Borane catalysed cyclopropenation of arylacetylenes

Article abstract of DOI:10.1039/d1cc01856f

Triarylboranes have gained substantial attention as catalysts for C-C bond forming reactions due to their remarkable catalytic activities. Herein, we report B(C₆F₅)₃catalysed cyclopropenation of a wide variety of arylacetylenes using donor-acceptor diazoesters. A mild reaction protocol has been developed for the synthesis of functionalised cyclopropenes (33 examples) in good to excellent yields.

Full text of DOI:10.1039/d1cc01856f

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Borane catalysed cyclopropenation
of arylacetylenes†
Cite this: Chem. Commun., 2021,
57, 6736
Katarina Stefkova,
Rebecca L. Melen
Matthew J. Heard, Ayan Dasgupta * and
*
Received 7th April 2021,
Accepted 7th June 2021
DOI: 10.1039/d1cc01856f
rsc.li/chemcomm
Triarylboranes have gained substantial attention as catalysts for using diazoester precursors, a carbene transfer reactions can be
C–C bond forming reactions due to their remarkable catalytic carried out using B(C6F5)3 as a catalyst.10
activities. Herein, we report B(C6F5)3 catalysed cyclopropenation
Carbene transfer reactions are one of the most fundamental
of a wide variety of arylacetylenes using donor–acceptor diazoe- reactions in organic synthesis and widespread studies have
sters. A mild reaction protocol has been developed for the synthesis been conducted to explore the synthetic utility of carbenes for
of functionalised cyclopropenes (33 examples) in good to excellent making a variety of novel compounds.11 Recently, we12 and
yields.
Wilkerson-Hill13 observed that catalytic amounts of B(C6F5)3
enable the cyclopropanation reactions of styrenes (Scheme 1A)
Transition metal catalysed C–C bond forming reactions over- using a-aryl a-diazoesters. This exciting outcome motivated us
whelm the chemical literature.1 Although the use of precious to investigate this reactivity further to see if arylacetylenes could
transition metal catalysts has achieved immense success, metal also be used as substrates in reactions with a-aryl a-diazoesters
impurities in the final compounds are often unavoidable. This using B(C6F5)3 as a catalyst. This reaction, cyclopropenation,
is particularly significant when considering products taken into has been largely investigated using precious transition metals,
the body where toxic metal contamination must be kept to a such as Rh,14 Ir,15 Ag,16 and Au.17 Nonetheless, the use of
minimum. Over the last few years, main group-based catalysts non-precious transition metals, including Cu18 and Co19
have been extensively investigated as substantial alternative to (Scheme 1B), have also been reported. Typically, in the presence
the precious transition metals.2 More precisely, the Lewis acidic of a metal catalyst, diazoesters afford a metal-carbenoid species
triarylboranes3 have found multitude applications towards C–C
bond forming reactions.4,5 The presence of empty d-orbitals in
transition metals allows them to lend or remove electrons from
the coupling partners, and thus can be employed as a catalyst
for wide variety of reactions.6 Likewise, the empty p-orbital of
the central boron atom of Lewis acids renders them strongly
electrophilic in nature and therefore they can readily react with
Lewis bases by accepting a lone pair of electrons.7 Relating to
this, an important initial contribution made by Zhang in 2016,8
showed that B(C6F5)3 could act as a catalyst for the ortho-
selective C–H alkylation of unprotected phenols with a-aryl
a-diazoesters. The mechanism for this reaction was revealed
computationally to be the activation of the diazoester through
O - B adduct formation to generate carbenes.9 Therefore, by
Cardiff Catalysis Institute, School of Chemistry, Cardiff University, Main Building,
Park Place, Cardiff, CF10 3AT, Cymru/Wales, UK.
E-mail: DasguptaA3@cardiff.ac.uk, MelenR@cardiff.ac.uk
† Electronic supplementary information (ESI) available: Experimental proce-
Scheme 1 General approach for cyclopropenation/cyclopropanation
reaction.
dures, NMR data, X-ray data. CCDC 2072872 and 2072873. For ESI and crystal-
lographic data in CIF or other electronic format see DOI: 10.1039/d1cc01856f
6736 | Chem. Commun., 2021, 57, 6736–6739
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which then readily undergoes a [2+1] cycloaddition with an desired carbocycle 3i of 32% (Table 1, entries 9 and 10).
