Stereoselective Bromoboration of Acetylene with Boron Tribromide: Preparation and Cross-Coupling Reactions of (Z)-Bromovinylboronates

Article abstract of DOI:10.1021/acs.joc.0c00341

The mechanism of acetylene bromoboration in neat boron tribromide was studied carefully by means of experiment and theory. Besides the syn-addition mechanism through a four-center transition state, radical and polar anti-addition mechanisms are postulated, both triggered by HBr, which is evidenced also to take part in the Z/E isomerization of the product. The proposed mechanism is well supported by ab initio calculations at the MP2/6-31+G? level with Ahlrichs' SVP all-electron basis for Br. Implicit solvation in CH₂Cl₂ has been included using the PCM and/or SMD continuum solvent models. Comparative case studies have been performed involving the B3LYP/6-31+G? with Ahlrichs' SVP for Br and MP2/Def2TZVPP levels. The mechanistic studies resulted in development of a procedure for stereoselective bromoboration of acetylene yielding E/Z mixtures of dibromo(bromovinyl)borane with the Z-isomer as a major product (up to 85%). Transformation to the corresponding pinacol and neopentyl glycol boronates and stereoselective decomposition of their E-isomer provided pure (Z)-(2-bromovinyl)boronates in 57-60% overall yield. Their reactivity in a Negishi cross-coupling reaction was tested. An example of the one-pot reaction sequence of Negishi and Suzuki-Miyaura cross-couplings for synthesis of combretastatin A4 is also presented.

Full text of DOI:10.1021/acs.joc.0c00341

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Article
Stereoselective Bromoboration of Acetylene with Boron Tribromide:
Preparation and Cross-Coupling Reactions of
(Z)‑Bromovinylboronates
‡
‡
‡
‡
́
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̌
́
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Jan Polasek, Jan Paciorek, Jakub Stosek, Hugo Semrad, Marketa Munzarova, and Ctibor Mazal*
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ABSTRACT: The mechanism of acetylene bromoboration in neat boron tribromide was studied carefully by means of experiment
and theory. Besides the syn-addition mechanism through a four-center transition state, radical and polar anti-addition mechanisms
are postulated, both triggered by HBr, which is evidenced also to take part in the Z/E isomerization of the product. The proposed
mechanism is well supported by ab initio calculations at the MP2/6-31+G* level with Ahlrichs’ SVP all-electron basis for Br. Implicit
solvation in CH2Cl2 has been included using the PCM and/or SMD continuum solvent models. Comparative case studies have been
performed involving the B3LYP/6-31+G* with Ahlrichs’ SVP for Br and MP2/Def2TZVPP levels. The mechanistic studies resulted
in development of a procedure for stereoselective bromoboration of acetylene yielding E/Z mixtures of dibromo(bromovinyl)borane
with the Z-isomer as a major product (up to 85%). Transformation to the corresponding pinacol and neopentyl glycol boronates and
stereoselective decomposition of their E-isomer provided pure (Z)-(2-bromovinyl)boronates in 57−60% overall yield. Their
reactivity in a Negishi cross-coupling reaction was tested. An example of the one-pot reaction sequence of Negishi and Suzuki−
Miyaura cross-couplings for synthesis of combretastatin A4 is also presented.
elimination of hydrogen bromide was discarded in that study
on the basis of the result obtained for hydrogen chloride in
analogous chloroboration.
INTRODUCTION
■
Bromoboration reaction of alkynes belongs to a standard
toolkit of synthetic organoboron chemistry. Introduced by
Lappert and Prokai in the 1960s,1 it fully manifested its
application potential in stereoselective syntheses of alkenes
developed by Suzuki in the late 1980s.2 The syntheses took
advantage of very good stereo- and regioselectivity of the
bromoboration, which proceeded strictly in a syn manner with
terminal alkynes1−3 but yielded only trans product with
acetylene. The latter result was attributed to isomerization of
a primarily formed cis adduct, (Z)-dibromo(2-bromovinyl)-
borane, (Z)-1, to the thermodynamically more stable (E)-1.
BBr3 was taken as a catalyst of such isomerization.1,4 This view
on the acetylene bromoboration mechanism was later
supported also by quantum chemical calculations made by
Wang and Uchyiama, who investigated halometalation
reactions of alkynes5 and concluded among others that BBr3
can catalyze the isomerization of its primarily formed cis
adduct with acetylene. The free energy barrier found for such
isomerization was quite high (30.0 kcal/mol) but comparable
to that of cis addition (25.9 kcal/mol) and still lower than the
barrier of a thermal process (54.6 kcal/mol). Interestingly, a
mechanism that would involve successive addition and
Since the catalytic effect of BBr3 was generally accepted, the
bromoboration pathway to cis-bromovinyl boron derivatives
was ignored even if it would offer a straightforward way to a
synthetically valuable precursor for introduction of a cis-
substituted CC double bond into more complex molecules,
analogously to the stereocontrolled syntheses of olefins
exploiting other alkyne bromoboration products.6 Never-
theless, the need for such precursor led recently to the
preparation of two cis-halovinylboronates, however, by multi-
step procedures.7 Their synthetic potential was proved
immediately.8 It also attracted our attention because one of
the authors had the opportunity to bromoborate acetylene in
the early 1990s,9 and their unpublished results indicated
Received: February 10, 2020
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strongly that some stereocontrol of the reaction is possible.
Therefore, we decided to reinvestigate the reaction in more
detail, now focusing on its stereochemistry. Here, we report on
novel experimental findings that resulted in better insight into
the reaction mechanism and in a straightforward procedure for
preparation of cis-bromovinylboronates. Our ab initio quantum
chemical calculations are in good agreement with experimental
data and support the proposed mechanistic pathways very well.
85:15 (Table 1, entry 2; SI, Figure S3). The usual
stereochemical outcome oscillated between 20% and 40% of
trans adduct. When we tried further to suppress the role of
HBr by addition of a small amount of triethylamine (TEA) to
the reaction mixture, we observed that contrary to our
expectations, the amount of trans adduct increased and so
did the reaction rate (Table 1, entries 4 and 5; SI, Figure S4).
