A Convenient Preparation of Chalcogenoenynes from β-Bromovinyl Ketene Chalcogenoacetals

Article abstract of DOI:10.1055/s-2003-41499

β-Bromovinyl ketene chalcogenoacetals have been synthesized stereoselectively via electrophilic addition of the benzene-selenenyl bromide to substituted alkynes. The palladium-catalyzed cross-coupling reaction of β-bromovinyl ketene chalcogenoacetals with

Full text of DOI:10.1055/s-2003-41499

1880
LETTER
A Convenient Preparation of Chalcogenoenynes from b-Bromovinyl Ketene
Chalcogenoacetals
C
onvenient Prepar
i
ationo
l
f
C
halc
s
ogenoeny
o
nes n Zeni,* Marcelo Paulo Stracke, Elizeo Lissner, Antonio Luiz Braga
Departamento de Química, Laboratório de Bioquímica Toxicológica, UFSM, 97105-900, Santa Maria, RS Brazil
E-mail: gzeni@quimica.ufsm.br
Received 24 June 2003
Abstract: b-Bromovinyl ketene chalcogenoacetals have been syn-
thesized stereoselectively via electrophilic addition of the benzene-
selenenyl bromide to substituted alkynes. The palladium-catalyzed
cross-coupling reaction of b-bromovinyl ketene chalcogenoacetals
with 1-alkynes gave the corresponding chalcogenoenynes in 62–
85% yields
Key-words: cross-coupling, chalcogenoenynes, palladium, telluri-
um, selenium, b-bromovinyl ketene chalcogenoacetals
Scheme 1
Ketene chalcogenoacetals play an important role in organ-
ic synthesis, especially in the development of methodolo-
gies for the synthesis of substituted alkenes.1 There are
several reasons for this; they have a widely varied synthet-
ic organochemical potential. The chalcogen atom exercis-
es a stabilizing effect on neighboring positive as well as
negative charges. This makes the double bond in ketene
chalcogenoacetals responsive towards both nucleophilic
and electrophilic attack an extremely useful feature for or-
ganic synthetic purposes.
tion was performed by adding organochalcogenenyl
bromide (10 mmol) to substituted alkynes 1 (10 mmol)
in benzene at room temperature to afford the desired b-
bromovinyl ketene chalcogenoacetals 2, isolated in good
yields after purification (Scheme 2).
On the other hand, the synthesis of enynes has been a sub-
ject of interest for the last 20 years. Accordingly, a variety
of new methodologies based on palladium-catalyzed
reactions2 have been developed. The cross coupling reac-
tion of vinyl bromides, iodides, chlorides, triflates3–7 and
tosylates8 with monosubstituted acetylenes has been
achieved in the presence of Pd(0) or Pd(II)/CuI catalysts
using an amine as base. The reaction has also been per-
formed using vinyl metals, like vinyl boron,9 copper,10
zinc,11 aluminum,12 magnesium,13 and tellurium re-
agents.14 Our continuous efforts in the synthesis of enynes
by cross-coupling reaction14a–d,15 led us to find out that the
b-bromovinyl ketene chalcogenoacetals can be effective-
ly applied to the synthesis of chalcogenoenynes via cross-
coupling reaction using palladium as catalyst.
Scheme 2
Concerning the stereochemistry of these tetrasubstituted
alkenes, we observed the formation of trans adducts.16
The geometry of the double bond of 2a–d could be con-
firmed from vinylic sulfide 5 which was obtained from 2c
after two stereoselective steps. Firstly, with the treatment
of b-bromovinyl ketene chalcogenoacetals 2c with n-
