Article
pubs.acs.org/joc
Synthesis of Geometrically Well-Defined Covalent Acene Dimers for
Mechanistic Exploration of Singlet Fission
Thomas J. Carey, Jamie L. Snyder, Ethan G. Miller, Tarek Sammakia,* and Niels H. Damrauer*
Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, Colorado 80309, United States
S Supporting Information
*
ABSTRACT: We report the first synthesis of norbornylbridged acene dimers (2 and 3) with well-defined and
controlled spatial relationships between the acene chromophore subunits. We employ a modular 2-D strategy wherein
the central module, common to all our compounds, is a
norbornyl moiety. The acenes are attached to this module
using the Diels−Alder reaction, which also forms one of the
acene rings. Manipulation of the Diels−Alder adducts provides
the desired geometrically defined bis-acenes. The modular
nature of this synthesis affords flexibility and allows for the
preparation of a variety of acene dimers, including functionalized tetracene dimers.
■
INTRODUCTION
Singlet fission (SF) is a nonradiative photophysical process by
which a singlet excited state in certain materials or molecular
systems converts to a singlet−coupled pair of triplets (1TT)
and then ultimately to a set of uncorrelated triplets according to
eq 1.1−4
k1
k2
k −1
k −2
S1S0 HooI 1TT HooI T + T
chromophores that have proven effective in the condensedphase settings.39−50 On a practical level, SF-active dimers may
be useful in dye-sensitized solar cells.4,6 More fundamentally,
dimersand the systematic variation of their structure and
electronic properties using synthesisoffer a platform for
exploring mechanistic details important for future development
of effective SF systems. Our group has been particularly
interested in understanding how to control interchromophore
electronic couplings that are tied to the magnitude of the k1 rate
constant in eq 1.12,51−53 In recent computational and
theoretical studies, we have explored the role of interchromophore bridge structure,53 orbital symmetry,51−53 and intramolecular vibrations and their symmetries.52 The structural
motif that is central to those studies underpins the synthetic
exploration herein. More generally, known dimers for SF39−44
have significant conformational flexibility that can lead to
uncertainty in the nature of the S1 reactant state as well as the
electronic coupling between it and the product 1TT. We have
been interested in identifying dimer platforms permitting
systematic exploration of factorselectronic coupling, reorganization energy, and driving forcethat fundamentally
control SF rates.
By way of controlling interchromophore couplings in dimers,
we were drawn to the work of Paddon-Row and co-workers
who developed platforms for exploring donor−acceptor
interactions relevant to both energy transfer and electron
transfer using bicyclic bridges based on norbornyl fragments.54,55 The norbornyl alkyl spacers provided superb
control over the spatial juxtaposition of electroactive moieties
by providing two covalent attachments to the bridge per
chromophore. This controls the geometric arrangement of the
(1)
Because spin is conserved in the initial forward reaction (k1),
the process can be rapid provided that it is not significantly
endergonic. While these photophysics were discovered more
than 45 years ago in molecular crystals of tetracene,1,5 recent
interest has blossomed as researchers attempt to develop nextgeneration strategies for solar energy conversion; SF offers
routes to process higher energy solar photons into pairs of
electronic excitations rather than wasting excess energy as
heat.4,6
While not an absolute requirement, it is generally the case
that SF-active systems involve the spatial juxtaposition of
multiple chromophore subunits (as is the case in a molecular
crystal), each of which has a low-energy triplet and a singlet
excited state that is approximately, or greater than, twice the
energy of the triplet. These conditions are important by way of
ensuring that the formation of 1TT is energetically accessible or
favorable. Longer polyacenes such as tetracene and pentacene
satisfy this condition and have played a major, although not
exclusive, role in the growth of the field.3,4,7−32
For much of the development of SF, condensed phase
systems including polycrystalline films,4,9,10,33 amorphous
films,8 and nanoparticle/supramolecular chromophore aggregates25,34−38 have been exploited. While much less developed,
there are good reasons to also consider molecular systems and
in particular covalent dimers comprised of the same types of
© XXXX American Chemical Society
Received: March 13, 2017
Published: April 10, 2017
A
DOI: 10.1021/acs.joc.7b00602
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■
Article
RESULTS AND DISCUSSION
As discussed in the introduction, we became interested in
polyacene dimer systems related to those originally synthesized
by Patney and Paddon-Row where interchromophore electronic coupling could be controlled using bicyclic alkyl
spacers.56 The general synthetic strategy described by these
workers involved the use of the Diels−Alder reaction wherein
the polyacene arm moieties bear diene functionalities that react
with norbornadiene. For example, a naphthalene dimer with a
single bicyclic bridge (BN1) was synthesized from α,α,α′,α′tetrabromo-o-xylene (4) which was subjected to in situ
reductive elimination of Br 2 with NaI to form the
corresponding dibromo-o-quinodimethane (5, Scheme 1).
