 2 esters is possible with non-nucleophilic lithium amides such
and 7 was subjected to a similar experiment. In this case, 2 as LDA, provided that the aryl hydrogens are sufficiently
was preferentially deprotonated and only a small amount activated. This can readily be achieved when two fluorine
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Functionalization of Dihalophenylboronic Acids by Deprotonation
166.4 (dd, J = 244.5, 11.0 Hz), 163.2 (dd, J = 247.5, 12.5 Hz), 136.7
(dd, J = 12.5, 8.5 Hz), 110.2 (dd, J = 18.5, 3.0 Hz), 102.8 (dd, J =
30.0, 23.5 Hz), 62.6, 58.0, 57.3, 26.7, 20.0, 13.6 ppm. 11B NMR
(CDCl3, 64.16 MHz): δ = 7 ppm. C14H20BF2NO2 (283.13): calcd.
C 59.39, H 7.12, N 4.95; found C 59.26, H 6.97, N 4.98.
atoms are attached to the aryl ring, whereas some dichlori-
nated analogues exhibit lower reactivities. The resulting
lithiated azaesters can be subsequently derivatized by treat-
ment with appropriate electrophiles, which provides access
to various functionalized halogenated arylboronic acids in
most cases not easily accessible by other methods.
6-Butyl-2-(3Ј,4Ј-difluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (4):
1
Yield 13.2 g (94%), m.p. 75–78 °C. H NMR (CDCl3, 400 MHz):
δ = 7.34 (m, 1 H, Ph), 7.26 (m, 1 H, Ph), 7.00 (m, 1 H, Ph), 4.12–
4.00 (m, 4 H, CH2O), 3.05–2.91 (m, 4 H, CH2N), 2.24–2.20 (m, 2
H, NCH2CH2CH2CH3), 1.48–1.40 (m, 2 H, NCH2CH2CH2CH3),
1.12–1.03 (m, 2 H, NCH2CH2CH2CH3), 0.76 (t, J = 7.0 Hz, 3 H,
NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3, 100.6 MHz): δ =
150.0 (dd, J = 248.5, 15.0 Hz), 149.8 (dd, J = 250.5, 15.0 Hz), 129.1
(dd, J = 6.0, 3.5 Hz), 121.3 (d, J = 13.5 Hz), 115.9 (d, J = 15.5 Hz),
62.9, 59.8, 57.3, 26.6, 20.0, 13.5 ppm. 11B NMR (CDCl3,
64.16 MHz): δ = 7 ppm. C14H20BF2NO2 (283.13): calcd. C 59.39,
H 7.12, N 4.95; found C 59.12, H 7.04, N 5.02.
Experimental Section
General: All reactions involving air- or moisture-sensitive reagents
were carried out under argon. Et2O and THF were stored over
sodium wire before use. All halogenated phenylboronic acids used
as starting materials are commercially available from Aldrich. This
is also the case for N-butyldiethanolamine and other important
reagents including nBuLi (10  solution in hexanes), diisopropyl-
amine, 2,2,6,6-tetramethylpiperidine, chlorotrimethylsilane, chloro-
tributyltin, dimethyl carbonate, dimethylformamide, iodine and tri-
isopropoxyborane, which were used as received. The NMR chemi-
cal shifts are given relative to TMS with the aid of known chemical
shifts of residual proton (1H) or carbon (13C) solvent resonances.
In the 13C NMR spectra the resonances of boron-bound carbon
atoms were not observed in most cases, due to their broadening by
quadrupolar boron nuclei.
6-Butyl-2-(2Ј,3Ј-difluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (5):
1
Yield 13.0 g (92%), m.p. 86–88 °C. H NMR (CDCl3, 400 MHz):
δ = 7.37 (m, 1 H, Ph), 7.06–6.94 (m, 2 H, Ph), 4.16–4.04 (m, 4 H,
CH2O), 3.18–3.11 (m, 2 H, CH2N), 3.09–3.02 (m, 2 H, CH2N),
2.60–2.55 (m, 2 H, NCH2CH2CH2CH3), 1.57–1.50 (m, 2 H,
NCH2CH2CH2CH3), 1.21–1.12 (m, 2 H, NCH2CH2CH2CH3), 0.82
(t, J = 7.0 Hz, 3 H, NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3,
100.6 MHz): δ = 153.4 (dd, J = 241.5, 10.5 Hz), 150.5 (dd, J =
246.5, 16.0 Hz), 130.2 (dd, J = 9.0, 4.0 Hz), 123.5 (m), 116.5 (d, J =
17.5 Hz), 62.7, 58.0, 57.4, 26.8, 20.1, 13.6 ppm. 11B NMR (CDCl3,
64.16 MHz): δ = 7 ppm. C14H20BF2NO2 (283.13): calcd. C 59.39,
H 7.12, N 4.95; found C 59.22, H 7.19, N 4.91.
