Polyynes to Polycycles: Domino Reactions Forming Polyfused Chalcogenophenes

Article abstract of DOI:10.1021/acs.orglett.0c00733

Polyfused chalcogenophenes are prepared in one step through polyelectrophilic cyclization of polyynes using the ambiphilic reagent MeACl (A = S, Se, or Te). Up to four new rings have been generated under mild conditions, including thiophenes, selenophenes, and tellurophenes.

Full text of DOI:10.1021/acs.orglett.0c00733

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Letter
Polyynes to Polycycles: Domino Reactions Forming Polyfused
Chalcogenophenes
Annaliese S. Dillon and Bernard L. Flynn*
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ABSTRACT: Polyfused chalcogenophenes are prepared in one step through polyelectrophilic cyclization of polyynes using the
ambiphilic reagent MeACl (A = S, Se, or Te). Up to four new rings have been generated under mild conditions, including
thiophenes, selenophenes, and tellurophenes.
Scheme 1. Electrophilic Cyclization of Diynes and Polyynes
inearly (3,2-b) fused chalcogenophenes have emerged as
Lextremely valuable functional π-systems in exciton science,
finding applications in organic solar cells, organic light-emitting
diodes, and semiconductors.1 To date, the exploration of
chalcogenophenes in materials science has been dominated by
thiophenes; however, considerable interest lies in exploiting the
superior properties of the heavier and more metallic chalcogens,
Se and Te, and their associated heterocycles, selenophenes and
tellurophenes.2 While synthetic approaches to polyfused
thiophenes are reasonably well developed,1 these do not always
translate well to selenophenes and even less so to tellurophenes.
Indeed, despite the significant interest in tellurophenes in
materials science, there are no previous reports of three or more
contiguously fused tellurophenes.3
An attractive strategy for gaining direct access to polyfused
chalcogenophenes is the conversion of polyynes to polycycles in
a single step.4−8 Recent advances in this approach have been
achieved through exploiting the capacity of chalcogens to
operate as either double electrophiles in double-electrophilic
cyclization (DEC) in the form of ACl2 (A = chalcogen) or
ambiphiles (possessing both electrophilic and nucleophilic
reactivity) in Fe-promoted cascade cyclization (Scheme 1,
previous work).5−8 In the case of the cascade cyclization, FeCl3
increases the electrophilicity of dibutyldiselenide conferring
ambiphilic reactivity. Herein, we report the use of simple chloro
methyl chalcogens (MeACl, where A = S, Se, or Te) as highly
effective ambiphiles in polyelectrophilic cyclization (PEC)
reactions, with excellent atom economy requiring no other
reagents to gain efficient access to up to four new chalcogen-
containing rings, including examples of contiguously fused
tellurophenes.
For this study, we prepared a series of alkyne and polyyne
substrates 1 from 2-iodothioanisole (Scheme 2). These
syntheses were accomplished in one or three steps and involved
Sonogashira couplings, silyl deprotections, and Cadiot−
Chodkiewicz couplings using terminal and bromo alkynes
Received: February 26, 2020
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© XXXX American Chemical Society
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Scheme 2. Synthesis of Alkynyl Substrates 1
Scheme 4. Formation of 2bS
This issue of competing addition of MeACl was much less
apparent in PEC reactions involving MeSeCl and MeTeCl.
These reactions generally went to completion between −20 and
0 °C for MeSeCl and at rt for MeTeCl, giving the respective
chalcogen-containing heteroacenes in good yield (50−100%).
Only in the case of tetracyclization to form 2eSe was the fully
annulated product formed in a complex mixture of other
byproducts (suspected MeSe/Cl addition products). Heating
this reaction mixture to reflux in DCE for 48 h led to a significant
increase in the level of formation of 2eSe at the expense of
bearing phenyl or silyl (SiR′3 = TMS or TIPS) substituents (see
the Supporting Information for details). In this way, a series of
mono-, di-, tri-, and tetraynes were efficiently prepared for use in
our PEC studies with ambiphilic MeACl (A = S, Se, or Te)
reagents.
