Recyclable heterogeneous metal foil-catalyzed cyclopropenation of alkynes and diazoacetates under solvent-free mechanochemical reaction conditions

Article abstract of DOI:10.1039/c8sc00443a

Silver and copper foil were found to be effective, versatile and selective heterogeneous catalysts for the cyclopropenation of terminal and internal alkynes under mechanochemical reaction conditions. This methodology enables the functionalization of a wide range of terminal or internal alkynes under ambient, aerobic, and solvent-free conditions. Finally, we have demonstrated a unique and versatile one-pot domino Sonogashira-cyclopropenation mechanochemical reaction for the formation of complex cyclopropenes.

Full text of DOI:10.1039/c8sc00443a

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Recyclable Heterogeneous Metal Foil-Catalyzed Cyclopropenation of Alkynes and Diazoacetates under
Solvent-Free Mechanochemical Reaction Conditions
Longrui Chen1, Devonna Leslie2, Michael G. Coleman2 and James Mack1
1.
2.
Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221-0037
School of Chemistry and Materials Science, Rochester Institute of Technology, Rochester, New
York 14623-5604
ABSTRACT
Silver and copper foil were found to be effective, versatile and selective heterogeneous catalysts for the
cyclopropenation of terminal and internal alkynes under mechanochemical reaction conditions. This
methodology enables the functionalization of a wide range of terminal or internal alkynes under
ambient, aerobic, and solvent-free conditions. Finally, we have demonstrated a unique and versatile
one-pot domino Sonogashira-cyclopropenation mechanochemical reaction for the formation of complex
cyclopropenes.
INTRODUCTION
The study of cyclopropenyl-containing compounds has been an active area of research for
several decades due to its high ring strain.1 A wide variety of chemical and physical transformations that
are not known for other π systems can be accessed by the release of the resultant potential energy.2-8 In
fact, the reactivity of the cyclopropenyl moiety has been harnessed via a rapid and selective inverse
demand Diels-Alder reaction with a tetrazine fluorescent tag for bioorthogonal chemical
reporting/imaging.9-17 Despite their broad molecular utility, the harsh reaction conditions, poor atom
economy, non-recoverable transition metal catalysts, large volumes of solvent required and slow syringe
pump additions used in traditional synthetic methods severely limits the accessibility of cyclopropenyl
compounds for study.2, 18-23 In order to circumvent these synthetic impediments, the conversion of
homogenous transition metal-catalyzed [2+1] cycloadditions of unsaturated hydrocarbons and
diazoacetates into heterogeneous catalytic processes has been the prevailing research strategy for
several decades. Towards that goal, laboratory scale continuous flow reactors have been developed for
the synthesis of cyclopropene and cyclopropane compounds via a stationary bed of immobilized
catalysts.24-31 Two impressive examples depicted here are as efficient and selective as their
homogeneous-catalyzed counterparts [Schemes 1 (a) and 1 (b)].26,25 Batch reactor processes have also
been extensively studied for the heterogeneous cyclopropanation of olefins and many forms of
immobilized catalysts have been developed.32-41,42-51,52-60,61-65,66-70 Appreciating the technical,

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environmental and economic challenges associated with the homogenous transition metal-catalyzed
[2+1] cycloadditions of unsaturated hydrocarbons and diazoacetates, our research group recently
developed a solvent-free mechanochemical ball milling reaction using a highly selective and active silver
foil catalyst in a stainless steel (S.S) vial [Scheme 1 (c)].71 A highlight of this batch reactor design is that
the silver-foil catalyst is recoverable, recyclable, shelf stable and commercially available. Moreover, this
batch reactor design is a general and experimentally straightforward operation. No additional
precautions such as inert atmospheric (Ar or N2), anhydrous reaction conditions, or freshly distilled
reagents are necessary to preserve the catalytic activity. We observed that the silver foil can be recycled
at least twenty times without any appreciable drop in yield or diastereoselectivity. Finally, forgoing the
long syringe pump additions of diazoacetate (~0.1 M) diluted in large volumes of solvent is a particularly
attractive ‘green’ feature attributed to this solvent-free mechanochemical cyclopropanation reaction.
Scheme 1. Heterogeneous Transition Metal-Catalyzed [2+1] Cycloaddition Reactions
Mechanochemistry is a ‘chemical reaction that is induced by the direct absorption of mechanical
energy.’72 While it is unlikely that the solvent-free mechanochemical laboratory procedure comes to the
mind of contemporary synthetic chemists as a useful and simple experimental procedure, it is one of the
earliest recorded chemical methods known to convert physical energy, namely heat and pressure, into
chemical energy.73, 74 This ancient synthetic method has been extensively used over the past century for
the formation of new macromolecular products, metal-organic frameworks, compositions and cocrystals
by grinding, extrusive and milling forces from poorly soluble solid-solid, solid-liquid and liquid-liquid
inorganic reactants.75-91 Mechanochemical methods have also been utilized for the dehalogenation of
pollutants that are resistant to degradation through chemical, biological, and photolytic processes.92-101
In recent years, solvent-free mechanochemistry has emerged as a ‘green’ alternative to the
unsustainable use of petroleum-based solvents in classic organic chemistry transformations.102-106 With
respect to fine chemical manufacturing, it is also an effective experimental procedure, known as

