Transition-metal-catalyzed regioselective aroyl- and trifluoro- acetylthiolation of alkynes using thioesters

Article abstract of DOI:10.1039/b900492k

Intermolecular CO-retained carbothiolation of alkynes using thioesters took place to afford β-SR substituted enone derivatives; the choice of catalyst (Pd(dba)₂-dppe) and the introduction of a CF₃ group into the thioesters are the key to achieving the transformation. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b900492k

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Transition-metal-catalyzed regioselective aroyl- and
trifluoro-acetylthiolation of alkynes using thioestersw
Yasunori Minami, Hitoshi Kuniyasu,* Kiyoshi Miyafuji and Nobuaki Kambe*
Received (in Cambridge, UK) 9th January 2009, Accepted 18th March 2009
First published as an Advance Article on the web 9th April 2009
DOI: 10.1039/b900492k
Intermolecular CO-retained carbothiolation of alkynes using
thioesters took place to afford b-SR substituted enone deriva-
tives; the choice of catalyst (Pd(dba)2–dppe) and the intro-
duction of a CF3 group into the thioesters are the key to
achieving the transformation.
Table 1 The effects of ligands under the Pd-catalyzed reaction of 1a
with 2aa
The development of efficient transition-metal-catalyzed
carbon–heteroatom bond-forming reactions has been one of
the most important subjects in synthetic chemistry. An
important example would be the addition reactions of carbon–
heteroatom bonds across C–C unsaturated bonds that form
new carbon–carbon bonds in a single procedure. A wide range
of substrates having C–S, C–Se, C–N, C–Si, C–Sn and C–B
bonds were employed for this purpose.1
Entry
Ligand
3a (%)
4a (%) (E/Z)
5a (%)
6a (%)
b
1
2
3
4
5
6
7
8
9
PPh3
None
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
75f
10 (61/39)
n.d.
9 (65/35)
n.d.
n.d.
1 (100/0)
6 (50/50)
8 (50/50)
6 (33/67)
53 (67/33)
78 (61/39)f
14 (0/100)
16(61/39)
15 (61/39)
8 (0/100)
50
n.d.
34
2
8
22
30
16
17
12
n.d.
n.d.
30
36
n.d.
20
n.d.
22
n.d.
5
38
22
16
6
14
16
n.d.
25
P(p-tolyl)3
P(o-tolyl)3
P(2-furyl)3
PCy3
P(n-Bu)3
PMe2Ph
dppm
dppe
dppe
dppe
dppp
We have already reported the Pt(PPh3)4-catalyzed inter-
molecular regio- and stereoselective decarbonylative arylthiolation
and arylselenation of alkynes HCRCR (1) by R1C(O)YR2
(2, R1 = aryl; Y = S, Se) (Scheme 1, left)1a,c to produce
vinylsulfides and selenides (3). Disclosed herein are the inter-
molecular regioselective aroylthiolation (R1 = aryl; Y = S) and
trifluoroacetylthiolation (R1 = CF3; Y = S) of 1 to afford enone
derivatives (4) (Scheme 1, right).2
10
11cde
12cg
13
14
15hi
The attempted reaction of 1-octyne (1a; R = n-C6H13,
1.2 mmol) with Ar1C(O)SAr2 (2a; Ar1 = p-tolyl, Ar2
dppb
Pt(PPh3)4
35
n.d.
