Palladium-mediated strategies for functionalizing the dihydroazulene photoswitch: Paving the way for its exploitation in molecular electronics

Article abstract of DOI:10.1021/jo400362u

The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has attracted interest as a molecular switch for advanced materials and molecular electronics. We report here two synthetic approaches using palladium catalysis for synthesizing dihydroazulene (DHA) photoswitches with thioacetate anchoring groups intended for molecular electronics applications. The first methodology involves a Suzuki coupling using tert-butyl thioether protecting groups. Conversion to the thioacetate using boron tribromide/acetyl chloride results in the formation of the product as a mixture of regioisomers mediated by a ring-opening reaction. The second approach circumvents isomerization by the synthesis of stannanes as intermediates and their use in a Stille coupling. Although fully unsaturated azulenes are formed as byproducts during the synthesis of the DHA stannanes, this approach allowed the regioselective incorporation of the thioacetate anchoring group in either one of the two ends (positions 2 or 7) or at both.

Full text of DOI:10.1021/jo400362u

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Article
Palladium Mediated Strategies for Functionalizing the Dihydroazulene
Photoswitch – Paving the Way for its Exploitation in Molecular Electronics
Martyn Jevric, Søren Lindbæk Broman, and Mogens Brøndsted Nielsen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo400362u • Publication Date (Web): 05 Apr 2013
Downloaded from http://pubs.acs.org on April 14, 2013
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Palladium Mediated Strategies for Functionalizing the
Dihydroazulene Photoswitch – Paving the Way for its
Exploitation in Molecular Electronics
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Martyn Jevric, Søren Lindbæk Broman, and Mogens Brøndsted Nielsen*
Department of Chemistry & NanoꢀScience Center, University of Copenhagen, Universitetsparken 5,
DKꢀ2100 Copenhagen Ø, Denmark
Eꢀmail: mbn@kiku.dk
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if
required according to the journal that you are submitting your paper to)
Graphical Abstract
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The dihydroazulene (DHA) / vinylheptafulvene (VHF) photo/thermoswitch has attracted interest as
a molecular switch for advanced materials and molecular electronics. We report here two synthetic
approaches using palladium catalysis for synthesizing dihydroazulene (DHA) photoswitches with
thioacetate anchoring groups for molecular electronics applications. The first methodology involves
a Suzuki coupling using tertꢀbutylthioether protecting groups. Conversion to the thioacetate using
boron tribromide / acetyl chloride results in the formation of the product as a mixture of
regioisomers mediated by a ringꢀopening reaction. The second approach circumvents isomerization
by the synthesis of stannanes as intermediates and their use in a Stille coupling. Although fully
unsaturated azulenes are formed as byꢀproducts during the synthesis of the DHA stannanes, this
approach allowed the regioselective incorporation of the thioacetate anchoring group in either one
of the two ends (positions 2 or 7) or at both.
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Keywords: Dihydroazulene, Molecular wire, Photoswitch, Stille coupling, Suzuki coupling
Introduction
Dihydroazulene (DHA, 1) is a fascinating molecule; it has photoswitching properties, whereby it
undergoes a 10ꢀelectron retroꢀelectrocyclization upon irradiation at ca. 360 nm to furnish a
vinylheptafulvene (VHF) and is coupled with a thermally induced ringꢀclosure reaction to revert
back to the bicycle (Scheme 1).1 The ringꢀclosure itself is believed to proceed via a zwitterionic
transition state.2
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Scheme 1. Reversible DHAꢀVHF Interconversions.
Recent developments in DHA chemistry notably include the selective functionalization of the 7ꢀ
position of the dihydroazulene core (for numbering, see Scheme 1) with bromine by the addition of
elemental bromine and an elimination sequence using lithium hexamethyldisilazide (LiHMDS).2, 3
The regioselective introduction of bromine to the 7ꢀposition has since been exploited by palladium
catalyzed crossꢀcoupling reactions, namely Sonogashira2a,b and to a greater extent Suzuki
protocols2c,3 to furnish DHAs bearing a variety of substituents at the 7ꢀposition. In addition, we
have recently optimized the protocol for DHA synthesis to allow its preparation in multiꢀgram scale
starting from acetophenone.4 These synthetic developments have fuelled the exploitation of this
photoactive compound in advanced systems; for example, suitable derivatives have recently been
the subject of conductivity studies in singleꢀmolecule molecular electronics devices.3, 5
The most commonly used anchoring group to gold is the thiol.6 This air sensitive group can be
conveniently masked as the thioacetate, which can be easily liberated upon treatment with mild base
and adhered to gold in situ. Recent studies have shown that a DHA incorporating an SAc anchoring
group at the 2ꢀposition (via a tolane linker) can be assembled on a gold surface at which reversible
DHAꢀVHF switchings were observed,7 which warrants the further exploitation of these molecules
in lightꢀcontrolled devices. Yet, unlike other more commonly employed photoswitches, such as for
example dithienylethenes,8 a DHA bearing two acetylꢀprotected thiolate anchoring groups has not
yet been reported. So far only the synthesis of a DHA functionalized with two SMe endꢀgroups has
been described.3 The possibility for stronger thiolate anchoring at two specific positions, one in
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each end of the molecule, by cleavage of acetylꢀprotecting groups is desirable for controlling the
positioning of molecules between for example two metal electrodes, although a strong coupling
between electrode and molecule may in some cases quench photoactivity.5 Here we present
synthetic protocols for obtaining such derivatives, which is particularly challenging on account of
the sensitive nature of the DHA system.
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Results and Discussion
It was envisaged that using palladium catalysis, one could synthesize a system where the
thioacetate moiety could be situated at opposing poles of the DHA. Our original Sonogashira
coupling approach was discarded as we had previously experienced instability of compounds with
an arylethynyl substituent group positioned at the 7ꢀposition of DHA if the aryl group did not
include also methyl substituents at the ortho positions relative to the alkyne, which renders
synthesis somewhat tedious.2b Instead, we turned first to the Suzuki reaction.9 The Suzuki reaction
too has its limits, in that not all functional groups are tolerated. A twoꢀstep strategy was investigated
where a Suzuki reaction was employed to introduce the masked thiol, now as a tertꢀbutylthioether at
the 2ꢀ and 7ꢀpositions. The group was introduced at position 2 according to the route shown in
Scheme 2. First, the known aryl bromide 210 was lithiated and treated with N,Nꢀdimethylacetamide
(DMA) to furnish the acetophenone derivative 3, which has previously been prepared by other
routes.11 A Knoevenagel condensation with malononitrile then afforded compound 4, which by
deprotonation with triethylamine reacted with tropylium tetrafluoroborate 5 to provide the product
6. Finally, hydride abstraction followed by deprotonation gave the VHF intermediate, which
converted to the DHA 7 upon heating.
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Scheme 2. Synthesis of DHA Functionalized with tertꢀbutylthio Substituent. DMA = N,Nꢀ
dimethylacetamide.
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The three DHA compounds 1, 7, and 812 (Scheme 3) were now subjected to the brominationꢀ
elimination protocol, which gave the 7ꢀbromoꢀsubstituted intermediates 9, 10, and 113. To our
delight, the thioether 7 was found to be compatible with these reaction conditions, despite the
presence of the potentially oxidatively sensitive thioether and it seemed no side reactions had
occurred during the brominationꢀelimination as verified by crude NMR analysis at each stage of the
preparation of the 7ꢀbromide. The three halogenated DHAs were then each treated with the known
4ꢀ(tertꢀbutylsulfanyl)phenylboronic acid13 (12) as coupling partner to furnish the final Suzuki
products 13, 14, and 15 in reasonable yields over the three steps. In all systems the Suzuki
chemistry was applicable at room temperature utilizing RuPhos / Pd(OAc)2 as the catalytic system
(RuPhos = 2ꢀdicyclohexylphosphinoꢀ2',6'ꢀdiisopropoxybiphenyl). Notably, the double Suzuki
reaction furnished the product 15 in an overall yield of 53%.
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Scheme 3. Functionalization via BrominationꢀElimination Protocol Followed by Suzuki Couplings
and SꢀProtection Group Interconversions.