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medicinal mechanochemistry, for the synthesis of many classes of organic compounds, active
pharmaceutical ingredients (APIs), and commercially-available drugs.75, 89, 105-113
Unlike solution-phase organic chemistry, solvent-free ball milling conditions are generally
conducted without the need for inert gas, external heat, or solvent. The stainless-steel reactors vials are
machined from stainless-steel rods and the organic/inorganic reactants are added in the open
atmosphere with one or more stainless-steel balls. In our previous work, diazoacetate and an excess of
the unsaturated hydrocarbon (trap) were added to a stainless steel vial lined with a silver foil catalyst
and a single stainless steel ball. Similar to the analogous solution-phase cycloaddition reactions, the
excess trap serves to suppress any undesired diazoacetate dimerization pathways and does not serve as
a solvent in this mechanochemical process. This work demonstrated that solid-solid ball milling of a
diazoacetate in the presence of excess alkene was as effective as liquid-liquid ball milling which
suggested that efficient mixing of the reaction media was achieved. The silver foil lined reaction vial was
mechanochemically ball milled using an SPEX 8000M vibratory mixer/mill® at 18 Hz to furnish
cyclopropane compounds in high yields (Figure 1).71 Moreover, the stainless-steel vials, metal foil, and
excess unsaturated hydrocarbons were easily recovered and recycled for later use.
Figure 1.
SPEX 8000M vibratory mixer/mill® and Reaction Vials
RESULTS
Encouraged by our previous results, we set out to test if our solvent-free mechanochemical
batch reactor design could also be utilized for the highly selective and efficient [2+1] cycloadditions of
unsaturated hydrocarbons by simply changing the catalytic foil insert. We began by measuring the
catalytic efficiency of copper and silver foils for the cyclopropenation of terminal and internal acetylenes
in a SPEX 8000M vibratory mixer/mill® at 18 Hz (Table 1) under various reaction conditions. After
optimizing the ratio of reactants (1 : 5; diazo : alkyne, respectively) and mixing time (16 hrs), the copper
foil-catalyzed cyclopropenation of phenyl acetylene afforded cyclopropene product 1 in 88% isolated
yield (entry 1). However, when 1-phenyl-propyne was treated to identical mechanochemical conditions,
a significantly lower yield of the corresponding cyclopropene product 2 was observed (entry 2). We then
simply replaced the copper foil with silver foil and milled phenyl acetylene and methyl
phenyldiazoacetate and did not observe any appreciable amount of cyclopropene product 1 (entry 3).

