Synthesis of a ferrocene-functionalized unsymmetrical benzo[b]thienyl- thienylethene photoswitch with a cyclopentene core

Article abstract of DOI:10.1016/j.tetlet.2013.01.033

A new and potentially general synthetic route toward unsymmetrical benzo[b]thienyl-thienylethene compounds is described, with specific focus on conjugation of a ferrocene to the benzo[b]thiophene subunit. The route proceeds in an overall yield of 17%. Copyright

Full text of DOI:10.1016/j.tetlet.2013.01.033

Tetrahedron Letters 54 (2013) 1482–1485
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of a ferrocene-functionalized unsymmetrical
benzo[b]thienyl-thienylethene photoswitch with a cyclopentene core
⇑
Nathaniel B. Zuckerman, Xiongwu Kang, Shaowei Chen, Joseph P. Konopelski
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A new and potentially general synthetic route toward unsymmetrical benzo[b]thienyl-thienylethene
compounds is described, with specific focus on conjugation of a ferrocene to the benzo[b]thiophene sub-
unit. The route proceeds in an overall yield of 17%.
Received 7 December 2012
Revised 4 January 2013
Accepted 8 January 2013
Available online 17 January 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Ferrocene
Microwave Stille
Ruthenium nanoparticles
Diarylethene photoswitch
Intervalence transfer
The desire to miniaturize electronic components and devices
has led to a renewed focus on organic compounds in the develop-
ment of molecular scale electronics. One such group of compounds
reagents that are relatively easy to attain and handle in comparison
to their fluorinated counterparts.
Our desire in pursuing the unsymmetrical cyclopentene-
bridged photoswitch scaffold 1 was driven by our continuing inter-
1
is that of diarylethenes, whose photochromic properties are ame-
nable to use in memory applications.2 The ideal components of
–5
est in organic monolayer-protected ruthenium nanoparticles. In
13
the photoswitch scaffold have been well documented over the past
recent publications we have demonstrated that ferrocene moieties
2
0+ years and include the desirable qualities of: (1) induced revers-
ible ring closure (light, acid, redox), (2) thermal irreversibility, and
3) fatigue resistance. Photochromism in the solid state is also a
conjugated to the metal nanoparticle via ruthenium–carbene p
bonds display an intervalence transfer at mixed valence.
Conversely, a single saturated carbon between the ferrocene and
nanoparticle negates any communication between the ferrocenyl
metal centers. Within this context, compound 1 provides an inter-
esting test case. Appended to a ruthenium nanoparticle through
olefin metathesis of the terminal alkene, photoisomerization of 1
to 2 (Fig. 1) provides for a fully conjugated pathway between the
(
very desirable characteristic.
Of the large variety of photoswitches developed over the years,
symmetric molecules that contain a perfluorinated cyclopentene
6
bridge have remained superior for use in materials applications.
However, if one requires an unsymmetrical perfluorocyclopenten-
e-bridged photoswitch without the tedious separation of a mixture
of compounds, there are few synthetic options. Such unsymmetri-
cal compounds are attractive to both materials and biological
1
4
ruthenium core and the ferrocenyl substituent. Reversion to the
open form (i.e., 1) breaks the conjugation and any interaction
between metal sites.
7
applications.
However, the synthesis of 1 poses certain challenges. There are
few examples of unsymmetrical photoswitch molecules and, to our
Within the last 15 years, there has been an expansion of re-
search regarding the synthesis of perhydrocyclopentene-bridged
photoswitches,
units thiophene and benzo[b]thiophene. Many of these com-
pounds have the key aforementioned requirements of a desirable
photoswitch. Additionally, the syntheses of these compounds are
generally more amenable to scale up, lower in cost, and use
8
–10
largely directed toward the more desirable sub-
1
1
12
λ
1
λ2
Fc
Fc
S
S
S
S
X
X
1
2
X = CH2 or Ru nanoparticle
⇑
Corresponding author. Tel.: +1 831 459 4676; fax: +1 831 459 2935.
E-mail address: joek@ucsc.edu (J.P. Konopelski).
Figure 1. Open (1) and closed (2) forms of photoswitch; Fc = ferrocene.
0
040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.01.033

