Dihydroazulene photoswitches: The first synthetic protocol for functionalizing the seven-membered ring

Article abstract of DOI:10.1002/ejoc.200900297

The first synthetic protocol for functionalizing the dihydroazulene (DHA) photoswitch in its seven-membered ring has been developed. This protocol is based on regioselective bromination, followed by regioselective elimination of HBr, and finally a palladi

Full text of DOI:10.1002/ejoc.200900297

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200900297
Dihydroazulene Photoswitches: The First Synthetic Protocol for
Functionalizing the Seven-Membered Ring
Michael Åxman Petersen,[a] Søren Lindbæk Broman,[a] Anders Kadziola,[a] Kristine Kilså,[a]
and Mogens Brøndsted Nielsen*[a]
Keywords: Alkynes / Cross-coupling / Dihydroazulene / Photoswitches / Vinylheptafulvene / Photochemistry
The first synthetic protocol for functionalizing the dihy-
droazulene (DHA) photoswitch in its seven-membered ring
has been developed. This protocol is based on regioselective
bromination, followed by regioselective elimination of HBr,
and finally a palladium-catalyzed cross-coupling reaction
with a terminal alkyne. The position of functionalization (C-
7) was confirmed by X-ray crystal structure analysis. Light-
induced ring opening of this compound to its vinylheptaful-
vene (VHF) isomer followed by thermal ring closure provides
a mixture of two DHA regioisomers in a ratio that depends
on the wavelength of irradiation and solvent polarity.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
pylium, but otherwise in accordance to the originally devel-
oped strategy, involving, however, tedious separation of 3
from other formed regioisomers. Unfortunately, the elimi-
nation reaction as presented in Scheme 2 only furnished the
DHA 4 in trace amounts, as judged from TLC and mass
spectrometric analyses.
Introduction
Molecular switches are systems that possess at least two
reversibly interconvertible molecular states and are in par-
ticular important within the field of molecular electronics.[1]
The dihydroazulene/vinylheptafulvene (DHA/VHF) system
represents one such switch: DHA undergoes a photochemi-
cally induced ring-opening reaction to VHF that in turn
undergoes a thermally assisted ring closure back to
DHA.[2,3] The pioneering work by Daub and co-workers[2]
has allowed ready functionalization of the five-membered
ring of DHA by an aryl group and the DHA/VHF system
1/2 (Scheme 1) has been investigated in detail. However,
functionalization of the seven-membered ring has not yet
been accomplished. For exploitation of the DHA/VHF sys-
tem as a light-controlled wire for molecular electronics, it is
highly desirable to attach two handles to the system, one in
each ring, in order to allow it to span two electrodes.
Scheme 2.
Instead of forming the DHA in the final step, we turned
to a strategy involving conversion of already formed DHA.
We have recently reported that bromination of 1 occurs se-
lectively at the 7,8-positions in quantitative yield to provide
the dibromide 5 (confirmed by X-ray crystal structure
analysis, Figure 1) as a pair of enantiomers.[4] In fact, treat-
ment with two molar equivalents of bromine selectively fur-
nished the tetrabromide 6, while treatment with three (or
more) equivalents furnished the hexabromide 7 as con-
firmed by X-ray crystal structure analysis (Figure 1). Treat-
ing dibromide 5 with ca. 3 molar equivalents of lithium ace-
tylide generated from trimethylsilylacetylene and butyllith-
ium produced the 7-bromo DHA 8. Highest yields (50–
60%) were obtained by adding the base in three subsequent
steps. Yields were judged from 1H NMR spectroscopic
analysis of the crude reaction mixtures. Isolation of 8 is
possible by column chromatography, but is unfortunately
Scheme 1.
Results and Discussion
In an initial approach, we synthesized the DHA precur-
sor 3 (Scheme 2) starting from an alkyne-functionalized tro-
[a] Department of Chemistry, University of Copenhagen,
Universitetsparken 5, 2100 Copenhagen Ø, Denmark
E-mail: mbn@kiku.dk
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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M. B. Nielsen et al.
