Highly stereoselective palladium-catalyzed dithiocarbonylation of propargylic mesylates with thiols and carbon monoxide

Article abstract of DOI:10.1021/jo047938l

(Chemical Equation Presented) Highly stereoselective dithiocarbonylation of propargylic mesylates with thiols and carbon monoxide has been developed by the use of tetrakis(triphenylphosphine)palladium(0) as the catalyst at 90 °C in THF. The reaction affords the corresponding dithioesters in good to excellent yields. For some secondary and tertiary propargylic alcohols with a terminal or internal triple bond, the reaction stereoselectively produces E-dithioesters as products. The dithiocarbonylation is believed to proceed via allenylpalladium and allenyl ester intermediates, and the high stereoselectivity might be rationalized by a mechanism where nucleophilic attack of a Pd(0)L_n species on the allenyl sp carbon occurs from the less hindered side of an alkyl substituent.

Full text of DOI:10.1021/jo047938l

Highly Stereoselective Palladium-Catalyzed Dithiocarbonylation
of Propargylic Mesylates with Thiols and Carbon Monoxide
Wen-Jing Xiao*,† and Howard Alper*,‡
Center for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa,
10 Marie Curie, Ottawa, Ontario K1N 6N5, Canada, and The Key Laboratory of Pesticide & Chemical
Biology, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road,
Wuhan, Hubei 430079, China
halper@uottawa.ca; wxiao@mail.ccnu.edu.cn
Received November 19, 2004
Highly stereoselective dithiocarbonylation of propargylic mesylates with thiols and carbon monoxide
has been developed by the use of tetrakis(triphenylphosphine)palladium(0) as the catalyst at 90
°C in THF. The reaction affords the corresponding dithioesters in good to excellent yields. For
some secondary and tertiary propargylic alcohols with a terminal or internal triple bond, the reaction
stereoselectively produces E-dithioesters as products. The dithiocarbonylation is believed to proceed
via allenylpalladium and allenyl ester intermediates, and the high stereoselectivity might be
rationalized by a mechanism where nucleophilic attack of a Pd(0)Ln species on the allenyl sp carbon
occurs from the less hindered side of an alkyl substituent.
Introduction
wide range of compounds, carbonylation chemistry has
still not achieved its full potential. The search for the
improvement of carbonylation technology continues, with
the goal of increasing the diversity of possible substrates
and reaction products.6 For example, the development of
transition-metal-catalyzed carbonylation involving the
formation of a thiocarbonyl unit and employing organo-
sulfur compounds, especially thiols and thiophenols, as
a direct substrate represents a challenging subject in
transition-metal-catalyzed reactions, because the strong
thiophilicity of transition metals7 may make catalytic
reactions ineffective.8 As part of our continuing studies
of the scope of transition-metal-catalyzed carbonylation
Transition-metal-catalyzed carbonylation is widely
recognized as one of the most important carbonyl-forming
reactions in organic synthesis.1 Examples include the
carbonylation reactions of alcohols,2 amines,3 carbon
nucleophiles,4 and organometallic reagents5 with other
substrates, affording esters, amides, ketones, and alde-
hydes, respectively. Although a large number of catalytic
systems have been developed for the carbonylation of a
† Central China Normal University.
‡ University of Ottawa.
(1) (a) Colquhoun, H. M.; Thompson, D. J.; Twigg, M. V. Carbony-
lation: Direct Synthesis of Carbonyl Compounds; Plenum Press: New
York, 1991. (b) Tsuji, J. Palladium Reagents and Catalysts; Wiley: New
York, 1995. (c) Khumtaveeporn, K.; Alper, H. Acc. Chem. Res. 1995,
28, 414.
(5) (a) Tamaru, Y.; Yasui, K.; Takanabe, H.; Tanaka, S.; Fugami,
K. Angew. Chem., Int. Ed. Engl. 1992, 31, 645. (b) Luong, T. J.;
Linstrumelle, G. Tetrahedron Lett. 1980, 21, 5019. (b) Tseng, H. R.;
Luh, T. Y. J. Org. Chem. 1996, 61, 8685. (c) Keinan, E.; Bosch, E. J.
Org. Chem. 1986, 51, 4006. (d) Moriya, T.; Miyaura, N.; Suzuki, A.
