Effects of π-extension on pyrrole hemithioindigo photoswitches

Article abstract of DOI:10.1016/j.tet.2019.130466

The most red-shifted hemithioindigo photoswitches have been identified through systematic introduction of aryl units to a parent pyrrole hemithioindigo photoswitch. Increasing the size of the 5′-aryl substituent is ineffective at producing further redshif

Full text of DOI:10.1016/j.tet.2019.130466

Accepted Manuscript
Effects of π-extension on pyrrole hemithioindigo photoswitches
Joshua E. Zweig, Tongil A. Ko, Junrou Huang, Timothy R. Newhouse
PII:
S0040-4020(19)30780-X
DOI:
https://doi.org/10.1016/j.tet.2019.130466
Article Number: 130466
Reference:
TET 130466
To appear in: Tetrahedron
Received Date: 15 February 2019
Revised Date: 30 April 2019
Accepted Date: 16 July 2019
Please cite this article as: Zweig JE, Ko TA, Huang J, Newhouse TR, Effects of π-extension on pyrrole
hemithioindigo photoswitches, Tetrahedron (2019), doi: https://doi.org/10.1016/j.tet.2019.130466.
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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Effects of π-Extension on Pyrrole Hemithioindigo Photoswitches
Joshua E. Zweig, Tongil A. Ko, Junrou Huang, and Timothy R. Newhouse*
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut
06520-8107, United States
Abstract: The most red-shifted hemithioindigo photoswitches have been identified through
systematic introduction of aryl units to a parent pyrrole hemithioindigo photoswitch. Increasing
the size of the 5’-aryl substituent is ineffective at producing further redshifted chromophores. A
second generation of 3’,5’-diarylated photoswitches which possess increased tunability is
reported. Experimental and computational evidence indicates the 4’ position is electronically
isolated from the bulk of the conjugated system.
1. Introduction: Visible-light activated small molecule photoswitches comprise a class of
molecular machines that are the subject of a great deal of interest in fields such as drug delivery,
data storage, and photomechanical polymers.1 Seminal advances in this field were accordingly
recognized with the Nobel Prize in Chemistry in 2016.2 A particular subclass of these
compounds, E/Z-type photoswitches, are of particular interest for controlling biological systems
due to the large geometric change conferred by double-bond isomerization.3 Although the history
of hemithioindigo photoswitches, such as 1, dates to the early 20th century, they have recently
received considerable attention in the last five years by Dube4 and our group5 in part due to their
longer wavelength absorption relative to the more well explored azobenzenes. Our laboratory has
recently reported a new class of E/Z-type photoswitches typified by structure 2, which are
designed to possess a key intramolecular hydrogen-bonding interaction in only one of the two
isomeric states (Figure 1).5 As a result of this interaction, these pyrrole hemithioindigo (PHTI)
photoswitches can undergo quantitative photoisomerizations using visible light for both
isomerization reactions.
Prior Work:
O
O
S
S
E-1
Z-1
incomplete photoisomerization
Newhouse (2017):
O
Ar
H
O
N
S
S
E-2
NH
Z-2
Ar
quantitative photoisomerization
This Work:
O
Ar
5’
H
O
N
4’
3’
Ar
S
S
NH
E-3
Z-3
Ar
Ar
quantitative photoisomerization
& improved tunability
Figure 1. Generations of hemithioindigo and pyrrole hemithioindigo photoswitches.

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While the photoswitches we reported undergo quantitative isomerization using blue light
for ZꢀE photoisomerization and red light for EꢀZ photoisomerization, it would be ideal to
induce both isomerizations using light in the infrared window for subsurface drug delivery
applications.6 The amino-substituted photoswitches described in our previous report undergo
isomerization at longer wavelengths than their oxygen-substituted analogs, however, they also
undergo photobleaching upon repeated irradiation. Therefore, we decided not to test even more
electron rich substrates due to photobleaching concerns. Rather, we chose to explore the effects
of creating more conjugated π-systems as a strategy towards longer-wavelength photoswitches.7
2. Results and Discussion
Figure 2. A library π-extended pyrrole hemithioindigo photoswitches. (λmax values in CH2Cl2,
photostationary states determined by HPLC. 1 Ref. 4.)
Upon reinvestigation of our previously described synthesis of arylpyrrole HTIs,5 it was
found that the condensation of appropriate pyrrole-2-carboxaldehydes with benzothiophen-3-one
was adequately catalyzed by piperidine, rather than using stoichiometric DBU. This eliminated
the need for removal of the DBU-water adduct and provided improved yields and purity (Figure
2). For example, while 2a was previously obtained in 44% using DBU as base, 2b-h were each
obtained in yields not lower than 76%. If was found that replacement of the 5’-phenyl group (2a)
with a 5’-(1-naphthyl) moiety (2b) provided a photoswitch with shorter wavelength absorption

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maxima.4 The 2-naphthyl isomer 2c, proved superior, affording longer absorption maxima than
2a or 2b. Anthracenyl derivatives 2d and 2e were prepared, and a similar trend was observed,
with the longer end-to-end 2-anthracenyl PHTI 2e absorbing at longer wavelength than the 9-
anthracenyl analog 2d (Z: 474 nm ꢀ 507 nm; E: 525 nm ꢀ 556 nm). This came at the cost of a
reduced bathochromic shift and poor photostationary state selectivity. Further extension of the π-
system with a pendant 1-pyrenyl moiety (2f) provided only a minimal redshift compared to the
5’-phenyl PHTI. Considering the drawbacks of such polycyclic arenes, namely poor solubility
and step-intensive routes for tuning polycyclic aromatic hydrocarbons via substituent effects, we
decided against further exploration of these avenues of π-extension.
At this point instead of employing larger fused aromatics, we turned our attention to
exploring biphenyl type moieties. In our previous report, we had previously observed that the
introduction of an aromatic group at the 5’-position not only resulted in a redshift, but also an
augmented bathochromic shift relative to a photoswitch without substitution on the pyrrole. It
had been hypothesized that this increased bathochromic shift was the result of the increased
change in geometry of the longer π-system. Therefore, 2g was synthesized to see if this effect
would manifest itself further. However, 2g was found to possess a redshift of only 4-6 nm of
either isomer was observed relative to the 5’-phenyl PHTI (2a). Introduction of an alkynyl linker
(2h) led to a further small redshift, potentially due to diminished out-of-plane distortion of the
two arenes. Unfortunately, these substantial increases in end-to-end distance change upon
isomerization did not translate to a substantial increase in the bathochromic shift of the two
isomers. Although some redshifting was observed with these compounds, the solubility and
synthetic challenges associated with the fused arenes are still present, albeit to a somewhat lesser
degree.
Figure 3. 4’,5’-bisarylated pyrrole hemithioindigo photoswitches.
Therefore, we hypothesized that instead of extending the 5’-substituent, installation of an
additional arene moiety on the pyrrole could induce the desired redshift. Synthesis of the 4,5-
diaryl photoswitches 4a-b was accomplished by double Suzuki-Miyaura coupling of 4,5-
dibromopyrrole-2-carboxaldehyde and then aldol condensation with benzothiophen-3-one.
Diphenyl photoswitch 4a (Figure 3), however, showed no discernible redshifting over its
monoarylated congener 2a. Installation of electron-donating methoxy substituents at the para
position of both arenes also proved inferior to the single 5’-p-methoxy photoswitch.