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Lastly, we turned our attention to 1-phenyl-propyne and methyl phenyldiazoacetate (1 eq) under silver
foil-catalyzed mechanochemical reaction conditions. To our delight, cyclopropene product 2 was
isolated (90% yield) after 16 hours of milling (entry 4). These initial results are in agreement with
previous work which demonstrated that silver(I) salts are effective homogeneous catalysts for the
cyclopropenation of internal acetylenic compounds, while ineffective for terminal alkynes.114
Table 1. Heterogeneous Metal-foil-catalyzed Cyclopropenation of Acetylenes Under Mechanochemical
Conditions
Ph CO2Me
Ph
foil
N2
R1
R2
+
S.S vial and ball
no solvent, air
R1
R2
MeO2C
1 eq
16h
5 eqs
Isolated Yield (%)a
Entry
foil
Cu
Cu
R1
R2
H
Product
1
2
Ph
Ph
1
2
88
10
CH3
Ag
Ag
1
2
3
4
Ph
Ph
H
trace
90
CH3
All reactions were performed on a 1 mmol scale of diazoacetate.
Cu with terminal alkyne (entry 1)
Ag with Internal alkyne (entry 4)
100%
80%
60%
40%
20%
0%
100%
80%
60%
40%
20%
0%
16
16
12
12
8
8
6
6
1 : 1 1 : 2 1 : 3 1 : 5
Mole ratio of diazo to alkyne
1 : 1 1 : 2 1 : 3 1 : 5
Mole ratio of diazo to alkyne
Having established the general boundaries for the catalytic activity and selectivity of metal foil-
catalyzed mechanochemical cyclopropenation reactions, various terminal alkynes were investigated
using copper foil (Table 2). Electron-rich and electron-poor terminal acetylenes were all obtained in
good to excellent yields (entries 1 – 10). 1-Cyclohexenyl acetylene afforded the cyclopropene product 13
exclusively in good yield (entry 11). 3-thiophenyl acetylene afforded the corresponding cyclopropene
product 14 in 90% yield (entry 12). Remarkably, 4-ethynylaniline cleanly underwent the
mechanochemical cyclopropenation in the presence of the unprotected aniline in excellent isolated
yield (entry 13). To the best of our knowledge, this is the first instance where an unprotected N-H bond
was chemically inert to carbene transfer and afforded cyclopropene 15 without additional protection
and deprotection steps.22, 115, 116 Next, we surveyed a range of electronically diverse diazoacetate

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compounds and determined that dimethyl diazomalonate and ethyl diazoacetate compounds were
ineffective for the copper foil-catalyzed cyclopropenation of phenyl acetylene under solvent-free
mechanochemical milling conditions (entries 14 – 16).

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Table 2.
Copper foil-catalyzed Mechanochemical Cyclopropenation of Terminal Alkynes
Ph
N2
H3CO2C
Ph
R1
CO2CH3
Cu foil
R1
S.S vial and ball
no solvent, air
16h
R1
Entry
Product
Isolated Yield (%)
1
2
4-(OCH3)Ph
4-(CH3)Ph
3
4
88
95
5
6
88
81
85
85
82
84
3
4
5
6
7
8
3-(CH3)Ph
4-(C(CH3)3)Ph
4-(F)Ph
7
8
4-(Br)Ph
9
2-(Cl)Ph
3-(Cl)Ph
10
9
2,4,6-(CH3)Ph
11
12
13
14
15
78
90
86
90
94
10
11
12
13
2-(CH3)-4-(OCH3)Ph
1-cyclohexenyl
3-thiophenyl
4-(NH2)Ph
14a
15b
16c
Ph
16
81
Ph
Ph
17
18
traced
traced
Reaction Conditions: diazoacetate (1.00 eq), alkyne (5.00 eq), and
copper foil added to a SPEX 8000M Mixer/Mill (18 Hz) for 16 hrs.
a 1 eq of methyl p-bromophenyldiazoacetate was used. b 1 eq of
ethyl diazoacetate was used. c 1 eq of dimethyl diazomalonate was
used. d recovered starting material

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Next, we investigated the scope of the silver foil-catalyzed mechanochemical cyclopropenation
reaction with various internally substituted acetylenic compounds (Table 3). 1-phenyl substituted
aliphatic alkynes (entries 1 and 2) were isolated in excellent yields (>92%). Interestingly, 1-TMS-2-
phenylacteylene underwent cyclopropenation in relatively low yield by GC analysis (entry 3). It is
important to note that the analogous solution phase, homogeneous, Ag(I)-catalyzed reaction is
completely unreactive.114 Increasing the steric bulk of the silyl group had a detrimental effect on the
reactivity of the mechanochemical cyclopropenation methodology (entries 4 and 5), while diaryl-
substituted acetylenes were efficiently converted into the cyclopropene products 24 – 26 in isolated
yields up to 85% (entries 6 - 8). Various electron rich and electron poor aryl diazoacetates were also
tested and all afforded excellent yields (>80%) of the corresponding cyclopropene products (entries 10 –
14). As stated earlier, the electronic character of the diazoacetate plays an important role in its reactivity
with the transition metal catalyst, and ultimately, the efficiency of the carbene transfer.117,118 For
example, homogeneous Ag(I) salts effectively catalyze an interesting C-Cl insertion with ethyl
diazoacetate when using methylene halide or haloform as solvents.114,119 We discovered that eliminating
dichloromethane as the commonly used solvent afforded the corresponding cyclopropene products 34
and 35, in the presence of ethyl diazoacetate, under solvent-free silver-foil catalyzed mechanochemical
reaction conditions (entries 16 and 17). Finally, diethyl diazomalonate was completely unreactive and
only starting materials were recovered (entry 18). This finding is in agreement with previous work that
stable metal-carbene complexes are observed in the solution phase reactions of diazomalonate
compounds and silver(I) salts.120,121

