Accelerated Discovery of α-Cyanodiarylethene Photoswitches

Article abstract of DOI:10.1021/jacs.1c03631

Cyanodiarylethene chromophores are able to undergo constitutional exchange via dynamic covalent chemistry (DCC). During this process, the central ethylene bridge of the molecular scaffold can be broken and thereby enables the assembly of a new combination of aryl moieties around the reformed ethylene bridge. The reversible CC double bond exchange has exemplarily been investigated using α-cyanostilbenes. Establishing a dynamic equilibrium reaction from α-cyanodiarylethene with arylacetonitriles under mild conditions has been the basis to access constitutional libraries of new photoswitches with potentially improved properties. When subject to irradiation with light of adequate wavelength, α-cyanodiarylethenes undergo Z/E isomerization followed by ring-closure. By screening the thus accessible dynamic chromophore libraries using a desired detection wavelength, we could identify specific dithienyl analogues that exhibit three-state photochromism. The combination of dynamic constitutional libraries of functional chromophores in combination with the light-guided screening and selection should lead to more rapid exploration of structural diversity dye chemistry.

Full text of DOI:10.1021/jacs.1c03631

pubs.acs.org/JACS
Article
Accelerated Discovery of α‑Cyanodiarylethene Photoswitches
Niklas F. König,† Dragos Mutruc,† and Stefan Hecht*
Cite This: J. Am. Chem. Soc. 2021, 143, 9162−9168
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: Cyanodiarylethene chromophores are able to undergo
constitutional exchange via dynamic covalent chemistry (DCC).
During this process, the central ethylene bridge of the molecular
scaffold can be broken and thereby enables the assembly of a new
combination of aryl moieties around the reformed ethylene bridge.
The reversible CC double bond exchange has exemplarily been
investigated using α-cyanostilbenes. Establishing a dynamic equili-
brium reaction from α-cyanodiarylethene with arylacetonitriles under
mild conditions has been the basis to access constitutional libraries of
new photoswitches with potentially improved properties. When
subject to irradiation with light of adequate wavelength, α-
cyanodiarylethenes undergo Z/E isomerization followed by ring-
closure. By screening the thus accessible dynamic chromophore
libraries using a desired detection wavelength, we could identify
specific dithienyl analogues that exhibit three-state photochromism. The combination of dynamic constitutional libraries of
functional chromophores in combination with the light-guided screening and selection should lead to more rapid exploration of
structural diversity dye chemistry.
barbiturates is feasible even at room temperature in the
presence of catalytic amounts of imines forming azetidine
intermediates.15
INTRODUCTION
■
The reversibility of chemical reactions is a fascinating principle
of nature thateven though macroscopically often not
tangibleenables chemical processes, catalytic cycles, and
reaction networks. By minimizing activation barriers, chemical
equilibria can rapidly be established to enable dynamic
constitutional systems and study their adaptive behavior.1 In
this context, dynamic covalent chemistry (DCC) examines
high-energy conversions: the making and breaking of covalent
bonds.2 Systems with dynamic C−C, C−N, C−O, C−S, B−O,
and S−S bonds provide access to dynamic constitutional
libraries that allow for the screening and selection of molecules
with desired properties,3,4 and moreover, enable the design of
responsive functional materials.5
α-Cyanodiarylethenes are photochromic Knoevenagel prod-
ucts obtained from aromatic aldehydes and benzylic nitriles
and they have mostly been studied for their aggregation-
induced (enhanced) emission.16 Their exchange capabilities
have not yet been exploited, although they are an emerging
class of “non-azo” E/Z photoswitches and are used as soft
smart materials in a variety of applications.16,17 Respective 1,2-
dicyanodithienylethenes undergo isomerization to a thermally
stable third state via a reversible photocyclization as first
reported by Irie and Mohri in their landmark paper in 1988.18
A similar switching behavior has more recently been found for
