Substituent parameters impacting isomer composition and optical properties of dihydroindolizine molecular switches

Article abstract of DOI:10.1021/jo500752p

In an attempt to understand which factors influence constitutional isomer control of 6′- and 8′-substituted dihydroindolizines (DHIs), a series of asymmetric pyridines was condensed with dimethyl spiro[cycloprop[2] ene-1,9′-fluorene]-2,3-dicarboxylate. The substituents on the pyridial derivatives ranged from donating to withdrawing and demonstrated control over the isomeric ratios for all DHIs. Substituent control proved to be selective for the highly donating amino, which exclusively formed the 8′ isomer. The same ratios were reproduced via photolytic experiments, which suggested that the condensation reaction is dominated by the products thermodynamic stability. The electronic influences of the substituents extends beyond isomer control, as it impacts the DHIs optical properties and electrocyclization (switching) rates to the spiro conformers. Our results allow us to predict the syntheses and properties of future 6′- or 8′-substituted DHIs, molecules that will be applied in understanding the role of the dipole vector orientation to work function switching.

Full text of DOI:10.1021/jo500752p

Article
pubs.acs.org/joc
Substituent Parameters Impacting Isomer Composition and Optical
Properties of Dihydroindolizine Molecular Switches
Matthew A. Bartucci and Jacob W. Ciszek*
Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, Illinois 60660, United
States
S
* Supporting Information
ABSTRACT: In an attempt to understand which factors influence constitutional isomer control of 6′- and 8′-substituted
dihydroindolizines (DHIs), a series of asymmetric pyridines was condensed with dimethyl spiro[cycloprop[2]ene-1,9′-fluorene]-
2,3-dicarboxylate. The substituents on the pyridial derivatives ranged from donating to withdrawing and demonstrated control
over the isomeric ratios for all DHIs. Substituent control proved to be selective for the highly donating amino, which exclusively
formed the 8′ isomer. The same ratios were reproduced via photolytic experiments, which suggested that the condensation
reaction is dominated by the product’s thermodynamic stability. The electronic influences of the substituents extends beyond
isomer control, as it impacts the DHIs’ optical properties and electrocyclization (switching) rates to the spiro conformers. Our
results allow us to predict the syntheses and properties of future 6′- or 8′-substituted DHIs, molecules that will be applied in
understanding the role of the dipole vector orientation to work function switching.
molecules would allow us to confirm the direct correlation
between the normal component of the molecular dipole and
the change in the work function.
INTRODUCTION
■
Photochromic molecules have often been discussed in the
context of smart electronics, with the photochromophore acting
as a stimuli-responsive switch or trigger.1 Toward that end,
photochromophores have been recently demonstrated to alter
the work function of a material in response to incident light.2−5
The correlation between molecular change and the work
function shift has even been demonstrated.5 This effect, if
incorporated into an organic thin-film transistor or organic
light-emitting diode configuration, could control the device’s
function. In this scenario, the photochromophore is at the
contact point of the leads and the bulk organic species, allowing
for tuning of the device’s contact resistance.6−12
Within these light-driven molecular switch systems, there are
questions that remain (e.g., distance dependence of switching,
the amount of free volume needed for a switch to occur,
etc.).13−15 Of particular importance is demonstrating the
relationship between the dipole of the molecule and the
surface’s work function change. On the basis of our recent work
function modulation data,5 it would be ideal to build
photochromophores that, when irradiated, have their respective
dipoles aligned at varying angles to the surface normal. Such
We explore this relationship via a particular class of
photochromophores: dihydroindolizines (DHIs).16,17 DHIs
are advantageous because of their ease of synthesis and array
of substitution patterns, which are ideal for tuning their
photochemical properties. More importantly, these same
substitutions can be used to tether the molecule to the surface
(R, Figure 1)5 and, depending on their position, control the
orientation of the molecular dipole relative to the surface
normal. Typically, monolayers on gold are oriented about 30°
with respect to the surface normal,18 and based on the alkyl
tethers of our previously studied 7′-substituted DHIs,5 a dipole
moment ∼28° from the surface normal was presumed. To
reorient the zwitterion dipole vector, the tether location on the
DHI can be relocated to the 6′ position, which should generate
a dipole nearly parallel to the surface normal after irradiation
(based on the most stable packing structures).19,20 Other
Received: April 1, 2014
Published: June 11, 2014
© 2014 American Chemical Society
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Scheme 1. Mechanism of the Condensation Reaction Using
a 3-Substituted Pyridine To Afford the 6′ and/or 8′ DHIs
Figure 1. Conformers of DHI, photoisomerization to the betaine
form, and orientation of the betaine dipole. The dipole vector, which is
relevant for surface/device applications, is indicated with respect to the
expected surface normal (dashed line) for molecules tethered to a
surface via substituent R. As the location of the tether is moved, so
does the corresponding zwitterion dipole orientation with respect to
the surface normal.
substitutions, such as 8′, would generate a similarly oriented
dipole to that of 7′ and thus serve as an effective positive
control molecule.
With these substitutions in mind, the synthetic route to
generate the asymmetric DHIs leads to an interesting challenge.
Because of the reaction pathway, a mixture of the spiro 6′ or 8′
isomers can be formed via synthesis from 3-substituted
pyridines, but the rules for isomer selectivity are not initially
obvious; in fact, the isomers have been generated only once
before.21 However, insight as to what controls the isomer
population may be gleaned by correlating the mechanism of
formation to substituent effects. Moreover, the changes
described above also impact the optical properties of these
photochromophores, which are strongly influenced by the
electron-donating or -withdrawing capacities of these sub-
stituents, adding a second factor to the molecular design.22−24
To elucidate the cause of selectivity over constitutional
isomers, we have synthesized a series of asymmetric DHIs and
shown a relative trend toward formation of the 6′ isomer as the
pyridial substituent (R) becomes more electron withdrawing.
We show that this can be readily explained via the
thermodynamic stability of the parent diene system. Although
more complex in origin, perturbation of this diene system also
provides justification for changes in absorption maxima
locations and intensities. Half-lives track similarly with isomer
formation and electron withdrawal, but they stem from
resonance stabilization of the pyridinium. We discuss these
results as well as the implications for switch design herein.
has formed, it resides in the trans form because once the cis
isomer is generated, formation of the 6′ or 8′ spiro species is
rapid.25 However, if the substituents on the pyridinium ion
actively donate or withdraw electron density to the positive
reaction center, the speed of the electrocyclization is altered
and has been correlated with their respective Hammett
parameters, showing a linear tendency.22,24 More germane to
the formed product(s), there is little within this mechanism to
suggest selectivity of one geometric isomer over the other as,
for example, transition state stabilization ortho to the
substituent rather than para is expected to be comparable. In
fact, the only obvious means for selecting between 6′ and 8′
isomers is steric effects.
