First use of an organobismuth reagent in C(sp3)–S bond formation: Access to aryl cyclopropyl sulfides via copper-catalyzed S–Cyclopropylation of thiophenols using tricyclopropylbismuth

Article abstract of DOI:10.1016/j.jorganchem.2019.04.032

The direct S-cyclopropylation of thiophenols using tricyclopropylbismuth is reported. The reaction is catalyzed by copper(II) acetate and operates under mild conditions to afford the corresponding aryl cyclopropyl sulfides in moderate to good yields. This reaction represents the first use of an organobismuth reagent in C(sp³)–S bond formation.

Full text of DOI:10.1016/j.jorganchem.2019.04.032

Accepted Manuscript
First use of an organobismuth reagent in C(sp [3])–S bond formation: Access to aryl
cyclopropyl sulfides via copper-catalyzed S–Cyclopropylation of thiophenols using
tricyclopropylbismuth
Emeline Benoit, Bianca Bueno, Catherine Choinière, Alexandre Gagnon
PII:
S0022-328X(19)30177-9
DOI:
https://doi.org/10.1016/j.jorganchem.2019.04.032
JOM 20782
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 5 April 2019
Revised Date: 25 April 2019
Accepted Date: 30 April 2019
Please cite this article as: E. Benoit, B. Bueno, C. Choinière, A. Gagnon, First use of an organobismuth
reagent in C(sp [3])–S bond formation: Access to aryl cyclopropyl sulfides via copper-catalyzed S–
Cyclopropylation of thiophenols using tricyclopropylbismuth, Journal of Organometallic Chemistry
(2019), doi: https://doi.org/10.1016/j.jorganchem.2019.04.032.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
First Use of an Organobismuth Reagent in C(sp3)–S Bond Formation: Access to Aryl
Cyclopropyl Sulfides via Copper-Catalyzed S–Cyclopropylation of Thiophenols using
Tricyclopropylbismuth
Emeline Benoit,a Bianca Bueno,a Catherine Choinièrea and Alexandre Gagnon*a
aDépartement de chimie, Université du Québec à Montréal, C. P. 8888, Succursale Centre-
Ville, Montréal, Québec, Canada, H3C 3P8
Abstract
The direct S-cyclopropylation of thiophenols using tricyclopropylbismuth is reported. The
reaction is catalyzed by copper(II) acetate and operates under mild conditions to afford the
corresponding aryl cyclopropyl sulfides in moderate to good yields. This reaction
represents the first use of an organobismuth reagent in C(sp3)–S bond formation.
Keywords
Organobismuth compounds, Tricyclopropylbismuth, Thiophenols, Benzenethiols, Aryl
cyclopropyl sulfides, Copper catalysis
Introduction
Organobismuth compounds are organometallic species that contain a C–Bi bond and that
are easily prepared from inexpensive and low-toxic inorganic bismuth salts.1,2
Organobismuth compounds are divided in trivalent and pentavalent species where bismuth
is at the +3 and +5 oxidation state, respectively. Trivalent bismuth compounds can be
further subdivided into triaryl and trialkyl species. While triarylbismuthines are stable to