an extended inverse 1,2-dicyano-substituted di(bithienyl)-
ethene.19
Knoevenagel products6 are particularly interesting entities
for DCC. Formed by nucleophilic addition of a CH-acidic
compound to a carbonyl group followed by elimination of
water from the formed Aldol intermediate, they provide broad
structural variety and easy accessibility. Importantly, the
condensation is reversible under basic and acidic conditions,7
which can be employed for syntheses that demand a high level
of thermodynamic control, e.g., to access covalent organic
frameworks.8−11 Knoevenagel exchange, beyond that, allows
for double bond metathesis in water-free systems using amines
as catalysts.12 Lehn and co-workers studied in detail the
Knoevenagel cross-exchange of benzylidene barbiturates and
respective malonates catalyzed by L-proline at elevated
temperatures.13,14 Fast exchange of benzylidene 1,3-dimethyl-
A growing number of studies uses other photochromic
molecules in DCC as a means to control and drive chemical
equilibria with light.20−28 Motivated by both, the unrivaled
spatiotemporal resolution of electromagnetic radiation and its
orthogonality to chemical stimuli, these studies aim to control
Received: April 6, 2021
Published: June 11, 2021
https://doi.org/10.1021/jacs.1c03631
J. Am. Chem. Soc. 2021, 143, 9162−9168
© 2021 American Chemical Society
9162

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
chemical systems and processes and to develop new functional
materials.29 Surprisingly, investigations on the dynamic
covalent assembly of photoswitches themselves are scarce.
Exchanges of (acyl)hydrazones based on hydrolysis/condensa-
tion have been reported30,31 but the potential of dynamic
constitutional libraries as a tool to screen for photochromic
molecules with desired properties has thus far not been
unfolded.
new α-cyanostilbene derivative and a new deprotonated nitrile.
The latter is still active and can either attack another
chromophore or deprotonate another nitrile. Overall, the
dynamic covalent exchange thus results in a thermodynamic
equilibrium of two α-cyanostilbenes (both in their thermally
more stable Z configuration34) and two (deprotonated)
nitriles.
Among the tested catalysts, only bases, such as sodium
bis(trimethylsilyl)amide (NaHMDS) and phosphazene bases
(e.g., P4-t-Bu) were sufficiently strong to deprotonate the
acetonitriles and thus enable an exchange of arylacetonitrile
moieties. Tests with bases such as DBU, sodium methoxide,
piperidine, and L-proline did either not induce exchange,
required prolonged reaction times and elevated temperatures
or were limited to highly acidic phenylacetonitriles. NaHMDS
was the base providing the widest substrate scope and
therefore used to establish a reliable and reproducible DCC
protocol for a broad range of α-cyanodiarylethenes with
different substituents. The exchange is very fast and from a
practical point of view easy to achieve: At room temperature,
an exchange equilibrium with a distinct composition can be
reached within seconds to minutes, depending on the base
equivalents, the nucleophilicity of the nitriles, and the
electrophilicity of the double bond (see Figures S6−S8,
section D.6).
RESULTS AND DISCUSSION
■
Here, we report on a novel dynamic covalent exchange of
Knoevenagel products, namely, α-cyanostilbenes, and the
respective thiophene analogues. We show how DCC can be
used to generate constitutional libraries of these chromophores
and how candidates with desired photochromic properties can
readily be selected. By discovering a novel family of three-state
switches, we demonstrate the general potential of our strategy
to facilitate the development of molecular photochromic
systems.
The chromophores were prepared by a Knoevenagel
condensation of various aromatic aldehydes with nitriles
(Figure 1a). The latter are readily accessible from the
corresponding aldehydes via a Van Leusen reaction.32
As a model system, the exchange of α-cyanostilbene 3c with
(4-methoxyphenyl)acetontrile b was investigated (Figure 2a).
Figure 1. (a) Conditions for Knoevenagel condensation to form α-
cyanostilbenes. (b) Base-catalyzed dynamic covalent exchange of an
α-cyanostilbene with a phenylacetonitrile and the proposed
mechanism.
