4 FLP-Mediated C–H-Activation
119
pair that can access a TS where the Lewis acid and the Lewis base are not neutralized and can cooperate for the activation of a bond”. According to this definition,
a FLP is defined by its reactivity, and therefore is a kinetic concept [24]. It also
correctly describes processes where FLP reactivity is observed with Lewis pairs that
do not have accessible Lewis acidic and/or Lewis basic sites at the resting state.
Looking back at the three main mechanisms proposed for TM catalysed transformations (Fig. 4.1), it is evident that most FLPs (especially the boron-based ones) cannot
easily operate through oxidative addition since most main group elements cannot
access readily more than one oxidation state. However, the σ-bond metathesis and
the electrophilic activation TS are accessible, with the Lewis acid acting as the LUMO
orbital (electrophile) and the Lewis base as the HOMO orbital (nucleophile).
Looking back at Fig. 4.2, we can see analogies in the σ-bond metathesis step,
which is typical of FLP activation processes, and the electrophilic activation. The
main difference between these two processes is the formation of an arenium ion
(Wheland intermediate) prior to the release of a proton in the electrophilic activation mechanism, whereas the corresponding structure is instead a TS in FLP chemistry. Since we know that H
+ does not exist freely and requires stabilization, can we
preclude the necessity of the Lewis base, as weakly as it might be, to abstract the
proton and for this reaction to proceed? If so, where is the defining line between
electrophilic and FLP processes in systems where the Wheland is high in energy and
doubtfully exist? We are not claiming that electrophilic activation is a FLP process,
but there is a grey zone between a FLP activation and an electrophilic activation and
one cannot review one process without writing about the other.
4.4 Functionalization of C–H Bonds Through Electrophilic
Activation
4.4.1 Electrophilic Borylation Starting from Haloboranes
The electrophilic pathway makes use of the reactivity of positively charged ions
towards aromatic C–H-bonds via a Wheland intermediate (Fig. 4.2). While several
examples of electrophilic addition have been reported, the electrophilic borylation
is the most pertinent reaction in line with FLP-type reactivity. The first mention of
metal-free borylation of arenes was reported by Muetterties et al. using BCl 3 and
AlCl 3 [25–28]. It was proposed by Ingleson [29] that this combination of reactants
under the harsh conditions described by Muetterties might form an unobserved boron
species related to [BCl 2 ][AlCl 4 ], which would be the active species responsible
for this reactivity. In 1960, Dewar reacted a thiophenol with BCl 3 and AlCl 3 to
form a cationic boron species (Int2) that carries on to react with the C2
-atom of
the thiophenol molecule to form an arenium intermediate (Int3) [30]. After proton
abstraction, the system rearomatizes to form a thiaborin derivative (Scheme 4.4).
119
pair that can access a TS where the Lewis acid and the Lewis base are not neutralized and can cooperate for the activation of a bond”. According to this definition,
a FLP is defined by its reactivity, and therefore is a kinetic concept [24]. It also
correctly describes processes where FLP reactivity is observed with Lewis pairs that
do not have accessible Lewis acidic and/or Lewis basic sites at the resting state.
Looking back at the three main mechanisms proposed for TM catalysed transformations (Fig. 4.1), it is evident that most FLPs (especially the boron-based ones) cannot
easily operate through oxidative addition since most main group elements cannot
access readily more than one oxidation state. However, the σ-bond metathesis and
the electrophilic activation TS are accessible, with the Lewis acid acting as the LUMO
orbital (electrophile) and the Lewis base as the HOMO orbital (nucleophile).
Looking back at Fig. 4.2, we can see analogies in the σ-bond metathesis step,
which is typical of FLP activation processes, and the electrophilic activation. The
main difference between these two processes is the formation of an arenium ion
(Wheland intermediate) prior to the release of a proton in the electrophilic activation mechanism, whereas the corresponding structure is instead a TS in FLP chemistry. Since we know that H
+ does not exist freely and requires stabilization, can we
preclude the necessity of the Lewis base, as weakly as it might be, to abstract the
proton and for this reaction to proceed? If so, where is the defining line between
electrophilic and FLP processes in systems where the Wheland is high in energy and
doubtfully exist? We are not claiming that electrophilic activation is a FLP process,
but there is a grey zone between a FLP activation and an electrophilic activation and
one cannot review one process without writing about the other.
4.4 Functionalization of C–H Bonds Through Electrophilic
Activation
4.4.1 Electrophilic Borylation Starting from Haloboranes
The electrophilic pathway makes use of the reactivity of positively charged ions
towards aromatic C–H-bonds via a Wheland intermediate (Fig. 4.2). While several
examples of electrophilic addition have been reported, the electrophilic borylation
is the most pertinent reaction in line with FLP-type reactivity. The first mention of
metal-free borylation of arenes was reported by Muetterties et al. using BCl 3 and
AlCl 3 [25–28]. It was proposed by Ingleson [29] that this combination of reactants
under the harsh conditions described by Muetterties might form an unobserved boron
species related to [BCl 2 ][AlCl 4 ], which would be the active species responsible
for this reactivity. In 1960, Dewar reacted a thiophenol with BCl 3 and AlCl 3 to
form a cationic boron species (Int2) that carries on to react with the C2
-atom of
the thiophenol molecule to form an arenium intermediate (Int3) [30]. After proton
abstraction, the system rearomatizes to form a thiaborin derivative (Scheme 4.4).