arylacetylene to form the 3-membered carbocycle. Recently, Additionally, we tested other triarylfluoroborane catalysts for
Koenigs et al. revealed that cyclopropenation of arylacetylenes the cyclopropenation reaction and we observed that although
using a-aryl a-diazoesters is also possible by employing visible 10 mol% (2,4,6-F3C6H2)3B [(2,4,6-ArF)3B] afforded 3i in poor
light (blue light; 470 nm).20
yields of 28%, the Lewis acidic boranes (3,4,5-F3C6H2)3B [(3,4,
We initiated our studies into the cyclopropenation reaction 5-ArF)3B] and (3,5-CF3C6H3)3B [(3,5-CF3-ArF)3B] completely
using phenylacetylene (1.3 equiv.) and a-aryl a-diazoester 1a failed to catalyse the reaction, and no product formation was
(1 equiv.) as model substrates (Table 1). The reaction between detected (Table 1, entries 11–13).
1a and phenylacetylene showed no formation of the cyclopro-
Interestingly, the yield of 3i was further improved to 75%
pene product (3i) in absence of any catalyst at both ambient when we used a slight excess of 1a (1.3 equiv.) (Table 1, entry
temperature and at reflux in CH2Cl2 (Table 1, entries 1 and 2). 14). Thus our optimised reaction conditions were a 1 : 1.3
Addition of BF3ꢀOEt2 as a Lewis acid catalyst (20 mol%) also stoichiometric ratio of phenylacetylene : 1a and carrying out
showed no formation of the desired carbocycle (3i) and only the reaction in C2H4Cl2 at 50 1C using 10 mol% B(C6F5)3.
decomposition of the diazo compound into the homocoupled
With the optimised conditions in hand, we then explored
product was observed (Table 1, entry 3). 40 mol% of the the scope of the reaction with various a-aryl a-diazoesters (1)
Brønsted acid (TfOH, triflic acid) also failed to promote the and arylacetylenes (Scheme 2). Firstly, terminal arylacetylenes
reaction (Table 1, entry 4). When 20 mol% B(C6F5)3 was were explored bearing electron-withdrawing, neutral, and elec-
employed for the reaction, no product formation was observed tron releasing groups, for the cyclopropenation reaction with
at ambient temperature, however reaction at 45 1C afforded 3i different a-aryl a-diazoesters (1a–g) to generate the products
in 48% yield after 24 h (Table 1, entries 5 and 6). Switching the 3a–3ae in 30–84% yields. Of these, products 3n and 3o could be
solvent from CH2Cl2 to C2H4Cl2 slightly improved the yield of 3i recrystallised by vapour diffusion from CH2Cl2/pentane and
to 57% but still did not give satisfactory results (Table 1, their structures elucidated by single crystal X-ray diffraction
entry 7). Increasing the reaction temperature further to 70 1C (Fig. 1). Lower yields were observed with strongly electron
however was detrimental to the reaction leading to the for- withdrawing (p-CF3) or electron releasing (p-OMe, p-Me) aryla-
mation of a complicated reaction mixture and the isolation of cetylenes giving 3a,b, u–w in less than 50% yield. Another
the desired product 3i failed (Table 1, entry 8). Reducing the observation was that the p-F or o-F substituted a-aryl
catalytic loading of B(C6F5)3 from 20 mol% to 10 mol% showed a-diazoesters (1a and 1b respectively) gave better yields than
improvement in the yield of 3i to 65%. However, reducing the p-OMe substituted a-aryl a-diazoester (1g) when combined
catalytic loadings further to 5 mol% gave lower yields of the with the same arylacetylene. Interestingly, the vinyl diazoace-
tate (methyl (E)-2-diazo-4-phenylbut-3-enoate, (1h), symmetrical
diisopropyl 2-diazomalonate (1i), diazodimedone (1j), ethyl 2-
diazoacetate (1k), and methyl 2-diazo-2-(3-fluorophenyl)acetate
Table 1 Optimisation of the reaction conditions
(1l) failed to react with arylacetylenes to afford the desired
carbocycles. Aliphatic terminal acetylenes including tert-
butylacetylene and hex-1-yne, as well as ethynyltrimethylsilane
were also unsuccessful for the reaction.
We then examined the reactivities of the internal alkynes in
the cyclopropenation reaction with limited success. However,
when 1-phenyl-1-propyne and hex-1-ynylbenzene (2a) were
reacted with 1c, the desired carbocycles 3af and 3ag were
isolated in poor yields of 15% and 26% respectively. Other
internal alkynes such as 1,2-diphenylethyne, trimethyl(phenyle-
thynyl)silane, and 1-(prop-1-yn-1-yl)-4-(trifluoromethyl)benzene
failed to react completely.