On the basis of mechanistic arguments, we hypothesize that
the pyridial substituents (R) affect the ratio of the 6′ and 8′
isomers primarily by thermodynamic considerations via the
Hammond postulate.26 To test this, substituents that vary in
their electronic-directing capabilities were incorporated at the
3-position, from the highly donating amino to the withdrawing
acetyl. Furthermore, these pyridine derivatives were selected
because of the commercial availability of the pyridine starting
materials and the ease of synthesis of the oligo(phenylene
ethynylene) (OPE) (Supporting Information, Scheme S1).27
As noted before,27 the formation of the DHIs is facile, and the
reaction progress is visually obvious. The seven substituents
that were examined (DHIs 7−13, Table 1) follow a loose
trend: as the R group becomes more electron withdrawing, the
percentage of the 6′ spiro isomer is increased. Of these, only
the aminopyridine forms exclusively one product (8′), and it
was rare to form the 6′ in excess, even with acetyl substitution.
We were slightly surprised at the different ratios for the iodo
and chloro species, especially as the iodo favored the more
sterically hindered 8′. However, overall the general electro-
negativity trend was consistent.
RESULTS AND DISCUSSION
■
Structural Isomer Formation. The target compounds are
generated via a condensation reaction between dimethyl
spiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicarboxylate and the
appropriate 3-substituted pyridine (Scheme 1). The reaction
mechanism begins via nucleophilic addition of the pyridine to
the spirocyclopropene, generating a cyclopropyl anion. From
there, the unstable three-membered ring opens to afford the
trans isomer of the zwitterion, and the local negative charge can
resonate between the C1 and C3 atoms.25 Once the zwitterion
To facilitate analysis, several experiments were performed in
order to examine whether the isolated products were indeed a
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substitution at the 6′ position generates a stabilized push−pull
olefin and is the more favored isomer.28
Table 1. Yields and Isomer Ratio of Targeted DHIs
It can be argued that if isomeric selectivity trends track with
electron-withdrawing ability, one should consider the possibility
that the effect is from the stabilization of the pyridinium in
Scheme 1. We discount this possibility for three reasons. First,
the aforementioned experiments suggested that we are
observing thermodynamically determined mixtures. Second,
invocation of the pyridinium does not provide justification of
the observed ratio of 6′ to 8 ′. Finally, no significant solvent
effects are observed, suggesting minimal impact of a charged
transition state (Supporting Information, Figure S4). It is also
worth mentioning that orbital control21 or other kinetic sources
could be invoked to explain the isomer distribution; however,
these are clearly heavily intertwined with the thermodynamics,
and attempts to differentiate them would not be meaningful.
Optical Properties. The characteristic feature in the optical
absorptions for the DHIs is the π to π* transition, the same
excitation responsible for initiating the molecular switch. We
have measured the λmax for DHIs 7−13 (Table 2, Figure 3) to
study substituent effects. The underpinnings of the transition
reside within the same diene system responsible for
determining isomeric distributions, and these can be classically
analyzed via substituent effects within Woodward−Fieser rules.
Specifically, methyl substituents are expected to red shift the
parent diene absorption maximum by approximately 5 nm29
(the unsubstituted DHI absorbs at 386 nm). The source of the
shift is understood to be purely inductive, as mesomeric effects
are inapplicable to the saturated carbon.30 Other simple
substituents such as chloro, methoxy, iodo, and amino are
only slightly more complex, involving both mesomeric and
inductive influences (Δλmax = 5, 4, 13, and 25 nm respectively;
Table 2 and Figure 3a); all are consistent with predicted
shifts.31 The more substantial shifts in the case of the iodo
species (compared to that of the chloro) arise from a change in
the nature of the optical excitation; in the case of the
iodoethylene, the I(5p⊥) is now the highest energy occupied
orbital and thus the lowest energy transition for these systems
is now the n to π* transition.32,33 The larger shift for the amino
group (when compared to those for the chloro and iodo) stems
from larger mesomeric effects associated with lone pairs in
period two elements.30 In all instances, the position of the
substituent on the diene (i.e., 6′ vs 8′) has a negligible effect on
λmax (Figure 3b), again mirroring experimental trends.31
thermodynamic result. We attempted to interconvert between
conformers thermally, but unfortunately, the barrier to
interconversion is sufficiently high: pure DHI-11 (either the
6′ or 8′ conformers) heated at 50 °C for 15 min show no
1
observable interconversion via their H NMR spectra. As an
alternative experiment, several of the DHIs were instead
interconverted photolytically (λ = 405 nm), and in all
experiments, the observed ratios were the same (within 10%)
as the ones generated during the condensation (Table 1).
Compounds examined in this manner include 8′-DHI-8, 8′-
DHI-13, and a 7:3 mixture of 6′/8′ DHI-13 (Supporting
Information, Figures S1−S3). In addition, when the con-
1
densation was monitored as a function of time via H NMR
spectroscopy, the isomer ratio was consistent and unaltered as
the reaction progressed.
A thermodynamic explanation for the isomer distributions in
Table 1 can be primarily described using the parent diene
system as a model (Figure 2), a valid assumption because the
The unsaturated substituents of DHI-12 and -13 require
explicit discussion, as two different effects must be considered
for the additional π systems. The first component is the
extension of conjugation, which can be modeled via the free
electron model (or MO theory for a more rigorous discussion).
Here, it is expected that the absorption maximum will red shift
with some proportionality to the length of the system/number
of electrons.30 The second component is the effect of cross-
conjugation, which is present in systems containing two
partially overlapping conjugated systems.34 For cross-con-
jugated systems, the longest linear system is generally the
primary determinant of the lowest energy of absorption, with
minor contributions from the cross-conjugation.35 These effects
allow us to interpret the absorption spectra of OPE-substituted
DHIs, where the substituent is at the 6′ (6′-DHI-12), 7′ (DHI-
1),27 and 8′ (8′-DHI-12) positions (Figure 4a). The simplest
system is that of 8′-DHI-12, where continuous conjugation
extends from the diene, through the ethynlene, and beyond
(Figure 4b). As this molecule contains no cross-conjugation, it
Figure 2. Parent diene system for 6′- and 8′-substituted DHIs. The R′
and R″ groups denote the 2,3-dihydropyrrole ring and are identical in
the two systems.
positions of the remaining substituents are identical. Control
stems from the location of the amine with respect to the R
group, either via a shared double bond or distal. Restated, in the
case of the 6′ conformer (Figure 2, left), both substituents have
a resonance and inductive effect on the same bond, and in the
case of 8′ (Figure 2, right), the interactions are via conjugation.
