Controlling covalent connection and disconnection with light

Article abstract of DOI:10.1002/anie.201310626

The on-going need for feature miniaturization and the growing complexity of structures for use in nanotechnology demand the precise and controlled formation of covalent bonds at the molecular level. Such control requires the use of external stimuli that offer outstanding spatial, temporal, as well as energetic resolution. Thus, photoaddressable switches are excellent candidates for creating a system that allows reversible photocontrol over covalent chemical connection and disconnection. Here we show that the formation of covalent bonds between two reagents and their scission in the resulting product can be controlled exclusively by illumination with differently colored light. A furyl-substituted photoswitchable diarylethene was shown to undergo a reversible Diels-Alder reaction with maleimide to afford the corresponding Diels-Alder adduct. Our system is potentially applicable in any field already relying on the benefits of reversible Diels-Alder reactions.

Full text of DOI:10.1002/anie.201310626

Angewandte
Chemie
DOI: 10.1002/anie.201310626
Remote-Controlled Reactivity
Controlling Covalent Connection and Disconnection with Light**
Robert Gçstl and Stefan Hecht*
Dedicated to the centennial of the MPI fꢀr Kohlenforschung
Abstract: The on-going need for feature miniaturization and
the growing complexity of structures for use in nanotechnology
demand the precise and controlled formation of covalent
bonds at the molecular level. Such control requires the use of
external stimuli that offer outstanding spatial, temporal, as well
as energetic resolution. Thus, photoaddressable switches are
excellent candidates for creating a system that allows reversible
photocontrol over covalent chemical connection and discon-
nection. Here we show that the formation of covalent bonds
between two reagents and their scission in the resulting product
can be controlled exclusively by illumination with differently
colored light. A furyl-substituted photoswitchable diarylethene
was shown to undergo a reversible Diels–Alder reaction with
maleimide to afford the corresponding Diels–Alder adduct.
Our system is potentially applicable in any field already relying
on the benefits of reversible Diels–Alder reactions.
a versatile and powerful diene, especially in the field of
[
20–23]
reversibly cross-linkable polymers
and the reversible
2
covalent functionalization of sp -hybridized carbon allo-
[
24,25]
tropes.
Temperature is the external stimulus for reaction
control for the popular furan/maleimide couple, with charac-
teristic reaction temperatures between 258C and 508C for the
forward reaction and above 708C to 1008C for the retro DA
reaction. In stark contrast to kinetically controlled, non-
dynamic DA reactions, the DA reaction between furan and
maleimide is fine-tuned to be controlled thermodynamically
and thus exists in a dynamic equilibrium at ambient con-
ditions. It is because of this high reversibility that the
temperature-dependent conversion into the adduct is gener-
ally not quantitative. Conversely, this dynamic character is the
prerequisite for the integration of light as an additional
stimulus that offers the possibility to reach a new level of
control over this type of reaction.
F
eature miniaturization and the growing complexity of
A number of photochromic molecules exist that could be
suitable for this task, with azobenzenes, spiropyranes, and
structures used in nanomaterials and nanotechnology demand
the precise and controlled formation of covalent bonds on the
diarylethenes (DAEs) being the most popular representa-
[1–3]
[4–6]
[26,27]
molecular scale.
In a conventional dynamic reaction,
tives.
However, thermal stability and high fatigue resist-
the distribution of products can be controlled by applying
different chemical and physical triggers, such as temperature,
ance in combination with large optical changes between their
ring-open (o) and -closed (c) forms render DAEs the
[7–9]
[28]
pressure, or light.
temporal, as well as energetic resolution, photoaddressable
As light delivers superior spatial,
photochromes of choice for this purpose. Indeed, Branda
and co-workers reported a series of photoswitchable DAEs
with a diene motif incorporated in their bridge moieties that
can undergo DA reactions with various dienophiles and
inhibit the retro DA reaction through photochemical cycliza-
[10,11]
molecular switches
are rendered promising candidates to
exploit the typical dynamic covalent reactions available to the
organic chemist (such as the reversible formation of imines,
hydrazones, oximes, thiols, aldols, boronates, or olefins by
[29–31]
tion of the adduct.
However, the intrinsic design margins
[
12–16]
metathesis).
In addition to these transformations, the
do not allow for locking the DA reaction to either the side of
the starting materials or the products by application of light.
This is only possible through choice of different diene–
dienophile combinations, as the unreacted diene is photo-
chemically inactive. Having the possibility of using light as
a stimulus to switch both the unreacted diene and the DA
adduct is thus highly desirable to achieve photocontrol over
the formation and scission of dynamic bonds (Scheme 1a).