ACCEPTED MANUSCRIPT
air and can be purified by simple silica gel chromatography, trialkylbismuthines are usually
pyrophoric and must be isolated by distillation or recrystallization under inert
atmosphere.3 Triarylbismuthines have been abundantly used in metal-catalyzed reactions.4-
6
For example, our group developed a series of copper-catalyzed N- and O-arylation
reactions of NH-containing heterocycles,7 phenols8 and amino alcohols9,10 using
triarylbismuthines. We also reported various methods for the palladium-catalyzed cross-
coupling reaction between triarylbismuthines and aryl and heteroaryl halides and
triflates.11 Examples of metal-catalyzed transformations involving trialkylbismuthines are
much more scarce and are limited to a few scattered reports of copper-catalyzed N-
alkylation of anilines and amines,12 and palladium-catalyzed cross-coupling reactions
between alkyldiarylbismuthines and arylchlorides.13 We also published
a more
comprehensive protocol for the palladium-catalyzed cross-coupling of trialkylbismuthines
with aryl and heteroaryl halides and triflates and demonstrated that triarylbismuthines are
not prone to β-hydride elimination.14,15
We disclosed in 2007 the first synthesis of tricyclopropylbismuth 1 by the addition of
cyclopropylmagnesium bromide to bismuth chloride (Scheme 1a).16 In sharp contrast to
most trialkylbismuthines, tricyclopropylbismuth 1 was found to be surprisingly stable to
air, suggesting that its chemical behavior might be closer to triarylbismuthines than
trialkylbismuthines. To test this hypothesis, we evaluated the ability of
tricyclopropylbismuth 1 to replicate the reactivity of triphenylbismuth in copper-catalyzed
N-arylation reactions. Using conditions reported by Barton17 and Chan18 for the N-arylation
of anilines and amides, we developed the first copper-catalyzed N-cyclopropylation
reaction of cyclic amides and NH-containing heterocycles 2 leading to C(sp3)–N bond
construction and formation of N-cyclopropylated compounds 3 (Scheme 1b).16 We then
investigated the use of tricyclopropylbismuth 1 in the construction of C(sp3)–C(sp2) bonds
through palladium-catalyzed cross-coupling reaction with aryl halides and triflates 4 to
form arylcyclopropanes 5 (Scheme 1c)19,20 and its extension to the carbonylative version to
generate aryl cyclopropylketones 7 (Scheme 1d).21 To further expand the scope of
tricyclopropylbismuth 1 in organic synthesis, we opted to explore its use in the
cyclopropylation of phenols and thiophenols, which, if successful, would result in the

ACCEPTED MANUSCRIPT
formation of C(sp3)–O and C(sp3)–S bonds. Although we were unable to identify conditions
to O-cyclopropylate phenols with tricyclopropylbismuth 1, we discovered that thiophenols
8 could be smoothly S-cyclopropylated under conditions similar to those reported
previously by us for the N-cyclopropylation of amides and azoles. We would thus like to
report herein our results on the first S-cyclopropylation reaction of thiophenols using
tricyclopropylbismuth 1 which also represents the first example of C(sp3)–S bond
formation using an organobismuth reagent (Scheme 1e).
Scheme 1. Synthesis of tricyclopropylbismuth 1 and use in metal-catalyzed N-, C- and S-
cyclopropylation reactions.

ACCEPTED MANUSCRIPT
Aryl cyclopropyl sulfides are present in numerous biologically active compounds, but in
most cases, the sulfur is at an elevated oxidation state. These oxidized derivatives include
aryl cyclopropyl sulfoxides,22–25 sulfones26–28 and sulfoximines,29,30 which can all be
prepared by controlled oxidation of the corresponding aryl cyclopropyl sulfides under
various conditions. LY-2608204 (10),31 PSN-GK1 (11)32 and compounds 1228 and 1327 are
investigational drugs that contain an aryl cyclopropyl sulfone and that were developed to
treat type 2 diabetes through glucokinase (GK) activation (Figure 1). Compound 14, which
contains an aryl cyclopropyl sulfoximine, increases cytosolic GK levels through binding to
glucokinase regulatory protein (GKRP).25 Roniciclib (15), also named BAY 1000394, is a
pan-cyclin-dependant kinase (CDK) inhibitor that contains an aryl cyclopropyl sulfoximine
and that entered phase 2 clinical studies in 2019 in patients with untreated small cell lung
cancer extensive disease (EC-SCLC).30,33
Figure 1. Biologically active compounds prepared from aryl cyclopropyl sulfides.