Treatment of each of these thioethers with the standard deprotection/acetylation conditions,10
namely boron tribromide (BBr3) and acetyl chloride (AcCl), resulted in the desired functional group
transformation of the thioethers into thioacetates (Scheme 3), but in each case also resulted in the
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temporary ring opening to VHF. Strong Lewis acids have previously been observed to induce ringꢀ
opening of DHA to VHF.14 All the reactions required a large excess of BBr3 to ensure complete
consumption of the starting material (ca. 5 equivalents per functional group). A sudden color
change during the reaction to a brilliant purple was indicative of suspected VHFꢀBBr3 complex
formation (Scheme 4).14a As previously described, quenching with water breaks up such a complex
to VHF, which ultimately converts thermally to DHA. To our dismay, in all cases, we isolated
DHAs where scrambling had occurred to a mixture of the phenylthioacetate situated either on the 6ꢀ
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1
or the 7ꢀposition (compounds 16/16’ 4:5, 17/17’ 2:3, 18/18’ 1:2, ratios obtained from H NMR
spectra). This scrambling effect has been observed previously during lightꢀheat cycle experiments
(DHA→VHF→DHA),2 but was in the present cases a result of the BBr3 induced ringꢀopening of
DHA to VHF as the reaction was conducted in the dark. The mechanism of the scrambling is due to
the free rotation about the fulvene bond on account of its significant singleꢀbond character; thus
there are two possibilities of reforming the bicyclic DHA structure (Scheme 4). Separation of these
sets of regioisomers was not accomplished (fractional crystallization proved fruitless, while tedious
purification using column chromatography could potentially result in some isomeric enrichment).
Scheme 4. Lewis Acid Induced Isomerizations Between 7ꢀ and 6ꢀSubstituted DHAs. R1 and R2
Correspond to Aryl Groups.
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It was decided to seek an alternate strategy to enforce a regioselective synthesis of 18. It has
been demonstrated in the literature that halogenated azulenes could be successfully transformed to
their corresponding stannanes by heating in the presence of hexabutyltin and catalytic Pd(PPh3)4.15
Indeed, unlike the Suzuki protocol, Stille coupling conditions have a greater tolerance of most
functional groups,16 and it was hoped that this methodology could be used to introduce the sulfur
directly as the thioacetate in the final step. The added advantage of this strategy was the fact that a
reactive coupling partner could be employed in the reaction, which was then not at the mercy of the
sometimes seemingly unreactive bromine at the 7ꢀposition. To probe the Stille reaction, two
standard tin end groups were chosen for this study, tributyl and trimethyl. Indeed, subjecting a
series of halogenated DHAs (8, 9, 11) with hexaalkyldistannanes gave the monoꢀ and bisꢀtin
compounds 19ꢀ22 in moderate to excellent yields (Scheme 5). The use of hexabutylditin led to a
lower yield of the stannane 19 and an increased amount of the corresponding fully unsaturated
azulene byꢀproduct (vide infra). Azulenes result from the loss of hydrogen cyanide, which usually
occurs under basic conditions.2, 17 In addition, the metallation of the 7ꢀposition, although possible in
moderate yield over three steps for the introduction of the trimethylstannyl moiety, did not allow for
significant quantities of the tributyl analogues to be synthesized and was not further explored. All
DHAs could be effectively separated from the azulenes using flash column chromatography in the
dark (to avoid ringꢀopening of the DHA).
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Scheme 5. Functionalizations via Stille Couplings. The starting materials 9 and 11 were freshly
prepared from 1 and 8, respectively, according to Scheme 3.
The stannanes were then subjected to Stille coupling conditions, using the catalytic system of
Pd2(dba)3 (dba
=
dibenzylideneacetone) and AsPh3 in refluxing toluene. Using 4ꢀ
iodophenylthioacetate 2318 as the coupling partner resulted in rapid formation of the desired
products 24, 16, and 18 in decent yields (except for the 7%ꢀyield of 24 obtained by conversion of
the tributylstannane 19) and, gratifyingly, as single regioisomers. It has previously been shown that
large rate enhancements of Stille couplings are obtained by using triphenylarsine as ligand;19
indeed, fast reactions were desirable due to the somewhat sensitive nature of the thioacetate group.
Usually, vinyl stannanes are more reactive than aryl stannanes,20 but conversion of DHA stannanes
20ꢀ22 required the same reaction times (15 min). Particularly noteworthy is the synthesis of our
main target molecule 18 (Figure 1) by the double Stille coupling. The down side is that a high
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catalyst loading was required for the reaction to be effective as reaction times needed to be short so
as to minimalize competitive side reactions, which are likely a reflection of the lability of the
thioacetate moiety and warrant further investigation.
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Figure 1. DHA Endꢀcapped with Two SAc Groups.
The fully unsaturated azulene byꢀproducts obtained from the stannation reactions all had a
characteristic purple color and their structures (25ꢀ28) and isolated yields are shown in Figure 2.
These compounds, which were all fully characterized, could be interesting precursors for further
azulene scaffolding, targeting electrochromic materials.21 Indeed, Stille crossꢀcouplings have
previously been used successfully for functionalization of azulenes at position 6.15, 22 Compounds
27 and 28 present instead convenient precursors for coupling reactions at position 7. The yields of
these byꢀproducts, were low, as desired in the present work in which high yields of the
dihydroazulenes 19ꢀ22 were instead targeted, but as HCN is so easily eliminated from the
dihydroazulenes, optimization of azulene formulation should be possible.
Figure 2. Azulene Byꢀproducts Formed in the Stannation Reactions.
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Conclusion
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In summary, it is possible to introduce the thioacetate groups to the 2ꢀ and 7ꢀpositions of DHA
using palladium catalysis. Future studies look to incorporate some of these compounds, in particular
compound 18, into break junction or other molecular electronics devices. Several techniques for
entrapping and measuring electrical properties of molecules in metallic contact gaps exist23 and the
bent structure of 18 is not expected to pose a problem in this regard.24 The Suzuki route gives rise to
an inseparable mixture of 6ꢀ and 7ꢀisomers after deprotection of the tertꢀbutylthioether facilitated by
the presence of BBr3. In light of this finding, efforts are under way to induce regioselective control
in ring closing reactions of substituted VHFs to afford an efficient synthesis of either the 6ꢀ or 7ꢀ
isomer. The convenient synthesis of stannanes holds much potential for further development of
DHA chemistry, although formation of fully unsaturated azulene byꢀproducts could not be avoided.
Such byꢀproducts could, however, show promise as building blocks for development of new
azulene derivatives. The Stille protocol worked particularly well for the trimethylstannanes, and in
this synthetic approach, the Lewis acid BBr3, inducing ringꢀopening of DHA, was conveniently
avoided. The DHA stannanes could be versatile synthons not only just for the introduction of SAc
groups to the DHA core, but possibly for introducing other anchoring groups, such as pyridyls or
fullerenes, for introducing fluorine to the 7ꢀposition, or for generating dimeric structures of DHA,
and hence molecules with potential for multimode switching.
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Experimental
General Methods. Chemicals were used as purchased from commercial sources. THF was
distilled from a sodium/benzophenone couple. Purification of products was carried out by flash
chromatography on silica gel (40−63 ꢁm, 60 Å). Thinꢀlayer chromatography (TLC) was carried out
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using aluminum sheets precoated with silica gel. H NMR (500 MHz) and 13C NMR (125 MHz)
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spectra were recorded on an instrument with a nonꢀinverse cryoprobe using the residual solvent as
the internal standard (CDCl3, 1H 7.26 ppm and 13C 77.16 ppm) All chemical shifts are quoted on the
δ scale (ppm), and all coupling constants (J) are expressed in Hz. In APT spectra, CH and CH3
correspond to negative signals and C and CH2 correspond to positive signals. Mass spectra (MS)
were acquired either using an electrospray method of ionization or by FAB. HRMS spectra were
obtained on a QꢀTOF instrument. IR spectra were recorded of neat samples using the attenuated
total reflectance (ATR) sampling technique. Melting points are uncorrected. For the stannanes, the
m/z for the most intense signal is listed.
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1-[4-(tert-Butylthio)phenyl]ethanone (3). To a stirring solution of the 4ꢀbromophenyl tertꢀbutyl
sulfide 2 (6.50 g, 26.5 mmol) in dry THF (100 mL) at ꢀ78 ºC was slowly added tertꢀbutyl lithium
solution (34 mL, 1.7M in pentane, 57.8 mmol) and the resulting yellow solution was stirred for 15
min. DMA (5.0 mL, 54 mmol) was added in one portion and the contents of the vessel were
allowed to reach rt, and stirring was allowed to continue for a further 30 min. The contents were
cooled in an ice bath and 1M HCl (100 mL) was added to the vessel. The mixture was diluted with
both water (200 mL) and diethyl ether (200 mL) and the phases separated. The aqueous phase was
extracted once with ether (200 mL) and the combined organic phases were dried over MgSO4,
filtered and the solvent removed in vacuo. The crude oil was further purified by flash column
chromatography (SiO2, toluene) to afford the title compound (4.28 g, 78%) as a colorless oil. TLC
1
(toluene): Rf = 0.35. H NMR (500 MHz, CDCl3) δ 7.89 (d, J = 8.5 Hz, 2H), 7.60 (d, J = 8.5 Hz,
2H), 2.60 (s, 3H), 1.31 (s, 9H) ppm. 13C NMR (125 MHz, CDCl3) δ 197.8, 139.5, 137.0, 136.9,
128.3, 47.0, 31.2, 26.8 ppm. MS (ESP+): m/z = 247 [M+K+]. Elem. anal. calc. for C12H16OS
(208.32): C: 69.20%, H: 7.75%, found: C: 69.10%, H: 7.84%.
