Trifluoromethylthiolation of α-Chloroaldehydes: Access to Quaternary SCF3-Containing Centers

Article abstract of DOI:10.1002/ejoc.201800418

In this study, a straightforward methodology was developed to access quaternary α-trifluoromethylthiolated chloroaldehydes. Using the Munavalli reagent as the electrophilic SCF₃ source, a base-catalyzed trifluoromethylthiolation reaction with a panel of α-chloroaldehydes was successfully achieved under mild reaction conditions. The α-trifluoromethylthiolated chloroaldehydes were obtained in moderate to high yields (up to 88 %). This approach demonstrated a good functional-group tolerance and offered access to highly functionalized quaternary trifluoromethylthiolated aldehydes, inaccessible so far. The development of an enantioselective version was investigated by using a chiral phase-transfer catalyst, giving the enantioenriched product in moderate enantiomeric excess.

Full text of DOI:10.1002/ejoc.201800418

DOI: 10.1002/ejoc.201800418
Communication
Trifluoromethylthiolation | Very Important Paper |
Trifluoromethylthiolation of α-Chloroaldehydes: Access to
Quaternary SCF3-Containing Centers
Fabien Gelat,[a] Thomas Poisson,[a,b] Akkattu T. Biju,[c] Xavier Pannecoucke,[a] and
Tatiana Besset*[a]
Abstract: In this study, a straightforward methodology was de- 88 %). This approach demonstrated a good functional-group
veloped to access quaternary α-trifluoromethylthiolated chloro-
aldehydes. Using the Munavalli reagent as the electrophilic SCF3
source, a base-catalyzed trifluoromethylthiolation reaction with
a panel of α-chloroaldehydes was successfully achieved under
mild reaction conditions. The α-trifluoromethylthiolated chloro-
aldehydes were obtained in moderate to high yields (up to
tolerance and offered access to highly functionalized quater-
nary trifluoromethylthiolated aldehydes, inaccessible so far. The
development of an enantioselective version was investigated
by using a chiral phase-transfer catalyst, giving the enantio-
enriched product in moderate enantiomeric excess.
Introduction
class of compounds. So far, most of the strategies relied on
the use of SCF3-containing building blocks to construct more
complex molecules[8] or the direct introduction of the SCF3 resi-
Molecules containing a fluorine atom and a fluorinated group
are ubiquitous in our daily life and more particularly in agro-
chemicals and medicinal chemistry[1] due to their unique fea-
tures.[2] Therefore, organofluorine chemistry is nowadays con-
sidered as a key research field and considerable advances are
continuously made by the organic chemistry community to
provide powerful synthetic tools as original transformations and
newly-designed emergent fluorinated groups.[3] Among these
emergent groups, the SCF3 group[4] features attractive physico-
chemical properties like its high lipophilicity (Hansch hydro-
phobic parameter, π = 1.44)[5] and its electron-withdrawing
character.[6] Moreover, its potential has already been demon-
strated in molecules of interest such as the insecticide Fipronil
or the Toltrazuril, a coccidiostatic drug, commercialized by BASF
and Bayer, respectively.
Therefore, the quest for the introduction of this fluorinated
residue onto molecules inspired the scientific community to de-
velop new strategies, offering a large tool box for the incorpora-
tion of this fluorinated group onto various scaffolds.[7] To date,
the formation of a C(sp2)–SCF3 bond has been intensively stud-
ied involving transition-metal-promoted transformations, or-
ganocatalyzed reactions or radical pathways. Conversely, the
functionalization of C(sp3) centers remains underdeveloped and
further progress has to be made to broaden the access to this
[a] Normandie Univ, INSA Rouen, UNIROUEN, CNRS, COBRA (UMR 6014),
76000 Rouen, France.
E-mail: tatiana.besset@insa-rouen.fr
http://www.lab-cobra.fr/
[b] Institut Universitaire de France,
103 boulevard Saint-Michel, 75005 Paris, France
[c] Department of Organic Chemistry, Indian Institute of Science,
Bangalore, 560012, India
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201800418.