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Figure 4. 3’,5’-bisarylated pyrrole hemithioindigo photoswitches. (λmax values in CH2Cl2,
photostationary states determined by 1H NMR in CD2Cl2.)
Steric distortion between the 4’,5’-diaryl groups may lead to these poor properties, thus, a
library of 3’,5’-diaryl photoswitches was synthesized. The precursor diarylpyrrole-2-
carboxaldehydes are conveniently synthesized from a chalcone starting material, enabling the
synthesis of differentially substituted diarylpyrrole photoswitches with complete
regioselectivity.8 Fortuitously, as shown in Figure 4, it was found that introduction of a 3’-aryl
group (3a) provided a 10 nm redshift when compared to 2a (Z: 491 nm ꢀ 501 nm; E: 550 nm ꢀ
560 nm). In addition to this redshift, introduction of a methoxy group to the 3’-arene (3b)
substituent provides a 4 nm redshift, roughly half as large of the 10 nm shift induced by addition
of a methoxy group to the 5’-arene (3c). Remarkably, these substituent effects appear to be
additive, with bis-p-methoxy photoswitch 3d displaying a redshift of approximately 15 nm
relative to the unsubstituted 3a. Like the previously disclosed first-generation 5’-aryl
photoswitches, these compounds undergo highly selective photoisomerization in both directions
using visible light. These photoswitches are also considerably more soluble in organic solvents.
This increase in solubility is sufficient for convenient observation and quantitation of the
photoisomerization via 1H NMR (Figure 5).

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pyrrole C4-H
H
O
N
H
S
E-3b
OMe
590 nm
OMe
O
S
H
N
H
Z-3b
460 nm
H
O
N
H
S
E-3b
OMe
1H δ (ppm)
Figure 5. NMR isomerization of 3b. Top to bottom: Prior to irradiation; after irradiation with
460 nm light; after irradiation again with 590 nm light (in CD2Cl2).
As described above, our initial hypothesis was that out-of-plane distortions between the
pendant aryl groups in 4a and 4b lead to diminished conjugation such that two non-planar aryl
groups provided similar redshifting to a single, more co-planar π-extension. Separating these
groups as in the series 3a-d allowed their effects to be additive. However, when monoarylated
photoswitches 5 and 6 were synthesized (by condensation of the appropriate pyrrole
carboxaldehydes with benzo[b]thiophen-3(2H)-one), we were surprised to observe that even in
the absence of an out-of-plane distortion, 4’-phenyl switch 5 was markedly less redshifted than
its 5’-phenyl isomer 2a (Figure 6). Photoswitch 6 was slightly redshifted relative to 5, although
still substantially blueshifted relative to 2a.
Figure 6. Monoarylated pyrrole hemithioindigos. (λmax values in CH2Cl2.)
After these observations were made, we turned to DFT calculations to understand the
physical basis of these disparate electronic effects between the arylpyrrole hemithioindigos

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analogs9. Structures for photoswitches 5, 6, 2a, 4a, and 3a, were optimized at the B3LYP/6-
31G* level of theory. While the out-of-plane distortions in 4a were apparent, another striking
trend was observed. Regardless of the presence of other arenes, the coefficients of the LUMO on
the 4’ aryl groups were minimal. This indicates that electronic insulation of the 4’ position is
responsible for the poor performance of photoswitches possessing aryl groups at this position.
The extent of the LUMO on 3’ phenyl groups was diminished but non-zero, in line with the
reduced redshifts observed by introduction of electron-donating substituents at this position (3b,
3d). These results suggest that the minimal redshifting of 4’ aryl pyrrole HTIS is primarily a
consequence of electronics, rather than steric out-of-plane distortions.
H
O
N
S
400
450
450
500
550
600
E-5
Expt’l: λmax = 517 nm
TD-DFT: λmax = 454 nm
E-5 (HOMO)
E-5 (LUMO)
H
O
N
S
400
500
550
600
E-6
E-6 (HOMO)
E-6 (LUMO)
Expt’l: λmax = 519 nm
TD-DFT: λmax = 453 nm
H
O
N
400
450
500
550
600
S
E-2a
Expt’l: λmax = 550 nm
TD-DFT: λmax = 472 nm
E-2a (HOMO)
E-2a (LUMO)
H
O
N
400
450
500
550
600
S
E-4a
E-4a (HOMO)
E-4a (LUMO)
Expt’l: λmax = 548 nm
TD-DFT: λmax = 476 nm
H
O
N
400
450
500
550
600
S
E-3a (HOMO)
E-3a (LUMO)
E-3a
Expt’l: λmax = 560 nm
TD-DFT: λmax = 484 nm
Figure 7. Molecular orbitals of arylated pyrrole hemithioindigos. Left: Molecular orbitals of
pyrrole HTI photoswitches. Calculations at the B3LYP/6-31G* level of theory. Right:
Experimental UV/Vis spectra (CH2Cl2, 0.01 mg/mL) Solid lines = Z-isomers, dashed lines = E-
isomers.

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3. Conclusion
In conclusion, we have mapped the effects of π-extension on the pyrrole moiety of
pyrrole hemithioindigos. Previously reported 5’-arylated pyrrole hemithioindigos are a uniquely
selective class of visible-light photoswitches. Substitution of the pyrrole unit with an aryl group
leads to increasing conjugation in the following order: 4’ < 3’ < 5’. Experimental and
computational evidence suggests the 4’ position is mostly electronically isolated from the
system. Combining 3’-and 5’-aryl substitution results in a system with improved solubility that
maintains the high selectivity of the first generation while providing more opportunities for
tuning and derivatization. Importantly, the computational results described herein demonstrate
that this system is amenable to redshift predictions based on DFT calculations.
4. Experimental
4.1 General Experimental Procedure
All reactions were carried out under an inert nitrogen atmosphere with dry solvents under
anhydrous conditions unless otherwise stated. All reactions were capped with a rubber septum,
or Teflon-coated silicon microwave cap unless otherwise stated. Stainless steel cannula or
syringe were used to transfer solvent, and air- and moisture sensitive liquid reagents. Reactions
were monitored by thin-layer chromatography (TLC) and carried out on 0.25 mm Merck silica
gel plates (60F-254) using UV light as the visualizing agent and potassium permanganate, an
acidic solution of p-anisaldehyde, a solution of 2,4-dinitrophenylhydrazine, or vanillin as
developing agents. Flash column chromatography employed SiliaFlash® P60 (40-60 µm, 230-
400 mesh) silica gel purchased from SiliCycle Inc.
4.2 Materials
All reaction solvents were purified using a Seca solvent purification system by Glass
Contour, except for n-butanol. Anhydrous n-butanol was purchased from Sigma-Aldrich and
degassed by bubbling N2 through the solvent while sonicating for 30 minutes. Pd(OAc)2 was
purchased from Strem Chemical Inc. XPhos (CAS: 564483-18-7) was purchased from Oakwood
Chemical. All other reagents were used as received without further purification, unless otherwise
stated.
4.3 Instrumentation
1
All new compounds were characterized by means of H-NMR, 13C-NMR, FTIR (thin
1
film), and HR-MS. Copies of the H- and 13C-NMR spectra can be found at the end of each
experimental procedure. NMR spectra were recorded using a Varian 400 MHz NMR
spectrometer, Varian 500 MHz NMR spectrometer, or a Varian 600 MHz NMR spectrometer.
All 1H-NMR data are reported in δ units, parts per million (ppm), and were calibrated relative to
the signals for residual dichloromethane in CD2Cl2 (5.32 ppm), residual chloroform (7.26 ppm)
13
in deuterochloroform (CDCl3), or residual DMSO (2.50 ppm) in DMSO-d6. All C-NMR data
are reported in ppm relative to CD2Cl2 (54.0 ppm), CDCl3 (77.16 ppm), or DMSO-d6 (39.52) and
1
were obtained with H decoupling unless otherwise stated. The following abbreviations or
combinations thereof were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q
= quartet, br = broad, m = multiplet, and a = apparent. All IR spectra were taken on an FT-
IR/Raman Thermo Nicolet 6700. High resolution mass spectra (HR-MS) were recorded on a