chromophores and their electronic interactions with high
fidelity and limited conformational flexibility. In particular, we
were inspired by a set of naphthalene dimers56,57 that exhibit an
elegant manifestation of controlled interchromophore interactions (Figure 1). For the molecule with the largest bridge,
Scheme 1. Patney and Paddon-Row Synthesis of Bridged
Naphthalene Derivatives
Figure 1. (a) Pictorial representation of Davydov splitting between
two chromophores (C1 and C2) and (b) naphthalene dimers studied
by Paddon-Row and co-workers that exhibit such an interaction.
BN3, a single absorption band is observed that is indicative of
two approximately uncoupled chromophores where the
transition is S3 ← S0. As the bridge size is decreased to BN2
and then to BN1, that band splits (so-called Davydov splitting)
to an increasing degree, indicating interchromophore interactions that are tunable via distance. The work herein reports
the first synthesis of tetracene analogues to BN1, 2 and 3
(Figure 2), while using the previously synthesized 158 as a
model that also provides the photophysical background for an
uncoupled chromophore of this type.
This species serves as the diene and reacts with 0.17 equiv of
norbornadiene as a dienophile to provide the bis-Diels−Alder
adduct, which undergoes spontaneous loss of 4 equiv of HBr to
provide BN1. By using an excess of norbornadiene (10 equiv)
the corresponding monoannulated polyacene (N1) can be
prepared by an analogous process.56
Motivated by their successful use of dibromo-o-quinodimethane, we wished to explore a related strategy using
homologues derived from tetrabromo-dimethylanthraquinone
(6, Scheme 2). The quinone functionality could then be
reduced to form the desired tetracene arms late in the synthesis.
These routes were explored; however, difficulty in accessing the
requisite tetrabromo starting materials, partly due to allergic
reactions observed among laboratory workers (we note that
benzyl halides are well-known lachrymators), led us to abandon
this approach. An alternate route to access o-quinodimethane 8
via the corresponding sultine (7) was then explored59 but
abandoned due to reactivity issues; extrusion of SO2 to provide
the requisite o-quinodimethane intermediate required excessively high temperatures leading to complex mixtures of
products even when attempts were made to trap the reactive
intermediate in situ.
With these preliminary results, we required an alternate route
and devised a different Diels−Alder strategy for obtaining 2 and
1 via quinones 9 and 12, respectively. In this new route, the role
of diene is assigned to the bridge, and that of the dienophile to
the eventual tetracene arm (Scheme 3). By this strategy, the
synthesis of 2 requires tetraene 1160 and anthraquinone 10,61
and the synthesis of 1 requires triene 13.62 All of these are
known in the literature.
There are two main challenges involved with this synthetic
strategy: accomplishing the Diels−Alder reaction and reduction
of the quinone carbonyls to the polyacene. We chose to initially
study these en route to the synthesis of the corresponding
model monomer, 1.
Figure 2. Dimeric targets and previously synthesized monomer.
It is noted here that 2 and 3 are not, at the outset, expected
to be optimal for SF, and studies confirming this have recently
been reported.45 Our previous theoretical and computational
explorations52,53 suggest that orbital symmetry manifests in
such a way that electronic coupling for SF goes to zero for C2vsymmetric acene dimers, even when interchromophore
electronic coupling that manifests in absorption (i.e., Davydov
splitting) is high. These dimer systems will allow us to test this
prediction and to explore the role of vibronic coupling for
enabling SF.12,52 Further, we expect the building blocks that are
explored in this initial synthesis to be highly useful in
developing design rules based on the control of electronic
coupling in SF via symmetry properties.51
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Scheme 2. Failed Approach toward 2
Scheme 3. Alternative Retrosynthesis for 2 and 1
Our synthesis of 1 proceeds via quinone 12, and begins with
a Diels−Alder reaction between dienophile 1061 and triene
1362 (Scheme 4). Subjection of 10 and 13 to thermal Diels−
optimization purposes, commercially available 5−12naphthacenequinone (15) was used as a model for this
transformation. Literature precedent suggests that reduction of
one of the carbonyls of the quinone can be accomplished via
hydrogenation with Pd/C. This transformation was observed
by Nuckolls and co-workers in 64% yield on 5,12-naphthacenequinone derivative 21 which bears bis-o-methoxy substitution
(Scheme 5).64 The product of this reduction is the keto-
Scheme 4. Synthesis of 12
Scheme 5. Initial Attempts at Reduction Sequence on the
Model System
Alder conditions (150 °C, toluene, sealed tube, 3 days)
provided 14. This material was not amenable to purification by
flash chromatography, as partial oxidation to 12 was observed.
