Unlocking the catalytic potential of tris(3,4,5-trifluorophenyl)borane with microwave irradiation

Article abstract of DOI:10.1039/C8CC09459D

The catalytic activity of tris(3,4,5-trifluorophenyl)borane has been explored in the 1,2-hydroboration reactions of unsaturated substrates. Under conventional conditions, the borane was found to be active only in the hydroboration of aldehyde, ketone and imine substrates, with alkenes and alkynes not being reduced effectively. The use of microwave irradiation on the other hand has permitted alkenes and alkynes to be hydroborated in good yields.

Full text of DOI:10.1039/C8CC09459D

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Unlocking the catalytic potential of
tris(3,4,5-trifluorophenyl)borane with
microwave irradiation†
Cite this: Chem. Commun., 2019,
55, 318
Received 28th November 2018,
Accepted 3rd December 2018
ab
a
Jamie L. Carden,a Lukas J. Gierlichs,a Duncan F. Wass,
Duncan L. Browne
a
and Rebecca L. Melen
*
DOI: 10.1039/c8cc09459d
rsc.li/chemcomm
The catalytic activity of tris(3,4,5-trifluorophenyl)borane has been benefits compared to traditional heating methods, including
explored in the 1,2-hydroboration reactions of unsaturated sub- the ability to heat reactions to higher temperatures and pressures in
strates. Under conventional conditions, the borane was found to be a safe manner, facilitating conventionally inaccessible chemistry,
active only in the hydroboration of aldehyde, ketone and imine and allowing rapid reaction screening when combined with modern
substrates, with alkenes and alkynes not being reduced effectively. autosamplers.28,29 The use of microwave assisted synthesis is now
The use of microwave irradiation on the other hand has permitted commonplace in organic chemistry, for example in Suzuki cross-
alkenes and alkynes to be hydroborated in good yields.
coupling reactions,30 but reports of microwave assisted catalytic
hydroboration are rarer and are limited to transition metal
Catalytic hydroboration is a well-known, efficient method of catalysts.31–33 The application of microwaves in main group
producing borylated substrates with wide synthetic applicability.1–3 chemistry is confined to just a single example in which micro-
Classically, there has been focus on the use of precious metal wave irradiation was used for frustrated Lewis pair catalysed
catalysts for this transformation,4–6 but recently there has been hydrogenation reactions.34 Microwave irradiation can enable
a surge of interest in using more abundant, non-toxic, and chemists to access higher reaction temperatures, increased
cheaper alternatives such as early transition metals and main reaction yields, reduced reaction times and may provide access
group elements.1,7–25 Recent work has shown that Lewis acidic to reactions that cannot take place using traditional heating
boranes and borocations can act as efficient catalysts for this methods. Previous work in our research groups has focused on
process (Fig. 1).11–14 For example, Oestreich explored the use the use of enabling technologies such as flow chemistry to
of tris[3,5-bis(trifluoromethyl)phenyl]borane (BArF3), whilst we advance the field of main group catalysis.35
have focused on the use of tris(2,4,6-trifluorophenyl)borane
(B(2,4,6-ArF)3),11,12 with both catalysts proving to be more active
than the archetypal tris(pentafluorophenyl)borane (B(C6F5)3).
The aforementioned borane catalysts work efficiently but are some-
times hindered by lengthy reaction times and limited substrate
scope, particularly in the case of ketones, alkenes and alkynes.
One potential method to eliminate these problems is by
employing microwave irradiation. The use of microwave assisted
heating for synthesis and catalysis was first reported by Giguere
and Gedye simultaneously in 1986.26,27 While early methods
of microwave assisted synthesis involved the use of modified
domestic microwave ovens, the field has expanded greatly
to become an enabling technology for organic synthesis and
catalysis.28,29 Microwave irradiation for heating offers many
a School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff,
Cymru/Wales, CF10 3AT, UK. E-mail: MelenR@cardiff.ac.uk
b School of Chemistry, University of Bristol, Cantock’s Close, Bristol, England,
BS8 1TS, UK
Fig. 1 Previous work on borane catalysed hydroboration with conventional
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c8cc09459d
conditions (top) and this work, assisted with enabling technologies (bottom).