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Table 3.
Silver Foil-Catalyzed Mechanochemical Cyclopropenation of Internal Alkynes
R2
CO2R3
R2
Ag foil
N2
+
R1
S.S vial and ball
no solvent, air
R3O2C
R1
16h
R1
R2
R3
Yield (%)a
Entry
Product
1
2
CH2CH3
Ph
Ph
CH3
CH3
19
20
92
95
(CH2)3CH3
3
Si(CH3)3
Ph
CH3
21
20b
4
5
Si(CH(CH2)3
Si(Ph)3
Ph
Ph
CH3
CH3
22
23
traced
traced
6
Ph
4-(CH3)Ph
4-(Br)Ph
3-thiophenyl
CH3
Ph
Ph
CH3
CH3
CH3
CH3
CH3
CH3
24
25
26
27
28
29
84
85
65
86
86
7
8
Ph
9
Ph
10
4-(OCH3)Ph
4-(C(CH3)3)Ph
4-BrPh
4-CF3Ph
4-BrPh
4-(CH3)Ph
H
11
CH3
84
89
88
80
79
12
13
14
15
16
CH3
CH3
CH3
CH3
30
31
32
33
34
(CH2)3CH3
(CH2)3CH3
CH3
CH3
CH3
80b
CH2CH3
85b
(CH2)3CH3
(CH2)3CH3
CH2CH3
17
H
35
traced
85
CO2CH3
Ph
CH3
CH3
18
36
37
19c
Reaction Conditions: diazoacetate (1.00 eq), alkyne (5.00 eq), and silver foil added to a SPEX 8000M
Mixer/Mill (18 Hz) for 16 hrs. a Isolated yields unless otherwise stated. b GC yield. c 4-octyne was
used. d Recovered starting material.

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Having established the efficiency of this mechanochemical reaction, we set out to explore
several intermolecular experiments to measure the chemoselectivity of the mechanochemical reaction
using an equimolar mixture of olefins and acetylenes in the presence of methyl phenyldiazoacetate
(Table 4). After 16h of mechanochemical milling, we discovered that silver foil highly favors the
cyclopropanation of olefins in the presence of terminal acetylenes (entry 1). These findings suggest that
the silver foil does not lose its catalytic activity despite known silver acetylide catalyst deactivation
pathways for the solution-phase, homogeneous silver-catalyzed counterpart.114 On the other hand,
copper foil was mildly chemoselective and favored the cyclopropenation pathway for a mixture
monosubstituted alkenes and terminal alkynes (entry 1). The silver foil-catalyzed [2+1] cycloaddition was
observed to be less selective for 1,2-disubstituted alkenes over their internally substituted acetylenic
counterparts (entries 2 - 5). While the copper foil-catalyzed [2+1] cycloaddition of 1,2-disubstituted
alkenes and internal alkynes favored the cyclopropanation reaction pathway (entries 2 - 5). Finally, the
mechanochemical milling of diphenyl-substituted olefins and diphenylacetylene resulted in a highly
chemoselective ratio of cycloaddition products (entries 6 and 7), where silver foil favored
cyclopropenation and copper foil favored cyclopropanation.
Table 4.
Metal Foil-Catalyzed Cycloaddition of Unsaturated Hydrocarbons with Methyl
Phenyldiazoacetate
In order to further test the chemoselectivity of this mechanochemical [2+1] cycloaddition
reaction, we extended this study to include compounds containing enyne moieties. The
mechanochemical metal foil-catalyzed cycloaddition of enyne moieties afforded astonishingly
chemoselective transformations (Table 5).

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Table 5.
Metal Foil-Catalyzed Cycloaddition of Enynes with Methyl Phenyldiazoacetate
The silver foil-catalyzed process resulted in the cyclopropenation exclusively for internal alkynes (entries
1 and 2). After simply switching the silver to copper foil, we observed the exclusive formation of the
corresponding cyclopropanation products (entries 1 and 2). Interestingly, 1-cyclohexenyl acetylene
resulted in complete deactivation of the silver foil catalyst and no cycloaddition product was isolated
(entry 3). This finding may suggest that the substrate was deactivated on the silver foil which is contrary
to the intermolecular process observed earlier (Table 4, entry 1). Copper foil effectively and selectively
converted the trisubstituted olefin into the cyclopropane product 13 in good yield (entry 3). However,
the cyclopropanation of 1,1-disubstituted alkene moiety yielded that same cyclopropane product 50 for
both silver and copper foil (entry 4). Overall, these highly chemoselective mechanochemical
transformations gave rise to interesting building blocks that are useful for other organic
transformations.
In addition to developing ‘solvent-free’ mechanochemical organic chemistry methods, we are
also interested in realizing strategies for the construction of complex organic compounds from two or
more synthetic steps in a single highly atom-economical ‘one-pot’ procedure. In recent years, several
multicomponent coupling reactions have been developed by combining well-established individual