Synlett 1994, 149. (e) Mandai, T.; Nakata, T.; Murayama, H.; Yamaoki,
H.; Ogawa, M.; Kawada, M.; Tsuji, J. J. Organomet. Chem. 1991, 417,
305.
(2) (a) Ishii, Y.; Gao, C.; Iwasaki, M.; Hidai, M. J. Org. Chem. 1993,
58, 6818. (b) Duprat, S.; Deweerdt, H.; Jenck, J.; Kalck, P. J. Mol.
Catal. 1993, 80, L9. (c) Tsuji, J.; Mandai, T. Angew. Chem., Int. Ed.
Engl. 1995, 34, 2589. (d) Piotti, M. E.; Alper, H. J. Org. Chem. 1997,
62, 8484.
(3) (a) Zhu, J.; Lu, X. Tetrahedron Lett. 1987, 28, 1987. (b) Zhu, J.;
Lu, X. Chem. Commun. 1987, 1318. (c) Marshall, J. A.; Wolf, M. A. J.
Org. Chem. 1996, 61, 3238. (d) Kimura, M.; Wakamiya, Y.; Horino,
Y.; Tamaru, Y. Tetrahedron Lett. 1997, 38, 3963. (e) Imada, Y.; Alper,
H. J. Org. Chem. 1996, 61, 6766.
(4) (a) Ito, Y.; Sawamura, M.; Matsuoka, M.; Mastsumoto, Y.;
Hayashi, T. Tetrhedron Lett. 1987, 28, 4849. (b) Lu, X.; Jiang, X. J.
Organomet. Chem. 1989, 359, 139. (c) Tsuji, J.; Watanabe, H.; Minami,
I.; Shimizu, I. J. Am. Chem. Soc. 1985, 107, 2196. (d) Tamaru, Y.; Goto,
S.; Tanaka, A.; Shimizu, M.; Kimura, M. Angew. Chem., Int. Ed. Engl.
1996, 35, 878. (e) Bienayme, H. Tetrahedron Lett. 1994, 35, 7387.
(6) (a) Dong, C.; Alper, H. J. Org. Chem. 2004, 69, 5011. (b)
Matsushima, Y.; Onitsuka, K.; Takahashi, S. Organometallics 2004,
15, 35. (c) Soderberg, B. C. G. Coord. Chem. Rev. 2003, 247, 79. (d)
von Seebach, M.; Grigg, R.; de Meijere, A. Eur. J. Org. Chem. 2002,
19, 3268. (e) Costa, M.; Della Ca, N.; Gabriele, B.; Massera, C.; Salerno,
G.; Soliani, M. J. Org. Chem. 2004, 69, 2469. (f) Wu, M. S.; Rayabarapu,
D. K.; Cheng, C. H. J. Am. Chem. Soc. 2003, 125, 12426. (g) Yang, F.
Y.; Shanmugasundaram, M.; Chuang, S. Y.; Ku, P.-J.; Wu, M. Y.;
Cheng, C. H. J. Am. Chem. Soc. 2003, 125, 12576. (h) Zweni, P. P.;
Alper, H. Adv. Synth. Catal. 2004, 346, 849. (i) Lu, S. M.; Alper, H. J.
Org. Chem. 2004, 69, 3558.
10.1021/jo047938l CCC: $30.25 © 2005 American Chemical Society
Published on Web 02/01/2005
1802
J. Org. Chem. 2005, 70, 1802-1807

Palladium-Catalyzed Dithiocarbonylation of Propargylic Mesylates
reactions, we investigated some interesting transforma-
tions employing organosulfur compounds as substrates.
Thus, we developed the Co2(CO)8-catalyzed desulfuriza-
tion and carbonylation of organosulfur agents,9 demon-
strating that sulfur compounds are compatible with
cobalt. Subsequently, Uemura, Ohe, and co-workers
reported the Co2(CO)8-catalyzed carbonylation of organic
diselenides or ditellurides.10 Remarkably, however, this
reaction remained largely underdeveloped for eight years
before Ogawa and co-workers were able to demonstrate
the first example of RhH(CO)(PPh3)3-catalyzed “thio-
formylation” of acetylenes with thiols and carbon mon-
oxide (eq 1).11
thioesterification,16 S-propargylation,17 and carbothiola-
tion18,19 of unsaturates. These findings have corrected the
widely accepted concept that “sulfur compounds are
poisons to transition metal catalysts”. Contrary to the
monocarbonylation of unsaturated substrates, catalytic
dicarbonylation20 is relatively rare due to the requirement
of harsh reaction conditions. To our knowledge, the
transition-metal-catalyzed dithiocarbonylation of thiols
has not been realized. Herein, we report the first ex-
amples of palladium-catalyzed dithiocarbonylation of
thiols with propargylic mesylates.
