Preparation of an indolylfulgimide-adamantane linker conjugate with nitrile anchoring groups through palladium-catalyzed transformations

Article abstract of DOI:10.1002/ejoc.200801199

We report the preparation, through palladium-catalyzed transformations, of the indolylfulgimide linker conjugate 1, containing an adamantane core and nitrile anchoring groups. The ethynylene-linker 12 for the final Sonogashira coupling was prepared throug

Full text of DOI:10.1002/ejoc.200801199

FULL PAPER
DOI: 10.1002/ejoc.200801199
Preparation of an Indolylfulgimide-Adamantane Linker Conjugate with Nitrile
Anchoring Groups through Palladium-Catalyzed Transformations
Sebastian Zarwell,[a] Steffen Dietrich,[a] Christine Schulz,[a] Paul Dietrich,[a]
Fabian Michalik,[a] and Karola Rück-Braun*[a]
Keywords: Fulgimides / Photochromism / Tripods / Cross-coupling / Cyanides
We report the preparation, through palladium-catalyzed
transformations, of the indolylfulgimide linker conjugate 1,
containing an adamantane core and nitrile anchoring groups.
The ethynylene-linker 12 for the final Sonogashira coupling
was prepared through palladium-mediated cyanation of an
iodo-substituted precursor with Zn(CN)2. The synthesis of
the 6-bromo-substituted indolylfulgimide coupling partner 2
was accomplished in seven steps. Model studies using phen-
ylacetylene and the 5-bromo-substituted indole 13 were con-
ducted to find conditions that would prevent homocoupling
of the ethynylene linker 12 in the final Sonogashira coupling
step. The use of Pd(PhCN)2Cl2 and [(tBu)3PH]BF4 in the pres-
ence of diisopropylamine, together with CuI as additive,
proved to be most efficient. Finally, the photochromic proper-
ties of conjugate 1 and indolylfulgimide 2 were studied.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Introduction
The rapid development of novel technologies in opto-
and bioelectronics has produced strong interest in novel
functional materials.[1] Photoswitchable organic molecules
are promising candidates in these areas of interest. A de-
tailed understanding of the elementary switching processes
on surfaces is of fundamental importance for the develop-
ment of photoswitches for nano- and optoelectronic de-
vices,[2] and these processes strongly depend upon the as-
sembling of the functional molecules on metals or semi-
conductors. Recently, rigid tripodal linker systems with
multiple anchoring groups for the immobilization of chro-
mophores have been developed by Galoppini and others.[3]
These linker scaffolds offer new opportunities to vary the
orientations of chromophore units and to influence their
lateral interactions in ensembles or monolayers on surfaces.
In continuation of our efforts directed towards the synthesis
of photoswitch linker conjugates[4] we present here the syn-
thesis of the indolylfulgimide linker conjugate 1, containing
an adamantane core at the center of the tetrahedral linker
scaffold and nitrile anchoring groups for immobilization on
metal surfaces (Figure 1). In the past, mainly thiol-based
strategies have been applied for metal–molecule contacts on
gold, silver, and copper. However, it has been shown that
nitrile groups can also be used.[5]
Figure 1. Structure of the fulgimide linker conjugate 1 (represented
as a mixture of E and Z isomers).
For applications in optoelectronics, photochromic com-
pounds have to fulfil certain requirements, such as thermal
stability of their photoisomeric states, potential for their in-
dividual states to be addressed specifically, and nondestruc-
tive read-out.[1] Fulgides and fulgimides show photochemi-
cal transitions between the ring-opened and the ring-closed
states at appropriate wavelengths, together with high photo-
chemical stabilities during repeated cycles of irradiation.[6]
The photochromism and the photophysical characteristics
of indolylfulgimide 2 (Scheme 1) in solution has already
been characterized by Braun, Zinth, and ourselves.[7]
Fulgimides have also been identified as highly thermally
and hydrolytically stable photochromic compounds.[8]
Furthermore, the imide moiety can be used for the attach-
ment of fluorophores.[9] Fulgimides and their parent ful-
gides each contain a hexa-1,3,5-triene structural element,
and can exist in three isomeric forms: the noncyclizable Z
form, the cyclizable E form, and the closed C form, which
is obtained upon photochemical 6π-electrocyclization. The
Z and E forms have similar optical properties and can be
converted into each other by irradiation with UV light.
[a] Institut für Organische Chemie, Technische Universität Berlin,
Straße des 17. Juni 135, Sekr. C3, 10623 Berlin, Germany
Fax: +49-30-314-286-25
E-mail: krueck@chem.tu-berlin.de
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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Photoswitch Linker Conjugate with Nitrile Anchor Groups
Scheme 1. Photochemical isomerization of the photoswitch linker conjugate 1 and the indolylfulgimide 2.
Only the E form undergoes the electrocyclic ring-closure
reaction upon irradiation with UV light, which results in
the formation of an almost planar cyclic
C form
(Scheme 1). The E form can be obtained by ring-opening
of the C form upon irradiation with white light.
Results and Discussion
The bromo-substituted indolylfulgimide 2 was synthe-
sized in seven steps starting from 3-acetyl-2-methyl indole
(3) in 10% overall yield (Scheme 2). Treatment of indole 3
with bromine in glacial acetic acid afforded compound 4 in
68% yield. N-Methylation was accomplished with dimethyl
carbonate (DMC), affording indole 5 in 78% yield after
workup and recrystallization.
The bottleneck of all fulgide syntheses is usually the
Stobbe condensation, for which potassium tert-butoxide
and LDA are commonly used as bases.[8,10] However, with
these bases the reaction between indole 5 and diethyl iso-
propylidenesuccinate (6) proceeded sluggishly, and the half-
ester (Z)-7 was isolated in poor yields. Fortunately, however,
with potassium hexamethyldisilazide (KHMDS) in THF
the half-ester (Z)-7 was obtained in 36% isolated yield. The
diacid was prepared next, by a two-step protocol. Firstly,
the half-ester (Z)-7 was treated with potassium tert-butox-
ide/tBuOH, and subsequently saponification was carried
out with hot aqueous ethanolic KOH to give diacid (Z)-8
in 86% yield. Anhydride formation by treatment with N-
ethyl-NЈ-[3-(dimethylamino)propyl]carbodiimide (EDC) af-
forded the fulgide 9 in 91% yield as a 93:7 mixture of the
Z and E isomers.
Scheme 2. Reagents and conditions: a) Br2, AcOH, room temp.,
72 h, 4: 68%; b) DMC, K2CO3, DMF, reflux, 5 h, 5: 78%; c) diethyl
isopropylidenesuccinate (6), KHMDS, THF, 0 °C Ǟ room temp.,
24 h, 7: 36%; d) 1. KOtBu/tBuOH, 80 °C, 2 h; 2. KOH/EtOH/H2O,
reflux, 2 h, 8: 86%; e) EDC, DCM, room temp., 18 h, 9: 91%;
f) MeNH2·HCl, NaHCO3, dioxane/H2O (4:1), room temp., 5 h,
then g) ZnCl2/ZnBr2, HMDS, benzene, 60 °C, 19 h, 2: 67%.
