Pd-catalyzed thiocarbamoylation of terminal alkynes with sulfenamide and carbon monoxide

Article abstract of DOI:10.1016/j.tetlet.2005.12.016

Regio- and stereoselective thiocarbamoylation of terminal alkynes successfully took place using 2,4,5-tri-Cl-C₆H₂SNEt ₂ as a reaction substrate and PdCl₂(PPh₃) ₂/PPh₃/n-Bu_4<

Full text of DOI:10.1016/j.tetlet.2005.12.016

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1141–1144
Pd-catalyzed thiocarbamoylation of terminal alkynes
with sulfenamide and carbon monoxide
Hitoshi Kuniyasu,* Tomohiro Kato, Shigehito Asano, Jia-Hai Ye,
Takumi Ohmori, Masaki Morita, Hiroshi Hiraike, Shin-ichi Fujiwara, Jun Terao,
Hideo Kurosawa and Nobuaki Kambe*
Department of Molecular Chemistry & Frontier Research Center, Graduate School of Engineering, Osaka University, Suita,
Osaka 565-0871, Japan
Received 15 November 2005; revised 1 December 2005; accepted 5 December 2005
Available online 28 December 2005
Abstract—Regio- and stereoselective thiocarbamoylation of terminal alkynes successfully took place using 2,4,5-tri-Cl-C6H2SNEt2
as a reaction substrate and PdCl2(PPh3)2/PPh3/n-Bu4NCl as a catalyst system.
Ó 2005 Elsevier Ltd. All rights reserved.
Various types of S–X activations (X: element or func-
tional group) with the aid of transition metal complexes
have been accomplished in the past decade.1 On the
other hand, sulfenamides (R1SNR2R3; 1), which possess
S–N bond with unique Sd+ and NdÀ polarity have been
utilized as reagents to introduce an R1S or an R2R3N
group in organic synthesis, additives in rubber industry,
and insecticides and fungicides in the agrichemical
industry.2 In 1999, we have succeeded in demonstrating
that azathiolation of CO by 1 was smoothly catalyzed
by Pd-complex to afford thiocarbamate (R1SC(O)-
NR2R3; 2), showing that 1 had great potential for the
substrate of transition metal-catalyzed S–X activation.3
Since then, Kondo and Mitsudo et al. have reported that
Ru-complexes smoothly catalyzed the regio- and stereo-
selective azathiolation of alkynes by 1.4 Furthermore,
Meyer and Knapton have reported that Pd-catalyzed
regio- and stereoselective selenocarbamoylation of
terminal alkynes (3) was achieved using 1, CO, and
(PhSe)2.5 Although this reaction is very fascinating,
since PhSe and R2R3NC(O) groups were simultaneously
introduced into alkynes by a single process, the forma-
tion of many by-products remains as a significant draw-
back with respect to the atom economy. As to the
intramolecular Pd-catalyzed thio- and selenocarbamoyl-
ation, we have recently found that the desired transfor-
mation was facilely realized by Pd(PPh3)4 as a catalyst
using thio- and selenocarbamate.6
Herein, we wish to report on the efficient intermolecular
Pd-catalyzed thiocarbamoylation of 3 employing 1 and
CO as reaction substrates under dichalcogenide-free
reaction conditions. First, we have examined the reaction
of PhSNEt2 (1a, 1.2 mmol) with 1-octyne (3a, 1.0 mmol)
in pressurized CO (20 kg/cm2) using [Pd(SPh)2(PPh3)]2
(4a, 0.01 mmol) and PPh3 (0.02 mmol) as catalysts in
CH3CN (0.5 mL) at 120 °C for 3 h (entry 1 of Table 1).
