A new route to the synthesis of (E)-and (Z)-2-alkene-4-ynoates and nitriles from vic-diiodo-(E)-alkenes catalyzed by Pd(0) nanoparticles in water

Article abstract of DOI:10.1021/ol0708121

An efficient procedure for the stereoselective synthesis of (E)- and (Z)-2-alkene-4-ynoates and -nitriles by a simple reaction of vic-diiodo-(E)-alkenes with acrylic esters and nitriles catalyzed by in situ prepared Pd(0) nanoparticles in water has been d

Full text of DOI:10.1021/ol0708121

ORGANIC
LETTERS
2007
Vol. 9, No. 12
2409-2412
A New Route to the Synthesis of (E)-
and (Z)-2-Alkene-4-ynoates and Nitriles
from vic-Diiodo-(E)-alkenes Catalyzed by
Pd(0) Nanoparticles in Water
Brindaban C. Ranu* and Kalicharan Chattopadhyay
Department of Organic Chemistry, Indian Association for the CultiVation of Science,
JadaVpur, Kolkata 700 032, India
ocbcr@iacs.res.in
Received April 5, 2007
ABSTRACT
An efficient procedure for the stereoselective synthesis of (E)- and (Z)-2-alkene-4-ynoates and -nitriles by a simple reaction of vic-diiodo-(E)-
alkenes with acrylic esters and nitriles catalyzed by in situ prepared Pd(0) nanoparticles in water has been developed. Addition of acrylic
esters leads to (E)-isomers exclusively, whereas (Z)-isomers are obtained in high stereoselectivity from reactions of acrylonitrile. The aqueous
slurry of Pd nanoparticles is recycled. A probable mechanism has been suggested.
The 1,3-enyne unit is of considerable interest in organic
synthesis as these moieties are present in many naturally
occurring and biologically active compounds1 such as
terbinafine,2 a potent drug for superficial fungal infections,
and calichemicin γ1,3 an effective antitumor antibiotic. The
enynoates are also very useful synthetic intermediates.4
Only a limited number of procedures for the synthesis of
conjugated enynes have been developed. One of the most
prevalent protocols was Pd-Cu-catalyzed coupling between
an alkyne or an organometallic alkyne and a vinyl halide.5,6
Palladium-catalyzed oxidative alkynylation of alkenes has
also been demonstrated to produce enynes.7b,c Another
alternative approach involved copper-catalyzed coupling of
alkynes or alkyne derivatives with vinyl iodides.8 However,
these methods suffer from some limitations such as prepara-
tion of an organometallic alkyne and stereodefined vinyl
halide through lengthy procedures, poor functional group
tolerance, and undesired side products resulting in low
yields.5a,7 We now report a new route involving a simple
reaction of Vic-diiodoalkenes with an activated alkene
catalyzed by Pd(0) nanoparticles in water (Scheme 1). The
use of metal nanoparticles in reactions generating carbon-
carbon bonds has attracted considerable attention in recent
times because of their high reactivity, selectivity, and
improved yields of products.9
(1) (a) Rudi, A.; Schleyer, M.; Kashman, Y. J. Nat. Prod. 2000, 63,
1434. (b) El-Jaber, N.; Estevez-Braun, A.; Ravelo, A. G.; Munoz-Munoz,
O.; Rodriguez-Afonso, A.; Murguia, J. R. J. Nat. Prod. 2003, 66, 722. (c)
Bohlmann, F.; Chemistry of Acetylenes; Viehe, H. G., Ed.; Mercel Dekker:
New York, 1969, p 977.
(2) Iverson, S. L.; Uetrecht, J. P. Chem. Res. Toxicol. 2001, 14, 175.
(3) Zein, N.; Sinha, A. M.; McGahren, W. J.; Ellestad, G. A. Science
1988, 240, 1198.
(7) (a) Negishi, E.-I.; Qian, M. X.; Zeng, F. X.; Anastasia, L.; Babinski,
D. Org. Lett. 2003, 5, 1597. (b) Nishimura, T.; Araki, H.; Maeda, Y.;
Uemura, S. Org. Lett. 2003, 5, 2997. (c) Jeffery, T. Synthesis 1987, 70.
(8) (a) Marshall, J. A.; Chobanian, H. R.; Yanik, M. M. Org. Lett. 2001,
3, 4107. (b) Hoshi, M.; Shirakawa, K. Synlett 2002, 1101. (c) Bates, C. G.;
Saejueng, P.; Venkataraman, D. Org. Lett. 2004, 6, 1441.
(4) Suemune, H.; Hayashi, N.; Funakoshi, K.; Akita, H.; Oishi, T.; Sakai,
K. Chem. Pharm. Bull. 1985, 33, 2168.
(5) (a) Lu, X.; Huang, X.; Ma, S. Tetrahedron Lett. 1992, 33, 2535. (b)
Takauchi, R.; Tanabe, K.; Tanaka, S. J. Org. Chem. 2000, 65, 1558.
(6) Negishi, E.-I.; Anastasia, L. Chem. ReV. 2003, 103, 1979.
(9) (a) Moreno-Manas, M.; Pleixats, R. Acc. Chem. Res. 2003, 36, 638.
(b) Reetz, M. T.; deVries, J. G. Chem. Commun. 2004, 1559. (c) Astruc,
D.; Lu, F.; Aranzaes, J. R. Angew. Chem., Int. Ed. 2005, 44, 7852.
10.1021/ol0708121 CCC: $37.00
© 2007 American Chemical Society
Published on Web 05/08/2007

