Electrophilic Cyanative Alkenylation of Arenes

Article abstract of DOI:10.1021/acs.orglett.0c01204

A variety of appropriately substituted internal alkynes were transformed into the corresponding cyano-substituted phenanthrenes, dihydronaphthalenes, and cyclohepta-1,3,5-trienes in moderate to excellent yields by treatment with imidazolium thiocyanate 1, which serves as an easy to handle [CN]+ precursor, in the presence of BCl3. The synthetic value of the method is additionally demonstrated by the transformation of the primarily obtained products into heavily substituted quinolines. Additionally, the dynamic properties of the prepared dibenzocyclohepta-1,3,5-trienes have been investigated.

Full text of DOI:10.1021/acs.orglett.0c01204

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Letter
Electrophilic Cyanative Alkenylation of Arenes
Mingyue Zhao, Alejandro G. Barrado, Kristin Sprenger, Christopher Golz, Ricardo A. Mata,
and Manuel Alcarazo*
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ABSTRACT: A variety of appropriately substituted internal alkynes were transformed into the corresponding cyano-substituted
phenanthrenes, dihydronaphthalenes, and cyclohepta-1,3,5-trienes in moderate to excellent yields by treatment with imidazolium
thiocyanate 1, which serves as an easy to handle [CN]+ precursor, in the presence of BCl3. The synthetic value of the method is
additionally demonstrated by the transformation of the primarily obtained products into heavily substituted quinolines. Additionally,
the dynamic properties of the prepared dibenzocyclohepta-1,3,5-trienes have been investigated.
Scheme 1. Structure and Reactivity of Representative S-
based Electrophilic Cyanation Reagents
he proton-promoted cascade cyclization of polyprenoid
Tchains into complex polycyclic scaffolds is widely
recognized as an iconic example of biosynthesis and also as
one of the most efficient methods ever transferred from nature
to the laboratory for the construction of complexity.1 In fact,
there are many examples of synthetic campaigns that have been
designed to make use of such a strategy.2 Whereas most of
these cation-π cyclization cascades are triggered by the
elimination of a leaving group or the activation of olefins by
protons or π-acid catalysts, synthetic chemists have also been
keen in expanding the scope of these transformations to
additional electrophiles.3 Hence, the ring closure event(s) can
be combined with the incorporation of an exocyclic
functionality into the final polycycle, making the obtained
products synthetically more appealing. Remarkable examples of
advances in this direction are the cyclization-cascade-promoted
halonium,4 selenenium,5 and sulfenium cations;6 however,
limitations still remain. For example, the utilization of carbon-
based electrophiles as cascade initiators is comparatively
underdeveloped, despite the fact that these transformations
ideally combine the cyclization step with the formation of
exocyclic C−C bonds.
During the past few years, we have been actively involved in
the development of sulfur-based platforms able to efficiently
promote the umpolung of typical organic building blocks, such
as the cyano group. That research crystallized in the
identification of imidazolium thiocyanate 1 and 5-(cyano)
dibenzothiazolium triflate 2 as effective sources of [CN]+
synthons (Scheme 1a).7 Both reagents efficiently transfer the
cyano unit to typical S-, N-, and C-nucleophiles under metal-
free conditions. Moreover, an equimolar mixture of 1/BCl3 is
able to promote the chlorocyanation of alkynes with exquisite
levels of regio- and stereoselection (Scheme 1b).8
Being aware of the multitude of reports available describing
the intramolecular, metal-free, elementoarylation of alkynes9
Received: April 6, 2020
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© XXXX American Chemical Society
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promoted by I-,10 Br-,11 S-,16 Se-,12 B-,13 and Si-based
electrophiles (Scheme 1c);14 we envisaged that by design of
the alkyne substrates, the annulative cyanoarylation of the
carbon−carbon triple bond might be favored at the expense of
the chlorocyanation (Scheme 1d). In this Letter, the feasibility
of this hypothesis is demonstrated, and the application of the
newly developed method to the synthesis of cyano-substituted
phenanthrenes, dihydronaphthalenes, and dibenzocyclohepta-
1,3,5-trienes of different substitution patterns is described. The
prevalence of the nitrile moiety in natural products,15
pharmaceuticals,16 agrochemicals,17 dyes,18 and high-perform-
ance materials19 anticipates a broad range of applications for
the protocol described herein.
