Arsenic Catalysis: Hydroboration of Aldehydes Using a Benzo-Fused Diaza-benzyloxy-arsole

Article abstract of DOI:10.1002/chem.201803508

The first example of a homogenous As^III catalyst for hydroboration has been established. The reaction of N,N′-diisopropylbenzene diamine or toluene-3,4-dithiol with AsCl₃ yielded the chloroarsoles (1 and 2), which upon reaction with

Full text of DOI:10.1002/chem.201803508

A Journal of
Accepted Article
Title: Arsenic Catalysis: Hydroboration of Aldehydes Using a Benzo-
Fused Diaza-benzyloxy-arsole
Authors: Rebecca Melen and Darren Ould
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To be cited as: Chem. Eur. J. 10.1002/chem.201803508
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Arsenic Catalysis: Hydroboration of Aldehydes Using a Benzo-
fused Diaza-benzyloxy-arsole
Darren M. C. Ould and Rebecca L. Melen*
Abstract: The first example of a homogenous As(III) catalyst for
hydroboration has been established. The reaction of N,N’-
diisopropylbenzene diamine or toluene-3,4-dithiol with AsCl3 yielded
the chloroarsoles (1 and 2) which upon reaction with benzyl alcohol
yielded the benzyloxy benzo-1,3,2-diazaarsole (3) and benzo-1,3,2-
dithiaarsole (4) respectively. 3 was found to be an excellent catalyst
for the hydroboration of aldehyde substrates.
In recent years, the chemistry of N-heterocyclic carbene (NHC)
analogues in which the divalent carbon atom is substituted by a
main group element has garnered attention.[1] Research in this
direction has been inspired by both fundamental insight into
structure and bonding and well as the applications of such
systems in catalysis.[1] In particular, the chemistry of phosphorus
(III) heterocycles has received consideration due to their ability to
act as hydride transfer reagents in reduction reactions both
stoichiometrically[2 ] and catalytically.[3 , 4 ] In this regard, Gudat
revealed that secondary 1,3,2-diazaphospholenes or N-
heterocyclic phosphanes (NHP-H) have hydridic character and
were found to undergo both stoichiometric 1,2- and 1,4-reduction
reactions of unsaturated substrates.[2] The catalytic 1,2-
hydroboration of carbonyls[3] and imines[4] as well as the catalytic
1,4-hydroboration of α,β-unsaturated carbonyl derivatives[4] were
then subsequently established by Kinjo and Speed. In the later
part of 2017 and 2018, interest in this area led to the rapid
development of chiral-diazaphospholenes for the asymmetric
variant of 1,2- and 1,4-reduction reactions by Speed[ 5 ] and
Cramer[6] respectively. In addition, diazaphospholenes have also
been shown to be active in the reduction of pyridines[7] and in
Scheme 1. Previous work using diazaphospholene catalysts for hydroboration
(top) and this work (bottom).
In our previous work, we have been interested in the structural,
photophysical
and
electronic
properties
of
arsenic
heterocycles.[13] Herein, we report the synthesis of novel arsenic
heterocyclic compounds and use these as pre-catalysts in the first
example of the homogeneous arsole catalysis in the
hydroboration of aldehydes with pinacolborane (HBPin).
Initially a series of potential arsenic(III) complexes were
prepared from the reactions of N,N’-diisopropylbenzene diamine
or toluene-3,4-dithiol with AsCl3 to yield the benzo-fused chloro-
arsoles (1 and 2). Subsequent reaction with benzyl alcohol then
yielded the benzo-fused diaza-benzyloxy-arsole (3) and benzo-
fused dithia-benzyloxy-arsole (4) which were both structurally
characterized by single crystal X-ray diffraction. Alternately,
abstraction of the halide from the chloro-arsoles 1 or 2 with
aluminium trichloride and trimethylsilyl trifluoromethanesulfonate
(TMSOTf) afforded the previously reported cationic arsenium
triflate (5a) and arsenium tetrachloroaluminates (5b and 6)
(Figure 1).[13]
other transformations including the transfer hydrogenation using
[ 8 ]
NH3BH3
as well as hydrosilylation of CO2.[ 9 ] Unlike their
phosphorus counterparts, the drive to develop main group
catalytic systems based upon the heavier pnictogen, arsenic, has
received little attention and the catalytic activity of As(III)
heterocycles has not been explored.