Figure 2. (a) Dynamic covalent exchange of 3c with b and
corresponding UPLC traces. (b) Dynamic covalent cross-exchange
of 3c and 4b with c as catalyst and corresponding UPLC traces
(experimental details and investigation of composition for both in
sections D.1 and D.4).
The dynamic covalent exchange of an α-cyanostilbene with
an acetonitrile is base-catalyzed (Figure 1b). The exchange is
initiated by deprotonation of the benzylic nitrile, providing the
active nucleophile. The latter attacks the electrophilic double
bond of the α-cyanostilbene, forming a Michael-type anionic
adduct. This negatively charged intermediate can undergo
proton transfer14,33 and subsequently dissociate again into a
The successful establishment of an equilibrium between
chromophores 3b and 3c was verified by ultraperformance
liquid chromatography coupled to mass spectrometry (UPLC-
MS) and the observed ratio was reproduced when starting the
equilibration from the “product side” with 3b and 3c as entries
(see Figure S5a, section D.5, and for details on the
9163
https://doi.org/10.1021/jacs.1c03631
J. Am. Chem. Soc. 2021, 143, 9162−9168

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
Figure 3. (a) Screening for photocyclizing three-state switch DCC setup: four stilbenes (1.0 equiv. each) and three nitriles (1.0 equiv. with respect
to the sum of the four stilbenes) are entries (all black); DCC results in a 4 × 4 = 16-membered library of Z-chromophores (blue); irradiation adds
16 E-isomers (green) and one closed-isomer (orange) to the 33-membered library. UPLC chromatograms of (b) library entries before DCC (abs.
265−600 nm), *note: entry 1c contains both isomers, (c) the equilibrated exchange mixture (abs. 265−600 nm), (d) the irradiated mixture (abs.
265−600 nm), (e) the irradiated exchange mixture (abs. 550−600 nm). *Note: All isomers were identified by a combination of their mass signal,
retention time and UV/vis absorption spectrum obtained from individual exchange experiments (see sections F.1.1−F.1.4).
9164
https://doi.org/10.1021/jacs.1c03631
J. Am. Chem. Soc. 2021, 143, 9162−9168

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
Figure 4. Targeted screening for three-state switches. (a) Exchange setup of 5c with eight different thiophenephenyl acetonitriles (d−k). (b, c)
Photoinduced and thermal isomerization of 5c and 5d−5k, respectively. UPLC chromatograms of (d) the equilibrated exchange mixture (abs.
265−600 nm; minor E isomers are depicted with green asterisks), (e) the irradiated exchange mixture (abs. 265−600 nm), and (f) the irradiated
exchange mixture (abs. 550−600 nm).
nomenclature, Figures S1−S3, section A). Upon reaching an
equilibrium, simultaneous backward and forward reactions are
constantly induced by “active” deprotonated phenylacetoni-
triles. Further investigations were performed to prove that the
system was still dynamic after the initial exchange. Indeed,
upon addition of another nitrile a, the new equilibrium
including 3a quickly formed, strictly following Le Chatelier’s
principle (see Figure S5b, section D.5). Further extending the
concept, we performed a cross-exchange setup (Figure 2b).
Here, we used two different α-cyanostilbenes 3c and 4b in a
1:1 ratio and added only a catalytic amount of deprotonated
nitrile c to trigger the exchange. Nitrile c equilibrates with 4b
to form 4c and nitrile b, which then reacts with 3c to form 3b,
resulting in a total of four different chromophores in this
dynamic equilibrium. Note that for all derivatives of α-
cyanostilbene under the reported equilibration conditions, only
Z isomers were detected, where the less sterically demanding
cyano group is in a Z configuration to the benzene ring. In
agreement with the related Knoevenagel condensation
mechanism, E isomers where identified as minor products
when less bulky and less aromatic substituents were
employed.35
unstable but can be trapped, e.g., when ortho substituents are
used to prevent irreversible oxidation36 or an enol-to-ketone
tautomerism stabilizes the structure against thermal ring-
opening.37 An alternative is the use of less aromatic moieties,
e.g., thiophenes, to attain thermally stable closed isomers that
characteristically absorb in the visible region of the spectrum.
