Linear and Angular Heteroacenes from Double-Electrophilic Cyclization (DEC) and DEC-Reductive Elimination of Diynes

Article abstract of DOI:10.1021/acs.orglett.7b00265

Linear and angular heteroacenes are prepared from terminal alkynes bearing tethered nucleophiles in two steps. Linear heteroacenes are formed from the homocoupling of these alkynes followed by reaction with a double electrophile (ECl₂) to induce a tricyclization reaction cascade involving double-electrophilic cyclization (DEC). Related angular heteroacenes are formed from the prior substitution of the chloro groups in ECl₂ with the same terminal alkyne followed by reaction with AuCl₃ to produce a DEC-reductive-elimination (DECRE) reaction.

Full text of DOI:10.1021/acs.orglett.7b00265

Letter
pubs.acs.org/OrgLett
Linear and Angular Heteroacenes from Double-Electrophilic
Cyclization (DEC) and DEC-Reductive Elimination of Diynes
Akhil Gupta and Bernard L. Flynn*
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville Victoria 3052,
Australia
S
* Supporting Information
ABSTRACT: Linear and angular heteroacenes are prepared
from terminal alkynes bearing tethered nucleophiles in two
steps. Linear heteroacenes are formed from the homocoupling
of these alkynes followed by reaction with a double electrophile
(ECl2) to induce a tricyclization reaction cascade involving
double-electrophilic cyclization (DEC). Related angular heter-
oacenes are formed from the prior substitution of the chloro
groups in ECl2 with the same terminal alkyne followed by
reaction with AuCl3 to produce a DEC-reductive-elimination
(DECRE) reaction.
Scheme 2. DEC and DECRE Reactions of Alkyne 6
nterest in the electronic and photonic properties of π-rich
Iheteroacenes of the general formula 3 and 5 (Scheme 1) has
risensharplyinthelast10years.1,2 Thegeneralformulaencompass
arangeofstructuresrepresentingstableconjugated(3)andcross-
conjugated(5)polyeneswhicharefindingincreasing applications
in electronic and photonic materials, in particular, as organic
semiconductors, light-emitting diodes, field-effecttransistors, and
photovoltaics.2 Most usually, 3 and 5 are prepared from existing
heterocycles,2 though some other stepwise approaches involving
alkyne cyclization have been reported.3 Herein, we describe our
investigationsintothepossibilityofformingtheseheterocyclesina
modular manner based on double-electrophilic-cyclization
(DEC) (Scheme 1).4 To access heterocycles 3, 1 is converted
into a 1,3-butadiyne 2 that is then reacted with a double
electrophile ECl2 (E = S, Se, Te) to initiate a DEC to produce 3
(involves electrofugal expulsion of MeCl). For heterocycles 5, 1 is
first reacted with ECl2 to give a dialkynyl chalcogen 4 that is then
reacted with double electrophile AuCl3 in a related DEC-
reductive-elimination (DECRE) process (Scheme 1).5
Our investigations began with a preliminary examination of the
utility of SCl2, SeCl2 and TeCl4 as double-electrophiles in the
proposed DEC reaction on a simple alkyne substrate 6 (Scheme
2).6 TeCl4 was used in this study instead of TeCl2 in view of the
former’s greater commercial availability and lower cost. All three
electrophiles performed well in the double-electrophilic cycliza-
tion of methyl 2-(phenylethynyl)phenyl sulfide 6 when reacted in
1,2-dichloroenthane (DCE) at 60 °C to give the dibenzo[b]-
thiophenyl sulfide 7a, selenide 7b, and telluride 7d, respectively
(56−68%). The reaction performed best upon slow addition of
ECl2 to a heated solution of 6, and this became an even more
importantcriteriuminitsapplicationtothetricyclizationreactions
involving butadiynes (see below). In the reaction of 6 with TeCl4,
the initial product formed was the dibenzo[b]thiophenyl
Scheme 1. DEC and DECRE Reaction Pathways
Received: January 25, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00265
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. DEC and DECRE in Heteroacene Synthesis
Scheme 5. DEC of an Unsymmetrical Butadiyne
Scheme 6. Double Iodocyclization
(EI-MS)gaveabasepeakcorrespondingtothemacrocyclicdimer
13; however, it is most likely that this material was only formed in
trace amounts or as a fragment in the EI-MS of the polymer 12, as
13 would be expected to have suitable solubility in NMR solvents
(CDCl3 or DMSO-d6). Formation of the polymer 12 was avoided
byslowadditionofboththeelectrophile(ECl2)andthediyne10to
asolutionof1,2-dicloroethaneheatedto60°C(Scheme3).These
conditionsgavetheheteroacenes14a−dingoodyield(65−76%).