Herein we present, to the best of our knowledge, the first
method for exerting such photocontrol over the connection
and disconnection of dynamic covalent bonds, by employing
a DAE as the diene and a maleimide as the dienophile in
a reversible DA reaction. The desired ability to photoswitch
both the unreacted DAE as well as the DA adduct sets certain
demands on the molecular design of the respective target
compound. The need to have a photoswitchable system that
removes the reactive double bonds in the diene as well as in
the adduct upon irradiation with light, thereby preventing
either the DA reaction or the retro DA reaction, led us to
replace one of the thienyl moieties of a dithienylethene by
Diels–Alder (DA) reaction unifies a number of advantageous
features: 1) tunable reversibility from endergonic, over highly
[
17,18]
reversible, to exergonic energy profiles,
2) no by-product
formation (self-containing nature), 3) catalysis is optional but
[19]
not necessary, and 4) applicability in solution as well as in
gels or the solid state. Furan, in particular, has proved to be
[
*] Dipl.-Chem. R. Gçstl, Prof. S. Hecht
Department of Chemistry, IRIS Adlershof
Humboldt-Universitꢀt zu Berlin
12489 Berlin (Germany)
E-mail: sh@chemie.hu-berlin.de
Homepage: http://www.hechtlab.de/
[**] Generous support by the German Research Foundation (DFG
through SFB 658) and the European Research Council through ERC-
2012-STG_308117 (Light4Function) is gratefully acknowledged.
BASF AG, Bayer Industry Services, and Sasol Germany are thanked
for generous donations of chemicals.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201310626.
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Figure 1. Locking the DA as well as the retro DA reaction with light:
UPLC diode array traces of a) the formation of exo-2o and endo-2o
after heating 1o and maleimide (MI) at 508C for 1 day. b) No adduct
formation is visible after heating 1c and maleimide at 508C for 1 day.
c) 1o after heating exo-2o at 1008C for 15 min (exo-2o before heating
is shown in gray with offset for comparison). d) No retro DA for exo-2c
is visible after heating a mixture of exo-2o and exo-2c at the PSS for
Scheme 1. Photocontrol over the formation and scission of a dynamic
bond using photoswitches as locks. a) Concept. b) The different
components 1o, 1c, 2o, 2c, and maleimide in the course of a photo-
controlled Diels–Alder reaction, with the respective photocyclization
and ring-opening quantum yields measured in toluene as well as the
irradiation wavelengths employed for the in situ reaction.
1
h at 1008C (PSS of exo-2o and exo-2c before heating is shown in
gray with offset for comparison). The concentration of switches 1o,
À5
À2
2
o, 1c, and 2c was 10 m, that of maleimide 10 m.
molecule from participating in the DA reaction; and 2) ring
closure of 2o to 2c removes the reactive double bond from
the oxanorbonene skeleton, thereby thermally locking the
adduct and preventing the retro DA reaction. As can be seen
in Figure 1a, the reaction of 1o with maleimide results in
conversion into adducts exo-2o and endo-2o even at very low
concentrations. To prove that the forward DA reaction can be
inhibited by photocyclization, 1o was irradiated to the PSS,
which consists almost only of 1c, and then submitted to the
same reaction conditions. No apparent conversion into the
DA adduct was observed (Figure 1b). In an analogous
manner, Figure 1c shows the smooth retro DA reaction
from exo-2o to 1o upon heating. However, heating a mixture
of exo-2c and residual exo-2o at the PSS clearly reveals that
the ring-closed adduct exo-2c is unreactive and stable under
these conditions and only the residual amount of the ring-
open isomer exo-2o can undergo the retro DA reaction
(Figure 1d). Effects caused by thermal ring-opening of the
ring-closed forms were ruled out by control experiments in
which only 1c or 2c were submitted to the same reaction
conditions in the dark; this resulted in no notable ring
opening being observed.
incorporation of a furyl residue as the reactive diene
(
compound 1o in Scheme 1b).
Target compound 1o can be synthesized in a straightfor-
[32]
ward manner on the basis of an established procedure.
DAE 1o can successfully undergo a DA reaction with
maleimide to yield the corresponding adduct 2o as a mixture
of exo and endo stereoisomers, the formation of which are
reversible at 1008C (Scheme 1b). Although both stereoiso-
mers were isolated and appear to exhibit the same spectral
characteristics, only the thermodynamically more stable exo-
2
o was employed for thorough analytical characterization
and photochemical investigations. Both switches 1o and exo-
o show fully reversible photochromism, with suitable photo-
2
cyclization and ring-opening quantum yields as well as almost
quantitative conversion into the ring-closed isomers at their
respective photostationary states (PSSs). Further details on
the synthesis and spectral characterization are described in
the Supporting Information.
Two main aspects can be extracted from Scheme 1b:
1
) Photocyclization of 1o to 1c removes the reactive cisoid
diene functionality of the furyl moiety and thus prevents the
2
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Figure 3. Relative amplification or inhibition of the formation of the
Diels–Alder (DA) adduct depending on the illumination wavelength.