Instead, the crude material was adsorbed on alumina and stirred
for 2 days under an oxygen atmosphere63 to provide 12 in 76%
crude yield. Compound 12 also proved difficult to purify due to
poor solubility in nonpolar solvents, which led to coelution
with close running bands. As such, a small quantity was purified
for characterization purposes and the crude was used in
subsequent steps.
We then turned our attention to the reduction of the
quinone moiety to the corresponding hydrocarbon. For
C
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Scheme 6. Forward Synthesis of 1
Scheme 7. Forward Synthesis of 9
studies, we found that subjecting 15 to NaBH4 provided the
corresponding diol (23) as a 2:1 mixture of diastereomers
(95%). Treatment of this product with HCl and SnCl2 provides
17 in 93% yield and an overall yield of 90% for the two
steps.70−72 A similar procedure was used in the synthesis of 1.
Treatment of 12 with NaBH4 provided diol 24 as a 1:1.4:1 ratio
of three diastereomers in 88% yield. Diol 24, however, is
sensitive to oxidation to the quinone; as such, a one-pot
procedure was used wherein quinone 12 was treated with
NaBH4 in MeOH/CHCl3 and then directly treated with SnCl2.
This procedure provides 1 in 71% yield over two steps.
We then turned our attention to the synthesis of the dimer 2
via bisquinone 9. We imagined subjecting tetraene 1160 to a
two-directional strategy that consists of two consecutive Diels−
Alder reactions in one pot using dienophile 10 in order to
install both arms in a single operation to provide 28 (Scheme
7). Subjecting 11 to 10 (1 equiv) in toluene at 70 °C provided
the mono-Diels−Alder product, 25, as the keto tautomer,67,68
presumably derived from endoaddition,60 as a single isomer to
the limits of NMR detection. We studied more forcing
conditions (refluxing toluene and 5 equiv 10) but were unable
to obtain the bis-Diels−Alder product, even in the presence of a
Lewis acid. Such reluctance to undergo consecutive Diels−
Alder reactions is known in related systems.73 Compound 25
undergoes oxidation during attempted purification, as do
related compounds in this series. As such, we were unable to
tautomer 22 rather than the aromatic phenol, a tautomeric
preference that is known for larger polyacenes wherein the
diminishing returns associated with aromatization65,66 are less
significant than the stability of ketones relative to enols.67,68 In
our case, monoreduction of compound 15 would provide
ketone 16, which could then be reduced to the corresponding
alcohol and subjected to elimination to provide tetracene 17.
Subjecting 15 to H2 and Pd/C (or other heterogeneous
catalysts) did not provide reduction of the ketone; instead,
reduction of the interior ring proximal to the quinone to
provide compound 18 was observed. We found this surprising,
especially in contrast to the comparatively electron-rich and,
thus, less reactive carbonyls in Nuckolls’ system. Attempts to
convert this to useful material by tautomerization to 19, or 20
via in situ mesylation of 19, were unsuccessful. We attributed
this to the known instability of diol 19 toward disproportionation to provide 15 and other products as described by
Fieser.69
The use of metal hydride reducing agents to convert 15 to 17
was then studied (Scheme 6). Interestingly, subjecting 15 to
LAH at reflux in toluene provided the fully reduced product
(17), albeit in modest yield (30%). This transformation
required reaction workup under nitrogen; otherwise, partial
conversion to oxidation productsincluding the starting
quinone (15), the corresponding diol (23), and other
unidentified specieswas observed. Subsequently in our
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study a subsequent Diels−Alder reaction on purified 25.
Instead, we simply added basic alumina to the crude reaction
product without removal of solvent and rapidly stirred the
slurry in air and obtained 27 in 60% yield from compound 11.
Interestingly, we found that oxidation of 25 to 27 can occur at
higher temperatures prior to exposure to air or alumina, and we
speculate that the starting 10 can act as an oxidant under these
reaction conditions. Evidence for this is the presence of 26 in
the reaction mixture wherein the isolated alkene has been
reduced.
We hypothesize that the steric demands of 25 hinder the
endo-approach of the dienophile and thereby preclude
subsequent Diels−Alder reactivity. In support of this
hypothesis, geometry optimized DFT calculations of 25
indicate that the newly added arm adopts a conformation
blocking endo-approach to the diene (Figure 3).
