A one-pot, stereoselective synthesis of (Z)-1,2-disubstituted vinyl sulfides by sequential hydrostannylation and Stille reaction of acetylenic sulfides with tributyltin hydride and then with aryl iodides

Article abstract of DOI:10.3184/030823407X228777

(Z)-1,2-Disubstituted vinyl sulfides can be stereoselectively synthesised in one pot under mild conditions, in good yields, by the palladium-catalysed hydrostannylation of acetylenic sulfides, followed by Stille coupling with aryl iodides.

Full text of DOI:10.3184/030823407X228777

418 RESEARCH PAPER
JULY, 418–419
JOURNAL OF CHEMICAL RESEARCH 2007
A one-pot, stereoselective synthesis of (Zꢀ)-1,2-disubstituted vinyl sulfides
by sequential hydrostannylation and Stille reaction of acetylenic sulfides
with tributyltin hydride and then with aryl iodides
Wenyan Hao, Dong Wang and Mingzhong Cai*
Department of Chemistry, Jiangxi Normal University, Nanchang 330022, P. R. China
(Z)-1,2-Disubstituted vinyl sulfides can be stereoselectively synthesised in one pot under mild conditions, in good
yields, by the palladium-catalysed hydrostannylation of acetylenic sulfides, followed by Stille coupling with aryl
iodides.
Keywords: acetylenic sulfide, hydrostannylation, (Z)-1,2-disubstituted vinylsulfide, Stille coupling, stereoselective synthesis
Many biologically active compounds occurring in nature
possess the structural skeleton of trisubstituted alkenes.1-5
Because disubstituted vinylsulfides can be stereospecifically
converted into trisubstituted alkenes by Ni-catalysed
cross-coupling reactions with nucleophiles,6 the high-
yield, stereoselective synthesis of disubstituted vinyl
sulfides is a highly desirable goal. The palladium-catalysed
hydrostannylation of alkynes and the Stille reaction are
acknowledged as useful tools for constructing complex
organic molecules. However, there has been no report on
the palladium-catalysed sequential hydrostannylation and
Stille reaction of alkynes with Bu3SnH and then with organic
halides to date. Herein we report that (Z)-1,2-disubstituted
vinyl sulfides can be stereoselectively synthesised in one
pot under mild conditions in good yields by the palladium-
catalysed hydrostannylation of acetylenic sulfides, followed
by Stille coupling with aryl iodides.
two reactions, in one pot, to prepare stereoselectively (Z)-1,2-
disubstituted vinyl sulfides (Scheme 1).
We found that hydrostannylation of acetylenic sulfides 1
with tributyltin hydride using 5 mol% Pd(PPh3)4 in benzene,
followed by solvent change (to DMF) and subsequent
reaction with aryl iodides and 75 mol% CuI, gave the
(Z)-1,2-disubstituted vinylsulfides in good yields. The
experimental results are summarised in Table 1. As shown
in Table 1, the hydrostannylation-Stille sequential reaction
of Bu3SnH with a variety of acetylenic sulfides and the aryl
iodides proceeded smoothly under very mild conditions to
afford the corresponding (Z)-1,2-disubstituted vinyl sulfides
3 stereoselectively. The Stille coupling reaction of the
intermediates 2 with aryl bromides was very slow under the
same reaction conditions, only traces of coupling products
were obtained after 48 h. The Stille coupling reaction of the
intermediates 2 with aryl chlorides did not occur at all.
Palladium-catalysed hydrostannylation of alkynes provides
a simple general route for the synthesis of vinylstannanes.7
In 1991, Magriotis et al. reported that the palladium-catalysed
hydrostannylation of phenylthioalkynes with Bu3SnH was
highly regio- and stereoselective, giving (E)-α-stannylvinyl
sulfides in high yields.8 (E)-α-Stannylvinyl sulfides are
difunctional group reagents, in which two synthetically
versatile groups are linked to the same olefinic carbon atom,
andcanbeconsideredbothasvinylstannanesandvinylsulfides.
The palladium-catalysed coupling reaction of organostannanes
with organic halides known as Stille coupling has already
been established as an efficient stereospecific method for the
formation of carbon–carbon bonds under mild conditions.9
Considering the fact that both the hydrostannylation and Stille
reactions are catalysed by Pd(PPh3)4, we tried to combine the
(Z)-1,2-Disubstituted vinyl sulfides
3
are effective
precursors for preparing stereodefined trisubstituted alkenes.
In the presence of the catalyst bis(triphenylphosphine)nickel
(II) chloride they can easily undergo cross-coupling reactions
with Grignard reagents providing an effective method for
synthesis of trisubstituted alkenes. Thus, compounds 3a and
3h afford the sulfur-free trisubstituted alkenes 5a and 5b in 61
and 65% yield, respectively (Scheme 2).
