Transition-Metal-Free Allylic Borylation of 1,3-Dienes

Article abstract of DOI:10.1021/acs.orglett.9b00531

This work explains the reactivity of diboron reagents with 1,3-dienes in a transition-metal-free context. The sole addition of Na₂CO₃ (30 mol %) to bis(pinacolato)diboron in MeOH allows the 1,4-hydroboration of cyclic and noncyclic 1,3-dienes. The electronic influence on the substrate guarantees the conjugated 1,4-hydroboration versus 1,2-diboration. DFT calculations show that the distribution of charge in the allylic anion intermediate governs the selectivity toward 1,4-hydroboration, while the favored trans configuration in diene reagents determines the preference for the E allyl boronate products.

Full text of DOI:10.1021/acs.orglett.9b00531

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Transition-Metal-Free Allylic Borylation of 1,3-Dienes
†
,†
,†
Ricardo J. Maza,† Elliot Davenport,†,‡ Nuria Miralles, Jorge J. Carbo,* and Elena Fernandez*
́
́
́
†
̀
Department Química Física i Inorganica, Universitat Rovira i Virgili, C/Marcel·lí Domingo l, 43007 Tarragona, Spain
‡Department of Chemistry, Edinburgh University, Edinburgh EH9 3FJ, United Kingdom
S
* Supporting Information
ABSTRACT: This work explains the reactivity of diboron reagents with 1,3-dienes in a transition-metal-free context. The sole
addition of Na2CO3 (30 mol %) to bis(pinacolato)diboron in MeOH allows the 1,4-hydroboration of cyclic and noncyclic 1,3-
dienes. The electronic influence on the substrate guarantees the conjugated 1,4-hydroboration versus 1,2-diboration. DFT
calculations show that the distribution of charge in the allylic anion intermediate governs the selectivity toward 1,4-
hydroboration, while the favored trans configuration in diene reagents determines the preference for the E allyl boronate
products.
(Scheme 1, bottom right). Transition-metal-free borylation
he borylation of 1,3-dienes represents a powerful
Tsynthetic tool to obtain diborated or monoborated allylic reactions have emerged within this decade as a convenient
synthetic methodology toward selective C−B bond formation.7
systems, depending on the transition-metal catalyst employed.
Our group has previously explored the allylic borylation of
tertiary allylic alcohols8 as well as the allylic borylation of vinyl
epoxides and vinyl aziridines9 by the addition of the acid−base
Lewis adduct [MeO-Bpin-Bpin]−[Hbase]+ through SN2′-type
mechanisms. To the best of our knowledge, the borylation of
1,3-dienes without metal catalysts was only precedented
through the uncatalyzed diboration of 1,3-butadiene using
the highly reactive B2Cl4 or B2F4 to produce 1,4-bis-
(dihalogenoboryl)-2-butene compounds.10,11
From Miyaura and co-worker’s breakthrough experiments on
Pt(PPh3)4-catalyzed 1,4-diboration of 1,3-dienes to synthesize
bis(allyl)boronates,1 the field has progressed by discovering
different catalytic systems based on Pt, Ni, and Cu. The most
explored strategy uses Pt complexes to catalyze both 1,2- and
1,4-diboration of 1,3-dienes, even in an asymmetric fashion.2,3
Nickel complexes are also explored as catalytic systems, and
unlike Pt complexes, the Ni catalytic systems can catalyze the
1,4-selective diboration of even sterically hindered 1,3-dienes.4
Contrary to Pt or Ni complexes, the Cu complexes catalyze the
monoboration of 1,3-dienes with B2pin2 primarily forming the
homoallyl boronate products (Scheme 1).5,6
However, the transition-metal-free borylation of 1,3-dienes
generates questions about why the conjugated 1,4-hydro-
boration might be favored versus 1,2-diboration in the
transition-metal-free context, as well as whether the E- or the
Z-allyl boronate products are going to be preferentially formed
in noncyclic systems.
