Highly Regioselective Thiocarbonylation of Allylic Alcohols with Thiols and Carbon Monoxide Catalyzed by Palladium Complexes: A New and Efficient Route to β,γ-Unsaturated Thioesters

Article abstract of DOI:10.1021/jo9812328

The reaction of allylic alcohols with thiols and carbon monoxide in the presence of catalytic quantities of Pd(OAc)₂ (3 mol %), triphenylphosphine (12 mol %), and p-TsOH (5 mol %) leads to a novel thiocarbonylation to afford β,γ-unsaturated thioesters in good to excellent yields. Other palladium catalyst systems such as Pd₂(dba)₃·CHCl₃-PPh₃-p-TsOH, Pd(PPh₃)₄-p-TsOH, and Pd(OAc)₂-dppb-p-TsOH are also effective for this transformation. The thiocarbonylation reaction is believed to proceed via a allylpalladium intermediate. The reaction occurs highly regioselectively at the least hindered allylic terminal carbon of the substrate to give the products. This new carbonylation procedure was readily applied to a variety of allylic alcohols and both aromatic and aliphatic thiols.

Full text of DOI:10.1021/jo9812328

J . Org. Chem. 1998, 63, 7939-7944
7939
High ly Regioselective Th ioca r bon yla tion of Allylic Alcoh ols w ith
Th iols a n d Ca r bon Mon oxid e Ca ta lyzed by P a lla d iu m Com p lexes:
A New a n d Efficien t Rou te to â,γ-Un sa tu r a ted Th ioester s
Wen-J ing Xiao and Howard Alper*
Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, Canada K1N 6N5
Received J une 25, 1998
The reaction of allylic alcohols with thiols and carbon monoxide in the presence of catalytic quantities
of Pd(OAc)2 (3 mol %), triphenylphosphine (12 mol %), and p-TsOH (5 mol %) leads to a novel
thiocarbonylation to afford â,γ-unsaturated thioesters in good to excellent yields. Other palladium
catalyst systems such as Pd2(dba)3‚CHCl3-PPh3-p-TsOH, Pd(PPh3)4-p-TsOH, and Pd(OAc)2-
dppb-p-TsOH are also effective for this transformation. The thiocarbonylation reaction is believed
to proceed via a allylpalladium intermediate. The reaction occurs highly regioselectively at the
least hindered allylic terminal carbon of the substrate to give the products. This new carbonylation
procedure was readily applied to a variety of allylic alcohols and both aromatic and aliphatic thiols.
In tr od u ction
The palladium complex catalyzed carbonylation of
allylic compounds has attracted considerable attention
in recent years.1 The reactions are considered to proceed
via a π-allylpalladium complex which is formed by the
oxidative addition of palladium(0) to various allylic
compounds (esters, carbonates, etc.), followed by insertion
of carbon monoxide into the palladium-carbon bond.
Although reactions using alcohols,2 amines,3 carbon nu-
of sulfur compounds. Reported herein is the carbonylation
reaction of allylic alcohols with thiols, another example
of organic chalcogen compounds as reactants with a
palladium catalyst. While effective methods have been
cleophiles,4 and organometallic reagents5 to intercept
allylpalladium intermediates have been well established,
much less attention has been paid to reactions with
organic sulfur compounds,6 in which thiopalladation
would be involved. This might be partly because chalco-
gen compounds often bind strongly to transition metals,7
thus poisoning the catalysts and inhibiting catalytic
reactions.8 We and other groups have recently described
a series of reactions in which chalcogen compounds are
employed as the substrates along with transition metal
catalysts.6a-d 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 1.6c Following this publication, a study showed that
the same products were obtained when the reaction was
carried out with diaryl disulfides as substrates.6d In the
case of allenes possessing mono- or disubstitution, the
thiocarbonylation is completely regioselective, in which
the thiophenyl group adds to the least-substituted double
bond of the allene (eq 2).6a These reactions demonstrate
the utility of transition metal catalysts in the reactions
(6) Thus far, there are no reports on transition-metal-catalyzed
reactions involving thiols and allylic alcohols. For examples of transi-
tion-metal-catalyzed reactions using organosulfur compounds, see: (a)
Xiao, W.-J .; Vasapollo, G.; Alper, H. J . Org. Chem. 1998, 63, 2609. (b)
Ogawa, A.; Obayashi, R.; Ine, H.; Tsuboi, Y.; Sonoda, N.; Hirao, T. J .
