Light-Controlled Regioselective Synthesis of Fullerene Bis-Adducts

Article abstract of DOI:10.1002/ange.202009235

Multi-functionalization and isomer-purity of fullerenes are crucial tasks for the development of their chemistry in various fields. In both current main approaches—tether-directed covalent functionalization and supramolecular masks—the control of regiosel

Full text of DOI:10.1002/ange.202009235

Angewandte
Eine Zeitschrift der Gesellschaft Deutscher Chemiker
Chemie
www.angewandte.de
Akzeptierter Artikel
Titel: Light-Controlled Regioselective Synthesis of Fullerene Bis-
Adducts
Autoren: Luka Đorđević, Lorenzo Casimiro, Nicola Demitri, Massimo
Baroncini, Serena Silvi, Francesca Arcudi, Alberto Credi, and
Maurizio Prato
Dieser Beitrag wurde nach Begutachtung und Überarbeitung sofort als
"akzeptierter Artikel" (Accepted Article; AA) publiziert und kann unter
Angabe der unten stehenden Digitalobjekt-Identifizierungsnummer
(DOI) zitiert werden. Die deutsche Übersetzung wird gemeinsam mit der
endgültigen englischen Fassung erscheinen. Die endgültige englische
Fassung (Version of Record) wird ehestmöglich nach dem Redigieren
und einem Korrekturgang als Early-View-Beitrag erscheinen und kann
sich naturgemäß von der AA-Fassung unterscheiden. Leser sollten
daher die endgültige Fassung, sobald sie veröffentlicht ist, verwenden.
Für die AA-Fassung trägt der Autor die alleinige Verantwortung.
Zitierweise: Angew. Chem. Int. Ed. 10.1002/anie.202009235
Link zur VoR: https://doi.org/10.1002/anie.202009235

10.1002/ange.202009235
Angewandte Chemie
RESEARCH ARTICLE
Light-Controlled Regioselective Synthesis of Fullerene Bis-
Adducts
Luka Ðorđević,a,b,c* Lorenzo Casimiro,d,e,f Nicola Demitri,g Massimo Baroncini,d,h Serena Silvi,d,e
Francesca Arcudi,a,b Alberto Credi,d,i,* and Maurizio Pratoa,j,l*
[a]
Department of Chemical and Pharmaceutical Sciences & INSTM, UdR Trieste, University of Trieste, via Licio Giorgieri 1, 34127 Trieste, Italy. E-mail:
dordevic.luka@gmail.com; prato@units.it
[b]
[c]
[d]
Present address: Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States
Present address: Simpson Querrey Institute, Northwestern University, 303 E. Superior, Suite 11-131, Chicago, Illinois 60611, United States
CLAN – Center for Light Activated Nanostructures, Università di Bologna and Consiglio Nazionale delle Ricerche, via Gobetti 101, 40129 Bologna, Italy. E-
mail: alberto.credi@unibo.it
[e]
[f]
Dipartimento di Chimica “G. Ciamician”, Università di Bologna, via Selmi 2, 40127 Bologna, Italy
Present address: Supramolecular and Macromolecular Photochemistry and Photophysics, ENS Paris-Saclay, CNRS, Université Paris-Saclay, 61 Avenue
du Président Wilson, 94235 Cachan, France
[g]
[h]
[i]
Elettra – Sincrotrone Trieste, S.S. 14 Km 163.5 in Area Science Park, 34149 Basovizza, Italy
Dipartimento di Scienze e Tecnologie Agro-alimentari, Università di Bologna, viale Fanin 44, 40127 Bologna, Italy
Dipartimento di Chimica Industriale “Toso Montanari”, Università di Bologna, viale del Risorgimento 4, 40136 Bologna, Italy
Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramón 182, 20014
Donostia San Sebastián, Spain
[j]
[l]
Basque Foundation for Science, Ikerbasque, Bilbao 48013, Spain
Supporting information for this article is given via a link at the end of the document.
Abstract: Multi-functionalization and isomer-purity of fullerenes are
crucial tasks for the development of fullerene chemistry in various
fields. In both current main approaches – tether-directed covalent
Isomerically pure fullerene bis-adducts have also beneficial
effects on the performance of OPV devices, when compared to
mixtures of isomers, due to their molecular packing.[7] Therefore,
devising synthetic approaches towards isomer-pure multi-
functionalized fullerenes is desirable for boosting their application,
including (but not limited to) the thin-film solar cells area.
Given the spherical nature of [60]fullerene, with its 30 [6,6]
double bonds, a precise control of the functionalization reactions
that lead to multiple adducts is highly challenging. Specifically, the
double addition of symmetric and identical moieties to
[60]fullerene can afford 8 regioisomers, which can be described
based on the position of the second addend in reference to the
first one (Figure 1a): the former can lie in the same hemisphere
(cis), at the equator (e), or in the opposite hemisphere (trans).[8]
To control the synthesis of the bis-adducts and avoid tedious and
time-consuming chromatographic separations, which are
necessary for sequential stoichiometric additions such as Bingel-
Hirsch cyclopropanation reactions (Figure 1b),[8] several covalent
and supramolecular approaches have been developed (Figure
1c-f).
functionalization and supramolecular masks
– the control of
regioselectivity requires multi-step synthetic procedures to prepare
the desired tether or mask. Herein, we describe light-responsive
tethers, containing an azobenzene photoswitch and two malonate
groups, in the double cyclopropanation of [60]fullerene. The formation
of the bis-adducts and their spectroscopic and photochemical
properties, as well as the effect of azobenzene photoswitching on the
regiochemistry of the bis-addition, have been studied. The behavior
of the tethers depends on the geometry of the connection between
the photoactive core and the malonate moieties. One tether lead to
strikingly different adduct distribution for the E and Z isomers,
indicating that the covalent bis-functionalization of C60 can be
controlled by light.