regioselective attack of the [CN]+ unit and seem to be critical
for obtaining high yields of the corresponding phenanthrenes
(Scheme 2). In fact, the reaction fails when the akyne moieties
Scheme 2. Scope of the Electrophilic Cyanation of 1-(Aryl)-
a
2-etynylbenzenes toward Phenanthrenes
Employing biphenyl 3a as the model substrate, its reaction
with thioimidazolium salt 1 in the presence of a range of Lewis
acids was evaluated. Only starting material was recovered when
AlCl3 was used as the promoter, whereas Al(TfO)3, Yb(TfO)3,
and BF3·OEt3 induced the formation of phenanthrene product
5a with excellent conversion (Table 1, entries 1−4).
Table 1. Reaction Optimization
a
entry
Lewis acid (equiv)
conv. (%)
additive
4a/5a
1
2
3
4
5
6
7
8
9
AlCl3 (1.0)
n.r.
Al(TfO)3 (1.0)
Yb(TfO)3 (1.0)
BF3·OEt3 (1.0)
BCl3 (1.0)
B(C6F5)3 (1.0)
BCl3 (1.0)
>95
>95
>95
>95
>95
n.r.
only 5a
only 5a
only 5a
1:1
1:1
b
DIPEA
b
BCl3 (1.0)
BCl3 (1.2)
78
95
6
b d
,
only 4a
only 4a
c
6
a
b
Conversions were determined by NMR. 6 = 2,6-di-tert-butylpyr-
c
d
idine, 1.0 equiv. Isolated yield. 1.2 equiv.
Interestingly, both BCl3 and B(C6F5)3 were able to enroll 1
in the desired cyclization, and cyano-substituted phenanthrene
4a could be obtained for the first time, albeit as an equimolar
mixture with 5a (Table 1, entries 5 and 6). Because the
annulation from 3a to 4a generates stoichiometric amounts of
protons and acids are known to catalyze the formation of 5a
from 3a, organic bases were incorporated in the reaction
mixture in an attempt to quench that reaction pathway.20
Interestingly, whereas DIPEA completely suppresses any
cyclization, much bulkier 2,6-di-tert-butylpyridine seems not
to interfere with the Lewis acid promoter, allowing the
conversion of 3a toward 4a in a selective manner (Table 1,
entries 7 and 8). Finally, increasing the amount of BCl3 up to
1.2 equiv substantially improved the conversion; the isolation
of 4a with an excellent (95%) yield was possible under these
conditions (Table 1, entry 9).
a
Standard conditions were used in all cases: 3a−n (1 equiv), 1 (1.2
equiv), 2,6-di-tert-butylpyridine (1.2 equiv), DCM, rt, 1 h.
are alkyl- or −NTs-substituted. In these cases, products of
alkyne chlorocyanation such as 7−9 are obtained. Contrarily,
there is relative tolerance regarding the substitution pattern at
the arene undergoing substitution. Even substrate 3c,
decorated with a strong electron-withdrawing −CF3 group,
affords the desired phenanthrene 4c in acceptable yield. The
cyclization has been successfully extended to substrates bearing
condensed arene moieties affording cyano-substituted [4]- and
[5]helicenes 4i−m. In all cases the use of 2,6-di-tert-
butylpyridine is essential to suppress the noncyanative
cyclization.
The connectivity of phenanthrene derivatives 4i and 4k and
chloroacrylonitrile 9 was confirmed by the X-ray analysis; their
structures are depicted in Figure 1 (for 4i and 9) and the
Supporting Information (for 4k).
