Synthesis of dihydroindolizines for potential photoinduced work function alteration

Article abstract of DOI:10.1016/j.tetlet.2010.10.097

Seeking to immobilize photochromophores on metallic surfaces, we have synthesized four molecules which contain both a photoresponsive dihydroindolizine (DHI) core and a sulfur containing moiety, which allow for their assembly onto gold substrates. Sonogashira, Suzuki, or Ullmann couplings are employed to generate pyridines with pendant thioacetates (or disulfides). The pyridines are condensed with spiro[2-cyclopropene-1, 9′-[9H]fluorene]- 2, 3-dimethyl ester affording the targeted DHIs.

Full text of DOI:10.1016/j.tetlet.2010.10.097

Tetrahedron Letters 51 (2010) 6839–6842
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of dihydroindolizines for potential photoinduced work
function alteration
Matthew A. Bartucci, Patrycja M. Wierzbicki, Chengeto Gwengo, Sunny Shajan, Syed H. Hussain,
⇑
Jacob W. Ciszek
Department of Chemistry, Loyola University Chicago, 1032 W. Sheridan Road, Chicago, IL 60660, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Seeking to immobilize photochromophores on metallic surfaces, we have synthesized four molecules
which contain both a photoresponsive dihydroindolizine (DHI) core and a sulfur containing moiety,
which allow for their assembly onto gold substrates. Sonogashira, Suzuki, or Ullmann couplings are
employed to generate pyridines with pendant thioacetates (or disulfides). The pyridines are condensed
with spiro[2-cyclopropene-1,90-[9H]fluorene]-2,3-dimethyl ester affording the targeted DHIs.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 22 July 2010
Revised 13 October 2010
Accepted 15 October 2010
Available online 25 October 2010
Applying a self-assembled monolayer (SAM) to a metal surface
is an effective means for altering the work function of that sub-
strate.1–4 When this SAM is placed between a metal and an organic
active material, as is present in organic solar cells, organic light
emitting diodes, and organic field effect transistors, the bulk organ-
ic and metal energy levels can be aligned resulting in highly effi-
cient devices.3,5 It is widely accepted that the work function shift
is directly proportional to the dipole of the corresponding mono-
layer.3,6 If the dipole could be dynamically altered via stimuli, then
a response in the work function could be induced. Recently, Einaga
and co-workers showed this to be possible via a photoresponsive
SAM which altered the magnetization and the work function of
gold.7
We have synthesized a series of dihydroindolizines (DHIs)
(Fig. 1) for further study of the same photoresponsive molecular
influence on the work function of gold. The immobilized DHI on
the surface should be able to switch from its neutral spirocyclic
form to its charged zwitterionic conformation when irradiated
CO2Me
CO2Me
N
AcS
N
AcS
CO2Me
CO2Me
2
1
CO2Me
N
MeO2C
N
MeO2C
CO2Me
CO2Me
N
MeO2C
MeO2C
CO2Me
N
O
O
S
S
S
S
3
4
Figure 1. Targeted compounds containing a DHI core and aromatic linker.
⇑
Corresponding author. Tel.: +1 773 508 3107; fax: +1 773 508 3086.
E-mail address: jciszek@luc.edu (J.W. Ciszek).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.097