ACCEPTED MANUSCRIPT
Aryl cyclopropyl sulfides are also very useful synthons in organic synthesis. For instance,
removal of the proton alpha to the sulfur with butyllithium results in the formation of a
lithium species which can then react with alkyl halides to afford the corresponding
alkylated adducts that can be converted into ketones by treatment with mercuric chloride.34
Reaction of these lithium cyclopropyl species with aldehydes leads to compounds which
rearrange to cyclobutanones35–37 and 1-arylcyclobutenes38 by treatment with Lewis or
Brønsted acids, and Burgess reagent, respectively. The acid-catalyzed ring expansion of 1-
(arylthio)cyclopropylcarbinols to cyclobutanone has been used as a key step in the
synthesis of natural products (±)-fragranol,39 (±)-grandisol,39 (±)-α-cuparenone40 and (±)-
herbertene.40 Phenylthiocyclopropanes have also been used as donor-acceptor dipoles in
the diastereoselective annulation reaction with ketene acetals, leading to complex
cyclopentane scaffolds.41
Aryl cyclopropyl sulfides are most frequently prepared by SN2 reaction of arylthiolates with
halocyclopropanes.27,28 However, because of geometric constraints inherent to the three-
membered ring which disfavor the planar transition state, these reactions usually require a
strong base and high temperatures, thus precluding the presence of many functional
groups.42 An alternative approach for the synthesis of aryl cyclopropyl sulfides consists of
adding a cyclopropane thiol to an arylfluoride through a SNAr reaction.30 However, the
necessity of having an electron-withdrawing group on the aromatic scaffold reduces the
applicability of this approach in the context of medicinal chemistry and organic synthesis.
Other methods to prepare aryl cyclopropyl sulfides include the addition of arylthiols to
cyclopropenes,43–46 the cyclization of 1,3-bis(phenylthio)propanes with butyllithium,47 the
Brønsted acid-catalyzed arythiol addition/ring contraction to α-hydroxybutanones,48 and
the [2+1] addition of phenylthio(trimethylsilyl)carbenes to alkenes.49
The lack of general procedures for the synthesis of aryl cyclopropyl sulfides gave us an
impetus to develop a method for the direct S-cyclopropylation of benzenethiols using
tricyclopropylbismuth 1. Reported protocols for the S-arylation of thiophenols using
pentavalent arylbismuth reagents50–52 and for the S-arylation of diaryl disulfides using

ACCEPTED MANUSCRIPT
triarylbismuthines53 comforted us in our hypothesis that 1 could be used as a
cyclopropylating agent towards thiophenols to form C(sp3)–S bonds.
Results and discussion
We began by testing the feasibility of S-cyclopropylating 4-tert-butylbenzenethiol 8a with
tricyclopropylbismuth 1 using reaction conditions that we developed for the N-
cyclopropylation of amides.16 In the event, treating 8a with 1.2 equivalents of
tricyclopropylbismuth 1, 1.0 equivalent of copper(II) acetate and 3.0 equivalents of
pyridine under argon atmosphere in dry dichloromethane at 50 °C during 16 h provided the
desired aryl cyclopropyl sulfide 9a in 67% yield along with 4% of the diaryl sulfide 16a
(Table 1, Entry 1). Replacing pyridine by the more basic triethylamine was well tolerated
(Table 1, Entry 2) but using the more hindered 2,6-lutidine led to a drastic erosion in the
yield of the reaction (Table 1, Entry 3). Using Cs2CO3 completely shut down the S-
cyclopropylation reaction, presumably due to the lack of coordination of the copper species,
and afforded instead the corresponding disulfide 16a in quantitative yield (Table 1, Entry
4). Changing the solvent for tetrahydrofuran or conducting the reaction at a higher
temperature in dichloroethane negatively impacted the yield of the reaction (Table 1, Entry
5 and 6). Using 2.5 equivalents of tricyclopropylbismuth 1 gave a substantial improvement
in the yield of the desired product 9a (Table 1, Entry 7) while reducing the reaction time to
4 hours resulted in a less efficient process (Table 1, Entry 8). For every entry, complete
consumption of the starting material was observed. This optimization shows that similar
conditions can be used for the cyclopropylation of NH- and SH-containing compounds with
tricyclopropylbismuth 1.
Table 1. Optimization of reaction conditions for the copper-catalyzed S-cyclopropylation of
4-tert-butylbenzenethiol 8a using tricyclopropylbismuth 1

ACCEPTED MANUSCRIPT
Entry Change from “standard conditions”
Yield 9ab
(%)
67
Yield 16ab
(%)
4
1
2
3
4
5
6
7
8
No changea
Et3N instead of pyridine
61
0
2,6-Lutidine instead of pyridine
Cs2CO3 instead of pyridine
47
0
0
99
1
THF instead of CH2Cl2
31
DCE at 80 °C instead of DCM at 50 °C
2.5 equiv of cPr3Bi (1) instead of 1.2
2.5 equiv of cPr3Bi (1) instead of 1.2 and 4 h
instead of 16 h
56
16
14
12
84
59
a Standard conditions: 4-tert-butylbenzenethiol (8a) (1.0 equiv), cPr3Bi (1) (1.2 equiv),
Cu(OAc)2 (1.0 equiv), pyridine (3.0 equiv), anhydrous dichloromethane (0.1 M), 50 °C, 16 h,
b
argon. Yields of isolated pure products. For every entry, no starting material was
recovered.
Because diaryl disulfides are common side products in copper-catalyzed reactions involving
benzenethiols and because these substrates are commercially available and do not have the
unpleasant smell associated with thiophenols, we attempted the S-cyclopropylation
reaction directly on bis(4-tert-butylphenyl)disulfide 16a. Unfortunately, using conditions
reported by Yasuike and Kurita for the S-arylation of diaryl disulfides,53 we obtained the
desired product 9a in a meager 10% yield (Equation 1). After unsucessful attempts at
improving this process through variation of the reaction conditions, we decided to pursue
our work with the S-cyclopropylation directly on thiophenols.