6-Butyl-2-(4Ј-fluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (1):
A
mixture of 4-fluorophenylboronic acid (7.0 g, 0.05 mol), N-butyldi-
ethanolamine (8.5 g, 0.052 mol), anhydrous MgSO4 (5 g) and ace-
tone (50 mL) was stirred for 1 h at 35 °C. The mixture was filtered
and concentrated under reduced pressure. Et2O (25 mL) was added
to the remaining solid residue, followed by filtration of the resulting
slurry. The crystalline product was washed with diethyl ether
(2ϫ20 mL) and dried to give the title compound, yield 13.0 g
(98%), m.p. 146–148 °C. 1H NMR (CDCl3, 400 MHz): δ = 7.54 (t,
J = 8.5 Hz, 2 H, Ph), 6.92 (t, J = 8.5 Hz, 2 H, Ph), 4.15–4.03
(m, 4 H, CH2O), 3.03–2.91 (m, 4 H, CH2N), 2.23–2.19 (m, 2 H,
NCH2CH2CH2CH3), 1.47–1.39 (m, 2 H, NCH2CH2CH2CH3),
1.12–1.02 (m, 2 H, NCH2CH2CH2CH3), 0.77 (t, J = 7.0 Hz, 3 H,
NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3, 100.6 MHz): δ =
162.9 (d, J = 243.0 Hz), 134.8 (d, J = 243.0 Hz), 113.8 (d, J =
19.0 Hz), 62.9, 59.7, 57.2, 26.7, 20.0, 13.6 ppm. 11B NMR (CDCl3,
64.16 MHz): δ = 8 ppm. C14H21BFNO2 (265.14): calcd. C 63.42, H
7.98, N 5.28; found C 63.25, H 8.01, N 5.33.
6-Butyl-2-(2Ј,5Ј-difluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (6):
1
Yield 13.5 g (96%), m.p. 71–74 °C. H NMR (CDCl3, 400 MHz):
δ = 7.32–7.26 (m, 1 H, Ph), 7.85–6.81 (m, 2 H, Ph), 4.12–4.00 (m,
4 H, CH2O), 3.14–3.00 (m, 4 H, CH2N), 2.58–2.54 (m, 2 H,
NCH2CH2CH2CH3), 1.54–1.46 (m, 2 H, NCH2CH2CH2CH3),
1.18–1.09 (m, 2 H, NCH2CH2CH2CH3), 0.80 (t, J = 7.0 Hz, 3 H,
NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3, 100.6 MHz): δ =
162.0 (d, J = 237.5 Hz), 158.7 (d, J = 241.5 Hz) 121.3 (dd, J =
21.5, 11.5 Hz), 115.8–115.3 (m, 2ϫCarom), 62.6, 57.9, 57.4, 26.6,
20.0, 13.5 ppm. 11B NMR (CDCl3, 64.16 MHz): δ = 7 ppm.
C14H20BF2NO2 (283.13): calcd. C 59.39, H 7.12, N 4.95; found C
58.98, H 7.24, N 5.33.
6-Butyl-2-(3Ј,5Ј-dichlorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (7):
Yield 15.3 g (97%), m.p. 137–139 °C. 1H NMR (CDCl3, 400 MHz):
δ = 7.44 (d, J = 2.0 Hz, 2 H, Ph), 7.21 (t, J = 2.0 Hz, 1 H, Ph),
7.20 (td, J = 8.0, 1.0 Hz, 1 H, Ph), 7.06 (td, J = 8.0, 1.5 Hz, 1 H,
Ph), 4.16–4.05 (m, 4 H, CH2O), 3.07–2.95 (m, 4 H, CH2N), 2.30–
6-Butyl-2-(3Ј,5Ј-difluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (2):
Yield 13.7 g (97%), m.p. 112–114 °C. 1H NMR (CDCl3, 400 MHz):
δ = 7.06 (dt, J = 7.0, 2.0 Hz, 2 H, Ph), 6.61 (tt, J = 7.0, 2.0 Hz, 1
H, Ph), 4.13–4.02 (m, 4 H, CH2O), 3.05–2.91 (m, 4 H, CH2N),
2.27–2.22 (m, 2 H, NCH2CH2CH2CH3), 1.48–1.40 (m, 2 H,
NCH2CH2CH2CH3), 1.13–1.04 (m, 2 H, NCH2CH2CH2CH3), 0.78
(t, J = 7.0 Hz, 3 H, NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3,
100.6 MHz): δ = 162.6 (dd, J = 248.5, 11.0 Hz), 114.9 (dd, J =
16.1, 4.5 Hz), 102.4 (t, J = 26.0 Hz), 63.0, 59.6, 57.3, 26.6, 20.0,
2.25 (m,
2 H, NCH2CH2CH2CH3), 1.51–1.43 (m, 2 H,
NCH2CH2CH2CH3), 1.17–1.08 (m, 2 H, NCH2CH2CH2CH3), 0.81
(t, J = 7.0 Hz, 3 H, NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3,
100.6 MHz): δ = 134.0, 131.3, 127.4, 63.1, 59.8, 57.5, 26.8, 20.0,
13.7 ppm. 11B NMR (CDCl3, 64.16 MHz):
δ
=
7 ppm.
