Metal-Free Synthesis of Benzothiophenes by Twofold C?H Functionalization: Direct Access to Materials-Oriented Heteroaromatics

Article abstract of DOI:10.1002/anie.201908319

Due to their ubiquity in nature and frequent use in organic electronic materials, benzothiophenes are highly sought after. Here we set out an unprecedented procedure for the formation of benzothiophenes by the twofold vicinal C?H functionalization of aren

Full text of DOI:10.1002/anie.201908319

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201908319
German Edition: DOI: 10.1002/ange.201908319
Polyaromatic Hydrocarbons
À
Metal-Free Synthesis of Benzothiophenes by Twofold C H
Functionalization: Direct Access to Materials-Oriented
Heteroaromatics
Jiajie Yan, Alexander P. Pulis, Gregory J. P. Perry, and David J. Procter*
Abstract: Due to their ubiquity in nature and frequent use in
organic electronic materials, benzothiophenes are highly
sought after. Here we set out an unprecedented procedure for
À
the formation of benzothiophenes by the twofold vicinal C H
functionalization of arenes that does not require metal
catalysis. This one-pot annulation proceeds through an inter-
rupted Pummerer reaction/[3,3]-sigmatropic rearrangement/
cyclization sequence to deliver various benzothiophene prod-
ucts. The procedure is particularly effective for the rapid
synthesis of benzothiophenes from non-prefunctionalized
polyaromatic hydrocarbons (PAHs).
H
eterocyclic systems are fundamental molecular motifs in
nature and key components in some of societyꢀs most
important molecules, including blockbuster drugs.[1] Benzo-
thiophenes are particularly sought-after heteroaromatics as,
not only are they found in many natural products and drug
molecules,[2] but they are also widely used in organic
electronic materials.[3] The most common approaches to
benzo-fused heteroaromatic ring synthesis employ a side
chain, destined to form the heterocyclic ring, already installed
on the benzene ring (red bonds) before fusion occurs to give
the target.[4,5] Thus, annulation can occur through; 1) an
intramolecular cyclization of an arene bearing a suitable
tethering group (I, II, III); or 2) an intermolecular reaction
between a heteroatom-substituted arene and a suitable
coupling partner (IV) (Scheme 1A).
Scheme 1. A) Current routes for heteroarene synthesis. B) Our strat-
egy: direct synthesis of benzo-fused heteroaromatics. C/D) Interrupted
Pummerer chemistry for benzothiophene synthesis. E) This work:
metal-free synthesis of (dihydro)benzothiophenes.
this strategy being used for the grafting of heteroaromatic
rings to polyaromatic hydrocarbons (PAHs).
We considered an alternative approach to benzo-fused
heteroaromatic ring synthesis that involves the fusion of
arenes, which do not require prefunctionalization, with
a suitable coupling partner (Scheme 1B). This is a direct
method for the construction of benzo-fused heteroaromatics
that proceeds via the twofold functionalization of arenes at
Interrupted Pummerer reactivity has been utilized in
À
recent years for transition metal-free C H bond functional-
ization[11] and for the synthesis of benzo-fused heteroarenes,
in particular benzothiophenes.[12] Oshima, Yorimitsu and co-
workers have described a method for the preparation of
benzothiophenes from aryl substituted ketene dithioacetal S-
oxides (Scheme 1C).[13] More recently, we reported the
combination of aryl sulfoxides and alkynes in a route to
substituted benzothiophenes (Scheme 1D).[14] These methods
are appealing as they avoid the use of platinum group metals,
which are costly, at risk in terms of supply, often toxic to living
systems,[15] and can affect the performance of organic
electronic materials.[16]
À
the expense of vicinal C H bonds. Our approach parallels the
À
C H annulation of simple arenes with simultaneous con-
struction of a new all-carbon aromatic region, recently termed
an annulative p-extension (APEX) reaction.[6] Recent
advancements by Itami,[7] Scott,[8,9] and others[10] have show-
cased this tool, which generally requires transition metals, for
the assembly of carbocyclic frameworks. We are unaware of
Here, we present a method for installing heteroaromatic
regions on the edge of aromatic rings (Scheme 1E). We utilise
a one-pot sequence of intermolecular interrupted Pummerer
reaction (Figure 1, i), [3,3]-sigmatropic rearrangement
(Figure 1, ii), H+ promoted cyclization (Figure 1, iii) and
demethylation (Figure 1, iv) to give dihydrobenzothiophene
products directly from arenes. Transition metals are not
required in this thienannulation reaction,[17] which proceeds
[*] Dr. J. Yan, Dr. A. P. Pulis, Dr. G. J. P. Perry, Prof. Dr. D. J. Procter
School of Chemistry, University of Manchester
Oxford Rd, Manchester M13 9PL (UK)
E-mail: david.j.procter@manchester.ac.uk
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under https://doi.org/10.