Org. Chem. 1998, 63, 881. (c) Xiao, W.-J .; Alper, H. J . Org. Chem. 1997,
62, 3422. (d) Ogawa, A.; Kuniyasu, H.; Sonoda, N.; Hirao, T. J . Org.
Chem. 1997, 62, 8361. (e) Arterburn, J . B.; Perry, M. C.; Nelson, S. L.;
Dible, B. R.; Holguin, M. S. J . Am. Chem. Soc. 1997, 119, 9309. (f)
Ogawa, A.; Kawakami, J .; Mihara, M.; Ikeda, T.; Sonoda, N.; Hirao,
T. J . Am. Chem. Soc. 1997, 119, 12380. (g) Galardon, E.; Maux, P. L.;
Simonneaux, G. J . Chem. Soc., Perkin Trans. 1 1997, 2455. (h) Ogawa,
A.; Kawakami, J .; Sonoda, N.; Hirao, T. J . Org. Chem. 1996, 61, 4161.
(i) Crudden, C. M.; Alper, H. J . Org. Chem. 1995, 60, 5579. (j)
Khumtaveeporn, K.; Alper, H. J . Chem. Soc., Chem. Commun. 1995,
917. (k) Ogawa, A.; Takeba, M.; Kawakami, J .; Ryu, I.; Kambe, N.;
Sonoda, N. J . Am. Chem. Soc. 1995, 117, 7564. (l) Khumtaveeporn,
K.; Alper, H. J . Org. Chem. 1994, 59, 1414. (m) Ishiyama, T.; Nishijima,
K.; Miyaura, N.; Suzuki, A. J . Am. Chem. Soc. 1993, 115, 7219. (n)
Kuniyasu, H.; Ogawa, A.; Sato, K.; Ryu, I.; Kambe, N.; Sonoda, N. J .
Am. Chem. Soc. 1992, 114, 5902. (o) Kuniyasu, H.; Ogawa, A.; Sato,
K.; Ryu, I.; Kambe, N.; Sonoda, N. J . Am. Chem. Soc. 1991, 113, 9796.
(p) Luh, T. Y.; Ni, Z. J . Synthesis 1990, 89. (q) Wang, M.-D.; Calet, S.;
Alper, H. J . Org. Chem. 1989, 54, 20. (r) Carpita, A.; Rossi, R.;
Scamuzzi, B. Tetrahedron Lett. 1989, 30, 2699. (s) Calet, S.; Alper, H.
Organometallics 1987, 6, 1625. (t) Osakada, K.; Yamamoto, T.;
Yamamoto, A. Tetrahedron Lett. 1987, 28, 6321. (u) Calet, S.; Alper,
H. Tetrahedron Lett. 1986, 27, 3573. (v) Antebi, S.; Alper, H. Can. J .
Chem. 1986, 64, 2010. (w) Antebi, S.; Alper, H. Organometallics 1986,
5, 596. (x) Cristau, H. J .; Chabaud, B.; Labaudiniere, R.; Christol, H.
J . Org. Chem. 1986, 51, 875. (y) Antebi, S.; Alper, H. Tetrahedron Lett.
1985, 26, 2609. (z) Shim, S. C.; Antebi, S.; Alper, H. J . Org. Chem.
1985, 50, 147.
(1) Tsuji, J . Palladium Reagents and Catalysts; J ohn Wiley &
Sons: New York, 1995. (b) Malleron, J .-L.; Fiaud, J .-C.; Legros, J .-Y.
Handbook of Palladium-Catalyzed Organic Reactions: Synthetic As-
pects and Catalytic Cycles; Academic Press: London, 1997.
(2) Ishii, Y.; Gao, C.; Iwasaki, M.; Hidai, M. J . Org. Chem., 1993,
58, 6818. (b) Duprat, S.; Deweerdt, H.; J enck, J .; Kalck, P. J . Mol.
Catal. 1993, 80, L9.
(3) Zhu, J .; Lu, X. Tetrahedron Lett. 1987, 28, 1987. (b) Zhu, J .; Lu,
X. Chem. Commun. 1987, 1318.
(4) Ito, Y.; Sawamura, M.; Matsuoka, M.; Matsumoto, Y.; Hayashi,
T. Tetrahedron Lett. 1987, 28, 4849. (b) Lu, X.; J iang, X. J . Organomet.
Chem. 1989, 359, 139.