Thus, it is not surprising that for an electron-donating
substituent, the additional electron density is best stabilized at
the distant 8′ position. In the case of a withdrawing group,
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Table 2. Optical and Half-Life Data for DHIs 7−13
6′
8′
DHI
R
λmax (nm)
ε × 10−3 (M−1 cm−1
)
λmax (nm)
ε × 10−3 (M−1 cm−1
)
zwitterion λmax (nm)
t1/2 (s)
7
NH2
MeO
Me
I
411
390
390
399
391
440
433
6.2
7.2
12
573
581
587
606
594
596
594
120
120
51
8
9
a
10
11
12
13
397
391
426
404
12
9.0
38
13
10.
8.0
17
19
a
Cl
45
a
OPE
Ac
14
a
5.0
2.1
a
All half-lives under 50 s were the average of two trials monitoring the decay of the zwitterion absorption after excitation.
Figure 4. (a) UV−vis spectra of spiro 6′, 7′,27 and 8′ OPE-substituted
DHI in dichloromethane. The two cross conjugated systems (6′ and 7′
isomers) display smaller red shifts than the extended conjugation of
the 8′ isomer. (b) Density functional theory calculations were used to
generate the molecular orbitals of 7′ and 8′ alkynyl-substituted
dihydropyridines. For the 7′ isomer, the contribution to the HOMO
from the alkynyl substituent is negligible, and the compound’s optical
properties are similar to those of an unsubstituted DHI. For the 8′
system, there is continuous conjugation from the diene to the OPE
system. The fluorene, OPE, and dimethyl maleate contribute
minimally and are not shown in the interest of clarity. Full diagrams
can be found in the Supporting Information (Figure S5).
Figure 3. (a) UV−vis spectra of 8′ DHI-7, -8, -13, (dashed) and H-
DHI (solid curve) in dichloromethane. The introduction of amino,
methoxy, or acetyl auxochromes red shifts the spiro λmax when
compared to that of H-DHI. (b) UV−vis spectra of spiro 6′ (solid
curve) and 8′ (dashed curves) isomers of DHI-10 and -11 in
dichloromethane.
has a substantial red shift (λmax = 440) because of the long,
extended π system. This is in contrast with the 6′ and 7′
systems, which are cross-conjugated and display dramatically
smaller red shifts (λmax = 426 and 398 nm, respectively) from
the unsubstituted species (H-DHI).
dipoles), the significant increase in absorption for the 6′
conformer is noteworthy. This effect is seen both in the acetyl-
and OPE-substituted systems, with the extinction coefficient
increasing roughly two to three times over the analogous 7′ or
8′ species. These effects have been seen before in cross-
conjugated systems, although these are quite large in
magnitude.39
Zwitterion Stability. To examine the effect of the
substituents on the zwitterion stability and the rate of
cyclization back to the spiro species, the spiro DHIs were
irradiated with 405 nm light (42 mW/cm2), which generated
the zwitterion. The zwitterion maxima for all DHIs fall well
within the accepted range (500−700 nm) of the presumed
charge transfer band22 and are the same for both of the isolated
conformers (Table 2). For the electrocyclization back to the
spiro conformer, the decay of the zwitterion was measured as a
function of time and, as predicted,22 followed a first-order rate.
The substituents have a substantial effect on the half-life of
the zwitterionic species (Table 2). As the electron-donating
ability of the substituent on the dihydropyridine increased, the
Although extended and cross-conjugation adequately explain
the observed spectra, there are two nuances that must be
mentioned. First, we cannot discount potential contributions of
π-stacking interactions with the conjugated fluorene moiety.
These interactions are ascribed to coplanar π systems with
interplanar distances on the order of 3.3−3.8 Å.36 As the
distance between the fluorene and the substituent was
calculated to be 3.3 Å for the 8′ species (Supporting
Information, Figure S5), such interactions are likely. Additional
evidence of π-stacking interactions can be garnered from the 1H
NMR spectra of DHI-13, where the deshielding cone of the
fluorene moiety substantially shifts the acetyl protons from 2.24
to 1.47 ppm for the 8′ species.37,38 Second, although we do not
wish to engage in substantial discussion of the relative
absorbance of the chromophores (and the nuances of transition
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half-life also increased. This effect has been demonstrated by a
linear relationship of DHIs half-lives with their appropriate
Hammett parameters and was previously noted22,24 with
asymmetric cyano DHIs. Any explanation for such results
should center on the influence of the substituents on the
isomerization process (trans to cis), which is the rate-
determining step in the relaxation.25
Two possible explanations suggest themselves. The first is
the weakening of the double-bond character and stabilization of
the transition state, which becomes more pronounced when
both electron-withdrawing and -donating substituents are
found, leading to a polarized ethylene and substantially lower
barrier to rotation. This explanation is common in thermal
isomerization literature.40,41 A second explanation is that the
destabilization of the zwitterion accelerates the transition. We
find the former mechanism to be less applicable (although not
necessarily negligible), as such stabilization generally requires
the ability to delocalize the double bond to the withdrawing
substituent (in our case the pyridinium), which is less favorable
for our system.21,22,24 Rather, the primary source is likely the
stabilization/destabilization of the pyridinium via substituent
effects. This is the more commonly accepted mechanism for the
similar cyclization events.21,42,43
Molecular Switch Design for Conformers. The above
results allow one to create predictive rules for generating other
similar photochromophores. To begin, cyclization occurring via
the condensation reaction (Scheme 1) and resulting from the
relaxation of the photoisomerized betaine produces the same
ratio of constitutional isomers. Thus, compounds generated as a
mixture of isomers are advantageous (providing access to both
6′ and 8′) despite the difficulties associated with their
separation, especially in the case of DHI-9. The data here
shows that for a wide range of substituents, the dimethyl
maleate system seems ideal for generating this mixture,
occurring for all but the extremely donating amino group.
This ability to generate both conformers is impressive
considering that the only prior attempt to do so generated
exclusively the 8′ for the majority of substituents (including
chloro, methyl, and methoxy).21 The difference, in our case,
stems from the methyl esters on the dihydropyrrole, which are
cyano groups for previous reports. In essence, the dihydro-
pyrrole substituent causes a substantial shift in thermodynamic
stability of the 6′ isomer relative to that of the 8′, but fine-
tuning of the isomer composition is dictated by the substituents
on the pyridine ring.