On treatment of fulgide 9 with methylamine hydrochlo-
ride in dioxane/water at room temperature in the presence
of NaHCO3 the regioisomeric succinamic acids were ob- in DCM for 12 h and purification by flash chromatography.
tained as an inseparable mixture. This crude product mix- The C isomer (C)-2, dissolved in DCM, was then irradiated
ture was used in the next step without purification. Treat- for 4 h with 545 nm light (1000 W, XBO) to yield the pure
ment with 1 equiv. of ZnCl2 and ZnBr2 in the presence of E isomer (E)-2 (Scheme 1), quantitatively.
HMDS (1.5 equiv.) in benzene at reflux gave fulgimide 2
The synthesis of adamantane building block 12 was ac-
(Scheme 2) in 67% yield over the two steps after workup complished by starting with the known Sonogashira coup-
and purification by flash chromatography as a 64:36 mix- ling between 1,3,5,7-tetrakis(4-iodophenyl)adamantane and
ture of the E and Z isomers.[8] The pure C isomer (C)-2 (trimethylsilyl)acetylene,[3a] furnishing a mixture of the tri-
(Scheme 1) was obtained in 54% yield by irradiation of a and diiodo-substituted compounds 10a and 10b. This crude
solution of a Z/E isomeric mixture at 365 nm (200 W HBO) product mixture was used in the next step because of a
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more convenient chromatographic separation after the cy- nated indoles were detected in these studies,. We therefore
anation reaction. selected the easily accessible 5-bromo-1-methyl-1H-indole
For the introduction of the cyano anchoring groups, sev- (13) and phenylacetylene (14) as model compounds
eral methods were investigated. Classical methods for the (Scheme 4). Under standard Sonogashira conditions[4]
conversion of aryl iodides into aryl nitriles, such as the Ro- [Pd(PPh3)2Cl2 (5%), CuI (10%), and triethylamine
senmund–von Braun reaction, generally require harsh reac- (30 equiv.) in THF at 60 °C], product 15 could not be de-
tion conditions (150–250 °C) and are only suitable for ro- tected, and only the homocoupled dimer of phenylacetylene
bust substrates. A useful alternative is represented by palla- (14) was obtained. Such Glaser-type side reactions often
dium-mediated reactions in the presence of an excess of al- occur during the application of copper salts in Sonogashira
kali or heavy metal cyanides,[11] which proceed at signifi- reactions at higher temperatures.[15] Next, to take advantage
cantly lower temperatures. In a first approach we used po- of the higher reactivities of aryl iodides in cross-coupling
tassium hexacyanoferrate(II) as a nontoxic cyanation agent reactions, coupling procedures including the exchange of
and Pd(OAc)2 in the presence of dppf and Na2CO3 in N,N- bromine for iodine prior to the cross-coupling were exam-
dimethylacetamide in a published procedure.[12] Unfortu- ined. Treatment of indole 13 in a one-pot procedure with
nately, the harsh reaction conditions (140 °C) led to decom- KI and 1,10-phenanthroline monohydrate in the presence
position of the starting material, so we attempted a milder of CuI at 110 °C, followed by standard Sonogashira condi-
Pd-mediated cyanation protocol with zinc cyanide.[13] Treat- tions (Scheme 4), furnished indole 15 in 59% yield after
ment of iodoadamantanes 10a and 10b with zinc cyanide in workup and flash chromatography.
the presence of Pd(dmdba)2, [(tBu)3PH]BF4, and zinc dust
in NMP at room temperature for 24 h gave the correspond-
ing nitrile 11 in 66% yield after workup and flash
chromatography. Fortunately, compound 11 was also ob-
tained in 80% yield on use of Pd(PPh3)4 and zinc cyanide
in DMF at 65 °C for 28 h (Scheme 3); smaller amounts of
by-products were formed during this procedure. Subsequent
removal of the trimethylsilyl group with tetrabutylammo-
nium fluoride (TBAF) afforded nitrile 12 in 91% yield
Scheme 4. Reagents and conditions: a) 1,10-phenanthroline mono-
hydrate, CuI, KI, DMF, 110 °C, 48 h; b) 5% Pd(PPh3)2Cl2, CuI,
NEt3, DMF, room temp., 19 h, 15: 59%.
(Scheme 3).
Analogously, the indolylfulgimide 2 was treated with the
tripodal linker 12 to yield the photoswitch linker conjugate
1 in 29% yield (17 µmol scale, E/Z = 79:21, Scheme 5).
However, by-product formation and a low reproducibility,
probably as a result of the harsh reaction conditions needed
for the bromine–iodine exchange and incomplete conver-
sion to the aryl iodide, forced us to examine other reaction
conditions.
Scheme 5. Reagents and conditions: a) 1,10-phenanthroline mono-
hydrate, CuI, KI, 110 °C, 36 h, DMF; b) 12, 5% Pd(PPh3)2Cl2,
CuI, NEt3, DMF, room temp. 18 h, 1: 29%.
Scheme 3. Reagents and conditions: a) Pd(PPh3)4, Zn(CN)2, DMF,
65 °C, 28 h, 11: 80%; b) TBAF, THF, room temp., 12 h, 12: 91%.
Model compound 13 was thus once more examined, this
time under alternative copper-free Sonogashira conditions
directed towards prevention of the formation of the homo-
The key reaction in the synthesis of the photoswitch coupled dimer discussed above (Table 1).
linker conjugate 1 is a palladium-mediated Sonogashira
With Pd(PPh3)4 as a catalyst in pyrrolidine at 50 °C, in-
coupling of the electron-rich and deactivated 6-bromoindo- dole 15 was obtained in 65% yield (Table 1, Entry 1). How-
lyl fulgimide 2 with the tripodal linker 12. To find the opti- ever, in diisopropylethylamine under otherwise identical re-
mum reaction conditions for the Sonogashira coupling, action conditions no conversion of the starting material was
model studies were carried out. Only a few examples of detected (Table 1, Entry 2). Therefore, as an additional al-
comparable palladium-mediated coupling reactions with ternative, some novel, highly reactive ligand systems were
halogenated indoles are known in the literature,[14] and no also explored. Fu and Buchwald have demonstrated that
differences in the reactivities of 5- and 6-substituted haloge- Pd(PhCN)2Cl2 in combination with the strongly basic and
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Photoswitch Linker Conjugate with Nitrile Anchor Groups
Table 1. Optimization of the Sonogashira coupling reaction be- forms were then converted into the closed indolylfulgimides
tween indole 13 and phenylacetylene (14) to furnish product 15.
by irradiation with 365 nm light. For the photoswitch linker
Time [h] % Yield[a]
conjugate 1 the pericyclic ring closure is accompanied by
an increasing absorption band at 567 nm, which is red-
shifted by about 16 nm in relation to indolylfulgimide 2.
Furthermore, decreases in the peaks at 318 nm (compound
1) and 354 nm (compound 2) are seen. Because of the Z-
to-E isomerization prior to cyclization, isosbestic points for
this electrocyclic ring-closure process are not observed. The
opposite ring-opening reactions to the E isomers occur on
irradiation with green light and are indicated by complete
disappearance of the bands at 567 nm (compound 1) or
551 nm (compound 2).