The hydroboration of unsaturated systems has widespread
applications in the synthetic laboratory and in the chemical
industry.[10] With carbonyl or imine functionalities, hydroboration
followed by hydrolysis provides access to alcohols or amines
respectively, while the reduction of C-C multiple bonds yields
borylated molecules for applications in cross-coupling reactions.
Although the hydroboration reaction has been rigorously explored
using transition metal catalysts,[ 11 ] metal-free alternatives are
seldom reported.[10] However, the use of metal-free hydroboration
catalysts such as those derived from diazaphospholenes or
borane Lewis acids has gathered momentum.[2-4,6,12]
Analysis of the solid-state structures of 3 and 4 revealed that
both compounds crystallize in the monoclinic space group P21/c.
For 3 two molecules were present in the asymmetric unit, with
metrics of the C2N2As ring similar to that previously reported for
1.[13b] The As–O bond length was found to be 1.82(2) Å, similar to
those reported previously for As(III)–O bonds,[14] and an As–O–C
interior bond angle of 119.06(12) – 120.79(12)°. With regards to
4, a similar story was found. One molecule was present in the
asymmetric unit and again the metrics of the C2S2As ring were
similar to that reported for 2.[14a] For 4 the As–O bond was slightly
shorter than in 3, at 1.789(2) Å, with an As–O–C interior bond
angle of 123.1(2)°.
[*]
Mr. D.M.C. Ould, Dr. R.L. Melen
School of Chemistry, Cardiff University, Main Building, Park Place,
Cardiff, CF10 3AT, Cymru/Wales, U.K.
E-mail: MelenR@cardiff.ac.uk
Supporting information for this article is given via a link at the end of
the document.
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10.1002/chem.201803508
Chemistry - A European Journal
COMMUNICATION
decrease in activity with 78% and 51% of the reduced product
being formed after 12 h respectively. Following this, solvent
effects were examined using both coordinating and non-
coordinating solvents. Toluene, CH2Cl2, CHCl3, Et2O, CD3CN and
C6D6 (Table 1, entries 14 and 17–21 respectively) showed
comparable results giving quantitative conversions in under 30
minutes, whereas THF and C6D5Br had a detrimental effect upon
the reaction (Table 1, entries 22 and 23 respectively). Although a
wide range of solvents were found to give quantitative yields for
the reaction, for the purposes of evaluating the scope, C6D6 was
used as the solvent of choice.
Table 1. Optimization of reaction conditions.
Entry
Catalyst
Loading
(mol%)
Solvent
Time
(h)
Conversion
(%)a
1
2
none
1
-
Toluene
Toluene
24
24
<10
49
10
3
2
3
10
10
10
10
10
10
10
10
10
10
10
5
Toluene
Toluene
Toluene
Toluene
CH2Cl2
MeCN
24
0.5
12
24
24
24
24
24
24
24
12
0.5
12
12
0.5
0.5
0.5
0.5
0.5
6
38
>95
64
4
5
4
6
5a
5a
5a
5a
5b
5b
5b
6
48
7
50
8
10
Figure 1. Top: arsoles 1–4 and arsenium cations 5 and 6. Bottom: solid-state
structures of 3 (left) and 4 (right). Thermal ellipsoids drawn at 50% probability
and H-atoms omitted for clarity.
9
C6D5Br
CH2Cl2
MeCN
15
10
11
12
13
14
15
16
17
18
19
20
21
22
23
27
19
With this range of arsole and arsenium compounds to hand,
we then tested the potential of these species as catalysts for the
C6D5Br
C6D5Br
Toluene
Toluene
Toluene
CH2Cl2
CHCl3
28
>95
>95
78
hydroboration
of
aldehydes
using
4-
3
(trifluoromethyl)benzaldehyde as the test substrate, as this
allowed for the reaction conversion to be easily monitored using
19F NMR spectroscopy. Using 10 mol% of the catalyst, the
chloride precursors 1 and 2 showed poor activity, giving only 49%
and 38% conversion respectively after 24 h (Table 1, entries 1
and 2). The benzyloxy substituted arsoles 3 and 4 on the other
hand showed remarkably improved activity, affording quantitative
conversion after just 30 minutes in the case of the benzo-fused
diaza-benzyloxy-arsole (3) and 64% conversion after 12 h for the
benzo-fused dithia-benzyloxy-arsole (4) (Table 1, entries 3 and 4).