=
p-MeOC6H4, 1.0 mmol) in the presence of Pd(PPh3)4
(0.05 mmol) under toluene reflux gave an aroylthiolation
product (Ar1C(O))(H)CQC(n-C6H13)(SAr2) (4a) in 10% yield
(E/Z = 61/39) together with 50% of an Ar1SAr2 (5a)3 and
20% of a hydrothiolation product H2CQC(n-C6H13)(SAr2)
(6a)4 (entry 1, Table 1). The effects of various ligands were
examined with Pd(dba)2 as a palladium(0) source. No reaction
occurred without an additional ligand (entry 2, Table 1). The
a
Unless otherwise noted, the solution of 1a (1.2 mmol), 2a (1.0 mmol),
Pd(dba)2 (0.05 mmol), and ligand (0.12 mmol for entries 3–8,
0.06 mmol for entries 9–14) was stirred under toluene (0.5 mL) reflux
for 12 h. Yields were determined by 1H NMR spectroscopy.
b
c
Pd(PPh3)4 (0.05 mmol) as
e
a
catalyst. Under benzene reflux.
d
20 h. The formation of Ar1C(O)CRCR was detected in 10%
yield. Isolated yield. 1 h. Pt(PPh3)4 (0.05 mmol) as a catalyst.
f
g
h
i
13 h. dba = dibenzylideneacetone, tolyl = methylphenyl, Cy =
cyclohexyl, dppm = 1,1-bis(diphenylphosphino)methane, dppe = 1,2-
bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)-
propane, dppb = 1,4-bis(diphenylphosphino)butane.
reactions using other monodentate ligands such as P(p-tolyl)3,
P(o-tolyl)3, P(2-furyl)3, PCy3, P(n-Bu)3 and PMe2Ph also were
not satisfactory: 5a and 6a were generated as major products
(entries 3–8, Table 1). On the other hand, the reaction with dppe
afforded 4a in 53% (E/Z = 67/33) yield with 12% of 5a and
14% of 6a (entry 10, Table 1). Gratifyingly, when the reaction
was carried out under benzene reflux, the formation of 5a was
suppressed and 4a was obtained in 78% yield (E/Z = 61/39)
with 10% of Ar1C(O)CRCR after 20 h (entry 11, Table 1).
When conducted for a short period of time (1 h), the reaction
selectively provided Z-4a (14%), which indicated that cis-
addition kinetically took place (entry 12, Table 1).5,6 The employ-
ment of other bidentate ligands such as dppm, dppp and dppb
Scheme 1 Decarbonylative vs. CO-retained carbothiolation of alkynes
(1) by thioesters (2).
Department of Applied Chemistry Graduate School of Engineering,
Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan.
E-mail: kuni@chem.eng.osaka-u.ac.jp; Fax: +81 6 6879 7390;
Tel: +81 6 6879 7389
w Electronic supplementary information (ESI) available: Typical
experimental procedures, and analytical data for the products. See
DOI: 10.1039/b900492k
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Table 2 Pd–dppe-catalyzed aroylthiolation of 1 by 2a
Table 3 Reaction of 1a with 7aa
Entry
Catalyst
Solvent
8a (%) (E/Z)
1b
2
3
4
Pd(dba)2–dppec
Pd(dba)2–dppec
Pt(PPh3)4
Pt(PPh3)4
Pt(PPh3)4
Benzene
Xylene
Xylene
Benzene
Toluene
Xylene
Xylene
Xylene
8 (64/36)d
15 (75/25)e
78 (82/18)f
8 (82/18)
39 (79/21)
15 (41/59)
7 (72/28)h
n.d.
Entry
1
2
Ar1
Ar2
4
(%) (E/Z)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2f
2g
2h
2i
p-Tolyl
p-Tolyl
p-Tolyl
p-Tolyl
Ph
p-FC6H4
3-Pyridyl
2-Furyl
p-Tolyl
t-Bu
p-Tolyl
p-Tolyl
p-Tolyl
p-Tolyl
p-Tolyl
p-Tolyl
PhC(O)SePh
p-MeOC6H4
Ph
p-FC6H4
p-NO2C6H4
Ph
p-Tolyl
p-Tolyl
p-Tolyl
CH2Ph
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
78 (61/39)
53 (72/28)
46 (72/28)
n.d.
66 (74/26)
57 (74/26)
74 (72/28)
55 (75/25)
10 (74/26)c
n.d.