The slow addition of both reagents at elevated temperature favors
unimolecular cyclization of the key intermediate 17 to 14 over its
reaction with another molecule of diyne 10 or ECl2 (Scheme 4).
Thedialkynylselenide11wasalsosubjectedtoDECwithSeCl2 to
give the bis(benzo[b]thiopheno)-1,4-diselinine 15 (60%).
Reaction of 11 with AuCl3 was successful in producing a
DECRE process to give the angular heteroacenes 16 (51%),
presumably via an intermediate gold(III) ring (not shown).
The unsymmetrical butadiyne 20 was formed from 9 by initial
Pd coupling of iodo(trimethylsilyl)acetylene followed by
desilylation to give 18 (41%) and Pd coupling to (2-iodophenyl)-
(methyl)selane 19 to give 20 (35%) (Scheme 5). DEC of 20 with
TeCl4 followed by reductive workup (Na2S2O3) produced 21
(62%) as the first reported heteroacene containing all three
thiophene, selenophene, and tellurophene heterocycles.
Scheme 4. Formation of Key Intermediate 17
dichlorotelluride 7c, which converted to 7d upon reductive
workup (Na2S2O3). Reaction of 6 with AuCl3 proceeded as
planned and gave the DECRE product 8 (61%).
To investigate the potential for the DEC and DECRE reactions
to be used in the conversion of diynes to heteroacenes, we
converted (2-ethynylphenyl)(methyl)sulfane (9) to 1,3-buta-
diyne 10 and dialkynylselenide 11. Initial attempts to achieve a
DEC by reaction of 10 with SeCl2 in dichloromethane (DCM) at
room temperature gave rapid formation of a white solid
(precipitate). The mass of the precipitate accounted for the total
amountofreactantsadded,andtherewasnodiscerniblematerialin
the filtrate. This solid proved insoluble in most solvents, was not
characterizablebyNMR,andwasconsideredtobeapolymerofthe
type 12 (unconfirmed). Electron ionization−mass spectrometry
B
DOI: 10.1021/acs.orglett.7b00265
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Experimental details, synthetic procedures, and 1H and 13C
NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: bernard.flynn@monash.edu.
ORCID
Bernard L. Flynn: 0000-0003-4410-2423
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by Australian Research Council
(DP150103131). We thank Drs. Jo Cosgriff and Carl Braybrook,
CSIRO Manufacturing, for MS analyses.
REFERENCES
■
(1) Of the ∼3000 research papers referencing structures of the general
formula3or5(EandNu=heteroatom),>90%havebeenpublishedsince
2006 (source: SciFinder).
(2) (a) Jiang, W.; Li, Y.; Wang, Z. Chem. Soc. Rev. 2013, 42, 6113.
(b) Casado, J.; Ortiz, R. P.; Navarrette, J. T. L. Chem. Soc. Rev. 2012, 41,
5672. (c) Mishra, A.; Ma, C.-Q.; Bauerle, P. Chem. Rev. 2009, 109, 1141.
̈
(d) Ye, Q.; Chi, C. Chem. Mater. 2014, 26, 4046. (e)Cinar, M. E.;Ozturk,
T. Chem. Rev. 2015, 115, 3036. (f) Hangarge, R. V.; Gupta, A.; Raynor, A.
M.; La, D. D.; Bilic, A.; Li, J.; Dalal, D. S.; Evans, R. A.; Bhosale, S. V. Dyes
Pigm. 2017, 137, 126. (g) Xiang, W.; Gupta, A.; Kashif, M. K.; Duffy, N.;
Bilic, A.; Evans, R. A.; Spiccia, L.; Bach, U. ChemSusChem 2013, 6, 256.