Although complex 4a has been proved to be an active
catalyst for the azathiolation of CO,3 the conversion
of 1a was low (11%) and anticipated thiocarbamoylation
product 5a was produced only in 4% yield with E/
Z = 25/75 together with 6% of thiocarbamate 2a.7
Although intramolecular thiocarbamoylation by thio-
carbamate was successfully catalyzed by Pd(PPh3)4
(4b),6 the yield of 5a was poor (5%) with low conversion
of 1a (30%) in this reaction system (entry 2). The
employment of PdCl2(PPh3)2 (4c) with an expectation
of better carbonylative addition to alkyne also resulted
in a miserable result (entry 3).8 Then the effects of a vari-
ety of catalysts, ligands, solvents, and additives were
next examined. Among those screened,9 the reaction
performed using 4c (2 mol %) as a catalyst precursor,
PPh3 (0.04 mmol) and n-Bu4NCl (0.08 mmol) as addi-
tives in CH3CN (0.5 mL) and CO (20 kg/cm2) resulted
in the best yield of 5a (57%) (entry 4).
*
Corresponding author. Tel.: +81 1668 797389; fax: +81 1668
797390; e-mail: kuni@chem.eng.osaka-u.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.12.016

1142
H. Kuniyasu et al. / Tetrahedron Letters 47 (2006) 1141–1144
Table 1. Pd-catalyzed thiocarbamoylation of 3a by 1aa
R
NEt2
catalyst (4)
PPh3
PhS
O
5a
salt
+
+
R
PhSNEt2
CO
CH3CN
O
R = n-C6H13
1a
3a
PhS
NEt2
2a
Entry
4
PPh3 (mmol)
Saltb
5a (%)c E/Z
2a (%)c
1
2
3
4
5
6
7
8
9
[Pd(SPh)2(PPh3)]2] 4a
Pd(PPh3)4 4b
PdCl2(PPh3)2 4c
4c
4c
4c
4c
4c
4c
0.02
—
—
0.04
0.04
—
0.04
0.04
0.04
—
—
—
4 (25/75)
5 (20/80)
6
7
11 (18/82)
57d (41/59)
34 (34/66)
27 (44/56)
31 (24/76)
7 (29/71)
50
37
25
45
31
80
80
n-Bu4NCl
—
n-Bu4NCl
NaCl
Et4NCl
CaCl2
17 (29/71)
a Conditions: 1a (1.2 mmol), 3a (1.0 mmol), 4 (0.02 mmol of Pd), CO (20 kg/cm2), and CH3CN (0.5 mL) at 120 °C for 3 h.
b 0.08 mmol.
c NMR yield.
d Isolated yield.
Elimination of either n-Bu4NCl or PPh3 decreased the
yields of 5a (entries 5 and 6). On the other hand, the
employment of NaCl, Et4NCl, and CaCl2 instead of
n-Bu4NCl also brought about lower yield of 5a (entries
7–9). Although the yield of 5a was increased, unlike
the case of selenocarbamoylation,5 a mixture of stereo-
isomers (E/Z = 41/59) was generated and the yield of
5a was still unsatisfactory.
ortho position showed a more remarkable effect.
Although 2-Me (1c) hampered the formation of desired
5c, the substrate with 2-Cl (1e) afforded 5e in 73% yield
with E/Z = 18/82 (entries 3 and 5). Moreover, it was
found that the reaction using 2,4,5-tri-Cl-C6H2SNEt2
(1g) produced the desired 5g in 86% isolated yield with
high Z-selectivity (E/Z = 2/98) (entry 7).10 On the other
hand, di-Cl substituents such as 2,4, 2,5, 2,6-di-Cl were
less effective than 1g for the formation of 5 (entries 8–
10). The results of Pd-catalyzed thiocarbamoylation of
some terminal alkynes with 1g and CO under the present
optimized conditions were summarized in Table 3.
