The First Examples of the Palladium-Catalyzed Thiocarbonylation of Propargylic Alcohols with Thiols and Carbon Monoxide

Full text of DOI:10.1021/jo970126n

3422
J . Org. Chem. 1997, 62, 3422-3423
Communications
Ta ble 1. P a lla d iu m -Ca ta lyzed Rea ction of 1a w ith P h SH
Th e F ir st Exa m p les of th e
a n d CO w ith or w ith ou t p-TsOH in THF a
P a lla d iu m -Ca ta lyzed Th ioca r bon yla tion of
P r op a r gylic Alcoh ols w ith Th iols a n d
Ca r bon Mon oxid e
isolated yield (%)
entry
catalyst system
Pd(PPh3)4
Pd(PPh3)4 + p-TsOH
Pd(OAc)2
2a
13
trace
23
16
trace
64
3a
4a
1
2
3
58
74
7
9
Wen-J ing Xiao and Howard Alper*
18 14
56
82 trace
16
4
5
6
7
Pd(OAc)2 + PPh3
8
Department of Chemistry, University of Ottawa,
10 Marie Curie, Ottawa, Ontario, Canada K1N 6N5
Pd(OAc)2 + PPh3 + p-TsOH
Pd(OAc)2 + dppp
5
Pd(OAc)2 + dppp + p-TsOH
Pd(dba)2
12
36
16
68 trace
13 trace
29 trace
Received J anuary 23, 1997
8b
9c
10
11c
Pd(dba)2 + p-TsOH
The use of transition metal complexes as homogeneous
catalysts in reactions involving organosulfur compounds
as substrates has been the subject of relatively few
investigations,1 while there are numerous publications
concerning the analogous oxo reactants.2 Perhaps the
widespread belief that organosulfur compounds are poi-
sons to catalysts has precluded intensive research in this
area.3 We have now examined the reaction of proparglic
alcohols with thiols and carbon monoxide in the presence
of palladium-based catalysts. Palladium(0) complexes
were found to exhibit excellent catalytic activity toward
the thiocarbonylation of propargylic alcohols, affording
thiofuranones (2), thioesters (3), or dithioesters (4) as the
principal product, depending on the reaction conditions.
To our knowledge, these are the first examples of the
transition-metal-catalyzed thiocarbonylation of propar-
gylic alcohols with thiols and CO.
Pd(dba)2 + PPh3
63
8
7
38
5
5
Pd2(dba)3CHCl3 + PPh3 + p-TsOH
a
Reaction conditions: 1a (2 mmol), cat. (0.06 mmol), ligand
PPh3 (0.24 mmol) or dppp (0.12 mmol), p-TsOH (0.1 mmol) (if
used), THF (5 mL), 400 psi CO, 100 °C, 48 h. After being cooled
to room temperature and releasing CO, the reaction mixture was
filtered through Celite with chloroform as an eluant. The crude
product was purified by preparative TLC (n-hexane:EtOAc ) 10:1
b
as eluant), affording analytically pure products. 14% of substrate
was recovered. c Some catalyst decomposition was observed.
The search for new methods for the preparation of thiol
esters and sulfur-containing γ-lactones is a topic of
current interest.4,5 Not only do these compounds consti-
tute a group of natural products,6 but they are also
attractive building blocks in the synthesis of complex
organic molecules.7 The reaction described herein (eq 1)
represents one of the most straightforward routes to
these compounds.
Table 1 shows the results of the carbonylation reaction
of 2-methyl-3-butyn-2-ol (1a ) with thiophenol using sev-
eral palladium catalysts. Initial catalyst screening in-
dicated that use of palladium(0) or palladium(II) com-
plexes with added phosphine ligands displayed the
highest catalytic activity toward the formation of 2a and
3a in THF. In particular, the use of 3 mol % palladium
acetate with 4 equiv of triphenylphosphine and 5 mol %
of p-toluenesulfonic acid (p-TsOH) was the most effective
catalyst system for the selective formation of 3a in 82%
yield (Table 1, entry 5).
