A monomer-dimer nanoswitch that mimics the working principle of the SARS-CoV 3CLpro enzyme controls copper-catalysed cyclopropanation

Article abstract of DOI:10.1039/c4dt01508h

A triangular framework with a terpyridine and shielded phenanthroline at its termini constitutes an open/close nanoswitch that is toggled by chemical inputs. In the presence of copper(i) ions, the open triangular framework (OPEN-I) firmly closes to a catalytically inactive heteroleptic [Cu(phen)(terpy)]⁺ complex (CLOSE). Reversible switching between CLOSE and OPEN-I states was demonstrated by successive addition and removal of Cu⁺. In contrast, after addition of iron(ii) ions to the CLOSE state a bishomoleptic dimeric [Fe(terpy)₂]²⁺ complex is formed with the copper(i) ions placed in the phenanthroline cavities (OPEN-II). Due to its coordinatively unsaturated [Cu(Phen)]⁺ sites the dimeric iron complex is able to serve as a catalyst in the cyclopropanation of Z-cyclooctene using ethyl diazoacetate.

Full text of DOI:10.1039/c4dt01508h

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A monomer–dimer nanoswitch that mimics the
working principle of the SARS-CoV 3CLpro
enzyme controls copper-catalysed
cyclopropanation†
Cite this: DOI: 10.1039/c4dt01508h
Soumen De, Susnata Pramanik and Michael Schmittel*
A triangular framework with a terpyridine and shielded phenanthroline at its termini constitutes an
open/close nanoswitch that is toggled by chemical inputs. In the presence of copper(I) ions, the open tri-
angular framework (OPEN-I) firmly closes to a catalytically inactive heteroleptic [Cu(phen)(terpy)]+
complex (CLOSE). Reversible switching between CLOSE and OPEN-I states was demonstrated by succes-
sive addition and removal of Cu+. In contrast, after addition of iron(II) ions to the CLOSE state a bishomo-
leptic dimeric [Fe(terpy)2]2+ complex is formed with the copper(I) ions placed in the phenanthroline
cavities (OPEN-II). Due to its coordinatively unsaturated [Cu(Phen)]+ sites the dimeric iron complex is able
to serve as a catalyst in the cyclopropanation of Z-cyclooctene using ethyl diazoacetate.
Received 22nd May 2014,
Accepted 28th May 2014
DOI: 10.1039/c4dt01508h
www.rsc.org/dalton
an active transition metal catalyst in its homodimeric form
and to be inactive in the collapsed monomeric state. To the
Introduction
The principles used by intricate biological machines to modu- best of our knowledge such a protocol to toggle catalysis is
late their activity with supreme efficacy have become both an without precedents.
inspiration and aspiration for many researchers who want to
For setting up an ON/OFF dimer/monomer toggle, we
design and investigate artificial molecular machines1 and devised nanoswitch 1 (Scheme 1) based on a triangular geome-
switches.2 A particularly strong fascination arises from the smart try, because such a design has proven its utility in a convincing
management of pronounced translational and/or rotational manner.5 Its function to undergo monomer-to-dimer switching
motions that trigger useful functions due to the spatial was implemented by considering the coordination preferences
rearrangement.3 Inspired by biological archetypes, very recently of copper(I) and iron(II) ions. While Cu+ prefers a tetrahedral
artificial nanoswitches have been introduced whose catalytic coordination, Fe2+ is strongly inclined toward the octahedral
action is controlled through pronounced translational and/or setting. We expected to lock the switch upon addition of
rotational motions.4 In this context, triangular nano-frameworks copper(I) ions and to reversibly convert [Cu(1)]+ either to its
have proven to be robust toggles for turning ON/OFF photo- and starting state 1 by removal of copper ions (Scheme 1) or to its
organocatalytic reactions in a fully reversible manner.5
bishomoleptic “dimeric” state [Fe(Cu(1))2)]4+ by adding
Nature has been very imaginative to accomplish spectacular Fe(ClO4)2. The latter state should reverse to [Cu(1)]+ by selective
catalytic processes that up to now do not have any analogy in removal of Fe2+ in the presence of Cu+. We anticipated that the
the abiological world. For example, the severe acute respiratory exposed copper site in the dimer is catalytically active (e.g. in a
syndrome coronavirus (SARS-CoV) 3C-like protease (3Clpro)6 is cyclopropanation reaction), which would allow us to mimic the
enzymatically active only as a homodimer. The monomeric overall working mode of the SARS-CoV 3C-like protease.