N. B. Zuckerman et al. / Tetrahedron Letters 54 (2013) 1482–1485
1483
knowledge, none contain a ferrocene moiety directly bonded to the
FcSnBu , CuO
3
1
5
X
aromatic ring. During the course of our research, a patent and
1
0% PdCl2 (dppf)
76%
1
6
S
Br
S
Fc
publication appeared that implicated molecules containing a
cyclopentene core and mixed thiophene/benzo[b]thiophene sub-
units as viable photoswitches, and thus provided validation of
the proposed target. Unfortunately, the published yields are quite
poor and too low for our purposes. Herein, we report the synthesis
of 1 via a route that offers considerable flexibility.
1
2
) LAB;
) MsCl;
9
8
X = CO Me
2
10
90%
X = Me
LiEt BH
3
2
I ,
86%
I ,
2
NaIO4 (0.1 mmol)
6
5%
NaIO4
I
I
As depicted in Scheme 1, the convergent synthesis of 1 relies
heavily on the well precedented intramolecular McMurry reaction
of diketones. In our case, the appended functional groups on the
thienyl and benzothienyl moieties of 3 were to be introduced prior
to the McMurry reaction. The decision to functionalize the thio-
phene with the vinyl group and the benzo[b]thiophene with the
ferrocene (and not vice versa) was driven by the anticipated reac-
tion conditions needed for coupling of compounds 4 and 5. Readily
S
Fc
S
Br
1
2
1
1
Scheme 2. Synthesis of varied benzo[b]thiophene subunits.
on Stille reactions. Optimization of conditions for the Stille cou-
pling of tributylstannyl ferrocene to 8 was conducted in a micro-
wave reactor. Also, a relatively more stable catalyst alternative to
Pd(PPh ) was sought, which led to the choice of PdCl (dppf) based
1
7
available anion 4, derived in four steps from 2-methylthiophene,
1
8
was expected to be used in excess as compared with lactol 5. In
order to furnish lactol 5 via DIBALH reduction, 6 and 7 would un-
dergo ferrocenylation via a microwave Stille reaction under CuO
mediated Gronowitz conditions.19 Friedel–Crafts acylation be-
tween glutaric anhydride (GA) and 8, followed by ester or Weinreb
amide formation, would provide 6 and 7.
3
4
2
2
3
on a procedure given by Guillaneux and Kagan. In only 20 min at
140 °C, compound 10 was furnished in 76% yield.
Although 8 was anticipated to undergo Friedel–Crafts acylation,
the expected competition between the benzothiophene ring and
the ferrocene moiety precluded the use of 10. However, halogena-
tion at the 3-position of 10 or 8 would provide two compounds
that could be easily converted into the appropriate lithium anion
via lithium-halogen exchange for future synthetic targets. The
oxidative conditions to iodinate 8 to give dihalide 11 were suc-
cessfully used on 10 on a 0.1 mmol scale to give 12 in 90% yield.
However, any scale-up led to much lower yields and a black insol-
uble precipitate. Alternative halogenation methods, either with
NBS or NCS, returned only decomposed material in a matter of
minutes.
4
Reduction of 9 with LiAlH led to some dehalogenation product
(Scheme 2). However, in only 5 min, 2.5 equiv of lithium dimethyl-
ammonium borohydride reduced 9 to the corresponding primary
alcohol on a 25 mmol scale without the unwanted side reaction.
Mesylation of the alcohol product followed by subsequent reduc-
tion with 2 equiv of lithium triethylborohydride yielded 8 in 91%
yield over two steps (86% for all three steps).
2
4
2
0
Ferrocene cross-coupling reactions have been reviewed, and
particular success for ferrocene/heteroaryl coupling has been seen
21,22
in the work of Ma and co-workers.
heteroaryl halides and tributylstannyl ferrocene23 was shown to be
enhanced by an equivalent of CuO in addition to the Pd(PPh cat-
The Stille coupling between
Friedel–Crafts acylation between 8 and glutaric anhydride (GA)
gave carboxylic acid 13 in 77% yield, and methanol esterification or
CDI coupling with N-methoxy-N-methylamine hydrochloride
provided 6 and 7, respectively, in quantitative yield (Scheme 3).
3 4
)
alyst. This is very similar to the original work of Gronowitz and co-
workers which first showed this effect of CuO and other additives
O
O
O
O
Fc
AlCl3
X
1
8
+ GA
R
77%
S
S
3
S
a. MeOH, cat. H
b. FcSnBu , CuO,
cat. PdCl (dppf), 65%
2
SO
, 98%
13 R = OH; X = Br
6 R = OMe; X = Br
7 R = NMe(OMe); X = Br
14 R = OMe; X = Fc
15 R = NMe(OMe); X = Fc
2
4
a
3
c
OH
b
Li
c. CDI, HNMe(OMe)•HCl, > 99%
d
. same as b, 69%
MeO
MeO
O
d
+
Fc
S
OH
4
5
S
1
or
4
O
DIBAL-H
Fc
15
O
O
anion 4
85%
5
90% from 14,
S
Br
9
1% from 15
X
S
OH
OH
S
Fc
X
6
7
X = OMe
X = NMe (OMe)
S
S
TPAP, NMO
8%
Ph P=CH , 16 X = O
3
2
6
Fc = Fe
8
6%
17 X = CH2
O
O
O
O
O
Br
Fc
+
TiCl , Zn
4
1
80%
S
S
S
GA
8
3
Scheme 1. Retrosynthesis of 1.
Scheme 3. Synthesis of 1.