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reactions without the need for extraneous use of solvent in workups or purification steps.122-128 Based on
the mechanochemical Sonogashira coupling reaction previously developed by our group,129 we
envisioned a three-component coupling of a terminal alkyne, aryl halide and a diazoacetate compound
as the first example of a transition-metal catalyzed domino mechanochemical reaction. At the outset,
we were cognizant that the terminal alkynes were susceptible to cyclopropenation with copper foil,
while silver(I) salts are inert to terminal alkynes but remain catalytically active. Previous work suggests
that silver foil may be capable of serving as an effective catalyst130 and co-catalyst131-138 for the
Sonogashira coupling reaction, and later, catalyzed the cyclopropenation of the newly formed internal
alkynes in the presence of a diazoacetate compound. To test this hypothesis, we first examined the
feasibility of the Pd(II)/silver foil-catalyzed Sonogashira mechanochemical reaction. Gratifyingly, we
observed good to excellent yields of the internal alkyne product by GC analysis (Table 6).

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Table 6.
Optimization of the Pd(II)/Silver foil-catalyzed Mechanochemical Sonogashira Reaction

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Our initial investigations of the cross coupling product of aryl iodides and bromides and phenyl
acetylene afforded excellent yields by GC analysis (80 – 95%) (entries 1 – 9). Similar to our original report
of the Sonogashira reaction under mechanochemical conditions, the reaction is much faster with iodine
than bromine and is virtually unreactive with chlorine.129 Such that entries 2 and 11 only provided
coupling across the carbon iodide bond. 1-Hexyne proved to be an equally effective cross coupling
partner with aryl iodides or bromides (entries 10 – 15). A diverse range of p-substituted arylacetylene
compounds (51 – 56) were observed by GC analysis from either iodobenzene or bromobenzene starting
materials in good yields (> 77%). No diyne byproducts resulting from homo coupling or multiple
Sonogashira couplings were detected. Para-substituted aryl iodides and bromides were easily coupled to
4-phenyl-1-butyne to afford the corresponding Sonogashira products (62 – 64, entries 25 – 27) in good
yield (>78%) by GC analysis.
Given the fact that silver foil is an effective co-catalyst for the cross coupling of aryl halides and
terminal acetylenic compounds via mechanochemical milling, we then turned our attention back
towards our initial hypothesis that a domino one-pot Sonogashira coupling followed by
cyclopropenation would be a straightforward and general method for the synthesis of a diverse library
of fully substituted cyclopropene compounds (Table 7).

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Table 7.
Optimization of the One-Pot Sonogashira Coupling/Cyclopropenation Mechanochemical
Reaction
Since the predictive models of mechanochemical catalysis are still in their infancy, we used surveyed
several reaction conditions and experimental procedures to determine which were optimal. First, we
attempted a one-pot domino reaction where methyl phenyl diazoacetate, phenylacetylene,
iodobenzene, 5% palladium tetrakis triphenylphosphine and potassium carbonate were all added to a
stainless steel reactor and ball milled for 16 hrs (Approach 1). In the absence of silver foil, no product
was observed irrespective of the reaction conditions (entries 1 -4, 9, and 17). However, upon the
addition of silver foil, the cross coupled/cyclopropenation product was isolated albeit in modest yield
(entries 5, 7 and 8). Catalytic amounts of palladium (II) acetate were found to be completely unreactive