13.5 ppm. 11B NMR (CDCl3, 64.16 MHz):
C14H20BF2NO2 (283.13): calcd. C 59.39, H 7.12, N 4.95; found C
59.25, H 7.10, N 5.03.
δ
=
7 ppm.
C14H20BCl2NO2 (316.04): calcd. C 53.21, H 6.38, N 4.43; found C
53.03, H 6.43, N 4.47.
6-Butyl-2-(3Ј,4Ј-dichlorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (8):
Yield 15.3 g (97%), m.p. 118–120 °C. 1H NMR (CDCl3, 400 MHz):
δ = 7.64 (d, J = 1.5 Hz, 1 H, Ph), 7.38 (dd, J = 8.0, 1.5 Hz, 1 H,
Ph), 7.30 (d, J = 8.0 Hz, 1 H, Ph), 4.13–4.01 (m, 4 H, CH2O), 3.04–
2.91 (m, 4 H, CH2N), 2.25–2.20 (m, 2 H, NCH2CH2CH2CH3),
6-Butyl-2-(2Ј,4Ј-difluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (3):
Yield 13.8 g (98%), m.p. 119–121 °C. 1H NMR (CDCl3, 400 MHz):
δ = 7.61 (q, J = 8.0 Hz, 1 H, Ph), 6.76 (dt, J = 8.5, 2.5 Hz, 1 H,
Ph), 6.64 (dt, J = 10.0, 2.5 Hz, 1 H, Ph), 4.14–4.02 (m, 4 H, CH2O),
3.14–3.00 (m, 4 H, CH2N), 2.56–2.51 (m, 2 H, NCH2CH2- 1.48–1.40 (m, 2 H, NCH2CH2CH2CH3), 1.13–1.04 (m, 2 H,
CH2CH3), 1.55–1.47 (m, 2 H, NCH2CH2CH2CH3), 1.20–1.10 (m,
H, NCH2CH2CH2CH3), 0.81 (t, 7.0 Hz, H,
NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3, 100.6 MHz): δ =
NCH2CH2CH2CH3), 0.78 (t, J = 7.0 Hz, 3 H, NCH2CH2-
CH2CH3) ppm. 13C NMR (CDCl3, 100.6 MHz): δ = 135.0, 132.6,
131.3, 131.1, 129.3, 63.9, 59.9, 57.4, 26.7, 20.0, 13.6 ppm. 11B NMR
2
J
=
3
Eur. J. Org. Chem. 2009, 4325–4332
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4329

K. Durka, P. Kurach, S. Lulin´ski, J. Serwatowski
(CDCl3, 64.16 MHz): δ = 7 ppm. C14H20BCl2NO2 (316.04): calcd. a stirred solution of LDA, freshly prepared from diisopropylamine
FULL PAPER
C 53.21, H 6.38, N 4.43; found C 53.10, H 6.18, N 4.52.
(1.52 g, 15 mmol) and nBuLi (10 , 1.5 mL, 15 mmol) in THF
(20 mL). After ca 30 min stirring at ca –75 °C (internal tempera-
ture) a mixture containing the lithiate 2-Li was quenched with di-
methyl carbonate (2.7 g, 30 mmol). The mixture was stirred for
30 min at –75 °C and was then hydrolysed with aq. H2SO4 (2 ,
10 mL). The water phase was separated, followed by extraction
with diethyl ether (2ϫ15 mL). The extracts were added to the or-
ganic phase, which was concentrated under reduced pressure. A
solid residue was filtered and washed consecutively with water
(2ϫ10 mL), toluene (5 mL) and hexane (5 mL). Drying in vacuo
afforded the title compound as a white powder, m.p. 148–151 °C
(dec), yield 1.9 g (88%). 1H NMR ([D6]acetone, 400 MHz): δ =
7.69 [br, 2 H, B(OH)2], 7.48 (d, J = 9.0 Hz, 2 H, Ph), 3.92 (s, 3 H,
OMe) ppm. 13C{1H} NMR ([D6]acetone, 100.6 MHz): δ = 162.4,
160.5 (dd, J = 255.0, 5.5 Hz), 117.5 (dd, J = 19.0, 5.0 Hz), 113.0
(t, J = 19.0 Hz), 53.1 ppm. 11B NMR ([D6]acetone, 64.16 MHz): δ
= 28 ppm. C8H7BF2O4 (215.95): calcd. C 44.50, H 3.27; found C
44.80, H 3.08.