ACCEPTED MANUSCRIPT
Using the optimized reaction conditions from Table 1, entry 7, we then investigated the
scope of the reaction and observed that the protocol is applicable to unsubstituted as well
as ortho, meta, para and disubstituted benzenethiols, giving the desired aryl cyclopropyl
thioethers 9b–g in yields ranging from 63 to 92% (Scheme 2). Thiophenols bearing
electron withdrawing (compounds 9h–9m) and donating groups (compound 9n) were also
smoothly cyclopropylated, affording the corresponding products in 41 to 90% yield. Lastly,
it was found that our reaction also tolerates the presence of a methyl ester at the ortho
position, as indicated by product 9o. Diaryl disulfides were isolated as side products in
yields ranging between 1 to 26%.
Scheme 2. Substrate scope in the copper-catalyzed S-cyclopropylation of thiophenols 8
using tricyclopropylbismuth 1. Numbers under parentheses indicates the yield of diaryl
disulfide side-product 16.

ACCEPTED MANUSCRIPT
We next investigated the efficiency of our protocol on an alkylthiol (as opposed to an
arylthiol) and found that benzylthiol 17 could be S-cyclopropylated using
tricyclopropylbismuth 1 to afford the desired S-cyclopropylated product 18, albeit in only
35% yield, along with 11% of the disulfide 19 (Equation 2). Although the yield is very low,
this result is nonetheless interesting since there are very few methods to S-cyclopropylate
non-aromatic thiols.43,64
The proposed mechanism for the copper-catalyzed S-cyclopropylation of thiophenols using
tricyclopropylbismuth is based on the one suggested by Barton for the N-arylation of
amines using triarylbismuthines.17 It is also modified according to mechanistic findings
published by Stahl for the Evans Chan Lam reaction.65 Thus, the process would begin by the
coordination of pyridine to copper(II) acetate to give, in agreement with precedents from
the literature, CuII(OAc)2Ln where L is a pyridine ligand and where n can be 1,66,67 2,66 3,68 or
467 (Step i, Scheme 3). Displacement of one pyridine ligand on species (I) by
tricyclopropylbismuth would then lead to adduct (II) (step ii) which would undergo
disproportionation with copper(II) acetate to generate the copper(III) species (III) that has
two acetate ligands and one cyclopropyl group, along with copper(I) acetate and
bis(cyclopropyl)bismuth acetate (IV) (step iii). Deprotonation of the arylthiol by pyridine
(most likely after complexation to a copper center to lower its pKa) then affords an
arylthiolate which displaces an acetate from species III to provide complex (V) where the
copper is simulatenously ligated to an acetate, a thiolate and a cyclopropyl group (step iv).
Reductive elimination from this species would then provide the expected S-cyclopropylated
thiol along with copper(I) acetate (step v). In many copper-catalyzed arylation reactions, the
copper(I) species can be converted back to the active copper(II) catalyst by action of
oxygen. However, in our case, since oxygen was found to be detrimental (presumably due to
reaction with tricyclopropylbismuth), this mechanism cannot be drawn as a catalytic cycle.

ACCEPTED MANUSCRIPT
Additionally, it should be emphasized here that although reasonable, this mechanism is
nonetheless speculative since there are no detailed studies on copper-catalyzed reactions
involving trialkylbismuthines.
Scheme 3. Proposed mechanism for the copper-catalyzed S-cyclopropylation of
thiophenols using tricyclopropylbismuth. L = pyridine (C5H5N); n = 1, 2, 3, 4.
Conclusion
In summary, we developed the first S-cyclopropylation reaction of thiophenols using
tricyclopropylbismuth. The reaction is performed under mild conditions and affords the
corresponding aryl cyclopropyl sulfides, a useful class of compounds for medicinal and
synthetic organic chemistry, in moderate to good yields. This reaction constitutes the first
use of an organobismuth reagent in C(sp3)–S bond construction.
Acknowledgments
This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. through a
Scientific Advancement Grant, by a provincial Fonds de Recherche du Québec, Nature et
Technologies (FRQNT) team grant and by the Centre in Green Chemistry and Catalysis
(CGCC).
References
[1] A. Gagnon, J. Dansereau, A. Le Roch, Synthesis 49 (2017) 1707-1745.
[2] A. Gagnon, E. Benoit, A. Le Roch, Science of Synthesis Updates 4 (2018) 1.