Introduction
The first rational approach towards regioselective synthesis was
based on tether-directed remote functionalization.[9] C60 was first
functionalized with a carboxylic acid anchor group through the
Bingel reaction, followed by condensation with a tether carrying a
reactive group – a 1,3-butadiene moiety capable of a Diels-Alder
addition – leading to the equatorial bis-adduct in 23% yield. This
approach was then extended to the tether-directed double
addition by exploiting tethered bis-malonates which, after reaction
with C60, afforded bis-adducts in a shorter synthetic route (Figure
1c).[10] Since then, numerous tether-controlled methods for
preparing bis-adducts by double Bingel, 1,3-dipolar or diazo
cycloadditions have been described.[11] Also notable is the
topochemically controlled Diels-Alder synthesis of trans-1 bis-
adducts (Figure 1d), which enabled further functionalization of the
available axial positions.[12]
Fullerenes and their derivatives, ever since their discovery,[1]
have gained interest in
a variety of fields ranging from
(bio)medical chemistry[2] to material science,[3] with notable
advances in thin-film solar cells, such as organic photovoltaic
(OPVs) and perovskite solar cells (PSCs).[4] These compounds
exhibit
a
robust electron-deficient character and great
semiconducting properties, which have prompted their
widespread use as electron acceptors in bulk heterojunction
OPVs. Furthermore, fullerenes have emerged as candidates for
use in PSC, due to their electron-transport properties and well-
matched energy levels with perovskites.[5]
Among fullerene derivatives, the bis-functionalized ones have
been the best performing ones in OPVs and PSCs. For example,
the pure α-bis-phenyl-C62-butyric acid methyl ester isomer (or α-
bis-PC60BM) has shown better performance and stability when
compared to the more popular mono-functionalized PC60BM.[6]
1
This article is protected by copyright. All rights reserved.

10.1002/ange.202009235
Angewandte Chemie
RESEARCH ARTICLE
Figure 1. Current synthetic strategies towards regioselective bis-functionalization of fullerene C60 (a) can be divided in two categories: covalent (b-d) and
supramolecular (e-f). The approach described in this work (g) belongs to the first category and takes advantage of tether-like compounds. RG = reactive group.
Another elegant approach towards the regiochemical control of
multiple addition makes use of supramolecular masks, which
could be removed after the reaction (Figure 1ef). This approach
consists in confining, before the cycloaddition reactions, C60 in
supramolecular receptors, such as coordination cages,[13] metal-
organic frameworks[14], covalent organic cages,[15] rotaxanes[16] or
cycloparaphenylene (CPP) hosts.[17] In particular, an inclusion
complex of diethyl ester C61(CO2Et)2 and [10]CPP, when
subjected to a Bingel cyclopropanation, yielded trans-3 and trans-
2 C62(CO2Et)4 in 24% and 20% yields, respectively (Figure 1e).
Recently, a metallosupramolecular cuboid box-shaped host was
used to complex C60, leaving four openings that direct the
cyclopropanation reactions in the equatorial position in 97% yield
(Figure 1f).[13c] However, all the regioselective methods reported
to date, despite their elegance, lack flexibility and require
significant efforts, because a specific tether or supramolecular
mask has to be designed and prepared to target one (or more)
regioisomers.
An appealing strategy towards more versatile routes to
regioselective fullerene bis-functionalization is to combine tether-
directed double addition methods with molecular switching by an
external trigger. Molecular switches – species that can be
reversibly interconverted between different forms in response to
chemical or physical stimuli – offer a wealth of possibilities in
terms of structure, properties, and nature of the control input.[18]
Light is a very convenient tool to operate molecular switches,
particularly in multi-component systems, because it is a non-
invasive signal that can be carefully modulated in time, space and
energy.[18-19] There have been previous reports of photoswitches
and fullerenes that have focused on the photoisomerization of
fullerene dimers[20] and used tweezer for the supramolecular
encapsulation of C60.[21]
Here we investigate the use of photoswitchable tethers for the
regioselective bis-addition to C60 fullerene (Figure 1g). As the
light-responsive moiety we chose azobenzene because of its
facile functionalization and well known photoisomerization
process.[22] Generally, the E isomer is thermodynamically stable
and it is converted to the Z isomer by UV light irradiation; the E
form can be regenerated thermally or by exposure to visible light.
As the E-Z transformation is accompanied by a large geometrical
rearrangement and a change in the length of the azobenzene
moiety, we envisaged that if the latter is endowed with two
terminal units capable of attacking the C60 double bonds, then the
E and Z isomers could undergo the bis-addition with different
regiochemical outcomes. On the other hand, the photochemical
properties of the azobenzene unit could be modified upon
covalent attachment to the fullerene. To investigate these points,
we prepared two molecular tethers consisting of an azobenzene
core and two malonate reactive end groups. The two tethers,
which differ in the substitution position of the malonate groups on
the phenyl rings of the azobenzene, were employed in both the E
and Z configurations for the double cyclopropanation reaction on
the C60 sphere. We also investigated the structural, spectroscopic
and photochemical properties of the tethers and their fullerene
bis-adducts.