318 | Chem. Commun., 2019, 55, 318--321
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In this work, we seek to develop the scope of main group isolated yield. Conversely, the more sterically demanding benzo-
reactions that can be performed using microwave irradiation as phenone substrate took 156 h to yield 2j in 84% yield. Aldimines
an enabling technology (Fig. 1).
were readily reduced to the amines (2k–s) typically giving
Initially we synthesised a range of Lewis acidic borane quantitative conversions and 86–96% isolated yields in up to
catalysts and screened these in the catalytic hydroboration of 60 h. The exception to this was in the synthesis of 2s which took
acetophenone using HBPin (1.1 equiv.) (Table 1). We were 156 h to undergo complete hydroboration. B(3,4,5-ArF)3 could
particularly interested in the tris(3,4,5-trifluorophenyl)borane also catalyse the hydroboration of the ketimine N,1-diphenylethan-
(B(3,4,5-ArF)3) as a hydroboration catalyst. While a single stoi- 1-imine yielding the boronate ester 1t which was found to be stable
chiometric reaction using this borane was reported, its catalytic to hydrolysis.
properties remain underexplored.12 It was postulated that as
While B(3,4,5-ArF)3 was found to be an efficient catalyst for
this triaryl borane is devoid of ortho-fluorines, like BArF3, it a range of unsaturated substrates, sometimes long reaction
would be an active catalyst for hydroboration reactions where times were required to reach quantitative conversion at room
B(C6F5)3 is not.12 This hypothesis was confirmed using 2 mol% temperature.
catalyst loading of B(3,4,5-ArF)3, which gave quantitative conversion
In response to this, we decided to test the catalytic properties
of acetophenone to the reduced boronate ester product after of B(3,4,5-ArF)3 at reflux in CDCl3. We focused our attention on
just one hour in CDCl3 at room temperature (entry 2, Table 1). substrates that proceeded slower (41 h) at room temperature.
Conversely, other boranes including BF3, BPh3, B(C6F5)3, and All of the aldehydes tested showed quantitative hydroboration
B(2,4,6-ArF)3 showed very poor conversions ranging from 3–27% to 1a–e within 0.5 h at 70 1C with isolated yields of 2a–e greater
after 24 h at room temperature (entries 3–6, Table 1). The reaction than 85% following hydrolysis. This demonstrates a significant
was also tolerant to both coordinating and non-coordinating reduction in reaction time from the 2–24 h reactions observed at
solvents (entries 7 and 8, Table 1). However, for the convenience room temperature. Ketone 1-(4-(trifluoromethyl) phenyl)ethan-
of in situ monitoring via 1H NMR spectroscopy, we decided to 1-one also showed quantitative conversion to 1h within 0.5 h
continue with deuterated chloroform for the substrate screening. giving the product 2h in 87% yield. Benzophenone also showed
Using 1 equivalent of HBPin saw a reduced conversion as observed a reduction in reaction time from 156 h to 30 h, with 85%
in other reports,11 and increasing the catalyst loading to 5 mol% conversion to 2j. Secondary amines 2k–s could be synthesised
did not significantly improve the rate of reaction (entries 9 and 10 quantitatively within 0.5–4 h, compared with reaction times up
respectively, Table 1). Other borylating agents such as 9-BBN to 60 h at room temperature. Ketimines also worked well giving
showed no reactivity after 24 h (entry 11, Table 1).
1t in 80% isolated yields after 0.5 h compared to the 24 h
With the optimised conditions in hand, we moved our reaction time needed at room temperature.
attention to the hydroboration of a range of aldehydes, ketones,
Having established that we have an active borane catalyst for
and imines with HBPin to explore the aptitude of our borane the hydroboration of CQX (X = O, N) we then decided to determine
catalyst at room temperature (Fig. 2). Hydrolysis of the boronate if we could improve the reaction in terms of (i) conditions and
ester products (1) yielded the corresponding alcohols 2. Aldehydes (ii) substrate scope using microwave irradiation. With the cap-
with both electron donating and withdrawing groups worked well ability of a Biotages microwave reactor, we were able to heat the
for this transformation giving the alcohols 2a–e in 87–98% isolated reaction samples safely to 180 1C to accelerate the hydroboration
yield following hydrolysis in less than 24 h. Ketones also worked reactions. Although chloroform is an uncommon solvent for
very well affording the secondary alcohols 2f–i in 89–96% microwave assisted reactions due to its low loss factor and
Table 1 Optimisation of room temperature reaction conditions
Entry
Catalyst
Loading (mol%)
Boron source (eq.)