SHORT COMMUNICATION
accompanied by substantial decomposition. Both 1 as well
Next, we subjected crude DHA 8 to a Sonogashira cross-
as 2-phenylazulene-1-carbonitrile were formed as by-prod- coupling reaction[5] with triisopropylsilylacetylene. First, 5
ucts. Using 1 molar equivalent of the acetylide only pro- was treated with LiN(SiMe3)2 in THF at room temp. for 2 h
vided the product 8 in a yield of ca. 20%. Employing in- to produce 8 (ca. 90%), and a subsequent cross-coupling
stead 1 molar equivalent of LiN(SiMe3)2 gave, however, 8 reaction provided the acetylenic DHA 10. The overall yield
in a yield of Ͼ90%. Bases such as pyridine, DBU, Et3N or of the conversion of 5 to 10 was 45% after column chroma-
Hünig’s base were all unable to generate the desired prod- tographic work-up. Single crystals of 10 were grown from
uct, while 2.5 molar equivalents of KOtBu (freshly sub- pentane and subjected to X-ray crystal structure analysis
limed) furnished 8 in a yield of 40–50%. Using a larger (Figure 1), confirming the proposed substitution pattern.
excess of KOtBu (3.6 molar equiv.) generated a mixture of The structure reveals that the seven-membered ring adopts
azulenes from which the 7-bromoazulene 9 was isolated a boat conformation, in agreement with previously reported
pure (9%) (Scheme 3). The X-ray crystal structure of 9 is structures.[3a] The alkyne unit is in the same plane as C6–
shown in Figure 1 together with the related 1,3-dicyano-2- C7–C8–C8a, which is twisted by 56.1° relative to the plane
phenylazulene, a decomposition product formed from solid defined by C2–C3–C3a–C4–C5. In consequence, the alkyne
5 upon standing.
unit is not in conjugation with the major part of the DHA
Figure 1. X-ray crystal structures of compounds 5 (a), 7 (b), 9 (c), 2-phenylazulene-1,3-dicarbonitrile (d), and 10 (e).
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Dihydroazulene Photoswitches
Scheme 3.
unit, which is nicely reflected in the fact that 10 exhibits a tion is readily explained by the fact that moving the alkyne
longest-wavelength absorption maximum of 355 nm, which unit to the 6-position renders it part of the larger conju-
is similar to that of DHA 1.
gated system of the boat-shaped DHA. The different ab-
The new DHA derivative 10 was subjected to photo- sorption characteristics open up for control of the ratio of
switching studies. Irradiating a sample in MeCN with light the regioisomers simply by changing the wavelength of irra-
of 355 nm resulted in conversion of the DHA unit to a diation. Thus, by irradiation with 430-nm light, it is possible
VHF unit exhibiting a characteristic absorption at 477 nm to change the ratio of regioisomers (10/13) to ca. 5.5:4.5
(Figure 2). The conversion was complete within the same (after three cycles). In principle, repeated cycles should ulti-
time needed to convert DHA 1 into VHF 2 (90 s under the mately change the ratio completely in favor of 10. The isom-
current conditions), which indicates that the quantum yield erization reaction is strongly solvent dependent. Thus, sub-
for converting 10 is similar to that of 1 (φDHA–VHF ≈ 0.55[6]). jecting 10 to irradiation/heat cycles in cyclohexane does not
Thermal VHF–DHA conversion proceeded smoothly, but result in formation of 13 but regeneration of 10 itself.