These pyridial substituents play a role in the optical
properties of the DHIs, just as they impact the isomer
composition of the spiro species. Again, from a design
standpoint, it would be ideal if the change in λmax could be
controlled via a parameter that is not correlated with electron
donation/withdrawal, as this tunes isomer composition, and
thus the optical properties could be controlled independently.
Conveniently, the two are quite uncorrelated, and instead,
control over the absorption properties is governed by the
Woodward−Fieser rules. Figure 5 demonstrates both the
decoupling of the λmax from the isomeric ratio and the
predictive ability of the Woodward−Fieser rules. For the
former, the shift in λmax is plotted against σR and σI (used as a
surrogate for thermodynamic stability) and shows no
correlation. For the latter, both the expected and measured
shifts match exquisitely in instances where both are available
(red diamonds vs black squares, e.g. −OMe). Despite the
successes of these models on simple substituents, conjugated
Figure 5. Shift in λmax, both measured and predicted, for DHIs.
Common data points for the measured (red diamonds) and of
empirical Woodward−Fieser31 (black squares) substituents for
butadiene systems are virtually identical, showing a strong predictive
ability of the Woodward−Fieser rules. When both sets of data for
Δλmax are plotted against their respective resonance (top) and
inductive (bottom) Hammett parameters,44 no correlation is seen,
indicating that these parameters can be tuned independently. In the
case of the OPE and Ac substituents, the reported λmax is for the 8′
isomer, as the effect of cross-conjugation is minimal for these species.
substituents at the 6′ or 7′ position are governed by cross-
conjugation and should be considered separately. For all of the
systems studied though, the isomer ratio can be controlled
independently from the absorbance maximum.
The final parameter is half-life, and here were find that the
property is correlated to the isomer ratio but not to the
excitation wavelength. The relationship between the isomer
composition and half-life should not surprise, as both have been
correlated to electron-donation ability/Hammett parameters,
and we have already described how λmax is relatively
independent of these paramenters. The correlation between
isomer composition and half-life, however, provides the one
limitation on the design of similar DHI photochromophores:
both a long half-life and generation of the 6′ conformer appear
mutually exclusive. It remains to be seen if other substitutions
(e.g., a dihydropyridazine- or dihydroisoquinoline-based
system) allow circumvention of this issue.
CONCLUSIONS
■
We synthesized a series of asymmetric DHIs containing both
electron-donating and -withdrawing substituents on the
dihydropyridine ring in order to investigate the substituents
influence over isomer control and their intertwined effects on
the optical properties and the molecular switch’s half-life. As
electron donors are introduced to the dihydropyridine, the
effect was 2-fold: the population of the 8′ isomer was favored
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peaks allowing for quantification assigned from crude mixture; 1H
NMR (500 MHz, CDCl3) δ 5.93 (s, 1H), 5.69−5.65 (m, 1H), 5.38−
5.36 (m, 1H), 4.66−4.63 (m, 1H), 4.01 (s, 3H), 3.56 (s, 3H).
8′-Isomer: Dimethyl 8′-Methoxy-8a′H-spiro[fluorene-9,1′-
indolizine]-2′,3′-dicarboxylate (8′-DHI-8). (100% CH2Cl2, Rf =
0.53). 1H NMR (500 MHz, CDCl3) δ 7.72−7.69 (m, 2H), 7.55 (d, J =
7.3 Hz, 1H), 7.44 (d, J = 7.3 Hz, 1H), 7.36 (dt, J = 7.4, 1.1 Hz, 1H),
7.34−7.29 (m, 2H), 7.18 (dt, J = 7.4, 1.0 Hz, 1H), 6.14 (d, J = 7.3 Hz,
1H), 5.58−5.57 (m, 1H), 5.20 (t, J = 6.8 Hz, 1H), 4.77 (dd, J = 6.6, 2.0
Hz, 1H), 3.98 (s, 3H), 3.25 (s, 3H), 2.75 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 164.1, 162.6, 150.6, 149.0, 147.8, 144.2, 142.1, 140.8,
128.1, 127.7, 127.4, 126.8, 123.2, 123.1, 119.8, 119.7, 117.7, 108.6,
104.9, 93.6, 70.0, 64.8, 54.5, 53.4, 51.1. IR (liquid film, cm−1): 3015,
2952, 2929, 2852, 1745, 1706, 1692, 1643, 1579, 1448, 1438, 1425,
1392, 1379, 1346, 1296, 1262, 1240, 1225, 1190, 1146, 1126, 1105,
1036. HRMS (ESI-TOF) calcd for C25H21NO5H+ [M + H]+,
416.1492; found, 416.1506.
and the generated DHIs displayed an enhanced stability in the
zwitterion form. With electron-withdrawing groups, the
electrocyclization rate was enhanced along with the increased
formation of the 6′ isomer. In contrast, the optical absorption
for the system could be tuned with relative independence of the
isomer ratio and half-life; this parameter is primarily governed
(empirically) by the Woodward−Fieser rules. Overall, both the
6′ and 8′ isomers were accessible for all substituents save one.
These form the basis for the design parameters to be used in
building more complex photoswitches for smart electronics.
EXPERIMENTAL SECTION
■
General Experimental Methods. NMR spectra were taken on a
1
500 MHz spectrometer. H chemical shifts (δ) for spectra acquired in
CDCl3 were referenced to tetramethylsilane (0 ppm). 8′-DHI-7 was
taken in, and referenced to, CD2Cl2 at 5.32 ppm, and DHI-10s, DHI-
11s, DHI-12s, and 6′-DHI-13 were taken in, and referenced to,
CD3CN at 1.94 ppm. All 13C spectra were referenced to CDCl3 at
77.23 ppm. Reactions were run under a nitrogen atmosphere unless
otherwise noted. All plug purifications and column chromatography
separations were carried out on silica gel 60 (40−63 μm from BDH).
Thin-layer chromatography (TLC) was performed on silica gel 60
(F254) with glass support. Dimethyl spiro[cycloprop[2]ene-1,9′-
fluorene]-2,3-dicarboxylate,27 3-methoxypyridine,45 Pd(PPh3)2Cl2,46
H-DHI,17 and DHI-127 were made according to previously reported
procedures. High-resolution mass spectra samples were ionized by ion
trap (IT) or electrospray ionization (ESI) and recorded via the time-
of-flight (TOF) method. Dichloromethane was used as the solvent for
all UV−vis spectra measurements, and IR spectra of either liquid films
or KBr samples were acquired on a FT-IR with a liquid nitrogen-
cooled MCT detector. Calculations of the two valence occupied
molecular orbitals in Figure 4b were performed with Spartan ′08 using
the B3LYP/6-31G* density functional theory method. The zwitterion
λmax for DHI-12 and -13 were obtained by means of a Gaussian fit.