The latter indicates that the trans isomer (E)-1 is formed not
solely by the isomerization of (Z)-1 but also by some
additional mechanism. Since the reaction of HBr with TEA
produces bromide anion, we decided to find out whether that
could play some role in the formation of (E)-1. When a small
amount of tetrabutylammonium bromide (TBAB) was added
to the reaction mixture, the rate of the bromoboration reaction
increased along with the relative amount of (E)-1. A larger
amount of TBAB further increased the reaction rate, but an
excessive amount of higher adducts11 was found in the reaction
mixture already after 90 min when the conversion was almost
RESULTS AND DISCUSSION
■
When a neat commercially available sample of BBr3 reacts with
gaseous acetylene at temperatures around 0 °C, mixtures of
(Z)-1 and (E)-1 are formed with the Z/E ratio varying from 0
to 0.4 (Table 1; entry 1). It is hard to predict the
a
Table 1. Bromoboration of Acetylene with BBr3
1
complete (see H and 11B NMR spectra in SI, Figure S5).
For the reasons discussed above, we concluded that apart
from the previously postulated isomerization of (Z)-1,5 an
alternative route to (E)-1 must exist. A direct anti-addition
pathway (Scheme 1) should be taken into account despite only
limited literature examples that usually require proper steric
prerequisites.12
entry
additive
time (h) conversion (%) (Z)-1/(E)-1
1
2
3
4
5
6
7
b
c
6−8
6−8
8
3:7 − 0
>95
90
66
90
90
95
85:15
d
30 μL of H2O
20 μL of TEA
100 μL of TEA
10 mg of TBAB
170 mg of TBAB
3:7
4
2:1
2:9
1:1
0.5
2.5
1.5
Scheme 1. Modified Reaction Scheme of Acetylene
Bromoboration
e
a
b
Typically acetylene was introduced into 0.5 mL of BBr3. BBr3 as
c
purchased. BBr3 purified by distillation with Mg turnings in an argon
atmosphere. More than 98% of (E)-1 after overnight standing. A
d
e
large amount of higher adducts was formed.
stereochemical outcome of the bromoboration which varies
with the quality of BBr3 used, but standard workup to the
corresponding boronates provides pure trans isomers in any
case. However, when we carried out the reaction in a gastight
NMR tube and stopped it at approximately 20% conversion,
the Z/E ratio of 1 isomers did not change, even after standing
overnight in the NMR tube at ambient temperature (SI, Figure
S1). Hence, the previously suggested mechanism of BBr3-
catalyzed isomerization5 does not apply under our exper-
imental setup. Therefore, we turned our attention to hydrogen
bromide, an inevitable impurity in BBr3. It was ruled out
previously for analogy with HCl but still appeared to us as the
most likely substance responsible for the stereoconversion. Its
presence in the reaction mixture was inferred from the
formation of vinyl bromide as a reaction byproduct and
subsequently confirmed by NMR spectra of neat BBr3. The
HBr proton signal was found at −3.80 ppm in pure BBr3 and at
−2.97 ppm in CDCl3 solutions.10 Depletion of HBr by its
addition to acetylene in the course of the reaction would also
explain why the isomerization ceases. Therefore, we added a
small amount of water to BBr3 prior to the reaction to increase
the HBr concentration. A larger amount of vinyl bromide and
even 1,2-dibromoethane was formed in such reaction, and the
trans adduct prevailed in the isomers mixture (Table 1, entry
3). Also, the isomerization reached completion overnight (SI,
Figure S2). This result well supported the proposed role of
HBr.
Theoretical data which could help to understand our
findings summarized in Scheme 1 were hardly available in
the literature. Although haloboration has been used in organic
synthesis for several decades, the only available computational
analysis of its mechanism including bromoboration with BBr3
is the already mentioned study of Wang and Uchiyama from
2012.5 Apart from stereoconversion mediated by boron halides
BX3, which is not observed in our system, the authors
considered also the isomerization promoted by hydrogen
halide and found it to be energetically even more demanding
(45 kcal/mol for HCl in chloroboration). To understand the
catalytic role of HBr and to explore the possibility of a direct
pathway to the trans adduct, we conducted a series of ab initio
calculations at the B3LYP and MP2 levels of theory.
Our results confirm the previously postulated5 four-center
transition state on the way from acetylene and BBr3 to (Z)-1
(TS1 in Figure 1) and the higher stability of (E)-1 with respect
to (Z)-1. Interestingly, MP2 calculation, which is in good
agreement with the previous results, predicts a significantly
higher (by 10 kcal/mol) activation barrier but a 2 kcal/mol
more stable product than B3LYP calculation. The MP2
method includes dispersion interaction per se and is tradition-
ally considered along with the much more demanding CCSD
approach, a benchmark for the approximate dispersion
correction schemes employed with DFT.13
To avoid a potential catalytic effect of HBr, we carefully
purified BBr3 prior to the reaction. Nevertheless, the best
stereochemical result did not overcome the cis/trans ratio of
B
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potential energy surface. This is probably also the reason why
some of the imaginary frequencies in Table S10 are very low,
with the legitimacy of all transition states being confirmed by
the IRC method.
Returning to counterintuitive energy ordering for TS6 vs
IM5, any transition state (or intermediate) is searched for as a
first-order saddle point (or local minimum) on the potential
energy surface (PES). Potential energy (denoted here as ETOT
)
is then given by the sum of the total electron energy and the
nuclear repulsion. For the thermodynamical and kinetical
parameters, ETOT must be transferred into Gibbs free energy by
adding the zero-point energy, the enthalpy correction terms,
and the entropy contribution. In particular, the latter term may
be significant and hard to describe with accuracy exceeding ca.
2 kcal/mol for continuum solvent models.15 Thus, while the
relative ordering of Gibbs free energies suggests a barrierless
transformations from IM4 to IM5 and from IM5 to (E)-1+Br•,
considering the 2 kcal/mol uncertainty in any of the Gibbs
energies, the transformations may as well proceed through very
small barriers. We note that neither use of different basis set
nor a different solvent model switched the counterintuitive
qualitative Gibbs free energies ordering of TS6, IM5, and TS7
(see SI Table S1). Note also that barrierless reactions have
been reported for radical reactions previously, including alkyne
hydroboration.15,16
However, from the quantitative point of view, it must be
stressed that solvent treatment influences the energies of
loosely bound IM5. Figure 2 covers the reaction profile with
the SMD model since with PCM model the energy of IM5
comes out unexpectedly high, see Figure S8. IM5 is already a
complex of products whose energy should not largely exceed
that of (E)-1+Br•, which is just a different weak complex of the
same two entities. The energy of IM5 is also by far the most
dramatic difference between Figures 2 and Figure S8. When
PCM is employed, calculations appear to be more basis-set
demanding in order to provide chemically realistic results than
in the case of the SMD model. A complete recomputation of
all data with a larger basis set as well as with inclusion of an
explicit solvent molecule is the subject of a separate study.