Entry Reaction conditions
1
2
3
Pd(PPh3)4 (5%), pyrrolidine, 50 °C
40
24
18
65
–
94
Pd(PPh3)4 (5%), DIEA, 50 °C
Pd(PhCN)2Cl2 (3%), CuI (2%),
[(tBu)3PH]BF4 (6%), room temp.,
DIPA, dioxane
[a] Isolated yield.
bulky tri-tert-butylphosphane serves as a versatile catalyst
system for Sonogashira reactions with a broad range of dif-
ferently substituted aryl bromides at room temperature.[16]
Fortunately, the air-sensitive tri-tert-butylphosphane can be
replaced by the stable tetrafluoroborate salt [(tBu)3PH]BF4
in the presence of a base.[17]
The indole 13 and phenylacetylene (14) were thus treated
with Pd(PhCN)2Cl2 and [(tBu)3PH]BF4, in the presence of
CuI (2%) and diisopropylamine (1.2 equiv.) at room tem-
perature in dioxane, to afford product 15 in 94% yield
(Table 1, Entry 3). Encouraged by these results, we em-
ployed similar reaction conditions for the reaction between
indolylfulgimide 2 and the tripodal linker 12, with the ex-
ception that CuI (4%) was used. The indolyl linker conju-
gate 1 was isolated in a reproducible 36% yield (41 µmol
scale, E/Z 74:26, Scheme 6) after workup and purification
by flash chromatography.
Scheme 6. Preparation of photoswitch linker conjugate 1. Reagents
and conditions: a) Pd(PhCN)2Cl2 (3%), [(tBu)3PH]BF4, CuI (4%),
DIPA, dioxane, room temp., 20 h, 1: 36%.
The photochromic behavior of compounds 1 and 2 was
investigated in benzene solution at room temperature (Fig-
ure 2). The absorption spectra of the mixture of the open
isomers of the photoswitch linker conjugate 1 showed two
significant bands at 318 and 341 nm. The maximum of the
open forms of the bromo-substituted indolylfulgimide 2 ap-
peared at 354 nm. A dominant influence of the linker sys-
tem in the region below 360 nm causes a significantly higher
absorption in this region, thereby complicating comparison
Figure 2. Top: ring-closure activated by irradiation at 365 nm
(200 W, HBO). a) Conjugate 1 (c = 5.06ϫ10–5 molL–1): after 0 s,
1 s, 2 s, 6 s, 10 s, 18 s, 40 s, 80 s, 120 s, 3 min, 15 min; b) fulgimide
2 (c = 1.05ϫ10–4 molL–1): after 0 s, 2 s, 5 s, 8 s, 10 s, 15 s, 20 s,
30 s, 40 s, 60 s, 90 s, 120 s, 180 s. Bottom: Ring-opening reaction
activated by irradiation at 545 nm (1000 W, XBO). c) Conjugate 1:
after 0 s, 1 s, 2 s, 4 s, 8 s, 14 s, 22 s, 36 s, 90 s, and d) fulgimide 2:
after 0 s, 2 s, 4 s, 6 s, 8 s, 10 s, 12 s, 15 s, 20 s, 30 s, 45 s, 60 s, 90 s;
of the absorption spectra of compounds 1 and 2. The open for further details see the Supporting Information.
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tetramethylsilane (TMS), and coupling constants are in Hz. MS
and HRMS spectra were recorded on a Finnigan MAT 95 SQ in-
strument and the samples were ionized at an ionization potential of
70 eV. Elemental analyses were carried out by the Microanalytical
Division of the Institute of Organic Chemistry at the University of
Mainz (Germany) or were measured with an Elementar Vario EI
instrument from Analytik Jena at the Institute of Chemistry,
TU Berlin. UV/Vis spectra were measured on a Shimadzu UV-1601
UV/Vis spectrometer in the solvents stated (Uvasol quality) in
1ϫ1ϫ4 cm quartz cuvettes at 25 °C. A 1000-W Xe-lamp (XBO,
Osram, Munich) in a lamp casing from Müller Elektronik was used
for the irradiation experiments at 545 nm and a 200-W mercury
Two isosbestic points (Table 2) reveal a clean conversion
of the C into the E isomers. The complete spectroscopic
data for both compounds are listed in Table 2.
Table 2. Spectroscopic data for the fulgimides 1 and 2.
λmax,Z/E[a], (ε)[b]
λmax,C[a], (ε)[b]
Isosbestic points[a]
1
2
318, (29430)
354, (7745)
346, (22453), 567, (11422)
551, (7211)
289, 375
321, 396
[a] [nm]. [b] [dm3 mol–1 cm–1].
The ratios of the isomers in the photostationary states
(pss) at 365 nm were examined by RP-HPLC. For the pho- short-arc lamp (HBO, Osram, Munich) for the experiments at
365 nm. Additionally, 25 mm interference filters (ø 25 mm; Ϯ2 nm)
from Amko, an IR-filter (Müller Elektronik; MHO 60) and a lens
were placed between lamp and probe.
toswitch linker conjugate 1 a Z/E/C ratio of 23.3:22.5:54.2
was determined in the pss, and similar results were obtained
for the indolylfulgimide 2 (Z/E/C = 26.9:19.8:53.3).
X-ray Crystallographic Analysis of (E)-2: C20H21BrN2O2 with Mr
= 398.27 gmol–1; crystal size 0.16ϫ0.26ϫ0.32 mm; monoclinic
crystal system with space group C2/c and Z = 8, a = 2105.98(10),
Conclusions
b = 860.41(4), c = 2356.21(12) pm; V = 3.8344(3) nm3, ρcalcd.
=
The indolylfulgimide linker conjugate 1 has been synthe-
sized from the 6-bromo-substituted indolylfulgimide 2 and
the ethynylene linker 12 by Sonogashira cross-coupling. The
key intermediate in the synthesis of fulgimide 2 is the
1.380 Mgm–3; F(000) = 1624; linear absorption coefficient µ =
2.158 mm–1; type of diffractometer: Siemens SMART CCD; T =
293(2) K; Mo-Kα radiation; θ range 1.90–25.00°; index ranges
–19ՅhՅ25, –9ՅkՅ10, –27ՅlՅ21; reflections collected 11079;
bromo-substituted indolylfulgide 9, which was synthesized independent reflections 3326 (Rint = 0.1200); observed reflections
226 [IϾ2σ(I)], reflection used for refinement 3326; program system
used: SHELXS-97, SHELXL-97, and SHELXTL; empirical ab-
sorption correction, direct methods, full-matrix refinement at F2
with all independent reflections, weighting scheme SHELXL;
goodness-of-fit parameter (based on F2) S = 0.927; residual densi-
ties ∆ρmax and ∆ρmin = 429 and 434 enm–3. Hydrogen atoms: re-
fined with riding model, refined with a temperature factor 1.5 times
Ueq of the carbon atoms; non-hydrogen atoms: refined anisotropi-
cally. Data/restraints/parameters: 3326/0/226; R index (all data):
wR2 (based on F2) = 0.2244; R index (conventional) [IϾ2σ(I)]: R1
by use of KHMDS in the Stobbe condensation and EDC
for the anhydride formation. For the synthesis of the ethyn-
ylene linker a practical palladium-catalyzed cyanation pro-
cedure with zinc cyanide was successfully applied. For the
Sonogashira coupling, model studies with the 5-bromo-sub-
stituted indole 13 and phenylacetylene (14) were investi-
gated, and a procedure using Pd(PhCN)2Cl2 and tri-tert-
butylphosphonium tetrafluoroborate in the presence of di-
isopropylamine as the catalyst system with CuI as additive
at room temperature proved to be most efficient for pre- (based on F) = 0.0775.[18]
venting homo-coupling of the ethynylene-linker 12. The
3-Acetyl-6-bromo-2-methylindole (4): Bromine (33.9 g, 10.9 mL,
UV/Vis data and photochromic properties of conjugate 1
and indolylfulgimide 2 in benzene have been determined
and discussed.