General Condensation Procedure. For the condensations,
dimethyl spiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicarboxylate was
mixed with the respective pyridial derivative in a 1:1 mole ratio. The
round-bottomed flask was purged with nitrogen for 30 min in the dark
at room temperature before the addition of chloroform, THF, or
dichloromethane. Reaction mixtures were allowed to stir for 2−24 h,
and the solvent was removed by rotary evaporation. All reactions were
purified via column chromatography except for 8′-DHI-7, which
proved to be metastable.
Dimethyl 8′-Amino-8a′H-spiro[fluorene-9,1′-indolizine]-
2′,3′-dicarboxylate (8′-DHI-7). Dimethyl spiro[cycloprop[2]ene-
1,9′-fluorene]-2,3-dicarboxylate (0.043 g, 0.14 mmol), 3-amino-
pyridine (0.13 g, 0.14 mmol), and CH2Cl2 (5 mL) were added to a
round-bottomed flask according to the general DHI procedure and
stirred for 5 h. 8′-DHI-7 (0.050 g, 0.12 mmol) was generated in 86%
yield as an orange oil. 1H NMR (500 MHz, CD2Cl2) δ 7.78−7.75 (m,
2H), 7.66 (d, J = 7.6 Hz, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.46−7.37 (m,
3H), 7.27 (dt, J = 7.4, 1.1 Hz, 1H), 6.09 (d, J = 7.5 Hz, 1H), 5.58 (s,
1H), 5.23 (t, J = 6.8 Hz, 1H), 4.73 (dd, J = 6.4, 2.0 Hz, 1H), 3.95 (s,
3H), 3.27 (s, 3H), 2.33 (s, 2H). 13C NMR (125 MHz, CDCl3) δ
164.0, 162.7, 148.3, 147.7, 143.9, 141.3, 139.8, 136.9, 128.9, 128.5,
128.1, 127.9, 124.2, 124.1, 120.4, 120.3, 115.6, 107.1, 107.0, 95.1, 70.2,
64.2, 53.4, 51.0. IR (liquid film, cm−1): 3361, 2952, 1742, 1691, 1642,
1575, 1438, 1390, 1348, 1301, 1242, 1191, 1147, 1127, 1105. HRMS
(IT-TOF) calcd for C24H19N2O4[M − H]−, 399.1350; found,
399.1361.
DHI-9s. Dimethyl spiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicar-
boxylate (0.043 g, 0.14 mmol), 3-picoline (0.013 g, 0.14 mmol), and
CH2Cl2 (10 mL) were added to a round-bottomed flask according to
the general DHI procedure and stirred for 4 h. The product, 8′-DHI-9
(0.034 g, 0.085 mmol), was isolated via column chromatography
(100% CH2Cl2, Rf = 0.17) in 61% yield of as a yellow oil.
1
Selective Indicative H NMR (500 MHz, CDCl3) Peaks for 6′-
Isomer: Dimethyl 6′-Methyl-8a′H-spiro[fluorene-9,1′-indoli-
zine]-2′,3′-dicarboxylate (6′-DHI-9). δ 6.21−6.19 (m, 1H), 5.40−
5.38 (m, 1H), 4.52 (d, J = 10.0 Hz, 1H), 4.01 (s, 3H), 3.26 (s, 3H),
1.73 (s, 3H).
8′-Isomer: Dimethyl 8′-Methyl-8a′H-spiro[fluorene-9,1′-in-
dolizine]-2′,3′-dicarboxylate (8′-DHI-9). (100% CH2Cl2, Rf
=
0.17) 1H NMR (500 MHz, CDCl3) δ 7.71 (d, J = 7.3 Hz, 2H), 7.57 (d,
J = 7.3 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.40−7.36 (m, 2H), 7.32 (dt,
J = 7.3, 1.2 Hz, 1H), 7.23 (dt, J = 7.5, 1.1 Hz, 1H), 6.32 (d, J = 7.6 Hz,
1H), 5.58 (s, 1H), 5.45−5.41 (m, 1H), 5.14 (dd, J = 7.4, 6.0 Hz, 1H),
3.98 (s, 3H), 3.24 (s, 3H), 0.63 (s, 3H). 13C NMR (125 MHz, CDCl3)
δ 164.1, 162.7, 148.5, 146.9, 144.2, 142.1, 140.6, 128.65, 128.60, 128.1,
127.6, 127.5, 124.2, 123.7, 122.7, 120.5, 120.2, 120.1, 108.9, 104.6,
72.7, 64.8, 53.4, 51.1, 17.7. IR (liquid film, cm−1): 2951, 2924, 2852,
1744, 1704, 1645, 1599, 1571, 1448, 1428, 1391, 1344, 1301, 1260,
1239, 1226, 1191, 1146, 1125, 1106, 1066. HRMS (IT-TOF) calcd for
C25H21NO4H+ [M + H]+, 400.1543; found, 400.1548.
DHI-10s. Dimethyl spiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicar-
boxylate (0.064 g, 0.21 mmol), 3-iodopyridine (0.043 g, 0.21 mmol),
and CH2Cl2 (10.5 mL) were added to a round-bottomed flask
according to the general DHI procedure and stirred for 14 h. The 8′-
isomer was isolated via column chromatography (3:1 hexanes/
EtOAc). The 6′ isomer was then separated from the reagents and
side products via a second column (100% CH2Cl2). DHI-10 (0.070 g,
0.14 mmol) was obtained in 67% combined yield as a yellow oil.
6′-Isomer: Dimethyl 6′-Iodo-8a′H-spiro[fluorene-9,1′-indoli-
zine]-2′,3′-dicarboxylate (6′-DHI-10). (0.008 g, 100% CH2Cl2, Rf =
0.63). 1H NMR (500 MHz, CD3CN) δ 7.82−7.78 (m, 2H), 7.59 (d, J
= 7.3 Hz, 1H), 7.44−7.40 (m, 3H), 7.35 (dt, J = 7.5, 1.1 Hz, 1H),
7.30−7.27 (m, 1H), 6.94−6.93 (m, 1H), 5.66 (ddd, J = 10.0, 2.6, 1.0
Hz, 1H), 5.54−5.52 (m, 1H), 4.28 (ddd, J = 10.1, 2.0, 1.0 Hz, 1H),
3.96 (s, 3H), 3.28 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 163.7,
161.9, 146.9, 145.6, 141.91, 141.87, 140.6, 131.1, 130.0, 128.8, 128.5,
128.0, 127.4, 124.9, 123.7, 120.3, 120.0, 119.0, 109.8, 68.2, 65.1, 64.3,
53.6, 51.3. IR (liquid film, cm−1): 2951, 2925, 2854, 1743, 1703, 1596,
1546, 1438, 1416, 1369, 1324, 1306, 1262, 1229, 1189, 1166, 1131,
1107, 1074, 1047. HRMS (IT-TOF) calcd for C24H18INO4H+ [M +
H]+, 512.0353; found, 512.0364.