Figure 1. Gibbs free energy profile for BBr3 addition to acetylene at
MP2/6-31+G* (black) and B3LYP+GD3BJ/6-31+G* (red) levels
with Ahlrichs’ SVP all-electron basis for Br. Implicit solvation in
CH2Cl2 has been included using the PCM model. Key to atom colors:
Br = red, B = pink, C = gray, H = white.
In order to elucidate our experimental results that supported
some role of HBr in the cis/trans isomerization process, we
conducted the calculations for addition−elimination of HBr.
The reaction barrier obtained, 41 kcal/mol (SI, Figure S6),
was, however, comparable with the previous results for HCl in
chloroboration5 and supported the conclusions made then that
declined such mechanism. Since formation of 1,2-dibromo-
ethane in the reaction mixture indicates that HBr prefers a
radical pathway of the addition to vinyl bromide in BBr3,14 we
suggested investigating also a free radical mechanism of Z/E
isomerization contrary to closed-shell pathways explored
previously. As shown in Figure 2, the open-shell pathway
assumes an attack of bromine radical initially formed by
homolysis of HBr to (Z)-1. It results in an intermediate IM1,
rotated through three transition states into IM4. Note that
bromine radical prefers to attack the double bond at the
“boron end”. The attack of the opposite end requires more
than double the energy barrier (cf. Figure S7). The
energetically most demanding step is the release of Br radical
from IM4 to form (E)-1. That TS6 is located below the
intermediate IM5 is due to a high entropy penalty estimated
for IM5 (cf. Table S10) combined with a relatively flat
Figure 2. Gibbs free energy (black) and total electronic energy (gray) profiles for Z/E isomerization of 1 catalyzed with bromine radical at the
MP2/6-31+G* level with Ahlrichs’ SVP all-electron basis for Br. Implicit solvation in CH2Cl2 has been included using the SMD model. Key to
atom colors: Br = red, B = pink, C = gray, H = white.
C
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Provided that vinyl bromide found in the reaction mixture
was formed in a radical addition of HBr to acetylene, we were
curious whether the intermediate bromovinyl radical can react
with BBr3 instead of trapping a hydrogen atom from another
molecule of HBr. Our calculations (Figure 3) show that the
can add BBr3 in the presence of bromide anion with a relatively
low energy barrier (10 kcal/mol) through transition states
TS10 and TS11 to the intermediate IM8 with quaternary
boron that releases bromide anion upon assistance of BBr3
through TS12, yielding (E)-1. It means that such anti-addition
pathway can compete with the syn-addition mechanism to (Z)-
1 very effectively when bromide anions are present (Figure 4).
Explicit solvation of Br− with BBr3 is essential for splitting the
B−Br bond of IM8; no local minimum on the PES was
detected otherwise. This is different from the polar addition−
elimination mechanism of Z/E isomerization by means of HBr
where ion-pair intermediates (cf. Figure S6), which should also
be solvent sensitive, were local minima not only with SMD but
also even in the gas phase. From this we conclude that the
orbital, “Lewis acidic” role of BBr3, necessary to break the
B−Br bond is more crucial than the electrostatic, ion-pair-
stabilizing role of this nonpolar solvent. An analogous
calculation as in Figure 4 has been performed at the B3LYP
+GD3BJ level with the same basis and solvent treatment. The
first activation barrier was 7 kcal/mol, the loosely bound IM7
has not been detected, and TS10 fell directly by −48 kcal/mol
into IM8.
Figure 3. Gibbs free energy profile for the formation of (E)-1 by
reaction of bromovinyl radical with BBr3. MP2/6-31+G* with
Ahlrichs’ SVP all-electron basis for Br, and implicit solvation in
CH2Cl2 has been included using the PCM model. Key to atom colors:
Br = red, B = pink, C = gray, H = white.
Our findings about the acetylene bromoboration are
summarized in Scheme 2. While (Z)-1 is formed only by a
synchronous syn addition of BBr3, several pathways lead to
(E)-1: Isomerization of (Z)-1 catalyzed by bromine radical,
radical anti addition of BBr3 with bromine radical as a chain
carrier, and polar anti addition of BBr3 and bromide anion.
We believe that hydrogen bromide is a source of bromine
radicals as well as the anions. The effect of both is catalytic, and
so even a small amount of HBr can affect the stereoselectivity
of bromoboration significantly, but since HBr is consumed by
addition to acetylene, formation of (E)-1 ceases in the course
of the reaction. The extent of the isomerization as well as the
anti additions can be diminished by careful purification of
starting BBr3, but even in the best runs, the content of (Z)-1 in
the reaction mixture did not exceed 85%.
more stable trans-bromovinyl radical17 reacts with BBr3
smoothly with a very low energy barrier, affording a radical
intermediate that is the same as IM4 in Figure 2 and after
release of bromine radical thus affords (E)-1. The same
calculation has been performed at the B3LYP+GD3BJ/6-
31+G* level with Ahlrichs’ SVP all-electron basis for Br. The
relative energies differed at most by 1.2 kcal/mol for the first
step and at most by 3 kcal/mol for the second step, where
explicit solvation by a single BBr3 molecule was considered in
the B3LYP approach. That means that HBr is not only causing
the isomerization of (Z)-1 but also opens an anti-addition
pathway to (E)-1. The reaction of bromovinyl radical with
BBr3 is an example of homolytic substitution that is rare with
carbon-centered radicals at a boron reaction center.18
Although we were unable to carry out the bromoboration of
acetylene with BBr3 with better stereoselectivity, we exploited
the reaction to develop a simple and straightforward procedure
for preparation of pure (Z)-bromovinylboronates. That was
To elucidate the reaction rate increase and predominant
formation of (E)-1 after addition of TEA or TBAB (Table 1), a
reaction system consisting of acetylene, BBr3, and bromide
anion was subjected to calculation. It showed that acetylene
Figure 4. Gibbs free energy (black) and total electronic energy (gray) profiles for BBr3 anti-addition catalyzed with bromine anion at the MP2/6-
31+G* level with Ahlrichs’ SVP all-electron basis for Br. Implicit solvation in CH2Cl2 has been included using the PCM model. For graphical
reasons, Gibbs energy values plotted in blue were added to a constant offset, making the energy of IM8+BBr3 equal to that of IM8. Key to atom
colors: Br = red, B = pink, C = gray, H = white.