Scheme 1. Trifluoromethylthiolation of aldehydes: state of the art and pro-
posed strategy.
Eur. J. Org. Chem. 0000, 0–0
1
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
due onto aliphatic compounds.[9] In the last case, the α-func- in a higher 72 % yield (entries 5–9). Using the best reaction
tionalization of a carbonyl group appeared as a privileged and conditions and switching the electrophilic source from the Haas
efficient approach to provide the targeted C–SCF3 bond reagent II to the Munavalli one I, 2a was obtained in a slightly
(Scheme 1).
better 19F NMR yield (80 %) and was isolated in 78 % yield (en-
try 10).
The α-trifluoromethylthiolation of carbonyl compounds con-
nected to a tertiary carbon center offers a straightforward ac-
cess to SCF3-substituted quaternary centers. The current meth-
ods relied on the functionalization of highly reactive carbonyl
compounds such as oxindoles, benzofuranones, malonates and
ꢀ-keto esters with electrophilic SCF3 sources via 1) organocata-
lyzed,[10] 2) transition-metal-catalyzed[11] and 3) base-pro-
moted[12] trifluoromethylthiolation reactions. Alternatively, the
direct introduction of a SCF3 group onto amides, N-acyl oxaz-
olidinones and ketones was also studied, albeit restricted to a
handful of examples.[10h,13]
In sharp contrast, the construction of a quaternary SCF3–
C(sp3) center on aldehyde derivatives at the α-position is scarce
(Scheme 1). Since the pioneering work by Haas in 1971,[14] few
reports dealt with the synthesis of α-trifluoromethylthiolated
aldehydes. Lu and Shen reported the trifluoromethylthiolation
of hydrocinnamaldehyde derivatives using enamine catalysis
with the morpholine hydrochloride salt in the presence of an
electrophilic SCF3 source.[10a] A similar transformation was then
reported by Shen using the N-trifluoromethylthiosaccharin rea-
gent.[10b] In both cases, only two examples were depicted. Bil-
lard and co-workers reported the trifluoromethylthiolation of
silyl enol ethers and described a single example with an alde-
hyde.[10c] The same group then developed a complementary
approach to access α-trifluoromethylthiolated aldehydes under
acid-catalysis.[15] The next year, Sun depicted the α-trifluoro-
methylthiolation of a wide range of aldehydes using enamine
catalysis, although a single tertiary aldehyde was functional-
ized.[16] It is worth to mention that the methods for the α-
trifluoromethylthiolation of aldehydes are restricted to very few
examples. In addition, the access to α-SCF3-containing quater-
nary centers is even more rare.
Table 1. Optimization of the base-catalyzed trifluoromethylthiolation of the
α-chloroaldehyde 1a.[a]
+
Entry
Base (x mol-%)
SCF3 reagent Solvent
Yield 2a [%][b]
1
2
3
4
5
6
7
8
9
K2CO3 (200)
DABCO (15)
DABCO (15)
DABCO (15)
DABCO (15)
DABCO (15)
DABCO (15)
DABCO (15)
DABCO (15)
DABCO (15)
I
I
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
1,4-dioxane
THF
CH3CN
toluene
DMF
17
3
22
NR
9
8
35
4
II
III
II
II
II
II
II
I
72
10
DMF
80 (78)[c]
+
[a] Reaction conditions: 1a (0.2 mmol), SCF3 reagent (0.2 mmol), base (x
mol-%), solvent (2 mL), 20 °C, 15 h, argon. [b] Yields determined by 19F NMR
analysis of the crude reaction mixture using α,α,α-trifluorotoluene as an in-
ternal standard. [c] Yield of isolated product. NR = no reaction.
With the best reaction conditions in hands, the scope of the
transformation was studied (Scheme 2). First, the substitution
on the aryl group of the α-chlorophenylpropanal backbone was
studied. Aryls bearing an electron-donating group (OMe, 2b)
and an electron-withdrawing one (CF3, 2c) were efficiently func-
tionalized; albeit with a somehow lower yield in the case of 2c.