ACCEPTED MANUSCRIPT
[3] G. Calingaert, H. Soroos, V. Hnizda, J. Am. Chem. Soc. 64 (1942) 392-397.
[4] M. Hébert, P. Petiot, E. Benoit, J. Dansereau, T. Ahmad, A. Le Roch, X. Ottenwaelder, A.
Gagnon, J. Org. Chem. 81 (2016) 5401-5416.
[5] S. Condon, C. Pichon, M. Davi, Org. Prep. Proc. Int. 46 (2014) 89-131.
[6] S. Shimada, M. L. N. Rao Top. Curr. Chem. 311 (2012) 199-228.
[7] P. Petiot, J. Dansereau, A. Gagnon, RSC Adv. 4 (2014) 22255-22259.
[8] C. Crifar, P. Petiot, T. Ahmad, A. Gagnon, Chem. Eur. J. 20 (2014) 2755-2760.
[9] P. Petiot, J. Dansereau, M. Hébert, I. Khene, T. Ahmad, S. Samaali, M. Leroy, F.
Pinsonneault, C. Y. Legault, A. Gagnon, Org. Biomol. Chem. 13 (2015) 1322-1327.
[10] T. Ahmad, J. Dansereau, M. Hébert, C. Grand-Maître, A. Larivée, A. Siddiqui, A. Gagnon,
Tetrahedron Lett. 57 (2016) 4284-4287.
[11] P. Petiot, A. Gagnon, Eur. J. Org. Chem. (2013) 5282-5289.
[12] D. H. R. Barton, N. Ozbalik, M. Ramesh, Tetrahedron Lett. 29 (1988) 857-860.
[13] O. Yamazaki, T. Tanaka, S. Shimada, Y. Suzuki, M. Tanaka, Synlett (2004) 1921-1924.
[14] A. Gagnon, V. Albert, M. Duplessis, Synlett (2010) 2936-2940.
[15] P. Petiot, A. Gagnon, Heterocycles 88 (2014) 1615-1624.
[16] A. Gagnon, M. St-Onge, K. Little, M. Duplessis, F. Barabé, J. Am. Chem. Soc. 129 (2007)
44-45.
[17] D. H. R. Barton, J.-P. Finet, J. Khamsi, Tetrahedron Lett. 28 (1987) 887-890.
[18] D. M. T. Chan, Tetrahedron Lett. 37 (1996) 9013-9016.
[19] A. Gagnon, M. Duplessis, P. Alsabeh, F. Barabé, J. Org. Chem. 73 (2008) 3604-3607.
[20] A. Gagnon, M. Duplessis, L. Fader, Org. Prep. Proc. Int. 42 (2010) 1-69.
[21] E. Benoit, J. Dansereau, A. Gagnon, Synlett 28 (2017) 2833-2838.
[22] X. Gu, X. Li, Y. Chai, Q. Yang, P. Li, Y. Yao, Green Chem. 15 (2013) 357-361.
[23] S. Meninno, A. Parrella, G. Brancatelli, S. Geremia, C. Gaeta, C. Talotta, P. Neri, A.
Lattanzi, Org. Lett. 17 (2015) 5100-5103.
[24] S. Gan, J. Yin, Y. Yao, Y. Liu, D. Chang, D. Zhu, L. Shi, Org. Biomol. Chem. 15 (2017) 2647-
2654.
[25] N. Nishimura, M. H. Norman, L. Liu, K. C. Yang, K. S. Ashton, M. D. Bartberger, S. Chmait,
J. Chen, R. Cupples, C. Fotsch, J. Helmering, S. R. Jordan, R. K. Kunz, L. D. Pennington, S. F.