Here, in this work, we present the results of the borylation of
1,3-dienes in a transition-metal-free context, with the sole
addition of MeOH and base to generate the corresponding
methoxide and form the adduct [MeO-Bpin-Bpin]−[Hbase]+
In order to answer all of the questions raised above, we
selected the model substrate trans-1-phenyl-1,3-butadiene (1)
and we carried out the borylation with 1.1 equiv of B2pin2 in
the presence of 15 mol % of Na2CO3 and MeOH as solvent (1
mL) at 90 °C. The analysis of the unpurified reaction mixture
Scheme 1. Previous Transition-Metal-Catalyzed Diboration
and Monoboration of 1,3-Dienes (an Alternative
Transition-Metal-Free Version Reported in This Work)
1
by H NMR spectroscopy established 47% conversion toward
the 1,4-hydroborated product 2 (E/Z = 2/1) (Scheme 2, top)
and 22% of polyborylated products12 without the consumption
of all the starting material. Decreasing the temperature to 70
°C and increasing the amount of base to 30 mol % allowed the
formation of 2 in 60% (E/Z = 3/1), minimizing the byproduct
formation. Remarkably, this is the first attempt to borylate 1,3-
Received: February 11, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00531
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Organic Letters
Letter
Scheme 2. Transition-Metal-Free 1,4-Hydroboration of
trans-1-Phenyl-1,3-butadiene (1) and 1,2-Diboration of
trans-1-Methyl-1,3-butadiene (4) and (Z)-Penta-1,3-dien-3-
Table 1. Transition-Metal-Free 1,4-Hydroboration of trans-
1-Aryl-1,3-butadienes
a
a
ylbenzene (6)
a
Percent NMR yields calculated in 1H NMR spectra with naphthalene
as internal standard (% isolated yields).
dienes in a transition-metal-free context, and the results seem
to be complementary to Huang and co-workers’ work,13 where
the same substrate 1 underwent 1,4-hydroboration with HBpin
in the presence of iminopyridine Fe complexes, but forming
principally the secondary (Z)-allylboronate. When trans-1-
methyl-1,3-butadiene (4) reacted with 1.1 equiv of B2pin2, 1,2-
diboration of the terminal alkene took place instead to form
product 5 in 58% NMR yield (33% isolated) (Scheme 2). It
seems that the competing 1,2-diboration is favored versus 1,4-
hydroboration for alkyl substituents at the C1 position,14,15 in
contrast to the Fe−Mg-catalyzed 1,4-hydroboration of 1-alkyl-
substituted 1,3-dienes or 2-alkyl-substituted 1,3-dienes, ob-
served by the groups of Huang and Ritter, respectively.13,16 To
confirm the previous observation, we conducted the transition-
metal free borylation of (Z)-penta-1,3-dien-3-ylbenzene (6),
and as expected, the 1,2-diborated product 7 was also formed
despite the presence of the phenyl group at the C2 position
(Scheme 2).
To extend the conjugative borylation on trans-1-aryl-1,3-
butadiene type substrates, we carried out a systematic study
with the optimized reaction conditions based on the addition
of B2pin2 (1.1 equiv) to a solution of MeOH that contains the
substrate and 30 mol % of Na2CO3. As can be seen in Table 1,
trans-1-aryl-1,3-butadienes that contain electron-donating and
electron-withdrawing substituents on the aryl group do not
affect the reaction outcome (Table 1, entries 1−3). However, a
slight increase in the E/Z ratio up to 4/1 was observed for
product 13. It is worth mentioning that substrate buta-1,3-
diene-1,1-diyldibenzene 14 was borylated with similar success
but the enhanced E/Z ratio (up to 9/1) indicated the
preference for the E isomer in compound 15 when the two aryl
groups are located at the terminal position (Table 1, entry 4).
We were also able to conduct the transition-metal-free 1,4-
hydroboration of (E)-2-(buta-1,3-dien-1-yl)furan 16 toward
the desired allyl boronate product 17, demonstrating the
a
Reaction conditions: substrate (0.2 mmol), B2pin2 (1.1 equiv)
b
Na2CO3 (30 mol %), MeOH (1 mL), 70 °C, 16 h. NMR yields
calculated in H NMR spectra with naphthalene as internal standard
(percent isolated yields). Na2CO3 (15 mol %), 90 °C.
1
c
compatibility with other conjugated systems (Table 1, entry 5).