The naphthyl derivative (1d) was also readily converted into 2d
in a decent 78 % yield. The transformation was not restricted
to arylated propanal derivatives since α-chloro nonanal 1e was
trifluoromethylthiolated in a high 77 % yield. The reaction
turned out to be compatible with a chlorine atom as a substitu-
ent, furnishing the expected compound 2f. Various functional
groups were suitable as demonstrated by the functionalization
of benzyl-protected alcohol (1g) and phthalimide (1h) deriva-
tives. Trifluoromethylthiolated aldehydes substituted with azide
Therefore, the development of complementary and more
general approaches to afford aldehydes bearing a α-trifluoro-
methylthiolated quaternary center is an appealing task. In that
context, we turned our attention to the α-chloroaldehydes as a
readily available starting material. Herein, we report the base-
catalyzed trifluoromethylthiolation of α-chloroaldehydes, offer-
ing an original access to new and valuable SCF3-containing
fluorinated building blocks bearing a quaternary C–SCF3 center.
Results and Discussion
At the outset of the study, α-chlorophenylpropanal 1a was se- (1i) and cyano (1j) groups were efficiently obtained in 64 % and
lected as the model substrate. When 1a was reacted in the 63 % yields, respectively. From a synthetic point of view, this
presence of the Munavalli reagent I and a stoichiometric functional-group tolerance opened great perspectives in term
amount of K2CO3 as a base at room temperature, the expected of post-functionalization reactions and for the construction of
product 2a was observed in 17 % yield (Table 1, entry 1). Using more complex molecules using these fluorinated chemical plat-
a catalytic amount of DABCO (15 mol-%), 2a was still detected forms. The versatility of this transformation was further demon-
albeit in traces (entry 2). Then, other electrophilic sources were strated by the trifluoromethylthiolation reaction of molecules
evaluated (entries 3–4), the Haas reagent II being the most effi- of interest such as citronellal (1k) and oleic acid (1l), offering
cient one. To further improve the yield, several solvents were an access to the corresponding SCF3-containing products in
tested, revealing that DMF provided the expected product 2a moderate yields (Scheme 2).
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
2
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
Scheme 4. Catalytic enantioselective trifluoromethylthiolation of the α-chlo-
roaldehyde 1a under phase-transfer catalysis.
Conclusions
In summary, a novel synthetic approach was developed for the
synthesis of the highly functionalized quaternary α-trifluoro-
methylthiolated aldehydes. Using a catalytic amount of DABCO,
various aldehydes were functionalized in moderate to good
yields under mild conditions. The transformation showed a
good functional-group tolerance. The enantioselective trifluoro-
methylthiolation reaction was studied by means of phase-trans-
fer catalysis affording the expected aldehyde in good yield and
moderate enantiomeric excess. These original fluorinated build-
ing blocks are of particular interest due to the presence of vari-
ous functional groups (CHO, Cl and SCF3) and would be very
useful to access new value-added SCF3-containing molecules
that have been inaccessible so far.
Scheme 2. Trifluoromethylthiolation of α-chloroaldehydes. Reaction condi-
tions: 1 (0.5 mmol), electrophilic SCF3 reagent I (1 equiv.), DABCO (15 mol-
%), DMF (0.1 M), 20 °C, 15 h, argon. Yields of isolated products were reported.
[a] Reaction performed on 0.2 mmol scale. [b] A diastereoisomeric ratio of
77:23 was obtained.