interestingly, the resulting DHA absorption is red-shifted to
376 nm. An Arrhenius plot provides an activation energy
for the thermal back reaction of Ea = 93.8 kJmol–1 and an
preexponential factor of A = 4.66ϫ1011 s–1, while those of
2 were previously reported to Ea = 84.9 kJmol–1 and A =
3.0ϫ1010 s–1.[6] By extrapolation, the rate constant and
half-life at 25 °C are found to k = 1.7ϫ10–5 s–1 and t1/2
=
670 min, while the values for 2 are k = 7.0ϫ10–5 s–1 and
t1/2 = 165 min.[6] Thus, the presence of the ethynyl group
slows down the back reaction relative to that of 2. The red-
shifted DHA absorption indicates that a new DHA is
formed. We therefore performed the photolysis and thermal
reactions in CD3CN and analyzed the products by 1H
NMR spectroscopy. It transpires that the two regioisomeric
VHFs 11 and 12 (Scheme 4) are formed during photolysis
of 10 as judged by two sets of iPr3 resonances and overlap-
ping resonances in the aromatic region. These two VHFs
are thermally converted into DHAs 10 and 13 in a ratio of
Figure 2. a) Irradiation of compound 10 in MeCN (3.0 mL,
3.6ϫ10–5 ) with light (353 nm) 0–90 s, 10-s steps. b) Thermal
back-reaction monitored at 70 °C, 2-min steps. The DHA absorp-
tion red-shifts after one cycle.
1
1:2. The two DHAs are readily distuingished by H NMR
spectroscopy, and a COSY spectrum confirmed substitu-
tion at the C-6 position of 13. Repeated ring-opening/clo-
sure cycles do not change the ratio between the regioiso-
In conclusion, we have developed the first procedure for
mers. The absorption maximum of 13 is estimated to ca. functionalizing dihydroazulenes in the seven-membered
381 nm by subtracting the absorption spectrum of 10 from ring. The reaction proceeds regioselectively to provide the
that of the mixture of 10 and 13. This red-shifted absorp- 7-substituted DHA, but this compound can be converted
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M. B. Nielsen et al.
SHORT COMMUNICATION
for 5 h, whereupon it was diluted with Et2O (100 mL) and washed
with saturated aqueous NH4Cl (2ϫ100 mL). The organic phase
was dried with MgSO4, filtered, and the solvents evaporated in
vacuo. Purification by column chromatography (SiO2, 40%
CH2Cl2/heptane) yielded 10 (196 mg, 45%) as a yellow to green
solid. Crystals were grown from pentane. M.p. 126–127 °C. 1H
NMR (300 MHz, CDCl3): δ = 7.72–7.76 (m, 2 H), 7.44–7.51 (m, 3
H), 6.88 (s, 1 H), 6.51–6.63 (m, 2 H), 6.31 (d, J = 5.9 Hz, 1 H),
6.16 (d, J = 4.6 Hz, 1 H), 3.80 (dd, J = 4.6, 1.5 Hz, 1 H), 1.09 (s,
21 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.3, 140.3, 132.7,
131.5, 130.5, 129.5, 126.6, 124.9, 123.3, 120.7, 115.1, 112.7, 105.3,
91.5, 51.0, 45.0, 18.9, 11.5 ppm; two overlapping signals.
C29H32N2Si (436.67): calcd. C 79.77, H 7.39, N 6.42; found C
79.66, H 7.49, N 6.33. HR-MS (ES): m/z = 437.2385 [MH+].
C29H33N2Si: m/z = 437.2413.
CCDC-718205 (for 7), 718204 (for 2-phenylazulene-1,3-dicar-
bonitrile), 718206 (for 9), 718207 (for 10) contain the supplemen-
tary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Scheme 4.
Supporting Information (see also the footnote on the first page of
this article): NMR spectra of 3, 10, and 13; spectral evolution upon
irradiation of 10 in comparison to 1; detailed photolysis experi-
ments on 10; frontier orbitals of 10–13 devoid of silyl substituents.
partly to the 6-substituted isomer by irradiation followed
by thermal ring closure in the polar solvent acetonitrile. As
the two regioisomers exhibit different absorption maxima,
their ratio can be controlled by the wavelength of irradia-
tion. Isomerization can, however, be completely avoided by
using a nonpolar solvent. Access to DHA derivatives func-
tionalized in both the five- and seven-membered rings is
important for the future exploitation of the DHA/VHF
switch in for example molecular electronics devices.
Acknowledgments
The Danish Research Agency is gratefully acknowledged for sup-
porting this work (272-08-0540).
