An efficient and general microwave-assisted copper-catalyzed Conia-ene reaction of terminal and internal alkynes tethered to a wide variety of carbonucleophiles

Article abstract of DOI:10.1002/adsc.201000351

This paper describes a highly efficient, microwave-assisted, Conia-ene reaction of alkynes bearing a stabilizing carbon nucleophile. The reaction, catalyzed by a commercially available copper catalyst, proceeds under neutral conditions and is generally applicable even to less reactive nucleophiles such as malonate, cyanoacetate, and sulfonylacetate derivatives. This copper-mediated cycloisomerization is also applicable to internal unactivated alkynes leading exclusively to the corresponding 5-membererd products having an E-olefinic chemistry.

Full text of DOI:10.1002/adsc.201000351

UPDATE
DOI: 10.1002/adsc.201000351
An Efficient and General Microwave-Assisted Copper-Catalyzed
Conia-Ene Reaction of Terminal and Internal Alkynes Tethered
to a Wide Variety of Carbonucleophiles
Sonia Montel,a Didier Bouyssi,a,* and Geneviꢀve Balmea,*
a
ICBMS, Institut de Chimie et Biochimie Molꢁculaire et Supramolꢁculaire – (UMR CNRS 5246) – Universitꢁ Lyon I,
ESCPE Lyon, Bꢂt Curien, 43 Bd du 11 novembre 1918, 69622 Villeurbanne, France
Fax : (+33)-4-7244-8232; e-mail: bouyssi@univ-lyon1.fr or balme@univ-lyon1.fr
Received: May 5, 2010; Published online: September 2, 2010
Abstract: This paper describes a highly efficient,
microwave-assisted, Conia-ene reaction of alkynes
bearing a stabilizing carbon nucleophile. The reac-
tion, catalyzed by a commercially available copper
catalyst, proceeds under neutral conditions and is
generally applicable even to less reactive nucleo-
philes such as malonate, cyanoacetate, and sulfonyl-
substrates. In this context, in 1994, a cobalt-mediated
ene-reaction under UV irradiation of various keto
ester-tethered alkynes was developed.[4] This was fol-
lowed by various transition metal- or Lewis acid-cata-
lyzed Conia-ene reactions developed under mild and
neutral conditions.[5] Although these processes are
synthetically very useful, they suffer from some limi-
tations since their applications are restricted to highly
enolizable b-keto esters or b-diketones as nucleo-
philes.[6] Other active methylene compounds such as
malonate or cyanoacetate derivatives remained unaf-
fected due to their lower acidity and enolizable abili-
ty. In 1991, our group had overcome this restriction in
successfully developing a general method allowing the
cyclization of a variety of d-acetylenic-stabilized car-
banions by using catalytic quantities of both a palladi-
um complex and potassium tert-butoxide.[7] More re-
cently, we communicated a similar cyclization reaction
using inexpensive copper salts such as CuI as catalyst
in place of palladium.[8] However, these two last
Conia-ene reactions require the presence of catalytic
ACHTUNGTRENNUNGacetate derivatives. This copper-mediated cycloiso-
merization is also applicable to internal unactivated
alkynes leading exclusively to the corresponding 5-
membererd products having an E-olefinic chemis-
try.
Keywords: alkynes; Conia-ene reaction; copper;
cyclization; microwave irradiation
Introduction
The importance of natural products of biological in- amounts of strong base that may limit their applicabil-
terest containing the cyclopentyl moiety has stimulat- ity in organic synthesis. In 2009, Li and co-workers
ed in recent years the development of various syn- have reported an efficient Conia-ene reaction of e-
thetic methods to gain access to such structures.[1] acetylenic b-keto esters in the presence of catalytic
Among them, the cyclization of terminal alkynes amounts of (CuOTf)2·C6H6 (0.1 equiv.) and AgBF4
bearing an enolizable carbonyl group (the so-called (0.1 equiv.) in DCE at 1008C. However, attempts to
Conia-ene type reaction) and leading to functional- extend these results to less reactive methine com-
ized methylenecyclopentanes has been extensively ex- pounds met with limited success.[9]
plored in recent decades. Indeed, after Coniaꢃs pio-
In an effort to overcome this limitation, we have re-
neering work on the thermal cyclization of e-acetylen- visited the copper-catalyzed Conia-ene reaction and,
ic carbonyl compounds at temperatures above in this update, we report the development of a new
3008C,[2] the first metal-catalyzed version of this reac- catalytic method for this process based on the use of
tion was developed in 1983 by the same group by use the inexpensive, stable to air, soluble, ready available
of HgCl2 in strong acidic media.[3] However the dras- cationic copper complex, Cu (PPh3)2]NO3,[10]
ACTHNUTRGENNU[G (phen)ACHTUGNTRENNUGN
tic reaction conditions required or the toxicity of mer- under low catalyst loading with the assistance of mi-
cury salts limited the scope of application of these crowave irradiation. This improved procedure allows
two cycloisomerization reactions. Therefore, further the reaction to proceed in high yields, under neutral
studies have been carried out with the aim of finding conditions, with only 1 mol% catalyst and is generally
milder conditions reactions or extending the scope of applicable even to the less reactive malonate, cyano-
the reaction to a wide variety of carbonucleophilic
ACHTUNGTRENaNGNU cetate, and sulfonylacetate derivatives. Moreover,
Adv. Synth. Catal. 2010, 352, 2315 – 2320
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2315