(5) Tamaru, Y.; Yasui, K.; Takanabe, H.; Tanaka, S.; Fugami, K.
Angew. Chem., Int. Ed. Engl. 1992, 31, 645.
(7) Dubois, M. R. Chem. Rev. 1989, 89, 1.
(8) Hegedus, L. L.; McCabe, 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.
10.1021/jo9812328 CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/16/1998

7940 J . Org. Chem., Vol. 63, No. 22, 1998
Xiao and Alper
Ta ble 1. Effects of P a lla d iu m Ca ta lysts on th e
developed for the carbonylation reaction of allyl carbon-
ates,9 esters,10 amines,11 and ethers,12 few investigations
have been made using allyl alcohols as substrates.13 The
present methodology is concerned with allyl alcohols as
direct starting materials under quite mild conditions.
There has been considerable interest in the preparation
of thioesters.14 The latter constitute a group of natural
products15 and are also useful building blocks in the
synthesis of complex organic molecules.16 The methodol-
ogy described herein (eq 3) is a simple and direct route
to â,γ-unsaturated thioesters.
Th ioca r bon yla tion of 1a w ith Th iop h en ol a n d CO in
a
CH2Cl2
time temp yield
entry
catalyst
additive
(h)
(°C)
(%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
none
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4/PPh3
Pd(PPh3)4/dppb
Pd(OAc)2
none
none
48
48
72
48
48
72
72
72
48
48
48
48
60
60
100
100
100
100
100
120
120
120
100
100
100
100
100
100
0
8
63
82
77
0
p-TsOH
p-TsOH
p-TsOH
none
p-TsOH
none
p-TsOH
p-TsOH
p-TsOH
HCl
Pd(OAc)2
0
4
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/dppb
Pd(OAc)2/dppp
Pd(OAc)2/PPh3
Pd(OAc)2/dppe
93
88
64
47
17
84
p-TsOH
Pd2(dba)3‚CHCl3/PPh3 p-TsOH
Resu lts a n d Discu ssion
a
Reaction conditions: 1a (2 mmol), 2a (2 mmol), catalyst (0.06
mmol), ligand PPh3 (0.24 mmol), dppb (0.12 mmol), dppp (0.12
mmol) or dppe (0.12 mmol) (if used), p-TsOH (0.1 mmol), or HCl
Rea ction Con d ition s for Th ioca r bon yla tion . We
chose 2-methyl-3-buten-2-ol (1a ) as a model substrate
and investigated its reaction with thiophenol (2a ), carbon
monoxide, and catalytic quantities of a variety of pal-
ladium complexes under different conditions. The effect
of different catalytic systems on the thiocarbonylation of
1a is presented in Table 1.
Among the catalytic systems examined, Pd(OAc)2 with
PPh3 and p-toluenesulfonic acid (p-TsOH) exhibited
excellent catalytic activity to afford the thiocarbonylation
product 3a in 93% isolated yield (Table 1, entry 9). In
the absence of catalyst or p-TsOH, 3a was not obtained
at all or was formed in very low yield (Table 1, entries 1,
2, 6, and 8). The function of p-TsOH is presumably to
protonate the hydroxyl group of the substrate so as to
eliminate H2O to form a π-allyl palladium complex. Using
HCl in place of p-TsOH (Table 1, entry 12), the reaction
also afforded 3a , but the yield was appreciably lower,
probably because the poor solubility of HCl in CH2Cl2
decreases the degree of protonation of the hydroxyl group.
b
(0.1 mmol) (if used), 400 psi CO and CH2Cl2 (10 mL). Isolated
yield based on thiophenol.
Thiocarbonylation of allylic carbonate 4a and phosphon-
ate 4b can be carried out without p-TsOH or HCl (eq 5).
It further demonstrates that the function of the acid is
to assist the elimination of the hydroxyl group.