Contrary to this, using 10 mol% of the arsenium cations 5a and
5b proved less effective, despite using a variety of solvents (Table
1, entries 6–12). For 5a the highest product conversion was 50%
when using CH2Cl2, whereas for 5b just 28% conversion was
found using C6D5Br. For comparison, the arsenium pre-catalyst 6
was synthesized, which proved highly insoluble in most solvents
except C6D5Br. Nevertheless, quantitative conversion occurred
within 12 hours (Table 1, entry 13), a significant increase
compared to 5b. With 3 proving to be the superior pre-catalyst,
the catalytic loading was reduced (Table 1, entries 14–16) with no
deleterious effect when using 5 mol% of the catalyst. Further
reduction of the catalyst loading to 2 mol% or 1 mol% showed a
3
2
3
1
51
3
5
>95
>95
>95
>95
>95
41
3
5
3
5
Et2O
3
5
CD3CN
C6D6
3
5
3
5
THF
3
5
C6D5Br
6
58
[a] Conversion measured via in situ 19F NMR spectroscopy.
Having observed that 4-(trifluoromethyl)benzaldehyde
readily underwent hydroboration with HBPin using catalyst 3
under the optimized conditions described above (Table 1, entry
21), the substrate scope was widened to include a variety of
aldehydes to test how effective 3 is as a catalyst (Scheme 2).
Electron withdrawing benzaldehydes proved very effective for the
catalysis, with most substrates undergoing complete conversion
within 30 minutes and giving high isolated yields. The fluorinated
aldehydes 4-fluorobenzaldehyde, 3-fluorobenzaldehyde and 2-
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fluorobenzaldehyde readily converted to 7b–d respectively within
30 minutes, as detected by both 1H NMR and 19F NMR
spectroscopy. In a similar vein, other aldehydes with bromo- or
chloro- substituents also worked well yielding 7g–h, 7j in isolated
yields >85%. Likewise, poly-halogenated aldehydes give 7e–f, 7i
quantitatively with isolated yields >90% although the reaction
times for the 2,4-difluorobenzaldehyde took slightly longer (2 h) to
reach completion. In addition to using halogenated aldehydes, the
electron withdrawing 2-formylbenzonitrile was used, which again
gave quantitative conversion to 7k within 30 minutes and an
isolated yield of 88%. Having established the high activity 3 has
for benzaldehydes bearing an electron withdrawing moiety, a
series of electron neutral and electron donating benzaldehydes
was subsequently examined. Benzaldehyde and methyl
substituted aldehydes also worked well but needed higher
catalytic loadings of 10 mol% to reach completion after just 30 min
giving 7l–o. 1-naphthaldehyde and 2-naphthaldehyde were also
successfully converted to 7p and 7q. When using 5 mol% of 3,
the 1-naphthaldehyde substrate failed to give quantitative
tetramethyl-1,3,2-dioxaborolane (BnO-BPin). Similar by-products
were also observed by Speed in the corresponding reaction of the
phosphole.[4,5] The other product formed in the reaction was the
arsenic hydride species (8) which could be detected by HRMS.
This species is thought to be the active catalyst for the reaction
by analogue to diazaphospholenes where the hydridic nature of
the P-H bond prompts catalytic hydroboration of imines.[4,5]
1
conversion within 24 hours, with H NMR spectroscopy showing
just 59% conversion occurred. Increasing the catalytic loading to
10 mol% however led to quantitative conversion within 30 minutes
to give 7p. More electron rich aldehydes were also successfully
reduced, with 4-methoxybenzaldehyde giving the hydroborated
product 7r in 92% isolated yield after 2h using 10 mol% catalyst.
