Theor Chem Acc (2016) 135:13
1 3
All previous experimental
11 B NMR work was carried out by Andreou et al. in both THF and bis(2-methoxyethyl)ether (diglyme) solvents [ 17 , 32 ]. THF solvent
was purchased from Acros, diglyme from Sigma-Aldrich,
and deuterated NMR solvents from Euriso-top.
11 B NMR
spectra were carried out using a Bruker Advance BBATM-500 MHz NMR spectrometer using BF 3 ·OEt 2 as a
reference.
Experimental work involved the following dienes:
α-terpinene (0.12 mL, 0.7340 mmol), γ-terpinene
(0.12
mL,
0.7340
mmol),
1,3-cyclohexadiene
(0.07 mL, 0.7340 mmol), 1,3-cyclooctadiene (0.09 mL,
0.7340 mmol), 1,3,5,5-tetramethyl-1,3-cyclohexadiene
(0.13 mL, 0.7340 mmol), 1,2,4,5-tetramethyl-1,4-cyclohexadiene (0.1 g, 0.7340 mmol), 1,5-cyclooctadiene (0.12 mL,
0.7340 mmol), 2,3-dimethyl-1,3-butadiene (0.09 mL,
0.7340 mmol).
In THF, the representative procedure for the hydroboration of dienes used BH 3 ·SMe 2 , utilizing the borane to
diene addition mode: BH 3 ·SMe 2 (0.14 mL, 1.4680 mmol)
was added dropwise to a solution of a diene dissolved in
THF (1 mL) pre-cooled to −40 °C. The reaction mixture
was left to stir under nitrogen at 0 °C for 1 h to give a clear
solution, which, depending on the diene used, contained a
white precipitate.
In diglyme, the representative procedure for the hydroboration of dienes used BH 3 ·SMe 2 , utilizing the borane
to diene addition mode: BH 3 ·SMe 2 (0.07 mL, 0.7340 mmol
or 0.14 mL, 1.4680 mmol) was added dropwise to a solution of a diene dissolved in diglyme (3.2 mL). The reaction
mixture was left to stir under nitrogen at 0 °C for 1 h to
give a clear solution, which, depending on the diene used,
contained a white precipitate.
4 Conclusions
Hydroboration is one of the most valuable chemical synthesis methods, due to many reasons, including its highly
specifi c regio- and stereoselectivity. However, in complex
reagents, the identity of the preferred anti-Markovnikov
product is not apparent at fi rst glance. The use of electrostatic potential-based atomic charges has proved to be a
useful tool in predicting the regioselectivity of hydroboration reactions. Here we studied 11 molecules, representing
10 cyclic dienes and a straight chain diene. In most examples, the regioselectivity for the preferred product was predicted both by the extended anti-Markovnikov rule, using
the atomic charges of the reactants, and also by transition
state theory—comparing the activation energies of all possible products. Here we identifi ed the 1,3-cyclohexadiene molecule as a key exception to the anti-Markovnikov
rule, which had an unforeseen preference toward the allyl
product according to the transition state barrier heights.
Our calculated activation energies accurately predicted the
selectivity favoring almost equally the allyl products, in
agreement with previous experimental studies [ 19 ], therefore validating our transition state theory-based calculation
results. The unexpected selectivity was suggested to arise
due to steric effects [ 19 ]. We found, however, that steric
effects do not directly contribute to the observed selectivity, leading to a deviation from the anti-Markovnikov rule.
Instead, the stability of the axial BH 2 group via conjugation
with the allyl double bond is a more important stabilizing
factor, which also relies on the unique structural properties
of the cyclohexene ring as additional required factors for
the paradoxical regioselectivity. We also introduced two
additional derivatives (I6 and J6) and confi rmed the similar
selectivity rules favoring allyl positions for these molecules
as well. These molecules lend themselves as additional
examples with exceptional regioselectivity against the antiMarkovnikov rule.
As the anti-Markovnikov rule follows the same general principle as the Markovnikov rule [ 23 ] in terms of the
most energetically favorable reaction pathway being determined by the attractive dipole–dipole interactions within
a carbon–carbon double bond and the reacting X–H substituent, our results therefore provide an exception (on the
basis of F6, I6, and J6) to these rules in general. We found
that the Lewis acid borane, and the second remaining double bond with Lewis base properties, resembling frustrated
Lewis pair-type moieties, worked synergistically to stabilize allyl–π bond interactions resulting in the unexpected
selectivity. Using this as a design principle, molecules with
similar electronic properties might provide an interesting
avenue for the exploration of synthetically useful exceptions to the Markovnikov rule, resulting in novel chemical
reactivity.
Although it is known that the process of hydroboration
can occur fully at all unsaturated sites within an alkene, the
precise nature of the unoxidized species formed after the
completion of the reactions still remains within a gray area.
11 B NMR results show that several hydroboration reactions
are possible, and that a variety of products may be formed.
Quantum chemical calculations together with NMR
measurements can thus shed light on why a subset of reactants does not polymerize, while others do, and what the
potential reaction pathways and stable products are. The
observation of a plethora of products indicates that competing pathways concurrently take place within hydroboration reactions. It was concluded that the position of the
double bonds, in relation to sterically demanding groups,
was a strongly infl uencing factor in determining the structure of the product [ 17 ]. We have elucidated the mechanism
for the formation of cyclic monohydroborated species, as
well as specifi c diborane species. Our results are in very
246
Reprinted from the journal
1 3
All previous experimental
11 B NMR work was carried out by Andreou et al. in both THF and bis(2-methoxyethyl)ether (diglyme) solvents [ 17 , 32 ]. THF solvent
was purchased from Acros, diglyme from Sigma-Aldrich,
and deuterated NMR solvents from Euriso-top.