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2-[1-(4-(tert-Butylthio)phenyl)ethylidene]malononitrile (4). A mixture consisting of the
acetophenone 3 (4.08 g, 19.6 mmol), malononitrile (5.62 g, 85.1 mmol), ammonium acetate (8.23 g,
107 mmol) in toluene (200 mL) and acetic acid (12 mL) was heated to reflux point using a Dean
Stark apparatus for 5 h (oil bath temperature ca. 180 ºC). The vessel was allowed to cool and the
contents diluted with ether (200 mL). The organic phase was washed with water (3 x 200 mL), then
with saturated brine (200 mL) and dried over MgSO4. Filtration and removal of the solvent under
reduced pressure gave a crude residue, which was purified by flash column chromatography (SiO2,
toluene) to give 4 as a pale yellow oil (4.30 g, 86%). TLC (toluene): Rf = 0.43. 1H NMR (500 MHz,
CDCl3) δ 7.64 (d, J = 8.5 Hz, 2H), 7.51 (d, J = 8.5 Hz, 2H), 2.63 (s, 3H), 1.33 (s, 9H) ppm. 13C
NMR (125 MHz, CDCl3) δ 174.5, 139.0, 137.2, 135.6, 127.4, 112.8, 84.9, 47.3, 31.2, 24.3 ppm, one
carbon masked. MS (ESP+): m/z = 279 [M+Na+]. Elem. anal. calc. for C15H16N2S (256.37): C:
70.27%, H: 6.29%, N: 10.93%, found: C: 70.20%, H: 6.19%, N: 10.71%.
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2-[2-Cyclohepta-2,4,6-trienyl-1-(4’-(tert-butylthio)phenyl)ethylidene]malononitrile (6). To a
stirring suspension of the crotonitrile 4 (4.21 g, 16.4 mmol) and freshly pulverized tropylium
tetrafluoroborate 5 (3.50 g, 19.7 mmol) in dry CH2Cl2 (200 mL), at ꢀ78 ºC, was added dropwise
NEt3 (2.60 mL, 18.0 mmol) during the course of 1 h. The contents were stirred for a further 10 min
and were then treated with 1M aqueous HCl (20 mL). The contents were then allowed to reach rt.
The crude reaction mixture was washed with water (2 x 100 mL), dried over MgSO4, filtered and
the solvent was removed in vacuo. The residue, a yellowish oil, was essentially pure 4 (5.60 g,
99%), only containing minor impurities. A small sample (ca. 100 mg) was subjected to flash
column chromatography (SiO2, toluene) to give pure the title compound as a pale yellow oil. TLC
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(toluene): Rf = 0.44. H NMR (500 MHz, CDCl3) δ 7.61 (d, J = 8.5 Hz, 2H), 7.36 (d, J = 8.5 Hz,
2H), 6.60 ꢀ 6.59 (m, 2H), 6.21 ꢀ 6.17 (m, 2H), 5.15 (dd, J = 9.1, 6.5 Hz, 2H), 3.17 (d, J = 8.0 Hz,
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2H), 2.03ꢀ1.98 (m, 1H), 1.32 (s, 9H) ppm. 13C NMR (125 MHz, CDCl3) δ 177.4, 138.4, 137.3,
134.5, 131.2, 127.4, 126.6, 122.9, 112.5, 112.5, 86.7, 47.2, 38.0, 37.9, 31.2 ppm. HRꢀMS (ESPꢀ):
m/z = 345.1447 [MꢀH]ꢀ; calc. for (C22H21N2Sꢀ): m/z = 345.1431.
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2-[4’-(tert-Butylthio)phenyl]-1,8a-dihydroazulene-1,1-dicarbonitrile (7). To a stirring solution
of the crotonitrile 6 (5.60 g, 16.2 mmol) in CH2Cl2 (200 mL) was added tritylium tetrafluoroborate
(5.90 g, 1.79 mmol) and the resulting mixture was stirred 8 h at rt, whilst protecting the vessel from
light. The vessel was placed in an ice bath and NEt3 (2.50 mL, 1.73 mmol) was added carefully
over 10 min and the mixture was stirred for 1 h. The solvent was removed in vacuo and the crude
residue was dissolved in acetonitrile (50 mL) and the vessel heated to 50 ºC for 20 min. The solvent
was removed and the crude material was purified by flash column chromatography (SiO2, 50%
CH2Cl2 / heptane) to afford pure 7 as a yellow solid (3.85 g, 69%). This compound could be
conveniently crystallized from CH2Cl2 / methanol. TLC (50% CH2Cl2 / heptane): Rf = 0.40. M.p. =
114.0 – 116.0 ºC. 1H NMR (500 MHz, CDCl3) δ 7.69 (d, J = 8.6 Hz, 2H), 7.62 (d, J = 8.6 Hz, 2H),
6.92 (s, 1H), 6.57 (dd, J = 11.3, 6.3 Hz, 1H), 6.49 (dd, J = 11.3, 6.1 Hz, 1H), 6.36 (br d, J = 6.3 Hz,
1H), 6.31 (ddd, J = 10.2, 6.1, 2.1 Hz, 1H), 5.82 (dd, J = 10.2, 3.8 Hz, 1H), 3.80 (dt, J = 3.8, 2.1 Hz,
1H), 1.33 (s, 9H) ppm. 13C NMR (125 MHz, CDCl3) δ 139.5, 138.6, 137.9, 135.7, 133.0, 131.2,
131.0, 130.6, 127.8, 126.1, 121.5, 119.6, 115.2, 112.8, 51.2, 47.0, 45.2, 31.2 ppm. MS (ESP+): m/z
= 367 [M+Na+]. Elem. anal. calc. for C22H20N2S (344.47): C: 76.71%, H: 5.85%, N: 8.13%, found:
C: 76.42%, H: 5.78%, N: 8.21%. UVꢀVis (MeCN): λDHA = 358 nm. λVHF = 478 nm.
2-[4’-(tert-Butylthio)phenyl]-7,8-dibromo-1,7,8,8a-tetrahydroazulene-1,1-dicarbonitrile
(precursor to 10). To a stirring solution of the DHA 7 (342 mg, 0.993 mmol), at ꢀ78 ºC, was added
dropwise a solution of Br2 in CH2Cl2 (1.28 mL, 0.78M, 1.00 mmol) and the reaction contents were
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allowed to stir for 1 h. The solvent was removed in vacuo to give the title compound (500 mg,
100%), which was essentially pure, but very unstable, as grey / green powder. M.p. = 132 ꢀ 145 ºC
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(decomposes). H NMR (500 MHz, CDCl3) δ 7.71 (d, J = 8.6 Hz, 2H), 7.63 (d, J = 8.6 Hz, 2H),
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7.01 (s, 1H), 6.29 (dd, J = 7.6, 2.5 Hz, 1H), 6.10 (dd, J = 12.2, 7.6 Hz, 1H), 5.93 (dd, J = 12.2, 5.6
Hz, 1H), 5.33 – 5.31 (m, 1H), 5.05 (dt, J = 2.5, 1.2 Hz, 1H), 4.66 (br s, 1H), 1.34 (s, 9H) ppm. 13C
NMR (125 MHz, CDCl3) δ 144.5, 139.0, 137.9, 136.1, 134.7, 130.2, 128.9, 126.3, 125.8, 121.7,
114.6, 111.7, 53.3, 51.5, 49.2, 47.4, 44.6, 31.2 ppm. Elem. anal. calc. for C22H20N2SBr2 (501.97): C:
52.40%, H: 4.00%, N: 5.56%, found: C: 52.29%, H: 4.13%, N: 5.55%.