Encouraged by the results obtained in the synthesis of
phenanthrenes from o-alkynyl biaryls, the cyclization of 1,4-
Having identified the optimal reaction conditions, the scope
and limitations of the new transformation were explored. As
expected from a cyclization proceeding through a carbocationic
intermediate, electron-rich substituents at the alkyne termini,
such as p-anisyl 3a,c−e,i or thioalkyl/aryl 3g,h, facilitate the
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uated. This cyclization toward seven-membered rings proved
to be more difficult than the ones already studied, and the use
of 2.0 equiv of BCl3 was required to accelerate the
transformation. Under these conditions, the model structure
12a smoothly underwent the desired cyclization to afford 13a
in a remarkable 73% isolated yield. However, products of
demethylation are observed in variable amounts for substrates
12b−f, all decorated with MeO groups, causing a systematic
drop in the yields of the desired cycloheptatrienes (Scheme 4).
Figure 1. Molecular diagram of the X-ray structure of 4j (left) and 9
(right). H atoms are removed for clarity, and ellipsoids are drawn at
50% probability.
Scheme 4. Cyclization of 1-Benzyl-2-etynylbenzenes into
Dibenzocyclohepta-1,3,5-trienes
diaryl-1-butynes 10a−g into the corresponding dihydronaph-
thalenes 11a−g was subsequently investigated. For this
transformation, the presence of a p-(methoxy)phenyl sub-
stituent directly attached to the alkyne moiety proved to be
essential. Once this condition was satisfied, the reaction
proceeded in moderate to good yield for a range of substrates.
Electron-donating, neutral or even moderate electron-with-
drawing substituents on the arene undergoing alkenylation are
tolerated (Scheme 3).
Scheme 3. Cyclization of 1,4-Diphenyl-1-butynes into
Dihydrophenanthrenes
For substrates containing exceptionally electron-rich aromatic
moieties, as in the case of 12h, the electrophilic cyanation at
the ring becomes a competitive reaction pathway (Scheme 4).
The X-ray structures of 13b,e−g indicate that the central
seven-membered ring adopts a boat-like conformation, and, as
consequence, these molecules are chiral, and if the inversion
barrier between the two possible boats is high enough, then the
resolution of the racemic mixture should be possible. (See the
Supporting Information for the X-ray structures of 13b,e−g.)21
In fact, from all cyclohepta-1,3,5-trienes prepared, only the
more sterically demanding 13e and 13f could be resolved into
the corresponding enantiomers by chiral stationary phase
chromatography (IG-u, Hex/iPrOH 99:1, 298 K for 13e; and
IG-u, Hex/iPrOH 97:3, 288 K for 13f). Moreover, for 13e,
which hardly racemizes at room temperature, the circular
dichroism spectra of both isolated fractions were measured.
(See the Supporting Information). As expected for enan-
tiomers, they display perfect mirror symmetry.
In all cases studied, the 6-endo-dig cyclization took place
exclusively over the alternative 5-exo pathway to afford
dihydrophenanthrenes; no trace of dihydrofulvene-type
products was observed. However, careful analysis of the
crude reaction mixtures allowed the detection of two groups of
minor side products. Namely, those derived from the
chlorocyanation of the triple bond in 10a−g and those
originated from the BCl3-promoted demethylation of the MeO
groups in 11a−g. The X-ray structures of 11a,c−e are reported
in the Supporting Information.
In a final effort to further expand the scope of this
cyanoannulation, the possibility of generating dibenzocyclo-
hepta-1,3,5-trienes from 1-benzyl-2-etynylbenzenes was eval-
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Density functional theory (DFT) calculations at the B3LYP-
D3/def2-TZVP level (with Becke−Johnson damping) addi-
tionally confirm that this is actually the case for compounds
13e and 13f.22 All calculations were carried out with the
Gaussian16 program package for the reaction pathway
optimization,23 applying the local quadratic approximation.24
The rate-determining step for the interconversion of the
enantiomers in both compounds is the flipping of the −CH2−
group in the cycloheptatriene ring. Surprisingly, the rotation of
the gear assembly formed by the naphthyl and p-(methoxy)-
phenyl moieties, or even the tBu- and p-(methoxy)phenyl ones
(in 13f and 13e, respectively), is not high enough to peak on
the calculated potential energy surface (Figure 2). The
In conclusion, an efficient method has been developed for
the cyanative cyclization of conveniently substituted alkynes
into phenanthrenes, dihydronaphthalenes, and dibenzocyclo-
heptatrienes of different substitution patterns employing
imidazolium thiocyanate 1 as a [CN]+ synthon. Substituents
such as MeO−, Cl−, Br−, Me3Si−, RS−, or CF3− are
tolerated, and the acrylonitriles obtained can be elaborated into
more complex materials by employing the rich chemistry of the
nitrile group.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01204.
