A novel method for the synthesis of thiols from the corresponding olefins by using thiocarbonates and Ti(IV) halides

Article abstract of DOI:10.1246/cl.2001.638

A convenient method for the preparation of secondary or tertiary thiols from the corresponding olefins was established by using thiocarbonate, titanium(IV) chloride or fluoride and copper(II) oxide. Various thiols were obtained regioselectively in good to excellent yields according to the Markovnikov rule.

Full text of DOI:10.1246/cl.2001.638

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Chemistry Letters 2001
A Novel Method for the Synthesis of Thiols from the Corresponding Olefins
by Using Thiocarbonates and Ti(IV) Halides
Teruaki Mukaiyama, Terunobu Saitoh, and Hideki Jona
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
(Received April 24, 2001; CL-010377)
A convenient method for the preparation of secondary or
Various titanium(IV) halides were examined further in order
to check their activities as Lewis acid under those reaction condi-
tions as listed in Table 1. Then, TiCl and TiF proved to be
tertiary thiols from the corresponding olefins was established
by using thiocarbonate, titanium(IV) chloride or fluoride and
copper(II) oxide. Various thiols were obtained regioselectively
in good to excellent yields according to the Markovnikov rule.
4
4
more effective reagents compared with TiI and TiBr (Table 1,
4
4
Entries 1–3, 6). In the latter cases, large amounts of side product
1 were formed. All these results indicated the reactions to be
1
influenced by size, nucleophilicity, and electronegativity of the
4
Recently, it was reported from our laboratory that diastere-
oselective pinacol coupling reaction of various aldehydes pro-
halogen atoms contained in the titanium salts. Next, various sol-
vents and reaction temperatures were examined by using both
TiCl and TiF (Table 1, Entries 3–5, 6–8). When TiCl was
used, the reaction proceeded smoothly at 0 °C in toluene to afford
the desired thiol 9 in good yield (Table 1, Entry 5). Thiol 9 was
also obtained in good yield when the reaction was carried out in
CH Cl at room temperature using TiF (Table 1, Entry 6). In
1
ceeded smoothly by using low valent titanium halides such as
4
4
4
2
chloride, bromide and iodide. Then, it was thought that reduc-
3
tive deoxygenation of thiocarbonate 1 would be effected by the
above low valent titanium species to afford the corresponding
olefins 2 along with the loss of CO via carbene intermediate
2
2
2
4
formed by desulfurization. Contrary to expectation, the desired
olefin 2 was not obtained at all when the reductive desulfuriza-
tion of thiocarbonate was tried by using low valent titanium
iodide formed in situ from titanium(IV) iodide and zinc powder
every case, the corresponding co-product of carbonate 10, formed
by oxygenation of thiocarbonate 8, was obtained without an
exception. Further, side product 11 was obtained in some cases,
but it was not hydrolyzed during the above work up procedure.
(Scheme 1). Next, in order to scavenge iodine originated from
titanium iodide, the same reaction was tried by adding of 2-
methyl-2-butene. It was found that carbonate 4, instead of the
desired olefin 2, was unexpectedly isolated together with adduct
6
(Scheme 2). The formation of 4 indicated the existence of
intermediate 3 which in turn afforded thiol 5 on hydrolysis.
This gave us an important hint that thiols would be prepared
from the corresponding olefins. Actually, thiol 5 was isolated
on careful treatment of the above reaction mixture with 1 M
aqueous HCl. After screening the reaction conditions, it was
found that the similar reaction proceeded smoothly by using
just TiCl without extra addition of such reducing agents as Zn
4
powder. In this communication, we would like to report a con-
venient method for the preparation of secondary and tertiary
thiols from the corresponding olefins by using thiocarbonate
and titanium(IV) halide.
Next, various Lewis acids and additives were examined
under the conditions as shown in Table 2. Concerning the effect
of Lewis acids, TiCl gave the best result. (Table 2, Entries
4
5
1
–4). Further, several metal oxides were added to the above
reaction mixture to improve the yield. Among the additives,
copper(II) oxide was the most effective and thiol 9 was
obtained in excellent yield. However the role of copper(II)
oxide is not yet clear (Table 2, Entries 5–8).
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
639
all thiols were obtained in perfectly regioselective manner
according to Markovnikov rule (Entries 1–4, 10, 11).
Finally, the mechanism of the present reaction using olefin,
thiocarbonate, and titanium(IV) halide was investigated by
quenching the reaction mixture with D O–DCl, and deuterated
2
thiol 16 and carbonate 17 were formed as shown in Scheme 3.
The result was thus explained by considering the initial forma-
tion of the key intermediate 14 by way of TiX -induced cyclic
4
six-membered transition state 13. The formed 14 was in turn
hydrolyzed on treatment with DCl–D O to afford the deuterated
2
thiol 16 and carbonate 17.
Thus, a novel method for direct synthesis of thiols from the
corresponding olefins by using of TiCl or TiF in the coexist-
4
4
ence of copper(II) oxide was established. Since there are only a
6
few reports on direct synthesis of thiols especially on that of the
7
hindered ones, this method provides a useful tool in the field of
organic synthesis.
The typical experimental procedure is as follows: to a
stirred suspension of CuO (8.0 mg, 0.1 mmol), 7 (28.9 mg, 0.2
mmol) and 12 (32.4 mg, 0.24 mmol) in toluene (3.0 mL) was
added TiCl (0.066 mL, 0.6 mmol) at 0 °C. After the reaction
4
mixture was stirred for 1 h at 0 °C, it was quenched by addition
of 1 M HCl aq. The mixture was stirred vigorously and aque-
ous layer was extracted with CH Cl . The combined organic
2
2
layer was washed with H O and brine. The yield was deter-
2
mined by GC analysis using an internal standard.
The present research is partially supported by Grant-in-
Aids for Scientific Research from Ministry of Education,
Science, Sports and Culture.
References
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4
5
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In order to extend the scope of the present thiol forming
reaction, various olefins were treated under the reaction condi-
tions shown in Table 3. Tertiary thiols were obtained in good
to excellent yields when geminal di-, tri-, or tetra-substituted
olefins were used (Table 3, Entries 1–5). In the cases of using
vicinal di- or mono-substituted olefins, on the other hand, sec-
6
7
N. Kornblum and J. Widmer, J. Am. Chem. Soc., 100,
ondary thiols were obtained in good yields only when TiF was
4
7
086 (1978).
used (Entries 6–11). Furthermore, it should be noted here that