1
The chalcogen reagents (MeACl) are most atom econom-
ically formed by addition of Cl2(g) to the associated dimethyl
dichalcogen (MeA-AMe). However, for our lab-scale studies,
SO2Cl2 has been employed as a more convenient chlorinating
agent on a small scale. Thus, SO2Cl2 was added to MeA-AMe in
dichloromethane (DCM) to generate MeACl [with loss of
SO2(g)] for direct use. These DCM solutions of MeACl were first
evaluated as suitable electrophiles by reaction with simple 2-
(phenylethynyl)-thioanisole 1a (n = 1; R = Ph). Efficient
formation of benzochalcogenophenes 2aS (88%), 2aSe (70%),
and 2aTe (81%) reflected effective formation of each respective
reagent MeACl (Scheme 3). This efficient initial installation of a
Me-A group also opened up the possibility of consecutive
cyclizations (PEC reactions) for polyynes 1b−e. These PEC
reactions with MeACl were generally successful and were most
successful for A = Se and Te (Scheme 3).
Despite performing well in the monocyclization of 1a to give
2aS, PEC of diyne 1c (R = Ph) with MeSCl gave a complex
mixture (not shown). By contrast, reaction of MeSCl with diyne
1b (R = TIPS) at 0 °C initially gave a monocyclized product
containing a MeS/Cl adduct 3 (kinetic product) (Scheme 4).
This material was successfully converted into the fully cyclized
benzothienothiophene 2bs (thermodynamic product, 49%)
upon heating. The mechanism of this reaction is discussed
below.
byproducts giving semipure 2eSe in 50% yield by H NMR.
Chromatographic separation of 2eSe from these byproducts
proved to be difficult, and recrystallization afforded pure 2eSe in
10% yield only.
We next considered the possibility of generating extended
heteroacenes through bidirectional PEC (biPEC). For this
purpose, we generated two substrates, tetraynes 6 and 9
(Scheme 5). Tetrayne 6 was prepared from 1,4-dibromo-2,5-
diiodobenzene 5 by initial Sonogashira coupling of TIPS-diyne
(TIPS-CC-CC-H), followed by lithiation and thiomethylation
to give 6 in an overall 90% yield (from 5). Preparation of
tetrayne 9 commenced with Sonogashira coupling of 89 to TIPS-
diyne, followed by desilylation and homocoupling, giving 9 in
67% yield (from 8).
Both the diverging biPEC, 6 + MeSeCl → 7Se (30%), and the
converging biPEC, 9 + MeACl → 10S (61%) and 10Se (81%),
were successful. The modest yield of 7Se was attributed to the
poor solubility of the product.
Attempts to perform the diverging and converging biPEC
with MeTeCl were complicated by poor solubility, in the case of
the reaction of 6, and the formation of complex mixtures, in the
case of the reaction of 9.
The structural characterization of these heteroacenes is
reflected mostly in the 13C NMR, where the alkyne carbons
are replaced with diagnostic chalcogenophene carbon reso-
Scheme 3. Polyelectrophilic Cyclization (PEC) of Polyynes 1 to Chalcogenophenes 2
a
b
Reaction required heating of an intermediate chlorochalcogen addition product to bring the cyclization to completion (see the main text). The
1
yield shown is based on conversion in the H NMR; the isolated yield from recrystallization was 10% (all other yields are isolated yields).
B
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in the polyyne substrate (11−13), but only 11 is productive in a
5-endo-digonal cyclization (Scheme 6A).
Scheme 5. Bidirectional Application of PEC
The precise nature of the electrophile−alkyne complex 11
may fluctuate among 11a−d (Scheme 6, box) and depends on
the nature of the substituents on the alkyne and the nature of the
chalcogen, A.10 In circumstances where either or both of the
alkyne substituents are capable of stabilizing a positive charge
(electron-donating groups), vinyl cations 11c and 11d may
dominate.10 Of these two vinyl cations, only 11c is capable of
cyclization (productive), though unproductive 11d may partake
in reversible addition [Cl− attack (not shown)]. The capacity of
the different chalcogens A to form cyclic activation complexes
11a and 11b may also vary, possibly in the order A = Te > Se > S.