Results and Discussion
Design, synthesis and spectroscopic characterization of the
azobenzene tethers
To gain insight on the role of azobenzene configuration, and
thus the effect of photoisomerization, on the formation of the C60
2
This article is protected by copyright. All rights reserved.

10.1002/ange.202009235
Angewandte Chemie
RESEARCH ARTICLE
bis-adducts, we designed two different
tethers in which the malonate units are
introduced either in meta or in para
positions on the azobenzene aromatic
rings
respectively, in Scheme 1). Molecular
modelling confirms that such
(compounds
4
and
6,
substitution patterns lead to different
isomer dependence of the distance
between the terminal malonates
(Supporting Information, Section 6).
Moreover, in the less symmetric meta
derivative the end-to-end distance can
also be affected by the rotation of
phenyl rings around the C–N bond.[23]
The synthetic route (Scheme 1)
involves the reductive coupling of m-
nitrobenzyl
alcohol,
using
glucose/NaOH[24] as reducing agent, to
give azobenzene 3. The azobenzene
diol was subsequently converted, with
ethyl malonyl chloride in presence of 4-
dimethylaminopyridine,[25] into bis-
Scheme 1. Synthesis of C60 bis-adducts by azobenzene tether-directed remote functionalization. Reagents and
conditions: a) D-glucose, NaOH, EtOH/H2O, 50 °C; b) EtOOCCH2COCl, DMAP, an. THF, 0 °C ® r.t., 16 h; c)
C60, I2, DBU, toluene, 0 °C, 2 h, dark. DMAP = 4-(dimethylamino)pyridine, THF = tetrahydrofuran, DBU = 1,8-
diazabicyclo[5.4.0]undec-7-ene.
malonate
4,
containing
meta-
substituted azobenzene. Bis-malonate
M–1 cm–1, and the π-π* band is slightly redshifted with respect to
6, with substituents in the para-position
4, peaking at 328 nm and with an ε = 27000 M–1 cm–1.
of azobenzene, whose structure was confirmed also by X-ray
crystallography (Supporting Information, Section 5), could be
obtained using the same sequence and reaction conditions
starting from p-nitrobenzyl alcohol. The spectroscopic and
(photo)isomerization properties of these two azobenzene
derivatives were then investigated in toluene at room temperature
(Table S1).
Irradiation of E-6 in the UV induces the E→Z isomerization (Figure
2b) until photostationary states, richer in Z isomer with respect to
4, are achieved. The PSS composition and the spectrum of the Z
form were determined as in the previous case. The percentage of
Z at the PSS resulted to be 97% at 365 nm and 68% at 313 nm.
The quantum yield for the E→Z isomerization, measured at 365
nm, is 0.14. As observed for 4, irradiation in the visible region (436
nm) converts preferentially the Z form into the E one, however
with a quantum yield (0.51) lower than that of compound 4. The
thermal back isomerization, in this case, possesses a rate
constant of 2.7 × 10–6 s–1 (Figure S18).
Compound E-4 shows the typical absorption spectrum of
azobenzene derivatives:[22a-f] a weak n-π* band centered at 450
nm, with a molar absorption coefficient (ε) of 500 M–1 cm–1, and a
more intense π-π* band in the UV region, with maximum at 322
nm and an ε of 22000 M–1 cm–1 (Figure S15). Irradiation of E-4 at
313 nm or 365 nm produces a strong decrease in the UV
absorption and an increase of the n−π* band (see Figure 2a),
which can be ascribed to an E→Z isomerization, until a
photostationary state (PSS) is achieved. The composition of the
PSS was determined from the corresponding absorption spectra
by applying the Fischer method[26] and resulted to be [Z]/[E] = 92:8
at 365 nm and 83:17 at 313 nm. With the same method, the
absorption spectrum of the Z isomer was also calculated. The
quantum yield for the E→Z isomerization, measured upon
irradiation at 365 nm, is 0.18. Upon irradiation in the visible region
of a solution previously exhaustively irradiated at 365 nm to reach
the PSS, back Z→E photoisomerization occurs, until a PSS of
85:15 [E]/[Z] is afforded. The quantum yield related to this process,
measured upon irradiation at 436 nm, resulted to be 0.64. The
thermal Z→E isomerization was studied by monitoring over
several days the absorption changes of a UV-irradiated solution
kept in the dark at room temperature. The data could be
satisfactorily fitted according to a first order kinetic law, giving a
rate constant of 1.4 × 10–6 s–1 (Figure S16).
Figure 2. Absorption changes of azobenzene tethers E-4 (a, 47 × 10–6 M) and
E-6 (b, 44 × 10–6 M) upon irradiation at 365 nm in toluene at room temperature.
In summary, the spectroscopic and photochemical behavior
of the two tethers is in line with that of azobenzene derivatives,
and indicate that the presence of the malonate substituents does
not hamper photoswitching. The thermal Z®E isomerization
process is also present, but it should be emphasized that under
the conditions employed to form the bis-adducts (0 °C, 2 h
reaction time; see Scheme 1) such reaction can be neglected for
both 4 and 6 (Figures S19-S20).
Compound E-6 shows an absorption spectrum similar to
compound E-4 (Figure S17), but with an overall higher absorption
coefficient. The n-π* band is centered at 450 nm, with an ε of 660
3
This article is protected by copyright. All rights reserved.