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Bruker microTOF mass spectrometer using ESI-TOF (electrospray ionization-time of flight). All
UV/Vis spectra were taken on a Cary 3E Spectrophotometer using quartz cuvettes purchased
from Starna Cells (P/N: 29-Q-10) and spectrometric or HPLC grade solvents. Photoirradiation
was carried out with LEDs purchased from Mouser Electronics (405, 460, 523, 567, 590, 623,
660, and 740 nm) or Roithner-LaserTechnik GmbH (420, 490, 505, 690, and 720 nm). For
photostationary state determination, samples were irradiated in borosilicate glass HPLC vials
purchased from Thermo Scientific (C4000-1). For part numbers of individual LEDs and detailed
description of the irradiation setup, see the accompanying Supplementary Information. HPLC
quantitation of photostationary state composition was performed using an Agilent 1260 HPLC
with a Chiralpak IA column ((250 x 4.6mm, 5µM particle size).
4.4 General Procedures
4.4.1 General Procedure for Suzuki coupling with solid aryl bromides
To a flame-dried 5 mL microwave vial flask equipped with a magnetic stir bar was added N-
Boc-pyrrole-2-boronic acid (316 mg, 1.5 mmol, 1.5 equiv), Pd(OAc)2 (4.5mg, 0.02 mmol, 0.02
equiv), XPhos (19.0 mg, 0.04 mmol, 0.04 equiv), K3PO4 (424 g, 2.0 mmol, 2.0 equiv), and aryl
bromide (1.0 mmol, 1.0 equiv). The flask was evacuated and backfilled with nitrogen three
times, and then the gas line adapter was quickly replaced with a rubber septum and a balloon of
nitrogen. To the flask was added degassed (by sonication for 30 minutes with N2 sparging),
anhydrous n-butanol [2 mL (0.5 M in ArBr)]. The heterogeneous reaction mixture was stirred
vigorously for 2 hours and then poured into ethyl acetate (~20 mL). This mixture was filtered
through a pad of silica and concentrated under reduced pressure by rotary evaporation. This
product was used without further purification.
To the flask containing the crude product of the crude Suzuki coupling product was added an
oven-dried magnetic stir bar. The flask was evacuated and backfilled with nitrogen three times,
and then the gas line adapter was quickly replaced with a rubber septum and a balloon of
nitrogen. To the flask was added anhydrous THF (10 mL) and then NaOMe (5 wt. % in MeOH;
342 µL, 1.5 mmol, 1.5 equiv). The reaction mixture was stirred until no more starting material
was observed by TLC (30 – 60 minutes). The reaction was quenched by the addition of sat. aq.
NH4Cl (10 mL). The organic layer was separated, and the aqueous layer was extracted with Et2O
(3 x 10 mL). The combined organic layers were then washed water (1 x 10 mL), brine (1 x 10
mL) and dried over anhydrous Na2SO4. . The combined organic layers were then filtered and
concentrated under reduced pressure by rotary evaporation. This product was used without
further purification.
The crude product from the deprotection was dried by azeotropic distillation with benzene under
reduced pressure by rotary evaporation three times. This flask was then evacuated and backfilled
with nitrogen, and then the gas line adapter was quickly replaced with a rubber septum and a
balloon of nitrogen. To this flask was added anhydrous CH2Cl2 (3 mL) and the flask was
sonicated to dissolve the solid.
To a flame-dried 25mL round bottomed flask equipped with a magnetic stir bar was added
anhydrous CH2Cl2 (1 mL), POCl3 (98 µL, 1.05 mmol, 1.05 equiv), and anhydrous DMF (92µL,
1.2 mmol, 1.2 equiv). After stirring for 5 minutes, the solution of 2-arylpyrrole in CH2Cl2 was

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transferred by syringe to this flask. Upon addition of the arylpyrrole, the solution immediately
became brightly colored (color depending on substrate).
After stirring for 8-16 hours, the reaction was concentrated first under a stream of N2 and then
under reduced pressure. When no solvent remained, the flask was backfilled with N2 and then the
gas line adapter was quickly replaced with a rubber septum and a balloon of nitrogen. To this
flask was added THF (2 mL) and 3M NaOH (aq) (2 mL). This biphasic mixture was stirred
vigorously for 30–60 minutes. To the flask was added H2O (5 mL) and Et2O (5 mL). The organic
layer was separated, and the aqueous layer was extracted with Et2O (3 × 10 mL). The combined
organic layers were washed with water (1 × 20 mL) and brine (1 × 20 mL). The combined
organic layers were then dried over anhydrous Na2SO4, filtered and concentrated under reduced
pressure by rotary evaporation. Purification by flash column chromatography on silica gel
afforded the corresponding aldehydes.
4.4.2 General Procedure for Suzuki coupling with liquid aryl bromides
To a flame-dried 5 mL microwave vial equipped with a magnetic stir bar was added N-
Boc-pyrrole-2-boronic acid (316 mg, 1.5 mmol, 1.5 equiv), Pd(OAc)2 (4.5mg, 0.02 mmol, 0.02
equiv), XPhos (19.0 mg, 0.04 mmol, 0.04 equiv), and K3PO4 (424 g, 2.0 mmol, 2.0 equiv),. The
flask was evacuated and backfilled with nitrogen three times, and then the gas line adapter was
quickly replaced with a rubber septum and a balloon of nitrogen. To the flask was added
degassed (by sonication for 30 minutes with N2 sparging), anhydrous n-butanol [2 mL (0.5 M in
ArBr)] and aryl bromide (1.0 mmol, 1.0 equiv). The heterogeneous reaction mixture was stirred
vigorously for 2 hours at room temperature and then poured into ethyl acetate (~20 mL). This
mixture was filtered through a pad of silica and concentrated under reduced pressure by rotary
evaporation. This product was used without further purification as described in the general
procedure above.
4.4.3 General Procedure for synthesis of ArylPyrrole–HTI photoswitiches
To a 5 mL flame-dried microwave flask was added benzo[b]thiophen-3(2H)-one (0.24
mmol, 0.12 equiv) and 5-aryl-2-formylpyrrole (0.2 mmol, 0.1 equiv). The flask was capped with
an aluminum–PTFE crimp cap, sealed, and evacuated and backfilled with nitrogen three times.
To the flask was then added anhydrous toluene (2 mL, 0.1 M in aldehyde) and piperidine (10 µL,
0.1 mmol, 0.5 equiv). The flask was transferred to a pre-warmed oil bath set to 111 ˚C and stirred
for two hours. After two hours the flask was removed from the oil bath and cooled to room
temperature and then to 0 ˚C in a water-ice bath. To the flask was added hexanes (5 mL) and the
flask was allowed to sit for an addition 10–30 minutes. The mixture was the filtered, and the
precipitate was then triturated with hexanes to until the filtrate ran clear to provide the pure
product as a red, blue, or purple solid depending on the substrate.
4.5 Precursor Synthesis
Benzo[b]thiophen-3(2H)-one, 4,5-bis(4-methoxyphenyl)-pyrrole-2-carboxalehyde, and 4-
phenyl-pyrrole-2-carboxaldehyde, and 3-phenyl-pyrrole-2-carboxaldehyde were synthesized
according to published procedures.
4.5.1 5-(naphthalen-1-yl)-1H-pyrrole-2-carbaldehyde (SI-1):

