changed. The molar ratio of palladium/phosphine had a sig-
ed hydroxy group was tolerated under the reaction condi-
tions (Table 2, entry 9).
A proposed mechanism for the palladium-catalyzed addi-
tion of 2a to alkynes 1a is illustrated in Scheme 2. Oxidative
addition of 2a onto zero-valent palladium would afford al-
kynylpalladium phenylthiolate A by selective cleavage of
[11]
nificant influence on yield, and a ratio of 1:2 was the best.
Pd (dba) ] was the best precursor, and palladium(II) com-
[
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
2
3
plexes, such as Pd ACHTUNGTRENNUNG( OAc) , were much less active.
2
[9a]
In analogy with our previous report, the triisopropylsil-
yl group of 2a was essential to attain satisfactory yields. The
reactions of the triethylsilyl analog 2b and the tert-butyldi-
methylsilyl analog 2c furnished the corresponding products
3
ab and 3ac in lower yields (Table 1, entries 2 and 3). We
assume that the fairly large triisopropylsilyl group would
play an important role to sterically prevent the CÀC triple
bond of 2 from undergoing undesired side reactions. Similar
trends were observed in the reactions of alkyl- and aryl-sub-
stituted 2 (2d vs. 2 f and 2e vs. 2g). In particular, the mesi-
tyl-substituted alkynyl sulfide 2d was converted into the cor-
responding adduct in good yield (Table 1, entry 4). The me-
sityl group would more effectively shield the adjacent triple
bond than the tert-butyl, phenyl, and hexyl groups. Triiso-
propylsilyl protection is necessary for 2 as the silyl group
can be subjected to a wide range of useful transformations,
whereas the mesityl group is virtually useless.
A variety of terminal alkynes efficiently underwent the
palladium-catalyzed addition reaction (Table 2). The elec-
tron-deficient arylacetylenes underwent the addition to yield
product 3ba in 56% yield (Table 2, entry 1). Exceptionally,
Scheme 2. A proposed mechanism.
tricyclohexylphosphine (PCy ) proved to be the best ligand
3
for the reactions of phenylacetylene 1a and para-trifluoro-
[11]
[12]
methylphenylacetylene 1b (Table 2, entries 2 and 3). The
reaction of para-chlorophenylacetylene 1c provided the cor-
responding adduct in good yield, thus leaving the chloro
moiety intact (Table 2, entry 4). The acceptor acetylenes are
not limited to arylacetylenes. 1,3-Enyne 1e also underwent
the reaction to yield the corresponding 3,5-dien-1-yne 3ea
the C(sp)ÀS bond.
The selective cleavage would result
from the favorable coordination of the alkyne moiety of 2a
to the palladium center prior to the oxidative addition.
[13]
Subsequent regio- and stereoselective insertion of alkyne 1a
into the PdÀS bond would occur to yield alkenylalkynylpal-
ladium B. B would be selectively formed by the migration
of the phenylthio group onto the alkyne with the triphenyl-
phosphine-coordinated bulkier palladium bound at the steri-
cally less hindered terminal carbon. Reported stoichiometric
investigations of the insertion of alkynes into a sulfur–metal
(
Table 2, entry 6). Although aliphatic alkynes such as 1-
octyne (1 f) participated in this reaction (Table 2, entry 7),
tert-butylacetylene (1g) was less reactive probably owing to
its steric bulkiness (Table 2, entry 8). Notably, an unprotect-
[14]
bond are suggestive of this mechanism although the path-
way through alkynylpalladation of alkyne instead of the thi-
opalladation would be also conceivable. Finally, reductive
elimination proceeds to furnish the alkynylthiolation prod-
uct and generates the initial palladium complex.
[15]
Table 2. Palladium-catalyzed addition of triisopropylsilylethynyl phenyl
[
a]
sulfide (2a) to terminal alkynes.
Attempted alkynylthiolation of an internal alkyne, instead
of terminal alkynes, resulted in very low yield [Scheme 3,
Eq. (1)]. The sterically hindered CÀC triple bond of an in-
ternal alkyne would hamper the insertion step. In order to
accelerate the slow, presumably rate-determining, bimolecu-
lar elementary reaction, the same reaction was investigated
at higher temperatures in higher concentrations of alkyne.
After extensive screening of reaction conditions, we were
glad to find that treatment of 2a with 4-octyne (1i, 8 equiv)
at 1308C for 24 hours without using any solvents afforded
the corresponding (Z)-1-phenylthio-1,3-enyne 3ia in 64%
yield [Scheme 3, Eq. (2)]. When less volatile 6-dodecyne
Entry
1
1
R
3
Yield [%]
1b
1a
1b
1c
1d
1e
1 f
1g
1h
p-CF
Ph
p-CF
p-Cl-C
2-Naphthyl
CH =CMe
nHex
tBu
3
3
-C
-C
6
H
H
4
4
3ba
3aa
3ba
3ca
3da
3ea
3 fa
3ga
3ha
56
88
89
62
81
69
88
41
84
[
b]
2
3
4
5
6
7
8
9
[
b]
6
6 4
H
2
HO
2 9
ACHTUNGRTNNGE(U CH )
(
1j, 4 equiv) was used at 1508C, the target adduct 3ja was
[
(
(
a] Conditions:
0.0125 mmol), PPh
0.050 mmol) was used.
1
(0.50 mmol),
(0.050 mmol), toluene (2 mL). [b] PCy
2a
(0.60 mmol),
[Pd
2
A
H
U
G
R
N
U
G
3
]
obtained in a higher yield of 73%. It is of note that the reac-
3
3
Chem. Asian J. 2011, 6, 3190 – 3194
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
3191