188
M. Heshmat et al.
conditions. Water-tolerant FLP catalysis is an emerging and developing direction in
FLP chemistry [69–82]. There have been significant and (partially) successful efforts
aiming to reduce the water-sensitivity by modifying the functional groups that coordinate the boron LA-center. For example, Soós et al. have developed new derivatives
of BCF by tuning the electron-deficiency of the boron center and increasing the strain
in the Lewis acid structure to reduce the complexation propensity with water [61, 71,
78]. Ashley and coworkers have used higher H 2 pressures and reaction temperatures
in hydrogenation reactions [79, 80]. Repo et al. have shown that sterically hindered
phosphinoborane could be stable in water [81].
Recent experimental studies have shown that ethereal solvents (e.g., dioxane,
THF, and Et 2 O) act as LB for hydrogen activation in the hydrogenation of carbonyl
compounds due to their large excess in solution. The Lewis base role as an electrondonor can also be performed by water. In a recent theoretical study, water has been
considered as an active Lewis base (LB) in the H 2 splitting and subsequent hydrogenation of the C = O group in wet ethereal solutions [82]. A strongly stabilized
borohydride/hydronium intermediate in the hydrogenation mechanism was indicated computationally. The proposed borohydride/hydronium intermediate with the
hydronium cation having three OH
… ether hydrogen bonds or a combination of the
OH
… ether/OH
… ketone hydrogen bonds (Fig. 5.5), appears to be as valid as the
previously considered borohydride/oxonium (BCF-H
(−)… ether-H
(+) -ether) or borohydride/oxocarbenium (BCF-H
(-)… ether-H
(+) -ketone) intermediates (Scheme 5.8).
This study showed that (1) the minimum energy path of H 2 splitting via a borohydride/hydronium intermediate changes to exergonic in comparison to the routes via a
borohydride/oxonium or borohydride/oxocarbenium intermediate, which are highly
endergonic; (2) the proton-coupled hydride transfer from the borohydride/hydronium
to a ketone has a reasonably low barrier. It is noteworthy to mention that strong LBs,
such as amine or phosphine, can grab the acidic proton of the activated water molecule
(throughout complexation of water to the BCF) and form the deactivated BCF-OH
−
anion. However, this is not the case when the LB is an ethereal solvent molecule with
rather small pK a of protonated LB, e.g., for 1,4-dioxane pK a has been measured −
2.92 in aqueous solution [80]. Hence, the possibility of strong hydrogen bonding
with ethereal solvent is more dominant than deprotonation of water.
Figure 5.6 shows the calculated transition states structures of the H 2 splitting
(TS
HH ) in panel a, and hydride transfer (TS
HT ), panel b, with water as the active LB
in the hydrogenation reaction of acetone in wet dioxane solvent.
5.4 Mechanistic Studies Using AIMD Simulation
The first dynamics investigation of intermolecular FLPs was reported in 2012
by Pápai and coworkers, who investigated the association of the intermolecular
tBu 3 P/BCF FLP in toluene. Using classical molecular dynamics simulations with
explicit solvent, they found a fast dynamic equilibrium between the separated donor
and acceptor states and the paired donor
… acceptor state. No significant free energy
M. Heshmat et al.
conditions. Water-tolerant FLP catalysis is an emerging and developing direction in
FLP chemistry [69–82]. There have been significant and (partially) successful efforts
aiming to reduce the water-sensitivity by modifying the functional groups that coordinate the boron LA-center. For example, Soós et al. have developed new derivatives
of BCF by tuning the electron-deficiency of the boron center and increasing the strain
in the Lewis acid structure to reduce the complexation propensity with water [61, 71,
78]. Ashley and coworkers have used higher H 2 pressures and reaction temperatures
in hydrogenation reactions [79, 80]. Repo et al. have shown that sterically hindered
phosphinoborane could be stable in water [81].
Recent experimental studies have shown that ethereal solvents (e.g., dioxane,
THF, and Et 2 O) act as LB for hydrogen activation in the hydrogenation of carbonyl
compounds due to their large excess in solution. The Lewis base role as an electrondonor can also be performed by water. In a recent theoretical study, water has been
considered as an active Lewis base (LB) in the H 2 splitting and subsequent hydrogenation of the C = O group in wet ethereal solutions [82]. A strongly stabilized
borohydride/hydronium intermediate in the hydrogenation mechanism was indicated computationally. The proposed borohydride/hydronium intermediate with the
hydronium cation having three OH
… ether hydrogen bonds or a combination of the
OH
… ether/OH
… ketone hydrogen bonds (Fig. 5.5), appears to be as valid as the
previously considered borohydride/oxonium (BCF-H
(−)… ether-H
(+) -ether) or borohydride/oxocarbenium (BCF-H
(-)… ether-H
(+) -ketone) intermediates (Scheme 5.8).
This study showed that (1) the minimum energy path of H 2 splitting via a borohydride/hydronium intermediate changes to exergonic in comparison to the routes via a
borohydride/oxonium or borohydride/oxocarbenium intermediate, which are highly
endergonic; (2) the proton-coupled hydride transfer from the borohydride/hydronium
to a ketone has a reasonably low barrier. It is noteworthy to mention that strong LBs,
such as amine or phosphine, can grab the acidic proton of the activated water molecule
(throughout complexation of water to the BCF) and form the deactivated BCF-OH
−
anion. However, this is not the case when the LB is an ethereal solvent molecule with
rather small pK a of protonated LB, e.g., for 1,4-dioxane pK a has been measured −
2.92 in aqueous solution [80]. Hence, the possibility of strong hydrogen bonding
with ethereal solvent is more dominant than deprotonation of water.
Figure 5.6 shows the calculated transition states structures of the H 2 splitting
(TS
HH ) in panel a, and hydride transfer (TS
HT ), panel b, with water as the active LB
in the hydrogenation reaction of acetone in wet dioxane solvent.
5.4 Mechanistic Studies Using AIMD Simulation
The first dynamics investigation of intermolecular FLPs was reported in 2012
by Pápai and coworkers, who investigated the association of the intermolecular
tBu 3 P/BCF FLP in toluene. Using classical molecular dynamics simulations with
explicit solvent, they found a fast dynamic equilibrium between the separated donor
and acceptor states and the paired donor
… acceptor state. No significant free energy