enzyme is inactive as its catalytic machinery is frozen in the
collapsed state. In the present work we describe the synthesis
and operation of nanoswitch 1 that is designed to constitute
Model study
To assess in advance the chances for the proposed monomer-
Center of Micro and Nanochemistry and Engineering, Organische Chemie I,
to-dimer switching, we studied the self-sorting of the putative
terminal ligands in the presence of both cations.7 When one
Universität Siegen, Adolf-Reichwein-Str. 2, D-57068 Siegen, Germany.
E-mail: schmittel@chemie.uni-siegen.de
equivalent of Cu+ was added to a 1 : 1 mixture of 2,9-dimesityl-
phenanthroline (2) and terpyridine (3), the heteroleptic
complex [Cu(2)(3)]+ (log β = 9.1)8 emerged exclusively as
†Electronic supplementary information (ESI) available: Full experimental pro-
cedures with assignment of 1H NMR signals, spectra of compounds, documen-
tation of catalysis. See DOI: 10.1039/c4dt01508h
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The fully orthogonal coordination scenario in Scheme 2
suggested to integrate the respective ligands into the covalent
triangular framework of nanoswitch 1 and to realise toggling
between monomer and dimer states as a function of the added
metal ions.
Results and discussion
Synthesis
The straightforward converging synthesis of nanoswitch 1
involves a series of Sonogashira couplings and deprotection
steps. At first, 4-ethynylterpyridine was selectively coupled to
one of the bromo substituents of compound 4 in a Sonoga-
shira reaction using Pd(PPh3)4 in THF and triethylamine
(TEA), then the TMS-protecting group was removed from
compound 5 in the presence of aqueous KOH to afford terpyri-
dine 6 (Scheme 3). In a similar way, 2,9-dimesityl-3-ethynyl
[1,10]phenanthroline (7) was reacted with (2-iodophenyl-
ethynyl)trimethylsilane in the presence of Pd(PPh3)4 to furnish
8 (Scheme 4). Finally, phenanthroline 10 was afforded by
Scheme 1 Switching between close and two open forms of nano-
switch 1.
1
verified from the H NMR data (Fig. S23, ESI†). Upon addition
of Fe2+ (0.5 equiv.) to [Cu(2)(3)]+, the heteroleptic complex
completely vanished, while the bishomoleptic complex [Fe
(3)2]2+ (log β = 16.9)9 formed exclusively releasing the coordina-
tively unsaturated [Cu(2)]+ (log K1 = 5.1) (Fig. S24†) into solu-
tion (Scheme 2).
Scheme 3 Synthesis of terpyridine building block 6.
Scheme 2 Switching the coordination mode in model ligand scenarios
depending on the metal ions.
Scheme 4 Synthesis of nanoswitch 1.
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removing the TMS-protection group in the presence of aqueous
KOH followed by reaction with 1,4-diiodobenzene in the pres-
ence of Pd(PPh3)4. Nanoswitch 1 was finally obtained in a Sono-
gashira coupling reaction between 6 and 10 in the presence of
Pd(PPh3)4 as a catalyst in a THF–TEA mixture. Characterisation
of the nanoswitch and of all other new compounds is described
in detail in the experimental part and in the ESI.†
Fig. 2 1H NMR (400 MHz, CD2Cl2, 298 K) of (top) [Fe(1)]2+ and (bottom)
[Fe(Cu(1))2]4+
.
Switching studies
At first, switching between open and close forms of 1 was
probed using Cu+ ions (Scheme 1). As expected, addition of
one equivalent of [Cu(CH3CN)4]PF6 to a solution of nanoswitch
1 (0.10 mM) in CD2Cl2 resulted in significant shifts in the
1H NMR spectrum. The diagnostic upfield shift of the signal
for the aromatic mesityl protons from 6.95 and 6.97 ppm
(Fig. 1, bottom) to 4.48, 5.89, 6.28, and 6.43 ppm due to shield-
ing from the terpyridine ring suggests the formation of the
intramolecular complex [Cu(1)]+. Further support for this
assignment was received from the simultaneous upfield shift
of the terpyridine protons a-H and b-H from 8.68 and
7.25 ppm to 6.66 and 6.78 ppm, respectively. Intramolecular
complexation was further supported by the concentration inde-
pendence of the 1H NMR signals (Fig. S16†). Moreover, the ESI
mass spectrum of the resulting complex shows a molecular
ion peak at m/z 1128.1 (Fig. S31†) corresponding to the mono-
meric complex [Cu(1)]+. Its experimental isotopic distribution
perfectly matches with the theoretical one. Thus, NMR and
ESI-MS unanimously validate intramolecular complexation.
