Regioselective control of the thiocarbonylation of terminal acetylenes with arylthiols catalyzed by Pd(II) and diphosphine ligands

Article abstract of DOI:10.1016/S0040-4039(00)02169-9

Control of the regioselective thiocarbonylation of terminal acetylenes 1a-e with arylthiols 2a,b was successfully achieved by using Pd(OAc)₂ and 1,4-bis(diphenylphosphino)butane (dppb), or 1,3-bis(diphenylphosphino)propane (dppp), as catalysts.

Full text of DOI:10.1016/S0040-4039(00)02169-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1567–1570
Regioselective control of the thiocarbonylation of terminal
acetylenes with arylthiols catalyzed by Pd(II) and diphosphine
ligands
B. El Ali,* J. Tijani, A. El-Ghanam and M. Fettouhi
Chemistry Department, KFUPM, 31261 Dhahran, Saudi Arabia
Received 16 October 2000; revised 15 November 2000; accepted 22 November 2000
Abstract—Control of the regioselective thiocarbonylation of terminal acetylenes 1a–e with arylthiols 2a,b was successfully
achieved by using Pd(OAc)2 and 1,4-bis(diphenylphosphino)butane (dppb), or 1,3-bis(diphenylphosphino)propane (dppp), as
catalysts. The formation of the thioesters 3 or 4 depends mainly on the type of ligand (dppp or dppb) and the solvent (THF or
CH2Cl2) under CO/H+ or syngas mixture. © 2001 Elsevier Science Ltd. All rights reserved.
The transition-metal-catalyzed carbonylation of organic
sulfur compounds has been the subject of a few investi-
gations.1,2 A variety of transition metal complexes has
been used as catalysts in the carbonylation of different
sulfur-containing compounds.3,4 A series of transition-
metal-catalyzed addition and carbonylation–addition
reactions of organic disulfides and thiols to acetylenes
leading to a,b-unsaturated thioesters has been devel-
oped.5–7 Recently, Alper and co-workers have intro-
duced new interesting methods of palladium-catalyzed
thiocarbonylation of various alkynes.8,9 The thioesters
represent attractive building blocks in the synthesis of
various complex molecules.10 The search for new
methodology for the synthesis of gem- and trans-a,b-
unsaturated thioesters is of high interest. We have now
examined the carbonylative addition of arylthiols to
terminal acetylenes in the presence of palladium(II)
catalysts and different phosphine ligands. Pd(OAc)2
was found to exhibit excellent catalytic activity and
regioselectivity toward thioester 3 or 4 depending on
the type of the phosphine ligand, the solvent, and the
additive (Eq. (1)).
The thiocarbonylation of 1-heptyne (R=C6H13) with
thiophenol (Ar=Ph) was chosen as a model reaction
and was carried out by changing the type of catalyst,
ligand, solvent, and additive.15 The results are summa-
rized in Table 1. No product of carbonylation was
obtained in the absence of p-TsOH (Table 1, entry 1).
The initial reaction conditions screening indicated that
the use of the catalytic system Pd(OAc)2/dppp/CO/p-
TsOH/THF (A) affords the thioester 3b as the main
product (Table 1, entry 2). Important loss of selectivity
or catalytic activity has been observed by replacing
p-TsOH with other additives such as PhCOOH or
CH3SO3H (Table 1, entries 3 and 4), or replacing dppp
in A with other bidentate ligands such as dppb or
monodentate phosphine ligand such as PPh3 (Table 1,
entries 7 and 8), or by using PdCl2(PPh3)2 or Pd(PPh3)4
in place of Pd(OAc)2 (Table 1, entries 8 and 9).
In addition, a significant decrease in the catalytic activ-
ity and/or the selectivity was observed when toluene,
CH2Cl2, CH3CN, or hexane was used in place of THF.
Also, the use of 300 psi of H2 in place of p-TsOH
(1)
Keywords: palladium; carbonylation; thiophenols; alkynes; thioesters; syngas.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02169-9