Following this we investigated the selectivity of the carbo-
cycle formation (cyclopropanation versus cyclopropenation)
when both alkene and alkyne functionalities are present. For
this competition study, the intramolecular alkene/alkyne com-
pounds 1-ethynyl-4-vinylbenzene (2b) and 1-ethynyl-2-vinyl-
benzene (2c) were tested in the B(C6F5)3 catalysed reaction with
1a. In both cases cyclopropanation was favoured over cyclopro-
penation giving the cyclopropane carbocycle as a single dias-
tereoisomer in 88% (3ah) and 41% (3ai) yields, respectively.
Unfortunately, attempts to synthesise 3-membered hetero-
cycles from the insertion of the carbene into CQO, CQN or
CRN bonds failed. Using the optimised reaction conditions,
Loading
(mol%)
Temp.
(1C)
Time
(h)
Yielda
(%)
Entry Catalyst
Solvent
1
2
None
None
—
—
20
40
20
20
20
20
10
5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
r.t.
45
45
45
r.t.
45
24
24
24
24
24
24
22
18
24
28
24
24
24
—
—
—
—
—
48
57
—
65
32
28
—
—
3
4
BF3ꢀOEt2
TfOH
5
6
7
8
B(C6F5)3
B(C6F5)3
B(C6F5)3
B(C6F5)3
B(C6F5)3
B(C6F5)3
C2H4Cl2 50
C2H4Cl2 70
C2H4Cl2 50
C2H4Cl2 50
C2H4Cl2 50
C2H4Cl2 40
C2H4Cl2 50
9
10
11
12
13
(2,4,6-ArF)3B 10
(3,4,5-ArF)3B 10
(3,5-CF3-
ArF)3B
10
10
b
14
B(C6F5)3
C2H4Cl2 50
24
75
All the reactions were carried out on a 0.1 mmol scale. 1a (1 equiv.),
phenylacetylene (1.3 equiv.), and 1.5 mL solvent. Reported yields are
isolated. Phenylacetylene (1 equiv.), 1a (1.3 equiv.), and 1.5 mL of
a
b
solvent.
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Scheme 2 Substrate scope for the cyclopropenation of arylacetylenes. Yields reported are isolated. All the reactions were carried out in 0.1 mmol scale,
10 mol% B(C6F5)3 was used. 1 (1.3 equiv.), phenylacetylene (1 equiv.), and 1.5 mL of solvents were used.
6738 | Chem. Commun., 2021, 57, 6736–6739
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of substrates were investigated and good to excellent yields of
the cyclopropenated products were obtained. This methodology
adds to the ever-increasing range of reactions that the Lewis
acid B(C6F5)3 can catalyse.
AD and RLM are grateful to the EPSRC for funding and the
awarding of an EPSRC Early Career Fellowship (EP/R026912/1).
Information about the data that underpins the results pre-
sented in this article, including how to access them, can be
found in the Cardiff University data catalogue at http://doi.org/
10.17035/d.2021.0136187455.
Fig. 1 Solid-state structure of compound 3n (left) and 3o (right). Thermal
ellipsoids drawn at 50% probability. Carbon: black; oxygen: red. H atoms
omitted for clarity.
Conflicts of interest
The authors declare no conflict of interest.
Notes and references
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the goal to produce the corresponding epoxide. However,
multinuclear spectroscopic data of the isolated compound
confirmed the formation of methyl 3-oxo-2,3-diphenylpro-
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hyde with the diazo compound (Roskamp–Feng reaction).21
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to proceed in a similar manner to that for the cyclopropanation
reaction reported in our previous studies12 (Fig. 2). Initially, the
Lewis acidic B(C6F5)3 binds effectively with the ester functionality
of the a-aryl a-diazoester 1. This facilitates loss of N2 forming the
highly electron deficient intermediate I and its resonance form I0.
Subsequently the reactive carbene intermediate can then react
with the nucleophilic arylacetylene forming intermediate II. The
generation of the carbocationic centre in II explains the need for
arylacetylenes in the reaction to stabilise this intermediate.
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then generates the product and regenerates the catalyst.
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´
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In conclusion, a metal-free mild reaction protocol has been
developed for the cyclopropenation of alkynes using diazo
compounds. Our studies demonstrate that catalytic amounts
of B(C6F5)3 readily react with a-aryl a-diazoesters to promote the
carbene transfer reaction when reacted with arylacetylenes
generating the desired 3-membered carbocycle. A wide range
´
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