Palladium(0) complexes, such as Pd(PPh3)4 and
Pd2(dba)3‚CHCl3 with added phosphine and p-TsOH are
also excellent catalytic systems for this transformation
(Table 1, entries 4, 5, and 14). However, palladium
catalysts without added phosphine ligand (Table 1,
entries 3 and 7) were less effective for this reaction. The
bidentate phosphines, 1,3-bis(diphenylphosphino)propane
(dppp), and 1,4-bis(diphenylphosphino)butane (dppb),
were also effective as added ligands for the Pd(OAc)2-
catalyzed reaction and afford 3a in 64 and 88% yield,
respectively (Table 1, entries 10 and 11), but 1,2-bis-
(diphenylphosphino)ethane (dppe) is almost ineffective.
This can be explained by the fact that CO insertion into
a Pd-C bond occurs faster for those alkylpalladium
diphosphine complexes containing a more flexible metal-
ligand chelate ring.17
(9) Tsuji, J .; Sato, K.; Okumoto, H. J . Org. Chem. 1984, 49, 1341.
(10) Murahashi, S.-I.; Imada, Y.; Taniguchi, Y.; Higashiura, S.
Tetrahedron Lett. 1988, 29, 4945. (b) Matsuzaka, H.; Hiroe, Y.; Iwasaki,
M.; Ishii, Y.; Koyasu, Y.; Hidai, M. J . Org. Chem. 1988, 53, 3832.
(11) Murahashi, S.-I.; Imada, Y.; Nishimura, K. J . Chem. Soc.,
Chem. Commun. 1988, 1578.
(12) Neibecker, D.; Poirier, J .; Tkatchenko, I. J . Org. Chem. 1989,
54, 2459. (b) Bonnet, M. C.; Coombes, J .; Manzano, B.; Neibecker, D.;
Tkatchenko, I. J . Mol. Catal. 1989, 52, 263.
(13) Itoh, K.; Hamaguchi, N.; Miura, M.; Nomura, M. J . Mol. Catal.
1992, 75, 117. (b) Knifton, J . F. J . Organomet. Chem. 1980, 188, 223.
(c) Tsuji, J .; Kiji, J .; Imamura, S.; Morikawa, M. J . Am. Chem. Soc.
1964, 86, 4350. (d) Naigre, R.; Alper, H. J . Mol. Catal. 1996, 111, 11.
(e) Amer, I.; Alper, H. J . Mol. Catal. 1989, 54, L33.
(14) Adamczyk, M.; Fishpaugh, J . R. Tetrahedron Lett. 1996, 37,
4305. (b) Murai, T.; Kakami, K.; Hayashi, A.; Komuro, T.; Takada, H.;
Fujii, M.; Kanda, T.; Kato, S. J . Am. Chem. Soc. 1997, 119, 8592. (c)
Izawa, T.; Terao, Y.; Suzuki, K. Tetrahedron: Asymmetry 1997, 8, 2645.
(15) Vogel, K. W.; Drueckhammer, D. G. J . Am. Chem. Soc. 1998,
120, 3275. (b) 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. (c) Corey, E.; Reichard, G. J . Am. Chem. Soc. 1992,
114, 10677.
Table 2 indicates some results of the effects of varying
the reaction conditions on the formation of 3a . Using the
Pd(OAc)2-PPh3/p-TsOH catalyst system, we found that
the reaction works well in CH2Cl2, 1,2-dimethoxyethane
(DME), or THF but less so in toluene or diethyl ether
(Table 2, entries 1-5). A decrease to 100 psi or increase
(16) Schmittberger, T.; Cotte, A.; Waldmann, H. J . Chem. Soc.,
Chem. Commun. 1998, 937. (b) Wallace, O. B.; Springer, D. M.
Tetrahedron Lett. 1998, 39, 2693. (c) Thuillier, A.; Metzner, P. Sulfur
Reagents in Organic Synthesis; Academic Press: New York, 1994. (d)
Brown, R. S.; Aman, A. J . Org. Chem. 1997, 62, 4816. (e) Castro, J .;
Moyano, A.; Perkas, M. A.; Riera, A. Synthesis 1997, 518.
(17) Dekker: G. P. C. M.; Elsevier: C. J .; Vrieze, K.; van Leeuwen,
P. W. N. M. Organometallics 1992, 11, 1598. (b) Dekker: G. P. C. M.;
Elsevier: C. J .; Vrieze, K.; van Leeuwen, P. W. N. M. J . Organomet.
Chem. 1992, 430, 357.