Scheme 8. Final Synthesis of 2
Scheme 9. Possible Mechanism for Reduction vs Elimination
with Only the Central Ring Shown for Clarity
Figure 3. Geometry optimized DFT calculation of 25 showing steric
blocking of subsequent Diels−Alder reactions (see Supporting
Information for computational details). Side view (left) and topdown view (right).
stoichiometry of SnCl2, increasing the concentration of the
reaction, and varying the solvent. We found that in certain
solvents, such as acetonitrile or chloroform/methanol, HCl is
unnecessary; presumably the Lewis acidity of SnCl2 enables the
loss of hydroxide and generation of the carbocation 31 as
shown in Scheme 9. The use of a large excess of SnCl2 (∼50
equiv) also favors reduction over elimination, leading to the
desired polyacene product. These conditions allow for the
conversion of tetraol 30 to the desired polyacene dimer 2 in
91% crude yield (Scheme 8).
Attempts to purify 2 proved challenging. Polyacenes can
suffer from partial oxidation on silica as well as aggregation,
which provides insoluble material that does not elute. Multiple
crystallization methods were attempted, but none were
successful. A workable solution was found in the differential
solubility of 2 relative to its impurities; 2 is less soluble in
chloroform than its oxidation products, such as 9. As a result,
pure samples can be obtained by subjecting crude material to
several chloroform extractions. While this provides material of
sufficient purity for spectroscopic studies, it reduces the amount
of pure 2 obtained. The reduction in the yield of 2 by this
procedure varies and can be 30% or more depending on the
scale and the run. Photophysical studies of 2, including a UV−
visible absorption spectrum, have been reported.45 The
absorption spectrum shows Davydov splitting of the S3 ← S0
transition in the UV region from ∼260−320 nm as expected for
2 versus 1 (see discussion in the Introduction).
The modularity of our synthesis allows us to prepare systems
with improved physical properties. For example, in order to
The synthesis then continued with 27, which we note is
linear and cannot adopt a bent conformation similar to that of
25 (Scheme 7). Compound 27 was treated with 3 equiv of 10
under solvent-free conditions (the solid reactants were first
taken up in chloroform, and then the solvent was removed
under reduced pressure to provide a homogeneous paste) and
heated to 220 °C under nitrogen. This provided 29, which was
oxidized in the presence of Al2O3 and air to form bis-quinone 9
in 65% yield from 27. The overall yield from 11 to 9 is 39%
over four steps after purification by flash chromatography.
The reduction of 9 to 2 was then studied, and we made use
of the NaBH4/SnCl2 procedure described above. Subjecting
bisquinone 9 to NaBH4 provided a complex diastereomeric
mixture of tetraols (30) in 74% yield (Scheme 8). Subsequent
reduction to the bisacene dimer 2 was not as facile as the model
system (17), and an unproductive side reaction to provide
ketonic products was partially observed. We speculate that this
reaction proceeds via the cation derived from protonation and
ionization of one of the alcohols of the tetraol (31, Scheme 9).
This intermediate can undergo either reduction with SnCl2
(desired) or loss of a proton to provide the phenol (32) which
preferentially exists as the keto-tautomer as described above.
Several aspects of the reaction were varied in order to
minimize this elimination pathway, including increasing the
E
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pounds 1061 and 1160 were prepared according to literature
procedures. Compound 1362 was prepared by a modification of a
literature procedure described below. 1H NMR spectroscopy was
performed at 500 MHz or at 300 MHz in CDCl3 using residual CHCl3
as an internal standard (7.26 ppm). 13C NMR spectroscopy was
performed at 75 MHz in CDCl3 using the center line of solvent (77.16
ppm) as an internal standard. High resolution mass spectra (HRMS)
were recorded using electrospray ionization (ESI q-TOF). HRMS was
calculated on the molecular ion [M]+, the protonated [M + H]+, or the
lithiated [M + Li]+ species. Molecular ions [M]+ were observed on
polyacene compounds 1, 2, and 3, and while this is unusual with ESI
ionization, it is not without precedent75,76 and has been observed in
related polyacenes.41,77
5,6-Dimethylidene-2-norbornene (13). A 350 mL glass sealed-tube
reactor was flame-dried, and 5,6-di(chloromethyl)-2-norbornene62
(3.0 g. 15.7 mmol, 1 equiv) was added by syringe followed by
potassium isopropoxide (77 mL of a 0.91 M solution in isopropanol;
70.1 mmol, 4.5 equiv). The flask was sealed and then heated to 120 °C
behind a plexiglass blast-shield. The reaction was monitored via TLC
(20:1 hexanes/EtOAc; KMnO4 visualization). Upon the disappearance
of starting material (∼48 h), the reaction was cooled to room
temperature and distilled pentane was added followed by deionized
water. The layers were separated, and the organic layer was washed five
times with water to remove residual alcohol. The organic layer was
dried over MgSO4, filtered, and concentrated by rotary evaporation
without heating to provide 13 as a light yellow oil (1.37 g, 11.6 mmol,
74%).62
1
H NMR (500 MHz, Chloroform-d) δ 6.22 (t, J = 1.8 Hz, 2H), 5.19
(s, 2H), 4.98 (s, 2H), 3.33 (app. pent, J = 1.7 Hz, 2H), 1.79 (A of
ABX2, J = 8.2, 1.6 Hz, 1H), 1.60 (B of ABX2, br, J = 8.2, 1.5 Hz, 1H);
13
C NMR (100 MHz, Chloroform-d) δ 149.1, 136.8, 101.6, 51.7, 50.9;
HRMS (ESI/Q-TOF) m/z: [M + H]+ calcd for C9H10H 119.0861;
found 119.0872.