6-Butyl-2-(2Ј,3Ј-dichlorophenyl)-(N–B)-1,3,6,2-dioxazaborocane (9):
Yield 15.1 g (96%), m.p. 147–148 °C. 1H NMR (CDCl3, 400 MHz):
δ = 7.71 (dd, J = 7.5, 1.5 Hz, 1 H, Ph), 7.34 (dd, J = 7.5, 1.5 Hz,
1 H, Ph), 7.10 (t, J = 7.5 Hz, 1 H, Ph), 4.18–4.07 (m, 4 H, CH2O),
3.29–3.22 (m, 2 H, CH2N), 3.07–3.02 (m, 2 H, CH2N), 2.62–2.58
(m,
2
H, NCH2CH2CH2CH3), 1.57–1.49 (m,
2
H,
NCH2CH2CH2CH3), 1.20–1.11 (m, 2 H, NCH2CH2CH2CH3), 0.82
(t, J = 7.0 Hz, 3 H, NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3,
100.6 MHz): δ = 136.6, 134.6, 132.9, 130.0, 126.6, 62.9, 58.1, 58.0,
26.9, 20.1, 13.7 ppm. 11B NMR (CDCl3, 64.16 MHz): δ = 7 ppm.
C14H20BCl2NO2 (316.04): calcd. C 53.21, H 6.38, N 4.43; found C
53.15, H 6.23, N 4.54.
6-Butyl-2-(3Ј,5Ј-dibromophenyl)-(N–B)-1,3,6,2-dioxazaborocane (10):
Yield 19.5 g (96%), m.p. 140–142 °C. 1H NMR (CDCl3, 400 MHz):
δ = 7.65 (d, J = 2.0 Hz, 2 H, Ph), 7.53 (t, J = 2.0 Hz, 1 H, Ph),
4.17–4.07 (m, 4 H, CH2O), 3.10–2.96 (m, 4 H, CH2N), 2.32–2.28
(m,
2
H, NCH2CH2CH2CH3), 1.54–1.46 (m,
2
H,
3,5-Difluoro-4-(trimethylsilyl)phenylboronic Acid Anhydride (2b):
This compound was prepared as described for 2a with use of Me3-
SiCl (2.17 g, 20 mmol, excess) dissolved in THF (5 mL) as electro-
phile. White powder, m.p. 160–163 °C, yield 1.8 g (85%). 1H NMR
([D6]acetone, 400 MHz): δ = 7.31 (d, J = 9.0 Hz, 2 H, Ph), 0.33 (t,
J = 1.0 Hz, 9 H, SiMe3) ppm. 13C{1H} NMR ([D6]acetone,
100.6 MHz): δ = 167.4 (dd, J = 241.5, 14.5 Hz), 116.6 (d, J =
26.0 Hz), 115.7 (t, J = 34.0 Hz), 0.2 ppm. 11B NMR ([D6]acetone,
64.16 MHz): δ = 28 ppm. C9H11BF2OSi (212.08): calcd. C 50.97,
H 5.23; found C 51.08, H 5.18.
NCH2CH2CH2CH3), 1.20–1.11 (m, 2 H, NCH2CH2CH2CH3), 0.84
(t, J = 7.0 Hz, 3 H, NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3,
100.6 MHz): δ = 134.7, 132.9, 122.6, 63.1, 59.9, 57.5, 26.9, 20.1,
13.7 ppm. 11B NMR (CDCl3, 64.16 MHz):
δ
=
7 ppm.
C14H20BBr2NO2 (404.94): calcd. C 41.53, H 4.98, N 3.46; found C
41.67, H 4.75, N 3.49.
2-(3Ј-Bromo-5Ј-fluorophenyl)-6-butyl-(N–B)-1,3,6,2-dioxazabor-
ocane (11): Yield 16.5 g (96%), m.p. 119–121 °C. 1H NMR (CDCl3,
400 MHz): δ = 7.49 (d, J = 2.0 Hz, 1 H, Ph), 7.21 (dd, J = 9.0,
2.0 Hz, 1 H, Ph), 7.08 (dt, J = 8.0, 2.0 Hz, 1 H, Ph), 4.15–4.04
(m, 4 H, CH2O), 3.07–2.94 (m, 4 H, CH2N), 2.29–2.24 (m, 2 H,
NCH2CH2CH2CH3), 1.50–1.42 (m, 2 H, NCH2CH2CH2CH3),
1.16–1.07 (m, 2 H, NCH2CH2CH2CH3), 0.80 (t, J = 7.0 Hz, 3 H,
NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3, 100.6 MHz): δ =
162.4 (d, J = 250.5 Hz), 131.7 (d, J = 2.5 Hz), 121.8 (d, J = 8.5 Hz),
118.2 (d, J = 18.0 Hz), 117.8 (d, J = 25.0 Hz), 63.0, 59.8, 57.4,
26.8, 20.0, 13.6 ppm. 11B NMR (CDCl3, 64.16 MHz): δ = 8 ppm.