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Prepared according to general procedure. Purification by flash column chromatography
on silica gel (hexanes/Et2O = 100:0 to 80:20) afforded the title compound (158 mg, 71%) as a
pink solid. Rf: 0.32 (hexanes:Et2O = 1:1) 1H NMR (600 MHz, CDCl3): δ 9.59 (s, 1H), 9.44 (br s,
1H), 8.20 – 8.15 (m, 1H), 7.95 – 7.89 (m, 2H), 7.60 – 7.49 (m, 4H), 7.13 (dd, J = 3.9, 2.5 Hz,
13
1H), 6.64 (dd, J = 3.9, 2.5 Hz, 1H). C NMR (151 MHz, CDCl3): δ 179.1, 138.9, 134.1, 133.3,
131.2, 129.5, 129.5, 128.8, 127.2, 127.1, 126.5, 125.5, 125.2, 121.9, 112.8. IR (cm-1): 3273,
1658, 1628, 1510, 1491, 1423, 1388, 1267, 1228, 1055, 810, 786, 771, 691, 566. ESI-MS (m/z):
[M+H]+ calc’d for C15H12NO+: 222.1; found: 222.1
4.5.2 5-(naphthalen-2-yl)-1H-pyrrole-2-carbaldehyde (SI-2):
Prepared according to general procedure. Purification by flash column chromatography
on silica gel (hexanes/Et2O = 100:0 to 80:20) afforded the title compound (201 mg, 91%) as a
lavender solid. Rf: 0.30 (hexanes:Et2O = 1:1) 1H NMR (600 MHz, CDCl3): δ 9.69 (br s, 1H),
9.56 (s, 1H), 8.07 (s, 1H), δ 7.91 (d, J = 8.5 Hz, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.85 (d, J = 7.2
Hz, 1H), 7.72 (dd, J = 8.6, 1.8 Hz, 1H), 7.55–7.49 (m, 2H), 7.07 (dd, J = 4.0, 2.4 Hz, 1H), 6.77
(dd, J = 3.9, 2.6 Hz, 1H). 13C NMR (151 MHz, CDCl3): δ 178.9, 139.9, 133.6, 133.3, 129.2,
129.2, 128.3, 128.0, 127.9, 127.1, 126.8, 124.1, 123.2, 122.7, 109.6. IR (cm-1): 3280, 1645,
1488, 1425, 1288, 1261, 1049, 1006, 787, 766, 718, 473. ESI-MS (m/z): [M+H]+ calc’d for
C15H12NO+: 222.1; found: 222.1
4.5.3 5-(anthracen-9-yl)-1H-pyrrole-2-carbaldehyde (SI-3):
Prepared on 2.0 mmol scale according to general procedure. Purification by flash column
chromatography on silica gel (hexanes/Et2O = 100:0 to 90:10) afforded the title compound (321
mg, 59%) as a yewllow solid. Rf: 0.50 (hexanes:Et2O = 1:1) 1H NMR (600 MHz, CDCl3): δ 9.66
(s, 1H), 9.37 (br s, 1H), 8.56 (s, 1H), 8.05 (d, J = 8.3 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.51 –
7.47 (m, 2H), 7.47 –7.43 (m, 2H), 7.26 – 7.24 (m, 1H), 6.62 (dd, J = 3.8, 2.5 Hz, 1H). 13C NMR
(151 MHz, CDCl3): δ 179.1, 136.4, 133.4, 131.4, 131.3, 128.9, 128.7, 126.8, 125.9, 125.8, 125.6,
121.6, 114.8. IR (cm-1): 3250, 1634, 1498, 1411, 1329, 1309, 1282, 1240, 1043, 908, 789, 762,
730, 621. ESI-MS (m/z): [M+H]+ calc’d for C19H14NO+: 272.1; found: 272.1
4.5.4 5-(anthracen-2-yl)-1H-pyrrole-2-carbaldehyde (SI-4):
Prepared according to general procedure. Purification by flash column chromatography
on silica gel (hexanes/Et2O = 100:0 to 80:20) afforded the title compound (101 mg, 37%) as a
yellow solid. Rf: 0.27 (hexanes:Et2O = 1:1) 1H NMR (600 MHz, CDCl3): δ 9.66 (br s, 1H), 9.57
(s, 1H), 8.44 (d, J = 19.6 Hz, 2H), 8.22 (s, 1H), 8.07 (d, J = 8.8 Hz, 1H), 8.04 – 7.98 (m, 2H),
7.69 (d, J = 8.9, 1H), 7.50 (td, J = 6.3, 5.7, 3.0 Hz, 2H), 7.09 (dd, J = 4.0, 2.4 Hz, 1H), 6.82 (at, J
= 3.2 Hz, 1H). 13C NMR (151 MHz, CDCl3): δ 178.8, 139.7, 133.5, 132.3, 132.2, 131.3, 131.0,
129.4, 128.2, 128.2, 127.2, 126.8 126.4, 125.9, 125.9, 123.9, 122.7, 122.7, 109.6. IR (cm-1):
3269, 1644, 1628, 1502, 1474, 1425, 11259, 1217, 1042, 896, 810, 775, 750, 476. ESI-MS
(m/z): [M+H]+ calc’d for C19H14NO+: 272.1; found: 272.1
4.5.5 5-(pyren-1-yl)-1H-pyrrole-2-carbaldehyde (SI-5):
Prepared according to general procedure. Purification by flash column chromatography
on silica gel (hexanes/Et2O = 100:0 to 0:100) afforded the title compound (156 mg, 52%) as a
green solid. Rf: 0.27 (hexanes:Et2O = 1:1) 1H NMR (600 MHz, CDCl3): δ 9.64 (s, 1H), 9.62 (br

ACCEPTED MANUSCRIPT
s, 1 H), 8.45 (d, J = 9.3 Hz, 1H), 8.23 (at, J = 7.9 Hz, 3H), 8.16 – 8.12 (m, 2H), 8.11 – 8.03 (m,
3H), 7.20 (dd, J = 3.8, 2.5 Hz, 1H), 6.79 (dd, J = 3.8, 2.5 Hz, 1H). 13C NMR (151 MHz, CDCl3):
δ 179.1, 139.5, 133.7, 131.8, 131.6, 131.0, 128.9, 128.9, 128.5, 127.4, 126.8, 126.6, 126.5, 126.0,
125.62, 125.3, 125.1, 124.8, 124.3, 122.2, 113.3. IR (cm-1): 3285, 2805, 1651, 1481, 1418, 1251,
1223, 1045, 1044, 1005, 847, 773, 712, 517. ESI-MS (m/z): [M+H]+ calc’d for C21H14NO+:
296.1; found: 296.1
4.5.6 5-([1,1'-biphenyl]-4-yl)-1H-pyrrole-2-carbaldehyde (SI-6):
Prepared according to general procedure. Purification by flash column chromatography
on silica gel (hexanes/Et2O = 100:0 to 80:20) afforded the title compound (153 mg, 62%) as a
grey solid. Rf: 0.24 (hexanes:Et2O = 1:1) 1H NMR (600 MHz, CDCl3): δ 9.53 (s, 1H), δ 9.53 (br
s, 1H), 7.68 (s, 4H), 7.65 – 7.60 (m, 2H), 7.47 (t, J = 7.7 Hz, 2H), 7.38 (td, J = 7.3, 1.2 Hz, 1H),
13
7.05 (dd, J = 4.0, 2.4 Hz, 1H), 6.69 (dd, J = 4.0, 2.6 Hz, 1H). C NMR (151 MHz, CDCl3): δ
178.7, 141.4, 140.1, 139.3, 133.3, 129.4, 128.9, 127.8, 127.7, 126.9, 125.5, 122.5, 109.1. IR (cm-
1): 3279, 1644, 1549, 1464, 1389, 1310, 1282, 1211, 1083, 1067, 835, 782, 759, 729, 706. ESI-
MS (m/z): [M+H]+ calc’d for C17H14NO+: 248.1; found: 248.1
4.5.7 5-(4-(phenylethynyl)phenyl)-1H-pyrrole-2-carbaldehyde (SI-7):
Prepared according to general procedure. Purification by flash column chromatography
on silica gel (hexanes/Et2O = 100:0 to 80:20) afforded the title compound (135 mg, 50%) as a
grey solid. Rf: 0.30 (hexanes:Et2O = 1:1) 1H NMR (600 MHz, CDCl3): δ 9.60 (br s, 1H), 9.53 (s,
1H), 7.59 (s, 4H), 7.56 – 7.52 (m, 2H), 7.38 – 7.34 (m, 3H), 7.03 (dd, J = 4.0, 2.4 Hz, 1H), 6.68
(dd, J = 3.9, 2.6 Hz, 1H). 13C NMR (151 MHz, CDCl3): δ 179.0, 139.0, 133.6, 132.5, 131.8,
130.3, 128.7, 128.6, 126.0, 125.1, 123.6, 123.1, 122.6, 109.6, 91.3, 89.0. IR (cm-1): 3172, 1639,
1489, 1426, 1286, 1261, 1225, 1070, 1052, 1028, 1000, 783, 766, 689, 542. ESI-MS (m/z):
[M+H]+ calc’d for C19H14NO+: 272.1; found: 272.1
4.5.8 4,5-diphenyl-1H-pyrrole-2-carbaldehyde (SI-8):
To a flame-dried 20 mL microwave vial equipped with a magnetic stir bar was added N-
4,5-dibromopyrrole-2-carboxaldehyde (121 mg, 0.48 mmol, 1.0 equiv), phenylboronic acid (292
mg, 2.4 mmol, 5.0 equiv), Pd(PPh3)4 (56 mg, 0.048 mmol, 0.10 equiv), and Na2CO3 (305 mg,
2.88 mmol, 6.0 equiv). The flask was evacuated and backfilled with nitrogen three times, and
sealed with an aluminum crimp cap. To the flask was added water (4.2 mL) and dioxane (4.2
mL, final concentration ~0.6M in pyrrole). The reaction apparatus was then transferred into a
pre-heated oil bath and stirred at 80˚C for two hours. After two hours the reaction was cooled to
room temperature, poured into H2O (20 mL), and extracted with EtOAc (3 × 20 mL). The
combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate,
filtered, and concentrated under reduced pressure by rotary evaporation to provide a crude brown
solid. Purification by flash column chromatography on silica gel (Et2O/hexanes = 0/10 to 2/8)
afforded SI-8 (107.2 mg, 73%) as a tan solid. Rf: 0.37 (hexanes:Et2O = 1:1) 1H NMR (600 MHz,
DMSO-d6): δ 12.44 (br s, 1H), 9.56 (s, 1H), 7.42 – 7.38 (m, 2H), 7.38 – 7.33 (m, 3H), 7.32 –
7.28 (m, 2H), 7.25 – 7.21 (m, 3H), 7.19 (d, J = 2.1 Hz, 1H). 13C NMR (151 MHz, CDCl3): δ
179.6, 136.6, 135.6, 133.0, 131.6, 129.0, 128.9, 128.87, 128.8, 128.7, 128.6, 126.8, 124.6. IR
(cm-1): 3252, 3225, 1634, 1608, 1508, 1457, 1381, 1249, 1180, 1032, 805, 745, 526.ESI-MS
+
(m/z): [M+H]+ calc’d for C19H18NO3 : 308.1; found: 308.1