General experimental procedures, characterization data,
and 1H and 13C NMR spectra of new compounds
(PDF)
Accession Codes
CCDC 1979429−1979440 and 1980636 contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/
cif, or by emailing data_request@ccdc.cam.ac.uk, or by
contacting The Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Figure 2. Reaction path profile for the inversion of 13f under the local
quadratic approximation calculated with B3LYP-D3/6-31+G(d).24
The Gibbs free energies (with the electronic energy recomputed at
the B3LYP-D3/def2-TZVP level of theory) are provided.
AUTHOR INFORMATION
■
Corresponding Author
Manuel Alcarazo − Institut fur Organische und Biomolekulare
̈
Chemie, Georg August Universitat Gottingen, 37077 Gottingen,
Germany; orcid.org/0000-0002-5491-5682;
̈
̈
̈
transition state and the minima were converged, and the free
energies were computed by applying the double-harmonic
approximation. The free energies of activation for these
inversions (ΔG#) are 24.6 (13f) and 28.2 kcal/mol (13e),
which means that their half lives at 25 °C are approximately 34
h and 1.7 years, respectively.
Finally, the synthetic utility of the building blocks obtained
is showcased by the transformation of dihydrophenanthrene
11g and cycloheptatriene 13g into quinoline derivatives 15 and
16, respectively, following an already described methodology
that consists of the addition of BuLi to the nitrile unit, the in
situ generation of a N-centered iminyl radical by treatment
with iodine, and the subsequent oxidative cyclization into the
desired quinoline (Scheme 5).25
Email: manuel.alcarazo@chemie.uni-goettingen.de
Authors
Mingyue Zhao − Institut fu
̈
r Organische und Biomolekulare
Chemie, Georg August Universitat Gottingen, 37077 Gottingen,
Germany
̈
̈
̈
Alejandro G. Barrado − Institut fu
Biomolekulare Chemie, Georg August Universitat Gottingen,
̈
r Organische und
̈
̈
̈
37077 Gottingen, Germany
Kristin Sprenger − Institut fu
̈
r Organische und Biomolekulare
̈
̈
̈
Chemie, Georg August Universitat Gottingen, 37077 Gottingen,
Germany
Christopher Golz − Institut fur Organische und Biomolekulare
̈
Chemie, Georg August Universitat Gottingen, 37077 Gottingen,
Germany
̈
̈
̈
Scheme 5. Transformation of Aryl Acrylonitriles into
a
Ricardo A. Mata − Institut fur Physikalische Chemie, Georg
̈
Polysubstituted Quinolines
̈
̈
̈
August Universitat Gottingen, 37077 Gottingen, Germany
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01204
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Support from the DFG (project identification numbers: AL
1348/7-1, INST 186/1237-1, INST 186/1324-1, and
405832858) is gratefully acknowledged. We also thank M.
a
̈
Simon (University of Gottingen) for HPLC analyses.
Reagents and conditions: (a) nBuLi, THF, 0 °C; then, I2, 60°C.
D
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Arenes and Heteroarenes with Alkynes. Chem. Rev. 2016, 116, 5894−
REFERENCES
■
5986.
(1) (a) Stork, G.; Burgstahler, A. W. The Stereochemistry of Polyene
Cyclization. J. Am. Chem. Soc. 1955, 77, 5068−5077. (b) Eschenmos-
er, A.; Ruzicka, L.; Jeger, O.; Arigoni, D. Zur Kenntnis der Triterpene.
190. Mitteilung. Eine stereochemische Interpretation der biogeneti-
schen Isoprenregel bei den Triterpenen. Helv. Chim. Acta 1955, 38,
1890−1904. (c) Eschenmoser, A.; Arigoni, D. Revisited after 50
Years: The ‘Stereochemical Interpretation of the Biogenetic Isoprene
Rule for the Triterpenes’. Helv. Chim. Acta 2005, 88, 3011−3050.