1
484
N. B. Zuckerman et al. / Tetrahedron Letters 54 (2013) 1482–1485
(
306 nm). The molecule displays distinct maxima typical to dithie-
nylethene compounds in the UV at 206 and 252 nm, as well as
shoulders at 284 and 360 nm (Fig. 2). There is also a weaker inten-
sity peak that extends from the UV into the visible region (maxi-
mum 450 nm), which can be attributed to ferrocene. Irradiation
of a dilute solution of 1 with UV light turns the solution from col-
orless to red and gives rise to a new peak at 505 nm. Over irradia-
tion time the intensity of the peaks below 350 nm decrease and
there is a noticeable hypsochromic shift from 252 to 242 nm. Also,
the shoulder at 284 nm is replaced with a more defined peak at
3
10 nm.
X-ray quality single crystals of 1 were formed upon slow evap-
oration from a mixture of hexanes and dichloromethane.26 The
ORTEP diagram of the structure is given in Figure 3. The distance
between the reactive carbon atoms, labeled C7 and C11 in Fig. 1,
is 3.67 Å, well below the determined necessary distance for solid-
2
7
state cyclization (ꢀ4.2 Å) upon irradiation with UV light at a
suitable wavelength. However, under UV irradiation, the yellow
crystals of 1 do not appear to photocyclize in the solid state. As
discussed above, in the solution phase a colorless or pale yellow
solution of 1 becomes pink to dark red upon irradiation with
Figure 2. Open to closed. UV–vis spectra of interval irradiation of 1 in heptane
À5
(
4.5 Â 10 M) with 306 nm light.
3
06 nm light. The yellow crystals of 1 do not change color follow-
ing irradiation with UV light.
Conclusions
A new synthetic route toward unsymmetrical benzo[b]thienyl-
thienylethene photoswitches, which allows the potential for an
extensive variation of subunits, is described. Each aryl subunit is
functionalized prior to the McMurry cyclization, which reduced
the handling of the photoactive compound. Further study of the
photoswitch properties of 1, together with experiments to attach
1
to ruthenium nanoparticles, is underway and will be reported
in due course.
Figure 3. X-ray crystal structure of 1.
Acknowledgments
Additionally, the previously described microwave Stille conditions
gave 14 and 15 in 65% and 69% yield, respectively.
This work was supported in part by the National Science Foun-
dation (Grants CHE-0832605). Thanks to Dr. Honghan Fei (UCSC)
for solving the X-ray structure. Single-crystal, X-ray diffraction
data were recorded on an instrument supported by the US National
Science Foundation Major Research Instrumentation (MRI) pro-
gram; grant no. CHE- 0521569.
One of the main goals of our synthesis of an unsymmetrical
photoswitch was to avoid the possibility of mixtures and the cor-
responding decreased overall yield. Methyl ester 14 or Weinreb
amide 15 would allow us to pursue this goal without the need to
directly protect the ketone portion of the molecule. Reduction of
both carbonyl functionalities of 14 or 15 with DIBAL-H provided
lactol 5, which bore the desired masked aldehyde functionality
that is revealed in the presence of excess lithium anion 4 (Scheme
Supplementary data
3
). Precedence for this type of reaction with complex anions is seen
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
01.033.
in the work toward the total synthesis of (+)-macbecin I by Martin
2
5
and co-workers. Multiple equivalents of nucleophile were neces-
sary to give a good yield of diol 16 as a noticeable color change
from red to brown above À40 °C signified possible anion decompo-
sition. It should be noted that the dimethyl acetal was readily
hydrolyzed during acidic workup to give diol 16. The utility of this
particular nucleophilic addition should be highly advantageous to
the creation of a variety of mixed photoswitches.
Aldehyde 16 was treated with excess methylenetriphenylphos-
phorane to give alkene 17 in 85% yield. Oxidation of diol 17 did not
proceed well under PCC, Swern, or Dess–Martin conditions, provid-
ing mostly decomposed product. However, Ley conditions pro-
vided a 68% yield of diketone 3. The McMurry reaction proceeded
smoothly to furnish 1 in 80% yield as orange crystals.12,16 The yield
of 1 from commercially available 9 over nine steps, through
Weinreb amide 15, is 17%.
References and notes
1
2
.
.
Irie, M. Chem. Rev. 2000, 100, 1685–1716.
Jakobsson, F. L. E.; Marsal, P.; Braun, S.; Fahlman, M.; Berggren, M.; Cornil, J.;
Crispin, X. J. Phys. Chem. C 2009, 113, 18396–18405.
3. Tsujioka, T.; Onishi, I.; Natsume, D. Appl. Opt. 2010, 49, 3894–3899.
4.
Wu, Y.; Chen, S.; Yang, Y.; Zhang, Q.; Xie, Y.; Tian, H.; Zhu, W. Chem. Commun.
012, 48, 528–530.
2
5.
Zou, Q.; Li, X.; Zhang, J.; Zhou, J.; Sun, B.; Tian, H. Chem. Commun. 2012, 48,
2095–2097.
6.
7.
8.
Irie, M. Photochem. Photobiol. Sci. 2010, 9, 1535–1542.
Singer, M.; Jäschke, A. J. Am. Chem. Soc. 2010, 132, 8372–8377.
Huang, Z.-N.; Xu, B.-A.; Jin, S.; Fan, M.-G. Synthesis 1998, 8, 1092–1094.
9. Lucas, L. N.; van Esch, J.; Kellogg, R. M.; Feringa, B. L. Chem. Commun. 1998,
2313–2314.
10. Xu, B. A.; Huang, Z. N.; Jin, S.; Ming, Y. F.; Fan, M. G.; Yao, S. D. J. Photochem.
Photobiol., A: Chem. 1997, 110, 35–40.
To investigate the degree of photocyclization, solutions of 1
were irradiated with monochromatic light from a xenon source
11. Lucas, L. N.; de Jong, J. J. D.; van Esch, J. H.; Kellogg, R. M.; Feringa, B. L. Eur. J.
Org. Chem. 2003, 155–166.