To anticipate improvement of the efficiency of the inter-
molecular thiocarbamoylation, the effects of substitu-
ents in Ar of 1 were next examined (Table 2). Clearly,
electron-donating groups significantly suppressed the
thiocarbamoylation, while electron-withdrawing groups
hardly improved the yield of 5 (entries 2, 4, and 6). It is
worth noting that the introduction of substituents at the
While the Pd-catalyzed selenocarbamoylation was not
applicable to phenyl acetylene (3b) or the alkyne with
a hydroxyl group,5 3b, 4-MeC6H4CCH (3c), and
Table 2. Effect of substituents in 1 on the thiocarbamoylation of 3aa
cat. 4c
PPh3
n-Bu4NCl
ArSNEt2
+
3a + CO
5
CH3CN
1
Entry
Ar
1
Yield of 5 (%)b
(E/Z)
1
2
3
4
5
6
7
8
9
10
Ph
4-MeC6H4
2-MeC6H4
4-ClC6H4
1a
1b
1c
1d
1e
1f
5a
5b
5c
5d
5e
5f
57
20
8
59
73
64
86c
68
61
37
(41/59)
(15/85)
(50/50)
(31/69)
(18/82)
(20/80)
(2/98)
(9/91)
(10/90)
(4/96)
2-ClC6H4
4-CF3C6H4
2,4,5-Tri-Cl-C6H2
2,4,Di-Cl-C6H3
2,5-Di-Cl-C6H3
2,6-Di-Cl-C6H3
1g
1h
1i
5g
5h
5i
1j
5j
a Conditions: 1 (1.2 mmol), 3a (1.0 mmol), CO (20 kg/cm2), 4c (0.02 mmol), PPh3 (0.04 mmol), n-Bu4NCl (0.08 mmol), and CH3CN (0.5 mL) at
120 °C for 3 h.
b NMR yield.
c Isolated yield.

H. Kuniyasu et al. / Tetrahedron Letters 47 (2006) 1141–1144
Table 3. Pd-catalyzed thiocarbamoylation of 3 by 1ga
1143
cat. 4c
PPh3
n-Bu4NCl
+
+
R
CO
1g
5
CH3CN
3
Entry
R
(3)
Isolated yield (%) of 5
(E/Z)
1
2
3
4
5
6
Ph
3b
3c
3d
3e
3f
5k
5l
72
81
86
70
62
64
(3/97)
(6/94)
(0/100)
(17/83)
(8/92)
(0/100)
4-MeC6H4
HO(CH2)3
NC(CH2)3
PhCH2
5m
5n
5o
5p
(Me)2NCH2
3g
Et2N
NEt2
7b
4
4
O
ArS
5q
SAr
O
3h
49 (0/100)
E
E
E
E
3i
8
ArS
NEt2
O
56
E = CO2 Me
(0/100)
5r
a Unless otherwise noted, 1.2 mmol of 1g, 1.0 mmol of 3, 4c (0.02 mmol), PPh3 (0.04 mmol), n-Bu4NCl (0.08 mmol), and CO (20 kg/cm2) in CH3CN
(0.5 mL) at 120 °C for 3 h.
b 2.0 mmol of 1g.
HO(CH2)3CCH (3d) smoothly underwent the thiocarb-
amoylation to give the corresponding b-sulfenyl acryl-
amide derivatives 5k, 5l, and 5m in good yields with
high Z-selectivity (entries 1–3). Other functional groups
such as –CN, –CH2Ph, and –NMe2 were also tolerant
toward the present thiocarbamoylation and double thio-
carbamoylation occurred when 1,7-octadiene (3h) was
employed (entries 4–7). The acetylene (3i) bearing a teth-
ered ene unit underwent chemoselective reaction at the
triple bond (entry 8). A possible reaction pathway of
the present Pd-catalyzed thiocarbamoylation is depicted
in Scheme 1. We wish to propose that the complex with
the formula PdCl(SAr)(PPh3)n (6) be an active catalyst
for intermolecular thiocarbamoylation of terminal alky-
nes 3.11,12 The cis-insertion of 3 into the S–Pd bond
would produce vinylpalladium 7,13 which would resist
the C–Cl bond-forming reductive elimination due to
the thermodynamic disadvantage. The insertion of CO
into the resultant C–Pd bond would follow to afford
acylpalladium 8 and subsequent r-bond metathesis be-
tween Pd–C of 8 and N–S bond of 1 through transition
state 9 to furnish the thiocarbamoylation product 5 with
the regeneration of 6. The roles of addition of n-Bu4NCl
and PPh3 are not clear at the moment but one possibility
is that these additives suppress the formation of catalyt-
ically less active Pd(SAr)2(PPh3)2 and more polymeric
Pd(SAr)2(PPh3)n.