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towards Sonogashira coupling by mechanochemical ball milling (entries 6 and 10). Copper foil was
observed to be effective for the Sonogashira coupling reaction (Approach 1, entry 9) but failed to yield
any appreciable amount of the cyclopropene product. In an effort to increase the efficiency of the
desired process, we elected to add the diazoacetate compound after ball milling the Sonogashira
reactants for 6 hours without purification. This was then followed by additional ball milling of the
solvent-free reaction mixture (Approach 2). Under traditional solution based conditions both the
Sonogashira and cyclopropenation reactions are typically conducted under strictly inert atmospheric
reaction conditions. To test this, we conducted the reaction using Pd(PPh3)4 under inert conditions using
a dry box (entries 7 and 11) and compared the reaction using PdCl2(PPh3)2 under aerobic conditions
(entries 5 and 13). In our previous report, we demonstrated both catalysts gave rise to similar yields of
Sonogashira products.129 Since both reactions under Approach 1 and Approach 2 gave similar reaction
yields, we concluded there is no preference for inert atmospheric mechanochemical ball milling reaction
conditions. After optimization of the milling time and palladium salt, the two-step reaction resulted in
good yields (60 – 75%) of the desired fully substituted cyclopropene product (entries 10 – 16). To the
best of our knowledge, this represents the first example of a catalytic one-pot multi-component
coupling/cycloaddition domino methodology for the organometallic synthesis of highly functionalized
organic compounds. Lastly, copper foil was an effective co-catalyst for only the Sonogasira coupling
reaction and no cyclopropenation of the internal alkyne was observed (entry 17).
To survey the general nature for the ‘one-pot’ Pd/Ag foil-catalyzed cross
coupling/cyclopropenation mechanochemical milling reaction, we studied a variety of alkynes, aryl
halides and aryl diazoacetates (Table 8).

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Table 8.
One-Pot Domino Sonogashira Coupling/Cyclopropenation Mechanochemical Reaction
Using Approach 2
Aliphatic and aryl alkynes coupled well with aryl iodides or bromides to afford internal alkynes, which
upon treatment with aryl diazoacetate, effectively produced the cyclopropene products 20, 24, 65 – 69
in good overall yields (55 – 80%). In order to test the reactivity of electron rich and electron poor aryl
diazoacetates for cyclopropenation, we subjected the coupling products of 1-hexyne and various aryl
halides to yield cyclopropene products (70 – 73) in good overall yields. Compounds 70 and 73 did not
produce any Sonogashira type reactivity at the aryl bromide site, presumably due the significant effect
substituents have on the rate of Sonogashira coupling of aryl bromides compared to iodides under
mechanochemical conditions.129 Overall, this multi-component strategy is highly general and atom
economical (e.g., atom economy ranges 68% - 73%) where no solvent or inert atmospheric conditions
are required.

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CONCLUSIONS
This mechanochemical ball milling reaction is a general, robust and straightforward
methodology for the synthesis of cycloadducts from unsaturated hydrocarbons and diazoacetate
compounds. The metal foil is switchable and recyclable without the need for solvent, inert gas, or heat.
Using the same batch reactor, we were able to insert silver foil to heterogeneously catalyze the
cyclopropenation of internal alkynes or insert copper foil to catalyze the cyclopropenation of terminal
alkynes in excellent overall yields. Our findings indicated that the solid-solid milling of a diazoacetate
and alkyne was equally as effective as liquid-liquid milling. Ethyl diazoacetate was used effectively for
cyclopropenation transformations that are not known for traditional systems due to side reactions
involving the halogenated solvent. An additional feature of this solvent-free mechanochemical [2+1]
cycloaddition chemistry is the highly selective cyclopropenation of substrates containing unprotected
amino and silyl groups. This feature obviates the need for synthetic operations such as the use of
blocking groups or temporary modifications to the reagent. Finally, a one-pot domino Sonogashira
coupling/cyclopropenation solvent-free mechanochemical reaction as an organometallic-catalyzed
three-component coupling of a terminal acetylene, aryl halide and diazoacetate was discovered that
resulted in good overall yields of a library of poly-substituted cyclopropene compounds. Due to lack of
commercially available alkynes, a linear synthetic approach to derive a library of cyclopropenyl-
containing compounds would be inefficient and require complex reaction set-ups and purification
procedures. Future work will explore and measure the selectivity and efficiency of other carbene
transfer reactions using solvent-free mechanochemical ball milling conditions.
ACKNOWLEDGEMENTS
This research is supported by the National Science Foundation grant number CHE-1465110, National
Science Foundation- REU grant number CHE-1156449 and the University of Cincinnati Research Council
(URC). We would also like to thank the Rochester Institute of Technology College of Science FEAD grant
for financial support.
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Ar
CO2CH3
N2
X
Pd catalyst (2.5 mol%)
R1
O
+
+
Ag foil, K2CO3
Ar
R1
S.S vial and ball
O
no solvent, air, 23oC
yield up to 80%
Solvent-free
Mild reaction conditions
Recyclable
High functional group tolerance
High chemoselectivity