Stereoselective synthesis of (Z)-enynes via Pd(II)/CuI(I)-catalyzed cross-coupling reaction of bis-Vinylic tellurides with 1-alkynes

Article abstract of DOI:10.1055/s-2001-16799

(Z)-bis-Vinylic tellurides undergo direct coupling reaction with terminal alkynes in the presence of palladium (II) at room temperature to give (Z)-enyne systems in good yields.

Full text of DOI:10.1055/s-2001-16799

LETTER
1473
Stereoselective Synthesis of (Z)-Enynes via Pd(II)/CuI(I)-Catalyzed Cross-
Coupling Reaction of bis-Vinylic Tellurides with 1-Alkynes
Gilson Zeni,*a Paulo H. Menezes,*b Angélica Venturini Moro,a Antonio L. Braga,a Claudio C. Silveira,a
Hélio A. Stefanic
aDepto. de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil
bDepto. de Química Fundamental, Universidade Federal de Pernambuco, Recife, PE, Brazil
cFaculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil
E-mail: gzeni@quimica.ufsm.br
Received 26 April 2001
mental tellurium in alkaline media.13 These compounds
are stable to oxygen and can be chromatographed and
stored in the dark at room temperature for several months.
Abstract: (Z)-bis-Vinylic tellurides undergo direct coupling reac-
tion with terminal alkynes in the presence of palladium (II) at room
temperature to give (Z)-enyne systems in good yields.
Since our initial research efforts were dedicated to devel-
op a good catalytic system, firstly we investigated the in-
fluence of the ligands in the palladium complex. Thus,
(Z)-bis-vinylic telluride 1a (1 equiv.) was treated in meth-
anol at room temperature with 2-propyn-1-ol (2 equiv.) 2a
in the presence of different catalysts and Et3N (1 equiv.)
as base (Scheme 2). As shown in Table 1, Pd(PPh3)4 or
Pd(PPh3)4/CuI did not exhibit catalytic activity in this re-
action (entries 1 and 2) and Pd (II) catalysts such as PdCl2/
PPh3, PdCl2(PPh3)2, Pd(OAc)2, PdCl2(PhCN)2 gave unsat-
isfactory yields of the desired enyne 3d (entries 3-6).
Key words: cross-coupling, enynes, palladium, tellurium
Calicheamycins, esperamycins and dynemycins are a new
class of antibiotic molecules recently emerged,1,2 among
the most potent antitumor agents known to date. All of
these molecules exhibit a common moiety, a conjugated
enediyne system able, upon DNA complexation and
chemical initiation, to rearrange with concomitant forma-
tion of biradical species. Since it is complexed to the DNA
minor groove, this biradical abstracts hydrogen atoms
from the desoxyribose part of DNA. Oxidation then leads
to DNA cleavage, and eventually to cell death.1
The reaction was greatly enhanced by increasing the
amount of PdCl2/CuI from 1% to 10% (entries 7-10) and
the enyne 3d was obtained in 85% isolated yield (entry
10).
The synthesis of enynes has received special interest dur-
ing the last 20 years and new methodologies using vinyl
halides or vinyl organometallic compounds have been re-
cently developed. The cross coupling of vinyl bromides,
iodides, chlorides and triflates with monosubstituted acet-
ylenes has been achieved in the presence of a Pd0 or PdII/
CuI catalyst using an amine as base.3-7 The synthesis of
enynes has been also performed using the coupling reac-
tion of bromoalkynes with vinyl metals, like vinyl boron,8
-copper,9 -zinc,10 -aluminum11 or -magnesium reagents.12
The use of vinylic tellurides13 to obtain enyne and ene-
diyne systems has been previously described using trans-
metalation with n-BuLi,14 cyanocuprates15 and directly
with terminal alkynes.16 In this paper we report the stere-
oespecific formation of (Z)-enyne systems by palladium
catalyzed cross coupling reaction of (Z)-bis-vinylic tellu-
rides with 1-alkynes (Scheme 1).17
Scheme 2
Table 1 Influence of the Ligands in the Palladium Complex.
Scheme 1
In this way, (Z)-bis-vinylic tellurides were easily obtained
from the reaction of the corresponding alkynes with ele-
Synlett 2001, No. 9, 1473–1475 ISSN 0936-5214 © Thieme Stuttgart · New York