C14H20BBrFNO2 (344.03): calcd. C 48.88, H 5.86, N 4.07; found
C 48.70, H 5.67, N 4.12.
2,6-Difluoro-1,4-phenylenediboronic Acid Monohydrate (2c): This
compound was prepared as described for 2a, with B(OiPr)3 (2.17 g,
12 mmol) as electrophile. White powder, m.p. Ͼ 350 °C, yield 2.0 g
(90 %). 1H NMR ([D6]acetone, 400 MHz): δ = 7.84 [br, 2 H,
B(OH)2], 7.54 [br, 2 H, B(OH)2], 7.31 (dd, J = 7.5 Hz, 2 H, Ph),
3.29 (br., 2 H, H2 O) ppm. 1 3 C{1 H} NMR ([D6]acetone,
100.6 MHz): δ = 165.5 (dd, J = 244.0, 14.0 Hz), 139.7 (br), 116.3
(dd, J = 20.0, 5.5 Hz), 114.4 (br) ppm. 11B NMR ([D6]acetone,
64.16 MHz): δ = 28 ppm. C6H6B2F2O4·H2O (219.75): calcd. C
32.80, H 3.67; found C 33.04, H 3.59.
6-Butyl-2-[2Ј-fluoro-5Ј-(trifluoromethyl)phenyl]-(N–B)-1,3,6,2-diox-
1
2,4-Difluoro-3-(methoxycarbonyl)phenylboronic Acid (3a): This
compound was prepared as described for 2a, starting with azaester
3. White powder, m.p. 220–225 °C, yield 1.8 g (83%). 1H NMR
([D6]acetone, 400 MHz): δ = 7.89 (q, J = 8.0 Hz, 1 H, Ph), 7.12
(td, J = 8.0, 1.0 Hz, 1 H, Ph), 3.91 (s, 3 H, OMe) ppm. 13C{1H}
NMR ([D6]acetone, 100.6 MHz): δ = 164.6 (dd, J = 254.0, 6.5 Hz),
162.6, 162.3 (dd, J = 255.0, 7.0 Hz), 140.2 (t, J = 11.0 Hz), 112.4
(dd, J = 10.5, 3.0 Hz), 53.1 ppm. 11B NMR ([D6]acetone,
64.16 MHz): δ = 28 ppm. C8H7BF2O4 (215.95): calcd. C 44.50, H
3.27; found C 44.71, H 3.12.
azaborocane (12): Yield 16.0 g (96%), m.p. 107–108 °C. H NMR
(CDCl3, 400 MHz): δ = 7.94 (m, 1 H, Ph), 7.46 (m, 1 H, Ph), 6.97
(t, J = 9.0 Hz, 1 H, Ph), 4.13–4.02 (m, 4 H, CH2O), 3.16–3.02 (m,
4 H, CH2N), 2.56–2.52 (m, 2 H, NCH2CH2CH2CH3), 1.54–1.46
( m , 2 H , N C H 2 C H 2 C H 2 C H 3 ) , 1 . 1 6 – 1 . 0 7 ( m , 2 H ,
N C H 2 C H 2 C H 2 C H 3 ) , 0 . 8 1 ( t , J = 7 . 0 H z , 3 H ,
NCH2CH2CH2CH3) ppm. 13C NMR (CDCl3, 100.6 MHz): δ =
168.1 (d, J = 246.5 Hz), 133.4 (m), 126.9 (m), 125.5 (q, J =
31.0 Hz), 124.4 (d, J = 271.5 Hz), 115 ppm. 1 (d, J = 28.0 Hz), 62.7,
58.1, 57.5, 26.6, 20.0, 13.4 ppm. 11B NMR (CDCl3, 64.16 MHz): δ
= 7 ppm. C15H20BF4NO2 (333.13): calcd. C 54.08, H 6.05, N 4.20;
found C 53.85, H 5.92, N 4.26.
2,4-Difluoro-3-(trimethylsilyl)phenylboronic Acid (3b): This com-
pound was prepared as described for 2b, starting with azaester 3.