10.1002/ange.202009235
Angewandte Chemie
RESEARCH ARTICLE
Synthesis and spectroscopic characterization of the C60 bis-
adducts
Indeed, irradiation of bis-adduct e-1 at 365 nm (Figure S22)
produced no appreciable variations, even for prolonged exposure
times. Thus, the Z stereoisomer of e-1 cannot be accumulated by
photoirradiation. This observation could be due either to the
suppressed photoreactivity of the azo unit (i.e., very low quantum
yield) or to a very fast Z®E back reaction. It can be hypothesized
that the covalent connection of the azobenzene to the fullerene
via the malonate tethers may constrain the former in the E
configuration.[29]
The reaction of bis-malonate meta-substituted azobenzene E-
4 with C60 by a modified Bingel-Hirsch reaction[27] yielded the
equatorial bis-adduct 1 in 32% isolated yield (Scheme 1, top). The
1H- and 13C-NMR spectra showed molecular C1-symmetry
(Supporting Information, Figures S5-S6). We were able to grow
single crystals of C60-azobenzene derivative e-1, from hexane
vapor diffusion into a chloroform solution, suitable for X-ray
crystallography (monoclinic, space group P 21/c). The crystal
structure confirmed the C1 symmetry of the molecule and the E-
configuration of the azobenzene tether (Figure 3). The
transesterification reaction[28] of e-1 yielded tetraethyl ester e-
C62(CO2Et)4 (7) with Cs symmetry. Furthermore, adduct 1 showed
an absorption spectrum (Figure S21) coherent with a bis-
functionalized C60 in equatorial position and superimposable with
the mathematic sum of the absorption spectra of the parent E-4
and the reference tetraethyl ester e-C62(CO2Et)4 (7), confirming
that the reaction occurred between the E isomer and the C60.
Interestingly, the para-substituted azobenzene tether
6
exhibited a completely different behavior (Scheme 1, bottom).
The modified Bingel-Hirsch reaction of E-6 with C60 afforded a
mixture that proved difficult to purify and characterize. However,
careful separation of the regioisomers by preparative TLC and
their subsequent characterization by UV-Vis spectroscopy, given
the characteristic features in the 400-700 nm region used as a
fingerprint,[25] allowed us to identify three regioisomers (Figure
S34). The main product is the trans-4 bis-adduct (91% relative
yield), together with two minor products consisting of the trans-2
and trans-3 regioisomers (7% and 2% relative yields,
1
respectively). Although trans-4-2 shows broad H NMR signals
(Figure S36), a comparison with the spectra of E- and Z-6 (Figure
S37) suggests that in the bis-adduct the azobenzene is in the E
configuration.
We then proceeded with the photoisomerization of E-6 to Z-6,
following the same procedure employed for the meta-substituted
azobenzene. The bis-malonate Z-6, obtained with isolated 75%
yield, was allowed to react with C60 under modified Bingel-Hirsch
conditions.[27] The equatorial derivative 2 was obtained as the
main product in 30% isolated yield. The relative positions of the
1
two cyclopropane rings on the C60 were discerned by H-NMR,
13C-NMR, UV-Vis spectroscopy and X-ray crystallography. The 1H
and 13C-NMR spectra confirmed the C1 symmetry of compound e-
2, especially evident from the 56 signals from the sp2 fullerene C
atoms (Supporting Information, Figure S28). We were also able
to grow single crystals of C60-azobenzene derivative e-2, from
hexane vapor diffusion into a chloroform solution, suitable for X-
ray crystallography (triclinic, space group P −1). The crystal
structure confirmed the Z configuration of the azobenzene unit
and the C1 symmetry of the molecule (Figure 4ab). Further
confirmations were obtained by UV-Vis spectroscopy, which
showed characteristic features of equatorial C60 bis-adducts in the
400-700 nm region (Figure 4c).[25] Finally, transesterification
reaction (K2CO3, anhydrous THF/EtOH 1:1 v/v, r.t.) of compound
e-2 yielded the known tetraethyl ester e-C62(CO2Et)4 (7) with Cs
symmetry.[8,28]
Figure 3. (a) Crystal structure (atomic displacement parameters are drawn at
the 50% probability level) and (b) crystal packing (molecules of CHCl3 are
omitted for clarity) of the equatorial bis-adduct 1.
Irradiation of compound e-2 in the visible region at 436 nm
produced little changes in the absorption spectrum, which could
be ascribed to a Z→E isomerization, with an estimated quantum
yield of 0.11. In another experiment, we irradiated the sample at
436 nm for a few minutes and then at 365 nm to trigger the E→Z
transformation (Figure 4d). The initial spectrum was regenerated,
confirming that the photoreaction is the ZDE isomerization. After
a successive irradiation at 436 nm, the solution was kept in the
dark and its absorbance monitored over time. The photoproduct
exhibits a relatively fast thermal back isomerization in the dark to
the initial Z-form; the transformation is complete within one hour
at room temperature (rate constant 1.0 × 10–3 s–1, Figure S24).
All these data suggest that the thermodynamically stable form of
the azo moiety in the bis-adduct e-2 is Z. Irradiation at 436 nm
can produce the E isomer, although with a much lower quantum
For the synthesis of C60 bis-adduct using the Z-4 isomer, the
E®Z photoisomerization of 4 had to be performed on a larger
scale and higher concentration (Supporting Information, Figure
S32) compared to the spectroscopic studies reported in the
previous section. Additionally, it was necessary to perform flash
chromatography to isolate the pure Z isomer (with 55% isolated
yield). The bis-malonate Z-4 was then allowed to react with C60
under modified Bingel-Hirsch conditions and, surprisingly, yielded
once again the equatorial-1 bis-adduct with the azobenzene in the
E configuration (Scheme 1, top). While the reaction was running,
monitoring with thin-layer chromatography (TLC) allowed us to
detect only equatorial-1 bis-adduct, which was confirmed, after
purification, by 1H- and 13C-NMR spectra and UV-Vis
spectroscopy.
