Photoswitching of stereoselectivity in catalysis using a copper dithienylethene complex

Article abstract of DOI:10.1002/anie.200462538

(Chemical Equation Presented) Light controls the outcome of a stereoselective reaction. Only in the ring-open form can the shown chelate copper(I) complex transfer its chirality to the cyclopropanation of styrene with ethyl diazoacetate. Irradiation with UV light triggers the ring-closing reaction of the ligand rendering it ineffective (see scheme).

Full text of DOI:10.1002/anie.200462538

Angewandte
Chemie
Molecular Switches
Photoswitching of Stereoselectivity in Catalysis
Using a Copper Dithienylethene Complex**
David Sud, Tyler B. Norsten, and Neil R. Branda*
Scheme 1. Interconversion of ring-open (o) and ring-closed (c) isomers
of 1 and 2.
Harnessing the changes in molecular structure and function
that occur when photoresponsive compounds are reversibly
toggled between thermally stable isomers is becoming
increasingly important to the development of molecular
devices containing switching elements.[1] Compounds that
undergo reversible photochemical transformations have been
investigated for use in optoelectronic technologies and to a
lesser extent, in influencing chemical reactivity. Although the
concept of using the geometric changes that accompany a
photoreaction to regulate chemical reactivity and catalysis
was introduced over 20 years ago, only a few examples have
been reported,[2–5] and all rely on azobenzene units as the
photoresponsive structure. The large molecular movements
that result from the cis–trans isomerization were shown to
influence ester hydrolysis within modified cyclodextrins[2] or
crowns ethers,[3] and amide formation in hydrogen-bonded
receptors.[4,5] Although they remain elegant examples of the
concept of photocontrolling catalysis, the photoresponsive
azobenzene derivatives are plagued by thermal reversibility,
which will significantly limit their practical use.
Our original work proved this anticipated metal-binding
mode to be incorrect and instead of forming a chelated
complex with copper(i), 1o forms a double helicate, [Cu2-
(1o)2], where two ligands are wrapped around two metals in a
stereospecific manner.[7] This result helps to explain why there
is no observable stereoselectivity when a metal-catalyzed
reaction (cyclopropanation, see entry 1 in Table 1) is carried
Table 1: Results of the cyclopropanation reactions of styrene with ethyl
diazoacetate using ligands 2 and 3, and CuOTf·0.5C6H6 in CH2Cl2.[a]
Entry
Ligand
ee [%][b]
d.r.[c]
trans
cis
Compounds constructed from the 1,2-dithienylethene
backbone represent a significant improvement over most
other photoresponsive structures primarily because they
undergo thermally irreversible photochemical ring-closing
and ring-opening reactions.[6] Our goals include using the
structural differences between the two photoisomers to
influence the outcome of metal-catalyzed reactions. We
prepared the chiral bis(oxazoline) ligand 1 with the expect-
ation that it can only chelate to a metal when the photoswitch
is in its flexible ring-open state, 1o (Scheme 1).[7] This
complexation places the metal center within a chiral environ-
ment ready to perform stereoselective reactions.[8] Irradiation
with UV light will generate the ring-closed form, 1c, which
cannot chelate the metal because the photochemically
produced rigid backbone forces the two oxazolines to exist
in a divergent relationship to each other.
1
2
3
4
2o
3o
0
30
11
5
0
50
37
5
–
55:45
70:30
63:37
23% 3c[d]
97% 3c[e]
[a] All values are averages of multiple runs using 10 mol% catalyst.[13]
[b] Determined by HPLC analysis using a CHIRACEL-OD column. The
values for the cis isomer are estimates owing to significant peak overlap
in the HPLC traces. [c] Determined by 1H NMR spectroscopic analysis of
the crude reaction mixture. The trans isomer was always found to be the
major product. [d] Represents the photostationary state generated by
irradiating a solution of the ligand with 313 nm light for 15 min.
[e] Isolated from the photostationary state by centrifugal chromatogra-
phy using 0.5% CH3OH in CH2Cl2. The remaining 3% is 3o.
out using the iso-propyl version of bis(oxazoline) 2o as the
ligand (10 to 25 mol%).[9] However, the fact that 2o may not
be conformationally well-defined around the metal center so
as to provide an appropriate chiral catalytic environment
cannot be ruled out.[10]
One of the appealing features of photoresponsive dithie-
nylethene compounds is the versatility with respect to what
can be attached onto the thiophene heterocycles. Relocating
the oxazoline groups onto the internal positions (thiophene
C2) provides ligand 3o that, according to computer modeling,
cannot form a helicate with metal ions such as copper(i). This
ligand is prepared from the known oxazoline 4 (Scheme 2) by
taking advantage of the oxazoline to direct the lithiation to
the C3 position on the thiophene.[11] Scheme 2 also illustrates
the significant differences between the metal-binding pocket
in the ring-open 3o and ring-closed 3c forms.
[*] D. Sud, Prof. N. R. Branda
Department of Chemistry
Simon Fraser University
8888 University Drive
Burnaby, BC V5A1S6 (Canada)
E-mail: nbranda@sfu.ca
T. B. Norsten
National Research Council of Canada
ICPET-Polymeric Materials Group
1200 Montreal Road, Ottawa, ON K1A0R6 (Canada)
[**] This work was supported by the Natural Sciences and Engineering
Research Council of Canada, the Canada Research Chair Program,
and Simon Fraser University. We thank Nippon Zeon Corporation
for supplying the octafluorocyclopentene needed to prepare the
photochromic compound.
Angew. Chem. Int. Ed. 2005, 44, 2019 –2021
DOI: 10.1002/anie.200462538
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2019