212 mmol) was added to a solution of 3-acetyl-2-methylindole (3,
18.4 g, 106 mmol) in glacial acetic acid (500 mL), and the resulting
suspension was stirred at room temp. for 72 h (TLC monitoring).
The reaction mixture was then poured into Na2S2O3 solution
(0.1 , 500 mL), and the precipitated crude product was filtered off
and redissolved in ethyl acetate (800 mL). The organic phase was
washed with concd. NaHCO3 solution (200 mL) and brine
(200 mL) and dried (MgSO4). The solvent was removed in vacuo
to give 4 as a yellow-white solid (18.2 g, 72.3 mmol, 68%), which
slowly turned red upon air contact. Compound 4 was used without
further purification; m.p. 179–181 °C; Rf = 0.69 (pentane/ethyl ace-
Experimental Section
General: Solvents were used in p.a. quality and were dried by stan-
dard procedures prior to use. NMP and DMF were purchased an-
hydrous from Fluka and were used without further purification.
The following compounds were prepared by literature procedures:
3-acetyl-2-methylindole (3), diethyl isopropylidenesuccinate (6)
1,3,5,7-tetraphenyladamantane, 1,3,5,7-tetrakis(4-iodophenyl)ada-
mantane, and 3,5,7-tris(4-iodophenyl)-1-{4-[2-(trimethylsilyl)eth-
ynyl]phenyl}adamantane (10a). All reactions were monitored by
analytical thin-layer chromatography (TLC, silica gel, Merck
60 F254 plates). Melting points were measured with a Büchi melt-
ing point determination apparatus and are uncorrected. IR spectra
were measured on a Nicolet Avatar 360 instrument as ATR (Atten-
uated Total Reflectance). The peaks are listed as wavenumbers
(cm–1) and the peak intensities were abbreviated as follows: vs =
1
3
tate, 2:1). H NMR (400 MHz, [D6]DMSO, 25 °C): δ = 7.97 (d, J
4
3
4
= 8.6 Hz, 1 H), 7.54 (d, J = 1.8 Hz, 1 H), 7.26 (dd, J = 8.3, J =
1.8 Hz, 1 H), 2.67 (s, 3 H), 2.49 (s, 3 H) ppm. 13C NMR (100 MHz,
[D6]DMSO, 25 °C): δ = 193.0, 145.0, 135.6, 126.0, 124.1, 122.3,
114.2, 113.7, 113.5, 30.8, 15.0 ppm. IR (ATR): ν = 3161 (m), 3121
˜
(m), 3088 (m), 2991 (m), 2909 (m), 1613 (s), 1571 (m), 1451 (m),
1412 (m), 1201 (w), 969 (w), 913 (w), 810 (m) cm–1. MS (EI, 70 °C):
m/z (%) = 251 (40) [M]+, 236 (100). HRMS: calcd. for C11H10BrNO
250.9946; found 250.9950.
1
very strong, s = strong, m = medium, w = weak, br = broad. H
3-Acetyl-6-bromo-1,2-dimethylindole (5): Indole
4
(19.5 g,
NMR and 13C NMR spectra were recorded on Bruker AC 200 or
AM 400 spectrometers. Solvents are mentioned for the particular
substances. The residual solvent protons or carbons were used as
internal standards, the chemical shifts are given in ppm relative to
77.4 mmol) was dissolved in DMF (400 mL). K2CO3 (16.0 g,
116 mmol) and dimethyl carbonate (20.9 g, 232 mmol) were added,
and the reaction mixture was heated at reflux for 5 h (TLC moni-
toring). The resulting solution was poured into water (1.93 L) and
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Photoswitch Linker Conjugate with Nitrile Anchor Groups
3
4
extracted with Et2O (3ϫ1.16 L). The organic layer was washed
with aqueous HCl (1 , 800 mL) and brine (800 mL), dried
(MgSO4), and concentrated in vacuo. The crude product was puri-
fied by recrystallization from MeCN to give 5 in 78% yield (16.1 g,
60.3 mmol) as a yellow solid, which was used without further puri-
7.10 (dd, J = 8.4, J = 1.6 Hz, 1 H), 3.65 (s, 3 H), 2.27 (s, 3 H),
2.16 (s, 3 H), 1.92 (s, 3 H), 1.88 (s, 3 H) ppm. 13C NMR (100 MHz,
[D6]DMSO, 25 °C): δ = 168.3, 168.0, 147.4, 139.6, 137.2, 134.3,
131.1, 126.6, 125.3, 121.6, 119.9, 114.2, 113.0, 112.0, 29.6, 23.6,
22.5, 21.8, 11.0 ppm. IR (ATR): ν = 3056 (s), 2976 (s), 2943 (m),
˜
1
fication; m.p. 103–105 °C. Rf = 0.48 (DCM). H NMR (400 MHz,
1680 (s), 1623 (m), 1550 (w), 1475 (m), 1428 (m), 1405 (m), 1366
CDCl3, 25 °C): δ = 7.84 (d, 3J = 8.3 Hz, 1 H), 7.45 (d, 4J = 2.0 Hz, (m), 1330 (m), 1250 (s), 1212 (m), 1182 (m), 1086 (w), 1054 (w),
3
4
1 H), 7.33 (dd, J = 8.3, J = 2.0 Hz, 1 H), 3.65 (s, 3 H), 2.74 (s, 3
965 (m), 902 (m), 818 (m), 801 (m) cm–1. MS (EI, 170 °C): m/z (%)
H), 2.63 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = = 405 (76) [M]+, 390 (100), 250 (20), 222 (72), 204 (36). HRMS
194.3, 145.6, 137.6, 125.3, 125.1, 122.1, 115.6, 114.4, 112.7, 31.7,
calcd. for C19H20BrNO4, 405.0576; found 405.0575.