ACCEPTED MANUSCRIPT
4.5.9 3,5-diphenyl-1H-pyrrole-2-carbaldehyde (SI-9):
To a flame-dried 5 mL microwave vial equipped with a magnetic stir bar was added
anhydrous CH2Cl2 (1 mL), POCl3 (98 ꢀL, 1.05 mmol, 1.05 equiv), and anhydrous DMF (92ꢀL,
1.2 mmol, 1.2 equiv). After stirring for 5 minutes, a solution of 2,4-diphenylpyrrole (219 mg, 1.0
mmol 1.0 equiv) in CH2Cl2 (3 mL) was transferred by syringe to this flask. After stirring for 16
hours, the reaction was concentrated first under a stream of nitrogen and then under reduced
pressure. When no solvent remained, the flask was backfilled with nitrogen and then the gas line
adapter was quickly replaced with a rubber septum and a balloon of nitrogen. To this flask was
added THF (2 mL) and 3M NaOH (aq) (2 ml). This biphasic mixture was stirred vigorously for
30–60 minutes. To the flask was added H2O (5 mL) and Et2O (5 mL). The organic layer was
separated, and the aqueous layer was extracted with Et2O (3 × 50 mL). The combined organic
layers were washed with water (1 × 100 mL) and brine (1 × 100 mL). The combined organic
layers were then dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure
by rotary evaporation. Purification by flash column chromatography on silica gel (hexanes/Et2O
= 100:0 to 70:30) afforded the title compound (132 mg, 53%) as a pink solid. Rf: 0.39
1
(hexanes:Et2O = 1:1) H NMR (600 MHz, CDCl3): δ 9.65 (s, 1H), 9.49 (br s, 1H), 7.65 (d, J =
8.4 Hz, 2H), 7.55 (d, J = 8.2 Hz, 2H), 7.47 (at, J = 7.6 Hz, 4H), 7.43 – 7.35 (m, 2H), 6.74 (dd, J
= 2.9, 1.2 Hz, 1H). 13C NMR (151 MHz, CDCl3): δ 179.3, 138.7, 138.1, 133.4, 130.4, 129.2,
129.2, 129.1, 128.8, 128.8, 123.0, 125.2, 109.0. IR (cm-1): 3282, 1640, 1467, 1449, 1260, 1078,
1008, 813, 758, 699, 685, 667, 486. ESI-MS (m/z): [M+H]+ calc’d for C17H14NO+: 248.1; found:
248.1
4.5.10 3-(4-methoxyphenyl)-5-phenyl-1H-pyrrole-2-carbaldehyde (SI-10):
Aldehyde SI-10 was prepared from 2.0 mmol 3-(4-methoxyphenyl)-4-nitro-1-
8
phenylbutan-1-one according to O’Shea’s procedure.
Without purification, this crude
diarrylpyrrole was then formylated as per the procedure for compounds SI-1–SI-7. Purification
by flash column chromatography on silica gel (hexanes/Et2O = 100:0 to 70:30) afforded the title
compound (164 mg, 29.5% over three steps) as a pink solid. Rf: 0.25 (hexanes:Et2O = 1:1) 1H
NMR (600 MHz, CDCl3): δ 9.62 (d, J = 1.1 Hz, 1H), 9.39 (s, 1H), 7.63 (d, J = 7.9 Hz, 2H), 7.52
– 7.43 (m, 4H), 7.43 – 7.34 (m, 1H), 7.04 – 6.92 (m, 2H), 6.69 (dd, J = 2.8, 1.1 Hz, 1H), 3.87 (s,
3H). 13C NMR (151 MHz, CDCl3): δ 179.2, 159.6, 138.7, 138.0, 130.4, 130.2, 129.2, 129.02,
128.8, 125.9, 125.2, 114.3, 108.8, 55.4. IR (cm-1): 3296, 3276, 1634, 1610, 1467, 1452, 1292,
+
1251, 1177, 1034, 805, 764, 685. ESI-MS (m/z): [M+H]+ calc’d for C18H16NO2 : 278.1; found:
278.1
4.5.11 5-(4-methoxyphenyl)-3-phenyl-1H-pyrrole-2-carbaldehyde (SI-11):
Aldehyde SI-11 was prepared from 1.0 mmol 1-(4-methoxyphenyl)-4-nitro-3-
8
phenylbutan-1-one according to O’Shea’s procedure.
Without purification, this crude
diarrylpyrrole was then formylated as per the procedure for compound SI-1–SI-7. Purification by
flash column chromatography on silica gel (hexanes/Et2O = 100:0 to 70:30) afforded the title
compound (68 mg, 24.5% over three steps) as a pink solid. Rf: 0.25 (hexanes:Et2O = 1:1) 1H
NMR (600 MHz, CDCl3): δ 9.61 (s, 1H), 9.43 (br s, 1H), 7.65 – 7.57 (m, 2H), 7.55 (dd, J = 6.9,
1.5 Hz, 2H), 7.46 (td, J = 7.4, 1.3 Hz, 2H), 7.43 – 7.34 (m, 1H), 7.06 – 6.88 (m, 2H), 6.64 (dd, J
= 2.8, 1.2 Hz, 1H), 3.87 (d, J = 1.2 Hz, 3H). 13C NMR (151 MHz, CDCl3): δ 179.1, 160.4,
139.1, 138.5, 133.7, 129.2, 129.0, 128.9, 128.1, 126.8, 123.2, 114.8, 114.8, 108.4, 55.6. IR (cm-