Sonia Montel et al.
UPDATE
this cycloisomerization reaction was successfully ex-
tended to the more challenging non-terminal alkynes,
leading exclusively to the corresponding trans-adducts
in good to excellent yields.
Results and Discussion
Application of microwave irradiations in organic syn-
thesis has become very popular over the past few
years.[11] Indeed, this new technology is now recog-
nized as a powerful tool to accelerate organic reac-
tions and to improve the yields and the substrate
scope. However, to the best of our knowledge, micro-
wave irradiation to enhance the Conia-ene type reac-
tions has never been explored. Therefore, with the
idea of finding a low copper catalyst loading proce-
dure using neutral conditions, we envisioned to per-
form the Conia reaction of a wide range of active me-
thine compounds bearing a 4-alkynyl group under mi-
crowave irradiation.
Preliminary microwave experiments were per-
formed on the diester-tethered alkyne 1a as model
substrate in order to determine the optimum condi-
tions for the cycloisomerization reaction. The reac-
tions were carried out at 1508C, with 1 mol% of
CuACHTUNGTRENNUNG[(phen)ACHTUNGTRENNUNG(PPh3)2]NO3, in several solvents including
THF, DMSO, CH3CN, MeOH, NMP, DCE, DME,
DMF, dioxane, diglyme and toluene. Only dioxane
was successful in this reaction leading to the corre-
sponding exo-cyclized product 2a in 77% yields after
45 min reaction while the use of THF afforded only
minor yields of product. In the case of the other
tested solvents, no conversion was detected while a
degradation of the starting material was observed. Im-
portantly, no reaction took place under conventional
heating conditions, even after a long reflux in dioxane
with 5 mol% catalyst loading. Other control experi-
Scheme 1. Copper-catalyzed Conia-ene reaction developed
[a]
on terminal alkynes.
All reactions were run at 1508C
under microwave irradiation in dioxane using 1 mol% of
[Cu(Phen)
(PPh3)2]NO3 as catalyst.[b] THF was used instead
of dioxane.[c] 2 mol% of catalyst were used.
A
ACHTUNGTRENNUNG
ments verified that no observable reaction occurred was also investigated. Indeed, earlier work in our lab-
in the absence of the copper catalyst, or in the sole oratory has shown that, in this case, due to the ability
presence of the phenanthroline ligand. The reaction of the resulting tertiary allylic sulfonyl group to act as
was also conducted in the presence of CuI as catalyst a leaving group, the CuI-catalyzed cycloisomerization
but only the starting material was recovered.
generates a carbenoid copper complex which evolves
To define the scope of this novel copper-catalyzed to the formation of a dimeric compound.[12] Pleasingly,
Conia-ene reaction performed under neutral condi- subjection of sulfonyl ester 1g to the above micro-
tions, several other active methine compounds bear- wave-mentioned conditions afforded predominantly
ing a 4-alkynyl group were examined using our the primary allylic sulfone 2g’ arising from the known
above-mentioned optimal conditions. Representative thermal 1,3-rearrangement of the initially formed ter-
results are shown in Scheme 1. Cyclization of the tiary sulfone 2g which was isolated as the minor com-
more acidic w-acetylenic b-keto esters 1b–d and dike- pound.[13] Similar results were obtained with the cor-
tone 1e proceeded efficiently leading to the corre- responding keto sulfone 1h.
sponding exocyclic substrates 2b–e in excellent yields.
Encouraged by these results, we further investigat-
The w-acetylenic b-cyano ester 1f also underwent the ed the application of the above-mentioned cycloiso-
desired cyclization reaction to give the corresponding merization to internal alkynes.[14] To the best of our
product in high yield after microwave irradiation at knowledge, only very few successful examples de-
1508C for 20 min (2 mol% catalyst). The reactivity of scribe the Conia-ene cycloisomerization of such sub-
the more challenging a-sulfonyl e-acetylenic ester 1g strates and they are limited to those having b-keto
2316
asc.wiley-vch.de
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2315 – 2320

An Efficient and General Microwave-Assisted Copper-Catalyzed Conia-Ene Reaction
esters as nucleophiles, and a competitive 5-exo/6-endo enhances the yield of the cyclization reaction[16] since
cyclization mode is also generally observed.[15] Our a 90% yield of 4a, having exclusively E-olefinic
first attempt to perform the cycloisomerization of the chemistry,[17] was obtained when using 20 mol% of
aryl-substituted alkyne 3a under our optimized condi- CaH2, 10 mol% of copper catalyst, after microwave ir-
tions failed to give a cyclized product. Increasing the radiation at 1508C for 30 min in dioxane (Scheme 2).
quantity of copper catalyst added from 2 mol% to Pleasingly, these latter conditions applied to the less
10 mol% led to the formation of the 5-exo cyclized reactive diesters 3b resulted in the exclusive forma-
product 4a along with other minor unidentified side tion of 4b in high yield. To explore the scope of this
products in a 60% global yield after microwave irradi- copper-mediated cyclization, we studied the reaction
ation at 1508C for 75 min. After several fruitless at- of several diester-tethered alkynes substituted with
tempts to improve the formation of 4a, we fortuitous- various substituents including aryl, heteroaryl and
ly found that catalytic addition of CaH2 significantly alkyl groups and the results are summarized in
Scheme 2. Copper-catalyzed Conia-ene reaction developed on internal alkynes.
Adv. Synth. Catal. 2010, 352, 2315 – 2320
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2317