DHI-8s. Dimethyl spiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicar-
boxylate (0.254 g, 0.83 mmol), 3-methoxypyridine (0.091 g, 0.83
mmol), and CHCl3 (40 mL) were added to a round-bottomed flask
according to the general DHI procedure and stirred for 5 h. The
product, 8′-DHI-8 (0.285 g, 0.69 mmol), was isolated via column
chromatography (100% CH2Cl2, Rf = 0.53) in 83% yield as a yellow
oil.
8′-Isomer: Dimethyl 8′-Iodo-8a′H-spiro[fluorene-9,1′-indoli-
zine]-2′,3′-dicarboxylate (8′-DHI-10). (0.062 g, 3:1 hexanes/
1
EtOAc, Rf = 0.68). H NMR (500 MHz, CD3CN) δ 7.79−7.75 (m,
2H), 7.58 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.46−7.41 (m,
2H), 7.36 (dt, J = 7.5, 1.1 Hz, 1H), 7.29 (dt, J = 7.4, 1.0 Hz, 1H), 6.62
(d, J = 7.3 Hz, 1H), 6.48 (dd, J = 6.2, 2.3 Hz, 1H), 5.89 (d, J = 2.5 Hz,
1H), 4.97−4.94 (m, 1H), 3.93 (s, 3H), 3.25 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 163.6, 162.1, 147.5, 145.9, 143.6, 142.5, 142.2, 136.0,
6′-Isomer: Dimethyl 6′-Methoxy-8a′H-spiro[fluorene-9,1′-
indolizine]-2′,3′-dicarboxylate (6′-DHI-8). Indicative 6′-isomer
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128.9, 128.4, 127.6, 127.4, 125.4, 124.4, 123.7, 120.20, 120.16, 111.5,
103.7, 83.7, 72.3, 66.4, 53.5, 51.3. IR (liquid film, cm−1): 2952, 2925,
2854, 1743, 1710, 1598, 1543, 1448, 1436, 1427, 1384, 1356, 1295,
1254, 1227, 1191, 1147, 1125, 1106. HRMS (IT-TOF) calcd for
C24H18INO4H+ [M + H]+, 512.0353; found, 512.0338.
120.2, 120.1, 111.8, 110.9, 104.1, 92.7, 87.9, 69.1, 64.7, 53.5, 51.3, 30.4.
IR (liquid film, cm−1): 2952, 2925, 2854, 1744, 1708, 1595, 1529,
1487, 1450, 1432, 1408, 1352, 1301, 1256, 1228, 1191, 1150, 1124,
1091, 1016. HRMS (ESI-TOF) calcd for C34H25NO5SH+ [M + H]+,
560.1526; found, 560.1531.
DHI-11s. Dimethyl spiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicar-
boxylate (0.150 g, 0.49 mmol), 3-chloropyridine (0.056 g, 0.49 mmol),
and CHCl3 (22 mL) were added to a round-bottomed flask according
to the general DHI procedure and stirred for 9 h. The crude mixture
was first passed through a silica plug (CH2Cl2), and then the two
eluted isomers were separated via column chromatography (3:1
hexanes/EtOAc) to afford DHI-11s (0.116 g, 0.28 mmol) in 57%
combined yield as a yellow oil.
DHI-13s. Dimethyl spiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicar-
boxylate (0.058 g, 0.19 mmol), 3-acetylpyridine (0.023 g, 0.19 mmol),
and CHCl3 (9.5 mL) were added to a round-bottomed flask according
to the general DHI procedure and stirred for 2 h. The product was
isolated via column chromatography (1:1 hexanes/EtOAc) to afford
the two isomers of DHI-13 (0.064 g, 0.15 mmol) in 79% combined
yield as a yellow oil.
6′-Isomer: Dimethyl 6′-Acetyl-8a′H-spiro[fluorene-9,1′-in-
dolizine]-2′,3′-dicarboxylate (6′-DHI-13). (0.039 g, Rf = 0.50).
1H NMR (500 MHz, CD3CN) δ 7.84−7.81 (m, 2H), 7.61 (d, J = 7.6
Hz, 1H), 7.57 (s, 1H), 7.47−7.41 (m, 2H), 7.40−7.35 (m, 2H), 7.28
(t, J = 7.6 Hz, 1H), 6.26 (dd, J = 10.3, 2.4 Hz, 1H), 5.61−5.59 (m,
1H), 4.35 (d, J = 10.0 Hz, 1H), 4.00 (s, 3H), 3.34 (s, 3H), 2.20 (s,
3H). 13C NMR (125 MHz, CDCl3) δ 193.0, 163.2, 161.3, 145.8, 144.4,
142.0, 141.2, 140.6, 134.4, 129.0, 128.8, 128.0, 127.5, 124.7, 123.6,
122.1, 120.5, 120.2, 117.7, 116.9, 115.2, 69.6, 64.6, 53.8, 51.7, 25.2. IR
(liquid film, cm−1): 2953, 2927, 1741, 1731, 1650, 1630, 1611, 1556,
1535, 1438, 1376, 1315, 1287, 1259, 1212, 1184, 1132, 1109, 1066,
1037. HRMS (ESI-TOF) calcd for C26H21NO5H+ [M + H]+,
428.1492; found, 428.1504.
6′-Isomer: Dimethyl 6′-Chloro-8a′H-spiro[fluorene-9,1′-in-
dolizine]-2′,3′-dicarboxylate (6′-DHI-11). (0.026 g, Rf = 0.40).