1002/anie.201908319.
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À
through twofold C H functionalization to give benzothio-
phene products. The method is particularly useful for the
direct construction of important polyaromatic benzothio-
phenes.[3]
The first stage of this process relies on an intermolecular
interrupted Pummerer reaction[18,19] between an activated
sulfoxide, 2a, and an arene 1a. (Figure 1, i). In contrast to the
intramolecular trapping of activated sulfoxides with arenes,[20]
intermolecular reactivity is more challenging.[19l,m,r] We iso-
lated the sulfonium intermediate 4a by activating allyl
sulfoxide 2a with triflic anhydride and subsequent intermo-
lecular trapping with anisole 1a. Upon heating the mixture,
the desired [3,3]-sigmatropic rearrangement of intermediate
4a (Figure 1, ii), followed by spontaneous acid-promoted
cyclization (Figure 1, iii) was observed. This provided diaste-
reoisomeric sulfonium salt 6a, which could be detected by
1H NMR and mass spectrometry. Although the allylthioani-
sole intermediate 5a was not observed under the standard
reaction conditions, it could be isolated upon addition of an
inorganic base to the standard reaction conditions. Addition
of a nucleophilic base, NEt3, to the same reaction pot led to
conversion of sulfonium 6a to the desired 2,3-dihydrobenzo-
thiophene product 3a in 79% isolated overall yield. Impor-
tantly, the transformation of 1a into 3a can be accomplished
in one-pot and the isolation of intermediates is not required.
Figure 1. Transition metal-free, one-pot synthesis of 2,3-dihydrobenzo-
thiophenes. [a] Stage 1: 1a (0.5 mmol), 2 (0.5 mmol, 1.0 equiv), Tf2O
(0.55 mmol, 1.1 equiv), DCE (2.0 mL), À308C to 908C (MW heating).
[b] Stage 2: Et3N (3.0 mmol, 6.0 equiv), 08C to 508C. [c] Stage 1: TFAA
(0.55 mmol, 1.1 equiv) used. [d] Stage 2: DBU (3.0 mmol, 6.0 equiv)
used. [e] Stage 1: T=08C to 1008C (conventional heating), 18 h.
DCE=1,2-dichloroethane; TFAA=trifluoroacetic anhydride;
Tf2O=trifluoromethanesulfonic anhydride; DBU=1,8-diazabicyclo-
[5.4.0]undec-7-ene.
Scheme 2. Scope of the transition metal-free, one-pot synthesis of (2,3-dihydro)benzothiophenes. [a] Stage 1: 1 (0.5 mmol, 1.0 equiv), 2
(0.5 mmol, 1.0 equiv), Tf2O (0.55 mmol, 1.1 equiv), DCE (2.0 mL), À308C to 908C (MW heating). [b] Stage 2: Et3N (3.0 mmol, 6.0 equiv), 08C to
508C. [c] Oxidation: 3 (1.0 equiv), DDQ (1.1–1.6 equiv), PhMe (1.0m), rt to 808C. Yield from 3. [d] Stage 1: 1 (2.5 mmol, 5.0 equiv). [e] NMR yield.
[f] Stage 1: À308C to 608C (MW heating). MW=microwave; DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone.