The general method was also applied to internal 1,3 dienes
such as ((1E,3E)-penta-1,3-dien-1-yl)benzene 18 and related
substrates 20 and 22. To our delight, the 1,4-hydroboration
took place toward the formation of the desired allylic
boronates 19, 21, and 23 without any reduction in the yield
or the E/Z ratio (Table 1, entries 6−8). The internal
substitution in substrate (E)-(2-methylbuta-1,3-dien-1-yl)-
benzene 24, also proved not to be influential to the reaction
outcome as product 25 was formed with similar conversion
and selectivity (Table 1, entry 9).
B
DOI: 10.1021/acs.orglett.9b00531
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We next considered the possibility to extend the transition-
metal-free allylic borylation methodology to cyclic 1,3-dienes.
We found that cyclohexadiene (26) was transformed into the
corresponding allyl boronate via 1,4-hydroboration under the
same reaction conditions as for non-cyclic systems except that
90 °C was required (Table 1, entry 10). This is interesting
because in this substrate there are no aryl substituents that
direct the conjugative borylation as in substrate 2, and so the
1,2 diborated product could be expected to form as in the
borylation of trans-1-methyl-1,3-butadiene (4) (see Scheme 2).
In extension, substrate 2-(2-ethylhexyl)cyclohexa-1,3-diene
(28) could be efficiently borylated toward the allylic
bororonate product 29, despite the added steric hindrance
provided by having a substituent in the internal position
(Table 1, entry 11). Even the disubstituted cyclic 1,3-diene 5-
isopropyl-2-methylcyclohexa-1,3-diene (30) was transformed
into the allylic boronate product 31, with an anti-configuration
of the Bpin moiety in relation to the isopropyl functional group
(Table 1, entry 12).
Scheme 4. Transition-Metal-Free 1,4-Hydroboration/
Oxidation of trans-1-Aryl-1,3-butadienes
Allyl boronate products are very important building
blocks,17 and in our hands, the allyl boronate product 2 has
been transformed into 1,2,3-triborated product 3 via
consecutive transition-metal-free diboration of the internal
double bond (Scheme 3). The triborated product 3 was
Scheme 3. Synthesis of 1,2,3-Triborated Products from the
Allyl Boronates
quantitatively formed and isolated from the reaction as a
unique product. The extension of this interesting trans-
formation has been recently explored with a detailed study
of the concomitant selective cross-coupling reaction from
triborated compounds.12 The in situ oxidative workup of the
allyl boronate compounds prepared in this work provide the
corresponding allylic alcohols in a transition metal-free context
with a preference for the E-isomer (Scheme 4). The formation
of allylic alcohols through borylation reactions was recently
observed in the Cu-catalyzed borylation of vinyl cyclic
carbonates via an SN2′ mechanism, also with preference on
the E isomer.18
A proposed reaction mechanism for the transition-metal-free
borylation of 1,3-dienes may involve first activation of the
B2pin2 with MeOH/base to form adduct [MeO-Bpin-
Bpin]−[Hbase]+ followed by nucleophilic attack of the
Bpin(sp2) moiety to the terminal double bond (Figure 1).
The conjugative borylation may generate two isomeric allylic
anion intermediates that can be protonated with MeOH used
as solvent.
Figure 1. Proposed mechanism for transition-metal-free borylation of
1,3-dienes.
intermediate.21 Figure 2 displays the computed potential
free-energy profile for the 1,4-hydroboration of 1-trans-
phenylbutadiene (1) to yield both the E and the Z
stereoisomeric products. The calculated free-energy barrier
for the initial nuclophilic Bpin transfer to the terminal carbon
of diene 1 is moderate (24.5 kcal·mol−1) and leads to a stable
anionic intermediate I1-E (E-path, solid lines). Similar to that
observed for allenamides,22 the anionic, 3-membered boracycle
intermediate opens to form a more stable allylic anion with an
alkyl boronate group attached to the terminal carbon.
Subsequent protonation of I1-E leads to the hydroborated
product. The observed regioselective protonation of C1 can be
rationalized from the charge distribution in the allylic
intermediate I1-E (Figure 2). Our calculations show that the
phenyl-substituted C1, supports a larger negative charge than
the allylic C2 and C3. Consequently, the C1 carbon should be
more reactive toward protonation in agreement with the
observed preference for 1,4- over the 3,4-hydroboration. In line
with this, the estimated barrier for protonation at C1 using a
single MeOH solvent molecule is quite low (5.1 kcal·mol−1).