4
This article is protected by copyright. All rights reserved.

10.1002/ange.202009235
Angewandte Chemie
RESEARCH ARTICLE
In the case of the meta-substituted tether (4),
we did not observe substantial differences, in
terms of regioisomer distribution and product
yields, between the E and Z forms. The dcore
parameter computed for the stable conformer of
E-4 (9.16 Å) is very similar to the analogous
distance measured from the X-ray structure of
e-1 (8.87 Å, Figure 3a). This observation
explains the ability of 4 in its E form to doubly
functionalize C60 with an equatorial pattern. On
the other hand, the stable conformer of Z-4 has
a much shorter extension (dcore = 5.45 Å), most
likely incompatible with an equatorial bis-
addition. This finding, together with the fact that
the reaction between Z-4 and C60 forms a bis-
adduct with the azobenzene unit in the E
configuration, indicates that the bis-addition can
only occur with the tether in its E form.
Furthermore, our data show that the thermal
isomerization of free Z-4 is too slow to account
for the formation of a significant amount of E-4
on the cyclopropanation time scale. Hence, we
propose that a mono-adduct between Z-4 and
C60 is formed first, in which the thermal Z→E
isomerization is strongly accelerated, possibly
because of electronic interactions between the
fullerene sphere and the dangling azobenzene
and/or malonate units. As the rate of the first
addition is likely unaffected by the isomeric form
Figure 4. (a) Crystal structure (atomic displacement parameters are drawn at the 50% probability level)
and (b) crystal packing (molecules of CHCl3 are omitted for clarity) of equatorial bis-adduct 2. (c)
Absorption spectrum of 2 (black full line) in toluene, together with the spectra of Z-6 (red dashed line)
and 7 (black dashed line). (d) Absorbance changes upon successive irradiations at 436 nm (purple
areas) and 365 nm (striped area), and final rest in the dark (grey area).
yield than that observed for the same reaction in the free tether 6
of the azobenzene unit, e-1 is obtained in similar yields
irrespective of the initial configuration of the tether. Finally, the
impossibility to accumulate the Z form of e-1 by light irradiation is
consistent with such a scenario.
(Table S1). Interestingly, the metastable form of e-2 reverts back
to the stable configuration with a rate constant three orders of
magnitude faster than that of the analogous process in tether 6.
Structural features of the tethers and regioselectivity of the
bis-adducts
Aimed at rationalizing the observed results, we compared the
outcomes of the four bis-addition cyclopropanation reactions, and
attempted to correlate them with the structure of the tethers. A
conformational/configurational analysis performed by DFT
calculations enabled us to determine the length of the switchable
unit of tethers 4 and 6 in their E and Z forms, taken as the distance
between the methylene carbon atoms connecting the
azobenzene core with the malonate moieties (dcore; Supporting
Information, Section 6). Although the conformational freedom of
each malonate group can also play a role in the bis-addition, it
can be reasoned that the separation between the malonates will
be largely determined by the more rigid and switchable
azobenzene core.
In brief, the calculations show that for both tethers the E
configuration is more stable than the Z (Tables S3-S4), albeit in 4
the energy difference (3.5 kcal mol−1) is much smaller than that of
6 (9.8 kcal mol−1) and of plain azobenzene (ca. 12 kcal mol−1)[22a]
.
In both cases the E→Z isomerization causes a significant
decrease of dcore (35-40%); however, in the case of 4 the “off-axis”
meta-substitution determines, in each configuration, the presence
of syn and anti conformations of the malonates with respect to the
azobenzene main axis, in which dcore can change by ±10% (Table
S3 and Figure S39). On the contrary, dcore in the para-derivative 6
depends exclusively on the azobenzene configuration (Table S4
and Figure S40).
Figure 5. Relative reaction yields of the regioisomeric Bingel-Hirsch bis-adducts
of E-6 (blue bars) and Z-6 (red bars) azobenzene tethers, in comparison with
published data[8] in the absence of tethers (grey bars).
The results are markedly different – and more interesting – in
the case of the para-substituted tether 6, with the E- or Z-6 bis-
malonate tethers exhibiting different regioselectivities (Figure 5,
Figures S34-S37). Subjecting bis-malonate E-6 to the modified
5
This article is protected by copyright. All rights reserved.

10.1002/ange.202009235
Angewandte Chemie
RESEARCH ARTICLE
Bingel-Hirsch reaction gave bis-adducts trans-4, trans-3 and
trans-2 in 91%, 2% and 7% relative yields, respectively.
Conversely, the Z-isomer of 6 afforded bis-adducts e, cis-3, trans-
4, trans-3 and trans-2 in 81%, 10%, 6%, 1% and 2% relative
yields,[30] respectively. DFT Calculations show that in E-6 dcore can
be as large as 12.5 Å, whereas it is 7.96 Å in Z-6. The
experimental distance found in the crystal structure of e-2 (9.02 Å,
Figure 4a) correlates reasonably well with the latter value,
whereas it is considerably shorter than the former one. This
comparison provides a rationale for both the propensity of Z-6 to
equatorial bis-addition and the stabilization of the Z-azobenzene
unit with respect to the E-form in the adduct e-2. On the other
hand, the larger dcore in E-6 could favor trans bis-addition patterns
with respect to the equatorial one, thus qualitatively explaining the
This work was supported by the University of Trieste and the
Maria de Maeztu Units of Excellence Program from the Spanish
State Research Agency (Grant No. MDM-2017-0720). Additional
financial support from the Ministero dell'Istruzione, Università e
Ricerca (PRIN grants 2017PBXPN4, 20173L7W8K and
201732PY3X, and FARE grant R16S9XXKX3), the University of
Bologna, and the National Research Council of Italy is gratefully
acknowledged. We thank Prof. Tatiana Da Ros and Dr. Giulio
Ragazzon (University of Trieste), and Profs. Ettore Fois and
Gloria Tabacchi (University of Insubria) for their help with the
HPLC and DFT calculations, respectively.
