Synthetic uses of thioesters of trifluoromethylated acids. Part 2: Reactions with alkenes

Article abstract of DOI:10.1016/S0040-4039(00)00337-3

The photolysis of trifluoromethanethiosulfonates (CF₃SO₂SR) or trifluorothioacetates (CF₃COSR) in the presence of alkenes provides (trifluoromethyl)alkanes or β-sulfanyl (trifluoromethyl)alkanes. The formation of these compounds can be controlled by the nature and the ratio of the reactants. (C) 2000 Published by Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00337-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3069–3072
Synthetic uses of thioesters of trifluoromethylated acids. Part 2:
Reactions with alkenes
Thierry Billard, Nicolas Roques † and Bernard R. Langlois ∗
Université Claude Bernard-Lyon 1, Laboratoire de Synthèse, Electrosynthèse et Réactivité des Composés Organiques Fluorés
(UMR CNRS 5622), 43 Bd du 11 Novembre 1918 (Blg 303), 69622 Villeurbanne, France
Received 29 January 2000; accepted 22 February 2000
Abstract
The photolysis of trifluoromethanethiosulfonates (CF3SO2SR) or trifluorothioacetates (CF3COSR) in the pre-
sence of alkenes provides (trifluoromethyl)alkanes or β-sulfanyl (trifluoromethyl)alkanes. The formation of these
compounds can be controlled by the nature and the ratio of the reactants. © 2000 Published by Elsevier Science
Ltd. All rights reserved.
Keywords: trifluoromethanethiosulfonates; trifluorothioacetates; photolysis; (trifluoromethyl)alkanes.
The steadily growing interest for fluorinated compounds and, especially, trifluoromethylated products,
requires new methods to introduce directly the CF3 moiety.1 Among all the presently available strategies,2
radical trifluoromethylation constitutes the most versatile tool.
We recently described the synthesis3,4 and the photolytic behavior4 of thioesters of trifluoroacetic
(CF3COSR) or triflic (CF3SO2SR) acids and reported that, under UV irradiation, they generate trifluoro-
methyl radicals which can be trapped by disulfides to yield trifluoromethyl sulfides.
We have now extended this reaction to alkenes as trapping substrates in order to obtain trifluoro-
methylated alkanes. The procedure is typically the same as that for disulfides.5 The results are summari-
zed in Table 1.
In all cases phenyl trifluoromethanethiosulfonate (1) led to a mixture of products resulting from a for-
mal addition of CF3-SR (compounds 4) and products resulting from a formal hydrotrifluoromethylation
(compounds 5) whereas trifluorothioacetates (2) generally delivered 4 only. The high regioselectivity of
these reactions must be noticed since, in all cases, the ·CF3 radical reacted on the less hindered carbon
of the double bond. Such a sensitivity to steric factors explains that best results were obtained from
terminal olefins (Table 1, entries 5–9). The different behaviors of 1 and 2 can be rationalized through the
mechanism proposed in Scheme 1.
∗
†
Corresponding author. Fax: +33 (0)4 72 43 13 23; e-mail: bernard.langlois@univ-lyon1.fr (B. R. Langlois)
Present address: Rhodia, Centre de Recherche de Lyon, 85 av. des Frères Perret, BP 62, 69192 St Fons cedex, France.
0040-4039/00/$ - see front matter © 2000 Published by Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00337-3
tetl 16617

3070
Table 1
Photolysis of 1 or 2 in presence of alkenes (3)
Scheme 1. Principle of the trifluoromethylation
·
After addition of the electrophilic CF3 radical onto the substrate, a new carbon-centered radical A
is formed. However, radical A has a weak nucleophilic character6 which needs to react with a highly
electrophilic sulfur atom to deliver 4. We recently demonstrated that trifluoromethanethiosulfonates are
very electrophilic sulfenylating agents because of the high electron-withdrawing character of the CF3SO2
moiety,7 whereas trifluorothioacetates are not.8

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Thus, 4 can only result from the reaction of A with 1. In the other cases, A abstracted a hydrogen atom
from the medium and delivered 5.
Such a mechanism is consistent with the fact that the formation of 4 increased when an excess of
CF3SO2SR (versus alkene) was used (Table 1, entries 1, 2 and 5–7). On the contrary, an excess of olefin
(versus 1 or 2) led to an increased yield of 5 (Table 1, entries 1, 3 and 5, 8). This means that 5 resulted
predominantly from the abstraction of an allylic hydrogen of the substrate by radical A.
In order to determine if the solvent is also able to transfer hydrogen atoms to A, we repeated some
reactions in a perhalogenated solvent (Table 2).
Table 2
Photolysis in different solvents
These experiments showed that the solvent did not provide hydrogen atoms to A in a significant way
since almost the same amount of 5 was obtained in CFCl2CF2Cl and CH2Cl2. The dismutation of radical
A can also be considered as a minor route to 5 since, in some cases, trifluoromethylated olefins (7 and
8) were formed as by-products but usually in a far lesser amount than trifluoromethylated alkanes 5. The
different routes to 5 are reported in Scheme 2.
Scheme 2. General mechanism
Trifluoromethylated sulfides ·(CF3SR (6)) were also formed, as shown in Table 1. These compounds
resulted from the reaction of CF3 with the disulfide produced by dimerization of RS· radicals as
described in Part 1 of this study.4
The complete mechanism of the photolytic process is summarized in Scheme 2.
After reaction of 2 with the various alkenes, the mixtures of saturated products 5 and unsaturated
ones (7+8) can be reduced to yield selectively a single compound as illustrated in Table 3. Thus,
2-trifluoromethylcyclohexanol (9g) can be prepared from cyclohexanone (via 3f), in three steps only
(enolisation, photolysis, reduction).