(3)Forotherheteroacenesynthesesinvolvingthecyclizationofalkynes,
see: (a) Okamoto, T.; Kudoh, K.; Wakamiya, A.; Yamaguchi, S. Org. Lett.
2005, 7, 5301. (b)Okamoto, T.;Kudoh, K.;Wakamiya, A.;Yamaguchi, S.
Chem. - Eur. J. 2007, 13, 548. (c) Bilheri, F. N.; Stein, A. L.; Zeni, G. Adv.
Synth. Catal. 2015, 357, 1221. (d) Aurelio, L.; Volpe, R.; Halim, R.;
Scammells,P.J.;Flynn,B.L.Adv.Synth.Catal.2014,356,1974.(e)Gupta,
A.; Flynn, B. L. J. Org. Chem. 2016, 81, 4012. (f) Chen, H.; Delaunay, W.;
Li,J.;Wang,Z.;Bouit,P.-A.;Tondelier,D.;Geffroy, B.;Mathey,F.;Duan,
Z.; Reau, R.; Hissler, M. Org. Lett. 2013, 15, 330.
(4) For a recent review on the electrophilic activation of alkynes, see:
Godoi, B.; Schumacher, R. F.; Zeni, G. Chem. Rev. 2011, 111, 2937.
(5) For the use of AuCl3 in a 5-exo-dig cyclization of an amide onto a
tethered alkyne followed by reductive elimination, see: Egorova, O. A.;
Seo, H.;Kim, Y.;Moon, D.;Rhee, Y. M.;Ahn, K. H. Angew. Chem., Int. Ed.
2012, 51, 4511.
Figure 1. Absorption spectra of key intermediates in their chloroform
solutions (solution concentration 2 μM).
The double-iodocyclization of butadiynes can also be used to
generateheteroacenesinaseparatestep.3f,7Thus,conversionof10
to diiodide 227 gives access to the fulvene 23 (62%) by double-
Heck8 reaction, the pyrroloheteroacene 24 (42%) by a double-
Ullman-typereaction,9andthegermole25(60%)bylithiationand
reaction with Me2GeCl2 (Scheme 6).10
Giventheimportanceoftheseheterocycles, weinvestigatedthe
optical properties of key targets by measuring their UV−vis
absorption spectra in chloroform solution (Figure 1). Most of the
materials absorbed strongly in the high energy area, i.e., <400 nm
(typically 250−380 nm), with few materials exhibiting weak
absorption in the visible region (∼450 nm; 14a−d). The longest
wavelength absorption maximum (λmax) of 14b was red-shifted
morethan14a,whichinturnexertedmorered-shiftthan14d,thus
indicating that changing a heteroatom can alter the absorption
profile, and hence optical band gap, of a target chromophore. The
chemistryproposed herein provides such flexibility, andthe target
chromophores it generated can be utilized for organic electronic
applications, for example, organic field-effect transistors.
(6)FortheuseofArECl(E=S,Se)inelectrophiliccyclizations,see:Yue,
D.; Larock, R. C. J. Org. Chem. 2002, 67, 1905.
(7) Mehta, S.; Larock, R. C. J. Org. Chem. 2010, 75, 1652.
(8) Kickova, A.; Horvath, B.; Kerner, L.; Putala, M. Chem. Papers 2013,
67, 101−109.
(9)Martin,R.;Larsen,C.H.;Cuenca,A.;Buchwald,S.L.Org.Lett.2007,
9, 3379−3382.
(10) Zong, K.;Deininger, J. J.; Reynolds, J. R. Org. Lett. 2013, 15, 1032−
1035.
In conclusion, the DEC of butadiynes bearing internal
nucleophiles 2 with ECl2 (SCl2, SeCl2, and TeCl4) provides
concise, modular access to linear heteroacenes 3. This is
complimented by the double-iodocyclization of the same
butadiyne substrates to enable access to other linear heteroacenes
and by the DECRE cyclization that enables related substrates 4 to
form angular heteroacenes 5.
ASSOCIATED CONTENT
* Supporting Information
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TheSupportingInformationisavailablefreeofchargeontheACS
Publications website at DOI: 10.1021/acs.orglett.7b00265.
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DOI: 10.1021/acs.orglett.7b00265
Org. Lett. XXXX, XXX, XXX−XXX