White powder, m.p. 88–90 °C, yield 2.1 g (90%). 1H NMR ([D6]-
acetone, 400 MHz): δ = 7.80 (q, J = 8.0 Hz, 1 H, Ph), 7.20 [d, J =
2.5 Hz, 2 H, B(OH)2], 6.91 (t, J = 8.0 Hz, 1 H, Ph), 0.36 (t, J =
1.5 Hz, 9 H, SiMe3 ) ppm. 1 3 C{1 H} NMR ([D6 ]acetone,
100.6 MHz): δ = 172.2 (dd, J = 243.5, 15.0 Hz), 169.4 (dd, J =
245.0, 17.0 Hz), 140.1 (t, J = 10.5 Hz), 113.1 (dd, J = 38.0,
34.0 Hz), 111.7 (dd, J = 25.0, 3.5 Hz), 0.3 (t, J = 3.0 Hz) ppm.
11B NMR ([D6]acetone, 64.16 MHz): δ = 28 ppm. C9H13BF2O2Si
(230.09): calcd. C 46.98, H 5.69; found C 47.16, H 5.46.
6-tert-Butyl-2-(3Ј,5Ј-difluorophenyl)-(N–B)-1,3,6,2-dioxazaborocane
(13): Yield 14.0 g (99 %), m.p. 212–215 °C. 1H NMR (CDCl3,
400 MHz): δ = 7.24 (dt, J = 7.0, 2.0 Hz, 2 H, Ph), 6.66 (tt, J = 9.0,
2.5 Hz, 1 H, Ph), 4.16 (t, J = 6.0 Hz, 4 H, CH2O), 3.10 (br., 4 H,
CH2N), 1.14 (s, 9 H, tBu) ppm. 13C NMR (CDCl3, 100.6 MHz): δ
= 162.4 (dd, J = 245.5, 11.0 Hz), 116.4 (dd, J = 14.0, 4.5 Hz), 102.7
(t, J = 26.0 Hz), 63.1, 61.7, 53.5, 26.4 ppm. 11B NMR (CDCl3,
64.16 MHz): δ = 8 ppm. C14H20BF2NO2 (283.13): calcd. C 59.39,
H 7.12, N 4.95; found C 59.17, H 7.00, N 5.04.
3,5-Difluoro-4-(methoxycarbonyl)phenylboronic Acid (2a): A solu-
tion of 2 (2.84 g, 10 mmol) in THF (20 mL) was added at –75 °C to
2,4-Difluoro-3-formylphenylboronic Acid (3c): This compound was
prepared as described for 3a, with Me2NCHO as electrophile.
4330
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4325–4332

Functionalization of Dihalophenylboronic Acids by Deprotonation
White powder, m.p. 225–230 °C, yield 1.8 g (83%). 1H NMR ([D6]-
acetone, 400 MHz): δ = 10.31 (s, 1 H, CHO), 8.02 (q, J = 8.0 Hz,
1 H, Ph), 7.50 [br, 2 H, B(OH)2], 7.12 (td, J = 8.0, 1.0 Hz, 1 H,
3,5-Dichloro-4-(trimethylsilyl)phenylboronic Acid Anhydride (7b):
This compound was prepared by starting with azaester 7 as de-
scribed for 2b. White powder, m.p. 285–290 °C, yield 2.3 g (95%).
Ph) ppm. 13C{1H} NMR ([D6]acetone, 100.6 MHz): δ = 185.2, 1H NMR ([D6]acetone, 400 MHz): δ = 7.72 (s, 2 H, Ph), 0.48 (s, 9
167.9 (dd, J = 254.0, 4.5 Hz), 164.9 (dd, J = 264.5, 6.0 Hz), 143.7
H, SiMe3) ppm. 13C{1H} NMR ([D6]acetone, 100.6 MHz): δ =
(t, J = 12.0 Hz), 114.4 (t, J = 13.0 Hz), 113.0 (d, J = 20.0 Hz), 141.8, 138.6, 134.7, 2.9 ppm. 11B NMR ([D6]acetone, 64.16 MHz):
53.1 ppm. 11B NMR ([D6]acetone, 64.16 MHz): δ = 28 ppm. δ = 28 ppm. C9H11BCl2OSi (244.99): calcd. C 44.12, H 4.53; found
C7H5BF2O3 (185.92): calcd. C 45.22, H 2.71; found C 45.24, H
2.64.
C 44.52, H 4.35.
2-[3Ј,5Ј-Dibromo-4Ј-(trimethylsilyl)phenyl]-4,4,5,5-tetramethyl[1,3,2]-
dioxaborolane (10a): This compound was prepared by starting with
azaester 10 as described for 7b. The crude boronic acid was mixed
with pinacol (1.18 g, 10 mmol) and MgSO4 (1.0 g) in Et2O (30 mL).
