Rhodium-catalyzed reaction of thiols with polychloroalkanes in the presence of triethylamine

Article abstract of DOI:10.1021/ol0501673

(Chemical Equation Presented) RhCl(PPh₃)₃ catalyzes a reaction of thiols with polychloroalkanes in the presence of triethylamine. This reaction serves as a convenient new method to produce formaldehyde dithioacetals, ethylenedithioethers, thioformates, and dithiocarbonic esters under mild conditions.

Full text of DOI:10.1021/ol0501673

ORGANIC
LETTERS
2
005
Vol. 7, No. 8
537-1539
Rhodium-Catalyzed Reaction of Thiols
with Polychloroalkanes in the Presence
of Triethylamine
1
Ken Tanaka* and Kaori Ajiki
Department of Applied Chemistry, Graduate School of Engineering, Tokyo UniVersity
of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
tanaka-k@cc.tuat.ac.jp
Received January 25, 2005
ABSTRACT
3 3
RhCl(PPh ) catalyzes a reaction of thiols with polychloroalkanes in the presence of triethylamine. This reaction serves as a convenient new
method to produce formaldehyde dithioacetals, ethylenedithioethers, thioformates, and dithiocarbonic esters under mild conditions.
Many methods for the synthesis of formaldehyde dithio-
acetals (RSCH SR) are known, including the reaction of
3
not. Recently, we reported a cationic rhodium(I)/PPh -
2
complex-catalyzed dehydrogenation of alkanethiols to di-
8
thiols with diiodomethane, dibromomethane, or dichloro-
sulfides under inert atmosphere. We found that the form-
1
methane under strongly basic conditions and the reaction
aldehyde dithioacetal was obtained along with the disulfide
of thiols with formaldehyde derivatives under acidic condi-
tions. Demonstrably, the simplest method yet reported is
the reaction of thiols with dichloromethane in the presence
2 2
through reaction of octanethiol with CH Cl when dehydro-
2
(
4) Reviews, see: (a) Ogawa, A. In Main Group Metals in Organic
Synthesis; Yamamoto, H., Oshima, K., Eds.; Wiley-VCH: Weinheim, 2004;
p 813. (b) Ali, B. E., Alper, H. In Handbook of Organopalladium Chemistry
for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York,
of strong organic base (1,8-diazabicyclo[5,4,0]undec-7-ene,
3
DBU), as reported by Ono et al. The present study explored
2002; Chapter VI.2.1.1.2. (c) Ogawa, A. In Handbook of Organopalladium
a rhodium-catalyzed reaction of thiols with polychloroalkanes
in the presence of weak organic base (Et N); the reaction
3
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New
York, 2002; Chapter VII.6. (d) Kuniyasu, H. In Catalytic Heterofunction-
alization; Togni, A., Gr u¨ tzmacher, H., Eds.; Wiley-VCH: Weinheim, 2001;
p 217. (e) Kuniyasu, H.; Kurosawa, H. Chem. Eur. J. 2002, 8, 2660. (f)
Ogawa, A. J. Organomet. Chem. 2000, 611, 463. (g) Kondo, T.; Mitsudo,
T. Chem. ReV. 2000, 100, 3205. (h) Han, L.-B.; Tanaka, M. J. Chem. Soc.,
Chem. Commun. 1999, 395. (i) Beletskaya, I.; Moberg, C. Chem. ReV. 1999,
allows both simple operation and mild reaction conditions.
In general, thiols are believed to be poisons of transition
metal catalysts. However, several recent reports concerning
transition-metal-catalyzed reactions of thiols have explained
the utility of transition metal catalysts in synthesis of sulfur
9
9, 3435.
(5) For recent reports concerning transition-metal-catalyzed reactions of
thiols, see: (a) Kawakami, J.; Takeda, M.; Kamiya, I.; Sonoda, N. Ogawa,
A. Tetrahedron 2003, 59, 6559. (b) Ogawa, A.; Ikeda, T.; Kimura, K.; Hirao,
T. J. Am. Chem. Soc. 1999, 121, 5108. (c) Ohtaka, A.; Kuniyasu, H.;
Kinomoto, M.; Kurosawa, H. J. Am. Chem. Soc. 2002, 124, 14324. (d)
Xiao, W.-J.; Alper, H. J. Org. Chem. 2001, 66, 6229. (e) Xiao, W.-J.;
Vasapollo, G.; Alper, H. J. Org. Chem. 2000, 65, 4138. (f) McDonald, F.