1474
G. Zeni et al.
LETTER
Table 2 Enynes 3 Prepared According to Scheme 2
ayield of isolated pure product.
The nature of the amine was critical for the success of the no reaction was observed. By using Et2NH, n-PrNH2 or n-
coupling. When (Z)-bis-vinylic telluride 1a (1 equiv.) was BuNH2, moderated yields were observed (15% to 28%).
treated at room temperature with 2-propyn-1-ol (2 equiv.) However, by using Et3N, the enyne 3d was obtained in
2a and PdCl2 (10%)/CuI (10%) in MeOH (10 mL) using 85% isolated yield and the reaction was completed within
pyrrolidine, piperidine or morpholine (1 equiv.) as base, 6 h.
Synlett 2001, No. 9, 1473–1475 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Stereoselective Synthesis of (Z)-Enynes
1475
(4) (a) Alami, M.; Linstrumelle, G.; Tetrahedron Lett. 1991, 32,
6109. (b) Alami, M.; Peyrat, J.-F.; Brion, J.-D. Synthesis 2000,
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K. J. Org. Chem. 1985, 50, 2302.
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624, 114.
(8) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J. Am.
Chem. Soc. 1985, 107, 972.
Thus, the optimum condition for the coupling in Scheme
1 was found to be the use of PdCl2(10 mol%)/CuI (10
mol%), MeOH (10 mL), (Z)-bis-vinylic telluride 1 (1
mmol), the appropriate alkyne 2 (2 mmol) and Et3N (1
mmol) at 25 C.17 Extending the coupling reaction to other
alkynes, various Z-enynes 3 were obtained in good yields
(Table 2). Although in all cases an excess of alkyne was
used, the transfer of only one vinylic group was observed.
The formation of the enynes was confirmed by the analy-
sis of the 1H NMR spectrum. The stereoisomeric purities
of the enynes 3a-j were similar to that of starting bis-vi-
nylic tellurides 1,18 due to a complete retention of config-
uration in this type of reaction. The stereochemistry of the
obtained enynes was easily established. As an example,
the 1H NMR spectrum of compound 3d, showed a double
triplet at 5.75 ppm with coupling constants of 12 Hz and
2 Hz, typical of cis positioned hydrogen (hydrogen at car-
bon 4). The hydrogen at carbon 5 resonates at 6.63 ppm as
a doublet with coupling constant of 12 Hz.
(9) (a) Normant, J. F.; Commerçon, A.; Villièras, J. Tetrahedron
Lett. 1975, 1465. (b) Alexakis, A.; Cahiez, G.; Normant, J. F.;
Synthesis 1979, 826.
(10) Magriotis, P. A.; Scott, M. E.; Kim, K. D. Tetrahedron Lett.
1991, 32, 6085.
(11) Negishi, E. I.; Okukado, N.; King, A. O.; Van Horn, D. E.;
Spiegel, B. I. J. Am. Chem. Soc. 1978, 100, 2254.
(12) Dang, H. P.; Linstrumelle, G. Tetrahedron Lett. 1978, 191.
(13) Barros, S. M.; Dabdoub, M. J.; Dabdoub, V. B.; Comasseto, J.
V. Organometallics 1989, 8, 1661.
(14) Dabdoub, M. J.; Dabdoub, V. B. Tetrahedron 1995, 51, 9839.
(15) (a) Barrientos-Astigarraga, R. E.; Moraes, D. N.; Comasseto,
J. V. Tetrahedron Lett. 1999, 40, 265. (b) De Araujo, M. A.;
Comasseto, J. V. Synlett 1995, 1145.