In conclusion, we have developed an efficient and
stereoselective one-pot method for the synthesis of (Z)-
1,2-disubstituted vinyl sulfides. The present method has
the advantages of readily available starting materials, a
straightforward and simple procedure, mild reaction conditions
and good yields.
R
SAr
SnBu3
Scheme 1
Table 1 Synthesis of (Z)-1,2-disubstituted vinyl sulfides 3a–h
SAr
R1
R
H
R1I, CuI
Bu3SnH, Pd(PPh3)4
SAr
R
benzene, r.t.
H
DMF, r.t., 24 h
1
2
3
Entry
R
Ar
R1
Product
Yielda/%
1
2
3
4
5
6
7
8
n-C4H9
n-C4H9
n-C4H9
n-C4H9
CH3OCH2
CH3OCH2
Ph
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-CH3C6H4
Ph
Ph
3a
3b
3c
3d
3e
3f
82
80
74
79
76
78
79
81
4-ClC6H4
4-CH3C6H4
4-CH3C6H4
Ph
Ph
4-CH3C6H4
4-CH3C6H4
Ph
Ph
Ph
3g
3h
Ph
aIsolated yield based on the acetylenic sulfide 1 used.
* Correspondent. E-mail:caimzhong@163.com
PAPER: 07/4698

JOURNAL OF CHEMICAL RESEARCH 2007 419
R
H
SAr
R1
R
H
R2
R1
NiCl2(PPh3)2
+
R2MgBr
THF, reflux, 48 h
4
5a R = Bu, R1= Ph, R2= Me, 61%
3
5b R = R1= Ph, R2= Me, 65%
Scheme 2
Compound 3f: IR (film): ν (cm-1) 3056, 2922, 1719, 1582, 1478,
Experimental
1
1368, 1119, 1024, 809, 740; H NMR: δ 7.46 (m, J* = 8.0 Hz, 2H),
7.15–7.01 (m, 7H), 6.44 (t, J = 6.0 Hz, 1H), 4.38 (d, J = 6.0 Hz, 2H),
3.40 (s, 3H), 2.25 (s, 3H); 13C NMR: δ 138.0, 136.4, 136.2, 135.2,
134.1, 129.0, 128.8, 128.7, 127.6, 125.8, 70.9, 58.4, 21.1; MS: m/z
270 (M+, 28), 136 (37), 119 (63), 91 (42), 77 (11), 45 (100); Anal.
Calcd. for C17H18OS: C, 75.52; H, 6.71. Found: C, 75.3; H, 6.5.
Compound 3g: IR (film): ν (cm-1) 3021, 2925, 1725, 1582, 1478,
1440, 1180, 1024, 739; 1H NMR: δ 7.71 (m, J* = 7.6 Hz, 2H), 7.54 (d,
J = 8.0 Hz, 2H), 7.36–7.00 (m, 11H), 2.27 (s, 3H); 13C NMR: δ 138.1,
137.9, 136.9, 135.6, 135.3, 134.4, 129.5, 129.0, 128.9, 128.7, 128.2,
127.9, 127.8, 125.7, 21.2; MS: m/z 302 (M+, 100), 193 (77), 178 (67),
135 (79), 115 (49), 91 (21), 77 (18); Anal. Calcd. for C21H18S: C,
83.40; H, 5.99. Found: C, 83.2; H, 5.7.
THF and benzene were distilled from sodium-benzophenone
immediately prior to use. DMF was dried and distilled before use.
IR spectra were obtained on a Perkin-Elmer 683 instrument as
neat films. 1H NMR spectra were recorded on a Bruker AC-300
(300 MHz) spectrometer using CDCl3 as solvent. 13C NMR spectra
were recorded on a Bruker AC-300 (75 MHz) spectrometer using
CDCl3 as solvent. Mass spectra were determined on a Finnigan
8230 mass spectrometer. Microanalyses were measured using a
Yanaco MT-3 CHN microelemental analyser. Methylmagnesium
bromide was purchased from Aldrich and Ni(PPh3)2Cl2 was prepared
according to the procedure described by Venanzi.10
General procedure for the synthesis of (Z)-1,2-disubstituted vinyl
sulfides 3a–h
Compound 3h: IR (film): ν (cm-1) 3057, 3021, 1724, 1582, 1478,
1
1445, 1075, 1025, 762, 691; H NMR: δ 7.73 (d, J = 7.6 Hz, 2H),
A 25 ml, two-necked, round-bottom flask equipped with a magnetic
stirring bar, was charged sequentially with acetylenic sulfide 1
(1 mmol), benzene (4 ml), Pd(PPh3)4 (0.05 mmol) and Bu3SnH
(1.05 mmol) under argon. The mixture was stirred at room
temperature for 8 h. The solvent was removed under reduced pressure
and the residue was dissolved in DMF (10 ml). Then aryl iodide
(1.1 mmol) and CuI (0.75 mmol) were added and the mixture was
stirred at room temperature for 24 h. The reaction mixture was diluted
with Et2O (30 ml), filtered and then treated with 20% aqueous KF
(10 ml) for 30 min before the organic layer was taken, dried
(MgSO4) and concentrated. The residue was purified by column
chromatography on silica gel using light petroleum ether as eluent.