7-Bromo-2-[4’-(tert-butylthio)phenyl]-1,8-dihydroazulene-1,1-dicarbonitrile (10). To a stirring
solution of the DHA 7 (344 mg, 1.00 mmol) in CH2Cl2 (20 mL), at ꢀ78 ºC, was added dropwise a
solution of bromine in CH2Cl2 (1.28 mL, 0.78M, 1.00 mmol) and the resulting solution was stirred
for 1 h. The cold bath was removed and immediately the solvent was removed using a diaphragm
pump, whilst keeping the vessel cold. The crude residue was dissolved in THF (20 mL) and cooled
in an ice bath. To this solution was added LiHMDS (1.10 mL, 1.10 mmol, 1M in toluene) and the
contents of the vessel stirred for 2 h. The reaction was quenched by the addition of saturated
aqueous NH4Cl (5 mL) and diluted with both water (50 mL) and diethyl ether (50 mL). The phases
were separated and the organic phase was dried over MgSO4, filtered and the solvent removed in
vacuo. The crude residue was purified by flash chromatography (SiO2, gradient elution 50ꢀ75%
toluene / heptane) to afford 10 (85 mg, 20%) as a bright yellow solid. TLC (60% toluene / heptane):
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Rf = 0.50. M.p. = 175 ꢀ 179 ºC (decomposes). H NMR (500 MHz, CDCl3) δ 7.68 (d, J = 8.6 Hz,
2H), 7.63 (d, J = 8.6 Hz, 2H), 6.59 ꢀ 6.48 (m, 2H), 6.34 (d, J = 5.5 Hz, 1H), 6.12 (d, J = 4.4 Hz,
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1H), 3.81 (dd, J = 4.4, 1.8 Hz, 1H), 1.34 (s, 9H) ppm. C NMR (125 MHz, CDCl3) δ 141.1, 140.9,
137.9, 136.5, 133.2, 132.2, 132.1, 130.1, 126.3, 120.5, 120.3, 120.0, 114.6, 112.4, 51.2, 47.2, 44.7,
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31.2 ppm. MS (ESP+): m/z = 445 [M+Na+]. Elem. anal. calc. for C22H19BrN2S (423.37): C:
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62.41%, H: 4.52%, N: 6.62%, found: C: 62.69%, H: 4.47%, N: 6.69%.
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7-[4-(tert-Butylthio)phenyl]-2-phenyl-1,8a-dihydroazulene-1,1-dicarbonitrile (13). To a stirring
solution of the DHA 1 (512 mg, 2.00 mmol) in CH2Cl2 (30 mL), at ꢀ78 ºC, was added dropwise a
solution of bromine in CH2Cl2 (2.56 mL, 0.78M, 2.00 mmol) and the resulting solution was stirred
for 1 h. The cold bath was removed and immediately the solvent was removed using a diaphragm
pump. The residue was dissolved in THF (30 mL) and cooled in an ice bath. To this solution was
added LiHMDS (2.10 mL, 1M solution in toluene, 2.10 mmol) and the contents of the vessel stirred
for 2 h. The reaction was quenched by the addition of saturated aqueous NH4Cl (5 mL) and was
diluted with both diethyl ether (100 mL) and water (100 mL). The phases were separated and the
aqueous phase extracted with diethyl ether (100 mL). The combined organics were dried over
MgSO4, filtered and the solvent removed in vacuo. Toluene (100 mL) and water (10 mL) were
added to the residue (containing 9) and the contents purged with argon. To this biphase was added
4ꢀ(tertꢀbutylthio)phenylboronic acid 12 (625 mg, 2.97 mmol), K3PO4 (1.35 g, 6.36 mmol),
Pd(OAc)2 (25 mg, 0.11 mmol), and RuPhos (105 mg, 0.225 mmol). The mixture was allowed to
stir in the dark for 16 h. The contents of the vessel were diluted with diethyl ether (100 mL) and
water (100 mL) and the phases were separated. The aqueous phase was extracted with CH2Cl2 (100
mL). The combined organic phase was dried over Na2SO4, filtered and the solvent removed by
rotary evaporation. The residue was subsequently purified by flash column chromatography (SiO2,
gradient elution 50ꢀ75% toluene / heptane) to afford 13 (561 mg, 67% over 3 steps) as a yellow
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crystalline solid. TLC (75% toluene / heptane): Rf = 0.53. M.p. = 150.5 ꢀ 152.5 ºC. H NMR (500
MHz, CDCl3) δ 7.76 (d, J = 7.2 Hz, 2H), 7.54 ꢀ 7.43 (m, 5H), 7.37 (d, J = 8.2 Hz, 2H), 6.91 (s, 1H),
6.83 (dd, J = 11.5, 5.7 Hz, 1H), 6.77 (d, J = 11.5 Hz, 1H), 6.37 (br d, J = 5.7 Hz, 1H), 6.03 (d, J =
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4.6 Hz, 1H), 3.85 (dd, J = 4.6, 1.5 Hz, 1H), 1.30 (s, 9H) ppm. 13C NMR (125 MHz, CDCl3) δ 141.4,
140.8, 140.4, 139.2, 137.7, 132.9, 132.8, 131.8, 131.7, 130.4, 129.4, 127.8, 126.5, 120.4, 116.8,
115.3, 113.1, 51.1, 46.4, 45.2, 31.1 ppm, one carbon masked. MS (FAB+): m/z = 420 [M+]. Elem.
anal. calc. for C28H24N2S (420.57): C: 79.96%, H: 5.75%, N: 6.66%, found: C: 79.92%, H: 5.54%,
N: 6.72%.
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2,7-Bis[4-(tert-butylthio)phenyl]-1,8a-dihydroazulene-1,1-dicarbonitrile (14). To a stirring
solution of the DHA 7 (1.32 g, 3.84 mmol) in CH2Cl2 (50 mL), at ꢀ78 ºC, was added dropwise a
solution of bromine in CH2Cl2 (5.0 mL, 0.78M, 3.9 mmol) and the resulting solution was stirred for
1 h. The cold bath was removed and immediately the solvent was removed using a diaphragm
pump. The residue was dissolved in THF (50 mL) and cooled in an ice bath. To this solution was
added LiHMDS (4.0 mL, 1M solution in toluene, 4.0 mmol) and the contents of the vessel stirred
for 2 h. The reaction was quenched by the addition of saturated aqueous NH4Cl (5 mL) and diluted
with both diethyl ether (200 mL) and water (200 mL) and the phases separated. The organic phase
was dried over MgSO4, filtered and the solvent removed in vacuo. The residue (containing 10) was
taken up in toluene (100 mL) and water (10 mL) and the contents degassed with argon. To this
solution was added 4ꢀ(tertꢀbutylthio)phenylboronic acid 12 (1.37 g, 6.52 mmol), K3PO4 (2.76 g,
13.0 mmol), Pd(OAc)2 (70 mg, 0.312 mmol), and RuPhos (276 mg, 0.591 mmol). The mixture was
allowed to stir in the dark for 48 h. The contents of the vessel were diluted with diethyl ether (200
mL) and water (200 mL) and the phases separated. The aqueous phase was extracted with CH2Cl2
(100 mL) and the combined organic phase was dried over Na2SO4, filtered and the solvent removed
under reduced pressure. The residue was subsequently purified by flash column chromatography
(SiO2, gradient elution 50ꢀ75% toluene / heptane) to afford 14 (1.15 g, 59% over the 3 steps) as a
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yellow orange powder. TLC (60% toluene / heptane): Rf = 0.43. M.p. = 140 ꢀ 142 ºC. H NMR (500
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MHz, CDCl3) δ 7.71 (d, J = 8.6, 2H), 7.63 (d, J = 8.6, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4
Hz, 2H), 6.93 (s, 1H), 6.83 (dd, J = 11.4, 5.8 Hz, 1H), 6.78 (d, J = 11.4 Hz, 1H), 6.39 (d, 5.8 Hz,
1H), 6.02 (d, J = 4.7 Hz, 1H), 3.85 (dd, J = 4.7, 1.7 Hz, 1H), 1.34 (s, 9H), 1.29 (s, 9H) ppm. 13C
NMR (125 MHz, CDCl3) δ 140.6, 140.4, 139.3, 137.9, 137.7, 136.0, 133.0, 132.7, 132.2, 132.1,
130.5, 127.8, 126.2, 120.8, 116.8, 115.1, 113.0, 51.1, 47.1, 46.4, 45.0, 31.2, 31.1 ppm; one carbon
masked. MS (FAB+): m/z = 508 [M+]. Elem. anal. calc. for C32H32N2S2 (508.74): C: 75.55%, H:
6.34%, N: 5.51%, found: C: 75.68%, H: 6.01%, N: 5.40%.