70 (67/33)
50 (72/28)
80 (75/25)
66 (73/27)
65 (53/47)
40 (25/75)
3 (1/499)c
5
6g
7
Pt(PPh3)4
Pd(PPh3)4
Ni(cod)2–PPh3
i
8
a
Unless otherwise noted, the solution of 1a (0.75 mmol), 7a
(0.5 mmol), catalyst (0.025 mol) and solvent (0.5 mL) was stirred
under reflux for 10 h. Yields were determined by 1H NMR spectro-
b
c
scopy. 20 h. Pd(dba)2 (0.025 mmol) and dppe (0.03 mmol).
d
(CH3)(p-MeC6H4S)CC(H)(n-C5H11) (9a) was obtained in 16%
2j
2a
2a
2a
2a
2a
2a
2k
e
yield. 9a was obtained in 31% yield. Isolated yield. 30 min.
f
g
h
i
9a was obtained in 52% yield. Ni(cod)2 (0.025 mmol) and PPh3
(0.1 mmol).
1g
1a
Table 4 Pt-catalyzed trifluoroacetylthiolation of 1 by 7a
a
1 (1.2 mmol), 2 (1.0 mmol), Pd(dba)2 (0.05 mol) and dppe (0.06 mol)
b
under benzene (0.5 mL) reflux for 20 h. Isolated yield. NMR yield.
c
significantly decreased the yield of 4a (entries 9,13,14, Table 1).7
It must be noted that 3a, the product of Pt(PPh3)4-catalyzed
decarbonylative arylthiolation (entry 15, Table 1), was not
detected under Pd-catalysis (entries 1–14, Table 1). No formation
of 4a was confirmed with Pt[(CH2QCHSiMe2)2O], Ni(cod)2
(cod = cyclooctadiene) or RhCl(cod)2 in the presence of dppe.
The results of the Pd–dppe-catalyzed aroylthiolation of
alkyne (1) by Ar1C(O)SAr2 (2) are summarized in Table 2.
The reaction with 2a (Ar2 = p-MeOC6H4) afforded a better
yield of desired 4 (78% of 4a, entry 1, Table 2) compared to
the reactions with 2b (Ar2 = Ph, 53% of 4b, entry 2 Table 2)
and 2c (Ar2 = p-FC6H4, 46% of 4c, entry 3, Table 2). In sharp
contrast to the Pt-catalyzed decarbonylative arylthiolation, no
reaction took place when a thioester with Ar2 = p-NO2C6H4
(2d) was employed (entry 4, Table 2). Phenyl and p-FC6H4
groups at Ar1 somewhat lowered the reactivity (entries 5–6
Entry
1
7
8
(%) (E/Z)b
1
2
3
4
5
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
7a (R0 = p-tolyl)
7d (R0 = p-MeOC6H4)
7e (R0 = Ph)
7f (R0 = p-ClC6H4)
7g (R0 = CH2Ph)
7h (R0 = n-C10H21
7e (R0 = Ph)
7e (R0 = Ph)
7e (R0 = Ph)
7e (R0 = Ph)
8a
8d
8e
8f
8g
8h
8i
8j
8k
8l
78 (82/18)
64 (89/11)
82 (76/24)
69 (66/34)
51 (70/30)
41 (82/18)
83 (71/29)
79 (71/29)
87 (74/26)
70 (64/36)
6
)
7c
8c
9c
10
a
Unless otherwise noted, 1 (0.75 mmol), 7 (0.5 mmol), Pt(PPh3)4
b
(0.025 mmol), and xylene (0.5 mL) under reflux for 10 h. Isolated
c
yield. Xylene (2.0 mL).