Results and Discussion
Initial studies were focused on examining the feasibil-
ity of the dicarbonylation reaction, and optimizing reac-
tion conditions that could be applied to a variety of
propargylic compounds and thiols. On the basis of
knowledge gained from previous findings,12 2-methylbut-
3-yn-2-ol (7) and thiophenol (8) were first used as
substrates. The reaction between 7 (1 equiv) and 8 (2
equiv) was initially carried out in THF at 120 °C for 48
h in the presence of Pd(OAc)2 (3 mol %), PPh3 (12 mol
%), and p-TsOH (5 mol %) under an atmosphere of 400
psi CO, leading to complete conversion of substrate 7 (eq
3).
Recently, the groups of Ogama and Hirao, as well as
our own, have discovered a series of carbonylation
reactions of various organosulfur compounds with other
substrates.12 For example, thiols react with propargyl
alcohols in the presence of a palladium(0) catalyst to
afford â-(arylthio)-R, â-unsaturated lactones, as shown
in eq 2.12a
Other examples developed in the past few years include
the thioboration,13 thiosilylation,14 thiophosphorylation,15
(7) (a) Dubois, M. R. Chem. Rev. 1989, 89, 1. (b) Roberto, A. S. D.
Organometallic Modeling of the Hydrosulfurization and Hydrodeni-
trogenation Reaction; Kluwer Academic: Dordrecht, 2002. (c) Weber,
T.; Prins, R.; Santen, R. A. Transition Metal Sulphides Chemistry and
Catalysis; Kluwer Academic: Dordrecht, 1997.
(8) (a) Hegedus, L. L.; McCable, R. W. Catalyst Poisoning, Marcel
Dekker: New York, 1984. (b) Hutton, A. T. In Comprehensive Coor-
dination Chemistry; Wilkinson, G.; Gillard, R. D., McCleverty, J. A.,
Eds.; Pergamon Press: Oxford, U. K., 1984; Vol. 5, p 1151. (c) Stiefel,
E. I.; Matsumoto, K. Transition Metal Sulfur Chemistry: Biological
and Industrial Significance; American Chemical Society: Washington,
DC, 1996.
The reaction gave promising results, with three prod-
ucts, 9, 10, and 11, obtained, including the dithiocarbon-
ylation product 11, which was isolated in 7% yield.
Encouraged by this result, we pursued alternate reaction
conditions and substrates in order to form 11 as the sole
product. We also tried to understand how 9 and 10 were
formed (eq 3) so as to minimize their formation. A
possible catalytic cycle for the formation of the thiolac-
tonization product 9 is outlined in Scheme 1.
(9) (a) Shim, S. C.; Antebi, S.; Alper, H.J. Org. Chem. 1985, 50, 147.
(b) Antebi, S.; Alper, H. Tetrahedron Lett. 1985, 26, 2609. (c) Antebi,
S.; Alper, H. Tetrahedron Lett. 1985, 26, 1935.
By analogy to the hydrothiolation of rhodium21 and
platinum22 complexes, the thiolactonization reaction may
also start by oxidative addition of thiophenol to Pd(0) to
form the phenylthiopalladium complex 12, which then
(10) (a) Ohe, K.; Takahashi, H.; Uemura, S.; Sugita, N. J. Orga-
nomet. Chem. 1987, 326, 35. (b) Takahashi, H.; Ohe, K.; Uemura, S.;
Sugita, N. J. Organomet. Chem. 1987, 334, C43.
(11) Ogawa, A.; Takeba, M.; Kawakami, J.; Ryu, I.; Kambe, N.;
Sonoda, N.J. Am. Chem. Soc. 1995, 117, 7564.