New and Efficient Route to â,γ-Unsaturated Thioesters
J . Org. Chem., Vol. 63, No. 22, 1998 7941
(E)-isomers. As Murahashi20a observed in the alkoxycar-
bonylation of diethyl cinnamyl phosphate and diethyl
geranyl phosphate, cinnamyl alcohol (1h ) and geraniol
(1l) undergo the thiocarbonylation to afford stereoselec-
tively (E)-phenyl-4-phenyl-3-butenethioate (3k ) and (E)-
phenyl-4,8-dimethyl-3-nonenethioate ((E)-3l), respec-
tively (Table 3, entries 15 and 19).
The regioselectivity of the reaction was further inves-
tigated using linalool (1i) and geraniol (1l) as reactants.
While linalool afforded a 3:1 mixture of E/Z 3l, only (E)-
3l was isolated when geraniol was the substrate (eqs 6
and 7).
Ta ble 2. In flu en ce of Solven t, P r essu r e, a n d
Tem p er a tu r e on th e P a lla d iu m -Ca ta lyzed
Th ioca r bon yla tion of 1a w ith Th iop h en ol a n d COa
temp
(°C)
pressure
(psi)
time
(h)
yield
(%)b
entry
solvent
1
2
CH2Cl2
DME
THF
toluene
ether
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
100
100
100
100
100
100
100
50
400
400
400
400
400
100
800
400
400
400
48
48
48
48
48
60
48
48
48
80
93
90
3
90
4
54
5
6
7
8
47
53c
87d
61e
74
9
150
100
10
58
a
Reaction of 2 mmol of 1a and 2 mmol of PhSH in the presence
0.06 mmol of Pd(OAc)2, 0.24 mmol of PPh3, and 0.1 mmol of
p-TsOH. b Isolated yield based on thiophenol. c 7% of the substitu-
tion reaction product, phenyl 3-methyl-2-butenyl sulfide, was
d
formed. 3% of dithiocarbonylation product was isolated. e 23% of
substrate was recovered.
to 800 psi of CO pressures resulted in the formation of
byproducts (Table 2, entries 6 and 7). Prolonged heating,
80 h versus 48 h, and increasing or decreasing reaction
temperature reduced the yield of 3a (Table 2, entries
8-10). In addition, use of an excess of 1a did not change
the yield of 3a , but resulted in lactonization of unreacted
alcohol.18
Th ioca r bon yla tion of Th iols w ith Va r iou s Acyclic
Allylic Alcoh ols. The carbonylative coupling reaction
of a series of acyclic allylic alcohols (1a -n ) was effected
using 1 equiv of thiols or mercaptans, 3 mol % of Pd-
(OAc)2, 12 mol % of PPh3, and 5 mol % of p-TsOH, in
CH2Cl2 at 400 psi CO for 48 h at 100 °C, affording â,γ-
unsaturated thioesters in isolated yields of 56-93%
(Table 3). Arenethiols and alkanethiols can be success-
fully employed in the reaction (Table 3, entries 1-7)
together with primary, secondary, and tertiary acyclic
allylic alcohols (Table 3, entries 8, 11, and 16). It is
noteworthy that allylic alcohols containing terminal or
internal CdC bonds with alkyl or phenyl substituents
reacted with similar efficiency. The reaction exhibits high
regioselectivity, with insertion of carbon monoxide oc-
curring at the least-substituted terminal allylic carbon
to give linear rather than branched thioesters (Table 3,
entries 8-10, 16, and 20). R,â-Unsaturated thioesters
were not formed in these reactions despite the facile
known isomerization of â,γ-unsaturated to R,â-unsatu-
rated esters.19 An isomeric mixture of â,γ-unsaturated
thioesters were obtained when some alcohols were em-
ployed as substrates. To consider the question of double
bond integrity of the product, the thiocarbonylation
reactions of (E)- and (Z)-2-hexen-1-ol ((E)-1g and (Z)-1g)
were examined under the standard conditions (Table 3,
entries 13 and 14). (E)-1g and (Z)-1g were converted into
a 4:1 mixture of (E)- and (Z)-phenyl-3-heptenethioate (3j),
irrespective of the stereochemistry of the starting alcohol.