To showcase the synthetic utility of these functionalized scaf-
folds, post-functionalization reactions were conducted. The al-
dehyde 2a was smoothly reduced with NaBH4 into the corre-
sponding alcohol 3 in 87 % yield. Then, the aldehyde 2a was
efficiently converted in one-step into the corresponding methyl
ester 4 in 76 % yield via NHC catalysis (Scheme 3).[17] This
method afforded a straightforward and functional-group toler-
ant access to α-SCF3 ester derivatives under mild conditions,
which are usually synthesized using a stoichiometric amount of
a strong base (LDA) from the corresponding esters.[10c]
Experimental Section
In an oven-dried tube equipped with a magnetic stirrer, DABCO
(0.075 mmol, 15 mol-%) was added to a solution of the α-chloro-
aldehyde derivative 1 (0.5 mmol, 1 equiv.) and phthalimide-SCF3
reagent I (0.5 mmol, 1 equiv.) in DMF (5 mL) under argon. The
reaction mixture was stirred at 20 °C for 15 h. Then, brine (15 mL)
was added and the aqueous layer was extracted with Et2O (3 ×
15 mL). Organic layers were combined and washed with brine (2 ×
15 mL), dried with Na2SO4, filtered and concentrated under reduced
pressure at 20 °C under 100 mbar. The residue was purified by flash
column chromatography on silica gel (petroleum ether/dichloro-
methane) to afford the desired trifluoromethylthiolated ester deriv-
ative 2.
Acknowledgments
This work was supported by the Indo-French Centre for the
Promotion of Advanced Research (IFCPAR-CEFIPRA, Project No:
5505-1). This work was partially supported by INSA Rouen,
Rouen University, CNRS, EFRD, Labex SynOrg (ANR-11-LABX-
0029), Région Normandie (Crunch Network) and the IUF (Insti-
tut Universitaire de France). F. G. thanks IFCPAR-CEFIPRA for a
post-doctoral fellowship.
Scheme 3. Post-functionalization reactions. DIPEA = N,N-diisopropylethyl-
amine.
Keywords: Fluorinated compounds ·
Trifluoromethylthiolation · Quaternary centers · Building
blocks · Phase-transfer catalysis · Aldehydes
Finally, the catalytic asymmetric trifluoromethylthiolation of
α-chloroaldehydes was studied using 1a and a phase-transfer
catalyst. After extensive investigations, we found that 1-{[4-
(trifluoromethyl)phenyl]methyl}cinchonidinium chloride 5 was
the best catalyst. Using 5 (20 mol-%), Cs2CO3 as a base in tolu-
ene, the enantioenriched aldehyde 2a was isolated in good
yield and moderate enantiomeric excess (79 %, 37 % ee,
Scheme 4).
[1] a) J. Wang, M. Sánchez-Roselló, J. L. Aceña, C. del Pozo, A. E. Sorochinsky,
S. Fustero, V. A. Soloshonok, H. Liu, Chem. Rev. 2014, 114, 2432–2506; b)
S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008,
37, 320–330; c) E. P. Gillis, K. J. Eastman, M. D. Hill, D. J. Donnelly, N. A.
Meanwell, J. Med. Chem. 2015, 58, 8315–8359; d) E. A. Ilardi, E. Vitaku,
J. T. Njardarson, J. Med. Chem. 2014, 57, 2832–2842.
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
3
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
[2] D. O'Hagan, Chem. Soc. Rev. 2008, 37, 308–319.
[8] For selected examples, see: a) S.-G. Li, S. Z. Zard, Org. Lett. 2013, 15,
5898–5901; b) Z. Zhang, Z. Sheng, W. Yu, G. Wu, R. Zhang, W.-D. Chu, Y.
Zhang, J. Wang, Nat. Chem. 2017, 9, 970–976; c) L. Xu, H. Wang, C. Zheng,
G. Zhao, Adv. Synth. Catal. 2017, 359, 2942–2948; d) H.-B. Yang, X. Fan,
Y. Wei, M. Shi, Org. Chem. Front. 2015, 2, 1088–1093.
[3] a) T. Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2013, 52,
8214–8264; Angew. Chem. 2013, 125, 8372; b) C. Ni, J. Hu, Chem. Soc.
Rev. 2016, 45, 5441–5454; c) G. Landelle, A. Panossian, F. R. Leroux, Curr.
Top. Med. Chem. 2014, 14, 941–951; d) G. Landelle, A. Panossian, S. Paze-
nok, J.-P. Vors, F. R. Leroux, Beilstein J. Org. Chem. 2013, 9, 2476–2536; e)
P. A. Champagne, J. Desroches, J.-D. Hamel, M. Vandamme, J.-F. Paquin,
Chem. Rev. 2015, 115, 9073–9174; f) E. Merino, C. Nevado, Chem. Soc.