We wanted to confirm that these trends in stability known
from stilbenes and DAEs are also valid for the presented α-
cyanodiarylethenes. Without the need to tediously synthesize a
broad variety of switches for such a study, we used our DCC
cross-exchange tool.
Consequently, we submitted only four generic entries 1c, 2c,
3c, and 5c in equimolar amounts and three arylacetonitriles a,
b, and f (see Figure 3a, b, structures in black) to access a 4 × 4
matrix of α-cyanodiarylethenes. Fragment 5 in 5c and nitrile f
are phenylthiophenes to mimic the structure of commonly
studied DAEs. The resulting library of 16 photoswitches
(Figure 3c) was irradiated for 4 min with UV light (334 nm).
The chromatogram obtained by UPLC-MS (Figure 3d) shows
a complex mixture of more than 32 (2 × 16) different α-
cyanodiarylethene isomers. In addition to Z and E isomers
(Figure 3a, blue and green, respectively), formation of
thermally stable closed isomers was detected by limiting the
UPLC UV/vis detector to the visible region of 550−600 nm
(Figure 3e). Only one peak was observed that can undoubtedly
Apart from E/Z isomerization, stilbenes can undergo a
photoinduced conrotatory ring-closure from their Z config-
uration to yield dihydrophenanthrenes. The latter are usually
9165
https://doi.org/10.1021/jacs.1c03631
J. Am. Chem. Soc. 2021, 143, 9162−9168

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
be attributed to isomer 5f by its corresponding mass signal. It
is the only photochromic motif in our mixture consisting of
two thiophene motifs−one on each side of the cyanoethylene
bridge. Interestingly, the other combinations having only one
thiophene moiety 1f, 2f, 3f, 5a, 5b, and 5c did not yield a
thermally stable closed isomer.
can be observed until the global PSSUV of three isomers is
reached after 2 min. The so-attained closed isomer can then
selectively be addressed with red light, transforming it solely to
the respective E isomer within 3 min. As mentioned above, the
conditioned library experiment (depicted for switches 5c−5k
in Figure 4; for 7c−7k and 9c−9k in Figures S9 and S10,
section D.7 and D.8) yielded valuable information concerning
the molecular design of three-state switches with desired
properties. When just comparing the UV/vis spectra of the Z,
E, and closed isomers of one switch qualitatively, excitation
wavelengths can be selected that lead to PSS with lower or
higher concentration of a chosen isomer. Closed 5d, for
example, shows a red-shifted absorption band in the UV region
at 390 nm, whereas the Z and E isomers show absorption
maxima at 331 and 321 nm, respectively. This band separation,
i.e., the relatively low absorption of closed 5d at 334 nm, can be
used to specifically accumulate the closed isomer in the
PSS334 nm (see Figure 5a). Indeed, when comparing 5d with
5jthe latter having overlapping UV absorption bands with
λUVmax at 329, 317, and 293 nm for Z, E, and closed isomers,
respectivelythe effect is striking. Although the PSS334 nm
composition for 5j shows only 25% closed isomer (see Figure
5b), the PSS334 nm of 5d reaches a significantly higher amount
of 69% closed isomer.