The stereochemistry of the carbon-carbon double bond
in 3j may be due to π-σ-π-isomerization of intermediate
π,π-allylpalladium complexes 5 and 7 (Scheme 1),20 with
some selectivity for the thermodynamically more stable
It is conceivable that 8 is favored over 9 on steric
grounds and the ease of generation of 8/9 from 1i and 1l
governs the isomer distribution.
Th ioca r bon yla tion of Th iop h en ol to Cyclic Allylic
Alcoh ols. Although acyclic allylic alcohols undergo thio-
carbonylation readily under mild conditions, cyclic allylic
alcohols show quite low reactivity toward the carbonyl-
ative coupling reactions with thiophenol and carbon
monoxide. When carveol (10) was treated under the
optimized conditions for the thiocarbonylation of acyclic
substrates, the corresponding thioester 11 was obtained
only in 27% yield, with recovery of 52% of the substrate
(eq 8).
Optimization of the reaction conditions resulted in the
thiocarbonylation reaction proceeding to afford thioesters
in higher yield at 120 °C for 3 to 7 days (other conditions
being the same as those for acyclic substrates).21
The scope and limitations of the palladium-catalyzed
carbonylative coupling reaction of cyclic allylic alcohols
with thiophenol and CO are summarized in Table 4.
When 2-cyclohexen-1-ol (12) was allowed to react under
the optimal conditions, phenyl 2-cyclohexenyl formthioate
(13) was formed in 84% yield (Table 4, entry 2); but under
(18) El-Ali, B.; Alper, H. J . Org. Chem. 1991, 56, 5357.
(19) Alcock, S. G.; Baldwin, J . E.; Bohlmann, R.; Harwood: L. M.;
Seeman, J . I. J . Org. Chem. 1985, 50, 3526.
(20) Murahashi, S.-I.; Imada, Y.; Taniguchi, Y.; Higashiura, S. J .
Org. Chem. 1993, 58, 1538. (b) Mackenzie, P. B.; Whelan, J .; Bosnich,
B. J . Am. Chem. Soc. 1985, 107, 2046. (c) Faller, J . W.; Thomsen, M.
E.; Mattina, M. J . J . Am. Chem. Soc. 1971, 93, 2642.
(21) The reaction was monitored by TLC (SiO2, EtOAc-hexane 1:10).

7942 J . Org. Chem., Vol. 63, No. 22, 1998
Xiao and Alper
Ta ble 3. P a lla d iu m -Ca ta lyzed Th ioca r bon yla tion of Acyclic Allyl Alcoh ols w ith Th iols a n d Ca r bon Mon oxid ea

New and Efficient Route to â,γ-Unsaturated Thioesters
J . Org. Chem., Vol. 63, No. 22, 1998 7943
Ta ble 4. P a lla d iu m -Ca ta lyzed Th ioca r bon yla tion of Cyclic Allylic Alcoh ols w ith Th iop h en ol a n d Ca r bon Mon oxid ea
the same reaction conditions, thiocarbonylation of myrtenol
(14) was inactive (Table 4, entry 3). In most cases, the
reactions were clean and no byproduct was formed
(except entry 5). Carvyl carbonate (19) was smoothly
thiocarbonylated to give the corresponding â,γ-unsatu-
rated thioester in excellent yield (Table 4, entry 6), while
the same reaction of carveol (10) needed a longer reaction
time (five vs two days, Table 4, entry 1). Some functional
groups, such as hydroxyl (Table 4, entries 7 to 9),
trimethylsilyl (Table 4, entry 9), and vinyl (Table 4,
entries 1, 4, and 6) groups, did not affect the thiocar-
bonylation reactions. The reaction proceeded regio-
selectively. Substituted cyclic alcohols with unsym-
metrical allylic species, such as 15, 17, 22, and 24,
undergo thiocarbonylation exclusively at the less-substi-
tuted end of the allylic group (Table 4, entries 4, 5, 8,
and 9), while substrates with symmetrical allylic units
can, of course, only afford one product (Table 4, entries
1, 2, 6, and 7).
addition of protonated allylic alcohol to Pd(0) gives the
π-allylpalladium complex 26,23 which may undergo sub-
stitution of H2O by SPh to form the π-allylpalladium
sulfide complex 27. Insertion of CO to 27 affords the
acylpalladium complex 28.6a Reductive elimination of
Pd(0) would form â,γ-unsaturated thioesters.