N. B. Zuckerman et al. / Tetrahedron Letters 54 (2013) 1482–1485
1485
1
1
2. Krayushkin, M. M.; Migulin, V. A.; Yarovenko, V. N.; Barachevskii, V. A.;
Vorontsova, L. G.; Starikova, Z. A.; Zavarzin, I. V.; Bulgakova, V. N. Mendeleev
Commun. 2007, 17, 125–127.
3. (a) Chen, W.; Chen, S.; Ding, F.; Wang, H.; Brown, L. E.; Konopelski, J. P. J. Am.
Chem. Soc. 2008, 130, 12156–12162; (b) Kang, X.; Zuckerman, N. B.; Konopelski,
J. P.; Chen, S. J. Am. Chem. Soc. 2012, 134, 1412–1415.
19. Gronowitz, S.; Björk, P.; Malm, J.; Hörnfeldt, A.-B. J. Organomet. Chem. 1993,
460, 127–129.
20. Mamane, V. Mini-Rev. Org. Chem. 2008, 5, 303–312.
21. Liu, C.-M.; Luo, S.-J.; Liang, Y.-M.; Ma, Y. X. Synth. Commun. 2000, 30, 2281–
2285.
22. Liu, C.-M.; Chen, B.-H.; Liu, W.-Y.; Wu, X.-L.; Ma, Y.-X. J. Organomet. Chem. 2000,
1
1
1
4. For another ferrocene-substituted photoswitch, see Sun, L.; Tian, H.
Tetrahedron Lett. 2006, 47, 9227–9231.
5. Krayushkin, M. M.; Migulin, V. A.; Russian Patent No. RU 2,421,453 C1,
598, 348–352.
23. Guillaneux, D.; Kagan, H. B. J. Org. Chem. 1995, 60, 2502–2505.
24. Impagnatiello, N.; Heynderickx, A.; Moustrou, C.; Samat, A. Mol. Cryst. Liq. Cryst.
2
011.
2005, 430, 243–248.
6. Migulin, V. A.; Krayushkin, M. M.; Barachevsky, V. A.; Kobeleva, O. I.; Valova, T.
M.; Lyssenko, K. A. J. Org. Chem. 2012, 77, 332–340.
25. Martin, S. F.; Dodge, J. A.; Burgess, L. E.; Hartmann, M. J. Org. Chem. 1992, 57,
1070–1072.
1
1
7. Gilat, S. L.; Kawai, S. H.; Lehn, J.-M. Chem. Eur. J. 1995, 1, 275–284.
8. Plaumann, D. E.; Fitzsimmons, B. J.; Ritchie, B. M.; Fraser-Reid, B. J. Org. Chem.
26. CCDC 876470.
27. Kobatake, S.; Uchida, K.; Tsuchida, E.; Irie, M. Chem. Commun. 2002, 2804–
1
982, 47, 941.
2805.