Table 2). Thioesters 2g (Ar1 = 3-pyridyl) and 2h (Ar1
=
(1a, 0.75 mmol) with CF3C(O)SC6H4p-Me (7a; X = F,
0.5 mmol) in the presence of Pd–dppe under benzene and
xylene reflux both gave trifluoroacetylthiolation product 8a in
low yields; (CH3)(p-MeC6H4S)CQC(H)(n-C5H11) (9a) derived
from 6a was generated as a major product (entries 1 and 2,
Table 3). Intriguingly, the reaction using Pt(PPh3)4 as a
catalyst under xylene reflux conditions remarkably improved
the yield of 8a (78%, E/Z = 82/18),8,9 compared to benzene or
toluene reflux conditions (entries 3–5, Table 3). Intercepting
the reaction at the early stage (E/Z = 41/59 after 30 min) also
indicates the involvement of cis-addition (Entry 6). Inferior
catalyses were shown by Pd(PPh3)4 (entry 7, Table 3) and
Ni(cod)2–4PPh3 (entry 8, Table 3). On the other hand, the
reaction employing CH3C(O)SC6H4p-Me (7b; X = H) and
CCl3C(O)SC6H4p-Me (7c; X = Cl) in the presence of
Pt(PPh3)4 hardly produced the corresponding 8b and 8c.
2-furyl) reacted with 1a to furnish the corresponding adducts
4g and 4h in 74% and 55% yields, respectively (entries 7 and 8,
Table 2). On the other hand, a thioester with a benzyl group
on sulfur (2i) gave a low yield of 4i (10%, entry 9, Table 2),
and the reaction with t-BuC(O)SC6H4p-OMe (2j) did not
produce 4j (entry 10, Table 2). Terminal alkynes having
chlorine (1b), a cyano group (1c), a methoxy carbonyl group
(1d), a cyclopentyl group (1e), (CH2)2CHMe2 (1f) and a
phenyl group (1g) all underwent an aroylthiolation by 2a to
afford 4k–p in moderate to good yields (entries 11–16, Table 2).
The reactions of 1a with a selenoester (2k; PhC(O)SePh) took
place to provide the aroylselenation product 4q, albeit in a
very low yield (entry 17, Table 2).
Next, the reactions with CX3-substituted thioesters
(7; CX3C(O)SAr) were examined. The treatment of 1-octyne
ꢀc
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N. Kambe, Org. Lett., 2008, 10, 101; (d) M. Toyofuku, S. Fujiwara,
T. Shin-ike, H. Kuniyasu and N. Kambe, J. Am. Chem. Soc., 2008,
130, 10504; (e) V. P. Ananikov, N. V. Orlov, M. A. Kabeshov,
I. P. Beletskaya and Z. A. Starikova, Organometallics, 2008, 27, 4056;
(f) K. Yamashita, H. Takeda, T. Kashiwabara, R. Hua, S. Shimada
and M. Tanaka, Tetrahedron Lett., 2007, 48, 6655; (g) M. Toyofuku,
E. Murase, S. Fujiwara, T. Shin-ike, H. Kuniyasu and N. Kambe,
Org. Lett., 2008, 10, 3957; (h) Y. Kajita, S. Matsubara and
T. Kurahashi, J. Am. Chem. Soc., 2008, 130, 6058; (i) Y. Nakao,
J. Satoh, E. Shirakawa and T. Hiyama, Angew. Chem., Int. Ed., 2006,
45, 2271; (j) Y. Shi, S. M. Peterson, W. W. Haberaecker III and
S. A. Blum, J. Am. Chem. Soc., 2008, 130, 2168; (k) M. Suginome,
A. Yamamoto and M. Murakami, Angew. Chem., Int. Ed., 2005, 44,
2380; (l) M. Suginome, M. Shirakura and A. Yamamoto, J. Am.
Chem. Soc., 2006, 128, 14438.