Pd(PPh3)4 is also an excellent catalyst for this reaction
(Table 1, entry 2). However, other palladium catalysts,
such as Pd(dba)2 (Table 1, entries 8-10), Pd2(dba)3‚CHCl3
(Table1, entry 11), and Pd(OAc)2, without added phos-
phine ligand (Table 1, entry 3), were less effective for this
transformation. Use of Pd(dba)2, with triphenylphos-
phine, but in the absence of p-TsOH, gave 2a in good
yield (Table 1, entry 10). The bidentate phosphine, 1,3-
bis(diphenylphosphino)propane (dppp), was also effective
as an added ligand for the Pd(OAc)2-catalyzed reaction,
and good yields of 2a and 3a resulted in the absence and
presence of p-TsOH (Table 1, entries 6 and 7). In
contrast to these palladium catalyst systems, [Rh(COD)-
Cl]2, which is active for the carbonylation of sulfur-
substituted heterocycles,8 was ineffective for the reaction
of 1a with PhSH and CO. In addition, Ir4(CO)12 and Ru3-
(1) (a) Crudden, C. M.; Alper, H. J . Org. Chem. 1995, 60, 5579. (b)
Ogawa, A.; Takeba, M.; Kawakami, J .; Ryu, I.; Kambe, N.; Sonoda, N.
J . Am. Chem. Soc. 1995, 117, 7564. (c) Ogawa, A.; Kawakami, J .;
Sonoda, N.; Hirao, T. J . Org. Chem. 1996, 61, 4161. (d) Shim, S. C.;
Antebi, S.; Alper, H. J . Org. Chem. 1985, 50, 147. (e) Antebi, S.; Alper,
H. Tetrahedron Lett. 1985, 26, 2609. (f) Calet, S.; Alper, H. Tetrahedron
Lett. 1986, 27, 3573. (g) Calet, S.; Alper, H. Organometallics 1987, 6,
1625. (h) Antebi, S.; Alper, H. Can. J . Chem. 1986, 64, 2010. (i) Wang,
M. D.; Calet, S.; Alper, H. J . Org. Chem. 1989, 54, 20.
(2) (a) Falbe, J . New Syntheses with Carbon Monoxide; Springer-
Verlag: Berlin, 1980; p 1. (b) Colquhoun, H. M.; Thompson, D. J .;
Twigg, M. V. Carbonylation; Plenum Press: New York, 1991. (c) Stille,
J . K. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Perga-
mon: Oxford, 1991; Vol. 4, p 913. (d) Tsuji, J .; Mandai, T. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2589.
(3) Hutton, A. T. In Comprehensive Coordination Chemistry; Wilkin-
son, G., Gillard, R. D., McCleverty, J . A., Eds.; Pergamon Press:
Oxford, U.K., 1984; Vol. 5, p 1151. Although sulfur is considered to be
a potential catalyst poison, there are many examples where sulfur-
containing compounds are useful ligands: Frost, C. G.; Williams, J .
M. J . Tetrahedron Lett. 1993, 34, 2015. See also ref 5.
(4) Adamczyk, M.; Fishpaugh, J . R. Tetrahedron Lett. 1996, 37, 4305.
(5) Oeveren, A. V.; Feringa, B. L. J . Org. Chem. 1996, 61, 2920.
(6) (a) Halcomb, R. L.; Boyer, S. H.; Wittman, M. D.; Olson, S. H.;
Denhart, D. J .; Liu, K. K. C.; Danishefsky, S. J . J . Am. Chem. Soc.
1995, 117, 5720. (b) Corey, E.; Reichard, G. J . Am. Chem. Soc. 1992,
114, 10677.
(7) (a) Thuillier, A.; Metzner, P. Sulfur Reagents in Organic
Synthesis; Academic Press: New York, 1994. (b) Fukuyama, T.; Lin,
S.; Li, L. J . Am. Chem. Soc. 1990, 112, 7050. (c) Penn, J .; Owens, W.
Tetrahedron Lett. 1992, 33, 3737.
(8) Khumtaveeporn, K.; Alper, H. J . Chem. Soc., Chem. Commun.
1995, 917.