Changes in the conversion into 2 (2o, 2c exo and endo combined) on
treating DAE 1o (ca. 10 m) with maleimide (ca. 10 m) under
irradiation either at 335 nm and 535 nm for 6 h (amplification) or at
Figure 2. Comparison of the absorption spectra of 1o, 1c, exo-2o, and
exo-2c in acetonitrile at 258C. The residual absorbance of exo-2c above
À5
À2
5
00 nm is attributed to a minor retro DA reaction taking place during
375 nm for 24 h (inhibition) compared to the corresponding dark
the irradiation process.
reaction as a function of temperature. See the Supporting Information
for absolute values.
The ability to lock 1o as well as 2o by converting them
into 1c and 2c, respectively, with UV irradiation is remark-
able and offers manifold possibilities to employ these switch
prototypes as photocontrollable locks. However, the true
value of the system arises from the ability to selectively
induce the reverse photoprocesses so as to unleash either the
reactive diene or DA adduct by choosing the proper
irradiation wavelength. Comparing the absorption spectra
of the two ring-closed forms reveals a considerable spectral
separation (Dlmax = 86 nm) between the absorption maxima
of 1c, which absorbs in the green region, and exo-2c, which
absorbs in the blue region (Figure 2). Thus, and despite the
fact that 1c absorbs slightly in the region where exo-2c is
addressed, this allows for almost independent initiation of
ring-opening reactions while irradiating a mixture of the two
ring-closed derivatives—the key to achieving control over
a dynamic system with light.
well as 2o to 2c, but simultaneously addresses the visible band
of the ring-closed adduct 2c, thereby also inducing ring-
opening to give 2o (Figure 2). According to Le Chꢀtelierꢁs
principle, diene 1o is removed from the dynamic DA
equilibrium by conversion into 1c and thus the reaction is
effectively inhibited compared to the dark—that is, solely
thermal—DA reaction (red bars in Figure 3).
In addition to the applied irradiation wavelength, the
amount of amplification or inhibition is strongly dependent
on the applied temperature (Figure 3). However, rationaliza-
tion of the process is difficult, since the overall outcome is
a result of a superposition of thermal and photochemical
equilibria in the ground as well as in the excited states.
Elevated temperatures, for example, not only promote the
retro DA reaction but also increase the ring-opening quantum
[33]
yields, which noticeably affects the composition at the PSS.
Indeed, irradiation of a mixture of 1o and maleimide with
light enables in situ control over the outcome of the DA
reaction. Although thermal reactions of 1o (at low concen-
trations of 10 m suitable for optical spectroscopy) with
maleimide to form 2o occur with conversions of 18–35% after
Furthermore, amplification works best at temperatures typ-
ically unfavorable for the DA reaction (i.e. in the highly
reversible regime), while inhibition works best at temper-
atures that already result in high conversion in the dark. This
indicates that the possibility for amplification and inhibition
are greatest when the reaction rate constant for the thermal
DA reaction at a given temperature favors the opposite
direction.
À5
2
4 h, depending on the applied temperature, the formation of
the DA adduct and subsequent formation of the respective
ring-closed isomers can be amplified or inhibited by irradi-
ation with light of the appropriate wavelength (Figure 3).
Irradiating a mixture of 1o and maleimide with light at
a wavelength of 335 nm and 535 nm induces cyclization of
both ring-open isomers 1o and 2o, but ring-opening of 1c
only (Figure 2). This effectively leads to an enrichment of 2c
in the reaction mixture and an amplification of DA adduct
formation, compared to the dark DA reaction, after 6 h
We have been able to selectively either amplify or inhibit
a DA reaction by illumination with light of different wave-
lengths, thus broadening the repertoire of DCC. In addition to
this general approach of manipulating the formation and
scission of a covalent chemical bond by light, our prototypic
DAE has tremendous potential for a variety of possible
applications, ranging from reversibly cross-linkable polymers
2
(
green bars in Figure 3). The heating time was reduced, as
to the reversible covalent functionalization of sp -hybridized
prolonged irradiation and heating result in degradation. The
same method, but using different wavelengths, can also be
applied to bias the DA reaction in favor of adduct inhibition.
Using light with a wavelength of 375 nm cyclizes 1o to 1c as
carbon allotropes, such as graphene and carbon nanotubes.
Received: December 7, 2013
Published online: && &&, &&&&
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Keywords: diarylethenes · Diels–Alder reaction ·
dynamic covalent chemistry · photochromism
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Angew. Chem. Int. Ed. 2014, 53, 1 – 5
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Angewandte
Chemie
Communications
Remote-Controlled Reactivity
R. Gçstl, S. Hecht*
&&&& — &&&&
Controlling Covalent Connection and
Disconnection with Light
Remote-controlled equilibrium: Gating
both sides of a reversible covalent Diels–
Alder reaction by a photoswitch allows
control over the connection and discon-
nection of two chemical entities and
shifting of their equilibrium by light. This
approach should prove particularly pow-
erful when designing dynamic cross-
linked polymers and for reversible cova-
lent functionalization of sp2-hybridized
carbon allotropes, such as graphene and
carbon nanotubes.
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!