29.8, 12.8 ppm. IR (ATR): ν = 3068 (w), 3049 (w), 2941 (w), 2923
˜
3-[1-(6-Bromo-1,2-dimethyl-1H-indol-3-yl)ethylidene]-4-(propan-2-
ylidene)-3,4-dihydrofuran-2,5-dione (9): N-Ethyl-NЈ-[3-(dimeth-
ylamino)propyl]carbodiimide (EDC, 598 mg, 3.86 mmol) was
added to a solution of (Z)-8 (1.05 g, 2.58 mmol) in DCM (100 mL).
The reaction mixture was stirred for 18 h at room temp. (TLC mon-
itoring). The solution was then diluted with DCM (100 mL) and
washed with aqueous HCl (0.1 , 75 mL). The organic layer was
washed with brine (75 mL), dried (MgSO4), and concentrated in
vacuo to give fulgide 9 in 91% yield (905 mg, 2.34 mmol, mixture
(w), 1637 (s), 1515 (s), 1471 (s), 1402 (s), 1213 (m), 1152 (m), 1032
(m), 935 (m), 804 (m), 746 (m) cm–1. MS (EI, 100 °C): m/z (%) =
265 (40) [M]+, 250 (100), 187 (25), 172 (70), 143 (20), 115 (20).
HRMS: calcd. for C12H12BrNO 265.0102; found 265.0103.
C12H12BrNO (266.13): C 54.16, H 4.54, N 5.26; found C 54.18, H
4.58, N 5.27.
4-(6-Bromo-1,2-dimethyl-1H-indol-3-yl)-3-(ethoxycarbonyl)-2-(pro-
pan-2-ylidene)pent-3-enoic Acid (7): Hexamethyldisilazane potas-
sium salt (KHMDS, 4.20 g, 21.0 mmol) was dissolved in THF
(250 mL) and the solution was cooled to 0 °C. A solution of diethyl
isopropylidenesuccinate (6) (4.67 g, 21.8 mmol) in THF (40 mL)
was added, and the resulting orange-yellow reaction mixture was
stirred for 30 min at 0 °C. A solution of 5 (4.00 g, 15.0 mmol) in
THF (40 mL) was then added over 30 min at 0 °C. The reaction
mixture was allowed slowly to reach room temp. and stirred for
18 h (TLC monitoring). Aqueous HCl (2 , 250 mL) was then
added and the reaction mixture was extracted with Et2O
(4ϫ125 mL). The combined organic layers were washed with brine
(125 mL), dried (MgSO4), and concentrated in vacuo. The crude
product was purified by recrystallization from MeCN to give (Z)-
7 in 36% yield [2.33 g, 5.38 mmol, Z/EՆ95:5 by 1H NMR] as a
yellow solid. Z isomer: M.p. 173–175 °C. Rf = 0.27 (DCM/MeCN,
10:1) 1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.39 (d, 3J = 1.6 Hz,
1
of Z/E isomers 93:7, H NMR); m.p. 196–198 °C (mixture). Rf =
0.58 (DCM). 1H NMR (400 MHz, CDCl3, 25 °C): Z isomer: δ =
4
3
3
7.46 (d, J = 1.3 Hz, 1 H), 7.40 (d, J = 8.5 Hz, 1 H), 7.22 (dd, J
4
= 8.5, J = 1.4 Hz, 1 H), 3.70 (s, 3 H), 2.46 (s, 3 H), 2.36 (s, 3 H),
2.35 (s, 3 H), 2.03 (s, 3 H) ppm. E isomer: δ = 3.65 (s, 3 H), 2.77
(s, 3 H), 2.20 (s, 3 H), 2.19 (s, 3 H), 0.94 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): Z isomer: δ = 164.0, 161.3, 152.3, 147.4,
141.4, 138.1, 125.0, 123.8, 122.1, 120.7, 120.2, 115.2, 112.7, 112.4,
30.3, 27.3, 24.9, 22.5, 12.3 ppm. E isomer: δ = 30.2, 26.4, 23.7, 22.9,
12.3 ppm. IR (ATR): ν = 3067 (w), 2927 (m), 2856 (m), 1805 (s),
˜
1753 (s), 1589 (m), 1474 (m), 1440 (m), 1404 (m), 1227 (s), 1134
(m), 958 (m), 924 (s) cm–1. MS (EI, 160 °C): m/z (%) = 387 (40)
[M]+, 344 (20), 316 (20), 224 (50), 143 (30), 56 (100). HRMS: calcd.
for C19H18BrNO3 387.0470; found 387.0471. C19H18BrNO3
(388.26): C 58.78, H 4.67, N 3.61; found, C 58.72, H 4.69, N 3.54.
3
3
4
1 H), 7.25 (d, J = 8.4 Hz, 1 H), 7.15 (dd, J = 8.4, J = 1.7 Hz, 1
H), 3.93–3.76 (m, 2 H), 3.63 (s, 3 H), 2.30 (s, 3 H), 2.26 (s, 3 H),
2.06 (s, 3 H), 1.97 (s, 3 H), 0.73 (t, 3J = 7.1 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3, 25 °C): δ = 170.5, 169.4, 151.9, 143.8,
137.6, 133.7, 129.5, 125.7, 125.1, 122.7, 120.0, 114.6, 114.5, 111.9,
3-[1-(6-Bromo-1,2-dimethyl-1H-indol-3-yl)ethylidene]-1-methyl-4-
(propan-2-ylidene)pyrrolidine-2,5-dione (2): NaHCO3 (648 mg,
7.72 mmol) and methylamine hydrochloride (521 mg, 7.72 mmol)
were added to a solution of fulgide 9 (1.50 g, 3.86 mmol, Z/E mix-
ture) in 1,4-dioxane (200 mL) and water (50 mL), and the solution
was stirred for 5 h at room temp. (TLC monitoring). After addition
of ethyl acetate (100 mL) the organic layer was separated and
washed with aqueous HCl (1 , 75 mL). The aqueous layer was
extracted with ethyl acetate (100 mL) and the combined organic
layers were washed with brine (75 mL), dried (MgSO4), and con-
centrated in vacuo to give the crude product as a brown solid in
95 % yield (1.53 g, 3.65 mmol); mixture of isomers, ratio I:II =
60.8, 29.8, 24.0, 22.8, 22.5, 13.7, 11.3 ppm. IR (ATR): ν = 3064
˜
(m), 2979 (m), 2936 (m), 1687 (s), 1619 (m), 1551 (w), 1515 (w),
1474 (s), 1405 (m), 1231 (s), 1207 (s), 1178 (s), 1054 (m), 966 (m),
902 (m), 865 (w), 802 (m), 748 (w) cm–1. MS (EI, 240 °C): m/z (%)
= 435 (100) [M + H]+, 418 (76), 388 (12), 344 (24), 249 (20), 223
(40), 204 (30), 194 (24), 168 (16). HRMS: calcd. for C21H24BrNO4
433.0889; found 433.0888. C21H24BrNO4 (434.32): C 58.07, H 5.57,
N 3.22; found C 58.43, H 5.57, N 3.35.
1
66:33, H NMR spectroscopy.