Rev. 2014, 43, 6598–6608; g) H. Egami, M. Sodeoka, Angew. Chem. Int.
Ed. 2014, 53, 8294–8308; Angew. Chem. 2014, 126, 8434; h) M.-C. Bel-
homme, T. Besset, T. Poisson, X. Pannecoucke, Chem. Eur. J. 2015, 21,
12836–12865; i) T. Besset, T. Poisson, X. Pannecoucke, Chem. Eur. J. 2014,
20, 16830–16845; j) T. Besset, P. Jubault, X. Pannecoucke, T. Poisson, Org.
Chem. Front. 2016, 3, 1004–1010.
[4] a) F. Toulgoat, S. Alazet, T. Billard, Eur. J. Org. Chem. 2014, 2415–2428; b)
X.-H. Xu, K. Matsuzaki, N. Shibata, Chem. Rev. 2015, 115, 731–764; c) S.
Barata-Vallejo, S. Bonesi, A. Postigo, Org. Biomol. Chem. 2016, 14, 7150–
7182; d) M. Li, J. Guo, X.-S. Xue, J.-P. Cheng, Org. Lett. 2016, 18, 264–267.
[5] C. Hansch, A. Leo, S. H. Unger, K. H. Kim, D. Nikaitani, E. J. Lien, J. Med.
Chem. 1973, 16, 1207–1216.
[9] For selected examples, see: a) S. Guo, X. Zhang, P. Tang, Angew. Chem.
Int. Ed. 2015, 54, 4065–4069; Angew. Chem. 2015, 127, 4137; b) H. Wu,
Z. Xiao, J. Wu, Y. Guo, J.-C. Xiao, C. Liu, Q.-Y. Chen, Angew. Chem. Int. Ed.
2015, 54, 4070–4074; Angew. Chem. 2015, 127, 4142; c) H.-Y. Xiong, T.
Besset, D. Cahard, X. Pannecoucke, J. Org. Chem. 2015, 80, 4204–4212;
d) L. Candish, L. Pitzer, A. Gomez-Suarez, F. Glorius, Chem. Eur. J. 2016,
22, 4753–4756; e) M. Jiang, F. Zhu, H. Xiang, X. Xu, L. Deng, C. Yang, Org.
Biomol. Chem. 2015, 13, 6935–6939; f) Y. Huang, X. He, X. Lin, M. Rong,
Z. Weng, Org. Lett. 2014, 16, 3284–3287; g) J. Zheng, R. Cheng, J.-H. Lin,
D.-H. Yu, L. Ma, L. Jia, L. Zhang, L. Wang, J.-C. Xiao, S. H. Liang, Angew.
Chem. Int. Ed. 2017, 56, 3196–3200; Angew. Chem. 2017, 129, 3244.
[10] For selected examples, see: a) X. Shao, X. Wang, T. Yang, L. Lu, Q. Shen,
Angew. Chem. Int. Ed. 2013, 52, 3457–3460; Angew. Chem. 2013, 125,
3541; b) C. Xu, B. Ma, Q. Shen, Angew. Chem. Int. Ed. 2014, 53, 9316–
9320; Angew. Chem. 2014, 126, 9470; c) S. Alazet, L. Zimmer, T. Billard,
Chem. Eur. J. 2014, 20, 8589–8593; For selected examples of enantio-
selective transformations, see: d) T. Bootwicha, X. Liu, R. Pluta, I. Atodire-
sei, M. Rueping, Angew. Chem. Int. Ed. 2013, 52, 12856–12859; Angew.
Chem. 2013, 125, 13093; e) X. Wang, T. Yang, X. Cheng, Q. Shen, Angew.
Chem. Int. Ed. 2013, 52, 12860–12864; Angew. Chem. 2013, 125, 13098;
f) X.-L. Zhu, J.-H. Xu, D.-J. Cheng, L.-J. Zhao, X.-Y. Liu, B. Tan, Org. Lett.