BuLi in hexane followed by hydrolysis we obtained the
compounds 4, stereoselectively (Scheme 3).17 Secondly,
the treatment of ketene chalcogenoacetals 4 with n-BuLi
in THF followed by hydrolysis gave the vinylic sulfide 5
We found that direct coupling of b-bromovinyl ketene (Scheme 4).18 The coupling constant of 15.5 Hz between
chalcogenoacetals 2 with 1-alkynes in the presence of the vinylic hydrogens was consistent with an E configura-
tetrakis(triphenylphosphine) palladium (0) as catalyst in tion.
pyrrolidine affords the desired chalcogenoenynes 3a–n in
good yields (Scheme 1).
Our initial research efforts were dedicated to develop the
reaction parameters such as the nature of the catalyst
The starting b-bromovinyl ketene chalcogenoacetals were [Pd(PPh3)4, PdCl2/PPh3, PdCl2(PPh3)2, Pd(OAc)2,
readily available by stereoselective addition of the ben- PdCl2(PhCN)2], the base [n-PrNH2, n-BuNH2, Et2NH,
zeneselenenyl bromide to substituted alkynes. The reac- Et3N, pyrrolidine, piperidine] and the solvent [N,N-DMF,
MeCN, THF, MeOH].
SYNLETT 2003, No. 12, pp 1880–1882
2
9
.0
9
.2
0
0
3
Careful analysis of the optimization reactions revealed
that the system Pd(PPh3)4/pyrrolidine was the most effi-
cient to furnish the desired chalcogenoenyne. The use of
Advanced online publication: 19.09.2003
DOI: 10.1055/s-2003-41499; Art ID: S15403ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Scheme 3
Convenient Preparation of Chalcogenoenynes
1881
Table 1 Chalcogenoenynes 3 Prepared According to Scheme 1
solvent did not improve our results. In this way, the
optimum condition for the coupling was of Pd(PPh3)4
(5 mol%), pyrrolidine (5 mL), b-bromovinyl ketene chal-
cogenoacetals 2 (1 mmol) and the appropriate 1-alkyne
(2 mmol) at 25 °C.19 By extending the coupling reaction
to other alkynes, various chalcogenoenynes 3 were ob-
tained in good yields (Table 1). The reaction occurs with
retention of the double bound geometry since starting
from pure trans adduct of the b-bromovinyl ketene chal-
cogenoacetals, only Z chalcogenoenynes 3 were obtained.
Entry
6
Chalcogenoenynes 3
Time (h)
12
Yield (%)
73
SePh
Ph
SeCH3
3f
OH
7
8
9
13
10
12
83
78
75
Ph
SePh
SeCH3
The geometry of the chalcogenoenynes 3 were de-
termined by NOE experiments on their derivatives 6,
prepared using Se/Li selective exchange reaction
(Scheme 4).18 When compound 6 was irradiated at the sig-
nal attributed to vinylic hydrogen (6.35 ppm), an enhance-
ment of the allylic hydrogens (2.42 ppm) was observed,
showing a cis relation between them.
3g
OH
SePh
Ph
SeCH3
3h
OH
C5H11
SePh
SCH3
3i
OH
C5H11
10
11
12
14
82
85
Scheme 4
SePh
SCH3
Table 1 Chalcogenoenynes 3 Prepared According to Scheme 1
3j
Entry
1
Chalcogenoenynes 3
Time (h) Yield (%)
OH
C5H11
10
65
C5H11
SePh
SePh
SCH3
SeCH3
C4H9
C5H11
3a
3b
3k
OH
2
12
73
SePh
12
13
14
9
75
79
75
Ph
SePh
SCH3
SeCH3
3l
SePh
SCH3
OH
OH
3
4
5
12
10
9
79
81
62
C5H11
SePh
12
10
Ph
SeCH3
3c
3m
OH
OH
C5H11
SePh
Ph
SePh
SCH3
SeCH3
3d
3n
OH
Ph
OH
SePh
SeCH3
In summary, in this paper we present a facile stereoselec-
tive synthesis of chalcogenoenynes by palladium cata-
lyzed cross-coupling reaction. All compounds reported
C4H9
3e
Synlett 2003, No. 12, 1880–1882 © Thieme Stuttgart · New York