D
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in satisfactory overall yields, 60% and 57%, respectively
(Scheme 3).
Scheme 2. Possible Reaction Pathways of Acetylene
Bromoboration
Scheme 3. Preparation of (Z)-Bromovinylboronates
Naturally, we tried to prove the usefulness of the (Z)-
bromovinylboronates in cross-coupling reactions. In our
preliminary experiments, (Z)-3 was used for its expected
better stability. The Negishi cross-coupling reaction ran with
full retention of configuration and with very good conversion.
However, the low stability of the resulting vinylboronates 5 on
a silica gel column decreased the isolated yields markedly
(Scheme 4).
possible since (E)-bromovinylboronates are much more
sensitive to a base elimination due to the trans configuration
that favors leaving of bromide anion after base attack of
boronate function. The crude mixture of both isomers of 1 was
first reacted with diethyl ether to get an E/Z mixture of diethyl
boronates 2, which were then transesterified to more stable
cyclic boronates 3 and 4 by reaction with pinacol and 2,2-
dimethylpropylene glycol (DMPG), respectively. The way
through diethyl boronates was used because the reaction of 1
with ether, contrary to that with glycol, does not produce HBr
that could catalyze the isomerization.
a
Scheme 4. Negishi Cross-Coupling Reaction of (Z)-3
To compare the different stability of cyclic boronates
stereoisomers, a pentane solution of 3 with a majority of the
E-isomer was treated with a methanolic solution of potassium
acetate, and the diastereoisomer content was analyzed by GC.
While the E-isomer decomposed completely in 0.5 h, the
content of (Z)-3 remained almost unchanged (Figure 5).
In a preparative procedure the E/Z mixtures of cyclic
boronates 3 or 4 with about 70% of (Z)-isomer were treated
with potassium acetate suspended in pentane and methanol
(12:1) and gave the pure bromovinylboronates (Z)-3 or (Z)-4
a
In a general reaction 100 mg of (Z)-3 reacted with 2 equiv of
b
c
organozinc chloride. de > 94%. de > 96%
The issue of a low stability of vinyl boronates was
circumvented already by Suzuki4b who used a one-pot
procedure that reacted the Negishi coupling products in a
subsequent Suzuki−Miyaura reaction without isolation. We
used the one-pot procedure for synthesis of combretastatin A4
(6), a potent target in cancer chemotherapy,19 which is often
used as a benchmark of diastereoselective synthesis of cis-
stilbenes.20 The reaction sequence that used the fluoride anion
in the Suzuki−Miyaura step21 was found to be superior to that
with hydroxide base, probably because it suppresses ionization
of the bromophenol 7, which can make the oxidative addition
of palladium catalyst into the C−Br bond of the corresponding
phenolate more difficult. The isomer (Z)-6 was isolated in 70%
yield (over both coupling steps) with excellent stereoselectivity
(Scheme 5).
Figure 5. Composition of an E/Z mixture of boronates 3 under the
influence of potassium acetate and methanol in pentane. Concen-
tration of (Z)-3 fluctuates because the samples taken from the stirred
heterogeneous reaction mixture contained small droplets of a polar
methanolic phase dispersed in pentane. Basic droplets contained only
(Z)-3 as (E)-3 readily decomposed in there.
In summary, we developed a simple, efficient, and highly
stereoselective protocol for preparation of valued synthetic
precursors, (Z)-bromovinylboronates 3 and 4. Our findings
E
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glycol (25.4 mmol) in diethyl ether (10 mL) was added, and the
reaction mixture was stirred for 1 h at room temperature. The
reaction mixture was poured into pentane (50 mL), filtered, washed
with water (50 mL), dried over MgSO4, and carefully evaporated (300
mbar, 40 °C), which afforded a mixture of (Z)- and (E)-
bromovinylboronates in a 65:35 ratio. The mixture was dissolved in
pentane (120 mL), then AcOK (2.17 g, 22.1 mmol) and methanol
(10 mL) were added, and the resulting mixture was stirred at room
temperature for 1.5 h. The mixture was then filtered, washed with
water (50 mL × 3), dried over MgSO4, and evaporated (300 mbar, 40
°C), which afforded (Z)-bromovinylboronate in satisfactory purity.
(Z)-2-(2-Bromovinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane,
(Z)-3. Pinacol was used in place of the glycol, yielding 2.30 g, 9.9
Scheme 5. Preparation of Combretastatin A4 in a One-Pot
Procedure
1
were based on a careful experimental and computational study
of the reaction mechanism of acetylene bromoboration with
boron tribromide. Besides the syn addition through a four-
center transition state, we proposed two other addition
mechanisms, a radical one and a polar one, both triggered by
hydrogen bromide and both yielding the thermodynamically
more stable (E)-isomer of product that can be also formed by a
HBr-catalyzed Z/E-isomerization. Careful removal of HBr
from the reaction mixture thus increases the stereoselectivity of
the reaction.
mmol, 60%, as a yellowish liquid. H NMR (CDCl3, 300 MHz, 30
°C) δ 6.98 (d, J = 9.3 Hz, 1H), 6.31 (d, J = 9.3 Hz, 1H), 1.31 (s,
12H) ppm; 13C{1H} NMR (CDCl3, 75 MHz, 30 °C) δ 124.6, 84.0,
25.0. The boron-bound carbon signal was not observed. 11B{1H}
NMR (CDCl3, 96 MHz, 30 °C) δ 29.4; HRMS (APCI) m/z calcd for
[C8H1479Br11BO2 + H]+ 233.0345; found 233.0343; IR ν
̃
2979, 1605,
1355, 1329, 1242, 1139, 967, 847, 744 cm−1.
(Z)-2-(2-Bromovinyl)-5,5-dimethyl-1,3,2-dioxaborinane, (Z)-4.