2014, 16, 2192–2195; g) M. Rueping, X. Liu, T. Bootwicha, R. Pluta, C.
Merkens, Chem. Commun. 2014, 50, 2508–2511; h) K. Liao, F. Zhou, J.-S.
Yu, W.-M. Gao, J. Zhou, Chem. Commun. 2015, 51, 16255–16258; i) B.-L.
Zhao, D.-M. Du, Org. Lett. 2017, 19, 1036–1039.
[11] For selected examples, see: a) Y.-D. Yang, A. Azuma, E. Tokunaga, M.
Yamasaki, M. Shiro, N. Shibata, J. Am. Chem. Soc. 2013, 135, 8782–8785;
b) Q.-H. Deng, C. Rettenmeier, H. Wadepohl, L. H. Gade, Chem. Eur. J.
2014, 20, 93–97.
[12] For selected examples, see: a) X. Shao, C. Xu, L. Lu, Q. Shen, J. Org. Chem.
2015, 80, 3012–3021; b) E. V. Vinogradova, P. Müller, S. L. Buchwald,
Angew. Chem. Int. Ed. 2014, 53, 3125–3128; Angew. Chem. 2014, 126,
3189; c) H. Zhang, X. Leng, X. Wan, Q. Shen, Org. Chem. Front. 2017, 4,
1051–1057.
[13] For selected examples, see: a) H. Chachignon, E. V. Kondrashov, D. Ca-
hard, Adv. Synth. Catal. 2018, 360, 965–971; b) W. Wu, X. Zhang, F. Liang,
S. Cao, Org. Biomol. Chem. 2015, 13, 6992–6999.
[14] A. Haas, W. Hinsch, Chem. Ber. 1971, 104, 1855–1862.
[15] S. Alazet, E. Ismalaj, Q. Glenadel, D. Le Bars, T. Billard, Eur. J. Org. Chem.
2015, 2015, 4607–4610.
[6] C. Hansch, A. Leo, R. W. Taft, Chem. Rev. 1991, 91, 165–195.
[7] For selected examples, see: a) B. Exner, B. Bayarmagnai, F. Jia, L. J.
Goossen, Chem. Eur. J. 2015, 21, 17220–17223; b) M. Hu, J. Rong, W.
Miao, C. Ni, Y. Han, J. Hu, Org. Lett. 2014, 16, 2030–2033; c) F. Hu, X.-X.
Shao, D.-H. Zu, L. Lu, Q. Shen, Angew. Chem. Int. Ed. 2014, 53, 6105–6109;
Angew. Chem. 2014, 126, 6219; d) J.-B. Liu, X.-H. Xu, Z.-H. Chen, F.-L. Qing,
Angew. Chem. Int. Ed. 2015, 54, 897–900; Angew. Chem. 2015, 127, 911;
e) T. Yang, L. Lu, Q. Shen, Chem. Commun. 2015, 51, 5479–5481; f) K.-Y.
Ye, X. Zhang, L.-X. Dai, S.-L. You, J. Org. Chem. 2014, 79, 12106–12110; g)
Z. Huang, Y.-D. Yang, E. Tokunaga, N. Shibata, Org. Lett. 2015, 17, 1063–
1065; h) G. Danoun, B. Bayarmagnai, M. F. Gruenberg, L. J. Goossen,
Chem. Sci. 2014, 5, 1312–1316; i) K. Zhang, J.-B. Liu, F.-L. Qing, Chem.
Commun. 2014, 50, 14157–14160; j) L. Jiang, J. Qian, W. Yi, G. Lu, C. Cai,
W. Zhang, Angew. Chem. Int. Ed. 2015, 54, 14965–14969; Angew. Chem.
2015, 127, 15178; k) Y. Yang, L. Xu, S. Yu, X. Liu, Y. Zhang, D. A. Vicic,
Chem. Eur. J. 2016, 22, 858–863; l) L. D. Tran, I. Popov, O. Daugulis, J. Am.