E.; Burova, S. A.; Huffman, L. G., Jr. Synthesis 2000, 7, 970. (g) Gabriele,
B.; Salerno, G.; Fazio, A. Org. Lett. 2000, 2, 351. (h) Ali, B. E.; Tijani, J.;
El-Ghanam, A.; Fettouhi, M. Tetrahedron Lett. 2001, 42, 1567. (i) Kondo,
T.; Kanda, Y.; Baba, A.; Fukuda, K.; Nakamura, A.; Wada, K.; Morisaki,
Y.; Mitsudo, T. J. Am. Chem. Soc. 2002, 124, 12960. (j) Inada, Y.
Nishibayashi, Y.; Hidai, M.; Uemura, S. J. Am. Chem. Soc. 2002, 124,
15172. (k) Tsutsumi, K.; Fujimoto, K.; Yabukami, T.; Kawase, T.;
Morimoto, T.; Kakiuchi, K. Eur. J. Org. Chem. 2004, 504. (l) Kwong, F.
Y.; Buchwald, S. L. Org. Lett. 2002, 4, 3517. (m) Bates, C. G.; Gujadhur,
R. K.; Venkataraman, D. Org. Lett. 2002, 4, 2803 and references therein.
4
-6
compounds. Although platinum-catalyzed formaldehyde
dithioacetal formation using thiols and CH has been
reported, a catalytic method using thiols and CH Cl has
2 2
I
7
2
2
(
1) (a) Bertaina, B.; Rouvier, E.; Fayn, J.; Cambon, A. J. Fluorine Chem.
1
994, 66, 287. (b) Weissflog, E. Phosphorus Sulfur 1981, 12, 89. (c) Dou,
H. J. M.; Ludwikow, M.; Hassanaly, P.; Kister, J.; Metzger, J. J. Heterocycl.
Chem. 1980, 17, 393. (d) Feher, F.; Vogelbruch, K. Chem. Ber. 1958, 91,
9
96.
2) (a) Aggarwal, V. K.; Davies, I. W.; Franklin, R.; Maddock, J.; Mahon,
(
M. F.; Molloy, K. C. J. Chem. Soc., Perkin Trans. 1 1994, 17, 2363. (b)
Patney, H. K. Org. Prep. Proc. Int. 1994, 26, 377. (c) Kamada, T.; Gama,
Y.; Wasada, N. Bull. Chem. Soc. Jpn. 1989, 62, 3024.
(3) Ono, N.; Miyake, H.; Saito, T.; Kaji, A. Synthesis 1980, 11, 952.
1
0.1021/ol0501673 CCC: $30.25
© 2005 American Chemical Society
Published on Web 03/18/2005

genation of octanethiol was conducted in CH
temperature in the presence of Et N (eq 1).
2
Cl
2
at room
examined, PPh
use of [Ir(cod)
3
was the most effective (entries 1-8). The
]BF or [Rh(cod)Cl] and the elimination of
3
2
4
2
treatment of the catalyst with hydrogen engendered very low
catalytic activity (entries 9-11). The highest catalytic activity
was obtained using RhCl(PPh
Finally, employing excess amounts of Et
desired methylenedithioether in 81% isolated yield (entry
3
)
3
as a catalyst (entry 12).
3
N furnished the
9
1
3). No reaction was observed in the absence of rhodium
catalyst (entry 14).