S0022-3263(97)00126-6 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 11, 1997 3423
Ta ble 2. P a lla d iu m -Ca ta lyzed Rea ction of P r op a r gylic Alcoh ols w ith Th iols a n d CO (400 p si) a t 100 °C
isolated yield (%)
entry
1
thiol (R4)
Ph
p-CH3C6H4
p-FC6H4
n-octyl
Ph
Ph
Ph
Ph
Ph
Ph
Ph
p-FC6H4
Ph
Ph
solvent
catalytic system
2
3
4
1
2
3
1a
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
toluene
toluene
DME
DME
DME
DME
DME
DME
DME
Pd(PPh3)4 + p-TsOH
Pd(PPh3)4 + p-TsOH
Pd(PPh3)4 + p-TsOH
Pd(OAc)2 + PPh3 + p-TsOH
Pd(PPh3)4 + p-TsOH
Pd(PPh3)4 + p-TsOH
Pd(PPh3)4 + p-TsOH
Pd(PPh3)4 + p-TsOH
Pd(PPh3)4 + p-TsOH
Pd(OAc)2 + PPh3 + p-TsOH
Pd(PPh3)4
trace
trace
trace
8
trace
6
74
9
85
52
68
76
73
64
72
63
72
0
trace
18
trace
4
4
5a
1b
1c
1d
1e
1f
6b
5
7
13
10
trace
4
14
trace
66
74
8c
9d
0
10
11e,f
12e,f
13f-h
14f-h
15
16
17
18
19
20
21
1g
1a
trace
0
Pd(PPh3)4
0
0
7
4
5
Pd(PPh3)4 + p-TsOH
Pd(PPh3)4 + p-TsOH
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
trace
trace
67
73
74
70
88
85
76
77
73
1e
1a
Ph
4
p-BrC6H4
n-octyl
Ph
Ph
Ph
7
trace
0
10
4
trace
trace
trace
1f
1e
1d
1a
4
trace
trace
0
furanyl
a
b
d
g
E/Z ) 1.4:1. E/Z ) 2.3:1. c E/Z ) 1.4:1. E/Z ) 1.5:1. e Reaction temperature 90 °C. f ROH/RSH ) 1:2.5. Reaction temperature 110
h
°C. 600 psi of CO.
(CO)12 afforded complicated mixtures of products, none
of which were 2a , 3a , or 4a .
11 and 12). The reaction in DME and in the absence of
p-TsOH selectively afforded the sulfur-substituted fura-
nones 4 in 67-88% yield (Table 2, entries 15-21).
The results for the palladium-catalyzed carbonylative
coupling reaction of propargylic alcohols with thiols and
CO are presented in Table 2. Arenethiols and alkanethi-
ols can be employed successfully in the reaction (Table
2, entries 1-4) together with primary, secondary, and
tertiary acyclic propargyl alcohols containing a terminal
acetylene (Table 2, entries 1, 5, and 10). In addition, the
use of a propargyl alcohol bearing a substituent at the
acetylene terminus with benzenethiol under the same
conditions gave the thioester (3a ) as the only product in
72% isolated yield (Table 2, entry 10). We have also
found that propargyl alcohols can be thiocarbonylated
selectively to give monothioester, dithioester, or sulfur-
containing furanones, depending on the reaction condi-
tions. When the reaction is conducted in THF with a
catalytic amount of p-TsOH and the ratio of propargyl
alcohol to thiol is 1:1, the thioester was formed as a major
product in 52-85% yield (Table 2, entries 1-10). The
reaction was carried out in toluene under more severe
conditions (110 °C, 600 psi CO) to afford mainly dithio-
carbonylation products (Table 2, entries 13 and 14). Tert-
iary propargylic mesylates with a terminal triple bond
are very reactive and give a high yield of the dithioester
under milder conditions (90 °C, 400 psi) (Table 2, entries
In conclusion, we have developed a palladium-cata-
lyzed carbonylative coupling reaction of propargyl alco-
hols and thiols. By using different reaction conditions,
one can produce monothioesters, dithioesters, or sulfur-
containing furanones in good to excellent yield and
selectivity. Not only is this methodology attractive for
the preparation of thioesters and sulfur-substituted
lactones, but it also demonstrates the utility of transition-
metal catalysts in the reactions of sulfur compounds. We
are currently examining the application of this method
to different classes of substrates.
Ack n ow led gm en t. We are grateful to the Natural
Sciences and Engineering Council of Canada for support
of this research.
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal procedures and characterization data for all products and
1H-NMR spectra for new compounds (21 pages).
J O970126N