For 1H NMR AA'XX' systems, J* = J23 + J25.
7.63 (d, J = 7.6 Hz, 2H), 7.38–7.00 (m, 12H); 13C NMR: δ 141.0,
136.8, 135.7, 135.3, 134.7, 129.6, 129.2, 128.7, 128.2, 128.1, 127.9,
127.8, 125.9; MS: m/z 288 (M+, 100), 178 (97), 121 (53), 77 (28);
Anal. Calcd. for C20H16S: C, 83.29; H, 5.59. Found: C, 83.1; H, 5.4.
General procedure for the synthesis of stereodefined trisubstituted
alkenes 5a–b
To a stirred suspension of NiCl2(PPh3)2 (0.05 mmol) and the (Z)-1,2-
disubstituted vinyl sulfide 3 (1 mmol) in THF (6 ml) was added a
3.0 M THF solution of Me MgBr (15 mmol) at room temperature
under argon. The mixture was stirred at reflux temperature for 48 h.
After being cooled to room temperature, the mixture was quenched
with sat. aq NH4Cl (15 ml) and extracted with Et2O (2 × 30 ml).
The organic layer was washed with water (3 × 10 ml) and dried
(MgSO4). Removal of solvent under reduced pressure gave an oil,
which was purified by column chromatography on silica gel using
light petroleum ether as eluent.
Compound 3a: IR (film): ν (cm-1) 3057, 2957, 2856, 1595, 1475,
1
1389, 1093, 1012, 813, 759, 696; H NMR: δ 7.51 (m, J* = 7.6 Hz,
2H), 7.24–7.02 (m, 7H), 6.42 (t, J = 7.2 Hz, 1H), 2.56–2.50 (m,
2H), 1.50–1.34 (m, 4H), 0.92 (t, J = 7.6 Hz, 3H); 13C NMR: δ 140.6,
140.1, 134.7, 133.0, 131.2, 129.4, 128.8, 128.3, 127.6, 127.4, 31.5,
30.8, 22.5, 14.0; MS: m/z 302 (M+, 35Cl, 76), 259 (27), 159 (36), 147
(39), 117 (64), 91 (100); Anal. Calcd. for C18H19SCl: C, 71.39; H,
6.32. Found: C, 71.1; H, 6.1.
(E)-2-Phenylhept-2-ene (5a): IR (film): ν (cm-1) 3021, 2957,
2928, 1646, 1597, 851, 753; 1H NMR: δ 7.37–7.10 (m, 5H), 5.71 (t,
J = 6.4 Hz, 1H), 2.24–2.05 (m, 2H), 2.02 (s, 3H), 1.47–1.21 (m, 4H),
0.89 (t, J = 7.2 Hz, 3H); Anal. Calcd. for C13H18: C, 89.59; H, 10.41.
Found: C, 89.3; H, 10.3.
Compound 3b: IR (film): ν (cm-1) 2957, 2857, 1718, 1591, 1475,
1
(E)-1-Methyl-1,2-diphenylethene (5b): IR (film): ν (cm-1) 3057,
1390, 1093, 1012, 814, 743; H NMR: δ 7.44 (m, J* = 8.8 Hz, 2H),
1
7.18 (m, J* = 8.8 Hz, 2H), 7.09 (m, J* = 8.4 Hz, 2H), 7.03 (m, J* =
8.4 Hz, 2H), 6.38 (t, J = 7.2 Hz, 1H), 2.55–2.49 (m, 2H), 1.50–1.35
(m, 4H), 0.92 (t, J = 7.2 Hz, 3H); 13C NMR: δ 140.9, 138.6, 134.2,
133.4, 132.2, 131.6, 129.6, 128.9, 128.7, 128.4, 31.5, 30.8, 22.5,
14.0; MS: m/z 336 (M+, 35Cl, 45), 293 (23), 181 (25), 151 (94), 125
(100), 81 (36), 55 (79); Anal. Calcd. for C18H18SCl2: C, 64.09; H,
5.38. Found: C, 63.8; H, 5.2.
2925, 1651, 1528, 1422; H NMR: δ 7.52–7.03 (m, 10H), 6.71 (m,
1H), 2.15 (d, J = 1.3 Hz, 3H); Anal. Calcd. for C15H14: C, 92.74; H,
7.26. Found: C, 92.5; H, 7.0.
We thank the National Natural Science Foundation of China
(Project No. 20462002) and the Natural Science Foundation
of Jiangxi Province of China (Project No. 0420015) for
financial support.