(12) For the palladium-catalyzed thiocarbonylation, see: (a) Xiao,
W.-J.; Alper, H. J. Org. Chem. 1997, 62, 3422. (b) Xiao, W.-J.;
Vasapollo, G.; Alper, H. J. Org. Chem. 1998, 63, 2609. (c) Xiao, W.-J.;
Alper, H. J. Org. Chem. 1998, 63, 7939. (d) Xiao, W.-J.; Vasapollo, G.;
Alper, H. J. Org. Chem. 1999, 64, 2080. (e) Xiao, W.-J.; Alper, H. J.
Org. Chem. 1999, 64, 9646. (f) Xiao, W.-J.; Vasapollo, G.; Alper, H. J.
Org. Chem. 2000, 65, 4138. (g) Xiao, W.-J.; Alper, H. J. Org. Chem.
2001, 66, 6229. For the rhodium- or platinum-catalyzed thiocarbony-
lation, see: (h) Ogawa, A.; Kawakami, J.; Mihara, M.; Ikeda, T.;
Sonoda, N.; Hirao, T. J. Am. Chem. Soc. 1997, 119, 12380. (i) Ogawa,
A.; Kuniyasu, H.; Sonoda, N.; Hirao, T. J. Org. Chem. 1997, 62, 8361.
(j) Ogawa, A.; Obayashi, R.; Ine, H.; Tsuboi, Y.; Sonoda, N.; Hirao, T.
J. Org. Chem. 1998, 63, 881. (k) Kawakami, J.; Takeba, M.; Kamiya,
I.; Sonoda, N.; Ogawa, A. Tetrahedron 2003, 59, 6559. (l) Kawakami,
J.; Mihara, M.; Kamiya, I.; Takeba, M.; Ogawa, A.; Sonoda, N.
Tetrahedron 2003, 59, 3521.
(16) Hua, R.; Takeda, H.; Onozawa, S.; Abe, Y.; Tanaka, M. J. Am.
Chem. Soc. 2001, 123, 2899.
(17) (a) Kondo, T.; Morisaki, Y.; Uenoyama, S.; Wada, K.; Mitsudo,
T. J. Am. Chem. Soc. 1999, 121, 8657. (b) Kondo, T.; Kanda, Y.; Baba,
A.; Fukuda, K.; Nakamura, A.; Wada, K.; Morisaki, Y.; Mitsudo, T. J.
Am. Chem. Soc. 2002, 124, 12960.
(18) 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.
(19) (a) Ogawa, A. In Handbook of Organopalladium Chemistry for
Organic Synthesis; Negishi, E., Ed.; Wiley: New York, 2002; Vol. II, p
2841. (b) El Ali, B.; Alper, H. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley: New York,
2002; Vol. II, p 2333.
(20) (a) Weston, W. S.; Cole-Hamilton, D. J. Inorg. Chim. Acta 1998,
280, 99. (b) Duprat, S.; Deweerdt, H.; Jenck, J.; Kalck, P. J. Mol. Catal.
1993, 80, L9. (c)Li, J.; Jiang, H.; Chen, M. Synth. Commun. 2001, 31,
3131. (d) Aeby, A.; Bangerter, F.; Consiglio, G. Helv. Chim. Acta 1998,
81, 764.
(13) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(14) Han, L.-B.; Tanaka, M. J. Am. Chem. Soc. 1998, 120, 8249.
(15) Han, L.-B.; Tanaka, M. Chem. Lett. 1999, 863.
J. Org. Chem, Vol. 70, No. 5, 2005 1803

Xiao and Alper
SCHEME 1. A Possible Catalytic Cycle for the
Formation of 9
SCHEME 2. Thiocarbonylation of Propargylic
Alcohol to Mono- and Dithioesters
According to these experimental results and the mecha-
nistic analysis, we believed that propargylic alcohols were
not the ideal substrates for the dithiocarbonylation and
we envisioned that the dithiocarbonylation of propargylic
mesylates with thiols and carbon monoxide should be
carried out instead.
All propargylic mesylates were prepared from the
corresponding alcohols by modification of a published
procedure.23 Using n-BuLi as the base, in place of
triethylamine, greatly improved the yields of the mesy-
lates. The reaction of 1,1-dimethyl-prop-2-ynyl mesylate
(22a) and thiophenol (8) with carbon monoxide was
chosen as the model reaction, and we then examined the
effect of varying the catalyst, ligand, solvent, base, and
reaction temperature on this reaction.