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We next set out to determine the generality of the
procedure (Scheme 2). As the electron-donating ability of the
aryl substituent was reduced, the overall yield of the process
decreased (3a–3e). Toluene represents the current limit of
the scope of our process; for example, benzene is unreactive
under our current conditions. Aniline derivatives can also be
used in the annulation; triphenylamine undergoes annulation
to give 3 f in 50% NMR yield. For substrates where ortho and
para substitution could arise, high para-selectivity was seen in
the sulfenylation event. Disubstituted substrates also gave
products in high yields (3g–3m). Halogen substituents were
tolerated under the reaction conditions, but they reduced the
yield of the reaction, likely due to a reduction in the
nucleophilicity of the arene (3j–3k). 1,4-Disubstituted
arenes reacted to provide sterically congested 4,7-disubsti-
tuted-dihydrobenzothiophenes (3l–3m). Sulfoxide coupling
partners bearing alternative R1 substituents gave 2,2-disub-
stituted-2,3-dihydrobenzothiophenes (3n, 3o). Finally, poly-
aromatic hydrocarbons (PAHs) were tested in the reaction.
Naptho-fused dihydrobenzothiophenes were prepared in
good yield (3p–3r) and more complex polyaromatics, such
as fluoranthrene and triphenylene, were transformed into
polycyclic dihydrobenzothiophenes 3s and 3u in a highly
regioselective twofold functionalization. Pyrene performed
well under the reaction conditions to give the desired product
3t in high yield.
It was clear that the oxidation/aromatisation of the 2,3-
dihydrobenzothiophene products would lead to target mole-
cules of considerable interest in the field of organic elec-
tronics.[3] By exposing the products 3 to 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ) we gained access to ben-
zothiophene products 3’ (Scheme 2), including the p-
extended benzothiophenes, 3p’, 3q’, 3t’ and 3u’. Interestingly,
crystallographic analysis[21] of 3u’ revealed this compound to
adopt a slightly helical structure and the interplanar (dihe-
dral) angle between the terminal rings of this [4]-thiahelicene
derivative was calculated to be 11.88 (c.f. 268 for the parent
[4]-helicene).[22] Overall, our approach constitutes a metal-
free synthesis of various multiply substituted benzothio-
phenes from non-prefunctionalized arenes.
A more direct, one-pot approach to benzothiophenes
from simple arenes could be achieved using a modified
sulfoxide reagent: submitting readily-available sulfoxide 2a’
and an arene 1 to the standard reaction conditions formed
intermediate 6’ and subsequent treatment with base resulted
in dealkylation and elimination of chloride to give benzo-
thiophene products 3’ directly (Scheme 3). The use of
a chloride substituent as a place-holder for an alkene unit
allows an additional oxidation step to be avoided in the
formation of benzothiophenes. Furthermore, the equivalent
of HCl formed is trapped and removed by the amine base.
This constitutes an efficient, one-pot synthesis of benzothio-
phenes through a metal-free, thienannulative p-extension
reaction. Our methodology proved amenable to the annula-
tive p-extension of a range of arenes (3a’, 3b’, 3g’–3i’, 3l’).
Importantly, the use of polyaromatic hydrocarbons such as
naphthalene, fluoranthrene, pyrene and corannulene directly
delivered a range of interesting polyaromatic benzothiophene
products (3p’–3t’, 3v’).[3] The regiochemistry of the trans-
Scheme 3. Scope of the transition metal-free, one-pot synthesis of p-
extended benzothiophenes. [a] Stage 1: 1 (0.5 mmol, 1.0 equiv), 2a’
(0.5 mmol, 1.0 equiv), Tf2O (0.55 mmol, 1.1 equiv), DCE (2.0 mL),
À308C to 908C (MW heating). [b] Stage 2: Et3N (3.0 mmol, 6.0 equiv),
08C to 508C. [c] Yield on a larger scale; 0.50 g of 1t gave 0.36 g of 3t’.