ACCEPTED MANUSCRIPT
1): 3274, 1623, 1601, 1472, 1436, 1381, 1267, 1244, 1189, 1030, 836, 762, 699. ESI-MS (m/z):
+
[M+H]+ calc’d for C18H16NO2 : 278.1; found: 278.1
4.5.12 3,5-bis(4-methoxyphenyl)-1H-pyrrole-2-carbaldehyde (SI-12):
Aldehyde SI-12 was prepared from 2.0 mmol 3-(4-methoxyphenyl)-4-nitro-1-
phenylbutan-1-one according to O’Shea’s procedure.8,* Without purification, this crude
diarrylpyrrole was then formylated as per the procedure for compound SI-1–SI-7. Purification by
flash column chromatography on silica gel (hexanes/Et2O = 100:0 to 50:50) afforded the title
compound (269.6 mg, 17% over four steps) as a purple solid. *Note: In a variation from the
reported procdure procedure,8 the Paal-Knorr cyclization step was conducted at 50˚C for 30
minutes to minimize degradation, and then immediately formylated. Rf: 0.11 (hexanes:Et2O =
1:1) 1H NMR (600 MHz, CDCl3): δ 9.58 (s, 1H), 9.35 (s, 1H), 7.57 (d, J = 8.7 Hz, 2H), 7.47 (d,
J = 8.6 Hz, 2H), 7.07 – 6.94 (m, 4H), 6.59 (d, J = 2.8 Hz, 1H), 3.87 (s, 3H), 3.86 (s, 3H). 13C
NMR (151 MHz, CDCl3): δ 179.0, 160.3, 159.8, 139.1, 138.4, 130.3, 128.8, 126.8, 126.2, 123.3,
114.8, 114.4, 108.2, 55.57, 55.54. IR (cm-1): 3252, 3225, 1634, 1608, 1508, 1457, 1381, 1249,
+
1180, 1032, 805, 745, 526. ESI-MS (m/z): [M+H]+ calc’d for C19H18NO3 : 308.1; found: 308.1
4.6 Product Characterization
4.6.1 Photoswitch 2b:
Prepared according to general procedure. Obtained as a red solid (62.9 mg, 89%).1H
NMR (600 MHz, DMSO-d6): δ 12.30 (s, 1H), 8.24 (d, J = 7.8 Hz, 1H), 8.06 – 8.01 (m, 1H), 7.99
(d, J = 7.7 Hz, 1H), 7.98 (s, 1H), 7.86 – 7.79 (m, 2H), 7.76 – 7.69 (m, 1H), 7.67 (d, J = 7.3 Hz,
1H), 7.62 (ddd, J = 13.4, 7.4, 2.5 Hz, 3H), 7.40 (td, J = 8.0, 7.5, 1.9 Hz, 1H), 7.04 – 6.91 (m,
13
1H), 6.81 (t, J = 2.2 Hz, 1H). C NMR (151 MHz, DMSO-d6): δ 186.5, 144.2, 136. 7, 135.1,
133.6, 131.0, 130.3, 129.5, 129.3, 128.6, 128.5, 126.9, 126.8, 126.3, 126.0, 125.8, 125.6, 125.1,
124.5, 123.4, 123.1, 116.1, 114.3. IR (cm-1): 3264, 1649, 1582, 1555, 1484, 1332, 1286, 1215,
1093, 1059, 803, 782, 734, 718. ESI-MS (m/z): [M+H]+ calc’d for C23H16NOS+: 354.1; found:
354.1. UV-Vis: λmax(Z) = 482 nm, λmax(E) = 537 nm; 0.01mg/mL in CH2Cl2.
4.6.2 Photoswitch 2c:
Prepared according to general procedure. Obtained as a red solid (59.7 mg, 84%).1H
NMR (600 MHz, DMSO-d6): δ 12.40 (s, 1H), 8.31 (s, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.99 (s,
1H), 7.93 (td, J = 8.6, 3.1 Hz, 3H), 7.84 (d, J = 7.6 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.70 (t, J =
7.5 Hz, 1H), 7.56 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.4 Hz, 1H), 7.40 (t, J = 7.4 Hz, 1H), 7.13 (s,
13
1H), 6.92 (s, 1H). C NMR (151 MHz, DMSO-d6): δ 186.9, 144.5, 138.1, 135.5, 133.7, 132.7,
131.4, 130.4, 129.1, 128.8, 128.3, 128.2, 127.3, 126.7, 126.4, 126.3, 125.0, 124.0, 123.5, 123.1,
123.0, 117.3, 112.1. IR (cm-1): 3289, 1649, 1581, 1543, 1441, 1281, 1209, 1071, 1065, 1051,
889, 783, 732, 678, 473. ESI-MS (m/z): [M+H]+ calc’d for C23H16NOS+: 354.1; found: 354.1.
UV-Vis: λmax(Z) = 495 nm, λmax(E) = 555 nm; 0.01mg/mL in CH2Cl2.
4.6.3 Photoswitch 2d:

ACCEPTED MANUSCRIPT
Prepared according to general procedure. Obtained as a red solid (63.8 mg, 79 %).1H
NMR (600 MHz, DMSO-d6): δ 12.42 (s, 1H), 8.77 (s, 1H), 8.19 (d, J = 8.2 Hz, 2H), 7.92 (s,
1H), 7.86 – 7.76 (m, 4H), 7.72 (t, J = 7.6 Hz, 1H), 7.60 – 7.49 (m, 4H), 7.41 (t, J = 7.5 Hz, 1H),
7.11 (t, J = 2.9 Hz, 1H), 6.75 (t, J = 3.0 Hz, 1H). 13C NMR (151 MHz, DMSO-d6): δ 186.6,
144.2, 135.1, 134.1, 131.0, 130.8, 130.6, 129.1, 128.5, 128.0, 126.6, 126.0, 125.8, 125.6, 124.6,
123.3, 123.0, 116.0, 115.8. IR (cm-1): 3223, 1654, 1595, 1581, 1562, 1330, 1288, 1219, 1088,
1043, 880, 782, 614. ESI-MS (m/z): [M+H]+ calc’d for C27H18NOS+: 404.1104; found: 404.1.
UV-Vis: λmax(Z) = 474 nm, λmax(E) = 525 nm; 0.01mg/mL in CH2Cl2.
4.6.4 Photoswitch 2e:
1
Prepared according to general procedure. Obtained as a red solid (62.0 mg, 77%). H
NMR 1H NMR (600 MHz, DMSO-d6) δ 12.46 (br s, 1H), 8.57 (s, 2H), 8.47 (s, 1H), 8.17 (d, J =
8.9 Hz, 1H), 8.13 (d, J = 7.3 Hz, 1H), 8.10 – 8.07 (m, 1H), 8.01 (s, 1H), 7.95 (d, J = 8.9 Hz, 1H),
7.84 (d, J = 7.6 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.71 (t, J = 7.5 Hz, 1H), 7.57 – 7.47 (m, 2H),
7.41 (t, J = 7.4 Hz, 1H), 7.20 – 7.18 (m, 1H), 7.00 – 6.87 (m, 1H). 13C NMR (126 MHz, DMSO-
d6 @ 120˚C): 186.9, 144.8, 138.3, 135.2, 132.6, 132.1, 132.0, 131.8, 131.1, 130.9, 129.3, 128.5,
128.4, 126.5, 126.5, 126.3, 126.2, 126.1, 126.0, 124.7, 124.7, 124.5, 123.7, 123.2, 123.0, 117.3,
112.1 IR (cm-1): 3287, 1642, 1578, 1544, 1441, 1306, 1279, 1205, 1084, 1069, 894, 776, 728,
476. ESI-MS (m/z): [M+H]+ calc’d for C27H18NOS+: 404.1; found: 404.1. UV-Vis: λmax(Z) =
507 nm, λmax(E) = 556 nm; 0.01mg/mL in CH2Cl2.
4.6.5 Photoswitch 2f:
Prepared according to general procedure. Obtained as a brown/red solid (64.2 mg, 76%).
1H NMR (600 MHz, DMSO-d6): δ 8.52 (d, J = 9.2 Hz, 1H), 8.36 (d, J = 8.0 Hz, 1H), 8.34 – 8.29
(m, 2H), 8.29 – 8.18 (m, 5H), 8.16 – 8.04 (m, 2H), 7.86 (dd, J = 7.7, 1.4 Hz, 1H), 7.76 (d, J = 7.9
Hz, 1H), 7.69 (td, J = 7.5, 1.3 Hz, 1H), 7.40 (td, J = 7.5, 1.1 Hz, 1H), 7.08 (d, J = 3.9 Hz, 1H),
6.93 (d, J = 3.9 Hz, 1H). 13C NMR (151 MHz, DMSO-d6, 120˚C): δ 13C NMR (126 MHz, dmso)
δ 185.9, 143.8, 136.5, 134.1, 130.7, 130.6, 130.01, 130.00, 129.5, 127.4, 127.3, 127.1, 126.6,
126.6, 126.3, 125.8, 125.3, 125.0, 124.8, 124.5, 124.2, 124.0, 123.9, 123.7, 123.6, 123.4, 122.5,
115.8, 114.1. IR (cm-1): 32576, 3037, 1649, 1597, 1553, 1421, 1310, 1211, 1093, 1062, 1019,
839, 733. ESI-MS (m/z): [M+H]+ calc’d for C29H18NOS+: 428.1; found: 428.1. UV-Vis: λmax(Z)
= 493 nm, λmax(E) = 552 nm; 0.01mg/mL in CH2Cl2.
4.6.6 Photoswitch 2g:
Prepared according to general procedure. Obtained as a bright red solid (62.8 mg,79 %).
1H NMR (500 MHz, DMSO-d6 @ 120˚C): δ 1H NMR (500 MHz, DMSO-d6) δ 11.91 (br s, 1H),
8.01 (s, 1H), 7.84 (t, J = 7.8 Hz, 3H), 7.77 – 7.69 (m, 5H), 7.66 (t, J = 7.5 Hz, 1H), 7.48 (t, J =
7.6 Hz, 2H), 7.37 (t, J = 7.3 Hz, 2H), 6.93 (t, J = 3.3 Hz, 1H), 6.91 (t, J = 2.4 Hz, 1H) 13C NMR
(125 MHz, DMSO-d6 @ 120˚C): δ 185.8, 143.7, 139.1, 138.7, 136.9, 134.0, 130.7, 129.6, 129.4,
128.2, 126.7, 126.5, 125.8, 125.2, 124. 9, 124.5, 123.6, 123.2, 122.1, 116.1, 110.2. IR (cm-1):
3279, 1644, 1549, 1464, 1389, 1310, 1282, 1211, 1083, 1067, 835, 782, 759, 729, 706. ESI-MS
(m/z): [M+H]+ calc’d for C25H18NOS+: 380.1; found: 380.1. UV-Vis: λmax(Z) = 495 nm, λmax(E)
= 556 nm; 0.01mg/mL in CH2Cl2.
4.6.7 Photoswitch 2h:

ACCEPTED MANUSCRIPT
Prepared according to general procedure. Obtained as a red/brown solid (62.8mg, 77%).
1H NMR (600 MHz, DMSO-d6): δ 12.31 (br s, 1H), 7.94 (s, 1H), 7.83 (ad, J = 7.8 Hz, 3H), 7.79
(d, J = 7.9 Hz, 1H), 7.73 – 7.67 (m, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.58 – 7.52 (m, 2H), 7.50 –
13
7.42 (m, 2H), 7.40 (t, J = 7.4 Hz, 1H), 7.06 (d, J = 4.0 Hz, 1H), 6.88 (d, J = 4.0 Hz, 1H). C
NMR (151 MHz, DMSO-d6): δ 186.5, 144.1, 136.7, 135.1, 132.1, 131.4, 130.9, 130.9, 130.2,
128.9, 128.8, 126.0, 125.9, 124.6, 124.5, 124.0, 122.5, 122.3, 120.9, 116.7, 111.8, 90.5, 89.4. IR
(cm-1): 3279, 1646, 1578, 1556, 1318, 1091, 831, 780, 731, 679, 657. ESI-MS (m/z): [M+H]+
calc’d for C27H18NOS+: 404.1; found 404.1. UV-Vis: λmax(Z) = 498 nm, λmax(E) = 558 nm;
0.01mg/mL in CH2Cl2.
4.6.8 Photoswitch 3a:
Prepared according to general procedure (0.25 mmol scale of aldehyde). Obtained as a
red/purple solid (77.0 mg, 73 %). 1H NMR (500 MHz, CD2Cl2): δ 8.03 (d, J = 7.9 Hz, 1H), 7.90
(d, J = 7.7 Hz, 2H), 7.54 (ddt, J = 20.5, 14.7, 7.3 Hz, 8H), 7.42 (q, J = 7.1 Hz, 2H), 7.35 (d, J =
3.4 Hz, 2H), 6.98 (d, J = 2.6 Hz, 1H). 13C NMR (126 MHz, CD2Cl2): δ 185.1, 145.9, 138.2,
137.9, 135.4, 134.3, 134.2, 131.3, 130.0, 129.9, 129.8, 129.34, 129.1, 128.6, 128.2, 127.1, 125.5,
125.1, 124.0, 123.4, 111.3. IR (cm-1): 3057, 1630, 1588, 1521, 1480, 1448, 1290, 1263, 1213,
1074, 1039, 1028. ESI-MS (m/z): [M+H]+ calc’d C25H18NOS+: 380.1; found 380.1. UV-Vis:
λmax(Z) = 501 nm, λmax(E) = 560 nm; 0.01mg/mL in CH2Cl2.
4.6.9 Photoswitch 3b:
1
Prepared according to general procedure. Obtained as a red solid (65.4 mg, 80%). H
NMR (600 MHz, CD2Cl2): δ 8.03 (d, J = 7.8 Hz, 1H), 7.90 (d, J = 7.2 Hz, 2H), 7.60 – 7.51 (m,
4H), 7.46 (d, J = 8.5 Hz, 2H), 7.42 – 7.38 (m, 1H), 7.35 (ddd, J = 8.1, 6.8, 1.4 Hz, 1H), 7.33 (s,
1H), 7.04 (d, J = 8.6 Hz, 2H), 6.94 (d, J = 2.6 Hz, 1H), 3.88 (s, 3H). 13C NMR (151 MHz,
CD2Cl2): δ 184.8, 160.1, 145.9, 138.3, 138.0, 134.3, 134.0, 131.30, 131.0, 130.1, 129.8, 129.1,
128.8, 127.7, 127.0, 125.5, 125.1, 124.0, 122.9, 114.8, 111.0, 55.9. IR (cm-1): 1630, 1605, 1588,
1503, 1443, 1368, 1272, 1246, 1211, 1169m 1071, 921, 759, 596. ESI-MS (m/z): [M+H]+ calc’d
for: C26H20NO2S+:410.1; found 410.1. UV-Vis: λmax(Z) = 505 nm, λmax(E) = nm; 0.01mg/mL in
CH2Cl2.
4.6.10 Photoswitch 3c:
Prepared according to general procedure. Obtained as a red solid (65.3 mg, 80%).1H
NMR (600 MHz, CD2Cl): δ 8.02 (d, J = 7.8 Hz, 1H), 7.85 (d, J = 8.5 Hz, 2H), 7.61 – 7.46 (m,
6H), 7.42 (t, J = 7.2 Hz, 1H), 7.37 – 7.29 (m, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 2.5 Hz,
1H), 3.89 (s, 3H). 13C NMR (151 MHz, CD2Cl2): δ 184.5, 160.9, 145.8, 138.8, 138.4, 135.4,
134.4, 133.84, 129.9, 129.9, 129.4, 128.6, 128.2, 127.1, 126.9, 125.0, 124.0, 123.9, 122.4, 115.3,
110.8, 56.0. IR (cm-1): 1631, 1607, 1586, 1504, 1489, 1445, 1366, 1274, 1264, 1179, 1024, 921,
744, 662. ESI-MS (m/z): [M+H]+ calc’d for: C26H20NO2S+: 410.1; found: 410.1. UV-Vis:
λmax(Z) = 511 nm, λmax(E) = 573 nm; 0.01mg/mL in CH2Cl2.
4.6.11 Photoswitch 3d:
1
Prepared according to general procedure. Obtained as a purple solid (67.5 mg, 77%). H
NMR (500 MHz, CD2Cl2) δ 8.02 (d, J = 7.9 Hz, 1H), 7.84 (d, J = 8.7 Hz, 2H), 7.60 – 7.53 (m,
2H), 7.46 (d, J = 8.6 Hz, 2H), 7.34 (td, J = 6.0, 5.4, 3.4 Hz, 1H), 7.30 (s, 1H), 7.07 (d, J = 8.6 Hz,