To explain the formation of the observed Z product, the E
path has to undergo an isomerization process at some point in
the catalytic cycle. The isomerization of the allylic intermediate
I1-E to I1-Z via rotation around the C2−C3 bond is unlikely
because the computed barrier of 19.3 kcal·mol−1 is significantly
We performed DFT studies19 on the mechanism depicted in
Figure 1 in order to understand the stereo- and regioselectivity
in the transition-metal-free borylation of cyclic and 1-aryl-
substituted 1,3-dienes. Previous computational studies have
demonstrated the nucleophilic character of the sp2 boron
moiety20 in the acid−base Lewis adduct [MeO-Bpin-
Bpin]−[Hbase]+ and that the electron-withdrawing substitu-
ents can favor the hydroboration over the diboration of CC
double bonds by stabilizing the anionic monoborylated
C
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Figure 3. Proposed reaction mechanism for the 1,4-hydroboration of
cyclohexadiene by B2pin2 in MeOH/base. Relative free-energies and
barriers in kcal·mol−1.
formation. 1,4-Hydroborations are favored versus 1,2-dibora-
tion for 1-trans-arylbutadienes. Computational studies identify
the key steps in the transition-metal-free conjugative borylation
that rationalize the preference for 1,4-hydroborated products
as well as the E stereoisomerism in the allylic boronate
products.
ASSOCIATED CONTENT
* Supporting Information
■
S
Figure 2. Potential free-energy profiles (kcal·mol−1) for the 1,4-
hydroboration of 1-trans-phenyl-1,3-butadiene (1) by B2pin2 in
MeOH/base. Solid and dashed lines correspond to the paths yielding
the E and Z stereoisomeric products.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b00531.
Experimental procedures and spectral data, 1H, 13C, and
11B spectral images, and computational studies (PDF)
higher than that for the forward protonation reaction (5.1 kcal·
mol−1). Instead, we propose that the trans diene isomerizes to
the cis conformation. The computed barrier (8.4 kcal·mol−1)
and the energy difference (+3.6 kcal·mol−1) might allow it.
Borylation of the cis conformer yields intermediate I1-Z with
the alkyl boronate group cis to C1 (dashed lines in Figure 2).
The lower stability of the cis isomer is partially compensated by
a lower free-energy barrier for borylation (22.6 vs 24.5 kcal·
mol−1). Interestingly, the higher reactivity of cis conformations
of α,β-unsaturated aldehydes and ketones has been explained
from secondary orbital interactions which allow a better
stabilization of the developing negative charge.23 Overall, the
transition state for the Z path (TS1-Z) is only 1.7 kcal·mol−1
higher than the corresponding transition state for the E path
(TS1-E). This results in a small preference for the E over the Z
products, in full agreement with experimental observations.
For cyclic 1,3-dienes, we propose the same type of
mechanism, in which only the Z-path is possible due to the
cis configuration of the diene (Figure 3). The computed barrier
for the nucleophilic Bpin transfer to the cyclohexadiene 26 is
somewhat larger (27.4 kcal·mol−1) than that for 1-trans-
phenylbutadiene (24.5 kcal·mol−1) but still reasonable for a
reaction occurring at 90 °C. In this case, the absence of the
phenyl substituent yields a less stable allylic anion intermediate
I1c and makes possible the formation of the boracyclic species
I′c. These intermediates, I1c and I′c, are close in energy and
interconvert easily. In line with the observed regioselectivity
toward 1,4-hydroboration, the C1 carbon of both species
supports the largest negative charge favoring its protonation,
for which we found very small electronic energy barriers (<1
kcal·mol−1).
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: mariaelena.fernandez@urv.cat.
*E-mail: j.carbo@urv.cat.
ORCID
́
Jorge J. Carbo: 0000-0002-3945-6721
́
Elena Fernandez: 0000-0001-9025-1791
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The present research was supported by the Spanish Ministerio
de Economia y competitividad (MINECO) through Project
No. FEDER-CTQ2016-80328-P and Generalitat de Catalunya
through Project No. 2017SGR629. We thank AllyChem for the
gift of diboranes.
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