(2) (a) Yoder, R. A.; Johnston, J. N. A Case Study in Biomimetic
Total Synthesis: Polyolefin Carbocyclizations to Terpenes and
Steroids. Chem. Rev. 2005, 105, 4730−4756. (b) Snyder, S. A.;
Levinson, A. M. In Comprehensive Organic Synthesis, 2nd ed.; Knochel,
P., Molander, G. A., Eds.; Elsevier: Amsterdam, 2014; Vol. 3, pp 268−
292. (c) Baunach, M.; Franke, J.; Hertweck, C. Terpenoid
Biosynthesis Off the Beaten Track: Unconventional Cyclases and
Their Impact on Biomimetic Synthesis. Angew. Chem., Int. Ed. 2015,
54, 2604−2626. (d) Barrett, A. G. M.; Ma, T.-K.; Mies, T. Recent
Developments in Polyene Cyclizations and Their Applications in
Natural Product Synthesis. Synthesis 2019, 51, 67−82.
(3) Ungarean, C. N.; Southgate, E. H.; Sarlah, D. Enantioselective
polyene cyclizations. Org. Biomol. Chem. 2016, 14, 5454−5467.
(4) (a) Snyder, S. A.; Treitler, D. S.; Brucks, A. P. Simple Reagents
for Direct Halonium-Induced Polyene Cyclizations. J. Am. Chem. Soc.
2010, 132, 14303−14314. (b) Chung, W.-J.; Vanderwal, C. D.
Stereoselective Halogenation in Natural Product Synthesis. Angew.
Chem., Int. Ed. 2016, 55, 4396−4434. (c) Schevenels, F. T.; Shen, M.;
Snyder, S. A. Isolable and Readily Handled Halophosphonium Pre-
reagents for Hydro- and Deuteriohalogenation. J. Am. Chem. Soc.
́
(10) (a) Barluenga, J.; Gonzalez, J. M.; Campos, P. J.; Asensio, G.
Iodine-Induced Stereoselective Carbocyclizations: A New Method for
the Synthesis of Cyclohexane and Cyclohexene Derivatives. Angew.
Chem., Int. Ed. Engl. 1988, 27, 1546−1547. (b) Goldfinger, M. B.;
Swager, T. M. Fused Polycyclic Aromatics via Electrophile-Induced
Cyclization Reactions: Application to the Synthesis of Graphite
Ribbons. J. Am. Chem. Soc. 1994, 116, 7895−7896. (c) Yao, T.;
Campo, M. A.; Larock, R. C. Synthesis of Polycyclic Aromatics and
Heteroaromatics via Electrophilic Cyclization. J. Org. Chem. 2005, 70,
3511−3517. (d) Zhang, X.; Sarkar, S.; Larock, R. C. Synthesis of
Naphthalenes and 2-Naphthols by the Electrophilic Cyclization of
Alkynes. J. Org. Chem. 2006, 71, 236−243. (e) Likhar, P. R.; Subhas,
M. S.; Roy, S.; Kantam, M. L.; Sridhar, B.; Seth, R. K.; Biswas, S.
Synthesis of highly substituted 2-perfluoroalkyl quinolines by
electrophilic iodocyclization of perfluoroalkyl propargyl imines/
amines. Org. Biomol. Chem. 2009, 7, 85−93.
(11) Huo, Z.; Gridnev, I. D.; Yamamoto, Y. A Method for the
Synthesis of Substituted Quinolines via Electrophilic Cyclization of 1-
Azido-2-(2-propynyl)benzene. J. Org. Chem. 2010, 75, 1266−1270.
(12) Zhang, X.; Campo, M. A.; Yao, T.; Larock, R. C. Synthesis of
Substituted Quinolines by Electrophilic Cyclization of N-(2-Alkynyl)-
anilines. Org. Lett. 2005, 7, 763−766.
(13) Warner, A. J.; Lawson, J. R.; Fasano, V.; Ingleson, M. J.