Table 1. Palladium (II)-catalyzed thiocarbonylation of 1-heptyne with thiophenola
Entry
Catalyst
Ligand
Solvent
H+ (mmol)
CO (psi)
H2 (psi)
Yieldb (%) (3b+4b)
Product distributionc (%)
Yieldb 5b (%)
3b
4b
1
2
3
4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2(PPh3)2
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2(PPh3)2
Pd(PPh3)4
dppp
dppp
dppp
dppp
dppp
dppp
dppp
PPh3
dppp
dppp
dppp
dppb
dppb
dppp
dppp
dppp
dppb
dppb
dppb
dppb
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
–
300
300
300
300
300
300
300
300
300
300
300
300
300
600
100
500
100
100
300
300
–
–
–
–
–
–
–
–
–
Traces
87
61
96
55
77
64
13
50
74
40
30
96
Traces
95
92
47
30
–
–
–
–
32
–
5
28
31
24
36
38
48
79
–
76
75
40
48
34
57
–
12
32
2
15
15
11
–
8
5
15
–
32
–
–
–
–
–
–
–
p-TsOH (0.04)
p-TsOH (0.12)
PhCOOH (0.04)
CH3SO3H (0.04)
p-TsOH (0.04)
p-TsOH (0.04)
p-TsOH (0.04)
p-TsOH (0.04)
100
100
68
100
95
72
69
76
64
62
52
21
–
24
25
60
52
66
43
5
6d
7
/
8
9
10
11
12
13
14
15
16
17
18
19
20
p-TsOH (0.04)
–
–
–
–
–
–
–
–
–
–
–
300
300
300
–
500
100
100
100
300
300
4
(
0
CH2Cl2
CH2Cl2
65
84
a Reaction conditions: Pd(OAc)2 (0.02 mmol), ligand (0.08 mmol), 1-heptyne (2.0 mmol), thiophenol (2.0 mmol), solvent (10 ml), 6 h (entries 1–9) and 24 h (entries 10–19).
b Isolated yields.
c The ratio 3/4 was determined by GC and 1H NMR.
d 120°C.

B. El Ali et al. / Tetrahedron Letters 42 (2001) 1567–1570
1569
affects the yield and the selectivity of the reaction
(Table 1, entry 11). It is important to note that the
presence of p-TsOH and dppp enhances the formation
of the a,b-unsaturated carboxylic acid 5b (Table 1,
entries 2, 3, 5–7, 9, and 15). The origin of 5b is
probably from the direct hydrocarboxylation of alkynes
in the presence of p-TsOH as additive,11 and/or from
the acid hydrolysis of thioester 3b. Interestingly, the
catalytic system including Pd(OAc)2/dppb/CO/H2/
CH2Cl2 (B) gave trans-thioesters 4b as the major prod-
ucts (Table 1, entry 13). No reaction was observed in
the absence of H2 (Table 1, entry 14). Low total yields
and selectivities toward 4b were obtained by using THF
in place of CH2Cl2 (Table 1, entry 12). The change of
the CO/H2 ratio did not affect the selectivity of the
reaction. A lower total pressure of 200 psi (CO/H2=
1:1) decreases the total yield as well the selectivity
(Table 1, entry 17). The use of PdCl2(PPh3)2 or
Pd(PPh3)4 in place of Pd(OAc)2 decreases the catalytic
activity of system B.
zenethiol 2b with 1-pentyne and 1-heptyne (Table 2,
entries 1–8) in the presence of the catalytic system A or
B. The selectivity of 3 is almost independent of the
electronic and steric effects of the group attached to the
terminal acetylene. However, low total yields of
thioesters were obtained with 1c due probably to a
steric effect (Table 2, entries 9 and 11). The selectivity
of the thioester 4 is strongly sensitive to the steric effect
(Table 2, entries 10 and 12) and to the electronic effect
of the substituent (Table 2, entries 14, 16, and 18). The
steric and electronic effects of the substituent groups
have been previously observed in different hydrocar-
boxylation reactions of alkynes.11–14 The mechanism of
the formation of gem-a,b-unsaturated thioesters is
probably similar to those proposed for the hydrocar-
boxylation of alkynes;11,14 however, the mechanism of
the selective formation of the trans-thioesters 4 is still
under investigation.
In conclusion, we have developed novel palladium(II)
catalyst systems that allow total control of the regiose-
lectivity of the thiocarbonylation of terminal alkynes
with arylthiols and provide significant improvement
over the current systems. Both catalyst systems A and B
have Pd(OAc)2 as the catalyst and can be easily selected
by changing the ligand, solvent, and by using CO/addi-
tive or syngas.
The results of the carbonylation of different alkynes
1a–e with arylthiols 2a,b are summarized in Table 2.
The representative results of the catalytic thiocarbony-
lation of different terminal acetylenes and arylthiols
showed excellent control of the regioselectivity of the
thiocarbonylation of thiophenol 2a and 4-methylben-
Table 2. Palladium (II)-catalyzed thiocarbonylation of terminal acetylenes with arylthiolsa
Entry
Alkyne R (1)
Thiol 2
Catalytic systemb
Yieldc (3+4) (%)
Product distributiond (%) Yieldc 5a–e (%)
3a–e
4a–e
CH3CH2CH2 (1a)
1
2
3
4
1a
1a
1a
1a
2a
2a
2b
2b
A
B
A
B
86
93
88
96
100
15
100
17
–
85
–
8
–
10
–
83
CH3(CH2)3CH2 (1b)
5
6
7
8
1b
1b
1b
1b
2a
2a
2b
2b
A
B
A
B
87
96
82
90
100
21
100
20
–
79
–
12
–
12
–
80
(CH3)3C (1c)
9
1c
1c
1c
1c
2a
2a
2b
2b
A
B
A
B
25
95
13
90
71
–
77
–
29
100
23
7
–
10
–
10
11
12
100
CNCH2CH2CH2 (1d)
13
14
15
16
1d
1d
1d
1d
2a
2a
2b
2b
A
B
A
B
85
96
84
98
100
37
100
33
–
63
–
13
–
10
–
67
Ph (1e)
1e
1e
17
18
2a
2a
A
B
84
75
100
65
–
35
15
–
a Reaction conditions: Pd(OAc)2 (0.02 mmol), dppb (0.08 mmol) or dppp (0.04 mmol), alkyne (2.0 mmol), thiol (2.0 mmol), p-TsOH (0.04 mmol),
solvent (10 ml).
b Catalytic system: A: Pd(OAc)2/ dppp/p-TsOH /THF/CO(300 psi)/110°C/6 h; B: Pd(OAc)2/dppb/CO(300 psi)/H2 (300 psi)/CH2Cl2/110°C/24 h.
c Isolated yields.
d The ratio 3/4 was determined by GC and 1H NMR.