2,2-Dimethylpropane-1,3-diol was used in place of the glycol.
Kugelrohr distillation (50 °C bath/0.1 Torr) yielded 2.04 g, 9.3
mmol, 57% as a colorless liquid. 1H NMR (CDCl3, 300 MHz, 30 °C)
δ 6.83 (d, J = 9.1 Hz, 1H), 6.20 (d, J = 9.3 Hz, 1H), 3.65 (s, 4H), 0.97
(s, 6H); 13C{1H} NMR (CDCl3, 75 MHz, 30 °C) δ 122.0, 72.3, 31.9,
22.0. The boron-bound carbon signal was not observed. 11B{1H}
NMR (CDCl3, 96 MHz, 30 °C) δ 25.7; HRMS (APCI) m/z calcd for
EXPERIMENTAL SECTION
■
General Information. Unless otherwise noted, all reactions were
carried out under an atmosphere of dry argon using standard Schlenk
techniques. The commercially available reagents and starting materials
employed were used without any further purification, unless otherwise
specified, or prepared following reported methods as indicated. Boron
tribromide was purified by stirring with magnesium turnings for
several minutes and subsequent distillation under an argon
atmosphere. Acetylene was bubbled through concentrated sulfuric
acid before it entered the reaction apparatus. Diethyl ether and THF
were distilled prior to use with sodium and benzophenone under an
argon atmosphere. Organozinc compounds were prepared from the
corresponding bromo or iodo derivatives by lithiation with t-BuLi and
transmetalation with ZnCl2 solution in THF except MeZnCl, PhZnCl,
and vinylzinc chloride where commercial MeLi, PhMgBr, and
vinylmagnesium bromide solutions were used, respectively. 5-
Bromo-2-methoxyphenol was prepared from guaiacol according to
the literature procedures.22
[C7H1279Br11BO2 + H]+ 219.0188, found 219.0190; IR ν
̃
2961, 1600,
1477, 1420, 1328, 1234, 1199, 1072, 1004, 813, 733, 691 cm−1.
General Procedure B: Negishi Cross-Coupling Reaction. To a
previously prepared solution of organolithium or Grignard reagent
(0.86 mmol) in THF or diethyl ether (1 mL) in a 50 mL Schlenk
flask, ZnCl2 (175 mg, 1.29 mmol) in THF or diethyl ether (2 mL)
was added under an Ar atmosphere at −78 °C. The resulting solution
was stirred for 0.5 h and allowed to warm up to room temperature.
Then Pd(PPh3)4 (25 mg, 5 mol %) and (Z)-3 (100 mg, 0.43 mmol)
in THF (2 mL) were added dropwise. The reaction flask was covered
with aluminum foil and stirred for 2 h at room temperature. The
reaction was quenched with a degassed saturated solution of NH4Cl
in water (1 mL) and extracted with diethyl ether (2 × 10 mL). The
combined organic layers were washed with water (10 mL) and brine
(10 mL), dried over MgSO4, and evaporated.
GC analysis was made on a 56.7 m × 0.25 mm i.d. fused silica
capillary column with 25 μm of (5%-phenyl)methylpolysiloxane
stationary phase and helium as a carrier gas at 140 °C. Aliquots of the
reaction mixture (10 μL) were diluted with diethyl ether (1 mL) prior
to analysis.
(Z)-2-(Prop-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, (Z)-
5a. General procedure B was followed with MeLi (0.54 mL, 1.6 M in
diethyl ether, 0.86 mmol). Kugelrohr distillation (40 °C bath/0.1
Torr) afforded (Z)-5a as a colorless liquid (47 mg, 0.278 mmol, 65%
yield). 1H NMR (CDCl3, 300 MHz, 30 °C) δ 6.52 (m, 1H), 5.35 (dq,
J = 13.5, 1.5 Hz, 1H), 1.97 (dd, J = 6.8, 1.5 Hz, 3H), 1.27 (s, 12H);
13C{1H} NMR (CDCl3, 75 MHz, 30 °C) δ 149.7, 83.0, 25.0, 18.6.
NMR spectra were recorded on a 300 MHz spectrometer, and the
chemical shifts are reported in delta units (δ). The 1H NMR chemical
shifts are given relative to residual CHCl3 in CDCl3 (δ 7.26). The 13
C
The boron-bound carbon signal was not observed. 11B{1H} NMR
(CDCl3, 96 MHz, 30 °C) δ 29.8; HRMS (APCI) m/z calcd for
[C9H1711BO2 + H]+ 169.1396, found 169.1395. The analytical data
matched those published previously.23
NMR chemical shifts are referenced to CDCl3 (δ 77.16). The
11B{1H} NMR spectra were measured in a borosilicate glass NMR
tube, and the chemical shifts are referenced to the 11B signal of BF3·
OEt2 (δ 0.00 ppm) as an external standard. IR spectra were recorded
on a FTIR-ATR spectrometer on ZnSe crystal.
(Z)-2-(Buta-1,3-dienyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane,
(Z)-5b. General procedure B was followed with vinylmagnesium
bromide (0.86 mL, 1 M in diethyl ether, 0.86 mmol). Kugelrohr
distillation (40 °C bath/0.1 Torr) afforded (Z)-5b as a colorless
liquid (55 mg, 0.305 mmol, 71% yield). 1H NMR (CDCl3, 300 MHz,
30 °C) δ 7.17 (dtd, J = 16.9, 10.5, 0.9 Hz, 1H), 6.85 (t, J = 11.9 Hz,
1H), 5.42 (d, J = 13.4 Hz, 1H), 5.37−5.27 (m, 2H), 1.28 (s, 12H);
13C{1H} NMR (CDCl3, 75 MHz, 30 °C) δ 151.0, 137.3, 121.3, 83.3,
General Procedure A: Synthesis of (Z)-Bromovinylboronates. To
a flame-dried 50 mL Schlenk flask which was previously charged with
magnesium turnings (50 mg, 2.1 mmol), thoroughly flushed with
argon and acetylene, and cooled to 0 °C, freshly distilled BBr3 (2 mL,
21.1 mmol) was added. The reaction mixture was stirred at room
temperature until 80% of the expected amount of acetylene (400 mL,
16.4 mmol) was consumed. A sample for NMR (0.05 mL) was taken
that showed a mixture of bromovinyldibromoboranes. (Z)-1: 1H
NMR (CDCl3, 300 MHz, 30 °C) δ 7.50−7.30 (bs, 1H), 6.94 (d, J =
9.9 Hz, 1H); 11B{1H} NMR (CDCl3, 96 MHz, 30 °C) δ 53.7. (E)-1:
1H NMR (CDCl3, 300 MHz, 30 °C) δ 7.97 (d, J = 14.8 Hz, 1H), 7.08
(d, J = 14.8 Hz, 1H); 11B{1H} NMR (CDCl3, 96 MHz, 30 °C) δ 52.5.
