152
Y. Soltani and F.-G. Fontaine
conditions, which is using 10 mol% of catalyst with a slight excess of HBPin in the
absence of solvent (HBpin serves as the solvent), the borylation of indoles at the
3-position was possible under 4 h at 80 °C. The practicability of this process was
demonstrated by carrying out the borylation of 1 kg of 1-Me-indole with over 95%
yield at a fraction of the cost required to prepare the same product using typical
iridium borylation catalysts [88] (Scheme 4.45).
The stability of the fluoroborate salts allowed for the preparation of several
styrene analogues (Scheme 4.46). These derivatives were polymerized using AIBN to
generate polystyrene materials that are active for the C–H borylation (Scheme 4.46)
[89]. As expected, the catalytic activity of the polymers is lower than that of the
homogeneous catalysts. The piperidine analogue proved to be the most efficient for
the borylation reaction, but presented stability issues after recycling the polymer,
going from 95% yield for the borylation of 1-Me-pyrrole in the first run, to 31% in
the third run. They proposed that the presence of cyclohexanol within the material,
which could not be removed in the polymerization procedure, is responsible for the
deactivation of the catalyst and the loss of efficiency. This was demonstrated by
looking at the activity of the diethylamine derivative with and without the removal of
the cyclohexanol during the polymer purification. It was observed that the presence of
cyclohexanol significantly decreases the recyclability of the catalyst (Scheme 4.47).
4.7 Isodesmic Borylation: Auto-Assembled FLPs
This FLP-catalysed borylation is possible using hydroboranes, notably HBPin, as
borylation agents. While this transformation gives a high atom economy (the only side
product is H 2 ), the chemistry needs to be handled under nitrogen atmosphere because
the –BH moieties, present in the borylation agent and in the catalyst, are highly
moisture-sensitive. Indeed, while the borylation is quite efficient with heteroaromatic
molecules, protic moieties (alcohols, amines) and functional groups that can undergo
hydroboration (alkenes, alkynes, ketones) inhibit completely the catalytic activity.
While transition metal catalysts are more tolerant than FLP catalysts for the C–H
borylation reaction, many systems exhibit undesired side reactivity with hydroboranes, that are either used as borylation agent or are generated in situ following
the C–H activation by diboranes [90]. The Fontaine group tried to circumvent these
problems by using arylboronates instead of hydroboranes as borylation agent using
the concept of isodesmic reactivity (Fig. 4.14) [91].
The general catalyst design was inspired by species 26, reported by Repo and
co-workers (Scheme 4.48) [82]. The molecule 26 was shown to be active in the
borylation of thiophene and indoles in the presence of HBCat. The mechanism is
somewhat different than the chemistry observed with aminoboranes since no σ-bond
metathesis is required for the borylation to take place. Nevertheless, the practicality
of this system is limited by the low catalytic activity, the synthetic complexity of this
catalyst and the requirement of using HBCat, which is known to degrade in solution
and is moisture sensitive [5].
Y. Soltani and F.-G. Fontaine
conditions, which is using 10 mol% of catalyst with a slight excess of HBPin in the
absence of solvent (HBpin serves as the solvent), the borylation of indoles at the
3-position was possible under 4 h at 80 °C. The practicability of this process was
demonstrated by carrying out the borylation of 1 kg of 1-Me-indole with over 95%
yield at a fraction of the cost required to prepare the same product using typical
iridium borylation catalysts [88] (Scheme 4.45).
The stability of the fluoroborate salts allowed for the preparation of several
styrene analogues (Scheme 4.46). These derivatives were polymerized using AIBN to
generate polystyrene materials that are active for the C–H borylation (Scheme 4.46)
[89]. As expected, the catalytic activity of the polymers is lower than that of the
homogeneous catalysts. The piperidine analogue proved to be the most efficient for
the borylation reaction, but presented stability issues after recycling the polymer,
going from 95% yield for the borylation of 1-Me-pyrrole in the first run, to 31% in
the third run. They proposed that the presence of cyclohexanol within the material,
which could not be removed in the polymerization procedure, is responsible for the
deactivation of the catalyst and the loss of efficiency. This was demonstrated by
looking at the activity of the diethylamine derivative with and without the removal of
the cyclohexanol during the polymer purification. It was observed that the presence of
cyclohexanol significantly decreases the recyclability of the catalyst (Scheme 4.47).
4.7 Isodesmic Borylation: Auto-Assembled FLPs
This FLP-catalysed borylation is possible using hydroboranes, notably HBPin, as
borylation agents. While this transformation gives a high atom economy (the only side
product is H 2 ), the chemistry needs to be handled under nitrogen atmosphere because
the –BH moieties, present in the borylation agent and in the catalyst, are highly
moisture-sensitive. Indeed, while the borylation is quite efficient with heteroaromatic
molecules, protic moieties (alcohols, amines) and functional groups that can undergo
hydroboration (alkenes, alkynes, ketones) inhibit completely the catalytic activity.
While transition metal catalysts are more tolerant than FLP catalysts for the C–H
borylation reaction, many systems exhibit undesired side reactivity with hydroboranes, that are either used as borylation agent or are generated in situ following
the C–H activation by diboranes [90]. The Fontaine group tried to circumvent these
problems by using arylboronates instead of hydroboranes as borylation agent using
the concept of isodesmic reactivity (Fig. 4.14) [91].
The general catalyst design was inspired by species 26, reported by Repo and
co-workers (Scheme 4.48) [82]. The molecule 26 was shown to be active in the
borylation of thiophene and indoles in the presence of HBCat. The mechanism is
somewhat different than the chemistry observed with aminoboranes since no σ-bond
metathesis is required for the borylation to take place. Nevertheless, the practicality
of this system is limited by the low catalytic activity, the synthetic complexity of this
catalyst and the requirement of using HBCat, which is known to degrade in solution
and is moisture sensitive [5].