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2-(4'-(tert-Butylthio)-[1,1'-biphenyl]-4-yl)-7-[4-(tert-butylthio)phenyl]-1,8a-dihydroazulene-
1,1-dicarbonitrile (15). To a stirring solution of the DHA 8 (762 mg, 2.00 mmol) in CH2Cl2 (40
mL), at ꢀ78 ºC, was added dropwise a solution of bromine in CH2Cl2 (2.56 mL, 0.78M, 2.00 mmol)
and the resulting solution was stirred for 1 h. The cold bath was removed and immediately the
solvent was removed using a diaphragm pump. The crude mixture was dissolved in THF (50 mL)
and cooled in an ice bath. To this solution was added LiHMDS (2.1 mL, 1M solution in toluene, 2.1
mmol) and the contents of the vessel stirred for 2 h. The reaction was quenched by the addition of
saturated aqueous NH4Cl (5 mL), followed by water (100 mL) and diethyl ether (100 mL) and the
phases separated. The organic phase was dried over MgSO4, filtered and the solvent removed in
vacuo. The crude residue (containing 11) was taken up in toluene (100 mL) and water (10 mL) and
degassed 15 min before adding Pd(OAc)2 (45 mg, 0.20 mmol), RuPhos (188 mg, 0.403 mmol), and
K3PO4 (2.35 g, 11.1 mmol) and 4ꢀ(tertꢀbutylthio)phenylboronic acid 12 (1.13 g, 5.38 mmol). The
biphasic mixture was then stirred for 16 h at rt. The contents of the vessel were diluted with water
(100 mL) and diethyl ether (100 mL) and the phases separated. The aqueous phase was extracted
with CH2Cl2 (100 mL) and the combined organic phases were dried over MgSO4, filtered and the
solvent removed in vacuo. The crude residue was subjected to flash column chromatography (SiO2,
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gradient elution 50ꢀ75% toluene / heptane) to furnish 15, which was crystallized from CH2Cl2 /
ethanol giving 15 as a light yellow fibrous solid (626 mg, 53% over 3 steps). TLC (75% toluene /
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heptane): Rf = 0.43. M.p. = 169 ꢀ 171 °C. H NMR (500 MHz, CDCl3) δ 7.84 (d, J = 8.6, 2H), 7.72
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(d, J = 8.6 Hz, 2H), 7.63 (d, J = 8.5 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.37
(d, J = 8.4 Hz, 2H), 6.96 (s, 1H), 6.84 (dd, J = 11.5, 6.0 Hz, 1H), 6.78 (d , J = 11.5 Hz, 1H), 6.40
(broad d, J = 6.0 Hz, 1H), 6.04 (d, J = 4.7 Hz, 1H), 3.87 (dd, J = 4.7, 1.6 Hz, 1H), 1.34 (s, 9H), 1.30
(s, 9H) ppm. 13C NMR (125 MHz, CDCl3) δ 142.2, 140.9, 140.8, 140.4, 140.1, 139.3, 133.0, 132.9,
132.8, 131.9, 131.6, 129.7, 128.0, 127.8, 127.1, 127.0, 120.5, 116.8, 115.3, 113.1, 51.1, 46.4, 46.4,
45.1, 31.2, 31.1 ppm; two carbons masked. MS (ESP+): m/z = 607 [M+Na+]. Elem. anal. calc. for
C38H36N2S2•0.2CH2Cl2 (584.84): C: 76.24%, H: 6.10%, N: 4.65%; found C 75.79%, H 6.02%, N
4.40%.
Mixture of 16 and 16’. To a degassed stirring solution of 13 (81 mg, 0.193 mmol) in CH2Cl2 (20
mL), toluene (2 mL) and acetyl chloride (1.0 mL) was added periodically over 3 h a solution of
BBr3 (1.0 mL, 1M in CH2Cl2, mmol). Ice was added to the reaction vessel and the mixture was
diluted with water (100 mL) and CH2Cl2 (100 mL) and the phases separated. The aqueous phase
was extracted with CH2Cl2 (50 mL) and the combined organics dried over Na2SO4. The solution
was filtered and the solvent removed under reduced pressure and the crude residue purified by flash
column chromatography (SiO2, 0.8% ethyl acetate / toluene) to afford an isomeric mixture (5:4 ratio
of the 6 isomer to the 7 isomer) as a viscous orange oil (63 mg, 80%). TLC (1% ethyl acetate /
toluene): Rf = 0.38. 1H NMR (CDCl3, 500 MHz) δ 7.78ꢀ7.76 (m, 4H), 7.52ꢀ7.40 (m, 14H), 6.97 (d, J
= 6.7 Hz, 1H), 6.95 (s, 1H), 6.91 (s, 1H), 6.83 (dd, J = 11.5, 6.0 Hz, 1H), 6.75 (d, J = 11.5 Hz, 1H),
6.53 (d, J = 10.4 Hz, 1H), 6.47 (dd, J = 6.9, 1.4 Hz, 1H), 6.37 (dd, J = 6.0, 1.4 Hz, 1H), 6.04ꢀ6.01
(m, 2H), 3.85ꢀ3.82 (m, 2H), 2.45 (s, 3H), 2.43 (s, 3H) ppm. 13C NMR (CDCl3, 125 MHz) δ 194.0,
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194.0, 142.3, 142.0, 141.5, 141.2, 140.7, 139.6, 139.1, 134.8, 134.7, 132.9, 132.1, 131.6, 131.6,
130.5, 130.4, 130.3, 129.4, 128.9, 128.6, 128.4, 127.9, 127.8, 127.5, 126.5, 126.4, 120.8, 120.6,
120.3, 117.1, 115.2, 115.2, 113.0, 112.9, 51.1, 51.1, 45.1, 45.1, 30.4, 30.4 ppm; three carbons
masked. MS (ESP+): m/z = 429 [M+Na+]. HRMS (C26H18N2OSNa+): calcd 429.1032; found
429.1032 [M+Na+].
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Mixture of 17 and 17’. To a degassed stirring solution of 14 (135 mg, 0.265 mmol) in dry CH2Cl2
(50 mL), toluene (5 mL) and acetyl chloride (2.0 mL) was added a solution of BBr3 periodically
over 6 h (2.8 mL, 1.0M in CH2Cl2, 2.8 mmol). Ice was added to the vessel, followed by water (100
mL) and CH2Cl2 (100 mL) and the phases separated. The organic phase was dried over Na2SO4,
filtered and the solvent removed in vacuo. The crude residue was purified by column
chromatography (SiO2, 2% ethyl acetate / toluene) to afford an isomeric mixture (3:2 ratio of the 6
isomer to the 7 isomer) (96 mg, 75%) as a yellow solid. TLC (2% ethyl acetate / toluene): Rf = 0.39.
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M.p. = 138ꢀ141 °C. H NMR (500 MHz, CDCl3) δ 7.83ꢀ7.80 (m, 4H), 7.57ꢀ7.45 (m, 12H), 7.02 (s,
1H), 7.00 (d, J = 6.9 Hz, 1H), 6.98 (s, 1H), 6.86 (dd, J = 11.5, 6.0 Hz, 1H), 6.80 (d, J = 11.5 Hz,
1H), 6.56 (d, J = 10.3 Hz, 1H), 6.53 (dd, J = 6.9, 1.4 Hz, 1H), 6.43 (dd, J = 6.0, 1.4 Hz, 1H), 6.07ꢀ
6.04 (m, 2H), 3.88ꢀ3.86 (m, 2H), 2.49 (s, 3H), 2.49 (s, 3H), 2.48 (s, 3H), 2.46 (s, 3H) ppm. 13C
NMR (125 MHz, CDCl3) δ 194.0, 193.1, 193.1, 142.4, 142.2, 141.1, 140.4, 140.4, 139.6, 139.2,
139.2, 135.1, 134.8, 134.7, 133.2, 132.9, 132.8, 132.0, 131.4, 131.3, 130.6, 130.5, 128.8, 128.6,
128.5, 128.0, 127.9, 127.5, 126.9, 126.9, 121.6, 121.1, 120.6, 117.1, 115.0, 115.0, 112.8, 112.7,
51.0, 51.0, 45.0, 45.0, 30.5, 30.4, 30.4 ppm; three carbons masked. MS (ESP+): m/z = 503
[M+Na+]. Elem. anal. calc. for C28H20N2S2O2 (480.60): C: 69.97%, H: 4.19%, N: 5.83%, found C
69.68%, H 4.05%, N 5.61%.