In summary, this letter demonstrated that the intermo-
lecular Pd-catalyzed thiocarbamoylation of terminal
alkynes by sulfenamide and CO was successfully realized
using 2,4,5-tri-Cl-C6H2SNEt2 as the reaction substrate
and PdCl2(PPh3)2/PPh3/n-Bu4NCl as the catalyst sys-
tem. The scope and limitations of the present reaction
system as well as the details about the reaction mecha-
nism are now in progress.
Acknowledgment
Thanks are due to the Instrumental Analysis Center,
Faculty of Engineering, Osaka University, for assistance
in obtaining mass spectra with a JEOL JMS-DX303
instrument.
PdCl(SAr)Ln
6
3
Ar
S
- 5
L = PPh3
R
Et2N
PdClLn
R
ArS
PdClLn
References and notes
7
ArS
O
CO
1. (a) Kuniyasu, H. In Catalytic Heterofunctionalization;
1g
9
R
PdClLn
Togni, A., Grutzmacher, H., Eds.; Wiley-VCH: Wein-
¨
ArS
O
heim, 2001; Chapter 7; (b) Han, L.-B.; Tanaka, M. Chem.
Commun. 1999, 395; (c) Beletskaya, I.; Moberg, C. Chem.
Rev. 1999, 99, 3435; (d) Ogawa, A. In Main Group Metals
in Organic Synthesis; Yamamoto, H., Oshima, K., Eds.;
8
Scheme 1. A proposed reaction pathway of thiocarbamoylation of 3.

1144
H. Kuniyasu et al. / Tetrahedron Letters 47 (2006) 1141–1144
Wiley-VCH: Weinheim; pp 813–866; (e) El Ali, B.; Alper,
(m, 12H), 1.36–1.46 (m, 2H), 2.12 (t, J = 7.6 Hz, 2H), 3.38
(q, J = 7.2 Hz, 2H), 3.45 (q, J = 7.1 Hz, 2H), 6.28 (s, 1H),
7.67 (s, 1H), 7.70 (s, 1H). NOE study: Irradiation of vinyl
singlet at d 6.28 resulted in 2.1% increase at d 2.12
(methylene triplet); 13C NMR (100 M Hz, CDCl3) d 13.3,
14.1, 14.7, 22.5, 28.6, 28.8, 31.4, 36.8, 40.1, 42.6, 118.0,
130.9, 132.6, 133.0, 136.2, 136.8, 149.8, 165.4; IR (NaCl)
2958, 2930, 2857, 1633, 1574, 1434, 1379, 1361, 1315, 1260,
1221, 1151, 1114, 1059, 889, 868, 818 cmÀ1; mass spectrum
(EI) m/e 423 (M+, 13%), 351 (12%), 210 (100%), 100 (8%);
Anal. Calcd for C19H26Cl3NOS: C, 53.97; H, 6.20; N, 3.31.
Found: C, 54.01; H, 6.35; N, 3.35. E-Isomer. Yellow oil;
8.4 mg, 2%, 1H NMR (400 M Hz, CDCl3) d 0.80 (t,
J = 6.8 Hz, 3H), 0.96 (t, J = 7.2 Hz, 3H), 1.05 (t,
J = 7.2 Hz, 3H), 1.08–1.28 (m, 8H), 2.55 (t, J = 7.6 Hz,
2H) 3.13 (q, J = 7.1 Hz, 2H), 3.30 (q, J = 6.9 Hz, 2H),
5.52 (s, 1H), 7.54 (s, 1H), 7.57 (s, 1H); 13C NMR
(100 M Hz,CDCl3) d 13.3, 14.2, 14.4, 22.7, 29.10, 29.13,
31.7, 32.9, 40.0, 42.6, 118.4, 131.1, 131.2, 131.6, 133.8,
136.6, 149.8, 164.8, IR (NaCl) 2930, 2857, 1634, 1435,
1379, 1321, 1259, 1221, 1150, 1116, 1060, 874 cmÀ1; mass
spectrum (EI) m/e 421 (M+, 10%), 351 (9%), 320 (9%), 210
(100%), 100 (17%); exact mass (M+) calcd for
C19H26Cl3NOS; 421.0801 Found; 421.0796.