11 B NMR
spectra were carried out using a Bruker Advance BBATM-500 MHz NMR spectrometer using BF 3 ·OEt 2 as a
reference.
Experimental work involved the following dienes:
α-terpinene (0.12 mL, 0.7340 mmol), γ-terpinene
(0.12
mL,
0.7340
mmol),
1,3-cyclohexadiene
(0.07 mL, 0.7340 mmol), 1,3-cyclooctadiene (0.09 mL,
0.7340 mmol), 1,3,5,5-tetramethyl-1,3-cyclohexadiene
(0.13 mL, 0.7340 mmol), 1,2,4,5-tetramethyl-1,4-cyclohexadiene (0.1 g, 0.7340 mmol), 1,5-cyclooctadiene (0.12 mL,
0.7340 mmol), 2,3-dimethyl-1,3-butadiene (0.09 mL,
0.7340 mmol).
In THF, the representative procedure for the hydroboration of dienes used BH 3 ·SMe 2 , utilizing the borane to
diene addition mode: BH 3 ·SMe 2 (0.14 mL, 1.4680 mmol)
was added dropwise to a solution of a diene dissolved in
THF (1 mL) pre-cooled to −40 °C. The reaction mixture
was left to stir under nitrogen at 0 °C for 1 h to give a clear
solution, which, depending on the diene used, contained a
white precipitate.
In diglyme, the representative procedure for the hydroboration of dienes used BH 3 ·SMe 2 , utilizing the borane
to diene addition mode: BH 3 ·SMe 2 (0.07 mL, 0.7340 mmol
or 0.14 mL, 1.4680 mmol) was added dropwise to a solution of a diene dissolved in diglyme (3.2 mL). The reaction
mixture was left to stir under nitrogen at 0 °C for 1 h to
give a clear solution, which, depending on the diene used,
contained a white precipitate.
4 Conclusions
Hydroboration is one of the most valuable chemical synthesis methods, due to many reasons, including its highly
specifi c regio- and stereoselectivity. However, in complex
reagents, the identity of the preferred anti-Markovnikov
product is not apparent at fi rst glance. The use of electrostatic potential-based atomic charges has proved to be a
useful tool in predicting the regioselectivity of hydroboration reactions. Here we studied 11 molecules, representing
10 cyclic dienes and a straight chain diene. In most examples, the regioselectivity for the preferred product was predicted both by the extended anti-Markovnikov rule, using
the atomic charges of the reactants, and also by transition
state theory—comparing the activation energies of all possible products. Here we identifi ed the 1,3-cyclohexadiene molecule as a key exception to the anti-Markovnikov
rule, which had an unforeseen preference toward the allyl
product according to the transition state barrier heights.
Our calculated activation energies accurately predicted the
selectivity favoring almost equally the allyl products, in
agreement with previous experimental studies [ 19 ], therefore validating our transition state theory-based calculation
results. The unexpected selectivity was suggested to arise
due to steric effects [ 19 ]. We found, however, that steric
effects do not directly contribute to the observed selectivity, leading to a deviation from the anti-Markovnikov rule.
Instead, the stability of the axial BH 2 group via conjugation
with the allyl double bond is a more important stabilizing
factor, which also relies on the unique structural properties
of the cyclohexene ring as additional required factors for
the paradoxical regioselectivity. We also introduced two
additional derivatives (I6 and J6) and confi rmed the similar
selectivity rules favoring allyl positions for these molecules
as well. These molecules lend themselves as additional
examples with exceptional regioselectivity against the antiMarkovnikov rule.
As the anti-Markovnikov rule follows the same general principle as the Markovnikov rule [ 23 ] in terms of the
most energetically favorable reaction pathway being determined by the attractive dipole–dipole interactions within
a carbon–carbon double bond and the reacting X–H substituent, our results therefore provide an exception (on the
basis of F6, I6, and J6) to these rules in general. We found
that the Lewis acid borane, and the second remaining double bond with Lewis base properties, resembling frustrated
Lewis pair-type moieties, worked synergistically to stabilize allyl–π bond interactions resulting in the unexpected
selectivity. Using this as a design principle, molecules with
similar electronic properties might provide an interesting
avenue for the exploration of synthetically useful exceptions to the Markovnikov rule, resulting in novel chemical
reactivity.
Although it is known that the process of hydroboration
can occur fully at all unsaturated sites within an alkene, the
precise nature of the unoxidized species formed after the
completion of the reactions still remains within a gray area.
11 B NMR results show that several hydroboration reactions
are possible, and that a variety of products may be formed.
Quantum chemical calculations together with NMR
measurements can thus shed light on why a subset of reactants does not polymerize, while others do, and what the
potential reaction pathways and stable products are. The
observation of a plethora of products indicates that competing pathways concurrently take place within hydroboration reactions. It was concluded that the position of the
double bonds, in relation to sterically demanding groups,
was a strongly infl uencing factor in determining the structure of the product [ 17 ]. We have elucidated the mechanism
for the formation of cyclic monohydroborated species, as
well as specifi c diborane species. Our results are in very
246
Reprinted from the journal