Then diethyl ether (10 mL, 96.3 mmol) was added dropwise at 0 °C,
and the resulting mixture was stirred for 5 h. The corresponding
25.0. The boron-bound carbon signal was not observed. 11B{1H}
NMR (CDCl3, 96 MHz, 30 °C) δ 29.4; HRMS (APCI) m/z calcd for
[C10H1711BO2 + H]+ 181.1396, found 181.1394. The analytical data
matched those published previously.24
(Z)-2-(2-Phenylvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane,
(Z)-5c. General procedure B was followed with PhMgBr (0.86 mL, 1
M in diethyl ether, 0.86 mmol). Column chromatography on silica gel
with 5% EtOAc in hexanes afforded (Z)-5c as a colorless liquid (51
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1
mg, 0.223 mmol, 52% yield). H NMR (CDCl3, 300 MHz, 30 °C) δ
liquid (46 mg, 0.175 mmol, 41% yield). 1H NMR (CDCl3, 300 MHz,
30 °C) δ 7.54 (dd, J = 7.6, 1.6 Hz, 1H), 7.48 (d, J = 14.9 Hz, 1H),
7.28−7.22 (m, 1H), 6.91−6.82 (m, 2H), 5.61 (d, J = 14.9 Hz, 1H),
3.82 (s, 3H), 1.25 (s, 12H); 13C{1H} NMR (CDCl3, 75 MHz, 30 °C)
δ 157.3, 143.9, 130.0, 129.5, 128.0, 120.0, 110.4, 83.4, 55.6, 24.9. The
boron-bound carbon signal was not observed. 11B{1H} NMR (CDCl3,
96 MHz, 30 °C) δ 30.2 ppm; HRMS (APCI) m/z calcd for
[C15H2111BO3 + H]+ 261.1659, found 261.1655.
7.54 (m, 2H), 7.34−7.18 (m, 4H), 5.60 (d, J = 15.0 Hz, 1H), 1.30 (s,
12H); 13C{1H} NMR (CDCl3, 75 MHz, 30 °C) δ 148.3, 128.8, 128.1,
128.1, 83.6, 24.9. The boron-bound carbon signal was not observed.
11B{1H} NMR (CDCl3, 96 MHz, 30 °C) δ 30.2; HRMS (APCI) m/z
calcd for [C14H1911BO2 + H]+ 231.1553, found 231.1555. The
analytical data matched those published previously.25
(Z)-2-(2-(4-Methylphenyl)vinyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane, (Z)-5d. Organolithium was prepared by lithiation of 4-
iodotoluene (187 mg, 0.86 mmol) in THF (1 mL) with t-BuLi (0.9
mL, 1.9 M in pentane, 1.72 mmol) at −78 °C. Then general
procedure B was followed. Column chromatography on silica gel with
5% EtOAc in hexanes afforded the product (Z)-5d as a colorless
liquid (57 mg, 0.231 mmol, 54% yield). 1H NMR (CDCl3, 300 MHz,
30 °C) δ 7.46 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 14.9 Hz, 1H), 7.12 (d,
J = 8.1 Hz), 5.53 (d, J = 14.9 Hz, 1H), 2.35 (s, 3H), 1.30 (s, 12H);
13C{1H} NMR (CDCl3, 75 MHz, 30 °C) δ 148.6, 138.1, 135.9, 128.8,
(Z)-2-(2-(4-Chlorophenyl)vinyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane, (Z)-5i. Organolithium prepared by lithiation of 1-chloro-4-
iodobenzene (205 mg, 0.86 mmol) in THF (1 mL) with t-BuLi (0.9
mL, 1.9 M in pentane, 1.72 mmol) at −78 °C. Then general
procedure B was followed. Column chromatography on silica gel with
5% EtOAc in hexanes afforded the product (Z)-5i as a colorless liquid
1
(71 mg, 0.266 mmol, 62% yield). H NMR (CDCl3, 300 MHz, 30
°C) δ 7.49 (d, J = 8.5 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H), 7.15 (d, J =
15.0 Hz, 1H), 5.61 (d, J = 14.9 Hz, 1H), 1.29 (s, 12H); 13C{1H}
NMR (CDCl3, 75 MHz, 30 °C) δ 147.1, 137.1, 134.0, 130.2, 128.2,
83.8, 24.9. The boron-bound carbon signal was not observed. 11B{1H}
NMR (CDCl3, 96 MHz, 30 °C) δ 30.0; HRMS (APCI) m/z calcd for
[C14H1835Cl11BO2 + H]+ 265.1164, found 265.1167.
83.6, 25.0, 21.4. The boron-bound carbon signal was not observed.