Communications
irradiated with 313 nm light to form the photostationary
state[12] and the catalytic reaction is repeated using this
solution as the ligand source, the enantioselectivities drop
(entry 3). The small magnitude of the changes can be
explained by the fact that the photostationary state generated
under these conditions consists of 23% of the ring-closed
isomer, 3c, as identified by 1H NMR spectroscopy. Although
this low photostationary state is a temporary drawback, future
generations of photoswitchable ligands based on the 1,2-
dithienylethene scaffold will circumvent this limitation by
taking advantage of the electronic tuning that can be tailored
into the structure. Photostationary states containing a greater
amount of the ring-closed isomer can be expected to display
more significant differences in the product distribution when
used as ligands in catalytic reactions. This assumption is
confirmed when a purified sample of the ring-closed isomer,
3c, is used as the ligand, in this case the enantioselectivities
are insignificant (entry 4). The enantioselectivities can be
turned back on by converting the ring-closed isomer back into
its ring-open counterpart by irradiating the reaction mixture
containing all the ingredients with light of wavelength greater
than 434 nm[12] before the cyclopropanation reaction has
finished. When this experiment is performed, the original
values for the enantio- and diastereoselectivity are regener-
ated as a result of the photoinduced ring-opening reaction to
regenerate 3o, (3c!3o). This observation clearly demon-
strates the in situ photoswitching of stereoselective catalysis
and is the first example of its kind.
Scheme 2. Synthesis and photochemical cyclization of bis(oxazoline)
3o.
Bis(oxazoline) 3o can be toggled between its ring-open
and ring-closed isomers by alternate irradiation with appro-
priate wavelengths of light as is best demonstrated using UV/
Vis absorption spectroscopy (Figure 1). Irradiation of a
The photoinduced ring-closing reaction (3o!3c), how-
ever, is inhibited when the metal is present and irradiation of
CH2Cl2 solutions of ligand 3o and CuOTf·0.5C6H6 results in
no changes in the color or in the observed stereoselectivities.
This inhibition is caused by the copper being too tightly bound
within the ligandꢀs chelation site to allow for photoswitching.
The presence of the copper center prevents the ligand from
undergoing the necessary geometric changes during the
photoreaction. This problem is overcome by adding a small
amount (5%) of the more competitive coordinating solvent
CH3CN to the CH2Cl2 solutions. When the cyclopropanation
reactions are repeated using this solvent mixture, the outcome
of the reaction can be photoregulated. For example, the
enantioselectivity of the trans isomer of the cyclopropane
product can be decreased from 23% to 10% by irradiating
the CH3CN/CH2Cl2 reaction mixture containing 3o and
CuOTf·0.5C6H6 with 313 nm light to convert the ring-open
isomer into the photostationary state.
Figure 1. Changes in the UV/Vis absorption spectra of 3o upon irradia-
tion with 313 nm light. Irradiation periods are 0, 5, 10, 20, 30, and
60 s.
CH2Cl2 solution of 3o with 313 nm light[12] results in the
appearance of an absorption band in the visible spectral
region (lmax = 510 nm) and a visual change from colorless to
deep red owing to the generation of the ring-closed isomer,
3c. Irradiation of 3c at wavelengths greater than 434 nm
triggers the ring-opening photoreaction and the regenerates
the original absorption spectrum corresponding to 3o.
One reaction involving bis(oxazolines) as chelating
ligands is the copper-catalyzed cyclopropanation of olefins
with diazoesters, and is a good reaction to illustrate our