Following the identification of the first DCC-assembled
three-state switch, these α-cyanodithienylethenes were further
examined. The impact of different substitution patterns on the
photocyclization and the corresponding absorption spectra was
investigated. For this reason, we synthesized additional
phenylthiophene aldehydes 6−12 (see Figure S2, section A),
their corresponding acetonitriles d−k (see Figure 4a) as well as
two additional cyclization-mute precursor chromophores 7c
and 9c. This approach proved to be especially elegant, as the
synthesis and purification of different α-cyanodithienylethene
switches were to be individually optimized. In contrast, the
Knoevenagel products from c could be obtained by a
standardized protocol. The precursor chromophores 5c
(dimethylamino-substituted, see Figure 4a), 7c (unsubstituted
derivative), and 9c (trifluoromethyl-substituted derivative)
were each subject to a cross-exchange with phenylthiophene
acetonitriles d−k to generate three 1 × 9 matrices of switches
(see Figures S9 and S10 in sections D.7 and D.8 for 7c and 9c,
respectively). Figure 4 shows this screening approach for
precursor molecule 5c: The 1 × 9 matrix consists of nine
photochromes 5c−5k (Figure 4d). Detailed analysis shows
that the corresponding E isomers are also formed to a minor
extent during the exchange (Figures 3c and 4d, green
asterisks), in contrast to stilbene derivatives. The equilibrated
mixture was further irradiated with 334 nm for 4 min and
analyzed by UPLC-MS (see Figure 4e). The formation of
thermally stable closed isomers was again visualized by limiting
the UPLC UV/vis-detector to the visible region (see Figure
4f). Eight peaks were observed corresponding to the closed
isomers 5d−5k. We were able to confirm that α-cyanodithie-
nylethenes are three-state switches with Z, E, and the closed
state (Figure 4b, c). In a very fast and efficient way, three 1 × 9
matrices were used to identify 24 new three-state switches and
to obtain the absorption spectra of a total of 72 isomers
(photophysical data are detailed in Tables S1 and S2, section
A). Detailed analysis of their closed isomers’ visible absorption
band maxima exposes insightful trends: Compared with the
“unsubstituted” version 7f with an absorption maximum at
542 nm in the visible region, closed 5d (λmax = 590 nm), 7d
(λmax = 572 nm), and 9d (λmax = 582 nm) show a significant
red-shifted visible absorption of 30 to 48 nm that can be
attributed to the push−pull effect between the conjugated
cyano (bridge) and the dimethylamino (phenyl) substituents.
Another trend in red shifts can be explained by the extended π-
conjugation along the entire molecule including both phenyl
moieties. Combinations of strong electron donating and
withdrawing groups lead to larger red-shifts. Accordingly, 5j
with the strongest push−pull substitution pattern (NMe2 and
CN) shows the largest effect with a maximum visible
absorption at 620 nm (shift of 78 nm compared to 7f).
To further analyze their photochemical properties several
three-state switches were synthesized and isolated (see section
C). We found that UV light irradiation of α-cyanodithienyle-
thenes establishes a Z/E pseudo-photostationary state (PSS)
within four seconds. While the Z/E ratio is staying constant,
the E isomer is also in photodynamic equilibrium with the
closed isomer and a decrease in Z and E isomer concentration
Figure 5. Chemical structure (Z isomer shown) of (a) 5d and (b) 5j
and corresponding UV/vis absorption spectra of the PSS mixtures
upon irradiation with UV (λirr = 334 nm for 2 min) and red light (λirr
= 617 nm for 3 min) in acetonitrile at 298 K (17 μM for 5d and 14
μM for 5j). PSS composition according to UPLC-MS analysis (see
section E).
9166
https://doi.org/10.1021/jacs.1c03631
J. Am. Chem. Soc. 2021, 143, 9162−9168

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
Notes
Further investigation of α-cyanodithienylethenes revealed
that they are to be categorized as P-type photoswitches as the
thermal ring-opening of closed-5d was determined to be less
than 10% after 12 days at 80 °C in acetonitrile (see Figure S13,
section E).
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Dedicated to Ben Feringa on the occasion of his 70th birthday.
Generous support by the Deutsche Forschungsgesellschaft
(DFG via EXC 2008−390540038 UniSysCat and via SFB 951,
project A3) is gratefully acknowledged.