Hexacyclo[18.2.1.02,19.04,17.06,15.08,13]tricosa-2(19),3,6,8,10,12,14,17,21-nonene-5,16-dione (12). Compounds 13 (0.20 g, 1.69 mmol,
1.25 equiv), 1061 (0.282 g, 1.36 mmol, 1 equiv), and toluene (7 mL)
were added to a 150 mL glass sealed-tube reactor, and the vessel was
sealed and heated to 150 °C behind a blast-shield. The reaction was
monitored via TLC (20:1 hexanes/EtOAc; KMnO4 visualization) for
the disappearance of starting material (∼48 h) upon which the
solution was cooled and concentrated at reduced pressure to provide a
brown solid. This material was not purified but was instead subjected
to oxidative aromatization by the addition of basic alumina (∼16 g).
This suspension was stirred for 10 min, and then the solvent was
removed by rotary evaporation to provide a homogeneous orange
powder. This adsorbent was stirred dry under an atmosphere of O2 for
2 days. Aliquots were removed, and the reaction was monitored by 1H
NMR (an aliquot was flushed with 1:1 CHCl 3/EtOAc and
concentrated). Upon disappearance of starting material, the powder
was washed thoroughly with EtOAc to provide a yellow solid upon
concentration at reduced pressure (333 mg, 1.03 mmol, 76% yield).
Purification of the bulk sample was difficult due to poor solubility. As
such a small aliquot was purified for the purposes of characterization,
and the crude product was taken on to the next step.
1
H NMR (400 MHz, Chloroform-d) δ 8.81 (s, 2H), 8.19 (s, 2H),
8.10−8.08 (m, 2H), 7.69−7.67 (m, 2H), 6.83 (t, J = 1.9 Hz, 2H), 4.11
(app. pent, J = 1.6 Hz, 2H), 2.46 (A of ABX2, J = 7.7, 1.5 Hz, 1H), 2.33
(B of ABX2, br, J = 7.7, 1.5 Hz, 1H); 13C NMR (100 MHz,
Chloroform-d) δ 183.5, 159.3, 142.7, 135.2, 132.9, 130.2, 130.0,
129.39, 129.36, 119.7, 69.3, 50.7; HRMS (ESI/Q-TOF) m/z: [M +
H]+ calcd for C23H14O2H 323.1072; found 323.1061.
Hexacyclo[18.2.1.0 2,19 .0 4,17 .0 6,15 .0 8,13 ]tricosa-2(19),3,5,7,9,11,13,15,17,21-decene (1). To a flame-dried 50 mL round-bottom
flask (RBF) was added 12 (55 mg, 0.171 mmol, 1 equiv), in CHCl3 (2
mL) and MeOH (2 mL). The solution was cooled in an ice bath,
NaBH4 (13.5 mg, 0.355 mmol, 2.0 equiv) was added in a single solid
portion, and the reaction was warmed to room temperature. The
reaction was monitored by TLC (CHCl3 eluent, UV visualization) for
the disappearance of the starting material (∼1 h), upon which
stannous chloride (324 mg, 1.71 mmol, 10 equiv) was added. This
circumvent the aforementioned difficulties tied to purification,
solubility, and study of 2, an analogue, 3, bearing
triisopropylsilyl (TIPS) acetylene substituents was targeted
for synthesis (Scheme 10). Such substitution is known to
Scheme 10. Final Synthesis of 3
increase the stability of acene systems toward oxidation while at
the same time increasing solubility in organic media.71,74 To
accomplish this, 9 was subjected to alkynylation with the
Grignard reagent derived from TIPS-acetylene to provide the
corresponding tetraol as a mixture of diastereomers (33). This
material was not isolated, but instead treated directly with
SnCl2/HCl to obtain the tetra-alkyne substituted polyacene 3
in 81% yield. As in the case of the parent system, the UV−
visible absorption spectrum of this material also shows Davydov
splitting in the region from ∼275 to 350 nm (see Figure S1 in
the Supporting Information).