Table 1 shows the results of the reaction using several
palladium catalysts and mono- or bis-phosphine ligands,
with or without Et3N. Among the catalytic systems
examined, palladium(0) complexes, such as Pd(PPh3)4
and Pd2(dba)3‚CHCl3, exhibit high activity for the dithio-
carbonylation reaction (Table 1, entries 9-12). In par-
ticular, the use of 3 mol % Pd(PPh3)4 (relative to 1,1-
dimethyl prop-2-ynyl mesylate) was the most effective
catalyst, resulting in the formation of 11 in 88% yield
(Table 1, entry 10). Palladium acetate with mono- or
bidentate phosphine ligands can also catalyze the dithio-
carbonylation; however, it catalyzes the reaction at a
slower rate with lower efficiency (Table 1, entries 1-8).
The base, triethylamine, does not affect the reaction
(Table 1, entries 1, 3, and 9). Therefore, it was decided
to use Pd(PPh3)4 as the catalyst and to examine the effect
of different solvents, reaction pressures, and tempera-
tures on the dithiocarbonylation reaction.
coordinates with the electron-rich carbon-carbon triple
bond and the hydroxyl group of the propargylic alcohol
to form complex 13. Subsequent insertion of the triple
bond into the Pd-S bond (intramolecular cyclization) and
elimination of hydrogen would form the palladocycle 14.
The introduction of carbon monoxide into either the
palladium-carbon bond or the palladium-oxygen bond
could give the acylpalladium intermediate 15 or 16, and
then reductive elimination would afford the â-phenylthio-
γ-lactone 9 as well as regenerate the active catalyst
species. Note that the generation of H2 is probably the
key to the formation of the monothiocarbonylation prod-
uct 10. We believe that both 10 and 11 may arise from
intermediate 17, which reacts further with either thiophe-
nol and carbon monoxide to form the dithiocarbonylation
product 11, or hydrogen to afford the reduction product
10 (Scheme 2).
Although we did not study the possible mechanisms
in detail, we did find that the yield of 10 could be
dramatically increased if we employed a mixture of CO
and H2 (1:1, 800 psi) for the reaction. Furthermore, the
reaction of deuterated thiophenol and 2-methylbut-3-yn-
2-ol under the same conditions afforded the deuterated
product 20 (eq 4).
It can be concluded from the results summarized in
Table 2 that the reaction is significantly influenced by
the solvent, temperature and pressure. For example, the
dithiocarbonylation works very well in THF and CH2Cl2
and gives the dithioester 11 in 88 and 86% isolated yields,
respectively (Table 2, entries 1 and 3); however, under
the same conditions, using CH3CN as the solvent, the
(21) Ogawa, A.; Ikeda, T.; Kimura, K.; Hirao, T. J. Am. Chem. Soc.
1999, 121, 5108.
(22) Ogawa, A.; Kawabe, K.; Kawakami, J.; Mihara, M.; Hirao, T.;
Sonoda, N. Organometallics 1998, 17, 3111.
(23) (a) Marshall, J. A.; Xie, S. J. Org. Chem. 1995, 60, 7230. (b)
Marshall, J. A.; Adams, N. D. J. Org. Chem. 1999, 64, 5201.
1804 J. Org. Chem., Vol. 70, No. 5, 2005

Palladium-Catalyzed Dithiocarbonylation of Propargylic Mesylates
TABLE 1. Optimization of Catalyst Systems for the
Palladium-Catalyzed Dithiocarbonylationa
SCHEME 3. Possible Mechanism for the
Dithiocarbonylation of Propargylic Mesylates
entry
catalyst
Pd(OAc)2
ligand base time (h) yieldb (%)
1
2
PPh3
PPh3
PCy3
PCy3
PBu3
dppb
dppp
dppe
PPh3
none
PPh3
none
Et3
48
48
48
48
36
30
36
48
24
24
24
24
57
53
42
41
52
58
60
55
86
85
85
75
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd2(dba)3CHCl3
none
Et3N
none
none
none
none
none
Et3
3
4
5
6
7
8
9
10
11
12
none
none
none
a Reaction conditions: thiophenol (4 mmol), 1-1-dimethyl prop-
2-ynyl mesylate (2 mmol), Pd catalyst (0.06 mmol), PPh3, PCy3,
or PBu3 (0.24 mmol, in the case of Pd(OAc)2 (if used), or 0.06 mmol
in the case of Pd(PPh3)4 (if used)), 1,4-Bis(diphenylphosphino)bu-
tane (dppb), 1,3-bis(diphenylphosphino)propane (dppp), or 1,2-
bis(diphenylphosphino)ethane (dppe) (0.12 mmol, if used), CO (400
psi), THF (10 mL) 120 °C. b Isolated yield.