[d] Overall yield from 3p’.
formation is also noteworthy— whereas transition metal-
À
catalyzed procedures have shown selectivity for C H func-
tionalization at the K-region (4,5-positions) of pyrene, we
observed exclusive p-extension at the 1,2-positions (3t’).[7] We
have also demonstrated an iterative functionalization of
simple arenes to obtain benzodithiophene (BDT) com-
À
pounds. Thus, by consecutive C H functionalization/p-exten-
sion we were able to prepare the cross-fused napthodithio-
phene derivative 3w’, further illustrating the potential of this
methodology for the rapid construction of interesting thie-
noacene materials.[3,23]
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[5] a) D. F. Taber, P. K. Tirunahari, Tetrahedron 2011, 67, 7195 –
7210; b) B. Wu, N. Yoshikai, Org. Biomol. Chem. 2016, 14,
5402 –5416.
In conclusion we have developed a direct, metal-free
method for the synthesis of benzothiophenes from non-
prefunctionalized arenes and allyl sulfoxides. The method
utilizes an interrupted Pummerer/[3,3] sigmatropic rearrange-
[6] a) Y. Segawa, T. Maekawa, K. Itami, Angew. Chem. Int. Ed.
2015, 54, 66 –81; Angew. Chem. 2015, 127, 68 –83; b) H. Ito, K.
Ozaki, K. Itami, Angew. Chem. Int. Ed. 2017, 56, 11144 –11164;
Angew. Chem. 2017, 129, 11296 –11317; c) H. Ito, Y. Segawa, K.
Murakami, K. Itami, J. Am. Chem. Soc. 2019, 141, 3 –10.
[7] For select publications, see: a) K. Mochida, K. Kawasumi, Y.
Segawa, K. Itami, J. Am. Chem. Soc. 2011, 133, 10716 –10719;
b) K. Ozaki, K. Kawasumi, M. Shibata, H. Ito, K. Itami, Nat.
Commun. 2015, 6, 6251; c) W. Matsuoka, H. Ito, K. Itami,
Angew. Chem. Int. Ed. 2017, 56, 12224 –12228; Angew. Chem.
2017, 129, 12392 –12396; d) Y. Yano, N. Mitoma, K. Matsushima,
F. Wang, K. Matsui, A. Takakura, Y. Miyauchi, H. Ito, K. Itami,
Nature 2019, 571, 387 –392.
À
ment/cyclization sequence to affect twofold C H functional-
ization. The utility of the procedure is demonstrated through
the facile synthesis of polyaromatic benzothiophenes by a one
pot, p-extension process. We expect the process to be of
particular value for the preparation of a wide-range of
materials-oriented heteroaromatic frameworks.
Acknowledgements
We thank the EPSRC (Established Career Fellowship to
D.J.P. ; EP/M005062/1), the University of Manchester (Lec-
tureships to A.P.P. and G.J.P. P), the Swedish Chemical Society
(Stiftelsen Bengt Lundqvists Minne Postdoc Fellowship to
J.Y.), the Manchester X-ray Crystallography Service, and
Prof. Kenichiro Itami, Assoc. Prof. Kei Murakami, Assoc.
Prof. Hideto Ito, Wataru Matsuoka, Shu Jan Yip, Kou
Kawahara and all the Itami group for discussions and for
the gift of corannulene.
[8] For select publications, see: a) E. H. Fort, P. M. Donovan, L. T.
Scott, J. Am. Chem. Soc. 2009, 131, 16006 –16007; b) E. H. Fort,
L. T. Scott, Angew. Chem. Int. Ed. 2010, 49, 6626 –6628; Angew.
Chem. 2010, 122, 6776 –6778; c) E. H. Fort, L. T. Scott, Tetrahe-
dron Lett. 2011, 52, 2051 –2053.
[9] K. Kawasumi, Q. Zhang, Y. Segawa, L. T. Scott, K. Itami, Nat.
Chem. 2013, 5, 739 –744.
[10] For select publications, see: a) Y.-T. Wu, K.-H. Huang, C.-C.
Shin, T.-C. Wu, Chem. Eur. J. 2008, 14, 6697 –6703; b) J. Cai, P.
Ruffieux, R. Jaafar, M. Bieri, T. Braun, S. Blankenburg, M.