Solvent
Time (h)
Conversiona (%)
1
2
3
4
5
6
7
8
No catalyst
B(3,4,5-ArF)3
BF3ÁEt2O
—
2
2
2
2
2
2
2
2
5
2
HBPin (1.1)
HBPin (1.1)
HBPin (1.1)
HBPin (1.1)
HBPin (1.1)
HBPin (1.1)
HBPin (1.1)
HBPin (1.1)
HBPin (1)
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
Et2O
Toluene
CDCl3
CDCl3
CDCl3
24
1
24
24
24
24
2
16
24
1
0
495
18
27
3
BPh3
B(C6F5)3
B(2,4,6-ArF)3
B(3,4,5-ArF)3
B(3,4,5-ArF)3
B(3,4,5-ArF)3
B(3,4,5-ArF)3
B(3,4,5-ArF)3
21
495
495
79
495
0
9
10
11
HBPin (1.1)
9-BBN (1.1)
24
a
Acetophenone (0.2 mmol, 24 mg). Conversion determined by 1H NMR spectroscopy with mesitylene standard (0.1 mmol, 14 mL).
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Fig. 2 Hydroboration of aldehydes, ketones, and imines with HBPin using B(3,4,5-ArF)3. Conversions determined by 1H NMR spectroscopy. Isolated
yields given in parentheses. a Time taken to reach quantitative conversion at room temperature. b Time taken to reach quantitative conversion at 70 1C.
c Achieved maximum conversion of 85% at 70 1C and did not increase past this value. d Time taken and conversion in microwave at 180 1C. Isolated yields
given in parentheses.
dielectric constant,29 it was chosen as the reaction medium to encumberment of benzophenone resulted in 25% conversion after
negate any possible solvent influence on catalysis and to allow a 5 min. Attempts to improve the yield by increasing the reaction time
direct comparison to traditional heating methods. At this further to 0.5 h or 1 h showed a small increase in yield to 38% and
juncture, it was important to quench the reaction immediately 45% respectively.
after the heating process had ended to ensure that the conver-
After demonstrating that B(3,4,5-ArF)3 was not only an
sion reflected the microwave reaction only, and not a combi- excellent catalyst for the hydroboration of heteronuclear CQX
nation of the conversion in the microwave and a continuing (X = O, N) bonds both under conventional heating techniques
process in the reaction vessel after microwave irradiation had and with microwave irradiation, we turned our attentions to
ceased. Therefore, we performed a basic workup immediately more challenging substrates with homonuclear unsaturated
after microwave irradiation had ended to remove the catalyst bonds (CQC and CRC). Using phenylacetylene as our test
and to hydrolyse the boronate ester to give the corresponding substrate, we first explored the conventional hydroboration
alcohol or amine. The majority of substrates showed much reaction catalysed by B(3,4,5-ArF)3. Using 2 mol% B(3,4,5-ArF)3,
improved reactivity with microwave irradiation, giving full negligible conversion was observed after 24 h at 70 1C, and for
conversion (495%) within 5 minutes. These slower conversions 5 and 10 mol% B(3,4,5-ArF)3, it took 96 h for the reaction to reach
to 2h and 2n can be attributed to the more electron deficient ketone 50% and quantitative conversion respectively (entries 1 and 2,
or imine substrates which gave a slightly lower conversion of 71% Table 2). We then turned to microwave irradiation reactions to
after 5 min (2h) and 95% after 1 h (2n). The increased steric reduce the reaction time from days to something that would be
Table 2 Optimisation of microwave reaction conditions for the hydroboration of phenylacetylene using HBPin
Entry
Catalyst
Loading (mol%)
Temperature (1C)
Time (min)
Conversiona (%)
1
2
3
4
5
6
7
8
B(3,4,5-ArF)3
B(3,4,5-ArF)3
B(3,4,5-ArF)3
None
5
10
5
—
2
2
2
5
5
5
5
70 (no MW)
5760 (96 h)
5760 (96 h)
50
495
40
70 (no MW)
180 (no MW)b
90
90
20
40
90
20
40
90
90
180
180
180
180
180
180
180
180
o5
B(3,4,5-ArF)3
B(3,4,5-ArF)3
B(3,4,5-ArF)3
B(3,4,5-ArF)3
B(3,4,5-ArF)3
B(3,4,5-ArF)3
BH3ÁSMe2
47
63
71
77
86
495
11
9
10
11
Phenyl acetylene (0.4 mmol, 40.8 mg), HBPin (0.44 mmol, 63.8 mL), chloroform solvent (2 mL). Microwave reaction conditions À180 1C, 20 bar.
a
b
Conversion determined by 1H NMR spectroscopy. Reaction completed in an oven heated Parr acid digestion vessel.
320 | Chem. Commun., 2019, 55, 318--321
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allows enhanced reactivity of substrates that were formerly
recalcitrant under traditional approaches.
We would like to thank the EPSRC for funding (JLC,
EP/L016443/1; RLM, EP/R026912/1).
Conflicts of interest
There are no conflicts to declare.
Notes and references
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