1H NMR (500 MHz, CD3CN) δ 7.82−7.79 (m, 2H), 7.60 (d, J = 7.6
Hz, 1H), 7.44−7.40 (m, 3H), 7.36 (t, J = 7.4 Hz, 1H), 7.28 (t, J = 7.4
Hz, 1H), 6.76 (s, 1H), 5.69 (d, J = 10.0 Hz, 1H), 5.52−5.50 (m, 1H),
4.43 (d, J = 10.3 Hz, 1H), 3.96 (s, 3H), 3.28 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 163.7, 161.9, 147.0, 146.2, 142.0, 141.9, 140.6, 128.8,
128.5, 128.0, 127.4, 126.2, 124.8, 123.7, 122.3, 120.3, 120.0, 118.9,
112.2, 109.7, 69.1, 64.2, 53.6, 51.3. IR (liquid film, cm−1): 2952, 2925,
2854, 1743, 1705, 1596, 1558, 1439, 1421, 1392, 1369, 1324, 1303,
1262, 1228, 1131, 1108, 1069. HRMS (IT-TOF) calcd for
C24H18ClNO4H+ [M + H]+, 420.0997; found, 420.1007.
8′-Isomer: Dimethyl 8′-Chloro-8a′H-spiro[fluorene-9,1′-in-
dolizine]-2′,3′-dicarboxylate (8′-DHI-11). (0.090 g, Rf = 0.22).
1H NMR (500 MHz, CD3CN) δ 7.79−7.76 (m, 2H), 7.60 (d, J = 7.3
8′-Isomer: Dimethyl 8′-Acetyl-8a′H-spiro[fluorene-9,1′-in-
dolizine]-2′,3′-dicarboxylate (8′-DHI-13). (0.025 g, Rf = 0.55)
1H NMR (500 MHz, CDCl3) δ 7.70 (d, J = 7.6 Hz, 1H), 7.67 (d, J =
Hz, 1H), 7.48 (d, J = 7.3 Hz, 1H), 7.44−7.39 (m, 2H), 7.35 (dt, J =
7.4, 1.1 Hz, 1H), 7.28 (dt, J = 7.4, 1.0 Hz, 1H), 6.55 (d, J = 7.3 Hz,
1H), 5.90−5.84 (m, 2H), 5.17 (t, J = 7.0 Hz, 1H), 3.94 (s, 3H), 3.26
(s, 3H). 13C NMR (125 MHz, CDCl3) δ 163.7, 162.1, 147.7, 146.2,
142.9, 142.5, 141.4, 128.8, 128.2, 127.5, 127.3, 124.1, 123.8, 123.4,
123.2, 123.1, 120.2, 120.1, 111.1, 102.5, 71.7, 65.5, 53.5, 51.3. IR
(liquid film, cm−1): 2953, 2925, 2854, 1744, 1711, 1637, 1600, 1560,
1448, 1437, 1361, 1340, 1294, 1256, 1227, 1192, 1148, 1127, 1107,
1086. HRMS (IT-TOF) calcd for C24H18ClNO4H+ [M + H]+,
420.0997; found, 420.0979.
DHI-12s. Dimethyl spiro[cycloprop[2]ene-1,9′-fluorene]-2,3-dicar-
boxylate (0.038 g, 0.12 mmol), (4-thioacetylphenyl)(3-pyridyl)-
acetylene (0.030 g, 0.12 mmol), and THF (8 mL) were added to a
round-bottomed flask according to the general DHI procedure and
stirred for 15 h. The two isomers were isolated via column
chromatography (2:1 hexanes/EtOAc) to afford DHI-12 (0.062 g,
0.11 mmol) in 92% combined yield as a yellow oil.
6′-Isomer: Dimethyl 6′-((4-(Acetylthio)phenyl)ethynyl)-
8a′H-spiro[fluorene-9,1′-indolizine]-2′,3′-dicarboxylate (6′-
DHI-12). (0.034 g, Rf = 0.53). 1H NMR (500 MHz, CD3CN) δ
7.84−7.81 (m, 2H), 7.62 (d, J = 7.8 Hz, 1H), 7.46−7.41 (m, 5H),
7.39−7.35 (m, 3H), 7.30 (dt, J = 7.6, 1.0 Hz, 1H), 7.05 (d, J = 1.0 Hz,
1H), 5.78 (ddd, J = 10.0, 2.6, 1.0 Hz, 1H), 5.58−5.56 (m, 1H), 4.45−
4.42 (m, 1H), 3.99 (s, 3H), 3.31 (s, 3H), 2.39 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 193.7, 163.6, 161.8, 146.6, 145.6, 141.9, 141.8, 140.6,
134.4, 131.8, 130.0, 128.8, 128.5, 128.0, 127.5, 127.4, 125.6, 125.0,
124.8, 123.7, 120.4, 120.1, 117.0, 112.2, 99.8, 89.8, 88.8, 69.1, 64.4,
53.7, 51.4, 30.4. IR (liquid film, cm−1): 2952, 2924, 2853, 1742, 1707,
1632, 1559, 1551, 1488, 1438, 1421, 1373, 1309, 1264, 1226, 1191,
1121, 1105. HRMS (ESI-TOF) calcd for C34H25NO5S [M + H]+,
560.1526; found, 560.1534.
8′-Isomer: Dimethyl 8′-((4-(Acetylthio)phenyl)ethynyl)-
8a′H-spiro[fluorene-9,1′-indolizine]-2′,3′-dicarboxylate (8′-
DHI-12). (0.028 g, Rf = 0.40). 1H NMR (500 MHz, CD3CN) δ
7.76 (d, J = 7.1 Hz, 1H), 7.69 (d, J = 7.3 Hz, 1H), 7.64 (d, J = 7.1 Hz,
1H), 7.49 (d, J = 7.6 Hz, 1H), 7.40 (dt, J = 7.4, 1.1 Hz, 1H), 7.36 (dt, J
= 7.5, 1.2 Hz, 1H), 7.32 (dt, J = 7.4, 1.1 Hz, 1H), 7.27−7.24 (m, 3H),
6.83 (dd, J = 6.5, 1.8 Hz, 2H), 6.70 (d, J = 7.3 Hz, 1H), 6.19 (dd, J =
6.1, 2.2 Hz, 1H), 5.77−5.74 (m, 1H), 5.34 (dd, J = 7.3, 6.3 Hz, 1H),
3.96 (s, 3H), 3.26 (s, 3H), 2.39 (s, 3H). 13C NMR (125 MHz, CDCl3)
δ 193.7, 163.7, 162.2, 147.7, 145.8, 142.84, 142.77, 141.7, 133.7, 132.0,
131.3, 128.6, 128.1, 127.57, 127.55, 127.3, 126.3, 124.2, 124.1, 123.6,
7.6 Hz, 1H), 7.55 (d, J = 7.1 Hz, 1H), 7.50 (d, J = 7.3 Hz, 1H), 7.40
(dt, J = 7.3, 1.2 Hz, 1H) 7.37−7.30 (m, 2H), 7.16 (dt, J = 7.3, 1.0 Hz,
1H), 6.68 (d, J = 7.3 Hz, 1H), 6.52−6.50 (m, 1H), 6.01−5.99 (m,
1H), 5.28−5.24 (m, 1H) 3.97 (s, 3H), 3.24 (s, 3H), 1.48 (s, 3H). 13C
NMR (125 MHz, CDCl3) δ 194.1, 163.6, 162.0, 148.7, 145.1, 142.1,
142.0, 141.7, 131.7, 131.2, 129.4, 128.5, 127.7, 127.5, 126.3, 124.1,
122.3, 120.5, 119.7, 113.9, 101.9, 69.4, 65.9, 53.5, 51.4, 24.5. IR (liquid
film, cm−1): 2953, 2925, 2853, 1743, 1714, 1665, 1610, 1535, 1449,
1439, 1383, 1354, 1295, 1271, 1227, 1149, 1127, 1105, 1042, 1004.