Muoth, A. P. Seitsonen, M. Saleh, X. Feng, K. Müllen, R. Fasel,
Nature 2010, 466, 470 –473; c) J. Li, C. Jiao, K.-W. Huang, J. Wu,
Chem. Eur. J. 2011, 17, 14672 –14680; d) M. V. Pham, N. Cramer,
Angew. Chem. Int. Ed. 2014, 53, 3484 –3487; Angew. Chem. 2014,
126, 3552 –3555; e) F. Xu, X. Xiao, T. R. Hoye, Org. Lett. 2016,
18, 5636 –5639.
Conflict of interest
The authors declare no conflict of interest.
[11] a) A. P. Pulis, D. J. Procter, Angew. Chem. Int. Ed. 2016, 55,
9842 –9860; Angew. Chem. 2016, 128, 9996 –10014; b) T. Yanagi,
K. Nogi, H. Yorimitsu, Tetrahedron Lett. 2018, 59, 2951 –2959.
[12] a) K. Kobayashi, M. Horiuchi, S. Fukamachi, H. Konishi,
Tetrahedron 2009, 65, 2430 –2435; b) C. Du, S. Ye, J. Chen, Y.
Guo, Y. Liu, K. Lu, Y. Liu, T. Qi, X. Gao, Z. Shuai, G. Yu, Chem.
Eur. J. 2009, 15, 8275 –8282; c) K. Kobayashi, T. Suzuki, M.
Horiuchi, Y. Shiroyama, H. Konishi, Synthesis 2011, 2897 –2906;
d) S. Zhang, X. Qiao, Y. Chen, Y. Wang, R. M. Edkins, Z. Liu, H.
Li, Q. Fang, Org. Lett. 2014, 16, 342 –345; e) D. Vasu, J. N.
Hausmann, H. Saito, T. Yanagi, H. Yorimitsu, A. Osuka, Asian J.
Org. Chem. 2017, 6, 1390 –1393; f) K. Nobushige, K. Hirano, T.
Satoh, M. Miura, Org. Lett. 2014, 16, 1188 –1191.
Keywords: annulation ·benzothiophene ·Pummerer reaction ·
sulfur · p-extension
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Angew. Chem. 2019, 131, 15822–15826
[1] R. D. Taylor, M. MacCross, A. D. G. Lawson, J. Med. Chem.
2014, 57, 5845 –5859.
[2] R. S. Keri, K. Chand, S. Budagumpi, S. Balappa Somappa, S. A.
Patil, B. M. Nagaraja, Eur. J. Med. Chem. 2017, 138, 1002 –1033.
[3] a) K. Takimiya, S. Shinamura, I. Osaka, E. Miyazaki, Adv. Mater.
2011, 23, 4347 –4370; b) W. Jiang, Y. Li, Z. Wang, Chem. Soc.
Rev. 2013, 42, 6113 –6127; c) C. Wang, H. Dong, W. Hu, Y. Liu,
D. Zhu, Chem. Rev. 2012, 112, 2208 –2267; d) K. Takimiya, I.
Osaka, T. Mori, M. Nakano, Acc. Chem. Res. 2014, 47, 1493 –
[13] a) S. Yoshida, H. Yorimitsu, K. Oshima, Org. Lett. 2007, 9, 5573 –
5576; b) S. Otsuka, H. Yorimitsu, A. Osuka, Chem. Eur. J. 2015,
21, 14703 –14707.
[14] a) A. J. Eberhart, D. J. Procter, Angew. Chem. Int. Ed. 2013, 52,
4008 –4011; Angew. Chem. 2013, 125, 4100 –4103; b) A. J.
Eberhart, H. J. Shrives, E. lvarez, A. Carrr, Y. Zhang, D. J.
Procter, Chem. Eur. J. 2015, 21, 7428 –7434; c) J. A. Fernµndez-
Salas, A. J. Eberhart, D. J. Procter, J. Am. Chem. Soc. 2016, 138,
790 –793; d) A. J. Eberhart, H. Shrives, Y. Zhang, A. Carrr,
A. V. S. Parry, D. J. Tate, M. L. Turner, D. J. Procter, Chem. Sci.
2016, 7, 1281 –1285.