After filtration the solvent was removed in vacuo. Recrystallization
of the residue from hexane (20 mL) at –30 °C afforded the title
compound as a white powder, m.p. 140–143 °C, yield 2.4 g (55%).
1H NMR (CDCl3, 400 MHz): δ = 7.88 (s, 2 H, Ph), 1.32 (s, 12 H,
Me), 0.55 (s, 9 H, SiMe3 ) ppm. 1 3 C{1 H} NMR (CDCl3,
100.6 MHz): δ = 143.8, 138.5, 130.7, 84.4, 24.8, 3.8 ppm. 11B NMR
(CDCl3, 64.16 MHz): δ = 27 ppm. 11B NMR (CDCl3, 64.16 MHz):
δ = 28 ppm. C15H23BBr2O2Si (434.05): calcd. C 41.51, H 5.34;
found C 41.90, H 5.26.
3,4-Difluoro-5-(trimethylsilyl)phenylboronic Acid (4a): This com-
pound was prepared as described for 2b, starting with azaester 4,
except that the reaction mixture was allowed to warm to 0 °C after
the addition of Me3SiCl. White powder, m.p. 165–167 °C, yield
1
2.1 g (90%). H NMR ([D6]acetone, 400 MHz): δ = 7.73 (m, 1 H,
Ph), 7.68 (m, 1 H, Ph), 0.31 (d, J = 1.0 Hz, 9 H, SiMe3) ppm.
13C{1H} NMR ([D6]acetone, 100.6 MHz): δ = 156.4 (dd, J = 242.0,
11.5 Hz), 150.3 (dd, J = 248.0, 16.0 Hz), 136.8 (dd, J = 10.5,
4.0 Hz), 128.6 (d, J = 24.0 Hz), 124.3 (d, J = 15.0 Hz), –1.0 ppm.
11B NMR ([D6]acetone, 64.16 MHz): δ = 28 ppm. C9H13BF2O2Si
(230.09): calcd. C 46.98, H 5.69; found C 46.79, H 5.59.
4,5-Difluoro-1,3-phenylenediboronic Acid (4b): This compound was
prepared as described for 4a, with B(OiPr)3 (2.17 g, 12 mmol) as
electrophile. White powder, m.p. Ͼ 400 °C, yield 1.7 g (85%). 1H
NMR ([D6]acetone, 400 MHz): δ = 7.98 (d, J = 5.0 Hz, 1 H, Ph),
7.71 (m, 1 H, Ph), 7.42 [br, 2 H, B(OH)2], 7.37 [br, 2 H,
B(OH)2] ppm. 13C{1H} NMR ([D6]acetone, 100.6 MHz): δ = 156.1
(dd, J = 250.0, 11.5 Hz), 150.5 (dd, J = 246.0, 14.5 Hz), 137.8 (dd,
J = 7.5, 4.0 Hz), 131.3 (br), 124.7 (d, J = 15.0 Hz), 123.6 (br) ppm.
11B NMR ([D6]acetone, 64.16 MHz): δ = 28 ppm. C6H6B2F2O4
(201.73): calcd. C 35.72, H 3.00; found C 35.74, H 2.73.
2-{3Ј-Bromo-5Ј-fluoro-4Ј-iodophenyl}-4,4,5,5-tetramethyl[1,3,2]di-
oxaborolane (11a): This compound was prepared by starting with
11 as described for 2a, with iodine (2.8 g, 11 mmol) as electrophile
dissolved in THF (10 mL) at –80 °C. After hydrolysis with aq. sul-
furic acid (1.5 , 10 mL) the organic phase was consecutively sepa-
rated and concentrated under reduced pressure. The dark oily resi-
due was dissolved in Et2O (30 mL) and washed with aq. Na2S2O3
(20 wt.-%, 20 mL). After removal of ether the residue was washed
with water and hexane and dried. The crude boronic acid was
mixed with pinacol (1.18 g, 10 mmol) and MgSO4 (1.0 g) in Et2O
(30 mL). After filtration the solvent was removed in vacuo.
Recrystallization of the residue from hexane (20 mL) at –20 °C af-
forded the title compound as colourless crystals, m.p. 92–94 °C,
2,3-Difluoro-4-(trimethylsilyl)phenylboronic Acid (5a): This com-
pound was prepared as described for 4a, starting with azaester 5.