Keywords: molecular switch • photoswitch • azobenzene •
fullerene • C60 • Bingel-Hirsch cyclopropanation • regioselectivity
observed regioselectivity and the
E configuration of the
azobenzene unit in trans-4-2.
[1]
[2]
a) H. W. Kroto, J. R. Heath, S. C. O’Brien, R. F. Curl, R. E. Smalley,
Nature 1985, 318, 162-163; b) N. Martín, Chem 2019, 5, 733-738.
a) S. Bosi, T. Da Ros, G. Spalluto, M. Prato, Eur. J. Med. Chem. 2003,
38, 913-923; b) I. Nierengarten, J. F. Nierengarten, Chem. Asian J 2014,
9, 1436-1444; c) E. Castro, A. Hernandez Garcia, G. Zavala, L.
Echegoyen, J. Mater. Chem. B 2017, 5, 6523-6535; d) J. Ramos-Soriano,
J. J. Reina, B. M. Illescas, N. de la Cruz, L. Rodriguez-Perez, F. Lasala,
J. Rojo, R. Delgado, N. Martin, J. Am. Chem. Soc. 2019, 141, 15403-
15412.
Conclusion
Two photoswitchable azobenzene derivatives, each bearing two
malonate reactive groups in meta- or para- positions to the azo
moiety, were used as tethers for the preparation of [60]fullerene
bis-adducts. Molecular modelling shows that, despite the
structural similarity, the two compounds exhibit different behavior
with regard to photoinduced shape modifications. In the case of
the meta-substituted azobenzene tether, the bis-addition
regioselectivity does not change when using either the E or the Z
isomers. The main product, in both cases, is the equatorial bis-
adduct, in which the azobenzene unit is in the E configuration and
loses its photoswitching capacity because of the steric strain
caused by the covalent linkage to C60.
The para-substituted tether gives more interesting results, as
the regioselectivity of the double cyclopropanation reaction is
markedly different for the E and Z isomers. The E-tether,
characterized by a longer length of the azobenzene core, forms
preferentially trans-bis-adducts, whereas for the Z-tether the
equatorial bis-addition prevails. Furthermore, in the latter adduct
the azobenzene unit exists in the Z form, which becomes the
thermodynamically stable one as shown by single crystal X-ray
diffraction and spectroscopic and photochemical experiments.
These findings are significant because they show that the
[3]
[4]
a) A. Montellano López, A. Mateo-Alonso, M. Prato, J. Mater. Chem.
2011, 21, 1305-1318; b) L. Đorđević, T. Marangoni, F. De Leo, I.
Papagiannouli, P. Aloukos, S. Couris, E. Pavoni, F. Monti, N. Armaroli,
M. Prato, D. Bonifazi, Phys. Chem. Chem. Phys. 2016, 18, 11858-11868.
a) W. Yan, S. M. Seifermann, P. Pierrat, S. Bräse, Org. Biomol. Chem.
2015, 13, 25-54; b) T. Umeyama, H. Imahori, Dalton Trans. 2017, 46,
15615-15627; c) T. Gatti, E. Menna, M. Meneghetti, M. Maggini, A.
Petrozza, F. Lamberti, Nano Energy 2017, 41, 84-100; d) A.
Zieleniewska, F. Lodermeyer, A. Roth, D. M. Guldi, Chem. Soc. Rev.
2018, 47, 702-714; e) E. Castro, J. Murillo, O. Fernandez-Delgado, L.
Echegoyen, J. Mat. Chem. C 2018, 6, 2635-2651; f) S. Collavini, J. L.
Delgado, Sustain. Energy Fuels 2018, 2, 2480-2493; g) M. Izquierdo, B.
Platzer, A. J. Stasyuk, O. A. Stasyuk, A. A. Voityuk, S. Cuesta, M. Sola,
D. M. Guldi, N. Martín, Angew. Chem. Int. Ed. 2019, 58, 6932-6937.
a) J. Y. Jeng, Y. F. Chiang, M. H. Lee, S. R. Peng, T. F. Guo, P. Chen,
T. C. Wen, Adv. Mater. 2013, 25, 3727-3732; b) D. Luo, W. Yang, Z.
Wang, A. Sadhanala, Q. Hu, R. Su, R. Shivanna, G. F. Trindade, J. F.
Watts, Z. Xu, T. Liu, K. Chen, F. Ye, P. Wu, L. Zhao, J. Wu, Y. Tu, Y.
Zhang, X. Yang, W. Zhang, R. H. Friend, Q. Gong, H. J. Snaith, R. Zhu,
Science 2018, 360, 1442-1446; c) M. Hadadian, J.-H. Smått, J.-P.