[15] European Medicines Agency. in ICH Guideline Q3D on
Elemental Impurities (London, 2015) http://www.ema.europa.
eu/docs/en GB/document library/Scientific guideline/2015/01/
WC500180284.pdf.
[16] Ö. Usluer, M. Abbas, G. Wantz, L. Vignau, L. Hirsch, E. Grana,
C. Brochon, E. Cloutet, G. Hadziioannou, ACS Macro Lett.
2014, 3, 1134 –1138.
[17] K. Takimiya, M. Nakano, M. J. Kang, E. Miyazaki, I. Osaka, Eur.
J. Org. Chem. 2013, 217 –227.
˙
´
´
1502; e) M. Ste˛pien, E. Gonka, M. Zyła, N. Sprutta, Chem. Rev.
2017, 117, 3479 –3716; f) J. Chen, K. Yang, X. Zhou, X. Guo,
Chem. Asian J. 2018, 13, 2587 –2600; Methods for the synthesis
of polyaromatic benzothiophenes, related to those in this study,
are known, however, they require prefunctionalized arenes and/
or multi-step procedures. For prominent examples, see: g) J. D.
Tovar, A. Rose, T. M. Swager, J. Am. Chem. Soc. 2002, 124,
7762 –7769; h) L. Meng, T. Fujikawa, M. Kuwayama, Y. Segawa,
K. Itami, J. Am. Chem. Soc. 2016, 138, 10351 –10355; i) A. Nitti,
G. Bianchi, R. Po, T. M. Swager, D. Pasini, J. Am. Chem. Soc.
2017, 139, 8788 –8791.
[4] a) D. T. Davies in Aromatic Heterocyclic Chemistry, (Eds.: S. G.
Davies), Oxford University Press, New York, 1991; b) J. A.
Joule, K. Mils in Heterocyclic Chemistry, Wiley-Blackwell,
Chichester, 2010; c) M. Sainsbury in Heterocyclic Chemistry,
The Royal Society of Chemistry, Cambridge, 2001.
15678 www.angewandte.org
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Angewandte
Communications
Chemie
[18] For a review of the Pummerer reaction, see: L. H. S. Smith, S. C.
Angew. Chem. 2018, 130, 5861 –5866; t) G. Hu, J. Xu, P. Li, Org.
Coote, H. F. Sneddon, D. J. Procter, Angew. Chem. Int. Ed. 2010,
49, 5832 –5844; Angew. Chem. 2010, 122, 5968 –5980.
Chem. Front. 2018, 5, 2167 –2170; u) K. Higuchi, T. Tago, Y.
Kokubo, M. Ito, M. Tayu, S. Sugiyama, T. Kawasaki, Org. Chem.
Front. 2018, 5, 3219 –3225; v) B. Waldecker, F. Kraft, C. Golz, M.
Alcarazo, Angew. Chem. Int. Ed. 2018, 57, 12538 –12542; Angew.
Chem. 2018, 130, 12718 –12722; w) Z. Zhang, P. He, H. Du, J.
Xu, P. Li, J. Org. Chem. 2019, 84, 4517 –4524; x) Z. Zhang, Y.
Luo, H. Du, J. Xu, P. Li, Chem. Sci. 2019, 10, 5156 –5161; y) X.
Li, C. Golz, M. Alcarazo, Angew. Chem. Int. Ed. 2019, 58, 9496 –
9500; Angew. Chem. 2019, 131, 9596 –9600; z) M. Siauciulis, N.
Ahlsten, A. P. Pulis, D. J. Procter, Angew. Chem. Int. Ed. 2019,
58, 8779 –8783; Angew. Chem. 2019, 131, 8871 –8875.
[19] For a review of this subject see a) H. Yorimitsu, Chem. Rec. 2017,
17, 1156 –1167; For select publications on intermolecular
interrupted Pummerer chemistry with carbon nucleophiles see:
b) V. G. Nenajdenko, P. V. Vertelezkij, E. S. Balenkova, Syn-
thesis 1997, 351 –355; c) T. Shoji, J. Higashi, S. Ito, K. Toyota, T.