When [Cu(1)]+ was treated with one equivalent of cyclam,
the 1H NMR peaks at 4.48, 5.89, 6.28, and 6.43 ppm disap-
peared, whereas the 1H signals at 6.95 and 6.97 ppm emerged,
being diagnostic for nanoswitch 1 (Fig. S32†). These changes
indicate that the system is fully set back to the open form with
one equivalent of cyclam only. Quantitative multiple switching
between OPEN-I and CLOSE was initiated by alternate
additions of one equivalent of Cu+ and one equivalent of
cyclam for up to two cycles.
The terpyridine a-H protons shift upfield from 8.68 to
6.96 ppm, protons b-H from 7.25 to 7.01 ppm, and protons
d-H from 8.45 to 8.09 ppm. Protons e-H, in contrast, shift
slightly downfield from 8.70 to 8.77 ppm. Summing up, the
diagnostic changes in the 1H NMR signals unambiguously
support formation of [Fe(1)2]2+.
To evaluate the coordination preference of both metal ions
in a competitive scenario, we added 2.0 equiv. of Cu+ to the
1
above solution of [Fe(1)2]2+. The H NMR was fully consistent
with the formation of [Fe(Cu(1))2]4+ with the copper(I) ions
placed in both phenanthroline binding sites (OPEN-II). Diag-
nostically, the mesityl protons at 6.75 and 6.85 ppm of
[Fe(1)2]2+ (Fig. 2, top) are now shifted downfield to 6.95 and
6.96 ppm (Fig. 2, bottom). Similarly, the downfield shifts of
phenanthroline protons 4-H and 7-H from 8.45 and 8.09 ppm
to 8.73 and 8.62 ppm, respectively, confirm the existence of
Cu+-loaded phenanthroline sites. Actually, the metal ions are
occupying the same ligand sites as in the simple model system
1
(Scheme 2). Exactly the same H NMR spectrum was obtained
(Fig. S17†) upon addition of 0.5 equivalent of Fe(ClO4)2 to the
closed nanoswitch [Cu(1)]+ (CLOSE) suggesting quantitative
switching to the dimeric [Fe(Cu(1))2]4+ (OPEN-II).
Reversible switching between OPEN-II and CLOSE states
was accomplished by selective removal of Fe2+. After addition
of 4-N,N-dimethylaminoterpyridine to [Fe(Cu(1))2]4+ (OPEN-II),
a very strong known complexing agent for Fe2+ ions, we
observed the clean formation of CLOSE and [Fe(4-N,N-
dimethylaminoterpyridine)2]2+. The closed form [Cu(1)]+ was
identified by its mesityl protons that diagnostically reappear at
4.48, 5.89, 6.28, and 6.43 ppm in the 1H NMR spectrum
(Fig. S33†). The above observation is also consistent with a
model study: when two equivalents of 4-N,N-dimethylamino-
terpyridine were added to a 2 : 1 mixture of model complexes
[Cu(2)]+ and [Fe(3)2]2+, the Fe2+ ions were selectively removed
from complex [Fe(3)2]2+ to generate [Cu(2)(3)]+. Importantly,
reversible nanoswitching between monomer and dimer was
successfully accomplished for up to two cycles (Fig. S33†).
When 0.5 equiv. of Fe(ClO4)2 was added to nanoswitch 1
(OPEN-I), the homodimeric complex [Fe(1)2]2+ formed by using
exclusively the terminal terpyridine unit for complexation.
This choice is driven by the strong preference of Fe2+ for hexa-
coordination, as even visually perceptible from a distinct
colour change from light yellow to deep violet. Concordantly,
the 1H NMR spectrum shows the expected shifts of the terpyri-
dine protons after iron complex formation (Fig. 2, top).
