Potassium Fluoride-Catalyzed Hydroboration of Aldehydes and Ketones: Facile Reduction to Primary and Secondary Alcohols

Article abstract of DOI:10.1002/ejoc.201901514

A catalytic hydroboration of various ketones and aldehydes can be achieved in the presence of inexpensive and commercially available inorganic salts containing fluoride anion. As a result, the reduction of carbonyl moieties to the corresponding primary and secondary alcohols can be achieved at room temperature under mild conditions.

Full text of DOI:10.1002/ejoc.201901514

A Journal of
Accepted Article
Title: Potassium Fluoride-Catalyzed Hydroboration of Aldehydes and
Ketones: Facile Reduction to Primary and Secondary Alcohols
Authors: Krzysztof Kuciński and Grzegorz Hreczycho
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10.1002/ejoc.201901514
European Journal of Organic Chemistry
COMMUNICATION
Potassium Fluoride-Catalyzed Hydroboration of Aldehydes and
Ketones: Facile Reduction to Primary and Secondary Alcohols
Krzysztof Kuciński*[a], Grzegorz Hreczycho*[a,b]
Dedicated to Professor Bogdan Marciniec on the occasion of his forthcoming 79th birthday.
Abstract:
A
catalytic hydroboration of various ketones and
importance to scientists. The best evidence of this is the
dynamically growing number of scientific reports over recent
years (more than 200 articles annually in accordance with WoS).
Therefore, a wide range of different catalysts have already been
applied for this purpose, starting with transition metal[3] and rare-
earth element complexes,[4] through main group catalysts,[5] up
to the catalyst-free approaches (Figure 1).[6] More or less
significant drawbacks characterize all of them (e.g., expensive or
sensitive reagents/catalysts, elevated temperature, etc.).
aldehydes can be achieved in the presence of inexpensive and
commercially available inorganic salts containing fluoride anion. As a
result, the reduction of carbonyl moieties to the corresponding
primary and secondary alcohols can be achieved at rt under mild
conditions.
The hydroboration of unsaturated systems[1] (the sister’s process
to the hydrosilylation)[2] is becoming an issue of increasing
Figure 1. An illustration of various synthetic methodologies used in the hydroboration of unsaturated moieties.
The primary attention should be paid to synthetic solutions using
main-group compounds as catalysts, as well as on catalyst-free
approaches. Both of them provide the process to some extent
following green chemistry aspects. Recently, our group
developed some of procedures utilizing pinacolborane (HBPin)
in O-borylation of silanols/polyhedral oligomeric silsesquioxane
silanols (POSS silanols)[7,8] and hydroboration of carbonyls.[5u,6d]
Our studies have shown that aldehydes can be efficiently
transformed into their boronic ester derivatives under catalyst-
free and solvent-free conditions (mostly at elevated temperature).
However, ketones were inactive in this process. Last results
done by Wang et al., have shown that in case of ketones, a
higher temperature is necessary to improve the conversion
rates.[6e] Therefore, we continued our studies to find a solution,
which will be applicable to both carbonyl moieties. As a result, a
very efficient LiHBEt3-catalyzed procedure has been
discovered.[5u] Nonetheless, lithium triethylborohydride is very
sensitive and requires special care due to its high reactivity.
Consequently, in view of our previous reports, the aim of this
work was to check the possibility of utilizing inexpensive,
accessible, and non-sensitive main group specie as the catalyst
in the hydroboration of C=O moieties. Our studies resulted in a
very facile and sustainable method for a KF-catalyzed addition
of pinacolborane to both aldehydes and ketones under mild
conditions. In all cases, this is followed by the hydrolysis of the
obtained boronic ester to its corresponding primary or
secondary alcohol. To the best of our knowledge, unlike the
hydrosilylation,[9] this is the first study about the utilization of
[a]
[b]
Dr. Krzysztof Kuciński, Prof. Dr. Grzegorz Hreczycho
Faculty of Chemistry, Adam Mickiewicz University in Poznań,
Ul. Uniwersytetu Poznańskiego 8, 61-614 Poznań (Poland).
E-mail: kucinski.k@amu.edu.pl
Prof. Dr. Grzegorz Hreczycho
Center for Advanced Technologies, Adam Mickiewicz University,
Centre for Advanced Technologies, Ul. Uniwersytetu Poznańskiego
10, 61-614 Poznań (Poland),
Homepage: http://ghgroup.home.amu.edu.pl
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901514
European Journal of Organic Chemistry
COMMUNICATION
simple inorganic salts containing fluoride anion in the
hydroboration reaction.
formylbenzoate (1v) could be selectively converted at the
aldehyde, while preserving the ketone/ester functionality
(Scheme 1). Finally, the reaction of acetophenone (1a) with
pinacolborane (2b) also proceeded well on a gram scale,
providing 1-phenylethanol (3a, 1.35 g) in 90% yield (see the ESI).
In earlier literature, alkali metal fluorides showed great potential
in the hydrosilylation. Thus, cesium and potassium fluorides
were selected for screening to probe their effectiveness as the
catalysts for hydroboration. Initially, we began our studies by
exploring reaction conditions for the envisioned hydroboration of
acetophenone (1a) with pinacolborane (2b) using inexpensive