Correa-Baena, Energy Environ. Sci. 2020, 13, 1377-1407; d) X. Zheng,
Y. Hou, C. Bao, J. Yin, F. Yuan, Z. Huang, K. Song, J. Liu, J. Troughton,
N. Gasparini, C. Zhou, Y. Lin, D.-J. Xue, B. Chen, A. K. Johnston, N. Wei,
M. N. Hedhili, M. Wei, A. Y. Alsalloum, P. Maity, B. Turedi, C. Yang, D.
Baran, T. D. Anthopoulos, Y. Han, Z.-H. Lu, O. F. Mohammed, F. Gao,
E. H. Sargent, O. M. Bakr, Nat. Energy 2020, 5, 131-140.
[5]
light-responsive properties of
a molecular moiety can be
modulated by covalent attachment to the C60 sphere, in a way that
depends on the bis-functionalization pattern, thus creating new
opportunities in the field of photochromism.
Moreover, this work provides the basis for alternative routes
to fullerene functionalization, in which light can be employed as a
tool to direct the reaction outcome by taking advantage of
[6]
F. Zhang, W. Shi, J. Luo, N. Pellet, C. Yi, X. Li, X. Zhao, T. J. S. Dennis,
X. Li, S. Wang, Y. Xiao, S. M. Zakeeruddin, D. Bi, M. Grätzel, Adv. Mater.
2017, 29, 1606806.
molecular photoswitching. Such
a
general approach,
[7]
[8]
T. Umeyama, H. Imahori, Acc. Chem. Res. 2019, 52, 2046-2055.
A. Hirsch, I. Lamparth, H. R. Karfunkel, Angew. Chem. Int. Ed. 1994, 33,
437-438.
characterized by simplicity and versatility, could lead to the
controlled production of fullerene isomers of interest as active
materials in organic and perovskite solar cells. It is tempting to
think that this strategy, based on using light to control the
regiochemistry of a non-photochemical reaction, could be applied
to other fullerenes and multi-adducts, as well as other substrates
and (photo)switches.
[9]
L. Isaacs, R. F. Haldimann, F. Diederich, Angew. Chem. Int. Ed. 1994,
33, 2339-2342.
[10] J.-F. Nierengarten, V. Gramlich, F. Cardullo, F. Diederich, Angew. Chem.
Int. Ed. 1996, 35, 2101-2103.
[11] a) J. F. Nierengarten, T. Habicher, R. Kessinger, F. Cardullo, F.
Diederich, V. Grämlich, J. P. Gisselbrecht, C. Boudon, M. Gross, Helv.
Chim. Acta 1997, 80, 2238-2276; b) F. Diederich, R. Kessinger, Acc.
Chem. Res. 1999, 32, 537-545; c) C. Thilgen, F. Diederich, Cr. Chim.
2006, 9, 868-880; d) V. Garg, G. Kodis, M. Chachisvilis, M. Hambourger,
A. L. Moore, T. A. Moore, D. Gust, J. Am. Chem. Soc. 2011, 133, 2944-
Acknowledgements
6
This article is protected by copyright. All rights reserved.

10.1002/ange.202009235
Angewandte Chemie
RESEARCH ARTICLE
2954; e) G. Bottari, O. Trukhina, A. Kahnt, M. Frunzi, Y. Murata, A.
Rodríguez-Fortea, J. M. Poblet, D. M. Guldi, T. Torres, Angew. Chem.
Int. Ed. 2016, 55, 11020-11025; f) M. R. Cerón, L. Echegoyen, J. Phys.
Org. Chem. 2016, 29, 613-619.
[29] It cannot be excluded, however, that the behaviour of this particular
compound is determined by electronic interactions between the two
molecular units.
[30] It is probable that trans-2 and trans-3 bis-adducts are present in the
mixture due to the Z→E back isomerization that occurred before the C60
functionalization reaction (during chromatographic separation and rotary
evaporation).
[12] a) B. Kräutler, T. Müller, J. Maynollo, K. Gruber, C. Kratky, P.
Ochsenbein, D. Schwarzenbach, H.-B. Bürgi, Angew. Chem. Int. Ed.
1996, 35, 1204-1206; b) R. Schwenninger, T. Müller, B. Kräutler, J. Am.
Chem. Soc. 1997, 119, 9317-9318.
[13] a) W. Brenner, T. K. Ronson, J. R. Nitschke, J. Am. Chem. Soc. 2017,
139, 75-78; b) B. Chen, J. J. Holstein, S. Horiuchi, W. G. Hiller, G. H.
Clever, J. Am. Chem. Soc. 2019, 141, 8907-8913; c) C. Fuertes-
Espinosa, C. García-Simón, M. Pujals, M. Garcia-Borràs, L. Gómez, T.
Parella, J. Juanhuix, I. Imaz, D. Maspoch, M. Costas, X. Ribas, Chem
2020, 6, 169-186.
[14] N. Huang, K. Wang, H. Drake, P. Cai, J. Pang, J. Li, S. Che, L. Huang,
Q. Wang, H. C. Zhou, J. Am. Chem. Soc. 2018, 140, 6383-6390.
[15] V. Leonhardt, S. Fimmel, A.-M. Krause, F. Beuerle, Chem. Sci. 2020,
10.1039/D0SC03131C.
[16] M. Carini, T. Da Ros, M. Prato, A. Mateo-Alonso, ChemPhysChem 2016,
17, 1823-1828.
[17] Y. Xu, R. Kaur, B. Wang, M. B. Minameyer, S. Gsänger, B. Meyer, T.
Drewello, D. M. Guldi, M. Von Delius, J. Am. Chem. Soc. 2018, 140,
13413-13420.