ACCEPTED MANUSCRIPT
Poon, A. Siegmund, G. Sivits, D. J. Lloyd, C. Hale, D. J. St. Jean Jr., J. Med. Chem. 57 (2014)
3094-3116.
[26] J.-B. Feng, J.-L. Gong, X.-F. Wu, RSC Adv. 4 (2014) 29273-29275.
[27] W. Mao, M. Ning, Z. Liu, Q. Zhu, Y. Leng, A. Zhang, Bioorg. Med. Chem. 20 (2012) 2982-
2991.
[28] A. M. Deshpande, D. Bhuniya, S. De, B. Dave, V. P. Vyavahare, S. H. Kurhade, S. R.
Kandalkar, K. P. Naik, B. S. Kobal, R. D. Kaduskar, S. Basu, V. Jain, P. Patil, S. C. Joshi, G. Bhat,
A. A. Raje, S. Reddy, J. Gundu, V. Madgula, S. Tambe, P. Shitole, D. Umrani, A. Chugh, V. P.
Palle, K. A. Mookhtiar, Eur. J. Med. Chem. 133 (2017) 268-286.
[29] J.-F. Lohier, T. Glachet, H. Marzag, A.-C. Gaumont, V. Reboul, Chem. Commun 53 (2017)
2064-2067.
[30] U. Lücking, R. Jautelat, M. Krüger, T. Brumby, P. Lienau, M. Schäfer, H. Briem, J. Schulze,
A. Hillisch, A. Reichel, A. M. Wengner, A. G. Siemeister, ChemMedChem 8 (2013) 1067-1085.
[31] ClinicalTrials.gov identifier: NCT01247363: A study of LY2608204 in Patients With
Type 2 Diabetes.
[32] M. C. T. Fyfe, J. R. White, A. Taylor, R. Chatfield, E. Wargent, R. L. Printz, T. Sulpice, J. G.
McCormack, M. J. Procter, C. Reynet, P. S. Widdowson, P. Wong-Kai-In, Diabetologia 50
(2007) 1277-1287.
[33] M. Reck, L. Horn, S. Novello, F. Barlesi, I. Albert, E. Juhász, D. Kowalski, G. Robinet, J.
Cadranel, P. Bidoli, J. Chung, A. Fritsch, U. Drews, A. Wagner, R. Govindan, J. Thorac. Oncol.
14 (2019) 701-711.
[34] C. L. Bumgardner, J. R. Lever, S. T. Purrington, Tetrahedron Lett. 23 (1982) 2379-2382.
[35] T. W. Kwon, M. B. Smith, Synth. Commun. 22 (1992) 2273-2285.
[36] B. M. Trost, W. C. Vladuchick, Synthesis, 11 (1978) 821-821.
[37] J. H. Byers, T. A. Spencer, Tetrahedron Lett. 26 (1985) 717-720.
[38] B. M. Trost, D. E. Keeley, H. C. Arndt, M. J. Bogdanowicz, J. Am. Chem. Soc. 99 (1977)
3088-3100.
[39] A. M. Bernard, A. Frongia, F. Secci, G. Delogu, J. Ollivier, P. P. Piras, J. Salaün,
Tetrahedron 59 (2003) 9433-9440.
[40] A. M. Bernard, A. Frongia, F. Secci, P. P. Piras, Chem. Commun. (2005) 3853-3855.
[41] Y. Horiguchi, I. Suehiro, A. Sasaki, I. Kuwajima, Tetrahedron Lett. 34 (1993) 6077-6080.