Nucleophilic Cl− attack on an unproductive vinyl cation of the
type 11d was apparent in the reaction of dyne 1b with MeSCl
(Schemes 4 and 6B). As described above, this reaction initially
yields a product of sequential monocylization and MeSCl
addition to give 3, which upon heating gave 2bS (Scheme 4). It
is proposed that initial cyclization of 1b proceeds through any
one of the “productive” intermediates 11a−c (Scheme 6, box) to
give benzothiophene 14 (Scheme 6B). However, the 3-
(methylthio)-benzothiophenyl group in 14 acts as a strong
donor, favoring the “unproductive” vinyl cation 15 (akin to
11d). Intermediate 15 is stabilized by delocalization of the
positive charge into the ring and onto the two S atoms. It is
incapable of cyclization but can undergo Cl− attack to give 3
(kinetic product). Heating, promotes reversible expulsion of Cl−
from 3 back to 15 and sustained access to the less favored yet
productive thiirenium cation 16 (akin to 11b, likely to dominate
over the corresponding vinyl cation 11c, due to R′ = TIPS
nances in the product. Also, MS gave diagnostic isotopic
patterns for Se and Te compounds (correct HRMS also
obtained). UV spectra of selected products show a general right
shift in the absorption maxima with an increasing number of
heterocyclic rings, in particular tellurophenes such as 2eTe.9
Mechanistically for PEC, we envisage electrophilic MeACl (or
MeA+) may form an activation complex with any of the alkynes
Scheme 6. Mechanistic Consideration in PEC of Polyynes
C
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electronics), which undergoes irreversible cyclization to give 2bs
(thermodynamic product).11
AUTHOR INFORMATION
Corresponding Author
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The more facile access to PEC products 2b-eSe/Te may be
due to a stronger preference for the “productive” cyclic
activation complexes 11a and 11b (A = Se and Te) that reduce
the influence of unfavorable electronic bias.10b Alternatively, the
competing addition reactions are much more reversible, and the
thermodynamic PEC products form at lower temperatures.
In stark contrast to the complications arising from the PECs
involving MeSCl and polyynes 1b and 1c (1b gives addition
products 3 and 1c as a complex mixture), reaction of tetrayne 9
with MeSCl proceeded smoothly to give the symmetrical
tetracyclized product 10S, under kinetic conditions. We propose
that this arises from a seesawing mechanism involving
alternating shifts in electron density from one end of the
polyyne to the other with each cyclization step (Scheme 6C).
After the initial cyclization of symmetrical 9 with MeSCl to give
monocyclized product 17 (A = S), the resultant electron-rich 3-
(methylthio)-benzothiophenyl group (more electron rich than
the phenyl group) drives the electron density to distal alkynyl
carbon (indicated by δ−), favoring cyclization via stabilized
cation intermediate 18 to give diyne 19. Monocylization of
symmetrical 19, via 20, gives 21. In the final cyclization of
unsymmetrical 21, again, the more electron-dense 3-(methyl-
thio)-benzothiophenothiophenyl group directs attack of MeSCl
to the remote carbon, favoring cyclization via the most stabilized
cation 22 to give 10S. A similar scenario is likely for MeSeCl.
Attempts to observe or selectively form 17, 19, or 22 (A = S or
Se) by reducing the stoichiometry of MeACl returned only 10S/
Se and unreacted 9. Presumably, the accumulating electron
density in the polyyne with each incorporation of MeACl
(electron density in 21 > 19 > 17 > 9) increases the rate of each
subsequent cyclization, giving an accelerating domino reaction
terminating in 10S/Se.
Again, in stark contrast to the successful unidirectional PEC
reactions involving MeTeCl and substrates 1, reaction of 9 with
MeTeCl gave complex mixtures. Possibly, MeTeCl generates
predominantly the cyclic activation complexes 11a and 11b (A =
Te) that help overcome unfavorable electronic bias associated
with the unidirectional PEC, i.e., which avoids unproductive
complex 11d. However, in the converging biPEC, where similar
vinyl cation intermediates are favorably disposed to the seesaw
mechanism, the preference for 11a and 11b (A = Te) may lead
to a mixture of different unsymmetrical and symmetrical
cyclization products (to be confirmed).
In conclusion, MeACl (A = S, Se, or Te) reacts with suitable
polyynes to provide atom economical access to chalcogen-based
heteroacenes through PEC. This method generally requires no
purification as volatile MeCl is the sole byproduct. It can be used
to access thiophenes, selenophenes, and tellurophenes under
mild conditions. Both uni- and bidirectional (diverging and
converging) PEC reactions have been demonstrated to afford
efficient access to structural classes of significant interest to
emerging areas of photonic and electronic materials.
Bernard L. Flynn − Monash Institute of Pharmaceutical Sciences,
Monash University, Parkville 3052, Victoria, Australia;
Email: Bernard.flynn@monash.edu
Author
Annaliese S. Dillon − Monash Institute of Pharmaceutical
Sciences, Monash University, Parkville 3052, Victoria, Australia;
orcid.org/0000-0003-4410-2423
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c00733
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The authors thank Dr. Carl Braybrook, CSIRO Manufacturing,
for MS analyses.
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* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00733.
Description of synthesis and characterization (PDF)
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