in situ from this reagent system.11 The formation of Pd
nanoparticles was also detected by us from analysis of the
reaction mixture by transmission electron microscopy (TEM)
and Energy Dispersive X-ray spectroscopy (EDS). The TEM
image and EDS showed the palladium nanoparticles with a
size of 2-6 nm (Figures 1 and 2). The slurry of palladium
Scheme 1
To identify a suitable catalyst and standardize the reaction
condition the reaction of Vic-(E)-diiodostyrene with methyl
acrylate was studied with a variety of Pd catalysts at varied
experimental conditions. These include Pd(OAc)2/n-Bu4NBr/
Na2CO3, PdCl2/TBAB/Na2CO3/H2O, PdCl2/sodium dodecyl
sulfate (SDS)/Na2CO3/H2O, PdCl2/TBAI/Na2CO3, and Pd-
(dba)3/P(o-tol)3/Et3N/CH3CN. The results were summarized
in Table 1. As evident from the results, the PdCl2/TBAB/
Table 1. Standarization of Catalyst
yield
(%)
entry
catalytic system
time, condition
Figure 1. TEM image of Pd nanoparticle formed in the reaction
mixture.
1
2
Pd(OAc)2, TBAB, Na2CO3
Pd(OAc)2, TBAB, Na2CO3
24 h (rt)
microwave,
20
1 min (run time),
1 min (hold time),
100 °C, 100 W
6 h (80 °C)
nanoparticles in water was recycled for two runs without
any loss of efficiency. After two runs the reactivity decreases.
3
Pd(OAc)2, TBAB, Na2CO3
in water
65
82
4
5
6
7
PdCl2, TBAB, Na2CO3 in water 6 h (80 °C)
PdCl2, SDS, Na2CO3 in water 6 h (80 °C)
PdCl2, TBAI, Na2CO3 in water 12 h (80 °C)
10
25
Pd2(dba)3, P(o-tol)3, Et3N
in CH3CN
24 h (reflux)
Na2CO3/H2O system was found to produce the best results
in terms of reaction time and yield and thus this reagent
system is selected to be used for all the reactions.
The experimental procedure is very convenient.10 A simple
reaction of Vic-diiodoalkene and conjugated alkene in the
presence of the PdCl2/TBAB/Na2CO3/H2O system provided
the product. The palladium(0) nanoparticles were produced
(10) Representative Experimental Procedure for Enyne Synthesis
(entry 4, Table 2). To a stirred mixture of tetrabutylammonium bromide
(323 mg, 1 mmol) and PdCl2 (3.5 mg, 0.02 mmol) in water (3 mL) were
added 1-(1,2-diiodovinyl)-4-methylbenzene (370 mg, 1 mmol), methyl
acrylate (344 mg, 4 mmol; excess amount was used to avoid any loss during
reflux), and Na2CO3 (424 mg, 4 mmol). The mixture was then heated at 80
°C (oil bath) for 6 h (TLC). After being cooled the reaction mixture was
extracted with Et2O (3 × 10 mL). The ether extract was washed with water
and brine and dried (Na2SO4). The solvent was evaporated under reduced
pressure to leave a crude product that was purified by column chromatog-
raphy over silica gel (ether-hexane 5:95) to afford the pure product, 5-p-
tolylpent-2-en-4-ynoic acid methyl ester (156 mg, 78%) as a yellow solid:
Figure 2. Energy dispersive X-ray spectra with use of a Cu-grid.
mp 72-73 °C; IR (KBr) 2852, 2193, 1718, 1622 cm-1 1H NMR (300
;
MHz, CDCl3) δ 2.33 (s, 3H), 3.78 (s, 3H), 6.28 (d, J ) 15.7 Hz, 1H), 6.98
(d, J ) 15.7 Hz, 1H), 7.15 (d, J ) 8.1 Hz, 2H), 7.37 (d, J ) 8.1 Hz, 2H);
13C NMR (CDCl3, 75 Hz) δ 21.7, 51.9, 86.0, 99.0, 119.2, 125.7, 129.1,
129.3 (2C), 132.0 (2C), 139.8, 166.6. Anal. Calcd for C13H12O2: C, 77.98;
H, 6.04. Found: C, 77.88; H, 5.99. The combined aqueous layer and extract
was concentrated under reduced pressure and was used for the next reaction.
Several structurally diverse Vic-diiodoalkenes underwent
reactions with conjugated alkenes such as acrylic ester and
(11) Zhang, Z.; Zha, Z.; Gan, C.; Pan, C.; Zhou, Y.; Wang, Z.; Zhou,
M.-M. J. Org. Chem. 2006, 71, 4339.
2410
Org. Lett., Vol. 9, No. 12, 2007