(16) Zeni, G.; Comasseto, J. V. Tetrahedron Lett. 1999, 40, 4619.
(17) Pd(II) Catalyzed Cross-Coupling Reaction of (Z)-Bis-
Vinylic Tellurides with Alkynes: General Procedure: To a
solution of PdCl2 (10 mol%, 0.018 g), CuI (10 mol%, 0.02 g)
in MeOH (10 mL) at 25 C. under an argon atmosphere, were
added (Z)-bis-vinylic telluride 1 (1 mmol, 0.33 g) and the
appropriate alkyne (2 mmol). The mixture was stirred at room
temperature for the time indicated in Table 1, treated with
NH4Cl saturated solution (5 mL), extracted with ethyl acetate.
The organic layer was washed with brine and dried over
MgSO4. The solvent were evaporated and the residue was
purified by flash silica-gel chromatography eluting with
hexane (products 3h m) or hexane/ethyl acetate 7:3 (products
3a g) to give the product 3. Selected spectral and analytical
data for 3d: Yield 0.13 g (85%); 200 MHz 1H NMR (CDCl3)
= 7.83-7.27 (m, 5H), 6.63 (d, J = 12 Hz, 1H), 5.75 (dt,
J = 12.0, 2.0 Hz, 1H), 4.46 (d, J = 2 Hz, 2H), 2.10 (s, 1H); 50
MHz 13C NMR (CDCl3) = 139.10, 136.15, 132.55, 128.55,
128.25, 106.70, 93.80, 84.00, 51.70; IR (neat, cm-1) 3370,
3060, 2200, 1660, 786; LRMS (rel. int.) m/z 158 (15), 140
(19), 102 (100), 77 (30).
In summary, we have explored the Pd(II)/CuI catalyzed
cross-coupling reaction of the (Z)-bis-vinylic tellurides
with alkynes and established a new stereoselective route
to (Z)-enynes in good yields. Our approach is improved
compared to described methodologies, avoiding the prep-
aration of vinyl metals, haloalkynes or protection of hy-
droxyl group in propargylic alcohol. In comparison to our
previously described methodology the procedure has the
advantage of easy access and great stability of (Z)-bis-vi-
nylic tellurides. The use of this methodology for the syn-
thesis of polyacetylenic compounds is under study in our
laboratory. 19,20
Acknowledgement
The authors thank the following agencies for support: FAPERGS,
CNPq and FAPESP (98/10821-0). Professor Lothar W. Bieber (UF-
PE) is acknowledge for the revision of this manuscript.
References and Notes
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1996, 61, 4975. (b) Silveira, C. C.; Perin, G.; Boeck, P.; Braga,
A. L.; Petragnani, N. J. Organomet. Chem. 1999, 584, 44.
(19) Zeni, G.; Panatieri, R. B.; Lissner, E.; Menezes, P. H.; Braga,
A. L.; Stefani, H. A. Org. Lett. 2001, 3, 819.
(1) Nicolaou, K. C.; Smith, A. L. in: Stang, P. J.; Diederich, F.
(Eds.), Modern Acetylene Chemistry, VCH, Weinheim 1995.
(2) (a) Grissom J. W.; Gunawardena, G. U.; Klingberg, D.;
Huang, D. Tetrahedron 1996, 52, 6453. (b) Nicolaou, K. C.;
Daí, W. M. Angew. Chem. Int. Ed. Engl. 1991, 30, 1387.
(3) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 4467.
(20) Stefani, H. A.; Costa, I. M.; Zeni G. Tetrahedron Lett. 1999,
40, 9215.
Article Identifier:
1437-2096,E;2001,0,09,1473,1475,ftx,en;S04201ST.pdf
Synlett 2001, No. 9, 1473–1475 ISSN 0936-5214 © Thieme Stuttgart · New York