CONCLUSION
■
In this work, we demonstrated that α-cyanodiarylethenes can
be assembled using a novel DCC tool at room temperature
that makes use of the dynamic character of the switches’
central CC bond. Efficiently synthesized by a Knoevenagel
condensation, α-cyanodiarylethenes are easily accessible. Using
the combination of this DCC tool and UPLC-MS for analysis,
we were able to identify α-cyanodithienylethenes as a novel
class of three-state switches with three thermally stable
isomers. Additionally, we investigated a broad variety of
these chromophores with different substitution patterns and
the influence on the photochemistry of ring-closure. All this
information was gathered in rapid and efficient experiments
using the presented screening tool. Therefore, the laborious
individual synthesis of a large quantity of potentially photo-
chromic dyes was avoided. As α-cyanodiarylethenes have
proven valuable in the manufacturing of functional materials,5
this work is expected to aid future molecular design in this
particular field of research. Compared to the rich architectures
that are known from DAEs, we have covered only a small
fraction of the possible chemical space with α-cyanostilbenes
and their mono- and dithienyl analogues. On the basis of the
initial work presented herein, we aim to extend our method
with other exchange reactions to reshuffle functional
constituents and to combine it with computational algorithms
to access more complex chromophore systems with desired
properties.
REFERENCES
■
(1) Lehn, J.-M. From supramolecular chemistry towards constitu-
tional dynamic chemistry and adaptive chemistry. Chem. Soc. Rev.
2007, 36 (2), 151−160.
(2) Jin, Y.; Yu, C.; Denman, R. J.; Zhang, W. Recent advances in
dynamic covalent chemistry. Chem. Soc. Rev. 2013, 42 (16), 6634−
6654.
(3) Corbett, P. T.; Leclaire, J.; Vial, L.; West, K. R.; Wietor, J.-L.;
Sanders, J. K. M.; Otto, S. Dynamic Combinatorial Chemistry. Chem.
Rev. 2006, 106 (9), 3652−3711.
(4) Herrmann, A. Dynamic combinatorial/covalent chemistry: a tool
to read, generate and modulate the bioactivity of compounds and
compound mixtures. Chem. Soc. Rev. 2014, 43 (6), 1899−1933.
(5) Chakma, P.; Konkolewicz, D. Dynamic Covalent Bonds in
Polymeric Materials. Angew. Chem., Int. Ed. 2019, 58 (29), 9682−
9695.
̈
(6) Knoevenagel, E. Condensation von Malonsaure mit aromati-
schen Aldehyden durch Ammoniak und Amine. Ber. Dtsch. Chem. Ges.
1898, 31 (3), 2596−2619.
(7) Cope, A. C. Condensation Reactions. I. The Condensation of
Ketones with Cyanoacetic Esters and the Mechanism of the
Knoevenagel Reaction. J. Am. Chem. Soc. 1937, 59, 2327−2330.
(8) Zhuang, X.; Zhao, W.; Zhang, F.; Cao, Y.; Liu, F.; Bi, S.; Feng, X.
A two-dimensional conjugated polymer framework with fully sp2-
bonded carbon skeleton. Polym. Chem. 2016, 7 (25), 4176−4181.
(9) Jin, E.; Asada, M.; Xu, Q.; Dalapati, S.; Addicoat, M. A.; Brady,
M. A.; Xu, H.; Nakamura, T.; Heine, T.; Chen, Q.; Jiang, D. Two-
dimensional sp2 carbon−conjugated covalent organic frameworks.
Science 2017, 357 (6352), 673−676.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.1c03631.
(10) Bi, S.; Yang, C.; Zhang, W.; Xu, J.; Liu, L.; Wu, D.; Wang, X.;
Han, Y.; Liang, Q.; Zhang, F. Two-dimensional semiconducting
covalent organic frameworks via condensation at arylmethyl carbon
atoms. Nat. Commun. 2019, 10, 2467.
(11) Bi, S.; Thiruvengadam, P.; Wei, S.; Zhang, W.; Zhang, F.; Gao,
L.; Xu, J.; Wu, D.; Chen, J.-S.; Zhang, F. Vinylene-Bridged Two-
Dimensional Covalent Organic Frameworks via Knoevenagel
Condensation of Tricyanomesitylene. J. Am. Chem. Soc. 2020, 142
(27), 11893−11900.