Chem. Soc. 2012, 134, 18237–18240; m) C. Xu, Q. Shen, Org. Lett. 2014,
16, 2046–2049; n) C. Chen, X.-H. Xu, B. Yang, F.-L. Qing, Org. Lett. 2014,
16, 3372–3375; o) W. Yin, Z. Wang, Y. Huang, Adv. Synth. Catal. 2014, 356,
2998–3006; p) Q. Wang, F. Xie, X. Li, J. Org. Chem. 2015, 80, 8361–8366;
q) X.-G. Liu, Q. Li, H. Wang, Adv. Synth. Catal. 2017, 359, 1942–1946; r)
M. Bu, G. Lu, C. Cai, Org. Chem. Front. 2017, 4, 266–270; s) Q. Zhao, T.
Poisson, X. Pannecoucke, J. P. Bouillon, T. Besset, Org. Lett. 2017, 19,
5106–5109; t) Q. Lefebvre, E. Fava, P. Nikolaienko, M. Rueping, Chem.
Commun. 2014, 50, 6617–6619; u) M. Lübcke, W. Yuan, K. J. Szabó, Org.
Lett. 2017, 19, 4548–4551; v) L. Jarrige, A. Carboni, G. Dagousset, G. Levi-
tre, E. Magnier, G. Masson, Org. Lett. 2016, 18, 2906–2909; w) G. Dagous-
set, C. Simon, E. Anselmi, B. Tuccio, T. Billard, E. Magnier, Chem. Eur. J.
2017, 23, 4282–4286; x) X. Liu, R. An, X. Zhang, J. Luo, X. Zhao, Angew.
Chem. Int. Ed. 2016, 55, 5846–5850; Angew. Chem. 2016, 128, 5940; y) S.
Pan, Y. Huang, F.-L. Qing, Chem. Asian J. 2016, 11, 2854–2858; z) J. Zhang,
L. Wang, J.-H. Lin, J.-C. Xiao, S. H. Liang, Angew. Chem. Int. Ed. 2015, 54,
13236–13240; Angew. Chem. 2015, 127, 13434; aa) Y. Li, T. Koike, M. Akita,
Asian J. Org. Chem. 2017, 6, 445–448.
[16] L. Hu, M. Wu, H. Wan, J. Wang, G. Wang, H. Guo, S. Sun, New J. Chem.
2016, 40, 6550–6553.
[17] For a selection of reports dealing with the conversion of α-haloalde-
hydes into the corresponding esters via NHC catalysis, see: a) N. T. Reyn-
olds, J. Read de Alaniz, T. Rovis, J. Am. Chem. Soc. 2004, 126, 9518–9519;
b) J. Mahatthananchai, J. W. Bode, Chem. Sci. 2012, 3, 192–197.
Received: March 13, 2018
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
4
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
Trifluoromethylthiolation
F. Gelat, T. Poisson, A. T. Biju,
X. Pannecoucke, T. Besset* .............. 1–5
Trifluoromethylthiolation
of
α-
Chloroaldehydes: Access to Quater-
nary SCF3-Containing Centers
A new access to highly functionalized a panel of α-chloroaldehydes was suc-
quaternary α-trifluoromethylthiolated cessfully achieved under mild reaction
aldehydes was developed. Using the conditions via a base-catalyzed tri-
electrophilic Munavalli reagent, the di- fluoromethylthiolation reaction.
rect introduction of a SCF3 group onto
Base-catalyzed trifluoromethylthiolation of alpha-chloroaldehydes #OutstandingOrganics
Share your work on social media! The European Journal of Organic Chemistry has added Twitter as a means to promote
your article. Twitter is an online microblogging service that enables its users to send and read text-based messages of up
to 140 characters, known as “tweets”. Please check the pre-written tweet in the galley proofs for accuracy. Should you or
your institute have a Twitter account, please let us know the appropriate username (i.e., @accountname), and we will do
our best to include this information in the tweet. This tweet will be posted to the journal’s Twitter account @EurJOC (follow
us!) upon online publication of your article, and we recommend you to repost (“retweet”) it to alert other researchers
about your publication.
DOI: 10.1002/ejoc.201800418
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
5
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim