Synthesis of 1,3-enynes via Suzuki-type reaction of vinylic tellurides and potassium alkynyltrifluoroborate salts

Article abstract of DOI:10.1016/j.tetlet.2004.11.160

The palladium-catalyzed cross-coupling reaction between potassium alkynyltrifluoroborate salts and vinylic tellurides proceeds readily to afford 1,3-enynes with moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2004.11.160

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 563–567
Synthesis of 1,3-enynes via Suzuki-type reaction of vinylic
tellurides and potassium alkynyltrifluoroborate salts
a,
b
c
a
*
´
Helio A. Stefani, Rodrigo Cella, Felipe A. Do¨rr, Claudio M. P. Pereira,
Gilson Zenid and Marlito Gomes, Jr.a
a
´
ˆ
ˆ
Departamento de Farmacia, Faculdade de Ciencias Farmaceuticas, Universidade de Sa˜o Paulo, Sa˜o Paulo, SP, Brazil
b
´
Instituto de Quımica, Universidade de Sa˜o Paulo, Sa˜o Paulo, SP, Brazil
c
´
Departamento de Biofısica, Universidade Federal de Sa˜o Paulo, Sa˜o Paulo, SP, Brazil
´
Departamento de Quımica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
d
Received 20 September 2004; revised 30 November 2004; accepted 30 November 2004
Abstract—The palladium-catalyzed cross-coupling reaction between potassium alkynyltrifluoroborate salts and vinylic tellurides
proceeds readily to afford 1,3-enynes with moderate to good yields.
Ó 2004 Elsevier Ltd. All rights reserved.
The interest for chemistry of organotellurium com-
pounds has increased in the last 10 years, being the sub-
ject of many reviews1 as well as books.2 Among several
classes of tellurium compounds, vinylic tellurides are
one of the most useful. Several methods have been
developed for their preparation,1,2 and among them,
one of the most important is the hydrotelluration reac-
tion of alkynes,3 which provide exclusively the (Z)-vin-
ylic telluride. This kind of tellurium compound can be
transmetallated with many organometallic reagents to
generate the corresponding (Z)-vinyl organometallic
with retention of the double bond geometry, which
can react with several electrophiles like carbonyl com-
pounds,4 enones5 and epoxides.6
of the palladium-catalyzed cross-coupling of diaryl and
bis-vinyltellurium dichlorides with organoboronic acids
has recently been reported.12 However, to the best of
our knowledge, organotrifluoroborates, still in their in-
fancy as coupling reagents, have never been partnered
with organotellurides in Suzuki-type reactions.
Herein we report an efficient protocol for the synthesis
of 1,3-enynes from the potassium alkynyltrifluoroborate
salts13 and vinylic tellurides14 as a useful alternative to
the widely used organic halides. Our initial studies of
this process focused on developing an optimum set
of reaction conditions for the palladium-catalyzed
Palladium-catalyzed cross-coupling reaction of vinylic
tellurides with terminal alkynes was previously de-
scribed.7,8 The symmetrical diorganotellurium dichlo-
rides have also been used in cross-coupling reactions
with organostannanes9 and iodonium salts.10
Table 1. Study of catalyst effect on cross-coupling reaction
15 mol% cat.
TeBu-n
+
BF3K
30 mmol % CuI, Et3N
MeOH, reflux, 8 h
1a
2a
3a
The Suzuki palladium-catalyzed cross-coupling reaction
between arylboronic acids and aryl halides or triflates
has proven to be a very popular and versatile method
for forming carbon–carbon bonds.11 An investigation
Entry
Catalysts
Isolated yield (%)
1
2
3
4
5
6
7
PdCl2
53
16
55
77
40
68
66
Pd(PPh3)4
Pd(OAc)2
Pd(acac)2
Pd(dba)3
Keywords: 1,3-Enynes; Suzuki; Vinylic tellurides; Potassium alkynyl-
trifluoroborate salts.
[Pd(allyl)Cl]2
PdCl2(C6H5CN)2
*
Corresponding author. Tel.: +55 11 30913654; fax: +55 11 3815
4418; e-mail: hstefani@usp.br
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.11.160

564
H. A. Stefani et al. / Tetrahedron Letters 46 (2005) 563–567
coupling of potassium alkynyltrifluoroborate salts and
vinylic tellurides as electrophilic partners. The reaction
was optimized using potassium (phenylacetylene)trifluo-
roborate and vinylic telluride as standard substrates
(Table 1).
The cross-coupling in all studied reactions cases were
performed in the presence of 3 equiv of base. Bases such
as Cs2CO3 (39%), NaOH (35%), KOBu-t (34%) and KF
(34%) led to similar yields. K2CO3 improved the yield to
49%. We have found that amine bases such as Et3N
Table 2. Cross-coupling reaction of vinylic tellurides
C6H5
Pd(acac)2, CuI
R
R
TeBu-n
+
BF3K
Et3N, MeOH
reflux, 8h
1a-j
2a
3a-d, 3g-j
Entry
1
Vinylic tellurides
Cross-coupling product
(%) Yield
77
C6H5
TeBu-n
C6H5
1a
1b
3a
3b
TeBu-n
2
3
58
51
HO
HO
C6H5
n-BuTe
HO
HO
1c
1d
3c
3d
C6H5
TeBu-n
TeBu-n
4
68
N
5
6
7
—
—
NR
NR
58
O
1e
1f
N
TeBu-n
TeBu-n
OH
OH
C6H5
1g
3g
C6H5
HO
TeBu-n
8
9
63
65
HO
OH
OH
1h
3h
O
O
C6H5
TeBu-n
EtO
EtO
1i
3i
C6H5
C6H5
10
68
n-BuTe
C6H5
C6H5
C6H5
1j
3j

H. A. Stefani et al. / Tetrahedron Letters 46 (2005) 563–567
565
Table 3. Cross-coupling of vinylic telluride with different potassium alkynyltrifluoroborate salts
C6H5
Pd(acac)2, CuI
TeBu-n
R
BF3K
+
Et3N, MeOH
reflux, 8h
1a
2b-d
3k-m
Entry
1
Alkynyltrifluoroborates
Products
(%) Yield
C8H17
73
28
61
C8H17
BF3K
C6H5
C6H5
2b
2c
3k
3l
OMe
BF3K
2
3
MeO
BF3K
C6H5
2d
3m
(77%) in dry MeOH provided the best result in the cross-
coupling reaction between potassium alkynyltrifluoro-
borate salts and vinylic tellurides.
measuring the coupling constants of the vinylic hydro-
gens, showing a cis (J = 11.45 Hz) relationship between
them.
Solvents such as THF (38%), 1,4-dioxane (31%), DME
(31%), toluene (18%), isopropanol (37%) were also
considered. Among the solvents tested, MeOH (77%)
proved to be far the most effective.
In summary, we have demonstrated here a new transfor-
mation leading to the synthesis of 1,3-enynes. One fea-
ture of this protocol was the tolerance of a variety of
functional groups such OH, OCH3, EtO2C and conju-
gated C@C double bond under the reaction conditions.
No homocoupling products were observed, what is an
advantage on comparison with the usual Suzuki reac-
tion using organic halides. The use of potassium organo-
trifluoroborate salts, (Z)-vinylic tellurides and
commercially Pd(II) catalyst makes this methodology
useful and attractive for the synthesis of 1,3-enynes.
Further studies of this methodology and the mechanism
reaction are currently ongoing in our laboratory and
will be reported in due course.
The use of Pd(acac)2 with 3 equiv of Et3N in MeOH was
employed to study the catalyst loading. These results
indicate that the use of 15 mol % of Pd(acac)2 produces
the best yield.
Having established the viability of the presented meth-
odology, general applicability as well as the reactivity
of various potassium alkynyltrifluoroborate salts13 and
vinylic tellurides were also tested (Table 2). To this
end we have prepared a series of vinylic tellurides by
hydrotelluration of alkynes with lithium butyl telluro-
late generated by reaction of n-butyllithium with ele-
mental tellurium.14
Acknowledgements
The authors wish to thank FAPESP (Grant 03/01751-8,
04/01101-6, 03/13475-5), CAPES and CNPq agencies for
financial support.
Although the method for cross-coupling proved to be
general to prepare 1,3-enynes, no coupling occurred
with some organotelluride compounds (Table 1, entries
5 and 6). A probable explanation would be the suggested
coordination of the nitrogen and tellurium atoms with
the palladium forming a stable six-membered ring
complex.15
References and notes
1. (a) Comasseto, J. V.; Ling, L. W.; Petragnani, N.; Stefani,
H. A. Synthesis 1997, 373; (b) Comasseto, J. V.; Barrien-
tos-Astigarraga, R. E. Aldrichim. Acta 2000, 33, 66;
(c) Vieira, M. L.; Zinn, F. K.; Comasseto, J. V. J. Brazil.
Chem. Soc. 2001, 12, 586.
2. (a) Petragnani, N. Tellurium in Organic Synthesis: Best
Synthetic Methods; Academic: London, UK, 1994; (b)
Petragnani, N. In Organotellurium Compounds in Organic
Synthesis; McKillop, A., Ed.; Pergamon: New York, 1994;
Vol. 11, Chapter 14.
In an attempt to broaden the scope of the methodology,
the possibility of performing the reaction with other
potassium alkynyltrifluoroborate salts were also investi-
gated (Table 3). All compounds have had their structure
confirmed by 1H and 13C NMR, IR and mass analysis.16
The stereochemical outcome of the reaction shows that
it proceeds in a stereoconservative way, resulting in only
the (Z)-enyne. The stereochemistry was established by

566
H. A. Stefani et al. / Tetrahedron Letters 46 (2005) 563–567
3. Zeni, G.; Comasseto, J. V. Tetrahedron Lett. 2000, 41,
1311.
4. Barros, S. M.; Comasseto, J. V.; Barriel, J. N. Tetrahedron
Lett. 1989, 30, 7353.
5. (a) Tucci, F. C.; Chieffi, A.; Comasseto, J. V.; Marino, J.
P. J. Org. Chem. 1996, 61, 4975; (b) Moraes, D. N.;
Barrientos-Astigarraga, R. E.; Castelani, P.; Comasseto, J.
V. Tetrahedron 2000, 56, 3327.
6. (a) Marino, J. P.; Tucci, F. C.; Comasseto, J. V. Synlett
1993, 761; (b) Marino, J. P.; McLure, M. S.; Holub, D. P.;
Comasseto, J. V.; Tucci, F. C. J. Am. Chem. Soc. 2002,
124, 1664.
1H); 5.81 (dt, J = 10.90–1.44 Hz; 1H); 4.49 (d,
J = 5.53 Hz; 2H); 1.94 (s, 1H). 13C NMR (75 MHz,
CDCl3) d 141.29, 131.44, 128.48, 128.37, 122.93, 110.63,
95.25, 84.87, 61.09. IR (neat): 1025, 1608, 2349, 3042,
3398 cmÀ1. CG/MS: m/z (relative, %) 158 (42) [M+], 129
(100), 122 (38), 115 (71).
1
Compound 3c: H NMR (300 MHz, CDCl3) d 7.52–7.48
(m, 2H); 7.39–7.35 (m, 3H); 5.66–5.62 (m, 2H); 4.29 (s,
1H); 1.88 (b, 1H). 13C NMR (75 MHz, CDCl3) d 130.64,
130.16, 127.48. 127.32, 121.70, 119.49, 89.90, 85.91,
64.38. IR (neat): 1051, 1613, 2205, 3056, 3359 cmÀ1. CG/
MS: m/z (relative, %) 158 (83) [M+], 159 (10) [M+1]+, 127
(100).
7. Zeni, G.; Comasseto, J. V. Tetrahedron Lett. 1999, 40,
4619.
1
Compound 3d: H NMR (300 MHz, CDCl3) d 7.42–7.24
8. (a) Zeni, G.; Menezes, P. H.; Moro, A. V.; Braga, A. L.;
Silveira, C. C.; Stefani, H. A. Synlett 2001, 1473; (b) Zeni,
G.; Nogueira, C. W.; Panatieri, R. B.; Silva, D. O.;
Menezes, P. H.; Braga, A. L.; Silveira, C. C.; Stefani, H.
A.; Rocha, J. B. T. Tetrahedron Lett. 2001, 42, 7921; (c)
Braga, A. L.; Andrade, L. H.; Silveira, C. C.; Moro, A. V.;
Zeni, G. Tetrahedron Lett. 2001, 42, 8563; (d) Zeni, G.;
(m, 5H); 6.20 (d, J = 11.89 Hz; 1H); 6.00–5.96 (m, 1H);
5.51 (d, J = 11.93 Hz; 1H); 2.72–2.70 (m, 2H); 2.19–2.18
(m, 2H); 1.72–1.57 (m, 4H). 13C NMR (75 MHz, CDCl3) d
142.68, 137.24, 133.59, 130.98, 128.29, 127.89, 123.91,
103.42, 94.01, 89.20, 27.00, 26.17, 23.30, 22.20. IR (neat):
1596, 1712, 2196, 2939, 3056 cmÀ1. CG/MS: m/z (rela-
tive, %) 208 (38) [M+], 180 (93), 165 (100), 127 (12).
1
Ludtke, D. S.; Nogueira, C. W.; Panatieri, R. B.; Braga,
¨
Compound 3g: H NMR (300 MHz, CDCl3) d 7.46–7.41
A. L.; Silveira, C. C.; Stefani, H. A.; Rocha, J. B. T.
Tetrahedron Lett. 2001, 42, 8927; (e) Braga, A. L.; Vargas,
F.; Zeni, G.; Silveira, C. C.; Andrade, L. H. Tetrahedron
Lett. 2002, 43, 4399; (f) Zeni, G.; Perin, G.; Cella, R.;
Jacob, R. G.; Braga, A. L.; Silveira, C. C.; Stefani, H. A.
Synlett 2002, 975; (g) Zeni, G.; Braga, A. L.; Stefani, H. A.
Acc. Chem. Rev. 2003, 36, 731.
(m, 2H); 7.33–7.26 (m, 3H); 6.09 (d, J = 11.85 Hz; 1H);
5.73 (d, J = 11.87 Hz; 1H); 3.00 (s, 1H); 1.79–1.36 (m,
10H). 13C NMR (75 MHz, CDCl3) d 138.96, 131.47,
128.75, 128.66, 125.16, 121.09, 97.38, 79.87, 55.11, 33.10,
24.88, 21.59. IR (neat): 1451, 1595, 2932, 3046, 3374 cmÀ1
.
CG/MS: m/z (relative, %) 193 (5), 107 (100), 77 (18), 69 (8).
1
Compound 3h: H NMR (300 MHz, DMSO–d6) d 7.47–
9. Kang, S.-K.; Lee, S.-K.; Ryu, H.-C. Chem. Commun.
1999, 2117.
10. Kang, S.-K.; Lee, S.-K.; Kim, M.-S.; Kwon, H.-S. Synth.
Commun. 2001, 31, 1721.
11. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
12. Kang, S.-K.; Hong, Y.-T.; Kim, D.-H.; Lee, S.-H. J.
Chem. Res. (S) 2001, 283.
13. Molander, G. A.; Katona, B. W.; Machrouhi, F. J. Org.
Chem. 2002, 67, 8416.
14. Zeni, G.; Formiga, H. B.; Comasseto, J. V. Tetrahedron
Lett. 2000, 4, 1311.
15. (a) Khalid, A.; Khandelwal, B. L.; Singh, A. K.; Singh, T.
P.; Padmanabhan, B. J. Coord. Chem. 1994, 31, 19; (b)
Singh, H. B.; Sudha, N.; Butcher, R. T. Inorg. Chem. 1993,
31, 1431.
7.40 (m, 5H); 6.14 (t, J = 6.33 Hz; 1H); 5.25 (t,
J = 5.94 Hz; 1H); 4.91 (t, J = 5.53 Hz; 1H); 4.27 (t,
J = 5.86 Hz; 2H); 4.03 (d, J = 5.38 Hz; 2H). 13C NMR
(75 MHz, DMSO-d6) d 136.72, 131.23, 128.75, 128.69,
123.16, 122.47, 94.63, 85.99, 63.31, 59.47. IR (neat): 1182,
1626, 2350, 2958, 3058, 33,328 cmÀ1. CG/MS: m/z (rela-
tive, %) 188 (4) [M+], 86 (15), 77 (100).
1
Compound 3i: H NMR (300 MHz, CDCl3) d 7.55–7.52
(m, 2H); 7.36–7.26 (m, 3H); 6.02 (s, 1H); 4.23 (q,
J = 7.13 Hz; 2H); 2.36 (t, J = 7.53 Hz; 2H); 1.67 (q,
J = 7.2 Hz; 2H); 1.38–1.25 (m, 7H); 0.91 (t, J = 6.78 Hz;
3H). 13C NMR (75 MHz, CDCl3) d 165.27, 139.60, 132.04,
128.97, 128.34, 123.75, 122.88, 100.68, 87.73, 60.13, 38.84,
31.06, 27.76, 22.44, 14.36, 13.98. IR (neat): 1612, 1707,
2200, 2949, 3054 cmÀ1. CG/MS: m/z (relative, %) 270 (16)
[M+], 213 (34), 199 (48), 185 (100), 141 (60).
16. Suzuki-type reaction
1
Representative experimental procedure (3a): To a two-
necked 25 mL round-bottomed flask under N2 atmosphere
containing Pd(acac)2 (0.045 g, 15 mol %), CuI (0,060 g,
30 mol %), Et3N (0.5 mL) and dry methanol (8 mL) was
added the vinylic telluride 1a (0,287 g, 1.0 mmol) and the
potassium (1-phenylethynyl)trifluoroborate 2a (0,229 g,
1.1 mmol). The solution was heated at reflux for 8 h.
After this time the mixture was cooled and 10 mL of brine
was added to the flask. The resulting solution was then
extracted with diethyl ether; the combined organic layers
were dried over MgSO4. After filtering off the solid the
solvent was removed under reduced pressure to afford a
brown oil. This oil was purified by flash chromatography
silica gel (elution with 5% ethylacetate/hexane) to provide
Compound 3j: H NMR (300 MHz, CDCl3) d 7.76–7.73
(m, 2H); 7.63–7.5 (m, 4H); 7.44–7.32 (m, 9H); 6.58 (s, 1H).
13C NMR (75 MHz, CDCl3) d 136.69, 133.36, 131.76,
131.62, 128.86, 128.75, 128.61, 128.53, 128.44, 128.42,
127.98, 126.10, 125.87, 123.41, 123.09, 113.65,
89.00, 87.55. IR (KBr plate): 1546, 1594, 2179, 3045 cmÀ1
.
1
Compound 3k: H NMR (300 MHz, CDCl3) d 7.87–7.85
(m, 2H); 7.35–7.20 (m, 3H); 6.53 (d, J = 11.9 Hz; 1H); 5.69
(dt, J = 11.9–2.46 Hz; 1H); 2.42 (td, J = 7Hz–2.45 Hz;
2H); 1.64–1.28 (m, 12H); 0.88 (t, J = 7 Hz; 3H). 13C NMR
(75 MHz, CDCl3) d 137.22, 136.70, 128.45, 128.13, 128.10,
108.21, 97.91, 79.20, 31.89, 29.27, 29.22, 29.05, 28.63,
22.70, 19.94, 14.13. IR (neat): 1694, 2199, 2931,
3022 cmÀ1. CG/MS: m/z (relative, %) 240 (24) [M+], 183
(9), 169 (15), 155 (25), 141 (100).
1
the product 3a as a yellow oil in 77% yield (0.157 g). H
1
NMR (300 MHz, CDCl3) d 7.93–7.91 (m, 2H), 7.53–7.27
(m, 8H), 6.69 (d, J = 11.9 Hz; 1H), 5.91 (d, J = 11.9 Hz;
1H); 13C NMR (75 MHz, CDCl3) d 138.6, 136.5, 131.5,
128.72, 128.49, 128.37, 128.33, 128.25, 126.26, 107.34,
95.82, 88.22. IR (neat): 729.27, 1264.96, 1426.52, 2305.50,
2986.40, 3054.73 cmÀ1. CG/MS: m/z (relative, %) 204
(100) [M+], 203 (82) [MÀ1]+, 101 (26), 77(9), 50(13).
Compound 3l: H NMR (300 MHz, CDCl3) d 8.15–8.12
(m, 2H); 7.41–7.28 (m, 3H); 6.68 (d, J = 12.00 Hz; 1H);
5.77 (dt, J = 12.00–2.03 Hz; 1H); 4.36 (d, J = 1.95 Hz; 2H);
3.47 (s, 3H). 13C NMR (75 MHz, CDCl3) d 139.52, 136.66,
129.01, 128.71, 126.31, 107.24, 92.21, 85.20, 61.03, 58.16.
IR (neat): 1001, 1265, 1601, 2339, 2988 cmÀ1. CG/MS: m/z
(relative, %) 172 (51) [M+], 157 (30), 141 (63), 128 (100).
1
1
Compound 3b: H NMR (300 MHz, CDCl3) d 7.46–7.40
Compound 3m: H NMR (300 MHz, CDCl3) d 7.89–7.86
(m, 2H); 7.36–7.21 (m, 3H); 6.53 (d, J = 11.80 Hz; 1H);
(m, 2H); 7.34–7.29 (m, 3H); 6.14 (dt, J = 10.9 Hz–6.40 Hz;

H. A. Stefani et al. / Tetrahedron Letters 46 (2005) 563–567
567
5.70 (d, J = 11.50 Hz; 1H); 1.31 (s, 9H). 13C NMR
(75 MHz, CDCl3) 137.16, 136.70, 128.49, 128.08,
128.02, 108.15, 105.49, 77.92, 30.73, 28.47. IR (neat):
1600, 2206, 2929, 2968, 3022 cmÀ1. CG/MS: m/z (relative,
%) 185 (15) [MÀ1]+, 184 (100) [M+], 169 (84), 154 (85), 127
(15).
d