Catalysis
After the successful implementation of the monomer-to-dimer
switching process, we investigated the efficacy of the nano-
switch to act as a switchable transition metal catalyst. Cyclo-
propanation of Z-cyclooctene (11) with ethyldiazoacetate (12) is
a prototypical reaction accelerated by Cu+ ions (Scheme 5).
Fig. 1 1H NMR (400 MHz, CD2Cl2, 298 K) of switch 1 (top) and [Cu(1)]+
(bottom).
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Conclusions
In conclusion, we have elaborated the new triangular nano-
switch 1 that may be toggled between open and closed forms
by addition and removal of Cu+. Moreover, the closed switch
[Cu(1)]+ can be operated between a catalytically active dimeric
(OPEN-II) and an inactive monomeric (CLOSE) form by alter-
nate addition of Fe2+ and 4-N,N-dimethylaminoterpyridine. In
the active form, the nanoswitch [Fe(Cu(1))2]4+ = OPEN-II
exposes the catalytically relevant [Cu(phen)]+ sites that are
demonstrated to catalyse the cyclopropanation of Z-cyclo-
octene by ethyl diazoacetate.
In several ways, nanoswitch 1 mimics the mode of oper-
ation of the SARS-CoV 3C-like protease. Like the natural
enzyme, the monomeric 1 is inactive because its catalytic
machinery is frozen in the collapsed state, while it is catalyti-
cally active only as a homodimer.
Scheme 5 Catalytic reaction used in the present study.
We first confirmed that the reaction between 11 and 12
(1 : 1) does not proceed in the presence of complex10 [Cu(2)-
([1,10]-phenanthroline)]+ (10 mol%) (Fig. S36†), whereas the
coordinatively frustrated [Cu(2)]+ complex (10 mol%) catalyses
the formation of the cyclopropane 13 in 49 4% yield (55 °C,
4 h) while forming the known decomposition products 14 and
15 (Fig. S35†). A control experiment in the presence of Cu+
alone produced 30 4% of the product 13 (Fig. S34†).
When a 1 : 1 mixture of 11 and 12 was heated in the pres-
ence of 10 mol% of nanoswitch [Cu(1)]+ (0.10 mM) = CLOSE in
an NMR tube at 55 °C for 4 h, no cycloaddition product was
observed as evidenced from the 1H NMR spectrum (Fig. 3a).
However, when the same experiment was performed under the
same conditions with the help of dimer [Fe(Cu(1))2]4+
(0.10 mM, 10 mol%) = OPEN-II, 35 3% of cyclopropane 13
was afforded (Fig. 3b).
The overall protocol serves as a show case for how a metal-
ion signal (Fe2+ input) can turn ON a process that is catalysed
by a completely different metal ion. In principle, the same
mode of operation should be applicable to hide any catalyti-
cally active metal ion in the heteroleptic complex [M(1)]n+ and
expose its active site(s) after switching to the dimeric complex.
Finally, the in situ OFF/ON switching of catalysis was exe-
cuted. As before, the closed form of nanoswitch 1 = CLOSE did
not afford any cyclopropanation product 13 (Fig. S37†). After
addition of 0.5 equivalent of Fe(ClO4)2 to this very mixture and
heating at 55 °C for 4 h, the cyclopropane 13 emerged in 30
5% yield (Fig. S37†).
A further control experiment was performed, now with
homodimer [Fe(1)2]2+, to check whether the iron homodimeric
residue is responsible for catalysis. After adding 0.5 equiv. of
Fe(ClO4)2 to nanoswitch 1, the thus prepared [Fe(1)2]2+ was
exposed to a 1 : 1 mixture of 11 and 12 under the same con-
ditions as for catalysis. No cyclopropanation occurred
(Fig. S38†)! Catalytic activity returned, though, after further
addition of two equivalents of Cu+ to [Fe(1)2]2+ furnishing
dimer [Fe(Cu(1))2]4+. Now cyclopropane 13 was formed in 30
5% yield after heating the reaction mixture for 4 h at 55 °C.