■
CONCLUSION
Acene dimers 2 and 3 were synthesized via a modular Diels−
Alder approach. The syntheses proceed via bisquinone
intermediate 9 that can be subjected to either hydride addition
or alkynylation followed by SnCl2 reduction to provide the
aromatic product. The TIPS-alkyne derivative was synthesized
for its superior stability and solubility as compared to the parent
hydrocarbon. Our route has allowed us to prepare tetracene
compounds, and this route can be applied to the synthesis of
other geometrically defined acene derivatives. For example, we
have studied the extension of this chemistry to the pentacene
series, and while we have evidence that this route is viable for
the synthesis of the pentacene homologue of 3, we have
encountered issues of solubility, purification, and reactivity that
must be addressed before we can prepare analytically pure
material for photophysical studies. Finally, as a general
platform, acene dimers of this nature provide a framework for
testing hypotheses about the role of orbital symmetry in
determining state coupling for SF, and work is currently
underway to synthesize variants51 bearing Cs and C2 point
group symmetry by related routes.
■
EXPERIMENTAL SECTION
General Information. All reactions were run under a nitrogen
atmosphere unless otherwise specified. Tetrahydrofuran was distilled
from sodium benzophenone ketyl, and toluene from calcium hydride
prior to use. Hexanes was distilled prior to use to remove nonvolatile
impurities, and acetonitrile was HPLC grade and stored over 4 Å mol
sieves. Unless otherwise noted, all reagents were obtained from
commercial suppliers and used without further purification. ComF
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reduced pressure and redissolved in water, and the insoluble product
was filtered. The solids were allowed to dry overnight to yield 30 as a
light brown powder (18 mg, 0.032 mmol, 74%). This compound was
isolated as an inseparable mixture of up to seven diasteromers and
provided a complex 1H NMR spectrum that was not amenable to
tabulation.
HRMS (ESI/Q-TOF) m/z: [M + Li]+ calcd for C39H28O4Li
567.2148; found 567.2145.
Decacyclo[18.18.1.0 2,19 .04,17 .0 6,15.08,13 .0 21,38 .0 23,36 .025,34.027,32]nonatriaconta-2(19),3,5,7,9,11,13,15,17,21(38),22,24,26,28,30,32,34,36-octadecaene (2). Compounds 30 (15 mg, 0.027 mmol, 1
equiv) was dissolved in acetonitrile (5.4 mL) via sonication, and
stannous chloride (267 mg, 1.41 mmol, 52 equiv) was added. The
reaction was monitored by TLC (CHCl3 eluent, UV visualization) and
subjected to workup when 30 was no longer visible (∼30 min). The
reaction was concentrated under reduced pressure, redissolved in
toluene via sonication, and filtered to remove the insoluble metal salts,
and the filtrate was concentrated under reduced pressure to provide
crude 2 (12 mg, 0.024 mmol, 91%). This was rinsed with chloroform
(1 mL) to provide 2 as a yellow powder of sufficient purity for
spectroscopic studies and 1H NMR. Because this compound is poorly
soluble in common organic solvents, obtaining a 13C NMR was not
practical. In addition, using 119Sn NMR on a model system, we
confirmed by comparison with solutions of known concentration that
tin compounds are efficiently removed by the workup procedure. We
used a model system that is available in larger scale so as to have better
sensitivity in order to detect traces of tin.
1
H NMR (500 MHz, CDCl3) δ 8.57 (s, 4H), 8.48 (s, 4H), 7.97−
7.95 (m, 4H), 7.84 (s, 4H), 7.37−7.35 (m, 4H), 4.62 (s, 2H), 2.61 (s,
2H); HRMS (ESI/Q-TOF) m/z: [M]+ calcd for C39H24 492.1878;
found 492.1881.