11B{1H} NMR (CDCl3, 96 MHz, 30 °C) δ 30.2; HRMS (APCI) m/z
calcd for [C15H2111BO2 + H]+ 245.1710, found 245.1708. The
analytical data matched those published previously.25
(Z)-2-(2-(2-Methylphenyl)vinyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane, (Z)-5e. Organolithium was prepared by lithiation of 2-
iodotoluene (187 mg, 0.86 mmol) in THF (1 mL) with t-BuLi (0.9
mL, 1.9 M in pentane, 1.72 mmol) at −78 °C. Then general
procedure B was followed. Column chromatography on silica gel with
5% EtOAc in hexanes afforded the product (Z)-5e as a colorless liquid
(Z)-2-(2-(1-Naphthyl)vinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lane, (Z)-5j. Organolithium was prepared by lithiation of 1-
bromonaphthalene (178 mg, 0.86 mmol) in THF (1 mL) with t-
BuLi (0.9 mL, 1.9 M in pentane, 1.72 mmol) at −78 °C. Then general
procedure B was followed. Column chromatography on silica gel with
5% EtOAc in hexanes afforded the product (Z)-5j as a colorless liquid
1
(64 mg, 0.263 mmol, 61% yield). H NMR (CDCl3, 300 MHz, 30
°C) δ 7.42−7.33 (m, 2H) 7.21−7.05 (m, 3H), 5.66 (d, J = 14.9 Hz,
1H), 2.32 (s, 3H), 1.23 (s, 12H); 13C{1H} NMR (CDCl3, 75 MHz,
30 °C) δ 147.1, 138.2, 136.1, 129.8, 128.8, 128.1, 125.3, 83.5, 24.9,
20.0. The boron-bound carbon signal was not observed. 11B{1H}
NMR (CDCl3, 96 MHz, 30 °C) δ 30.3; HRMS (APCI) m/z calcd for
[C15H2111BO2 + H]+ 245.1710, found 245.1711. The analytical data
matched those published previously.25
(Z)-2-(2-(4-Methoxyphenyl)vinyl)-4,4,5,5-tetramethyl-1,3,2-diox-
aborolane, (Z)-5f. Organolithium was prepared by lithiation of 4-
iodoanisole (201 mg, 0.86 mmol) in THF (1 mL) with t-BuLi (0.9
mL, 1.9 M in pentane, 1.72 mmol) at −78 °C. Then general
procedure B was followed. Column chromatography on silica gel with
5% EtOAc in hexanes afforded the product (Z)-5f as a colorless liquid
1
(77 mg, 0.273 mmol, 64% yield). H NMR (CDCl3, 300 MHz, 30
°C) δ 8.05−8.02 (m, 1H), 7.91−7.77 (m, 3H), 7.57−7.38 (m, 4H),
5.88 (d, J = 14.4 Hz, 1H), 1.16 (s, 12H); 13C{1H} NMR (CDCl3, 75
MHz, 30 °C) δ 146.4, 136.5, 133.5, 131.8, 128.5, 128.4, 126.6, 126.1,
125.8, 125.2, 124.8, 83.4, 24.8. The boron-bound carbon signal was
not observed. 11B{1H} NMR (CDCl3, 96 MHz, 30 °C) δ 30.4;
HRMS (APCI) m/z calcd for [C18H2111BO2 + H]+: 281.1711, found
281.1706. The analytical data matched those published previously.27
Preparation of Combretastatin A4, (Z)-6. One-Pot Procedure for
Consecutive Negishi and Suzuki−Miyaura Cross-Coupling Reac-
tions. To a stirred solution of t-BuLi (0.9 mL, 1.9 M in pentane, 1.72
mmol) in THF (2 mL) in a 50 mL Schlenk flask, 5-bromo-1,2,3-
trimethoxybenzene (212 mg, 0.86 mmol) in THF (1 mL) was added
dropwise under an Ar atmosphere at −78 °C. The reaction mixture
was stirred for 5 min at −78 °C, and then ZnCl2 (175 mg, 1.29
mmol) in THF (2 mL) was added dropwise. The resulting mixture
was stirred for 0.5 h and allowed to warm to room temperature. Then
Pd(PPh3)4 (25 mg, 5 mol %) and (Z)-3 (100 mg, 0.43 mmol) in THF
(1 mL) were added dropwise. The reaction flask was covered with
aluminum foil and stirred for 1 h at room temperature. Water (0.1
mL) was added, and then cetyltrimethylammonium bromide
(CTMAB) (16 mg, 10 mol %) and KF·2H2O (800 mg, 8.50
mmol) in water (2 mL) were added dropwise. 5-Bromo-2-
methoxyphenol (175 mg, 0.86 mmol) in THF (1 mL) was added
dropwise. The resulting mixture was stirred at 80 °C for 18 h. A
saturated NH4Cl (5 mL) aqueous solution was added to the reaction
mixture followed by extraction with diethyl ether (3 × 10 mL). The
combined organic layers were washed with brine (10 mL), dried over
MgSO4, and evaporated. Column chromatography on silica gel with
25% EtOAc in hexanes afforded the product (Z)-6 as an off-white wax
1
(46 mg, 0.175 mmol, 41% yield). H NMR (CDCl3, 300 MHz, 30
°C) δ 7.55 (d, J = 8.8 Hz, 2H), 7.15 (d, J = 14.9 Hz, 1H), 6.84 (d, J =
8.8 Hz, 2H), 5.46 (d, J = 15.0 Hz, 1H), 3.82 (s, 3H), 1.30 (s, 12H);
13C{1H} NMR (CDCl3, 75 MHz, 30 °C) δ 159.8, 148.2, 131.5, 130.4,
113.5, 83.5, 55.4, 25.0. The boron-bound carbon signal was not
observed. 11B{1H} NMR (CDCl3, 96 MHz, 30 °C) δ 30.2; HRMS
(APCI) m/z calcd for [C15H2111BO3 + H]+ 261.1659, found
261.1661. The analytical data matched those published previously.26
(Z)-2-(2-(3-Methoxyphenyl)vinyl)-4,4,5,5-tetramethyl-1,3,2-diox-
aborolane, (Z)-5g. Organolithium was prepared by lithiation of 3-
bromoanisole (161 mg, 0.86 mmol) in THF (1 mL) with t-BuLi (0.9
mL, 1.9 M in pentane, 1.72 mmol) at −78 °C. Then general
procedure B was followed. Column chromatography on silica gel with
5% EtOAc in hexanes afforded the product (Z)-5g as a colorless
liquid (55 mg, 0.213 mmol, 50% yield). 1H NMR (CDCl3, 300 MHz,
30 °C) δ 7.33 (t, J = 1.9 Hz, 1H), 7.25−7.14 (m, 2H), 7.07 (d, J = 7.7
Hz, 1H), 6.83 (dd, J = 8.3, 2.3 Hz, 1H), 5.59 (d, J = 15.0 Hz, 1H),
3.83 (s, 3H), 1.30 (s, 12H); 13C{1H} NMR (CDCl3, 75 MHz, 30 °C)
δ 159.6, 148.4, 140.0, 129.0, 121.9, 114.6, 113.5, 83.6, 55.4, 25.0. The
boron-bound carbon signal was not observed. 11B{1H} NMR (CDCl3,
96 MHz, 30 °C) δ 30.1; HRMS (APCI) m/z calcd for [C15H2111BO3
+ H]+ 261.1659, found 261.1657. The analytical data matched those
published previously.20c
1
(95.1 mg, 0.301 mmol, 70% yield). H NMR (CDCl3, 300 MHz, 30
°C) δ 6.92 (d, J = 1.9 Hz, 1H), 6.80 (dd, J = 8.3, 1.9 Hz, 1H), 6.73 (d,
J = 8.3 Hz, 1H), 6.53 (s, 2H), 6.47 (d, J = 12.2 Hz, 1H), 6.41 (d, J =
12.2 Hz, 1H), 5.52 (s, 1H), 3.86 (s, 3H), 3.84 (s, 3H), 3.70 (s, 6H);
13C{1H} NMR (CDCl3, 75 MHz, 30 °C) δ 152.9, 145.8, 145.3, 137.3,
132.7, 130.7, 129.5, 129.1, 121.1, 115.1, 110.4, 106.2, 60.9, 56.0;
HRMS (APCI) m/z calcd for [C18H20O5 + H]+ 317.1384, found
317.1382. The analytical data matched those published previously.20c
(Z)-2-(2-(2-Methoxyphenyl)vinyl)-4,4,5,5-tetramethyl-1,3,2-diox-
aborolane, (Z)-5h. Organolithium was prepared by lithiation of 2-
bromoanisol (161 mg, 0.86 mmol) in THF (1 mL) with t-BuLi (0.9
mL, 1.9 M in pentane, 1.72 mmol) at −78 °C. Then general
procedure B was followed. Column chromatography on silica gel with
5% EtOAc in hexanes afforded the product (Z)-5h as a colorless
G
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Article
diisopropoxyborane. A New Building Block for (E)-Olefins. Chem.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c00341.