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Mixture of 18 and 18’. To a degassed stirring solution of 15 (202 mg, 0.368 mmol) in dry CH2Cl2
(65 mL), toluene (5 mL) and acetyl chloride (2.0 mL) was added a solution of BBr3 (3.8 mL, 1.0M
in CH2Cl2, 3.8 mmol) and the resulting solution was stirred 16 h at rt. Ice was added to quench the
reaction, followed by the addition of water (100 mL) and CH2Cl2 (100 mL). The phases were
separated and the aqueous component was extracted with CH2Cl2 (50 mL). The combined organics
were dried over MgSO4, filtered and the solvent removed in vacuo. The crude residue was purified
by column chromatography (SiO2, 2% ethyl acetate / toluene) to afford an isomeric mixture (2:1
ratio of the 6 isomer to the 7 isomer) (125 mg, 65%) as an orange yellow solid. TLC (2% ethyl
acetate / toluene): Rf = 0.37. M.p. = 213ꢀ225 °C. 1H NMR (500 MHz, CDCl3) δ 7.86ꢀ7.84 (m, 4H),
7.73ꢀ7.70 (m, 4H), 7.68ꢀ7.66 (m, 4H), 7.53ꢀ7.50 (m, 6H), 7.46ꢀ7.41 (m, 6H), 6.99 (s, 1H), 6.98 (d, J
= 6.9 Hz, 1H), 6.96 (s, 1H), 6.84 (dd, J = 11.5, 6.0 Hz, 1H), 6.76 (d, J = 11.5 Hz, 1H), 6.54 (d, J =
10.3 Hz, 1H), 6.49 (dd, J = 6.9, 1.3 Hz, 1H), 6.39 (dd, J = 6.0, 1.4 Hz, 1H), 6.06ꢀ6.03 (m, 2H),
3.87ꢀ3.84 (m, 2H), 2.47 (s, 3H), 2.46 (s, 3H), 2.45 (s, 3H), 2.43 (s, 3H) ppm. 13C NMR (125 MHz,
CDCl3) δ 194.0, 194.0, 194.0, 142.3, 142.1, 141.9, 141.8, 142.1, 141.0, 140.9, 140.7, 140.2, 139.5,
139.1, 135.1, 134.8, 134.7, 132.9, 132.1, 131.7, 131.7, 129.9, 129.8, 128.8, 128.6, 128.4, 128.1,
127.9, 127.9, 127.9, 127.5, 127.0, 126.9, 121.0, 120.6, 117.1, 115.2, 115.2, 113.0, 112.9, 51.1, 51.0,
45.0, 45.0, 30.4, 30.4, 30.4 ppm; nine carbons masked. MS (ESP+): m/z = 579 [M+Na+]. Elem.
anal. calc. for C34H24N2S2O2 (556.70): C: 73.36%, H: 4.35%, N: 5.04%, found C: 73.18%, H:
3.91%, N: 4.75%.
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2-[4-(Tributylstannyl)phenyl]-1,8a-dihydroazulene-1,1-dicarbonitrile (19). To an argon
degassed solution consisting of DHA 8 (383 mg, 1.00 mmol) and Bu6Sn2 (1.0 mL, 2.29 mmol) in
dry benzene (50 mL) was added Pd(PPh3)4 (80 mg, 0.0692 mmol) and the resulting solution was
heated at reflux point until either TLC had indicated consumption of starting material or 16 h. The
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solvent was removed in vacuo and the crude residue was purified by flash column chromatography
(SiO2, gradient elution of 25% toluene / heptane to toluene) to afford 19 as an orange oil (355 mg,
65%), and the corresponding azulene 25 as a dark purple oil (104 mg, 20%). DHA 19: TLC (50%
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toluene / heptane): Rf = 0.50. H NMR (500 MHz, CDCl3) δ 7.67 (d, J = 8.3 Hz, 2H), 7.58 (d, J =
8.3 Hz, 2H, Sn satellites JSnH = 36.5, 34.9 Hz), 6.90 (s, 1H), 6.57 (dd, J = 11.3, 6.4 Hz, 1H), 6.47
(dd, J = 11.3, 6.1 Hz, 1H), 6.34ꢀ6.29 (m, 2H), 5.83 (dd, J = 10.2, 3.8 Hz, 1H), 3.79 (dt, J = 3.8, 2.0
Hz, 1H), 1.61ꢀ1.51 (m, 6H), 1.35 (h, J = 7.3 Hz, 6H), 1.16ꢀ1.04 (m, 6H), 0.90 (t, J = 7.3 Hz, 9H)
ppm. 13C NMR (125 MHz, CDCl3) δ 146.3 (Sn satellites JSnC = 361, 345 Hz), 140.8, 139.0, 137.4
(Sn satellites JSnC = 30 Hz), 131.9, 131.1, 130.9, 129.9, 127.8, 125.3 (Sn satellites JSnC = 40 Hz),
120.8, 119.6, 115.4, 113.0, 51.3, 45.2, 29.2 (Sn satellites JSnC = 21 Hz), 27.5 (Sn satellites JSnC
=
58, 56 Hz), 13.8 , 9.8 (Sn satellites JSnC = 342, 327 Hz) ppm. MS (ESP+): m/z = 569 [M+Na+].
Elem. anal. calc. for C30H38N2Sn (545.35): C: 66.05%, H: 7.03%, N: 5.14%, found C: 65.93%, H:
7.09%, N: 5.18%. 2-[4-(Tributylstannyl)phenyl]azulene-1-carbonitrile (25): TLC (50% toluene /
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heptane): Rf = 0.20. H NMR (500 MHz, CDCl3) δ 8.63 (d, J = 9.8 Hz, 1H), 8.40 (d, J = 9.8 Hz,
1H), 8.03 (d, J = 8.1 Hz, 2H), 7.77 (t, J = 9.8 Hz, 1H), 7.65 (d, J = 8.1 Hz, 2H, Sn satellites JSnH
=
37.5, 36.0 Hz), 7.56 (s, 1H), 7.53 (t, J = 9.8 Hz, 1H), 7.47 (t, J = 9.8 Hz, 1H), 1.63ꢀ1.54 (m, 6H),
1.36 (h, J = 7.3 Hz, 6H), 1.18ꢀ1.04 (m, 6H), 0.91 (t, J = 7.3 Hz, 9H) ppm. 13C NMR (125 MHz,
CDCl3) δ 152.6, 145.9, 145.0 (Sn satellites JSnC = 369, 354 Hz), 142.7, 138.8, 137.9, 137.4 (Sn
satellites JSnC = 30 Hz), 135.7, 133.9, 128.0, 127.9, 127.8 (Sn satellites JSnC = 40 Hz), 118.3,
116.5, 94.3, 29.3 (Sn satellites JSnC = 20 Hz), 27.6 (Sn satellites JSnC = 57, 56 Hz), 13.8, 9.8 (Sn
satellites JSnC = 341, 326 Hz) ppm. MS (ESP+): m/z = 542 [M+Na+]. Elem. anal. calc. for
C29H37NSn (518.32): C: 67.18%, H: 7.20%, N: 2.70%, found C: 67.01%, H: 6.90%, N: 2.51%.
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2-[4-(Trimethylstannyl)phenyl]-1,8a-dihydroazulene-1,1-dicarbonitrile (20). To a degassed
solution consisting of the DHA 8 (382 mg, 1.00 mmol) and Me6Sn2 (0.50 mL, 2.4 mmol) in dry
benzene (50 mL) was added Pd(PPh3)4 (62 mg, 0.0537 mmol) and the resulting solution was heated
at reflux point for 16 h. The solvent was removed in vacuo and the crude residue was purified by
column chromatography (SiO2, 3% THF / heptane) to afford 20 as a yellow oil (386 mg, 92%) and
the corresponding azulene 26 as a dark purple solid (12 mg, 3%). DHA 20: TLC (30% THF /
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heptane): Rf = 0.54. H NMR (500 MHz, CDCl3) δ 8.62 (d, J = 9.7 Hz, 1H), 8.39 (d, J = 9.7 Hz,
1H), 8.03 (d, J = 8.1 Hz, 2H), 7.76 (t, J = 9.7 Hz, 1H), 7.68 (d, J = 8.1 Hz, 2H, Sn satellites JSnH
=
42.0, 40.2 Hz), 7.54ꢀ7.50 (m, 2H), 7.46 (t, J = 9.7 Hz, 1H), 0.36 (s, 9H, Sn satellites JSnH = 55.5,
53.0 Hz) ppm. 13C NMR (125 MHz, CDCl3) δ 146.2 (Sn satellites JSnC = 437, 418 Hz), 140.6,
138.9, 136.7 (Sn satellites JSnC = 36 Hz), 132.1, 131.0, 127.8, 125.5 (Sn satellites JSnC = 44 Hz),
121.0, 119.6, 115.3, 112.9, 51.2, 45.2, ꢀ9.4 (Sn satellites JSnC = 355, 339 Hz) ppm. MS (ESP+): m/z
= 443 [M+Na+]. Elem. anal. calc. for C21H20N2Sn (419.11): C: 60.16%, H: 4.81%, N: 6.69%, found
C: 60.27%, H: 4.82%, N: 6.29%. 2-[4-(Trimethylstannyl)phenyl]azulene-1-carbonitrile (26):
TLC (30% THF / heptane): Rf = 0.40. M.p. = 123 ꢀ 126 ºC. 1H NMR (500 MHz, CDCl3) δ 8.62 (d, J
= 9.7 Hz, 1H), 8.39 (d, J = 9.7 Hz, 1H), 8.03 (d, J = 8.1 Hz, 2H), 7.76 (t, J = 9.7 Hz, 1H), 7.68 (d, J
= 8.1 Hz, 2H, Sn satellites JSnH = 43.2, 41.3 Hz), 7.76 (t, J = 9.7 Hz, 1H), 7.54 (s, 1H), 7.54 (t, J =
9.7 Hz, 1H), 7.46 (t, J = 9.7 Hz, 1H), 0.36 (s, 9H, Sn satellites JSnH = 55.5, 53.0 Hz) ppm. 13C
NMR (125 MHz, CDCl3) δ 152.5, 145.8, 144.9 (Sn satellites JSnC = 445, 426 Hz), 142.6, 138.9,
137.9, 136.7 (Sn satellites JSnC = 36 Hz), 135.7, 134.2, 128.1, 128.0, 127.8, 118.2, 116.6, 94.3, ꢀ9.4
(Sn satellites JSnC = 353, 337 Hz) ppm. MS (ESP+): m/z = 807 [2M+Na+], 416 [M+Na+]). Elem.
anal. calc. for C20H19NSn (392.08): C: 61.25%, H: 4.89%, N: 3.57%, found C: 61.05%, H: 4.61%,
N: 3.53%.