2-[1-(6-Bromo-1,2-dimethyl-1H-indol-3-yl)ethylidene]-3-isopropyl-
idenesuccinic Acid (8): Solid potassium tert-butoxide (7.43 g,
66.2 mmol) was added to a solution of (Z)-7 (5.75 g, 13.2 mmol)
in tert-butanol (150 mL). The mixture was stirred at 80 °C for 2 h
(TLC monitoring). The solvent was then removed in vacuo and the
residue was redissolved in ethanol (50 mL). A solution of potas-
sium hydroxide (186 g, 331 mmol) in water (50 mL) was added, and
the mixture was heated at reflux for 2 h (TLC monitoring). The
reaction mixture was then poured into aqueous HCl (2 )/ice
(200 mL). The aqueous layer was saturated with neat NaCl and
extracted with ethyl acetate (3ϫ100 mL). The organic layer was
washed with brine (100 mL), dried (MgSO4), and concentrated in
vacuo to give the crude diacid (Z)-8 (4.64 g, 11.4 mmol, 86%) as a
brown solid, which was used without further purification, m.p.
For the following reaction step, the crude product (419 mg,
1.00 mmol) was dissolved in benzene (40 mL) and heated to 60 °C.
At this temperature ZnBr2 (225 mg, 1.00 mmol) and HMDS
(240 mg, 1.50 mmol) were added, whereupon a voluminous precipi-
tate was observed. ZnCl2 (1.00 mmol, 1  in Et2O) was then added,
and the precipitate partially redissolved. The reaction mixture was
stirred for 19 h at 60 °C (TLC monitoring). Afterwards the mixture
was allowed to cool to room temp. and DCM (100 mL) was added.
The reaction solution was then washed with brine (75 mL), dried
(MgSO4), and concentrated in vacuo. The crude product was puri-
fied by flash chromatography on silica (DCM/MeCN, 100:1) to give
2 as a yellow solid in 67% yield (279 mg, 697 µmol, E/Z mixture
1
of isomers 64:36, H NMR) calculated over two steps. For X-ray
203 °C. Rf = 0.77 (MeOH). 1H NMR (400 MHz, [D6]DMSO, analysis compound (E)-2 could be separated by recrystallisation
4
3
25 °C): δ = 7.64 (d, J = 1.6 Hz, 1 H), 7.24 (d, J = 8.4 Hz, 1 H),
from DCM as yellow prisms; m.p. 75–80 °C (mixture). Rf = 0.32
Eur. J. Org. Chem. 2009, 2088–2095
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2093

K. Rück-Braun et al.
FULL PAPER
1
(DCM/MeOH, 10:1). H NMR (400 MHz, CDCl3, 25 °C): E iso-
phenyl)-1,3-bis{4-[2-(trimethylsilyl)ethynyl]phenyl}adamantane
(10b); (750 mg, 10a/10b = 1:3), Pd(PPh3)4 (94.8 mg, 82.0 µmol),
and zinc cyanide (289 mg, 2.46 mmol). The reaction tube was evac-
uated and refilled with nitrogen (3ϫ), and DMF (1 mL) was then
added. The yellow suspension was stirred for 28 h at 65 °C, diluted
with ethyl acetate (40 mL), filtered, and washed with water
mer: δ = 7.42 (d, 4J = 1.6 Hz, 1 H), 7.26 (d, 3J = 8.4 Hz, 1 H), 7.21
3
4
(dd, J = 8.4, J = 1.6 Hz, 1 H), 3.63 (s, 3 H), 3.11 (s, 3 H), 2.74
(s, 3 H), 2.17 (s, 3 H), 2.13 (s, 3 H), 0.90 (s, 3 H) ppm. Z isomer: δ
4
3
= 7.43 (d, J = 1.6 Hz, 1 H), 7.35 (d, J = 8.4 Hz, 1 H), 7.17 (dd,
4
3J = 8.4, J = 1.6 Hz, 1 H), 3.69 (s, 3 H), 2.92 (s, 3 H), 2.45 (s, 3
H), 2.34 (s, 3 H), 2.26 (s, 3 H), 1.99 (s, 3 H) ppm. 13C NMR (3 ϫ 50 mL) and brine (50 mL). The organic layer was dried
(100 MHz, CDCl3, 25 °C): E isomer: δ = 169.4, 168.9, 147.7, 142.5,
138.0, 134.9, 124.5, 124.0, 123.9, 123.5, 120.9, 117.4, 115.3, 112.3,
30.1, 26.2, 23.9, 22.8, 22.1, 12.1 ppm. Z isomer: δ = 169.0, 166.4,
146.5, 140.7, 139.5, 137.8, 125.3, 125.0, 124.7, 123.2, 120.5, 114.6,
(MgSO4) and the solvents were evaporated to dryness. Purification
by flash chromatography on silica (pentane/ethyl acetate, 8:1) gave
pure 11 as a white solid (101 mg, 165 µmol, 80%); m.p. Ͼ 290 °C.
Rf = 0.13 (pentane/ethyl acetate, 8:1). 1H NMR (400 MHz, CDCl3,
3
3
112.6, 112.4, 30.2, 27.1, 25.0, 23.7, 21.7, 12.0 ppm. IR (ATR): ν =
25 °C): δ = 7.67 (d, J = 8.6 Hz, 6 H), 7.57 (d, J = 8.6 Hz, 6 H),
˜
3
3
3435 (w), 2970 (w), 2929 (w), 2867 (w), 1765 (w), 1753 (w), 1699
7.47 (d, J = 8.4 Hz, 2 H), 7.37 (d, J = 8.4 Hz, 2 H), 2.15 (s, 12
(s), 1592 (m), 1547 (m), 1436 (m), 1384 (m), 1277 (m), 1018 H), 0.25 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ =
(w) cm–1. MS (EI, 150 °C): m/z (%) = 402 (100) [M + 2H]+, 358 153.5, 148.3, 132.6, 132.4, 126.0, 124.8, 121.8, 118.8, 110.7, 104.7,
(20), 330 (24), 300 (30), 265 (24), 250 (60), 223 (100), 84 (74).
HRMS: calcd. for C20H21BrN2O2 400.0787; found 400.0787.
C20H21BrN2O2 (400.08), C 59.86, H 5.27, N 6.98; found, C 59.82,
H 5.29, N 6.79.
94.6, 46.4, 46.4, 39.8, 39.3, 0.1 ppm. IR (ATR): ν = 3062 (w), 3041
˜
(w), 2956 (m), 2931 (m), 2902 (m), 2854 (w), 2227 (s), 2157 (m),
1706 (w), 1607 (m), 1505 (s), 1448 (w), 1405 (m), 1361 (m), 1262
(w), 1249 (m), 1220 (w), 1175 (w), 1116 (w), 1018 (m), 865 (vs), 839
(vs), 804 (m), 792 (m), 760 (m), 700 (w) cm–1. MS (EI, 300 °C):
m/z (%) = 611 (41) [M]+, 597 (48), 596 (100). HRMS: calcd. for
C42H37N3Si 611.2756; found 611.2755.