Experimental procedures
General information
All commercially available reagents were used without further
purification and all solvents were distilled prior to use for
column chromatography. We used silica gel 60 for thin-layer
and column chromatography. The 400 MHz 1H NMR spectra
were recorded using the deuterated solvent as the lock and
1
residual solvent as the internal reference. In H NMR assign-
ments, first, the chemical shift (in ppm) is given, followed, in
brackets, by the multiplicity of the signal (s: singlet, d:
doublet, t: triplet, dd: doublet of doublets, ddd: doublet of
doublet of doublets, td: triplet of doublets, m: multiplet, bs:
broad singlet), the value of the coupling constants in hertz
(Hz), the number of protons implied, and finally the assign-
ment of the proton where ever possible. Anhydrous tetrahydro-
furan (THF) was distilled over potassium and triethylamine
was dried over calcium hydride. The melting points of solid
compounds were not further corrected. IR spectra were
recorded on a Perkin-Elmer FT-IR 1750. Electrospray ionisation
mass spectra (ESI-MS) were recorded on a Thermo-Quest LCQ
Deca. Microanalyses were performed on a Euro elemental ana-
lyser from EuroVector. The preparation and detailed character-
isation of precursors 4–10 as well as full assignments for the
nanoswitch system are provided in the ESI.†
Synthesis
Nanoswitch
1 (OPEN-I). Phenanthroline 10 (210 mg,
Fig. 3 1H NMR (400 MHz, CD2Cl2, 298 K) after reacting 11 and 12 for
4 h at 55 °C either in the presence of (a) nanoswitch [Cu(1)]+ (CLOSE) or
(b) nanoswitch [Fe(Cu(1))2]4+ (OPEN-II). 4-Nitrobenzaldehyde is the
standard.
283 μmol) and terpyridine 6 (128 mg, 284 μmol) were placed in
a flask under an argon atmosphere. Then 30 mL of dry THF
and 30 mL of dry TEA were added. After the solution had been
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deaerated for 1 h by purging with argon, Pd(PPh3)4 (50.0 mg, [Cu(1)]+; calcd m/z
=
1128.3. Elemental analysis:
43.3 μmol) was added. The reaction was heated at 65 °C for C72H50BrCuF6N5P·0.5DCM; Calcd: C, 66.16; H, 3.91; N, 5.32.
18 h, and then the solvents were removed in vacuum. The Found: C, 66.19; H, 4.11; N, 5.07.
residue was dissolved in DCM and washed with water. The
Dimeric complex [Fe(Cu(1))2]4+ (OPEN-II). Switch
1
organic layer was dried over Na2SO4. The resulting solid (2.58 mg, 2.42 μmol) and [Cu(CH3CN)4]PF6 (903 µg, 2.42 μmol)
obtained after evaporating the solvents was chromatographed were put into an NMR tube, dissolved in CD2Cl2 and heated to
over silica gel (10% EtOAc in DCM) to furnish ligand 1 as a 40 °C for few seconds affording a reddish solution. A solution
white solid (Rf = 0.7 in DCM on neutral alumina). The ligand of Fe(ClO4)2·6H2O (439 µg, 1.21 μmol) in CD3CN was added to
