Theor Chem Acc (2016) 135:13
1 3
observed in F6. In J6, the most preferred substitution corresponds to carbon 2 according to our calculations, favoring the allyl position, and the most negatively charged
homoallyl carbon 4 is less preferred with a higher activation energy.
In summary, our results show that the regioselectivity
can be attributed to the interplay between two main factors
(1) the dipole–dipole interactions of the boron B-H bond
with the double bond and (2) the allyl position of a second
double bond providing favorable polarization in the sixmembered ring. In addition, the stereoselectivity is largely
controlled by the structural fl exibility of the cyclohexene
ring favoring the Re attack.
These results lend themselves to predicting the most
likely product of hydroboration reactions, as the molecule
with the lowest energy transition state should yield the
kinetic product. These results are also in correlation with
the anti-Markovnikov regioselectivity of the reaction: the
electropositive boron within a hydrogen-boron bond of the
borane electrostatically favors the most negatively charged
sp
2 carbon within the molecule. Intriguingly, 1,3-cyclohexadiene presents an important exception to the anti-Markovnikov rule, whereas transition state theory continues to
predict the selectivity of the reaction.
The observed product specifi city does depend not only
on the selectivity of the fi rst hydroboration step leading
to monosubstituted RBH 2 compounds, but also on subsequent hydroboration reactions as well. We showed previously that the RBH 2 products can be more reactive than the
borane, and we expect rapid formation of R 2 BH products
[ 17 ]. We assumed here that the selectivity remains similar using RBH 2 for hydroboration; however, future studies
aiming for fully quantitative results would need to take into
account subsequent steps. Here we further analyzed the
possible hydroboration products after the completion of the
hydroboration reactions.
2.2 Full hydroboration products of dienes
To better understand the nature of fi nal hydroboration
products before subsequent oxidation, we considered competing pathways of hydroboration reactions (Scheme 2 ).
The end product of the fi rst hydroboration step using an
activated ‘BH 3 ’ is a mixture of monosubstituted boranes
with a single double bond. Further borane addition can
take place in three different ways: by intermolecular hydroboration via the attached BH 2 substituent (pathway A in
Scheme 2 ), by another activated ‘BH 3 ’ molecule (pathway
B in Scheme 2 ), or by intramolecular hydroboration via
another monosubstituted borane (pathway C in Scheme 2 ).
Covalent polymers can thus form via pathway C [ 17 ], following the intermolecular hydroboration reaction pathway.
In pathway C, subsequent hydroboration of R 2 BH species
can further occur to form trialkyl boranes. Accordingly,
well-documented examples suggest that the corresponding
species are often found as homologues of trialkylboranes
(R 3 B) [ 20 , 31 ].
Immediately following the hydroboration reactions, the
high-energy trigonal boron species are stabilized by forming intermolecular (e.g., via pathway D) or intramolecular
(when possible, e.g., via pathway E) B–H–B bridges. Stabilization can also occur via adduct formation with the solvent or with BH 3 . Trialkyl species are exceptions, in that
they are generally stable trigonal boron species that do not
form adducts [ 17 ].
In Scheme 2 , dimeric or monomeric small-molecule
compounds form via pathways A and B + E. On the other
hand, polymers may form via pathways C or B + D. Here
we aimed to compare the A and B + E pathways and to
verify whether the species are also observed experimentally, and to infer their relative prevalence.
In hydroboration reactions described in our previous
study [ 17 ], two possible products were observed depending on the nature of the reactant dienes and the reaction
conditions: formation of cross-linked polymers, which
precipitate out of solution, or formation of soluble, smallmolecule products, which have been analyzed using
11 B
NMR. Previous analysis [ 17 ] of the experimental NMR
data (reproduced here as Figs. 5 and S6) suggested that a
range of fully hydroborated product species were present.
The substrates F6, 1,3-cycloheptadiene, 1,3-cyclooctadiene, G6, and E6 all yielded cross-linked polymers, whereas
substrates D8, B6, C6, and the control A4 all yielded clear
solutions. Interestingly, the excess equivalents of borane
used in the reaction can also affect the outcome of the reaction products for certain molecules, such as in the example
of 1,3,5,5-tetramethyl-1,3-cyclohexadiene (D6), which was
seen to form a clear solution when only one equivalent of
borane was used, but an insoluble precipitate was observed
when two equivalents were used [ 17 ]. The clear solution of
D6 eventually formed a precipitate after 2 h.
11 B NMR of the clear solutions of substrates reacted
with two equivalents of borane resulted in spectra with
many peaks, the origins of which were not all apparent.
The presence of peaks at −10.4 and −29.1 ppm was attributed to the presence of impurities in the BH 3 ·SMe 2 starting
material, but were found not to participate in the hydroboration reaction. The presence of a quartet at −20.4 ppm
was due to unreacted BH 3 ·SMe 2 . The main experimental
peaks of the hydroboration products are listed in Table 2
together with initial assignment of the corresponding species [ 32 ]. In this work, we calculated theoretical chemical
shifts for possible reaction products (Table S4) through the
use of quantum chemical calculations, and their concordance with reported experimental data was compared.