In the case of the bis aldehyde terephthalaldehyde, hydroboration
of both aldehyde functionalities was observed when using two
equivalents of HBPin, although 20 mol% of catalyst was required
and a longer reaction time of 6 h was needed in order to give the
product in 89% isolated yield. The use of aliphatic aldehydes was
attempted, using pentanal and cyclohexanal. Use of both 5 mol%
and 10 mol% of 3 was used in the reduction, however full
conversion was not found after 24 hours, with conversions of 33%
and 44% being found when using a 10 mol% loading of 3. In
addition, heating these reactions also proved unsuccessful
leading to catalyst decomposition.
The recent work of Speed and Kinjo demonstrated the
application of phospholene and phosphenium based pre-catalysts
in the reduction of pyridines with HBPin.[7] Thus, we probed the
arsenic based catalysts in the hydroboration reaction with both
pyridine and the more reactive 3,5-dibromopyridine. These
showed no reactivity after 24 h using 10 mol% of catalyst 3.
Indeed,
when
using
the
pyridyl
substituted
4-(2-
pyridyl)benzaldehyde, only reduction of the aldehyde was
observed giving 7t in 92% yield after 30 min using 10 mol% of 3.
This demonstrates clear reactivity and selectivity differences
between the phosphorus and arsenic based catalysts.
The mechanism for the reaction is proposed to proceed via
the pathway depicted in Scheme 3. Mechanistic insight was first
obtained through the stoichiometric reaction of pre-catalyst 3 with
HBPin, which gave a clear color change from orange to deep red
within 5 minutes. The 1H NMR spectrum in C6D6 measured after
Scheme 2. Hydroboration of aldehydes using benzyloxy-benzo-1,3,2-
diazaarsole (3). 0.6 ml C6D6 solvent, NMR yield calculated from in situ 1H NMR
spectrum, value in parentheses isolated yield. a5 mol% 3. b10 mol% 3. c20 mol%
3; 2 equiv. HBPin.
Interestingly, the 11B NMR spectrum for the 1:1 stoichiometric
reaction of 4 with HBpin reveals a slow reaction, requiring 6 h for
complete loss of the doublet resonance corresponding to HBPin.
15 minutes showed a shift for the CH2 protons on the benzyl group, This suggests that the rate of formation of 8 is much faster than
from 4.03 ppm to 4.77 ppm. Furthermore, analysis of the 11B NMR
spectrum revealed a loss of the doublet signal at 28.4 ppm and
formation of a new singlet at 22.8 ppm. These observations are
consistent with the formation of 2-(benzyloxy)-4,4,5,5-
that for the sulfur analogue and explains the poorer activity of the
benzo-1,3,2-dithiaarsole 4 in the catalytic studies. Further to this,
upon the 1:1:1 addition of 3 with HBpin and the aldehyde 4-
(trifluoromethyl)benzaldehyde, compound 9 could be detected by
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HRMS along with the side-product BnO-BPin further confirming
the proposed catalytic cycle.
In this work we have presented the first example of the use
of arsenic for homogeneous catalyst for the hydroboration of
aldehydes with HBPin. A benzo-fused diaza-benzyloxy-arsole
acts as a pre-catalyst and can be employed under mild conditions
to give rapid quantitative conversions to the reduced product with
most reductions requiring just 30 minutes to reach completion.
While the present arsenic species act as precursors for
hydroboration catalysis, similar to the analogous phospholene
and phosphenium cation-based pre-catalysts, the reduced Lewis
acidity provides unique functional group tolerances and
alternative selectivities. This provides new insight into the
reactivity and main group catalyst design which exploits the
reduced Lewis acidity of arsenic. The scope of catalytic reactions
that can be performed using homogenous arsenic based catalysts
are ongoing within our research group.
Keywords: Arsenic • Hydroboration • Catalysis • Main Group •
Scheme 3. Proposed catalytic cycle for the hydroboration of aldehydes with
HBPin using the benzo-fused arsole 3 in catalytic quantities.
Boron
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COMMUNICATION
Working with Arsoles:
The first examples of
Darren M. C. Ould, Rebecca
L. Melen*
homogenous
catalysis
demonstrated
arsenic(III)
Page No. – Page No.
has
been
the
in
Arsenic Catalysis:
Hydroboration of
Unsaturated Compounds
Using a Benzo-1,3,2-
diazaarsole
hydroboration of a series of
unsaturated
using
compounds
benzo-1,3,2-
diazaarsoles.
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