5,16,24,35-Tetra(2-(tri-isopropyl-silyl)-ethynyl)decacyclo[18.18.1.02,19.04,17.06,15.08,13.021,38.023,36.025,34.027,32]nonatriaconta-2(19),3,5,7,9,11,13,15,17,21(38),22,24,26,28,30,32,34,36-octadecaene (3). To an oven-dried round-bottom flask under N2 was
added isopropyl magnesium chloride (0.45 mL, 2.0 M in THF, 0.9
mmol, 25 equiv) followed by (triisopropylsilyl)acetylene (0.10 mL,
0.45 mmol, 12.5 equiv) and anhydrous toluene (1 mL). This was
slowly heated to 110 °C for 15 min. In a separate flask, compound 9
(20 mg, 0.036 mmol, 1.0 equiv) was dissolved via sonication in
anhydrous toluene (2 mL) and added to the reaction dropwise via
cannula while at reflux. The reaction was maintained at reflux
overnight and subjected to workup after 24 h, at which point 9 was no
longer visible by TLC (CHCl3 eluent, UV visualization). The reaction
was removed from the heat source and allowed to cool for 5 min, and
SnCl2 (2 mL of saturated SnCl2 in a 1.0 M HCl solution) was slowly
added dropwise while the solution was still warm. The reaction was
allowed to stir for 1 h and then filtered through a plug of silica
(CH2Cl2 eluent). The combined organics were washed with water (2
× 10 mL), dried over Na2SO4, and concentrated under reduced
pressure. The crude material was purified by flash chromatography on
silica gel (packed with hexanes then eluted with hexanes then 20:1
hexanes/EtOAc) to provide 3 as a red paste (35.6 mg, 0.029 mmol,
81%).
1
H NMR (500 MHz, CDCl3) δ 9.22 (s, 4H), 8.52 (s, 4H), 7.99−
7.97 (m, 4H), 7.44−7.42 (m, 4H), 4.65 (s, 2H), 2.68 (s, 2H), 1.39−
1.33 (m, 84H); 13C NMR (75 MHz, CDCl3) δ 146.4, 132.7, 132.0,
130.2, 128.6, 126.1, 125.9, 118.8, 118.3, 50.8, 19.1, 18.6, 11.8; HRMS
(ESI/Q-TOF) m/z: [M]+ calcd for C83H104Si4 1212.7215; found
1212.7214.
solution turned a light-yellow hue and then bright orange over the
course of 10 min. The flask was wrapped in aluminum, and the
solution was stirred overnight under N2 after which toluene (10 mL)
and water (10 mL) were added. The heterogeneous mixture was
filtered through a plug of Celite, washed with toluene, and the biphasic
mixture was separated. The organic layer was washed with water (3
times), dried over MgSO4, filtered, and then concentrated to a yellow
solid. Purification by flash chromatography (1:1 hexanes/chloroform)
provided 1 (35 mg, 0.122 mmol, 71%) as a yellow powder.
1
H NMR (500 MHz, Chloroform-d) δ 8.58 (s, 2H), 8.43 (s, 2H),
7.99−7.97 (m, 2H), 7.66 (s, 2H), 7.39−7.37 (m, 2H), 6.68 (s, 2H),
3.98 (s, br, 2H), 2.35 (A of AB, br, J = 7.8 Hz, 1H), 2.21 (B of AB, br, J
= 7.8 Hz, 1H); HRMS (ESI/Q-TOF) m/z: [M]+ calcd for C23H16
292.1252; found 292.1249.
21,22-Dimethylenehexacyclo[18.2.1.02,19.04,17.06,15.08,13]tricosa-2(19),3,6,8,10,12,14,17-octaene-5,16-dione (27). Compounds 1160
(208 mg, 1.44 mmol, 1.0 equiv) and 1061 (301 mg, 1.44 mmol, 1.0
equiv) were dissolved in toluene (40 mL) and stirred at 70 °C (sand
bath). The reaction was monitored by TLC (hexanes eluent, UV
visualization) and subjected to workup when 11 was no longer visible
(∼48 h). Basic alumina (∼3 g) was then added to the mixture, and the
solution stirred vigorously while exposed to air. The progress of the
reaction was followed by NMR, and the reaction was subjected to
workup when the initial Diels−Alder adduct was no longer visible
(∼48 h). The solution was then filtered, and the alumina was rinsed
with chloroform (∼400 mL). The filtrate was concentrated under
reduced pressure and purified by flash chromatography on silica gel
(packed with hexanes then eluted with 7:1 hexanes/EtOAc) to provide
compound 27 as a yellow powder (302 mg, 0.867 mmol, 60% over two
steps).