242
Reprinted from the journal
1 3
observed in F6. In J6, the most preferred substitution corresponds to carbon 2 according to our calculations, favoring the allyl position, and the most negatively charged
homoallyl carbon 4 is less preferred with a higher activation energy.
In summary, our results show that the regioselectivity
can be attributed to the interplay between two main factors
(1) the dipole–dipole interactions of the boron B-H bond
with the double bond and (2) the allyl position of a second
double bond providing favorable polarization in the sixmembered ring. In addition, the stereoselectivity is largely
controlled by the structural fl exibility of the cyclohexene
ring favoring the Re attack.
These results lend themselves to predicting the most
likely product of hydroboration reactions, as the molecule
with the lowest energy transition state should yield the
kinetic product. These results are also in correlation with
the anti-Markovnikov regioselectivity of the reaction: the
electropositive boron within a hydrogen-boron bond of the
borane electrostatically favors the most negatively charged
sp
2 carbon within the molecule. Intriguingly, 1,3-cyclohexadiene presents an important exception to the anti-Markovnikov rule, whereas transition state theory continues to
predict the selectivity of the reaction.
The observed product specifi city does depend not only
on the selectivity of the fi rst hydroboration step leading
to monosubstituted RBH 2 compounds, but also on subsequent hydroboration reactions as well. We showed previously that the RBH 2 products can be more reactive than the
borane, and we expect rapid formation of R 2 BH products
[ 17 ]. We assumed here that the selectivity remains similar using RBH 2 for hydroboration; however, future studies
aiming for fully quantitative results would need to take into
account subsequent steps. Here we further analyzed the
possible hydroboration products after the completion of the
hydroboration reactions.
2.2 Full hydroboration products of dienes
To better understand the nature of fi nal hydroboration
products before subsequent oxidation, we considered competing pathways of hydroboration reactions (Scheme 2 ).
The end product of the fi rst hydroboration step using an
activated ‘BH 3 ’ is a mixture of monosubstituted boranes
with a single double bond. Further borane addition can
take place in three different ways: by intermolecular hydroboration via the attached BH 2 substituent (pathway A in
Scheme 2 ), by another activated ‘BH 3 ’ molecule (pathway
B in Scheme 2 ), or by intramolecular hydroboration via
another monosubstituted borane (pathway C in Scheme 2 ).
Covalent polymers can thus form via pathway C [ 17 ], following the intermolecular hydroboration reaction pathway.
In pathway C, subsequent hydroboration of R 2 BH species
can further occur to form trialkyl boranes. Accordingly,
well-documented examples suggest that the corresponding
species are often found as homologues of trialkylboranes
(R 3 B) [ 20 , 31 ].
Immediately following the hydroboration reactions, the
high-energy trigonal boron species are stabilized by forming intermolecular (e.g., via pathway D) or intramolecular
(when possible, e.g., via pathway E) B–H–B bridges. Stabilization can also occur via adduct formation with the solvent or with BH 3 . Trialkyl species are exceptions, in that
they are generally stable trigonal boron species that do not
form adducts [ 17 ].
In Scheme 2 , dimeric or monomeric small-molecule
compounds form via pathways A and B + E. On the other
hand, polymers may form via pathways C or B + D. Here
we aimed to compare the A and B + E pathways and to
verify whether the species are also observed experimentally, and to infer their relative prevalence.
In hydroboration reactions described in our previous
study [ 17 ], two possible products were observed depending on the nature of the reactant dienes and the reaction
conditions: formation of cross-linked polymers, which
precipitate out of solution, or formation of soluble, smallmolecule products, which have been analyzed using
11 B
NMR. Previous analysis [ 17 ] of the experimental NMR
data (reproduced here as Figs. 5 and S6) suggested that a
range of fully hydroborated product species were present.
The substrates F6, 1,3-cycloheptadiene, 1,3-cyclooctadiene, G6, and E6 all yielded cross-linked polymers, whereas
substrates D8, B6, C6, and the control A4 all yielded clear
solutions. Interestingly, the excess equivalents of borane
used in the reaction can also affect the outcome of the reaction products for certain molecules, such as in the example
of 1,3,5,5-tetramethyl-1,3-cyclohexadiene (D6), which was
seen to form a clear solution when only one equivalent of
borane was used, but an insoluble precipitate was observed
when two equivalents were used [ 17 ]. The clear solution of
D6 eventually formed a precipitate after 2 h.
11 B NMR of the clear solutions of substrates reacted
with two equivalents of borane resulted in spectra with
many peaks, the origins of which were not all apparent.
The presence of peaks at −10.4 and −29.1 ppm was attributed to the presence of impurities in the BH 3 ·SMe 2 starting
material, but were found not to participate in the hydroboration reaction. The presence of a quartet at −20.4 ppm
was due to unreacted BH 3 ·SMe 2 . The main experimental
peaks of the hydroboration products are listed in Table 2
together with initial assignment of the corresponding species [ 32 ]. In this work, we calculated theoretical chemical
shifts for possible reaction products (Table S4) through the
use of quantum chemical calculations, and their concordance with reported experimental data was compared.
242
Reprinted from the journal