1570
B. El Ali et al. / Tetrahedron Letters 42 (2001) 1567–1570
8. Xiao, W. J.; Alper, H. J. Org. Chem. 1997, 62, 34222.
Acknowledgements
9. Xiao, W. J.; Vasapollo, G.; Alper, H. J. Org. Chem. 1999,
64, 2084.
We thank King Fahd University of Petroleum & Min-
erals (KFUPM, Saudi Arabia) for providing the facility
and for financial support of this project.
10. (a) Thuillier, A.; Metzner, P. Sulfur Reagents in Organic
Synthesis; Academic: New York, 1994; (b) Fukuyma, T.;
Lin, S.; Li, L. J. Am. Chem. Soc. 1990, 112, 7050; (c)
Oeveren, A. V.; Feringa, B. L. J. Org. Chem. 1996, 61,
2920.
11. (a) Kushimo, Y.; Itoh, K.; Minra, M.; Nomura, M. J.
Mol. Catal. 1994, 89, 151; (b) Jayasree, S.; Seayad, A.;
Gupta, S. P.; Chaudhari, R. V. Catal. Lett. 1999, 58, 213.
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14. (a) El Ali, B.; Alper, H. J. Mol. Catal. 1995, 96, 197; (b)
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15. Typical experimental procedure for the thiocarbonylation
of alkynes with arylthiols: A mixture of 2.0 mmol of
1-heptyne 1b, 2.0 mmol of thiophenol 2a, 0.020 mmol of
Pd(OAc)2, and 0.08 mmol of dppb was dissolved in
CH2Cl2 (10 ml) and placed in a 45 ml autoclave. The
autoclave was purged, pressurized (600 psi of CO+H2),
and then heated (110°C). After 24 h, the reaction mixture
was cooled to room temperature, filtered through Celite,
and concentrated by rotary evaporation. Thioesters 3b
and 4b were separated by preparative thin-layer chro-
matography using hexane–ethyl acetate (10:1) as solvent.
All thioesters 3 and 4 were clearly identified and charac-
1
terized by GC–MS, and H and 13C NMR spectroscopy.
.