alkali metal fluorides (M = K and Cs) as the catalysts (Table 1).
Most of the testing reactions were probed in DMF, in relation to
the issue of appropriate solubility of these inorganic salts.
Table 1. Optimization of the reaction conditions. [a]
Entry
Equiv. of MF
Time (min.)
Conversion (%)[b]
KF
0.1
1
2
3
5
30
60
24 h
24 h
60
99
99
99
89
99
0.05
0.01
0.005
0.01
0.01
CsF
0.1
0.05
0.01
0.005
TBAF
0.05
4
5[c]
6[d]
traces
Scheme 1. KF-catalyzed hydroboration of ketones/aldehydes, followed by the
6
7
8
9
5
30
60
99
99
99
85
hydrolysis to the corresponding alcohols.
24 h
In light of previous literature and stoichiometric reactions (please
see SI),[5n,6d,10] KF-catalyzed hydroboration of ketones and
aldehydes proceeds through B-H bond activation. The resulting
mixture of HBpin and KF was analyzed by 1H and 11B NMR
spectroscopy. It determines the formation of new hypervalent
“ate” specie. A fluoride anion increases the hydridic character of
the hydrogen atom and thus facilitates and accelerates the
further reduction of the carbonyl bond.
10
5
40
[a] Reaction conditions: rt, 1a (1.0 equiv.), 2b (1.2 equiv.), DMF (1 ml). [b]
Determined by GC. [c] THF as the solvent. [d] Solvent-free conditions.
It turned out that 1 mol% of KF is enough to give quantitative
conversion of acetophenone to its reduced boronate ester
product after 60 minutes (Table 1, entry 3). CsF showed similar
activity, however we decided to use KF due to its lower price.
The reaction can also be carried out in THF, but it needs a
longer time (24 h). Lastly, we also tested TBAF as the source of
the fluoride anion (Table 1, entry 10). In this case, the
conversion was lower (40%), and the symmetrical diboraxane
was formed in significant amount (30%). Overall, the formation
of pinB-O-Bpin was observed in all tests (approx. 5–10%),[5u]
therefore we transformed all of the afforded boronate esters
(despite their isolation) directly to corresponding alcohols (after
the hydrolysis with aqueous 1M NaOH solution).
In summary, we have developed the first example of a catalytic
hydroboration strategy that uses an easily available inorganic
salt containing fluoride ion – potassium fluoride (KF), under very
mild reaction conditions (air atmosphere, rt). As a result, the
numerous ketones and aldehydes, bearing a wide range of
electron-withdrawing and electron-donating groups, were
successfully reduced to the corresponding primary and
secondary alcohols (after the hydrolysis step). Taking into
account the combination of desirable features, such as operation
simplicity, an exclusive aldehyde selectivity over ketone, benign
reaction conditions, low cost of the catalyst as well as its
commercial availability, this reaction system is expected to
Next, we examined various ketones and aldehydes under the
conditions given in Table 1, entry 3. In some cases, the amounts
of the catalyst and HBpin were higher (marked with an asterisk
on Scheme 1). Thus, the reaction smoothly proceeded with
ketones/aldehydes 1a-u bearing electron-donating or electron-
withdrawing groups (see Scheme 1). In the majority of the cases,
less electron-rich reactants were more reactive than their
electron-rich counterparts. The halogenated substrates are well
tolerated (1c-d,1f-g), as well as nitrile (1e), and nitro (1q) groups
remain untouched during the process. We were particularly
delighted that 4-acetylbenzaldehyde (1u) and methyl 4-
provide
a promising alternative to existing methodologies.
Furthermore, the approaches around earth-abundant metals
make for an environmentally and economically attractive
synthetic solutions. Therefore, the possibility that such simple
inorganic salts may play
a pivotal role in some of the
organoboron transformations is under further investigation.
Experimental Section
General Information. All reactions were carried out under air
atmosphere and at ambient temperature. The dry solvent was used
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10.1002/ejoc.201901514
European Journal of Organic Chemistry
COMMUNICATION
throughout in case of solid substrates. Pinacolborane, potassium fluoride,
cesium fluoride, aldehydes, and ketones were purchased from Sigma-
Aldrich and were used as received. The structure of products was
determined by NMR spectroscopy. The 1H NMR (400 or 600 MHz) and
13C NMR (101 or 151 MHz) spectra were recorded on a Bruker Avance III
HD NanoBay spectrometer, using chloroform-d (CDCl3) as the solvent.
The deuterated solvent was purchased from Sigma-Aldrich (99.8 atom%
D) and used as received. All procedures and spectra are included in
Supporting Information File.
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Acknowledgements
This work was supported by a National Science Centre Grant
UMO-2018/30/E/ST5/00045 (GH).
Keywords: Hydroboration • Boranes • Carbonyls • Reduction •
Aldehydes and Ketones
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COMMUNICATION
Entry for the Table of Contents
Insert graphic for Table of Contents here.
Fluoride ion – not only for silicon: the first example of a catalytic hydroboration strategy that uses an easily available inorganic salt
containing fluoride ion – potassium fluoride (KF), under very mild reaction conditions (air atmosphere, rt).
Key Topic: Hydroboration of Carbonyls
Institute and/or researcher Twitter usernames: @SiBGeChem
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