2 For related transition-metal-catalyzed CO-retained additions, see:
(a) R. Hua, H. Takeda, S. Onozawa, Y. Abe and M. Tanaka,
J. Am. Chem. Soc., 2001, 123, 2899; (b) ref. 1g; (c) T. Kashiwabara,
K. Kataoka, R. Hua, S. Shimada and M. Tanaka, Org. Lett., 2005,
7, 2241; (d) R. Hua, S. Onozawa and M. Tanaka, Chem.–Eur. J.,
2005, 11, 3621; (e) T. Kashiwabara, K. Fuse, R. Hua and
M. Tanaka, Org. Lett., 2008, 10, 5469; (f) E. Shirakawa,
K. Yamasaki, H. Yoshida and T. Hiyama, J. Am. Chem. Soc.,
1999, 121, 2899.
Scheme 2 A plausible mechanism for the transition-metal-catalyzed
aroyl- and trifluoroacetylthiolation of alkynes (1) by thioesters (2 and 7).
The results of Pt-catalyzed trifluoroacetylthiolation of
alkyne (1) by CF3C(O)SR0 are shown in Table 4. Some
substituents in aryl-S groups (7d; R0 = p-MeOC6H4, 7e;
R0 = Ph, 7f; R0 = p-ClC6H4) hardly interfered with the
addition reactions (entries 2–4, Table 4). Unlike the case of
the reaction with 2, thioesters possessing an sp3-carbon
substituent such as benzyl (7g) and n-decyl groups (7h) on
sulfur also reacted with 1a to produce 8g and 8h in 51% and
41% yields, respectively (entries 5 and 6, Table 4). Addition of
7e to alkynes 1b–1e proceeded to afford the product 8i–l in
good yields (entries 7–10, Table 4). Contrary to the case of
Pt-catalyzed decarbonylative carbothiolation, the products of
decarbonylative trifluoromethylthiolation were not detected in
all cases even with the same catalyst.
3 For catalytic decarbonylation of thioesters, see: (a) K. Osakada,
T. Yamamoto and A. Yamamoto, Tetrahedron Lett., 1987, 28,
6321; (b) T. Kato, H. Kuniyasu, T. Kajiura, Y. Minami,
A. Ohtaka, M. Kinomoto, J. Terao, H. Kurosawa and
N. Kambe, Chem. Commun., 2006, 868.
4 For Pd- and Pt-catalyzed hydrothiolation of alkynes, see:
(a) H. Kuniyasu, A. Ogawa, K. Sato, I. Ryu, N. Kambe and
N. Sonoda, J. Am. Chem. Soc., 1992, 114, 5902; (b) J.-E. Backvall
¨
and A. Ericcson, J. Org. Chem., 1994, 59, 5850; (c) A. Ogawa, T. Ikeda,
K. Kimura and T. Hirao, J. Am. Chem. Soc., 1999, 121, 5108.
5 The stereochemistry of E-4a and Z-4a was determined by NOE
experiments between vinyl and allyl protons.
A plausible reaction mechanism of the present regioselective
CO-retained addition of thioesters (2 or 7; R1C(O)SR2
(R1 = aryl or CF3)) to alkynes (1; HCRCR) was depicted
in Scheme 2. The oxidative addition of 2 or 7 to M(0)Ln
(MLn = Pd(dppe) or Pt(PPh3)n) complex triggers the reaction
to afford MLn[C(O)R1](SR2) (10).10 Subsequent regio- and
stereoselective insertion of alkyne 1 into the S–M bond of 10
generates MLn[C(O)R1][(Z)–CHQC(SR2)(R)] (11),11 which
can react with another 1 to produce 6 and Ar1C(O)CRCR
as by-products. Finally, the C–C bond-forming reductive
elimination of Z-4 or Z-8 from 11 with regeneration of
M(0)Ln completes the catalytic cycle. Z-to-E isomerisation
of the product can be explained as follows: the oxidative
addition of a vinyl C–S bond of Z-isomer to a M(0)Ln complex
to produce MLn[(Z)–C(R)QC(H){C(O)R1}](SR2) (Z-12),12
Z-to-E isomerization of 12,13 and the reductive elimination
of E-4 and E-8 from E-12.