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2-Phenyl-7-(trimethylstannyl)-1,8a-dihydroazulene-1,1-dicarbonitrile (21). To
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solution of DHA 1 (512 mg, 2.00 mmol) in CH2Cl2 (30 mL), at ꢀ78 ºC, was added dropwise a
solution of bromine in CH2Cl2 (2.56 mL, 0.78M, 2.00 mmol) and the resulting solution was stirred
for 1 h. The cold bath was removed and immediately the solvent was removed using a diaphragm
pump. The crude mixture was dissolved in THF (20 mL) and cooled in an ice bath. To this solution
was added LiHMDS (2.1 mL, 1.0M in toluene, 2.1 mmol) and the contents of the vessel stirred for
2 h. The reaction was quenched by the addition of saturated aqueous NH4Cl and the phases
separated. The organic phase was dried over MgSO4, filtered and the solvent removed in vacuo.
The residue (containing 9) was taken up in dry benzene (100 mL) and hexamethylditin (0.90 mL,
4.34 mmol) was introduced to the vessel and the contents purged with argon. To this solution was
added Pd(PPh3)4 (165 mg, 0.143 mmol) and the contents of the vessel heated to reflux point for 16
h. The vessel was allowed to cool to rt and the solvent was removed by rotary evaporation. The
residue was subsequently purified by flash column chromatography (SiO2, 50% toluene / heptane)
to afford 21 (420 mg, 50% over 3 steps) as an orange oil. Additionally, the corresponding azulene
27 (85 mg, 11%) was isolated as a purple solid. DHA 21: TLC (50% toluene / heptane): Rf = 0.35.
1H NMR (500 MHz, CDCl3) δ 7.75 (d, J = 7.3 Hz, 2H), 7.49ꢀ7.42 (m, 3H), 6.86 (s, 1H), 6.66 (d, J
= 10.7 Hz, 1H, Sn satellites JSnH = 28.1 Hz), 6.51 (dd, J = 10.7, 6.2 Hz, 1H), 6.34 (broad d, J = 6.2
Hz, 1H), 5.67 (d, J = 4.1 Hz, 1H, Sn satellites JSnH = 57.1 Hz), 3.48 (dd, J = 4.1, 1.6 Hz, 1H), 0.26
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(s, 9H, Sn satellites JSnH = 55.2, 52.8 Hz) ppm. C NMR (125 MHz, CDCl3) δ 141.9 (Sn satellites
JSnC = 399, 382 Hz). 140.6, 137.6, 136.9 (Sn satellites JSnC = 32 Hz), 132.2, 130.8, 130.0, 129.4,
128.1 (Sn satellites JSnC = 44 Hz), 126.3, 123.6 (Sn satellites JSnC = 43 Hz), 120.3, 115.5, 113.2,
52.7 (Sn satellites JSnC = 58, 56 Hz), 44.6, ꢀ8.9 (Sn satellites JSnC = 352, 336 Hz) ppm. MS (ESP+):
m/z = 443 [M+Na+]. Elem. anal. calc. for C21H20N2Sn (419.11): C: 60.16%, H: 4.81%, N: 6.69%,
found C: 60.21%, H: 4.95%, N: 6.71%. 2-Phenyl-7-(trimethylstannyl)azulene-1-carbonitrile
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(27): M.p. = 120 ꢀ 122 ºC. TLC (50% toluene / heptane): Rf = 0.18. H NMR (500 MHz, CDCl3) δ
8.78 (s,1H, Sn satellites JSnH = 50.7 Hz), 8.31 (d, J = 9.6 Hz, 1H), 8.08ꢀ8.06 (m, 2H), 7.92 (d, J =
9.6 Hz, 1H, Sn satellites JSnH = 53.1 Hz), 7.55ꢀ7.52 (m, 2H), 7.48 (s, 1H), 7.47ꢀ7.43 (m, 1H), 7.40
(t, J = 9.6 Hz, 1H, Sn satellites JSnH = 5.2 Hz), 0.47 (s, 9H, Sn satellites JSnH = 55.0, 52.6 Hz) ppm.
13C NMR (125 MHz, CDCl3) δ 152.1, 146.6 (Sn satellites JSnC = 416, 397 Hz), 146.3 (Sn satellites
JSnC = 38 Hz), 145.0 (Sn satellites JSnC = 61, 59 Hz), 142.6 (Sn satellites JSnC = 44 Hz), 142.6,
137.4, 134.7, 129.4, 129.2, 128.7, 127.6 (Sn satellites JSnC = 58, 57 Hz), 118.4, 116.0, 93.4, ꢀ8.3
(Sn satellites JSnC = 352, 337 Hz) ppm. MS (ESP+): m/z = 807 [2M+Na+], 416 [M+Na+]. Elem.
anal. calc. for C20H19NSn (392.08): C: 61.25%, H: 4.89%, N: 3.57%, found C: 61.56%, H: 4.89%,
N: 3.50%.
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7-(Trimethylstannyl)-2-[4-(trimethylstannyl)phenyl]-1,8a-dihydroazulene-1,1-dicarbonitrile
(22). To a stirring solution of the DHA 8 (1.43 g, 3.74 mmol) in CH2Cl2 (50 mL), at ꢀ78 ºC, was
added dropwise a solution of bromine in CH2Cl2 (4.9 mL, 0.78M, 3.8 mmol) and the resulting
solution was stirred for 1 h. The cold bath was removed and immediately the solvent was removed
using a diaphragm pump. The crude mixture was dissolved in THF (50 mL) and cooled in an ice
bath. To this solution was added LiHMDS (4.0 mL, 1.0M in toluene, 4.0 mmol) and the contents of
the vessel stirred for 2 h. The reaction was quenched by the addition of saturated aqueous NH4Cl
and the phases separated. The organic phase was dried over MgSO4, filtered and the solvent
removed in vacuo. The residue (containing 11) was taken up in dry benzene (100 mL) and
hexamethylditin (3.2 mL, 15.4 mmol) was introduced to the vessel and the contents purged with
argon. To this solution was added Pd(PPh3)4 (435 mg, 0.376 mmol) and the reaction vessel was set
to reflux point for 16 h. The vessel was allowed to cool to rt and the solvent as removed by rotary
evaporation. The residue was subsequently purified by flash column chromatography (SiO2, 2%
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THF / heptanes) to afford 22 (1.11 g, 51% over 3 steps) as an orange oil. Additionally, the
corresponding azulene 28 (22 mg, 1%) was isolated as a purple solid. DHA 22: TLC (30% THF /
heptane): Rf = 0.58. 1H NMR (CDCl3, 500 MHz) δ 7.69 (d, J = 8.2 Hz, 2H), 7.60 (d, J = 8.2 Hz, 2H,
Sn satellites JSnH = 42.2, 40.3 Hz), 6.87 (s, 1H), 6.65 (d, J = 10.6 Hz, 1H, Sn satellites JSnH = 28.3
Hz), 6.51 (dd, J = 10.6, 6.0 Hz, 1H), 6.33 (broad d, J = 6.0 Hz, 1H), 5.67 (d, J = 4.1 Hz, 1H, Sn
satellites JSnH = 57.3 Hz), 3.48 (dd, J = 4.1, 1.6 Hz, 1H, Sn satellites JSnH = 11.0 Hz), 0.33 (s, 9H,
Sn satellites JSnH = 55.6, 53.2 Hz), 0.25 (s, 9H, Sn satellites JSnH = 55.2, 52.7 Hz) ppm. 13C NMR
(CDCl3, 125 MHz) δ 146.0 (Sn satellites JSnC = 439, 419 Hz), 141.9 (Sn satellites JSnC = 399, 382
Hz), 140.9, 137.8, 136.8 (Sn satellites JSnC = 32 Hz), 136.7 (Sn satellites JSnC = 36 Hz), 131.8,
130.4 (Sn satellites JSnC = 11 Hz), 128.2 (Sn satellites JSnC = 44 Hz), 125.4 (Sn satellites JSnC = 45
Hz), 123.7 (Sn satellites JSnC = 44 Hz), 120.2, 115.6, 113.3, 52.7 (Sn satellites JSnC = 58, 56 Hz),
44.5, ꢀ8.9 (Sn satellites JSnC = 351, 336 Hz), ꢀ9.4 (Sn satellites JSnC = 355, 339 Hz) ppm. MS
(ESP+): m/z = 605 [M+Na+]. Elem. anal. calc. for C24H28N2Sn2 (581.91): C: 49.51%, H: 4.85%, N:
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found C: 49.47%, H: 4.85%, N: 4.69%.