■
sı
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Walfish, I.; Blevins, D. W.; Kabalka, G. W. Chemoselective
Bromodeboronation of Organotrifluoroborates Using Tetrabutylam-
monium Tribromide: Application in (Z)-Dibromoalkene Syntheses.
Org. Lett. 2010, 12, 700−703. (e) Wang, C.; Xu, Z.; Tobrman, T.;
Negishi, E. Arylethyne Bromoboration−Negishi Coupling Route to E-
or Z-Aryl-Substituted Trisubstituted Alkenes of ≥ 98% Isomeric
Purity. New Horizon in the Highly Selective Synthesis of
Trisubstituted Alkenes. Adv. Synth. Catal. 2010, 352, 627−631.
(f) Negishi, E.; Tobrman, T.; Rao, H.; Xu, S.; Lee, C.-T. Highly
(≥98%) Selective Trisubstituted Alkene Synthesis of Wide Applic-
ability via Fluoride-Promoted Pd-Catalyzed Cross-Coupling of
Alkenylboranes. Isr. J. Chem. 2010, 50, 696−701.
Additional details of the bromoboration experiments,
computational details, and NMR spectra of all prepared
compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
Ctibor Mazal − Department of Chemistry, Faculty of Science,
Masaryk University, 611 37 Brno, Czech Republic;
orcid.org/0000-0001-6815-4098; Email: mazal@
chemi.muni.cz
■
Authors
́
̌
Jan Polasek − Department of Chemistry, Faculty of Science,
Masaryk University, 611 37 Brno, Czech Republic
Jan Paciorek − Department of Chemistry, Faculty of Science,
Masaryk University, 611 37 Brno, Czech Republic
̌
Jakub Stosek − Department of Chemistry, Faculty of Science,
Masaryk University, 611 37 Brno, Czech Republic
́
Hugo Semrad − Department of Chemistry, Faculty of Science,
Masaryk University, 611 37 Brno, Czech Republic
́
́
Marketa Munzarova − Department of Chemistry, Faculty of
Science, Masaryk University, 611 37 Brno, Czech Republic
(7) (a) Woerly, E. M.; Struble, J. R.; Palyam, N.; O’Hara, S. P.;
Burke, M. D. (Z)-(2-Bromovinyl)-MIDA boronate: a readily
accessible and highly versatile building block for small molecule
synthesis. Tetrahedron 2011, 67, 4333−4343. (b) Gillis, E. P.; Lee, S.
J.; Gray, K.; Burke, M. D.; Knapp, D. M. System for controlling the
reactivity of boronic acids. W.O. Patent 2009014550, 2009.
(8) (a) Feceu, A.; Sangster, L. E.; Martin, D. B. C. Unexpected
Alkene Isomerization during Iterative Cross-Coupling To Form
Hindered, Electron-Deficient Trienes. Org. Lett. 2018, 20, 3151−
3155. (b) Burke, M. D.; Gillis, E. P.; Ballmer, S. G. Apparatus and
methods for the automated synthesis of small molecules. U.S. Patent
9238597, 2016. (c) Go, E. B.; Wetzler, S. P.; Kim, L. J.; Chang, A. Y.;
Vosburg, D. A. Concise, diastereoconvergent synthesis of endiandric-
type tetracycles by iterative cross coupling. Tetrahedron 2016, 72,
3790−3794. (d) Woerly, E. M.; Roy, J.; Burke, M. D. Synthesis of
most polyene natural product motifs using just 12 building blocks and
one coupling reaction. Nat. Chem. 2014, 6, 484−491. (e) Burke, M.
D.; Gillis, E. P. Apparatus and methods for the automated synthesis of
small molecules using MIDA boronates. W.O. Patent 2012012756,
2012.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c00341
‡Author Contributions
́
̌
̌
́
J. Polasek, J. Paciorek, J. Stosek, and H. Semrad: These
authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Computational resources were supplied by the project “e-
Infrastruktura CZ” (e-INFRA LM2018140) provided within
the program Projects of Large Research, Development and
Innovations Infrastructures. Computational resources were
provided by the ELIXIR-CZ project (LM2015047), part of the
international ELIXIR infrastructure. The authors are indebted
to Masaryk University for financial support (projects MUNI/
A/1313/2018 and MUNI/A/1424/2019).
(9) Mazal, C.; Vaultier, M. A Simple, General and Stereoselective
Synthesis of 1-(Dialkoxyboryl)-1,3-Dienes. Tetrahedron Lett. 1994, 35,
3089−3090.
REFERENCES
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