[1] a) V. Balzani, M. Gómez-López, J. F. Stoddart, Acc. Chem.
Res. 1998, 31, 405–414; b) Molecular Switches (Ed.: B. L. Fer-
inga), Wiley-VCH, Weinheim, Germany, 2001; c) H. Tian, S. J.
Yang, Chem. Soc. Rev. 2004, 33, 85–97.
[2] a) J. Daub, T. Knöchel, A. Mannschreck, Angew. Chem. 1984,
96, 980–981; Angew. Chem. Int. Ed. Engl. 1984, 23, 960–961;
b) J. Daub, S. Gierisch, U. Klement, T. Knöchel, G. Maas, U.
Seitz, Chem. Ber. 1986, 119, 2631–2646; c) S. Gierisch, J. Daub,
Chem. Ber. 1989, 122, 69–75; d) S. Gierisch, W. Bauer, T. Burg-
emeister, J. Daub, Chem. Ber. 1989, 122, 2341–2349; e) J. Daub,
S. Gierisch, J. Salbeck, Tetrahedron Lett. 1990, 31, 3113–3116;
f) J. Achatz, C. Fischer, J. Salbeck, J. Daub, J. Chem. Soc.,
Chem. Commun. 1991, 504–507; g) H. Spreitzer, J. Daub,
Chem. Eur. J. 1996, 2, 1150–1158.
[3] a) M. Å. Petersen, L. Zhu, S. H. Jensen, A. S. Andersson, A.
Kadziola, K. Kilså, M. B. Nielsen, Adv. Funct. Mater. 2007, 17,
797–804; b) M. Å. Petersen, A. S. Andersson, K. Kilså, M. B.
Nielsen, Eur. J. Org. Chem. 2009, 1855–1858.
[4] M. Å. Petersen, K. Kilså, A. Kadziola, M. B. Nielsen, Eur. J.
Org. Chem. 2007, 1415–1418.
Experimental Section
2-Phenyl-7-[(triisopropylsilyl)ethynyl]-1,8a-dihydroazulene-1,1-dicar-
bonitrile (10): Dibromide 5 (416 mg, 1.00 mmol) was dissolved in
dry THF (20 mL) at 0 °C. Lithium bis(trimethylsilyl)amide
(1.00 mL, 1.00 mmol, 1  in toluene) was added dropwise, and the
solution was stirred for 2 h, while the temperature was slowly raised
to room temperature. The reaction mixture was diluted with Et2O
(100 mL) and then washed with saturated aqueous NH4Cl
(2ϫ100 mL). The organic phase was dried with MgSO4, filtered,
and the solvents evaporated in vacuo yielding a black solid contain-
ing the bromide 8 plus minor by-products (according to NMR
analysis). [8: 1H NMR (300 MHz, CDCl3): δ = 7.74 (m, 2 H), 7.48
(m, 3 H), 6.89 (s, 1 H), 6.52 (m, 2 H), 6.30 (m, 1 H), 6.13 (dd, J =
4.4, 0.9 Hz, 1 H), 3.80 (dd, J = 4.4, 1.8 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 141.6, 141.1, 132.9, 132.3, 131.8, 130.7,
131.1, 129.5, 126.6, 120.3, 120.2, 120.0, 114.8, 112.6, 51.2,
44.8 ppm.] The crude batch of 8 was redissolved in dry, argon-
degassed THF (10 mL). Then [PdCl2(PPh3)2] (70.19 mg,
0.10 mmol) and CuI (3.81 mg, 0.02 mmol) were added under ar-
gon, followed by iPr2NH (0.3 mL) and (triisopropylsilyl)acetylene
(0.5 mL, 2.2 mmol). The reaction mixture was stirred at 35–40 °C
[5] K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett.
1975, 16, 4467–4470.
[6] H. Görner, C. Fischer, S. Gierisch, J. Daub, J. Phys. Chem.
1993, 97, 4110–4117.
Received: March 19, 2009
Published Online: April 29, 2009
2736
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