1882
G. Zeni et al.
LETTER
1
herein showed purity and H NMR, 13C NMR, IR and
GCMS data in full agreement with their assigned struc-
tures. This reaction associated with the Ni/CuI-catalyzed
cross-coupling reaction of vinylic selenides15 with
alkynes, can constitute an interesting alternative route to
the regio-, and stereoselective preparation of enediynes
and derivatives. This novel approach to enynes function-
alized with organochalcogen could open economical
routes to biologically important enyne systems. The
pharmacological activity of these compounds is under
study in our laboratory.
(10) (a) Normant, J. F.; Commerçon, A.; Villièras, J. Tetrahedron
Lett. 1975, 1465. (b) Alexakis, A.; Cahiez, G.; Normant, J.
F. Synthesis 1979, 826.
(11) Magriotis, P. A.; Scott, M. E.; Kim, K. D. Tetrahedron Lett.
1991, 32, 6085.
(12) Negishi, E. I.; Okukado, N.; King, A. O.; Van Horn, D. E.;
Spiegel, B. I. J. Am. Chem. Soc. 1978, 100, 2254.
(13) Dang, H. P.; Linstrumelle, G. Tetrahedron Lett. 1978, 191.
(14) (a) Zeni, G.; Comasseto, J. V. Tetrahedron Lett. 1999, 40,
4619. (b) Zeni, G.; Menezes, P. H.; Moro, A. V.; Braga, A.
L.; Silveira, C. C.; Stefani, H. A. Synlett 2001, 9, 1473.
(c) 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. (d) Zeni,
G.; Lüdtke, D. S.; Nogueira, C. W.; Panatieri, R. B.; Braga,
A. L.; Silveira, C. C.; Stefani, H. A.; Rocha, J. B. T.
Tetrahedron Lett. 2001, 42, 8927. (e) Barrientos-
Astigarraga, R. E.; Moraes, D. N.; Comasseto, J. V.
Tetrahedron Lett. 1999, 40, 265. (f) De Araujo, M. A.;
Comasseto, J. V. Synlett 1995, 1145. (g) Barrientos-
Astigarraga, R. E.; Castelani, P.; Comasseto, J. V.; Formiga,
H. B.; Silva, N. C.; Sumida, C. Y.; Vieira, M. L. J.
Organomet. Chem. 2001, 623, 43.
Acknowledgment
The authors thank the following agencies for support: FAPERGS,
CNPq, CAPES and UFSM.
References
(1) (a) Silveira, C. C.; Perin, G.; Braga, A. L.; Dabdoub, M. J.;
Jacob, R. G. Tetrahedron 1999, 55, 7421. (b) Silveira, C.
C.; Perin, G.; Braga, A. L. Tetrahedron Lett. 1995, 36, 7361.
(c) Braga, A. L.; Reckziegel, A.; Silveira, C. C.; Comasseto,
J. V. Synth. Commun. 1994, 24, 1165. (d) Dabdoub, M. J.;
Cassol, T. M.; Barbosa, S. L. Tetrahedron Lett. 1996, 37,
831. (e) Stefani, H. A.; Comasseto, J. V.; Petragnani, N.;
Braga, A. L.; Menezes, P. H.; Gusevskaya, E. V.
Phosphorus, Sulfur Silicon Relat. Elem. 1997, 126, 211.
(f) Dabdoub, M. J.; Begnini, M. L.; Guerrero, P. G. Jr.
Tetrahedron 1998, 54, 2371. (g) Denis, J. N.; Desauvage,
S.; Hevesi, L.; Krief, A. Tetrahedron Lett. 1981, 22, 4009.
(2) Tamao, K. In Comprehensive Organic Synthesis, Vol. 3;
Trost, B. M.; Fleming, I., Eds.; Pergamon: New York, 1991,
435–480.
(3) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 4467.
(4) (a) Alami, M.; Linstrumelle, G. Tetrahedron Lett. 1991, 32,
6109. (b) Alami, M.; Peyrat, J.-F.; Brion, J.-D. Synthesis
2000, 1499.
(5) Dieck, H. A.; Heck, F. R. J. Organomet. Chem. 1975, 93,
259.
(6) Scott, W. J.; Peña, M. R.; Sward, K.; Stoessel, S. J.; Stille, J.
K. J. Org. Chem. 1985, 50, 2302.
(15) Silveira, C. C.; Braga, A. L.; Vieira, A. S.; Zeni, G. J. Org.
Chem. 2003, 68, 662.
(16) (a) Paulmier, C. Selenium Reagents and Intermediates in
Organic Synthesis, 1st ed.; Pergamon press: Oxford,
England, 1986. (b) Garrat, D. G.; Schmid, G. H. Chem. Scr.
1977, 11, 170.
(17) Braga, A. L.; Zeni, G.; de Andrade, L. H.; Silveira, C. C.
Synlett 1997, 595.
(18) Grobel, B. T.; Seebach, D. Chem. Ber. 1977, 110, 867.
(19) Pd(0) Catalyzed Cross-Coupling Reaction of b-
Bromovinyl Ketene Chalcogenoacetals 2b with 1-
Hexyne; General Procedure: To a solution of Pd(PPh3)
(5 mol%, 0.058 g), in pyrrolidine (5 mL) at r.t. under Ar
atmosphere, were added of b-bromovinyl ketene
chalcogenoacetals 2b (0.425 g, 1 mmol) and hexyne (0.164
g, 2 mmol). The mixture was stirred at r.t. for 10 h, treated
with NH4Cl saturated solution (5 mL) and then extracted
with EtOAc. The organic layer was washed with brine and
dried over MgSO4. The solvent was evaporated and the
residue was purified by flash silica gel chromatography
eluted with hexane to yield 3a in 65% yield (0.276 g). 1H
NMR (200 MHz, CDCl3): d = 7.74–7.41 (m, 2 H), 7.39–7.25
(m, 3 H), 2.46 (s, 3 H), 2.40 (t, J = 7.0 Hz, 2 H,), 1.63–1.25
(m, 8 H), 1.35–1.06 (m, 4 H), 0.95 (t, J = 7.0 Hz, 3 H), 0.92
(t, J = 7.0 Hz, 3 H). 13C NMR (50 MHz, CDCl3): d = 140.56,
135.02, 129.32, 128.85, 127.77, 116.11, 98.89, 76.90, 33.87,
31.13, 30.69, 28.11, 22.14, 21.95, 19.28, 16.70, 13.81,
13.50. IR (neat, cm–1): 2929, 2859, 2360, 1699, 1377. LRMS
(rel. int.): m/z = 426 (10), 332 (48) 270 (100), 176 (30), 71
(42), 57 (38).
(7) Alami, M.; Crousse, B.; Ferri, F. J. Organomet. Chem. 2001,
624, 114.
(8) Braga, A. L.; Emmerich, D. J.; Silveira, C. C.; Martins, T. L.
C.; Rodrigues, O. E. D. Synlett 2001, 3, 369.
(9) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J. Am.
Chem. Soc. 1985, 107, 972.
Synlett 2003, No. 12, 1880–1882 © Thieme Stuttgart · New York