Compound 3c: IR (film): ν (cm-1) 2957, 2926, 1712, 1610, 1475,
1
1389, 1093, 1012, 814, 743; H NMR: δ 7.41 (m, J* = 8.0 Hz, 2H),
7.09–7.01 (m, 6H), 6.39 (t, J = 7.2 Hz, 1H), 2.54–2.48 (m, 2H),
2.27 (s, 3H), 1.49–1.35 (m, 4H), 0.92 (t, J = 7.2 Hz, 3H); 13C NMR:
δ 139.8, 137.4, 137.2, 134.9, 132.8, 131.1, 129.3, 129.0, 128.8, 127.3,
31.6, 30.8, 22.5, 21.1, 14.0; MS: m/z 316 (M+, 35Cl, 34), 173 (21),
131 (63), 115 (36), 105 (100), 91 (31), 81 (68); Anal. Calcd. for
C19H21SCl: C, 72.02; H, 6.68. Found: C, 71.8; H, 6.6.
Received 13 June 2007; accepted 6 July 2007
Paper 07/4698 doi: 10.3184/030823407X228777
References
1
2
P.R. Marfat, P. McGuirk and P. Helquist, J. Org. Chem., 1979, 44, 3888.
M. Obayashi, K. Utimoto and H. Nozaki, Bull. Chem. Soc. Jpn, 1979, 52,
1760.
Compound 3d: IR (film): ν (cm-1) 2957, 2925, 1713, 1492, 1455,
1
1089, 1018, 803; H NMR: δ 7.43 (m, J* = 8.0 Hz, 2H), 7.05–7.00
3
Y. Masaki, K. Sakuma and K. Kaji, J. Chem. Soc., Chem. Commun., 1980,
434.
(m, 4H), 6.92 (m, J* = 8.0 Hz, 2H), 6.34 (t, J = 7.2 Hz, 1H), 2.54–
2.49 (m, 2H), 2.25 (s, 3H), 2.19 (s, 3H), 1.49–1.36 (m, 4H), 0.92 (t,
J = 7.2 Hz, 3H); 13C NMR: δ 139.1, 137.8, 137.1, 135.0, 133.5, 132.6,
129.4, 128.8, 128.3, 127.4, 31.6, 30.7, 22.5, 21.1, 20.9, 14.0; MS:
m/z 296 (M+, 32), 173 (12), 131 (46), 115 (21), 105 (100), 91 (26);
Anal. Calcd. for C20H24S: C, 81.03; H, 8.16. Found: C, 80.8; H, 7.9.
Compound 3e: IR (film): ν (cm-1) 3058, 2925, 1722, 1582, 1478,
4
5
X. Huang and A.M. Sun, J. Org. Chem., 2000, 65, 6561.
H.X. Wei, S.H. Kim, T.D. Caputo, D.W. Purkiss and G.G. Li, Tetrahedron,
2000, 56, 2397.
6
(a) T.Y. Luh and Z.J. Ni, Synthesis, 1990, 89; (b) E. Wenkert, T.W. Ferreira
and E.L. Michelotti, J. Chem. Soc., Chem. Commun., 1979, 637; (c) V.
Fiandanese, G. Marchese, F. Naso and L. Ronzini, J. Chem. Soc., Perkin
Trans. 1, 1985, 1115.
1
1440, 1119, 1024, 740; H NMR: δ 7.48 (d, J = 7.6 Hz, 2H), 7.14–
7
8
9
B.M. Trost and C.J. Li, Synthesis, 1994, 1267.
6.94 (m, 8H), 6.38 (t, J = 6.0 Hz, 1H), 4.31 (d, J = 5.6 Hz, 2H), 3.32
(s, 3H); 13C NMR: δ 139.2, 136.4, 134.9, 134.7, 128.9, 128.8, 128.3,
128.1, 127.7, 125.9, 70.8, 58.4; MS: m/z 256 (M+, 18), 147 (27), 121
(83), 103 (36), 91 (13), 77 (45), 45 (100); Anal. Calcd. for C16H16OS:
C, 74.96; H, 6.29. Found: C, 74.7; H, 6.1.
P.A. Magriotis, J.T. Brown, M.E. Scott, Tetrahedron Lett., 1991, 32, 5047.
(a) J.K. Stille, Angew. Chem. Int. Ed. Engl., 1986, 25, 508; (b) J.K. Stille
and B. L. Groh, J. Am. Chem. Soc., 1987, 109, 813. (c) T.N. Mitchell,
Synthesis, 1992, 803.
10 L.M. Venanzi, J. Chem. Soc., 1958, 719.
PAPER: 07/4698