Table 1 shows various rhodium(I) and iridium(I) catalysts
5% based on thiols) that we examined for their ability to
Table 2 shows the rhodium-catalyzed reactions of various
thiols with polychloroalkanes, as investigated in polychlo-
roalkane solvents. The reactions of both alkyl and aryl
(
1
0
Table 1. Screening of Catalysts for Reaction of Octanethiol
with Dichloromethanea
Table 2. Rhodium-Catalyzed Reaction of Thiols with
Polychloroalkanesa
entry
1c
catalyst
yield (%)b
[Rh(cod)2]BF4/2 PPh3
[Rh(cod)2]BF4/2 n-Bu3P
[Rh(cod)2]BF4/dppe
[Rh(cod)2]BF4/dppb
[Rh(cod)2]BF4/dcpe
[Rh(cod)2]BF4/dppf
[Rh(cod)2]BF4/Tol-BINAP
[Rh(cod)2]BF4/XANTPHOSd
[Ir(cod)2]BF4/2 PPh3
[Rh(cod)Cl]2/4 PPh3
[Rh(cod)2]BF4/2 PPh3
RhCl(PPh3)3
33
3
5
1
3
c
2
c
3
c
4
c
5
c
6
7
24
8
c
c
8
17
<1
<1
<1
39
c
9
1
1
1
1
1
0c
1
2
3
e
f
RhCl(PPh3)3
81
4
none
0
a
Rh or Ir catalyst (0.010 mmol), phosphine (0-0.020 mmol), Et3N (0.22
b
mmol), thiol (0.20 mmol), and CH2Cl2 (1.0 mL) were employed. Deter-
mined by H NMR. The catalysts were treated with hydrogen (1 atm, rt,
.5 h). 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene. RhCl(PPh3)3
1
c
d
e
0
(
0.025 mmol), Et3N (0.5 mL), thiol (0.50 mmol), and CH2Cl2 (2.0 mL)
f
were employed. Reaction time: 24 h. Isolated yield.
facilitate this transformation. Among the phosphine ligands
(
6) For recent reports concerning transition-metal-catalyzed synthesis of
sulfur compounds, see: (a) Dong, C.; Alper, H. Org. Lett. 2004, 6, 3489.
b) Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2002, 4, 4309. (c)
(
Knapton, D. J.; Meyer, T. Y. Org. Lett. 2004, 6, 687. (d) Hirai, T.; Kuniyasu,
H.; Kambe, N. Tetrahedron Lett. 2005, 46, 117. (e) Hirai, T.; Kuniyasu,
H.; Kambe, N. Chem. Lett. 2004, 33, 1148. (f) Sugoh, K.; Kuniyasu, H.;
Sugae, T.; Ohtaka, A.; Takai, Y.; Tanaka, A.; Machino, C.; Kambe, N.;
Kurosawa, H. J. Am. Chem. Soc. 2001, 123, 5108. (g) Kuniyasu, H.; Ohtaka,
A.; Nakazono, T.; Kinomoto, M.; Kurosawa, H. J. Am. Chem. Soc. 2000,
a Reactions were conducted using RhCl(PPh3)3 (0.025 mmol), Et N
3
(0.5 mL), thiol (0.50 mmol), and polychloroalkane (2.0 mL) at room
temperature for 24 h. b Isolated yields based on thiols. c At 80 °C.
d RhCl(PPh ) (0.10 mmol) and polychloroalkane (10 mL) were used.
3
3
1
22, 2375. (h) Arisawa, M.; Yamaguchi, M. J. Am. Chem. Soc. 2003, 125,
6
624. (i) Arisawa, M.; Suwa, A.; Fujimoto, K.; Yamaguchi, M. AdV. Synth.
Catal. 2003, 345, 560. (j) Arisawa, M.; Yamaguchi, M. Org. Lett. 2001, 3,
7
63. (k) Kondo, T.; Baba, A.; Nishi, Y.; Mitsudo, T. Tetrahedron Lett.
2 2 3 3
thiols with CH Cl in the presence of 5% RhCl(PPh )
2
004, 45, 1469. (l) Hua, R.; Takeda, H.; Onozawa, S.; Abe, Y.; Tanaka,
proceeded at room temperature to furnish the corresponding
formaldehyde dithioacetals in good yield (entries 1-6). A
hydroxy-substituted alkanethiol and a cysteine derivative can
M. J. Am. Chem. Soc. 2001, 123, 2899. (m) Taniguchi, N. J. Org. Chem.
004, 69, 6904. (n) Taniguchi, N.; Onami, T. J. Org. Chem. 2004, 69, 915.