6840
M. A. Bartucci et al. / Tetrahedron Letters 51 (2010) 6839–6842
VO(acac)2
N
SH
N
S
S
N
R1
t-BuOOH
88%
R1
16
λ ~400 nm
R1
N
R1
Scheme 4. Synthesis of short linker 16.
τ1/2
N
R2
R2
was converted to cyclopropene 7 by refluxing for 1 h, driving off
nitrogen.15
Figure 2. Fluorenyl DHIs 1–4 undergo photoswitching to the betaine form when
irradiated (kmax = 383–401 nm).8 The betaine then thermally relaxes back to the
spiro form.
Scheme 2 outlines the formation of the linker para-ethynylpyr-
idine-thioacetyl benzene (11), which is used in the generation of
the first DHI, 1. To begin, a low temperature Sandmeyer reaction
was employed to generate 4-iodopyridine (8) for subsequent
cross-coupling reactions.16 Originally, 4-bromopyridine was
utilized, however, its tendency to polymerize led to inconsistent
coupling results.17 Compound 8 was coupled to trimethylsilylacet-
ylene using standard Sonogashira conditions to generate 9 which
was readily deprotected with potassium hydroxide in methanol.18
In our hands, the free alkyne 10 discolors after a few hours. As a
result it was coupled to 4-iodophenyl thioacetate immediately,
again using Sonogashira protocol.19
The synthesis of the extended linker 15 was accomplished
through a series of Sonogashira couplings and deprotections
(Scheme 3). 1-Bromo-4-iodobenzene is coupled with 10 to afford
12, which was then coupled with trimethylsilylacetylene to gener-
ate diyne 13.20 The free alkyne 14 was generated by deprotecting
13 with potassium hydroxide,18 and much like Scheme 2, the ter-
minal acetylene was immediately coupled with 4-iodophenyl thio-
acetate to afford 15.19
with a specific wavelength of light (Fig. 2).8,9 This light induced
switch should alter the dipole of the molecule and the work func-
tion of the material.
We have incorporated several important parameters into the
design of our molecules. First, a rigid backbone allows the mole-
cule, and more importantly the change in dipole, to occur near
the surface normal.10 Second, conjugated-thiol based SAMs allow
for improved charge injection and better overall conductance of a
material.1 Third, we can study deprotection-based effects by exam-
ining thioacetyl terminated ‘linkers’ (the portion connecting the
DHI to the surface) versus the disulfides. Compounds 1–4 (Fig. 1)
meet these criteria and have the ability to bind to a gold surface.
The protecting acetyl groups can easily be removed11 from 1 and
2, and disulfides 3 and 4 will spontaneously assemble.12
All four target compounds can easily be generated by condens-
ing 7, spiro[2-cyclopropene-1,90-[9H]fluorene]-2,3-dimethyl ester,
with its respective pyridal linker. To generate this spirocyclopro-
pene (Scheme 1), fluorenone was converted to the hydrazone 5
via treatment with hydrazine in 1-butanol. Hydrazone 5 was
subsequently converted to diazofluorene (6) via oxidation with
mercuric oxide and sonication.13 Treatment of 6 with dimethyl
acetylenedicarboxylate generates a pyrazole14 intermediate which
The short linker, 16, contains a disulfide bond which should
readily attach to gold. Disulfide 16 (Scheme 4) was generated using
catalytic amounts of vanadyl acetylacetonate according to a procedure
reported by Raghavan et al.21 The precursor, 4-(4-thiophenyl) pyr-
idine, was made from a previous procedure by Nichols and co-
workers.22
NH2
MeO2C
CO2Me
CO2Me
O
N2
N
N2H4 H2O
1) MeO2C
HgO
89%
Δ
2)
1-butanol, Δ
75%
93%
5
6
7
Scheme 1. Synthesis of intermediate 7, used in condensations for forming 1–4.
AcS
I
1) NaNO2
TMS
Pd/Cu
77%
KOH
MeOH
67%
H2N
N
I
N
TMS
N
N
AcS
N
Pd/Cu
42%
2) KI
65%
8
9
10
11
Scheme 2. Synthesis of the first linker, para-ethynylpyridine-thioacetyl benzene.
10
Pd/Cu
81%
TMS
Pd/Cu
51%
I
Br
N
Br
N
TMS
12
13
I
SAc
KOH
N
H
N
SAc
MeOH
90%
Pd/Cu
8%
14
15
Scheme 3. Synthesis of extended linker 15.

M. A. Bartucci et al. / Tetrahedron Letters 51 (2010) 6839–6842
6841
TMS
TMS
S
SH
OH
S
8
1) TBAF
TMS
N
O
S
S
O
N
CuI
glycine
Cs2CO3
t-BuOOBu-t
2) air
44%
O
19
OH
67%
17
48%
N
18
Scheme 5. Generation of ether linker 19.
Table 1
Four linkers condensed with 7 to generate DHIs and yields
Linker
Ratio (7:linker)
DHI
Yield
1:1
1
2
3
4
68%
96%
71%
46%
N
N
N
N
SAc
1:1
SAc
S
S
N
2.1:1
2.1:1
O
S
S
O
N
The second disulfide, 19, contains an ether linkage for the
purpose of interrupting conjugation. The synthesis of 19
(Scheme 5) begins with 4-hydroxythiophenol which was pro-
tected with vinyltrimethylsilane to generate 17.23 This allowed
for Ullmann coupling with 8 to generate the ether 18.24,25 In
our first attempt, the thiol was protected as a methyl thioether.
However, in later deprotection steps, the thioether proved to be
too robust and our attempts at removal resulted in a cleavage of
the diaryl ether. 2-(Trimethylsilyl)ethyl is stable enough to with-
stand the Ullmann ether synthesis conditions but is easily re-
moved with tetrabutylammonium fluoride26 to generate the
thiolate which oxidizes upon exposure to air to yield 4-(4-pyri-
doxy)phenyldisulfide (19).
Supplementary data
Supplementary data (experimental procedures and character-
ization data) associated with this article can be found, in the online
version, at doi:10.1016/j.tetlet.2010.10.097.
References and notes
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linker was condensed with cyclopropene 7 under nitrogen in the
dark for 24 h.27 The pyridine linker attacks the electron deficient
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progress is visually obvious with an immediate color change to
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that column chromatography could be preformed without light
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from moderate to high (Table 1).
In conclusion, experimental routes have been provided to gen-
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gold in a stimuli-responsive manner. Various palladium and copper
catalyzed couplings were used to generate the linkers, and a gen-
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This work was supported in part by an award from the Illinois
State Academy of Science.

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