HRMS (ESI-TOF) calcd for C26H21NO5H+ [M + H]+, 428.1492;
found, 428.1499.
3-Iodopyridine. To a round-bottomed flask open to the
atmosphere, paratoulene sulfonic acid (9.393 g, 49.38 mmol) was
mixed with acetonitrile (60 mL) and was added to 3-aminopyridine
(1.500 g, 16.46 mmol). The mixture was cooled to 10 °C, and an
aqueous solution (10 mL) containing NaNO2 (2.27 g, 32.92 mmol)
and KI (6.831 g, 40.15 mmol) was added dropwise. The slurry was
stirred for 10 min at 10 °C and then brought to room temperature for
1 h. The reaction was brought to a pH 9−10 via 1 M NaHCO3(aq)
and then decolorized from a dark brown to a light orange with 2 M
Na2S2O3(aq). The reaction was then diluted and extracted (×3) with
ethyl acetate. The combined organic layers were dried with MgSO4
and filtered, the solvent was removed via rotary evaporation, and
column chromatography (2:1 hexanes/EtOAc, Rf = 0.53) was used to
isolate 3-iodopyridine (1.675 g, 8.171 mmol) in 48% yield as an off
white solid. mp 52−53 °C. 1H NMR (500 MHz, CDCl3) δ 8.85 (d, J =
1.5 Hz, 1H), 8.56 (dd, J = 4.9, 1.5 Hz, 1H), 8.03−8.00 (m, 1H), 7.12−
7.09 (m, 1H).47
3-(Trimethylsilylethynyl)pyridine. Pd(PPh3)2Cl2 (0.086 g, 0.12
mmol), 3-iodopyridine (1.258 g, 6.137 mmol), and CuI (0.047 g, 0.25
mmol) were added to a sealed tube that was evacuated and filled with
nitrogen five times. THF (12 mL), triethylamine (1.7 mL), and TMSA
(0.96 mL) were added via a syringe while stirring, and the brown
mixture was stirred for 12 h at 40 °C. The crude mixture was poured
into water, extracted with CH2Cl2 (×3), dried with MgSO4, and
filtered. The solvent was removed via rotary evaporation, and the
product was isolated by column chromatography (3:1 hexanes/EtOAc,
Rf = 0.45), which afforded 3-(trimethylsilylethynyl)pyridine (0.872 g,
4.97 mmol) as a dark oil in 81% yield. 1H NMR (500 MHz, CDCl3) δ
8.69 (d, J = 1.5 Hz, 1H), 8.53 (dd, J = 4.9, 1.7 Hz, 1H), 7.74 (dt, J =
7.8, 1.9 Hz, 1H), 7.25−7.21 (m, 1H), 0.27 (s, 9H).48
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3-Ethynylpyridine. 3-(Trimethylsilylethynyl)pyridine (1.000 g,
5.701 mmol) was dissolved in MeOH (9 mL) and CH2Cl2 (18 mL)
in a round-bottomed flask. Anhydrous KOH (0.640 g, 11.4 mmol) was
added to the mixture, which was then stirred for 1.5 h. The reaction
was partitioned between CH2Cl2 and water, and the aqueous layer was
further extracted two times with CH2Cl2. The combined organic
solution was then dried with MgSO4, and the solvent was removed by
rotary evaporation, which afforded 3-ethynylpyridine (0.581 g, 5.63
mmol) as an off-white solid in 99% yield. 1H NMR (500 MHz,
(CD3)2CO) δ 8.68 (d, J = 1.2 Hz, 1H), 8.58 (dd, J = 4.8, 1.3 Hz, 1H),
7.87 (dt, J = 7.8, 2.0 Hz, 1H), 7.42−7.38 (m, 1H), 3.88 (s, 1H).49
(4-Thioacetylphenyl)(3-pyridyl)acetylene. Pd(PPh3)2Cl2
(0.013 g, 0.018 mmol), 4-iodophenyl thioacetate (0.167 g, 0.600
mmol), 3-ethynylpyridine (0.068 g, 0.66 mmol), and CuI (0.007 g,
0.036 mmol) were added to a sealed tube that was evacuated and filled
with nitrogen five times. THF (15 mL) and triethylamine (0.48 mL,
3.4 mmol) were added via a syringe while stirring, and the dark brown
mixture was stirred for 18.5 h at 40 °C. The crude mixture was poured
into water, extracted with CH2Cl2 (×3), dried with MgSO4, and
filtered. Solvent was removed via rotary evaporation, and the product
was isolated by column chromatography (1:2 hexanes/EtOAc, Rf =
0.56), which afforded (4-thioacetylphenyl)(3-pyridyl)acetylene (0.030
g, 0.12 mmol) as an off white solid in 70% yield from recovered
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1
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ASSOCIATED CONTENT
■
S
* Supporting Information
1
IR, H NMR, and 13C NMR spectra of targeted DHIs and (4-
thioacetylphenyl)(3-pyridyl)acetylene and UV−vis spectrosco-
py of spiro and zwitterion DHIs. This material is available free
of charge via the Internet at http://pubs.acs.org.
́
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Spectroscopy; John Wiley and Sons, Inc.: New York, 1962.
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Products; Pergamon Press Ltd.: New York, 1964.
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137, 369.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jciszek@luc.edu. Phone: (773) 508-3107.
Notes
■
(33) Zou, P.; Strecker, K. E.; Ramirez-Serrano, J.; Jusinski, L. E.;
Taathes, C. A.; Osborn, D. L. Phys. Chem. Chem. Phys. 2008, 10, 713.
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
This work was supported in part by a grant from the National
Science Foundation (NSF), Career Award no. 1056400.
(38) Wang, W.; Li, L.-S.; Helms, G.; Zhou, H.-H.; Li, A. D. Q. J. Am.
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