(12) Bandar, J. S.; Coscia, R. W.; Lambert, T. H. Demonstration of
the facile reversibility of fulvene formation. Tetrahedron 2011, 67
(24), 4364−4370.
(13) Wilhelms, N.; Kulchat, S.; Lehn, J.-M. Organocatalysis of C =
N/C = N and C = C/C = N Exchange in Dynamic Covalent
Chemistry. Helv. Chim. Acta 2012, 95, 2635−2651.
Experimental procedures and characterization and
spectroscopic data (PDF)
AUTHOR INFORMATION
■
Corresponding Author
Stefan Hecht − DWI−Leibniz Institute for Interactive
Materials & Institute of Technical and Macromolecular
Chemistry, RWTH Aachen University, Aachen 52074,
Germany; orcid.org/0000-0002-6124-0222;
Email: hecht@dwi.rwth-aachen.de
(14) Kulchat, S.; Meguellati, K.; Lehn, J.-M. Organocatalyzed and
Uncatalyzed C = C/C = C and C = C/C = N Exchange Processes
between Knoevenagel and Imine Compounds in Dynamic Covalent
Chemistry. Helv. Chim. Acta 2014, 97, 1219−1236.
(15) Gu, R.; Flidrova, K.; Lehn, J. M. Dynamic Covalent Metathesis
in the C = C/C = N Exchange between Knoevenagel Compounds and
Imines. J. Am. Chem. Soc. 2018, 140 (16), 5560−5568.
(16) Martinez-Abadia, M.; Gimenez, R.; Ros, M. B. Self-Assembled
alpha-Cyanostilbenes for Advanced Functional Materials. Adv. Mater.
2018, 30, 1704161.
Authors
Niklas F. König − Department of Chemistry & IRIS
Adlershof, Humboldt-Universität zu Berlin, Berlin 12489,
Germany
Dragos Mutruc − Department of Chemistry & IRIS Adlershof,
Humboldt-Universität zu Berlin, Berlin 12489, Germany
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.1c03631
(17) Lin, S.; Gutierrez-Cuevas, K. G.; Zhang, X.; Guo, J.; Li, Q.
Fluorescent Photochromic α-Cyanodiarylethene Molecular Switches:
An Emerging and Promising Class of Functional Diarylethene. Adv.
Funct. Mater. 2021, 31, 2007957.
Author Contributions
†N.F.K. and D.M. contributed equally to this work. All authors
have given approval to the final version of the manuscript.
9167
https://doi.org/10.1021/jacs.1c03631
J. Am. Chem. Soc. 2021, 143, 9162−9168

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
(18) Irie, M.; Mohri, M. Thermally Irreversible Photochromic
Systems. Reversible Photocyclization of Diarylethene Derivatives. J.
Org. Chem. 1988, 53 (4), 803−808.
of a stable tautomer of the elusive dihydrophenanthrenes. J. Am.
Chem. Soc. 1970, 92 (21), 6371−6372.
(19) Guo, X.; Zhou, J.; Siegler, M. A.; Bragg, A. E.; Katz, H. E.
Visible-light-triggered molecular photoswitch based on reversible E/Z
isomerization of a 1,2-dicyanoethene derivative. Angew. Chem., Int. Ed.
2015, 54 (16), 4782−6.
(20) Göstl, R.; Hecht, S. Controlling covalent connection and
disconnection with light. Angew. Chem., Int. Ed. 2014, 53 (33), 8784−
8787.
(21) Vantomme, G.; Lehn, J. M. Reversible adaptation to
photoinduced shape switching by oligomer-macrocycle interconver-
sion with component selection in a three-state constitutional dynamic
system. Chem. - Eur. J. 2014, 20 (49), 16188−16193.
(22) Asadirad, A. M.; Boutault, S.; Erno, Z.; Branda, N. R.
Controlling a Polymer Adhesive Using Light and a Molecular Switch.
J. Am. Chem. Soc. 2014, 136 (8), 3024−3027.
(23) Fuhrmann, A.; Göstl, R.; Wendt, R.; Kotteritzsch, J.; Hager, M.