6 The treatment of isolated Z-4a with 2a and a catalytic amount of
Pd(dba)2 (5 mol%), dppe (6 mol%) and 1.6 equivalents of 1a led to
Z-to-E isomerization (E/Z = 61/39), while no isomerization took
place without 1a under otherwise identical conditions. This result
suggests that alkyne-coordinated Pd-complex induce the Z-to-E
isomerization.
7 While Pd(0)–dppp and Pd(0)–dppb catalyzed the decarbonylation
of 2a to provide 5a in 12% and 36% yield, respectively, the
decarbonylation hardly took place with Pd(0)–dppe (4%).
On the other hand, the reaction between p-MeC6H4I and
NaSC6H4p-OMe catalyzed by Pd(dba)2 (5 mol%)–dppe (6 mol%)
produced 5a in 83% yield. These facts indicated that dppe
suppresses the decarbonylation from thiocarbonyl complex, see:
G. P. C. M. Dekker, C. J. Elsevier, K. Vrieze and P. W. N. M.
Leeuwen, Organometallics, 1992, 11, 1598.
8 The stereochemistry of E-8a and Z-8a was determined by NOE
experiments between vinyl and allyl protons, and the regio-
chemistry of E-8a was determined by 1H-13C HMBC experiments.
9 See the ESI for further details.
10 For the oxidative addition of thioesters to platinum(0) complexes,
see: Y. Minami, T. Kato, H. Kuniyasu, J. Terao and N. Kambe,
Organometallics, 2006, 25, 2949, and references therein.
11 For stoichiometric insertion of alkynes into the S–M bond, see:
(a) K. Sugoh, H. Kuniyasu and H. Kurosawa, Chem. Lett., 2002,
31, 106; (b) H. Kuniyasu, F. Yamishita, J. Terao and N. Kambe,
Angew. Chem., Int. Ed., 2007, 46, 5929; (c) H. Kuniyasu,
K. Takekawa, F. Yamashita, K. Miyafuji, S. Asano, Y. Takai,
A. Ohtaka, A. Tanaka, K. Sugoh, H. Kurosawa and N. Kambe,
Organometallics, 2008, 27, 4788.
12 We have reported that an anion stabilizing group on the b-carbon
of the C–S bond of vinylsulfide promotes the oxidative addition to
Pt(0), see: (a) H. Kuniyasu, A. Ohtaka, T. Nakazono,
M. Kinomoto and H. Kurosawa, J. Am. Chem. Soc., 2000, 122,
2375; (b) ref. 1d.
In conclusion, the present study substantiated that the
decarbonylative arylthiolation of alkynes by thioesters is con-
verted into CO-retained, atom-economical, regioselective carbo-
thiolation simply by changing the catalysts from Pt(PPh3)4 to
Pd(dba)2–dppe or by employing CF3C(O) as a carbon function-
ality of thioesters even under Pt(PPh3)4-catalyzed conditions.
Our efforts will continue to focus on the extension of the present
CO-retained carbothiolation to other addition systems.
Notes and references
13 For isomerization of the alkenyl transition metal complexes, see:
(a) K. A. Brady and T. A. Nile, J. Organomet. Chem., 1981, 206,
299; (b) I. Ojima, N. Clos, R. J. Donovan and P. Ingallina,
Organometallics, 1990, 9, 3127; (c) M. Murakami, T. Yoshida,
S. Kawanami and Y. Ito, J. Am. Chem. Soc., 1995, 117, 6408.
1 For a review of carbochalcogenation of alkynes, see: (a) H. Kuniyasu
and N. Kambe, Chem. Lett., 2006, 35, 1320; For recent examples,
see: (b) R. Hua, H. Takeda, S. Onozawa, Y. Abe and M. Tanaka,
Org. Lett., 2007, 9, 263; (c) F. Yamashita, H. Kuniyasu, J. Terao and
ꢀc
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