obtained after column chromatography was furthermore puri- the mixture and after that the mixture was heated for about
fied over Bio-Beads S-X8 using toluene as an eluent. The 5 min at 40 °C affording a deep violet solution. The NMR was
middle fraction contained the target compound. Yield: 130 mg recorded without further purification. Yield: quantitative. MP:
1
(122 μmol, 43%). MP: decomposition >200 °C. IR (KBr): above 300 °C. H NMR (400 MHz, CD2Cl2–CD3CN = 3 : 1): δ =
˜ν 3053, 2919, 2854, 2209, 1714, 1586, 1460, 1389, 1254, 994, 1.32 (s, 6 H), 1.76 (s, 18 H), 2.32 (s, 6 H), 2.33 (s, 6 H), 2.47 (s,
1
847, 793, 749, 618, 543 cm−1. H NMR (400 MHz, CDCl3): δ = 6 H), 6.90 (d, 3J = 7.6 Hz, 2 H), 6.95 (s, 4 H), 6.96 (s, 4 H),
2.05 (s, 6 H), 2.06 (s, 6 H), 2.33 (s, 3 H), 2.37 (s, 3 H), 2.41 (s, 7.07–7.10 (m, 8 H), 7.21–7.25 (m, 2 H), 7.28–7.32 (m, 2 H), 7.45
3
3
3 H), 6.95 (s, 2 H), 6.97 (s, 2 H), 6.98–7.00 (m, 1 H), 7.24–7.29 (d, J = 7.6 Hz, 2 H), 7.66–7.71 (m, 8 H), 7.78 (d, J = 8.0 Hz,
3
4
3
3
(m, 3 H), 7.33 (dt, J = 7.6 Hz, J = 1.6 Hz 1 H), 7.48–7.50 (m, 2 2 H), 7.80–7.85 (m, 2 H), 7.92 (d, J = 8.4 Hz, 4 H), 8.04 (d, J =
H), 7.51 (d, J = 8.8 Hz, 1 H), 7.55–7.57 (m, 2 H), 7.61 (d, J = 8.8 Hz, 2 H), 8.07 (d, 3J = 8.8 Hz, 2 H), 8.15 (d, 3J = 7.6 Hz, 4 H),
8.8 Hz, 1 H), 7.68 (d, 3J = 8.4 Hz, 2 H), 7.73 (td, 3J = 7.6 Hz, 4J = 8.58 (d, 3J = 8.0 Hz, 2 H), 8.70 (s, 2 H), 8.80 (s, 4 H) ppm.
2.0 Hz, 2 H), 8.85 (d, 3J = 8.4 Hz, 2 H), 8.13 (d, 3J = 8.0 Hz, 1 H), 13C NMR (100 MHz, CD2Cl2–CD3CN = 3 : 1): δ = 19.6, 19.9,
3
3
8.31 (s, 1 H), 8.45 (ddd, J = 7.6 Hz, 4J = 1.2 Hz, 5J = 1.2 Hz, 21.0, 21.1, 21.1, 89.3, 89.4, 90.3, 90.8, 93.2, 95.2, 97.1, 97.6,
3
3
4
5
2 H), 8.68 (ddd, J = 8.4 Hz, J = 2.0 Hz, J = 1.2 Hz, 2 H), 8.70 122.3, 123.4, 123.9, 124.2, 124.5, 124.9, 125.2, 125.3, 125.6,
(s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.1, 20.5, 21.1 125.7, 126.5, 126.9, 127.6, 127.8, 128.1, 128.2, 128.2, 128.3,
(2C), 21.2, 89.3, 90.3, 91.1, 91.9, 92.0, 93.4, 93.6, 97.6, 119.8, 128.8, 129.4, 132.2, 132.3, 132.3, 132.7, 132.9, 132.9, 135.2,
121.1, 122.9, 123.3, 123.5, 124.1, 124.9, 125.0, 125.2, 125.5, 135.7, 135.9, 136.2, 137.1, 138.2, 138.9, 138.9, 139.1, 140.0,
125.6, 125.7, 126.5, 126.7, 126.8, 127.5, 128.0, 128.2, 128.3, 141.2, 142.2, 143.4, 153.1, 157.2, 160.1, 160.3, 161.5 ppm.
128.5, 131.6, 131.8 (2C), 132.0, 132.4, 132.9, 133.8, 136.0, 136.1 Elemental analysis: C144H100Br2Cl2Cu2F12FeN10O8P2·3CH2Cl2·
(2C), 136.7, 137.0 (2C), 137.4, 137.6, 137.7, 139.0, 139.7, 144.6, CH3CN; Calcd: C, 57.77; H, 3.55; N, 4.97. Found: C, 57.47;
145.6, 149.0, 155.5, 160.3, 161.5 ppm. ESI-MS: m/z (%) = 1065.9 H, 3.52; N, 5.32.
(100) [1·H]+; calcd m/z
=
1065.3. Elemental analysis:
C72H50N5Br·0.33DCM; Calcd: C, 79.46; H, 4.67; N, 6.41. Found:
C, 79.25; H, 4.42; N, 6.38.