Formation of C(sp2)-Boronate Esters by Borylative Cyclization of
Alkynes Using BCl3. Angew. Chem., Int. Ed. 2015, 54, 11245−11249.
(14) Arii, H.; Kurihara, T.; Mochida, K.; Kawashima, T. Silylium
ion-promoted dehydrogenative cyclization: synthesis of silicon-
containing compounds derived from alkynes. Chem. Commun. 2014,
50, 6649−6652.
̈
2017, 139, 6329−6337. (d) Arnold, A. M.; Pothig, A.; Drees, M.;
Gulder, T. NXS, Morpholine, and HFIP: The Ideal Combination for
Biomimetic Haliranium-Induced Polyene Cyclizations. J. Am. Chem.
Soc. 2018, 140, 4344−4353.
(15) Fleming, F. F. Nitrile-containing natural products. Nat. Prod.
Rep. 1999, 16, 597−606.
(16) Fleming, F. F.; Yao, L.; Ravikumar, P. C.; Funk, L.; Shook, B. C.
Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile
Pharmacophore. J. Med. Chem. 2010, 53, 7902−7917.
(5) (a) Marsden, S. P.; Depew, K. M.; Danishefsky, S. J.
Stereoselective Total Syntheses of Amauromine and 5-N-Acetylar-
deemin. A Concise Route to the Family of “Reverse-Prenylated”
Hexahydropyrroloindole Alkaloids. J. Am. Chem. Soc. 1994, 116,
(17) Pollack, P. Fine Chemicals: The Industry and the Business; John
Wiley & Sons: Hoboken, NJ, 2007.
́
́
11143−11144. (b) Lopez, C. S.; Perez-Balado, C.; Rodríguez-Grana,
̃
(18) Huang, S. T.; Hsu, Y. C.; Yen, Y. S.; Chou, H. H.; Lin, J. T.;
Chang, C. W.; Hsu, C. P.; Tsai, C.; Yin, D.-J. Organic Dyes
Containing a Cyanovinyl Entity in the Spacer for Solar Cells
Applications. J. Phys. Chem. C 2008, 112, 19739−19747.
(19) Zil’berman, E. N. The Reactions of Nitrile-containing
Polymers. Russ. Chem. Rev. 1986, 55, 39−48.
(20) Takahashi, I.; Fujita, T.; Shoji, N.; Ichikawa, J. Brønsted acid-
catalysed hydroarylation of unactivated alkynes in a fluoroalcohol−
hydrocarbon biphasic system: construction of phenanthrene frame-
P.; de Lera, A. R. Mechanistic Insights into the Stereocontrolled
Synthesis of Hexahydropyrrolo[2,3-b]indoles by Electrophilic Activa-
tion of Tryptophan Derivatives. Org. Lett. 2008, 10, 77−80. (c) Tayu,
M.; Hui, Y.; Takeda, S.; Higuchi, K.; Saito, N.; Kawasaki, T. Total
Synthesis of (+)-Gliocladin C Based on One-Pot Construction of a
3a-(3-Indolyl)pyrroloindoline Skeleton by Sulfonium-Mediated
Cross-Coupling of Tryptophan and Indole. Org. Lett. 2017, 19,
6582−6585. (d) Jiang, X.; Zhu, W.; Yang, L.; Zheng, Z.; Yu, C.
Hypervalent Iodine-Mediated Cyclization of Homotryptamine
Derivatives. Eur. J. Org. Chem. 2019, 2019, 2268−2274.
works. Chem. Commun. 2019, 55, 9267−9270.
̌
̌
́
́
́
(21) Landek, G.; Ozimec-Landek, I.; Pesic, D.; Mesic, M.; Sunjic, V.
Conformational properties and chiral separation of dibenzo[b,f ]-
thieno[3,4-d]-fused oxepines and thiepines. Monatsh. Chem. 2013,
144, 1825−1832.
(6) (a) Schevenels, F. T.; Shen, M.; Snyder, S. A. I2-Promoted
Povarov-Type Reaction Using 1,4-Dithane-2,5-diol as an Ethylene
Surrogate: Formal [4 + 2] Synthesis of Quinolines. Org. Lett. 2017,
19, 2−5. (b) Cole, C. J. F.; Chi, H. M.; DeBacker, K. C.; Snyder, S. A.