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Table 3
Hydrogenation of the mixture of 5, 7 and 8
In conclusion, this strategy could be an effective new method for the synthesis of trifluoromethylated
alkanes or β-sulfanyl (trifluoromethyl)alkanes, even if, at the moment, it seems difficult to exceed a
50% yield. It can be noticed that, because of their sulfanyl moiety, the latter compounds can undergo
further functionalization and constitute useful synthetic tools which are under study in our laboratory. On
the other hand, hydrotrifluoromethylation of alkenes with trifluorothioacetates can constitute a valuable
transformation of unsaturated organic substrates since we have demonstrated that the crude photolysis
mixtures can be reduced to a single product.
References
1. (a) Filler, R.; Kobayashi, Y.; Yagulpolskii, Y. L. Organofluorine Compounds in Medicinal Chemistry and Biomedical
Applications; Elsevier: Amsterdam, 1993. (b) Banks, R. E.; Smart, B. E.; Tatlow, J. C. Organofluorine Chemistry: Principles
and Commercial Applications; Plenum Press: New York, 1994. (c) Hudlicky, M.; Pavlath, A. E. Chemistry of Organic
Fluorine Compounds II. A Critical Review; ACS Monograph 187; American Chemical Society: Washington, DC, 1995.
2. McClinton, M. A.; McClinton, D. A. Tetrahedron 1992, 48, 6555–6666.
3. Billard, T.; Langlois, B. R.; Large, S.; Anker, D.; Roidot, N.; Roure, P. J. Org. Chem. 1996, 61, 7545.
4. Billard, T.; Roques, N.; Langlois, B. R. J. Org. Chem. 1999, 64, 3813–3820.
5. Thioesters and alkenes, dissolved in 20 mL of dichloromethane, were introduced in a quartz cylindrical flask (plane faces in
vertical position), fitted with a vertical reflux condenser. Air was blown off from this solution with nitrogen. Then, the stirred
reaction mixture was illuminated by a mercury vapor lamp (Phillips HPK125, 125 W), through the plane walls of the reactor.
6. Fossey, J.; Lefort, D.; Sorba, J. Les Radicaux Libres en Chimie Organique; Masson: Paris, 1993; p. 73.
7. Billard, T.; Langlois, B. Tetrahedron 1999, 55, 8065–8074.
8. Roques, N. Ph.D. Dissertation, University Claude Bernard-Lyon I, Villeurbanne (France), 1996.
1
9. Compounds 5b–e, 9g and 4b were characterized from isolated compounds. For example: 4b: H: 7.24–7.62 (massif, 5H),
3.33 (m, 1H), 2.2–2.5 (massif, 2H), 1.27 (massif, 16H), 0.88 (t, J=6 Hz, 3H). 13C: 133.71, 132.68, 129.14, 127.62, 126.13
(q, J=278 Hz) 42.44 (q, J=2.5 Hz), 39.17 (q, J=27.4 Hz), 33.81 (q, J=1 Hz), 31.91, 29.54, 29.45, 29.32, 29.28, 26.36, 22.72,
1
14.13. 19F: −63.95 (t, J=11.5 Hz). Compound 5b: H: 2.03 (m, 2H), 1.55 (m, 2H), 1.26 (m, 16H), 0.88 (t, J=6.4 Hz, 3H).
13C: 127.42 (q, J=277 Hz), 33.88 (q, J=28 Hz), 32.07, 29.78, 29.71, 29.51, 29.34, 28.87, 22.83, 21.99 (q, J=2 Hz), 14.16. 19F:
−66.9 (t, J=11.3 Hz). The others compounds 4 and 5 were identified by 19F NMR and mass spectrum. By-products 7 and
8 were identified by 19F NMR, mass spectrum and by analogy with the literature (Brookes, C. J.; Coe, P. L.; Pedler, A. E.;
Tatlow, J. C. J. Chem. Soc., Perkin Trans. 1 1978, 202–209.