concept because is provides a simple model reaction with an
easy to analyze and well characterized product distribution.
The results from the stereoselective cyclopropanation reac-
tions of styrene with ethyldiazoacetate using bis(oxazolines) 2
and 3 are listed in Table 1.[13]
Herein we have described the first example of photo-
regulation in metal catalysis using the established 1,2-
dithienylethene photoswitch. Future reports will focus on
expanding the range of reactions that will benefit from this
molecular-level control as well as optimizing the photochem-
istry to afford more versatile catalysts.
Received: November 6, 2004
Published online: February 23, 2005
The low enantioselectivities observed when 3o is used as
the ligand (entry 2) and copper(i) trifluoromethanesulfonate
(CuOTf·0.5C6H6) as the metal source (10 mol% of each) are
a result of the flexibility of the ligand around the metal center
and are adequate to evaluate the efficacy of the bis(oxazoline)
as a photoresponsive catalyst. When a solution of the 3o is
Keywords: copper · enantioselectivity · homogeneous catalysis ·
.
molecular switches · photochromism
2020
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[1] a) Molecular Switches (Ed.: B. L. Feringa), Wiley-VCH, Wein-
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[9] It was originally anticipated that the ring-open isomer 2o would
induce a greater amount of stereoselectivity in the cyclopropa-
nation reactions than the ring-closed isomer 2c. However, when
using 2o resulted in no observable stereoselectivity, 2c was never
tested as a ligand.
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[12] Standard lamps used for visualizing thin-layer chromatography
(TLC) plates (Spectroline E-series, 470 mWcmꢀ2) were used to
carry out the ring-closing reaction of 3o to 3c with and without
copper(i). The ring-opening reactions were carried out using the
light of a 150-W tungsten source that was passed through a
434 nm cutoff filter to eliminate higher energy light.
[13] In a typical reaction, the oxazoline ligand (7.6 mg; 1.1 equiv) was
dissolved in CH2Cl2 (1 mL) and CuOTf·0.5C6H6 (5.5 mg;
1 equiv, 10 mol%; OTf = [CF3SO3]ꢀ) was added. The solution
was cooled to 08C in an ice bath and stirred for 30 min at which
time an excess of styrene (100 mL) was added. After stirring for
an additional 30 min, ethyl diazoacetate (10 mL) in CH2Cl2
(1 mL) was added using a syringe pump over 4–6 h while
maintaining the solution at 08C. The solution was stirred
overnight at room temperature, then filtered through a small
plug of silica (CH2Cl2). The excess styrene was removed by
gradient flash chromatography (silica, hexanes to 1:1 hexanes/
ethyl acetate). The purity and identity of both diastereoisomers
1
was verified with H NMR spectroscopy. Both the cis and trans
enantiomeric mixtures were analyzed by chiral HPLC using a
CHIRACEL-OD chiral column (0.5 mLminꢀ1, 95:5 hexanes:2-
propanol). Detection was adjusted at 220 nm, which is
a
maximum in the absorption spectrum of the trans isomers. A
solution of trans enantiomers gave two peaks separated in their
retention time by 3.7 min. The cis isomers were only separated
by 0.4 min and were not baseline separated. It was however
possible to distinguish both maxima and by deconvoluting the
data using the software provided with the HPLC, the separate
peak areas were obtained. The amount of catalyst can be
lowered to 1 mol% with respect to the ethyl diazoacetate to
produce 120 mg (63%) of the cyclopropanated products as a
mixture of stereoisomers after workup and isolation by centri-
fugal chromatography (2% ethyl acetate/hexanes).
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