[18] a) Molecular Switches, 2nd ed., Wiley-VCH, Weinheim, 2011; b) J. D.
Harris, M. J. Moran, I. Aprahamian, Proc. Natl. Acad. Sci. U. S. A. 2018,
115, 9414-9422.
[19] a) M. Baroncini, M. Canton, L. Casimiro, S. Corra, J. Groppi, M. La Rosa,
S. Silvi, A. Credi, Eur. J. Inorg. Chem. 2018, 2018, 4589-4603; b) J.
Boelke, S. Hecht, Adv. Opt. Mater. 2019, 7; c) G. Naren, C. W. Hsu, S.
Li, M. Morimoto, S. Tang, J. Hernando, G. Guirado, M. Irie, F. M. Raymo,
H. Sunden, J. Andreasson, Nat. Commun. 2019, 10, 3996; d) Z. L.
Pianowski, Chem. Eur. J. 2019, 25, 5128-5144; e) D. Villaron, S. J.
Wezenberg, Angew. Chem. Int. Ed. 2020, 10.1002/anie.202001031.
[20] J. Zhang, K. Porfyrakis, J. J. L. Morton, M. R. Sambrook, J. Harmer, L.
Xiao, A. Ardavan, G. A. D. Briggs, J. Phys. Chem. C 2008, 112, 2802-
2804.
[21] a) M. Samanta, A. Rananaware, D. N. Nadimetla, S. A. Rahaman, M.
Saha, R. W. Jadhav, S. V. Bhosale, S. Bandyopadhyay, Sci. Rep. 2019,
9, 9670; b) H. Barbero, S. Ferrero, L. Alvarez-Miguel, P. Gomez-Iglesias,
D. Miguel, C. M. Alvarez, Chem. Commun. 2016, 52, 12964-12967.
[22] a) E. Merino, M. Ribagorda, Beilstein J. Org. Chem. 2012, 8, 1071-1090;
b) H. M. D. Bandara, S. C. Burdette, Chem. Soc. Rev. 2012, 41, 1809-
1825; c) M. Baroncini, G. Ragazzon, S. Silvi, M. Venturi, A. Credi, Pure
Appl. Chem. 2015, 87, 537-545; d) L. Dong, Y. Feng, L. Wang, W. Feng,
Chem. Soc. Rev. 2018, 47, 7339-7368; e) V. Y. Chang, C. Fedele, A.
Priimagi, A. Shishido, C. J. Barrett, Adv. Opt. Mater. 2019, 7, 1900091;
f) M. Baroncini, J. Groppi, S. Corra, S. Silvi, A. Credi, Adv. Opt. Mater.
2019, 7, 1900392; g) M. Lahikainen, H. Zeng, A. Priimagi, Nat. Commun.
2018, 9, 4148; h) C. Nacci, M. Baroncini, A. Credi, L. Grill, Angew. Chem.
Int. Ed. 2018, 57, 15034-15039; i) X. Liu, J. Zhang, M. Fadeev, Z. Li, V.
Wulf, H. Tian, I. Willner, Chem. Sci. 2019, 10, 1008-1016; j) A. Galanti,
J. Santoro, R. Mannancherry, Q. Duez, V. Diez-Cabanes, M. Valasek, J.
De Winter, J. Cornil, P. Gerbaux, M. Mayor, P. Samorì, J. Am. Chem.
Soc. 2019, 141, 9273-9283; k) D. Mutruc, A. Goulet-Hanssens, S.
Fairman, S. Wahl, A. Zimathies, C. Knie, S. Hecht, Angew. Chem. Int.
Ed. 2019, 58, 12862-12867; l) L. Pesce, C. Perego, A. B. Grommet, R.
Klajn, G. M. Pavan, J. Am. Chem. Soc. 2020, 142, 9792-9802.
[23] R. L. Klug, R. Burcl, J. Phys. Chem. A 2010, 114, 6401-6407.
[24] S. Ameerunisha, P. S. Zacharias, J. Chem. Soc. Perkin Trans. 2 1995,
0, 1679-1682.
[25] F. Djojo, A. Herzog, I. Lamparth, F. Hampel, A. Hirsch, Chem. Eur. J.
1996, 2, 1537-1547.
[26] E. Fischer, J. Phys. Chem. 1967, 71, 3704-3706.
[27] S. Sergeyev, M. Schar, P. Seiler, O. Lukoyanova, L. Echegoyen, F.
Diederich, Chem. Eur. J. 2005, 11, 2284-2294.
[28] J.-F. Nierengarten, T. Habicher, R. Kessinger, F. Cardullo, F. Diederich,
V. Gramlich, J.-P. Gisselbrecht, C. Boudon, M. Gross, Helv. Chim. Acta
1997, 80, 2238-2276.
7
This article is protected by copyright. All rights reserved.

10.1002/ange.202009235
Angewandte Chemie
RESEARCH ARTICLE
Entry for the Table of Contents
By incorporating azobenzene photochromic units in the tether-directed double functionalization of [60]fullerene, the regiochemistry of
the double cyclopropanation reaction could be controlled by using either the E or the Z isomeric forms of the photoswitch. Once
covalently linked to the C60 sphere, the azobenzene unit changes its light- and thermally-induced isomerization properties. These
findings have implications in both the synthesis of fullerene derivatives and organic photochromism.
Institute and/or researcher Twitter usernames: @UniTrieste @StampaCnr @UniboMagazine
8
This article is protected by copyright. All rights reserved.