Synthesis of Enhanced, Isolable Disulfanium Salts and their
Application to Thiiranium-Promoted Polyene Cyclizations. Synthesis
2018, 50, 4351−4358.
(22) (a) Becke, A. D. Density-functional thermochemistry. III. The
role of exact exchange. J. Chem. Phys. 1993, 98, 5648. (b) Weigend,
F.; Ahlrichs, R. Balanced basis sets of split valence, triple zeta valence
and quadruple zeta valence quality for H to Rn: Design and
assessment of accuracy. Phys. Chem. Chem. Phys. 2005, 7, 3297−3305.
(c) Grimme, S.; Ehrlich, S.; Goerigk, L. J. Effect of the damping
function in dispersion corrected density functional theory. J. Comput.
Chem. 2011, 32, 1456−1465.
(23) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Petersson,
G. A.; Nakatsuji, H.; Li, X.; Caricato, M.; Marenich, A. V.; Bloino, J.;
Janesko, B. G.; Gomperts, R.; Mennucci, B.; Hratchian, H. P.; Ortiz, J.
V.; Izmaylov, A. F.; Sonnenberg, J. L.; Williams-Young, D.; Ding, F.;
Lipparini, F.; Egidi, F.; Goings, J.; Peng, B.; Petrone, A.; Henderson,
T.; Ranasinghe, D.; Zakrzewski, V. G.; Gao, J.; Rega, N.; Zheng, G.;
Liang, W.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.;
(7) (a) Talavera, G.; Pena, J.; Alcarazo, M. Dihalo(imidazolium)-
̃
sulfuranes: A Versatile Platform for the Synthesis of New Electrophilic
Group-Transfer Reagents. J. Am. Chem. Soc. 2015, 137, 8704−8707.
(b) Li, X.; Golz, C.; Alcarazo, M. 5-(Cyano)dibenzothiophenium
Triflate: A Sulfur-Based Reagent for Electrophilic Cyanation and
Cyanocyclizations. Angew. Chem., Int. Ed. 2019, 58, 9496−9500.
́
(8) Barrado, A. G.; Zielinski, A.; Goddard, R.; Alcarazo, M. Regio-
and Stereoselective Chlorocyanation of Alkynes. Angew. Chem., Int.
Ed. 2017, 56, 13401−13405.
(9) (a) Godoi, B.; Schumacher, R. F.; Zeni, G. Synthesis of
Heterocycles via Electrophilic Cyclization of Alkynes Containing
Heteroatom. Chem. Rev. 2011, 111, 2937−2980. (b) Boyarskiy, V. P.;
Ryabukhin, D. S.; Bokach, N. A.; Vasilyev, A. V. Alkenylation of
E
https://dx.doi.org/10.1021/acs.orglett.0c01204
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Throssell, K.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.;
Bearpark, M. J.; Heyd, J. J.; Brothers, E. N.; Kudin, K. N.; Staroverov,
V. N.; Keith, T. A.; Kobayashi, R., Normand, J.; Raghavachari, K.;
Rendell, A. P.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.;
Millam, J. M.; Klene, M.; Adamo, C.; Cammi, R.; Ochterski, J. W.;
Martin, R. L.; Morokuma, K.; Farkas, O.; Foresman, J. B.; Fox, D. J.
Gaussian 16, revision A.03; Gaussian, Inc.: Wallingford, CT, 2016.
(24) Page, M.; Doubleday, C., Jr.; McIver, J. W., Jr. Following
steepest descent reaction paths. The use of higher energy derivatives
with ab initio electronic structure methods. J. Chem. Phys. 1990, 93,
5634−5642.
(25) Kishi, A.; Moriyama, K.; Togo, H. Preparation of Phenan-
thridines from o-Cyanobiaryls via Addition of Organic Lithiums to
Nitriles and Imino Radical Cyclization with Iodine. J. Org. Chem.
2018, 83, 11080−11088.
F
https://dx.doi.org/10.1021/acs.orglett.0c01204
Org. Lett. XXXX, XXX, XXX−XXX