TABLE 2. Influence of Solvents, Reaction Pressure, and
Temperature on the Dithiocarbonylation Reactiona
The reaction temperature is another critical factor for
the successful dithiocarbonylation, with the best result
being reached at 90 °C (Table 2, entry 12). Increasing
the temperature from 90 to 120 °C did not change the
reaction yield (Table 2, entries 1, 10, 11, and 12);
however, decreasing the temperature to 80 °C gave only
the dithiocarbonylation product in 34% yield after 55 h
(Table 2, entry 13).
The dithiocarbonylation reaction of a series of pro-
pargylic mesylates (22a-j) was effected using 2 equiv of
various thiols and 3 mol % of Pd(PPh3)4 in THF at 400
psi CO for 48 h at 90 °C, and representative results are
summarized in Table 3. Under these conditions, the
reaction proved to be general for substrates containing
different substituents. Arenethiols and alkanethiols can
be successfully employed in the reaction (Table 3, entries
1-5) together with primary, secondary, and tertiary
propargylic mesylates (Table 3, entries 5-13). It is
noteworthy that propargylic mesylates containing ter-
minal or internal carbon-carbon triple bonds with alkyl,
cycloalkyl, or phenyl substituents reacted with similar
efficiency (Table 3, entries 5-13). For some secondary
and tertiary propargylic mesylates, with a terminal or
internal triple bond, the reaction stereoselectively af-
forded E-dithioesters as the products (Table 3, entries
5-8 and 11). The E configuration for the double bond of
these compounds was assigned on the basis of NOESY
experiments.
entry
solvent
pressure (psi) T (°C) time (h) yield (%)
1
2
THF
400
400
400
400
400
400
600
800
200
400
400
400
400
120
120
120
120
120
120
120
120
120
120
100
90
48
48
48
48
48
48
36
30
48
48
48
48
55
88
79
86
67
73
58
87
82
37
88
85
88
34
benzene
CH2Cl2
toluene
Et2O
3
4
5
6
CH3CN
THF
7
8
THF
9
THF
10
11
12
13
THF
THF
THF
THF
80
a Reaction conditions: thiophenol (4 mmol), 1,1-dimethyl prop-
2-ynyl mesylate (2 mmol), Pd(PPh3)4 (0.06 mmol), CO (400-800
psi) solvent (10 mL), 80-120 °C. b Isolated yield.
yield of 11 decreased to 58% (Table 2, entry 6). Other
solvents, such as benzene, toluene, and diethyl ether, can
be employed as the solvent for the dithiocarbonylation,
but none of them appears to be as effective as THF (Table
2, entries 2, 4, and 5).
We did not rigorously examine the effect of CO pres-
sure on the dithiocarbonylation; however, we found that
the reaction proceeded well when the pressure of CO was
400-600 psi (Table 2, entries 1 and 7). When the
pressure of CO was reduced to 200 psi, only 37% of 11
was isolated (Table 2, entry 9). Increasing the pressure
of CO to 800 psi did increase the reaction rate, but the
yield of 11 decreased to 82% (Table 2, entry 8). Thus, in
subsequent studies, 400 psi of carbon monoxide was
usually used, consistent with our previous experience
with other thiocarbonylation reactions.12a-g
The reaction may proceed by the mechanism proposed
in Scheme 3. The first step of the catalytic reaction may
be oxidative addition of the propargylic mesylate (22a)
to the Pd(0) species to form a coordinatively unsaturated
Pd(II) intermediate 24.24 Ligand exchange would afford
a thiopalladium complex 25, followed by CO insertion and
reductive elimination to generate 17. It is expected that
(24) Yamamoto, H. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Heathcock, C. H., Eds.; Pergamon: Oxford, 1991; Vol.
2, p 81.