ACCEPTED MANUSCRIPT
[42] E. Masson, F. Leroux, Helv. Chim. Acta. 88 (2005) 1375-1386.
[43] S. I. Kozhushkov, M. Brandl, A. de Meijere, Eur. J. Org. Chem. (1998) 1535-1542.
[44] J. E. Banning, A. R. Prosser, B. K. Alnasleh, J. Smarker, M. Rubina, M. Rubin, J. Org. Chem.
76 (2011) 3968-3986.
[45] L. Volta, C. J. M. Stirling, Phosphorus, Sulfur, and Silicon 184 (2009) 1508-1522.
[46] H.-C. Lin, R.-T. Tsai, H.-P. Wu, H.-Y. Lee, G.-A. Lee, Tetrahedron 72 (2016) 184-191.
[47] K. Tanaka, H. Uneme, S. Matsui, A. Kaji, Bull. Chem. Soc. Jpn. 55 (1982) 2965-2972.
[48] S. Porcu, A. Luridiana, A. Martis, A. Frongia, G. Sarais, D. J. Aitken, T. Boddaert, R. Guillot,
F. Secci, Chem. Commun. 54 (2018) 13547-13550.
[49] T. Wagner, J. Lange, D. Grote, W. Sander, E. Schaumann, G. Adiwidjaja, A. Adam, J. Kopf,
Eur. J. Org. Chem. (2009) 5198-5207.
[50] D. H. R. Barton, J.-C. Blazejewski, B. Charpiot, D. J. Lester, W. B. Motherwell, M. T. Barros
Papoula, J. Chem. Soc., Chem. Commun. (1980) 827-829.
[51] D. H. R. Barton, J.-C. Blazejewski, B. Charpiot, W. B. Motherwell, J. Chem. Soc., Chem.
Commun. (1981) 503-504.
[52] D. H. R. Barton, J.-C. Blazejewski, B. Charpiot, J.-P. Finet, W. B. Motherwell, M. T. Barros
Papoula, S. P. Stanforth, J. Chem. Soc, Perkin Trans 1 12 (1985) 2667-2675.
[53] S. Yasuike, M. Nishioka, N. Kakusawa, J. Kurita, Tetrahedron Lett. 52 (2011) 6403-6406.
[54] T. Tsuritani, N. A. Strotman, Y. Yamamoto, M. Kawasaki, N. Yasuda, T. Mase, Org. Lett.
10 (2008) 1653-1655.
[55] S. Bénard, L. Neuville, J. Zhu, Chem. Commun. 46 (2010) 3393-3395.
[56] S. Jaegli, J.-P. Vors, L. Neuville, J. Zhu, Tetrahedron 66 (2010) 8911-8921.
[57] Y. B. Tambe, S. Sharma, A. Pathak, L. K. Reddy, Synth. Commun. 42 (2012) 1341-1348.
[58] S. Haneda, K. Sudo, M. Hayashi, Heterocycles 84 (2012) 569-575.
[59] S. A. Rossi, K. W. Shimkin, Q. Xu, L. M. Mori-Quiroz, D. A. Watson, Org. Lett. 15 (2013)
2314-2317.
[60] S. R. K. Battula, G. V. Subbareddy, I. E. Chakravarthy, Tetrahedron Lett. 55 (2014) 517-
520.
[61] E. Racine, F. Monnier, J.-P. Vors, M. Taillefer, Chem. Commun. 49 (2013) 7412-7414.
[62] L. M. Mori-Quiroz, K. W. Shimkin, S. Rezazadeh, R. A. Kozlowski, D. A. Watson, Chem.
Eur. J. 22 (2016) 15654-15658.

ACCEPTED MANUSCRIPT
[63] S. Bénard, L. Neuville, J. Zhu, J. Org. Chem. 73 (2008) 6441-6444.
[64] A. M. Bernard, A. Frongia, P. P. Piras, Synth. Commun. 33 (2003) 801-817.
[65] S. D. McCann, S. S. Stahl, Acc. Chem. Res. 48 (2015) 1756-1766.
[66] I. Y. Ahmed, A. L. Abu-Hijleh, Inorg. Chimica Acta 61 (1982) 241-246.
[67] J. H. Mathews, E. B. Benger, J. Phys. Chem. 19 (1914) 264-268.
[68] W. J. Evans, J. H. Hain Jr., R. N. R. Broomhall-Dillard, J. W. Ziller, J. Coord. Chem. 47
(1999) 199-209.

ACCEPTED MANUSCRIPT
First Use of an Organobismuth Reagent in C(sp3)–S Bond Formation: Access to Aryl
Cyclopropyl Sulfides via Copper-Catalyzed S–Cyclopropylation of Thiophenols using
Tricyclopropylbismuth
Emeline Benoit,a Bianca Bueno,a Catherine Choinièrea and Alexandre Gagnon*a
aDépartement de chimie, Université du Québec à Montréal, C. P. 8888, Succursale Centre-
Ville, Montréal, Québec, Canada, H3C 3P8
Highlights
• Arylcyclopropyl sulfides are found in biologically relevant compounds and are useful
synthons for organic chemistry.
• Efficient methods to prepare arylcyclopropyl sulfides are needed.
• The direct S-cyclopropylation of thiophenols can be accomplished using
tricyclopropylbismuth.
• The reaction is catalyzed by copper(II) acetate, operate under simple conditions and
affords the desired arylcyclopropyl sulfides in good yields.
• This reaction is the first example on the use of an organobismuth species to form C(sp3)–
S bonds.