(C)-3-[1-(6-Bromo-1,2-dimethyl-1H-indol-3-yl)ethylidene]-1-methyl-
4-(propan-2-ylidene)pyrrolidine-2,5-dione [(C)-2]: A solution of 2
(E/Z mixture, 120 mg, 0.33 mmol) in DCM (80 mL) was irradiated
in a 100 mL round-bottomed flask for 12 h with a high-pressure
mercury lamp (200 W HBO) and a 365 nm interference filter. The
deep blue solution was then concentrated in vacuo. The isomers
were separated in the dark by flash chromatography on silica gel
with DCM as eluent to give the C isomer (65 mg, 0.16 mmol, 54%)
as a deep blue solid, together with an E/Z mixture [E/Z = 72:28
(1H NMR), 55 mg, 0.14 mmol, 46%] as a yellow solid. C isomer:
M.p. 136–138 °C; Rf 0.46 (DCM/MeCN, 100:1). 1H NMR
(200 MHz, CDCl3, 25 °C): δ = 7.35 (d, 3J = 8.2 Hz, 1 H), 6.81 (dd,
4,4Ј,4ЈЈ-{7-[4-(Ethynyl)phenyl]adamantane-1,3,5-triyl}tribenzonitrile
(12): TBAF (1  in THF, 280 µmol) was added to a solution of
nitrile 11 (70.0 mg, 114 µmol) in THF (9 mL). The solution was
stirred for 12 h at room temp. After complete consumption of the
starting material (TLC monitoring) the mixture was treated with
water (15 mL) and extracted with DCM (3ϫ20 mL). The organic
layer was then dried (MgSO4), and the solvents were evaporated to
dryness. The crude product was purified by flash chromatography
on silica (hexane/DCM, 1:1) to give 12 as a white solid (56.1 mg,
104 µmol, 91%); m.p. 293 °C. Rf = 0.24 (hexane/DCM, 1:1). 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 7.66 (d, 3J = 8.4 Hz, 6 H),
4
4
3J = 8.2, J = 1.7 Hz, 1 H), 6.64 (d, J = 1.7 Hz, 1 H), 2.96 (s, 3
H), 2.86 (s, 3 H), 2.36 (s, 3 H), 1.74 (s, 3 H), 1.24 (s, 3 H), 1.13 (s,
3 H) ppm. 13C NMR (50 MHz, CDCl3, 25 °C): δ = 170.3, 169.5,
157.7, 148.2, 137.9, 136.9, 126.6, 125.8, 123.7, 120.9, 115.9, 111.0,
3
3
7.57 (d, 3J = 8.4 Hz, 6 H), 7.50 (d, J = 8.4 Hz, 2 H), 7.41 (d, J =
8.4 Hz, 2 H), 3.07 (s, 1 H), 2.17–2.16 (m, 12 H) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ = 153.5, 148.7, 132.6, 132.5, 126.1,
125.0, 120.7, 118.9, 110.7, 83.3, 77.6, 46.4, 46.4, 39.8, 39.3 ppm. IR
73.3, 40.0, 31.7, 23.5, 20.0, 18.9, 15.7, 13.8 ppm. IR (ATR): ν =
˜
3418 (w), 2982 (w), 2938 (w), 1742 (m), 1690 (s), 1601 (w), 1425
(m), 1369 (m), 1267 (w), 1019 (w) cm–1. MS (EI, 130 °C): m/z (%)
= 400 (84) [M]+, 385 (20), 328 (24), 300 (28), 248 (20), 223 (100).
HR-MS: calcd. for C20H21BrN2O2 400.0787; found 400.0784.
(ATR): ν = 3060 (w), 3032 (w), 2958 (m), 2931 (m), 2901 (m), 2855
˜
(m), 2673 (w), 2549 (w), 2155 (w), 1686 (vs), 1608 (m), 1571 (w),
1504 (w), 1422 (m), 1358 (w), 1320 (w), 1287 (m), 1250 (m), 1190
(m), 1122 (w), 1109 (w), 1016 (m), 864 (m), 853 (m), 843 (m), 761
(m), 705 (w) cm–1. MS (EI, 300 °C): m/z (%) = 539 (87) [M]+, 515
(23), 436 (19), 382 (22), 368 (53), 281 (40), 210 (43), 116 (53), 97
(53), 83 (60), 69 (72), 57 (100). HRMS: calcd. for C39H29N3
539.2361; found 539.2369.
(E)-3-[1-(6-Bromo-1,2-dimethyl-1H-indol-3-yl)ethylidene]-1-methyl-
4-(propan-2-ylidene)pyrrolidine-2,5-dione [(E)-2]: A solution of (C)-
2 (50 mg, 125 µmol) in DCM (80 mL) was irradiated in a 100 mL
round-bottomed flask for 4 h with a xenon lamp (1000 W, XBO)
and a 545 nm interference filter. The solvent was then removed in
vacuo to give the E isomer quantitatively as a pale yellow solid
(50 mg, 125 µmol). E isomer: M.p. 143–147 °C. Rf = 0.32 (DCM/
1-Methyl-6-(phenylethynyl)-1H-indole (15): A dried and nitrogen-
purged reaction tube was loaded with 5-bromo-1-methyl-1H-indole
(13, 200 mg, 952 µmol), Pd(PhCN)2Cl2 (10.9 mg, 28.6 µmol), (tri-
tert-butylphosphonium)tetrafluoroborate (16.6 mg, 57.2 µmol),
and copper(I) iodide (3.62 mg, 19.0 µmol) and was then evacuated
and refilled with nitrogen (3ϫ). Dioxane (4 mL), diisopropylamine
(115 mg, 1.14 mmol), and phenylacetylene (14, 116 mg, 1.14 mmol)
were then added by syringe, and the brown suspension was stirred
for 18 h at room temp. After complete consumption of the starting
material (TLC monitoring) the brown solution was diluted with
ethyl acetate (50 mL) and filtered, and the solvents were evaporated
to dryness. Purification by flash chromatography on silica (pentane/
ethyl acetate, 40:1) gave 15 as a yellow solid (206 mg, 891 µmol,
1
4
MeOH, 10:1). H NMR (400 MHz, CDCl3, 25 °C): δ = 7.42 (d, J
3
3
4
= 1.6 Hz, 1 H), 7.25 (d, J = 8.4 Hz, 1 H), 7.19 (dd, J = 8.4, J =
1.6 Hz, 1 H), 3.62 (s, 3 H), 3.10 (s, 3 H), 2.74 (s, 3 H), 2.16 (s, 3
H), 2.13 (s, 3 H), 0.89 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3,
25 °C): δ = 169.3, 168.9, 147.7, 142.4, 138.0, 134.9, 124.4, 123.9,
123.8, 123.5, 120.9, 117.3, 115.2, 112.2, 30.0, 26.2, 23.8, 22.7, 22.0,
12.1 ppm. IR (ATR): ν = 3509 (w), 2970 (w), 2938 (w), 2907 (w),
˜
1742 (m), 1689 (m), 1601 (w), 1473 (w), 1427 (m), 1369 (m), 1270
(m), 1018 (m) cm–1. MS (EI, 165 °C): m/z (%) = 400 (90) [M]+,
328 (28), 300 (30), 223 (100). HR-MS: calcd. for C20H21BrN2O2
400.0787; found 400.0788.