J. Org. Chem, Vol. 70, No. 5, 2005 1805

Xiao and Alper
TABLE 3. Palladium-Catalyzed Dithiocarbonylation of Propargylic Mesylatesa
a Reaction conditions: propargylic mesylates (2 mmol), thiol (4 mmol), Pd(PPH3)4 (0.06 mmol), 400 psi of CO, THF (10 mL), 90 °C.
b Isolated yield. c The stereochemistry was assigned as E by NOE experiments.
1806 J. Org. Chem., Vol. 70, No. 5, 2005

Palladium-Catalyzed Dithiocarbonylation of Propargylic Mesylates
SCHEME 4. Possible Mechanism for the
Formation of E-Dithioesters
Not only is this methodology attractive for the one-pot
synthesis of dithioesters, but it also further demonstrates
the utility of transition-metal catalysts for the synthesis
of sulfur compounds.
Experimental Section
Typical Procedure for the Palladium-Catalyzed Dithio-
carbonylation of Propargylic Mesylates with Thiols. An
autoclave, its glass liner, and a magnetic stirring bar were
dried in an oven and cooled in a drybox. The liner was charged
with Pd(PPh3)4 (0.0693 g, 0.06 mmol). The propargylic mesy-
late (2 mmol), thiol (4 mmol), and 10 mL of THF were then
added to the liner. An additional amount of THF (1-2 mL)
was placed in the autoclave prior to insertion of the liner. The
gauge and gauge block assembly were attached. The CO line
was flushed three times with CO, and the system was also
pressurized and flushed three times with CO, gradually
increasing the pressure to 400 psi. The autoclave was then
placed in the center of an oil bath on a heater stirrer preset to
90 °C. After 48 h, the autoclave was removed from the oil bath
and allowed to cool to room temperature. The excess gas was
discharged and the system disassembled. The reaction mixture
was filtered through Florisil and washed with diethyl ether.
The solvent was removed by rotary evaporation under reduced
pressure. The residue was separated by preparative TLC (silica
gel, eluant: n-hexane/ethyl acetate 9:1).
2-Isopropylidenedithiosuccinic acid di-S-phenyl ester
(11): oil; IR (neat) 1703, 1676 cm-1; 1H NMR (200 MHz, CDCl3)
δ 1.92 (s, 3H), 2.14 (s, 3H), 3.81 (s, 2H), 7.40-7.55 (m, 10H);
13C NMR (50 MHz, CDCl3) δ 23.8, 23.9, 45.3, 118.4, 129.7,
129.8, 130.0, 130.1, 132.6, 133.7, 134.8, 134.9, 135.4, 138.45,
148.6, 192.5, 195.2; MS (EI) m/z 342 (M+); HRMS calcd for
C19H18O2S2 342.0748, found 342.0741. Anal. Calcd for C19-
H18O2S2: C, 66.65; H, 5.30. Found: C, 66.72; H, 5.48.
compound 17 would be susceptible to Michael type
addition of Pd(0)Ln to the allenyl sp carbon25 followed by
reaction with thiophenol in the presence of Pd (0),
resulting in the formation of 26. Finally, the dithiocar-
bonylation product (11) resulted by a second CO insertion
into 26, and subsequent reductive elimination of Pd(0)
from the acyl palladium complex 27.
The formation of 17, although not detected directly,
could be supported by the observation that the E geom-
etry was obtained for the dithioesters as shown in entries
5-8 and 11 of Table 3, respectively. Such high stereo-
selectivity might be rationalized by a mechanism where
nucleophilic attack of a Pd(0)Ln species on the allenyl sp
carbon occurred from the less hindered side of an alkyl-
substituted (Rs) (Scheme 4).
Acknowledgment. We are grateful to the Natural
Sciences and Engineering Council of Canada, National
Key Project for Basic Research of China (2004CCA00100),
the Natural Science Foundation of China (20472021),
the Hubei Province Science Fund for Distinguished
Young Scholar (2004ABB011), and Central China Nor-
mal University for support of this research.
Conclusions
In summary, this research has resulted in the stereo-
selective carbonylation reaction of propargylic mesylates
with thiols and carbon monoxide catalyzed by a pal-
ladium complex, to form dithioesters in good to excellent
yields. To our knowledge, this is the first example of a
dithiocarbonylation employing thiols as direct reactants.
Supporting Information Available: Analytical data for
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
(25) Tsuji, J.; Mandai, T. Angew. Chem., Int. Ed. Engl. 1995, 34,
2589.
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