nitriles catalyzed by in situ prepared Pd(0) nanoparticles in
water to produce the corresponding 1,3-enyne esters and
nitriles in good yields. The results are summarized in Table
2. The substituents on the aromatic ring of the diiodoalkenes
The mechanism of this reaction has also been investigated.
Two alternative routes (a and b) as outlined in Scheme 2
Scheme 2. Possible Mechanism of the Coupling Reaction
Table 2. Cross-Coupling Reaction of Diiodo Compounds with
Activated Alkenes
have been considered. In route a the (E)-diiodoalkene is
proposed to undergo elimination of HI to form iodoalkyne,
which then couples with conjugated alkene in Heck fashion
catalyzed by Pd(0) to form the enyne. Route b proposes the
initial formation of an iodopalladium complex 1 via Heck
coupling with conjugated alkene followed by â-elimination
to form the hydridopalladium halide π complex 2, which
may give rise to two isomers A and B by hydridopalladium
halide elimination.13 Now, isomer A may lead to the product
by syn elimination of HI, and on the other hand, B may
produce the enyne through E-2 type elimination. On theoreti-
cal calculation it was found that A is energetically favorable
by 0.3 kcal/mol compared to B.14 Thus, the formation of
product through intermediate A is predicted.
(12) Beletskaya, I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009.
(13) Shi, M.; Liu, L.-P.; Tang, J. J. Org. Chem. 2005, 70, 10420.
(14) The ground state structural calculations for the intermediate products
such as cis and trans ester were computed by using Hartee-Fock (HF/
STo-3G) levels with GAUSSIAN software: Frisch, M. J.; Trucks, G. W.;
Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;
Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J.
M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara,
M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda,
Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.;
Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.;
Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala,
P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.;
Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J.
V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.;
Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D.
J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe,
M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.;
Pople, J. A. Gaussian 03, Revision B.03; Gaussian, Inc.: Pittsburgh, PA,
2003.
a Yields refer to those of purified products characterized by IR, 1H, and
13C NMR spectroscopic data b Reaction was carried out under sonication.
did not have any appreciable effect on the reaction. Both
aryl- and alkyl-substituted alkenes participated in this reac-
tion. However, reaction of dibromoalkenes in place of
diiodoalkenes produced relatively low yields (30-40%). This
method is compatible with a variety of substituents such as
OMe, Cl, Br, and methylenedioxy. Significantly, coupling
with acrylic esters always provided (E)-isomers exclusively,
whereas acrylonitriles pushed the reaction to give (Z)-alkenes
in high selectivity. This type of high selectivity with CO2R
compared to the relatively small CN group is well addressed
in Heck coupling.12
Org. Lett., Vol. 9, No. 12, 2007
2411

To check the feasibility of route a, a blank experiment
with the starting diiodoalkene under identical experimental
conditions without conjugated alkene was carried out, and
significantly, no iodoalkyne as predicted in route a was
obtained (eq 1). Thus, route a was eliminated. On the other
hand, a reaction of cis-diiodostyrene with the same conju-
gated alkene under identical reaction conditions produced
the corresponding 1,3-diene (eq 2). This certainly supports
route b.
this strategy for the stereoselective synthesis of conjugated
enynoates and nitriles from diiodoalkenes involving pal-
ladium nanoparticles is novel and not reported earlier.
Acknowledgment. We are pleased to acknowledge the
financial support from CSIR, New Delhi [Grant No. 01(1936)/
04] for this investigation. K.C. is thankful to CSIR for his
fellowship. We also thank Dr. N. Guchhait of Calcutta
University for his help in theoretical calculations.
In conclusion, the present protocol using in situ prepared
palladium(0) nanoparticles provides a very convenient and
efficient method for a one-pot synthesis of conjugated enyne
compounds from Vic-diiodoalkenes. The significant improve-
ments offered by this procedure are operational simplicity,
excellent stereoselectivity, general applicability, high isolated
yields of products, and reaction in aqueous medium avoiding
hazardous organic solvents. To the best of our knowledge
Supporting Information Available: Characterization (IR,
1H, and 13C NMR spectroscopic data and elemental analysis)
for the new compounds reported in Table 2 (listed in entries
4-12 and 14) and 13C NMR spectra of all compounds listed
in Table 2. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL0708121
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Org. Lett., Vol. 9, No. 12, 2007