1
94%); m.p. 118–120 °C. Rf = 0.29 (pentane/ethyl acetate, 40:1). H
4,4Ј,4ЈЈ-(7-{4-[2-(Trimethylsilyl)ethynyl]phenyl}adamantane-1,3,5-
triyl)tribenzonitrile (11): A nitrogen-purged reaction tube was
loaded with a crude mixture of 3,5,7-tris(4-iodophenyl)-1-{4-[2-(tri-
methylsilyl)ethynyl]phenyl}adamantane (10a) and 5,7-bis(4-iodo-
NMR (400 MHz, CDCl3, 25 °C): δ = 7.86 (d, 4J = 1.4 Hz, 1 H),
7.56 (dd, 3J = 8.4, 4J = 1.8 Hz, 2 H), 7.42 (dd, 3J = 8.4, 4J = 1.5 Hz,
3
3
1 H), 7.37–7.28 (m, 4 H), 7.08 (d, J = 3.1 Hz, 1 H), 6.50 (dd, J
= 3.1, J = 0.8 Hz, 1 H), 3.80 (s, 3 H) ppm. 13C NMR (100 MHz,
4
2094
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 2088–2095

Photoswitch Linker Conjugate with Nitrile Anchor Groups
CDCl3, 25 °C): δ = 136.5, 131.6, 129.9, 128.5, 128.4, 127.8, 125.3,
125.0, 124.2, 113.9, 109.4, 101.5, 91.3, 87.2, 33.1 ppm. IR (ATR):
[1]
[2]
V. Balzani, M. Venturi, A. Credi, Molecular Devices and Ma-
chines, Wiley-VCH, Weinheim, 2003.
ν = 3057 (w), 2928 (w), 2207 (w), 1596 (m), 1494 (s), 1443 (s), 1423
˜
(w), 1364 (m), 1336 (w), 1273 (w), 1242 (w), 1153 (w), 1070 (w),
1029 (w), 914 (w), 884 (w), 830 (w), 802 (m), 755 (s), 720 (m), 691
(s) cm–1. MS (EI, 160 °C): m/z (%) = 232 (18) [M + H]+, 231 (100)
[M]+, 230 (17), 202 (7), 189 (6), 116 (9). HRMS: calcd. for C17H13N
231.1048; found 231.1052.
a) M. Alemani, M. V. Peters, S. Hecht, K.-H. Rieder, F. Mo-
resco, L. Grill, J. Am. Chem. Soc. 2006, 128, 14446–14447; b)
P. Dietrich, F. Michalik, R. Schmidt, C. Gahl, G. Mao, M.
Breusing, M. Raschke, B. Priewisch, T. Elsässer, R. Mendel-
sohn, M. Weinelt, K. Rück-Braun, Appl. Phys. A: Mater. Sci.
Process. 2008, 93, 285–292.
4,4Ј,4ЈЈ-(7-{4-[(1,2-Dimethyl-3-{1-[1-methyl-2,5-dioxo-4-(propan-2-
ylidene)pyrrolidin-3-ylidene]ethyl}-1H-indol-6-yl)ethynyl]phenyl}-
adamantane-1,3,5-triyl)tribenzonitrile (1): A dried and nitrogen-
purged reaction tube was loaded with an E/Z mixture of indolylful-
gimide 2 (53.5 mg, 133 µmol), tripod 12 (60.0 mg, 111 µmol),
Pd(PhCN)2Cl2 (1.27 mg, 3.33 µmol), (tri-tert-butylphosphonium)
tetrafluoroborate (1.93 mg, 6.66 µmol), and copper(I) iodide
(870 µg, 4.57 µmol) and was then evacuated and refilled with nitro-
gen (3 ϫ). Dioxane (1 mL) and diisopropylamine (13.4 mg,
133 µmol) were added by syringe, and the brown suspension was
stirred for 20 h at room temp. The brown solution was diluted with
ethyl acetate (30 mL) and filtered, and the solvents were evaporated
to dryness. Purification by flash chromatography on silica (DCM/
MeCN, 100:1) afforded 1 as a slightly green solid [35.0 mg,
[3]
a) E. Galoppini, W. Guo, W. Zhang, P. G. Hoertz, P. Qu, G. J.
Meyer, J. Am. Chem. Soc. 2002, 124, 7801–7811; b) Y. Yao,
J. M. Tour, J. Org. Chem. 1999, 64, 1968–1971; c) L. Wei, K.
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1
40.7 µmol, 36%, E/Z mixture of isomers (74:26), H NMR]; m.p.
Ͼ 220 °C (decomposition). Rf = 0.09 (DCM/MeCN, 100:1). 1H
NMR (400 MHz, CDCl3, 25 °C): E isomer: δ = 7.67 (d, 3J = 8.7 Hz,
3
6 H), 7.59–7.54 (m, 8 H), 7.48 (s, 1 H), 7.43 (d, J = 8.6 Hz, 2 H),
3
7.35 (d, J = 8.2 Hz, 1 H), 7.29–7.27 (m, 1 H), 3.68 (s, 3 H), 3.11
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(s, 3 H), 2.77 (s, 3 H), 2.19–2.16 (m, 6 H from fulgimide, 12 H from
adamantane), 0.90 (s, 3 H) ppm. Z isomer: δ = 3.73 (s, 3 H), 2.93
(s, 3 H), 2.46 (s, 3 H), 2.38 (s, 3 H), 2.30 (s, 3 H), 2.00 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3, 25 °C): E isomer: δ = 169.4, 168.9,
153.6, 147.7, 147.7, 142.5, 136.8, 136.1, 132.6, 131.9, 126.0, 125.7,
125.0, 124.1, 123.9, 123.8, 122.4, 119.7, 118.8, 117.8, 115.8, 112.6,
110.8, 91.3, 87.9, 46.6, 46.5, 39.9, 39.3, 30.0, 26.1, 23.9, 22.9, 22.1,
12.2 ppm. Z isomer: δ = 30.2, 27.1, 25.0, 23.7, 21.7, 12.1 ppm. IR
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1389.
(ATR): ν = 3509 (w), 3060 (w), 2929 (m), 2853 (w), 2226 (s), 1741
˜
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(w), 1692 (vs), 1606 (s), 1506 (m), 1376 (m), 1364 (m), 1175 (m),
1018 (m), 835 (m), 793 (w), 753 (w) cm–1. MS (EI, 300 °C): m/z (%)
= 860 (12) [M + H]+, 859 (19) [M]+, 552 (15), 368 (20), 277 (43),
227 (80), 134 (62), 91 (100), 57 (59). HRMS: calcd. for C59H49N5O2
859.3886; found 859.3869.
Supporting Information (see also the footnote on the first page of
this article): 1H and 13C NMR spectra of all synthesized com-
pounds and spectroscopic data of compounds 1, 2 and 9.
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lographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgments
This work was funded by the Volkswagen Foundation, the Deut-
sche Forschungsgemeinschaft (DFG) (SFB 658 and GK 352), and
the Fonds der Chemischen Industrie.
Received: December 2, 2008
Published Online: March 22, 2009
Eur. J. Org. Chem. 2009, 2088–2095
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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