2
(o) Ananikov, V. P.; Beletskaya, I. P. Org. Biomol. Chem. 2004, 2, 284.
p) Tanaka, K.; Ajiki, K. Tetrahedron Lett. 2004, 45, 5677 and references
(
therein.
(7) (a) Page, P. C. B.; Klair, S. S.; Brown, M. P.; Smith, C. S.; Maginn,
(9) Not only tertiary amines but also secondary and primary amines
(n-Bu2NH and n-BuNH2) can be used for this reaction, although the reaction
rate is low.
(10) In all entries, <5% conversions were observed in the absence of
rhodium catalyst.
S. J.; Mulley, S. Tetrahedron 1992, 48, 5933. (b) Page, P. C. B.; Klair, S.
S.; Brown, M. P.; Harding, M. M.; Smith, C. S.; Maginn, S. J.; Mulley, S.
Tetrahedron Lett. 1988, 29, 4477.
(8) Tanaka, K.; Ajiki, K. Tetrahedron Lett. 2004, 45, 25.
1538
Org. Lett., Vol. 7, No. 8, 2005

be used (entries 4 and 5).11 The reaction of a vicinal
dichloride (CH ClCH Cl) proceeded at 80 °C to furnish the
2
2
corresponding ethylenedithioethers in good yield (entries 7
and 8). Importantly, although high catalyst loading and
diluted condition were required, the reaction of CHCl
3
and
CCl also proceeded at room temperature to give a thiofor-
4
mate and a dithiocarbonic ester, respectively, presumably
through hydrolysis of corresponding polythiomethanes by
silica gel chromatography (entries 9 and 10). The reaction
3 4
of CHCl and CCl serves as a convenient new method for
preparation of a thioformate and a dithiocarbonic ester
starting from a thiol.
Next, we investigated the rhodium-catalyzed reaction of
thiols with alkyl halides. The reaction proceeded cleanly in
into the thiol S-H bond, affording a rhodium(III) complex
A. Elimination of HX with Et N furnishes rhodium(I) thiolate
B, which reacted with alkyl halides in an S 2 fashion, thereby
3
N
furnishing sulfides and regenerating the rhodium(I) catalyst.
3
Et N without using excess alkylating reagents when a reactive
primary alkyl chloride (benzyl chloride, eq 2) or a primary
alkyl bromide (dodecyl bromide, eq 3) was used as an
alkylating reagent. No reaction was observed in the absence
of rhodium catalyst.
Scheme 1
3 3
In conclusion, we have established that RhCl(PPh )
catalyzes a reaction of thiols with polychloroalkanes in the
presence of triethylamine. This reaction serves as a conve-
nient new method to produce formaldehyde dithioacetals,
ethylenedithioethers, thioformates, and dithiocarbonic esters
under mild conditions.
The reaction of dodecanethiol with CDCl
to gain mechanistic insight into this reaction (eq 4).
Deuterium of CDCl was quantitatively incorporated into the
3
was investigated
3
formyl group. Furthermore, the reaction of benzyl mercaptan
with (R)-(1-chloroethyl)benzene (78% ee) furnished the
corresponding sulfide with complete inversion of configu-
ration (78% ee, eq 5).
Scheme 1 depicts a plausible mechanism of this reaction.
We believe that the rhodium(I) catalyst oxidatively inserts
Acknowledgment. This research was supported by Banyu
Pharmaceutical Company Award in Synthetic Organic
Chemistry, Japan. We thank Dr. M. Hirano for elemental
analysis.
Supporting Information Available: Experimental pro-
cedures and compound characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
(11) For synthesis of methylenedithioethers from cysteine derivatives
using tetrabutylammonium fluoride hydrate, see: Ueki, M.; Ikeo, T.; Hokari,
K.; Nakamura, K.; Saeki, A.; Komatsu, H. Bull. Chem. Soc. Jpn. 1999, 72,
8
29.
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