D.; Schubert, U. S.; Brademann-Jock, K.; Thunemann, A. F.; Nochel,
U.; Behl, M.; Hecht, S. Conditional repair by locally switching the
thermal healing capability of dynamic covalent polymers with light.
Nat. Commun. 2016, 7, 13623.
(24) Kathan, M.; Eisenreich, F.; Jurissek, C.; Dallmann, A.; Gurke, J.;
Hecht, S. Light-driven molecular trap enables bidirectional manipu-
lation of dynamic covalent systems. Nat. Chem. 2018, 10 (10), 1031−
1036.
(25) Fuhrmann, A.; Broi, K.; Hecht, S. Lowering the Healing
Temperature of Photoswitchable Dynamic Covalent Polymer Net-
works. Macromol. Rapid Commun. 2018, 39, 1700376.
(26) Accardo, J. V.; Kalow, J. A. Reversibly tuning hydrogel stiffness
through photocontrolled dynamic covalent crosslinks. Chem. Sci.
2018, 9 (27), 5987−5993.
(27) Zou, H.; Hai, Y.; Ye, H.; You, L. Dynamic Covalent Switches
and Communicating Networks for Tunable Multicolor Luminescent
Systems and Vapor-Responsive Materials. J. Am. Chem. Soc. 2019, 141
(41), 16344−16353.
(28) Ingerman, L. A.; Waters, M. L. Photoswitchable dynamic
combinatorial libraries: Coupling azobenzene photoisomerization
with hydrazone exchange. J. Org. Chem. 2009, 74 (1), 111−117.
(29) Goulet-Hanssens, A.; Eisenreich, F.; Hecht, S. Enlightening
Materials with Photoswitches. Adv. Mater. 2020, 32, 1905966.
(30) Vantomme, G.; Hafezi, N.; Lehn, J.-M. A light-induced
reversible phase separation and its coupling to a dynamic library of
imines. Chem. Sci. 2014, 5 (4), 1475−1483.
(31) Vantomme, G.; Jiang, S.; Lehn, J. M. Adaptation in
constitutional dynamic libraries and networks, switching between
orthogonal metalloselection and photoselection processes. J. Am.
Chem. Soc. 2014, 136 (26), 9509−9518.
(32) Leusen, D. V.; Leusen, A. M. V., Synthetic Uses of Tosylmethyl
Isocyanide (TosMIC). In Organic Reactions, Overman, L. E., Ed.; John
Wiley & Sons: Hoboken, NJ, 2004; Vol. 57.
(33) Kaumanns, O.; Lucius, R.; Mayr, H. Determination of the
electrophilicity parameters of diethyl benzylidenemalonates in
dimethyl sulfoxide: reference electrophiles for characterizing strong
nucleophiles. Chem. - Eur. J. 2008, 14 (31), 9675−82.
(34) In a unique example, Otto and co-workers could show how
thiol nucleophiles can catalyze the thermal Z→E isomerization of acyl
hydrazones: Cvrtila, I.; Fanlo-Virgós, H.; Schaeffer, G.; Monreal
Santiago, G.; Otto, S. Redox Control over Acyl Hydrazone
Photoswitches. J. Am. Chem. Soc. 2017, 139 (36), 12459−12465.
(35) Jones, G., The Knoevenagel Condensation. In Organic
Reactions; John Wiley and Sons: Hoboken, NJ, 1967; Vol. 15, pp
204−599.
(36) Muszkat, K.; Gegiou, D.; Fischer, E. The hexamethylstilbene−
hexamethyldithydrophenanthrene interconversion, an example of a
reversible photocyclization. Chem. Commun. 1965, 19, 447−448.
(37) Doyle, T. D.; Filipescu, N.; Benson, W. R.; Banes, D.
Photocyclization of. alpha.,. alpha.’-diethyl-4, 4’-stilbenediol. Isolation
9168
https://doi.org/10.1021/jacs.1c03631
J. Am. Chem. Soc. 2021, 143, 9162−9168