Con clu sion . Palladium complexes such as Pd(OAc)2,
Pd(PPh3)4, and Pd2(dba)3‚CHCl3 with added phosphine
ligands and p-TsOH are effective for the thiocarbonyl-
ation of acyclic and cyclic allyl alcohols with thiols and
carbon monoxide. These reactions occur in a highly
regioselective manner, at the less-hindered allylic ter-
minal carbon of the substrate, to give the corresponding
thioesters. Not only is this methodology attractive for the
preparation of thioesters and the direct carbonylation of
allyl alcohols, but it also further demonstrates the utility
of transition metal catalysts in the synthesis of chalcogen
compounds.
Mech a n istic Asp ects. A probable mechanism for the
thiocarbonylation of allylic alcohols is outlined in Scheme
2 (illustrated for allyl alcohol). It is well-known that
Pd(OAc)2 is easily reduced to Pd(0) in situ in the presence
of phosphine ligands and carbon monoxide.22 Oxidative
(22) Amatore, C.; J utand, A.; M’Barki, M. Organometallics 1992,
11, 3009. (b) Amatore, C.; Carre, E.; J utand, A.; M′Barki, M. Organo-
metallics 1995, 14, 1818.
(23) Yamamoto, T.; Akimoto, M.; Saito, O.; Yamamoto, A. Organo-
metallics 1986, 5, 1559.

7944 J . Org. Chem., Vol. 63, No. 22, 1998
Xiao and Alper
Sch em e 1
Sch em e 2
at 100-120 °C (oil bath temperature) for 2 to 7 days. After
cooling, excess CO was released, the reaction mixture was
filtered through Florisil, and the solvent was removed by
rotary evaporation. The residue was separated by preparative
TLC (silica gel, eluant: n-hexane/ethyl acetate 10:1).
Exp er im en ta l Section
Gen er a l Meth od s.6a Prior to use, THF, DME, and ether
were distilled from sodium benzophenone ketyl while CH2Cl2
and toluene were distilled from CaH2 under N2. All thiols and
allylic alcohols were purchased from Aldrich and were used
as received. Allyl carbonates (4a 24 and 1925) and phosphate
P h en yl 4-m eth yl-3-p en ten eth ioa te (3a ): oil; IR (neat)
1
1708 cm-1 (CdO); H NMR (200 MHz, CDCl3) δ 1.70 (s, 3H),
(4b)26 and Pd2(dba)3‚CHCl3 were prepared according to the
27
1.78 (s, 3H), 3.35 (d, 2H, J ) 7.4 Hz), 5.36 (t, 1H, J ) 7.4 Hz),
7.30-7.49 (m, 5H); 13C NMR (50 MHz, CDCl3) δ 18.10, 25.76,
43.10, 115.10, 127.76, 128.68, 129.07, 133.27, 137.82, 196.36;
MS (EI) m/z 206 (M+); HRMS calcd for C12H14OS 206.0765,
found 206.0790. Anal. Calcd for C12H14OS: C, 69.86; H, 6.84.
Found: C, 69.82; H, 6.90.
reported procedure.
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed Th io-
ca r bon yla tion of Allylic Alcoh ols w ith Th iols. To a 45 mL
Parr autoclave fitted with a glass liner and stirring bar was
added Pd(OAc)2 (0.06 mmol), PPh3 (0.24 mmol), p-TsOH (0.1
mmol), allylic alcohol (2.0 mmol), thiol (2.0 mmol), and dry
CH2Cl2 (10 mL). The CO line was flushed three times with
CO, the autoclave was filled and vented three times with CO
to displace the air, and subsequently the pressure was
increased to 400 psi. The mixture was stirred in the autoclave
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: Characterization
data for all products (4 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
(24) Tsuji, J .; Shimizu, I.; Minami, I.; Ohashi, Y.; Sugiura, T.;
Takahashi, K. J . Org. Chem. 1985, 50, 1523.
(25) Tsuji, Y.; Yamada, N.; Tanaka, S. J . Org. Chem. 1993, 58, 16.
(26) Tanigawa, Y.; Nishimura, K.; Kawasaki, A.; Murahashi, S.
Tetrahedron Lett. 1982, 23, 5549.
(27) Ukai, T.; Kawazura, H.; Shii, Y. J . Organomet. Chem. 1974,
65, 253.
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