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(trimethylstannyl)phenyl]azulene-1-carbonitrile (28): TLC (30% THF / heptane): Rf = 0.52. M.p.
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= 135 ꢀ 137 ºC. H NMR (500 MHz, CDCl3) δ 8.77 (s, 1H, Sn satellites JSnH = 50.7 Hz), 8.32 (d, J
= 9.5 Hz, 1H), 8.03 (d, J = 8.1 Hz, 2H), 7.92 (d, J = 9.5 Hz, 1H, Sn satellites JSnH = 53.0 Hz), 7.68
(d, J = 8.1 Hz, 2H, Sn satellites JSnH = 42.4 Hz), 7.50 (s, 1H), 7.41 (t, J = 9.5 Hz, 1H), 0.46 (s, 9H,
Sn satellites JSnH = 55.0, 52.6 Hz), 0.35 (s, 9H, Sn satellites JSnH = 55.3, 53.1 Hz) ppm. 13C NMR
(125 MHz, CDCl3) δ 152.4, 146.6 (Sn satellites JSnC = 416, 398 Hz), 146.3 (Sn satellites JSnC = 38
Hz), 145.1 144.8 (Sn satellites JSnC = 447, 427 Hz), 142.7, 142.6 (Sn satellites JSnC = 44 Hz),
137.4, 136.7 (Sn satellites JSnC = 36 Hz), 134.5 (Sn satellites JSnC = 11 Hz), 128.1 (Sn satellites
JSnC = 45 Hz), 127.5 (Sn satellites JSnC = 57 Hz), 118.4, 116.0, 93.5, ꢀ8.3 (Sn satellites JSnC = 352,
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337 Hz), ꢀ9.4 (Sn satellites JSnC = 353, 337 Hz) ppm. MS (ESP+): m/z = 578 ([M+Na]+). HRMS
(C23H27NSn2Na+): calcd 578.0073; found 578.0079 [M+Na+].
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S-[4'-(1,1-Dicyano-1,8a-dihydroazulen-2-yl)-(1,1'-biphenyl)-4-yl] ethanethioate (24). To a
stirring mixture of 4ꢀiodophenylthioacetate 23 (80 mg, 0.288 mmol), Pd2dba3 (32 mg, 0.0349
mmol) and AsPh3 (43 mg, 0.140 mmol) under an argon atmosphere in a microwave tube was added
a degassed toluene solution of the stannane 19 (94 mg in 4 mL, 0.172 mmol). The resulting solution
was heated to 110 ºC for 30 min. The cooled reaction mixture was directly loaded onto a flash
column and eluted (SiO2, 1% ethyl acetate / toluene) to afford 24 (8 mg, 7%) as a yellow solid. M.p.
= 155 ꢀ 157 ºC. TLC (1% ethyl acetate / toluene): Rf = 0.33. 1H NMR (500 MHz, CDCl3) δ 7.83 (d,
J = 8.6 Hz, 2H), 7.70 (d, J = 8.6 Hz, 2H), 7.66 (d, J = 8.5 Hz, 2H), 7.52 (d, J = 8.5 Hz, 2H), 6.94 (s,
1H), 6.58 (dd, J = 11.3, 6.2 Hz, 1H), 6.49 (dd, J = 11.3, 5.7 Hz, 1H), 6.37 (broad d, J = 5.7 Hz, 1H),
6.32 (ddd, J = 10.2, 6.2, 2.1 Hz, 1H), 5.84 (dd, J = 10.2, 3.8 Hz, 1H), 3.82 (dt, J = 3.8, 2.1 Hz, 1H)
2.46 (s, 3H) ppm. 13C NMR (125 MHz, CDCl3) δ 194.0, 141.7, 141.0, 139.7, 138.8, 135.0, 132.5,
131.1, 131.0, 129.9, 128.0, 127.9, 127.8, 126.9, 121.3, 119.6, 115.3, 112.9, 51.2, 45.3, 30.4 ppm;
one carbon masked. MS (ESP+): m/z = 429 [M+Na+]. Elem. anal. calc. for C26H18N2OS (406.50):
C: 76.83%, H: 4.47%, N: 6.90%, found C: 77.09%, H: 4.22%, N: 6.64%.
S-[4'-(1,1-Dicyano-1,8a-dihydroazulen-2-yl)-(1,1'-biphenyl)-4-yl] ethanethioate (24). To a
stirring mixture of 4ꢀiodophenylthioacetate 23 (140 mg, 0.503 mmol), Pd2dba3 (63 mg, 0.0688
mmol) and AsPh3 (79 mg, 0.258 mmol) under an argon atmosphere in a microwave tube was added
a degassed toluene solution of the stannane 20 (140 mg in 4 mL, 0.334 mmol). The resulting
solution was heated to 110 ºC for 15 min. The cooled reaction mixture was directly loaded onto a
flash column and eluted with 1% ethyl acetate / toluene to afford 24 (98 mg, 72%) as a yellow solid.
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S-[4-(3,3-Dicyano-2-phenyl-3,3a-dihydroazulen-5-yl)phenyl] ethanethioate (16). A thoroughly
degassed solution of the stannane 21 (67 mg, 0.160 mmol) in toluene (4 mL) was added via cannula
to a deoxygenated microwave vessel containing 4ꢀiodophenylthioacetate 23 (70 mg, 0.252 mmol),
Pd2dba3 (32 mg, 0.0349 mmol) and AsPh3 (39 mg, 0.127 mmol). The resulting solution was heated
to 110 °C for 15 min and then allowed to cool to ambient temperature. The solution was subjected
to flash column chromatography (SiO2, 2% ethyl acetate / toluene) to afford 16 (43 mg, 66%) as a
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yellow solid. M.p. = 132 ꢀ 134 ºC. H NMR (500 MHz, CDCl3) δ 7.76 (dd, J = 8.3, 1.3 Hz, 2H),
7.51ꢀ7.40 (m, 7H), 6.91 (s, 1H), 6.83 (dd, J =11.4, 6.0 Hz, 1H), 6.76 (d, J = 11.4 Hz, 1H), 6.37 (dd,
J = 6.0, 1.6 Hz, 1H), 6.02 (d, J = 4.7 Hz, 1H), 3.84 (dd, J = 4.7, 1.6 Hz, 1H), 2.43 (s, 3H) ppm. 13C
NMR (125 MHz, CDCl3) δ 194.0, 141.5, 141.2, 140.8, 139.1, 134.7, 132.9, 131.6, 130.4, 129.4,
128.6, 126.5, 120.3, 117.1, 115.2, 113.0, 51.1, 45.1, 30.4 ppm; three carbons masked. MS (ESP+):
m/z = 429 [M+Na+]. Elem. anal. calc. for C26H18N2OS (406.11): C: 76.83%, H: 4.47%, N: 6.90%,
found C: 76.93%, H: 4.48%, N 7.06%.
S-{4-[2-(4'-(Acetylthio)-[1,1'-biphenyl]-4-yl)-3,3-dicyano-3,3a-dihydroazulen-5-yl]phenyl}
ethanethioate (18). A thoroughly degassed solution of 22 (52 mg, 0.0894 mmol) in toluene (4 mL)
was added via cannula to a deoxygenated microwave vial containing 4ꢀiodophenylthioacetate 23
(80 mg, 0.288 mmol), Pd2dba3 (34 mg, 0.0371 mmol) and AsPh3 (43 mg, 0.140 mmol). The
resulting solution was heated to 110 °C for 15 min and then allowed to cool to ambient temperature.
The solution was then subjected to flash column chromatography (SiO2, 2% ethyl acetate / toluene)
to result in the isolation of 18 (16 mg, 33%) as a yellow solid. M.p. = 208 ꢀ 211 ºC. IR (ATR): ν
2920w, 2852vw, 1418w, 1396m, 1350w, 11116m, 1092m, 1014w, 1004m, 943m, 916w, 902w,
853w, 839w, 757m, 544m cmꢀ1. 1H NMR (500 MHz, CDCl3) δ 7.85 (d, J = 8.6 Hz, 2H), 7.72 (d, J
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