H. In Handbook of Organopalladium Chemistry for
Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience:
New York, 2002; Chapter VI. 2. 1. 1. 2; (f) Ogawa, A. In
Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York,
2002, Chapter VII. 6; (g) Kondo, T.; Mitsudo, T. Chem.
Rev. 2000, 100, 3205; (h) Ogawa, A. J. Organomet. Chem.
2000, 611, 463.
2. Craine, L.; Raban, M. Chem. Rev. 1989, 89, 689.
3. Kuniyasu, H.; Hiraike, H.; Morita, M.; Tanaka, A.;
Sugoh, K.; Kurosawa, H. J. Org. Chem. 1999, 64, 7305.
4. Kondo, T.; Baba, A.; Nishi, Y.; Mitsudo, T. Tetrahedron
Lett. 2004, 45, 1469.
5. (a) Knapton, D. J.; Meyer, T. Y. J. Org. Chem. 2005, 70,
785; (b) Knapton, D. J.; Meyer, T. Y. Org. Lett. 2004, 6,
687.
6. Toyofuku, M.; Fujiwara, S.; Shin-ike, T.; Kuniyasu, H.;
Kambe, N. J. Am. Chem. Soc. 2005, 127, 9706.
7. The stereo- and regiochemistry of 5a were determined by
the NOE experiment and the synthesis of a mixture of
stereoisomers of 5a by the reaction of (Z)-1,3-bis(phenyl-
thio)-2-nonen-1-one with Et2NH.
8. Kuniyasu, H.; Ogawa, A.; Miyazaki, S.; Ryu, I.; Kambe,
N.; Sonoda, N. J. Am. Chem. Soc. 1991, 113, 9796.
9. Catalyst: PdBr2(PPh3)2, PdI2(PPh3)2, PdCl2(AsPh3)2,
PdCl2(SbPh3)2, PdCl2[P(o-tolyl)3]2, PdCl2(dppf), PdCl2-
(dppe), PdCl2(PCy3)2, and PdCl[P(OPh)3]2 in CH3CN;
ligand: P(OMe)3, P(OEt)3, P(2-furyl)3, and P(o-tolyl)3 with
the combined use of Pd(dba)2; solvent: C6H6, xylene,
THF, dioxane, pyridine, CH3CN, and N-methylmorpho-
line in the presence of 4c; additive: n-Bu4NCl, NaCl,
CaCl2, and CaH2 in the presence of 4c.
11. The oxidative addition of 1g to Pd(0) did not take place in
CD3CN.
12. One possible explanation for giving 5 efficiently by
employing 1g is the stability of 6g against disproportion-
ation. Actually, the reaction of PdCl2(PPh3)2 with
Pd(SAr)2(PPh3)2 (Ar = 2,4,5-tri-Cl-C6H2) in C6D6 affor-
ded suspected 6g in 89% yield after 2.5 h at 25 °C.
13. We have already reported that the insertion of DMAD
into the S–Pd bond of Pd(SAr)2(DPPE) furnished vinyl-
palladium, see: Sugoh, K.; Kuniyasu, H.; Kurosawa, H.
Chem. Lett. 2002, 106.
10. Spectral data of 5g: Z-isomer. Yellow oil; 1H NMR
(400 M Hz, CDCl3) d 0.84 (t, J = 7.2 Hz, 3H), 1.08–1.26