ACCEPTED MANUSCRIPT
2H), 7.03 (d, J = 8.1 Hz, 2H), 6.86 (d, J = 2.6 Hz, 1H), 3.89 (s, 3H), 3.88 (s, 3H). 13C NMR (151
MHz, DMSO-d6): δ 184.2, 160.9, 160.1, 145.7, 138.9, 138.5, 134.6, 133.7, 131.0, 130.1, 128.7,
127.7, 127.1, 126.9, 125.0, 123.97, 123.9, 121.9, 115.3, 114.8, 110.6, 56.0, 55.9. IR (cm-1):
1608, 1588, 1499, 1276, 1250, 1178, 1032, 922, 832, 797, 735, 529. ESI-MS (m/z): [M+H]+
calc’d for: C27H22NO3S+:440.1; found: 440.1. UV-Vis: λmax(Z) = 515 nm, λmax(E) = 576 nm;
0.01mg/mL in CH2Cl2.
4.6.12 Photoswitch 4a:
Prepared according to general procedure (0.16 mmol of aldehyde scale). Obtained as a
red solid (43.4 mg, 72%). 1H NMR (600 MHz, DMSO-d6): δ 12.22 (s, 1H), 7.92 (s, 1H), 7.83 (d,
J = 7.6 Hz, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.74 – 7.65 (m, 1H), 7.45 – 7.37 (m, 5H), 7.37 – 7.30
(m, 5H), 7.31 – 7.25 (m, 1H), 6.90 (d, J = 2.4 Hz, 1H). 13C NMR (151 MHz, DMSO-d6): δ
187.0, 144.6, 135.7, 135.6, 134.8, 131.8, 131.3, 129.2, 129.1, 129.0, 128.7, 128.4, 128.1, 127.1,
126.4, 126.3, 125.0, 124.4, 123.0, 116.6. IR (cm-1): 3279, 1648, 1577, 1546, 1271, 1188, 1080,
813, 737, 695, 678, 543. ESI-MS (m/z): [M+H]+ calc’d for C25H18NOS+: 380.1; found: 380.1.
UV-Vis: λmax(Z) = 490 nm, λmax(E) = 548 nm; 0.01mg/mL in CH2Cl2.
4.6.13 Photoswitch 4b:
Prepared according to general procedure (0.14 mmol of aldehyde scale). Obtained as a red/brown
solid (49.2 mg, 82%). 1H NMR (500 MHz, DMSO-d6): δ 7.90 (s, 1H), 7.82 (d, J = 7.7 Hz, 1H),
7.78 (d, J = 7.9 Hz, 1H), 7.68 (t, J = 7.5 Hz, 1H), 7.38 (t, J = 7.5 Hz, 1H), 7.34 (d, J = 8.7 Hz,
2H), 7.23 (d, J = 8.7 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 2.4
Hz, 1H), 3.78 (s, 3H), 3.77 (s, 3H). 13C NMR (126 MHz, DMSO-d6): δ 182.7, 155.4, 154.4,
140.4, 131.3, 130.8, 127.5, 125.7, 125.3, 124.4, 124.0, 122.3, 122.1, 121.8, 120.9, 120.2, 119.5,
119.0, 112.7, 110.6, 110.5, 51.6, 51.5. IR (cm-1): 3285, 2951, 2833, 1640, 1576, 1543, 1453,
1277, 1211, 1179, 1081, 954, 827, 733, 676. ESI-MS (m/z): [M+H]+ calc’d for C27H22NO3S+:
440.1, found: 440.1. UV-Vis: λmax(Z) = 500 nm, λmax(E) = 562 nm; 0.01mg/mL in CH2Cl2.
4.6.14 Photoswitch 5:
1
Prepared according to the general procedure. Obtained as a red solid (39.6 mg, 65%). H
NMR (600 MHz, DMSO-d6): δ 7.84 (s, 1H), 7.84 – 7.78 (m, 3H), 7.72 – 7.68 (m, 1H), 7.67 –
7.64 (m, 2H), 7.43 – 7.33 (m, 3H), 7.27 – 7.17 (m, 1H), 7.08 (s, 1H). 13C NMR (151 MHz,
DMSO-d6): δ 187.1, 144.7, 135.6, 134.6, 131.3, 129.6, 129.3, 128.2, 126.6, 126.5, 126.3, 125.3,
124.9, 124.0, 123.5, 123.4, 111.6. IR (cm-1): 3252, 1658 1592, 1568, 1515, 1472, 1344, 1310,
1285, 1222, 1145, 1084, 1061, 751, 623, 511. ESI-MS (m/z): [M+H]+ calc’d for: C19H14NOS+:
304.1; found: 304.1. UV-Vis: λmax(Z) = 468 nm, λmax(E) = 517 nm; 0.01mg/mL in CH2Cl2.
4.6.15 Photoswitch 6:
1
Prepared according to the general procedure. Obtained as a red solid (42.6 mg, 70%). H
NMR (600 MHz, DMSO-d6): δ 7.87 – 7.75 (m, 3H), 7.70 (ddd, J = 8.2, 7.2, 1.4 Hz, 1H), 7.49
(dd, J = 8.6, 6.8 Hz, 2H), 7.44 – 7.36 (m, 4H), 7.34 (d, J = 2.7 Hz, 1H), 6.53 (d, J = 2.6 Hz, 1H).
13C NMR (151 MHz, DMSO-d6): δ 186.5, 144.3, 135.1, 135.1, 134.9, 130.6, 128.9, 128.8,
127.6, 127.2, 126.2, 125.8, 124.4, 123.6, 122. 6, 122.5, 111.7. IR (cm-1): 1632, 1586, 1496,

ACCEPTED MANUSCRIPT
1442, 1348, 1296, 1176, 1065, 1035, 738, 663. ESI-MS (m/z): [M+H]+ calc’d for C19H14NOS+:
304.1; found: 304.1. UV-Vis: λmax(Z) = 470 nm, λmax(E) = 519 nm; 0.01mg/mL in CH2Cl2.
Acknowledgments
Financial support for this work was provided by Yale University, the Sloan Foundation, Amgen,
and the National Science Foundation (GRFP to J.E.Z.). We gratefully acknowledge the National
Science Foundation for financial support in the establishment of the Yale University High
Performance Computing (HPC) Center (CNS 08-21132).
References and notes
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7
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9
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