Asao, M. Yasunami, K. Fujimori, N. Morita, Eur. J. Org. Chem.
2008, 1242 –1252; d) S. Yoshida, H. Yorimitsu, K. Oshima, Org.
Lett. 2009, 11, 2185 –2188; e) A. J. Eberhart, J. E. Imbriglio, D. J.
Procter, Org. Lett. 2011, 13, 5882 –5885; f) K. Higuchi, M. Tayu,
T. Kawasaki, Chem. Commun. 2011, 47, 6728 –6730; g) A. J.
Eberhart, C. Cicoira, D. J. Procter, Org. Lett. 2013, 15, 3994 –
3997; h) X. Huang, M. Patil, C. Far›s, W. Thiel, N. Maulide, J.
Am. Chem. Soc. 2013, 135, 7312 –7323; i) M. Tayu, K. Higuchi,
M. Inaba, T. Kawasaki, Org. Biomol. Chem. 2013, 11, 496 –502;
j) M. Tayu, K. Higuchi, T. Ishizaki, T. Kawasaki, Org. Lett. 2014,
16, 3613 –3615; k) M. Tayu, T. Ishizaki, K. Higuchi, T. Kawasaki,
Org. Biomol. Chem. 2015, 13, 3863 –3865; l) J. A. Fernµndez-
Salas, A. P. Pulis, D. J. Procter, Chem. Commun. 2016, 52, 12364 –
12367; m) P. Cowper, Y. Jin, M. D. Turton, G. Kociok-Kçhn, S. E.
Lewis, Angew. Chem. Int. Ed. 2016, 55, 2564 –2568; Angew.
Chem. 2016, 128, 2610 –2614; n) M. Tayu, Y. Suzuki, K. Higuchi,
T. Kawasaki, Synlett 2016, 27, 941 –945; o) I. Klose, A. Misale, N.
Maulide, J. Org. Chem. 2016, 81, 7201 –7210; p) H. J. Shrives,
J. A. Fernµndez-Salas, C. Hedtke, A. P. Pulis, D. J. Procter, Nat.
Commun. 2017, 8, 14801; q) M. Tayu, K. Nomura, K. Kawachi,
K. Higuchi, N. Saito, T. Kawasaki, Chem. Eur. J. 2017, 23, 10925 –
10930; r) M. Siauciulis, S. Sapmaz, A. P. Pulis, D. J. Procter,
Chem. Sci. 2018, 9, 754 –759; s) Z. He, H. J. Shrives, J. A.
Fernµndez-Salas, A. Abengózar, J. Neufeld, K. Yang, A. P. Pulis,
D. J. Procter, Angew. Chem. Int. Ed. 2018, 57, 5759 –5764;
[20] For example, the well-known trifluoromethylating agent, Ume-
motoꢀs reagent, is prepared via an intramolecular interrupted
Pummerer reaction: a) T. Umemoto, S. Ishihara, Tetrahedron
Lett. 1990, 31, 3579 –3582; b) T. Umemoto, S. Ishihara, J. Am.
Chem. Soc. 1993, 115, 2156 –2164.
[21] The X-ray crystallographic data for 3t, 3u’, 3s’, 3v’ and 3w’ can
be found at the Cambridge Crystallographic Data Centre
(CCDC) under deposition numbers CCDC 1934977, 1934978,
1934971, 1947281 and 1934972, respectively.
[22] a) Y. Shen, C.-F. Chen, Chem. Rev. 2012, 112, 1463 –1535;
b) “Thiahelicenes: From Basic Knowledge to Applications”: E.
Licandro, S. Cauteruccio, D. Dova in Advances in Heterocyclic
Chemistry, Vol. 118, Elsevier, Amsterdam, 2016, pp. 1 –46.
[23] K. Takimiya, I. Osaka, Chem. Rec. 2015, 15, 175 –188.
Manuscript received: July 5, 2019
Revised manuscript received: August 15, 2019
Accepted manuscript online: September 3, 2019
Version of record online: September 24, 2019
Angew. Chem. Int. Ed. 2019, 58, 15675 –15679
ꢀ 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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