White powder, m.p. 63–66 °C, yield 1.8 g (80%). 1H NMR ([D6]-
acetone, 400 MHz): δ = 7.46 (dd, J = 7.5, 5.0 Hz, 1 H, Ph), 7.41
[br, 2 H, B(OH)2], 7.18 (ddd, J = 7.5, 4.5, 1.0 Hz, 1 H, Ph), 0.32
(d, J = 1.0 Hz, 9 H, SiMe3) ppm. 13C{1H} NMR ([D6]acetone,
100.6 MHz): δ = 154.8 (dd, J = 240.0, 13.0 Hz), 154.2 (dd, J =
247.0, 14.0 Hz), 131.6 (d, J = 26.0 Hz), 131.1 (dd, J = 6.0, 3.0 Hz),
129.9 (dd, J = 9.0, 4.0 Hz), –1.1 ppm. 11B NMR ([D6]acetone,
64.16 MHz): δ = 28 ppm. C9H13BF2O2Si (230.09): calcd. C 46.98,
H 5.69; found C 47.35, H 5.43.
1
yield 3.1 g (73%). H NMR (400 MHz, CDCl3): δ = 7.81 (s, 1 H,
Ph), 7.34 (dd, J = 8.0, 1.0 Hz 1 H, Ph), 1.33 (s, 12 H, Me) ppm.
13C{1H} NMR (100.6 MHz, CDCl3): δ = 162.2 (d, J = 248 Hz),
133.9 (d, J = 2.5 Hz), 130.7, 119.0 (d, J = 23.0 Hz), 94.2 (d, J
= 27.0 Hz), 84.6, 24.8 ppm. 11B NMR (64.2 MHz, CDCl3): δ =
25.3 ppm. C12H14BBrFIO2 (426.86): calcd. C 33.77, H 3.31; found
C 34.12, H 3.00.
2-Fluoro-5-(trifluoromethyl)-1,3-phenylenediboronic Acid (12a): This
compound was prepared by starting with azaester 12 as described
for 2c, except that the reaction mixture was allowed to warm to
0 °C after the addition of B(OiPr)3. White powder, dec. Ͼ350 °C,
2,3-Difluoro-1,4-phenylenediboronic Acid (5b): This compound was
prepared as described for 5a, with B(OiPr)3 (2.17 g, 12 mmol) as
electrophile. White powder, m.p. Ͼ 400 °C, yield 1.8 g (90%). 1H
NMR ([D6]acetone, 400 MHz): δ = 7.41 (t, J = 1.5 Hz, 2 H,
Ph) ppm. 13C{1H} NMR ([D6]acetone, 100.6 MHz): δ = 154.2 (dd,
J = 246.0, 16.0 Hz), 130.4 (t, J = 6.0 Hz), 126.2 (br) ppm. 11B
NMR ([D6]acetone, 64.16 MHz): δ = 28 ppm. C6H6B2F2O4
(201.73): calcd. C 35.72, H 3.00; found C 35.86, H 2.62.
1
yield 2.1 g (83%). H NMR ([D6]acetone, 400 MHz): δ = 8.06 (d,
J
=
4.0 Hz,
100.6 MHz): δ = 173.1 (d, J = 251.0 Hz), 136.0 (d, J = 7.5 Hz),
126.1 (q, J = 32.0 Hz), 125.3 (q, J = 271.5 Hz), 122.3 (br) ppm. 11
NMR ([D6]acetone, 64.16 MHz): 28 ppm. C7H6B2F4O4
2
H, Ph) ppm. 13C{1H} NMR ([D6]acetone,
B
δ
=
(251.74): calcd. C 33.40, H 2.40; found C 33.56, H 2.37.
2-(3Ј,5Ј-Dichloro-4Ј-formylphenyl)-4,4,5,5-tetramethyl[1,3,2]dioxa-
borolane (7a): This compound was prepared by starting from 7 as
described for 3c. The crude boronic acid was mixed with pinacol
(1.18 g, 10 mmol) and MgSO4 (1.0 g) in Et2O (30 mL). After fil-
tration the solvent was removed in vacuo. Recrystallization of the
residue from hexane (20 mL) at –30 °C afforded the title compound
as pale yellow crystals, m.p. 130–132 °C, yield 2.6 g (87%). 1H
NMR (CDCl3, 400 MHz): δ = 10.44 (s, 1 H, CHO), 7.72 (s, 2 H,
Ph), 1.30 (s, 12 H, Me) ppm. 13C{1H} NMR (CDCl3, 100.6 MHz):
δ = 188.9, 135.9, 135.2, 131.9, 84.9, 24.7 ppm. 11B NMR (CDCl3,
64.16 MHz): δ = 27 ppm. C13H15BCl2O3 (300.98): calcd. C 51.88,
H 5.02; found C 51.84, H 5.04.
Acknowledgments
This work was supported by the Warsaw University of Technology
and by the Polish Ministry of Science and Higher Education (Grant
No. N N205 055633). The support by Aldrich Chemical Co., Mil-
waukee, WI, U.S.A., through continuous donation of chemicals
and equipment is gratefully acknowledged.
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Received: May 11, 2009
Published Online: July 20, 2009
4332
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