Model catalysis
[Cu(1)]+ (CLOSE). Switch 1 (2.57 mg, 2.41 μmol) and Catalytic cyclopropanation reactions were performed on a
[Cu(CH3CN)4]PF6 (0.899 mg, 2.41 μmol) were placed into an 10 mM scale. A mixture of Z-cyclooctene, ethyl diazoacetate
NMR tube and dissolved in CD2Cl2. The mixture was heated to and [Cu(CH3CN)4]PF6 was heated at 55 °C ( 0.1) for 4 h in an
40 °C for a few seconds affording a reddish solution. The NMR NMR tube in a HAAKE-N2 thermostat. The literature known
was recorded without purification. Yield: quantitative. MP: addition adducts 13, 14 and 15 were characterised by 1H NMR.
1
>300 °C. H NMR (400 MHz, CD2Cl2): δ = 1.05 (s, 3 H), 1.09 (s, The above reaction was also carried out by heating an equi-
3 H), 1.63 (s, 3 H), 1.82 (s, 3 H), 1.88 (s, 6 H), 2.43 (s, 3 H), 4.48 molar mixture of Z-cyclooctene and ethyl diazoacetate in the
3
(s, 1 H), 5.89 (s, 1 H), 6.28 (s, 1 H), 6.43 (s, 1 H), 6.67 (d, J = presence of 10 mol% of [Cu(2)]PF6 to mimic the situation in
4.8 Hz, 1 H), 6.78 (ddd, 3J = 7.6 Hz, 3J = 4.8 Hz, 4J = 1.2 Hz, [Fe(Cu(1))2)]4+.
3
1 H), 7.28 (d, J = 8.4 Hz, 2 H), 7.30–7.39 (m, 4 H), 7.43–7.45
3
(m, 2 H), 7.58 (d, J = 8.4 Hz, 2 H), 7.60–7.62 (m, 2 H), 7.64 (d,
3
3
Catalysis experiments using the nanoswitch
3J = 7.6 Hz, 1 H), 7.76 (d, J = 7.6 Hz, 1 H), 7.78 (d, J = 8.4 Hz,
4
3
4
1 H), 7.85 (d, J = 1.2 Hz, 1 H), 7.87 (td, J = 7.6 Hz, J = 1.2 Hz The catalytic reaction with the nanoswitch was probed at a
4
3
1 H), 8.03 (d, J = 1.2 Hz, 1 H), 8.15 (d, J = 4.8 Hz, 1 H), 8.18 similar scale using the same conditions as described above.
3
3
3
(d, J = 8.8 Hz, 1 H), 8.24 (d, J = 8.8 Hz, 1 H), 8.65 (d, J = 8.4 Equivalent amounts of Z-cyclooctene (677 µmg, 6.14 µmol)
Hz, 1 H), 8.81 (s, 1 H) ppm. 13C NMR (100 MHz, CD2Cl2): δ = and ethyl diazoacetate (701 µmg, 6.14 µmol) were mixed with
18.6, 19.9, 20.0, 20.5, 20.7, 21.2, 21.2, 88.5, 89.0, 89.1, 89.6, 10 mol% of nanoswitch 1 (654 µmg, 0.614 µmol) and
92.0, 93.6, 94.5, 96.9, 116.9, 120.9, 122.7, 123.0, 123.1, 123.2, [Cu(CH3CN)4]PF6 (229 µmg, 0.614 µmol). With the closed form
123.9, 124.3, 124.6, 124.6, 124.7, 124.9, 125.9, 126.5, 126.8, of the nanoswitch, i.e. [Cu(1)]PF6, no cyclopropanated product
126.9, 127.0, 127.2, 127.4, 127.6, 127.7, 127.8, 127.9, 128.6, 13 was formed in detectable amount. However, upon addition
128.9, 129.5, 131.3, 131.7, 132.4, 132.5, 132.9, 134.0, 134.5, of 0.5 equivalent of Fe(ClO4)2 (111 µmg, 0.306 µmol) with
134.7, 135.0, 135.0, 136.4, 136.6, 137.0, 137.1, 137.4, 137.4, respect to nanoswitch 1, the dimeric form [Fe(Cu(1))2]4+
138.3, 141.0, 141.0, 142.9, 144.4, 147.1, 148.1, 150.6, 152.7, should form. Indeed, after heating the mixture for 4 h at 55 °C
153.7, 153.8, 159.5, 159.9 ppm. ESI-MS: m/z (%) = 1128.1 (100) cyclopropane 13 was afforded.
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Acknowledgements
We are grateful to the Deutsche Forschungsgemeinschaft and
the Universität Siegen for financial support.
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