1
H NMR (300 MHz, CDCl3) δ 8.82 (s, 2H), 8.23 (s, 2H), 8.11−
8.06 (m, 2H), 7.71−7.66 (m, 2H), 5.29 (s, 2H), 5.19 (s, 2H), 4.06 (X
of ABX2, J = 1.5 Hz, 2H), 2.20 (A of ABX2, J = 9, 1.5 Hz, 1H), 2.07 (B
of ABX2, J = 9, 1.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 183.3,
153.3, 146.6, 135.3, 134.1, 130.2, 130.0, 129.51, 129.48, 119.8, 104.3,
52.8, 51.4; HRMS (ESI/Q-TOF) m/z: [M + Li]+ calcd for
C25H16O2Li 355.1310; found 355.1309.
Decacyclo[18.18.1.02,19.04,17 .06,15 .08,13 .021,38.023,36.025,34.027,32 ]nonatriaconta-2(19),3,6,8,10,12,14,17,21(38),22,25(34),26,28,30,32,36-hexadecaene-5,16,24,35-tetrone (9). Compounds 27 (201
mg, 0.577 mmol, 1.0 equiv) and 1061 (361 mg, 1.73 mmol, 3.0 equiv)
were dissolved in chloroform (50 mL). The chloroform was then
removed under reduced pressure to provide a red-orange paste that
was heated under nitrogen at 220 °C (sand bath). The reaction was
monitored by NMR and subjected to workup when 27 was no longer
visible (∼24 h). The solids were dissolved in chloroform (40 mL), and
basic alumina (∼3 g) was added to the mixture. The solution was then
stirred vigorously while exposed to air, and the progress of the reaction
was monitored by NMR. The reaction was subjected to workup when
the initial Diels−Alder adduct was no longer visible (∼24 h). The
mixture was then filtered, and the alumina was rinsed with chloroform
(∼400 mL). The filtrate was concentrated under reduced pressure and
purified by flash chromatography on silica gel (packed with hexanes
then eluted with CHCl3) to provide 9 as a brown powder (207 mg,
0.375 mmol, 65%).
1
H NMR (300 MHz, CDCl3) δ 8.81 (s, 4H), 8.36 (s, 4H), 8.09−
8.06 (m, 4H), 7.69−7.66 (m, 4H), 4.76 (s, 2H), 2.79 (s, 2H); 13C
NMR (75 MHz, CDCl3) δ 183.0, 155.5, 135.2, 133.8, 130.3, 129.7,
129.63, 129.58, 120.9, 51.7; HRMS (ESI/Q-TOF) m/z: [M + Li]+
calcd for C39H20O4Li 559.1522; found 559.1551.
Decacyclo[18.18.1.02,19.04,17 .06,15 .08,13 .021,38.023,36.025,34.027,32 ]nonatriaconta-2(19),3,6,8,10,12,14,17,21(38),22,25(34),26,28,30,32,36-hexadecaene-5,16,24,35-tetrol (30). Compound 9 (24 mg,
0.043 mmol, 1.0 equiv) was dissolved in methanol (3 mL) and
chloroform (0.4 mL) and cooled to 0 °C (ice water bath). NaBH4
(176 mg, 4.65 mmol, 107 equiv) was slowly added in three portions
(brief exposure to air) over 2 h. The reaction was then allowed to
slowly come to room temperature. The reaction was monitored by
TLC (CHCl3 eluent, UV visualization) and subjected to workup when
9 was no longer visible (∼24 h). The reaction was concentrated under
■
ASSOCIATED CONTENT
S Supporting Information
*
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.7b00602.
Proton and carbon NMR spectra for compounds 1, 2, 3,
9, 12, 13, and 27, UV−vis spectrum of 3, and
computational data for DFT geometry optimization of
25 (PDF)
G
DOI: 10.1021/acs.joc.7b00602
J. Org. Chem. XXXX, XXX, XXX−XXX
Article
The Journal of Organic Chemistry
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AUTHOR INFORMATION
Corresponding Authors
*E-mail: [email protected].
*E-mail: [email protected].
ORCID
Tarek Sammakia: 0000-0003-3703-5672
Niels H. Damrauer: 0000-0001-8337-9375
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
We thank Dr. Ryan Michael for experimental assistance and Dr.
Akin Akdag for useful discussions. We acknowledge support
from the Chemical Sciences, Geosciences, and Biosciences
Division, Office of Basic Energy Science, U.S. Department of
Energy through Grant DE-FG02-07ER15890. This work
utilized the Hopper supercomputer of the National Energy
Research Scientific Computing Center, which is supported by
the Office of Science of the U.S. Department of Energy under
Contract No. DE-AC02-05CH11231. The authors would like
to acknowledge the University of Colorado Boulder Central
Analytical Laboratory Mass Spectrometry Core Facility
(partially funded by NIH S10 RR026641) for mass
spectrometry analysis.
■
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