Sonia Montel et al.
UPDATE
Scheme 2. The cyclization reaction proceeds with reaction took place after microwave irradiation at
good to excellent yields with electron-deficient aryl- 1208C for 20 min in THF, in the presence of
and heteroaryl-substituted alkynes (4c–g). The reac- CuACHTUNTGRENNUG[(phen)AHCTUNGTREN(NUNG PPh3)2]NO3 (1 mol%) leading exclusively
tion occurred comparatively much more slowly with to the corresponding 5-methylene-4,5-dihydrofuran 7
the substituted-alkylalkyne 3i leading to 4i and with in 89% yield.[19]
the alkyne 3j substituted with a piperonyl moiety. In
this latter case, the 5-exo cyclized product 4j was ob-
tained in slightly lower yield (57%) along with 17% Conclusions
of the 6-endo cyclized monoester 5. Interestingly, a
functional group such as benzyl acetate is compatible In summary, we have developed an efficient, new,
with such conditions (4h). To clarify the mechanism copper-catalyzed Conia-ene cyclization which pro-
of this copper-mediated-cyclization,[18] the reaction of ceeds under neutral conditions and microwave irradi-
the deuterated alkyne substrate [D]-3b was undertak- ation, using a variety of tethered stabilized nucleo-
en and led to the exclusive formation of [D]-4b with philes. Moreover, the reaction was successfully ex-
deuterium syn to the diester moiety.
tended to internal unactivated alkynes leading in
This result suggests that this copper-mediated good yields to the corresponding 5-exo cyclized prod-
Conia-ene cyclization reaction proceeds via formation ucts with very high stereoselectivity.
of a copper enolate intermediate which adds in a cis
fashion across the triple bond. A subsequent intramo-
lecular deuteration of the copper metalate gives [D]- Experimental Section
4b and regenerates the copper catalyst (Scheme 3).
General Remarks
Proton magnetic resonance (1H NMR) spectra were mea-
sured at 300 MHz and carbon magnetic resonance
(13C NMR) spectra at 75 MHz with Bruker DRX 300 and
ALS 300 spectrometers. Chemical shifts are reported in
parts per million (ppm) from tetramethylsilane with the sol-
vent resonance of chloroform-d (d =7.26). Spectra were re-
ported as follows: chemical shift (d ppm), integration, multi-
plicity (s=singlet, d=doublet, t=triplet, q=quartet, m=
multiplet, br=broad), and coupling constants (reported in
Hz). High-resolution mass spectra were recorded on a Ther-
moquest Finnigan MAT 95 Xl. Melting points (mp) were
measured on a Bꢅchi B-540 and are uncorrected. Micro-
wave-assisted synthesis was carried out in an InitiatorTM
single mode microwave cavity producing controlled irradia-
tion at 2.45 GHz (Biotage AB, Uppsala). The reactions were
run in sealed vessels (0.5 to 20 mL) and magnetic stirring
was used. A variable power source was employed to reach
the desired temperature and then to maintain it in the
vessel during the programmed period of time.
General Procedure
In a microwave vial, were successively added 0.25 mmol of
Scheme 3. Proposed mechanistic pathway.
active methine compound 1a–h, 1 mol% of Cu
ACHTUNGTRENNUNG(Phen)-
AHCTUNGTRENNG(UN PPh3)2NO3 and 1 mL of dioxane. For compounds 3a–j, 10
or 20 mol% of copper complex and 20 mol% of CaH2 were
The copper-catalyzed Conia-ene reaction of the 2- used. The vial was capped and exposed to microwave heat-
ing at 1508C during the defined time (InitiatorTM single
propynyl-1,3-dicarbonyl derivative 6 was also briefly
mode microwave cavity producing controlled irradiation at
explored (Scheme 4). It was found that the cyclization
2.45 GHz, Biotage AB, Uppsala). After the completion of
the reaction (monitored by TLC), the reaction mixture was
filtered onto celite, and concentrated under vacuum. The
crude product was purified by flash chromatography on
silica gel to obtain the desired product 2a–h or 4a–j.
The product 4e (yield: 90%) was isolated as a colorless
viscous oil. 1H NMR (300 MHz, CDCl3): d=1.78–1.88 (m,
1H), 2.38 (t, 2H, J=7 Hz), 2.93 (t, 2H, J=7 Hz), 3.75 (s,
Scheme 4. Access to 5-methylene-4,5-dihydrofuran.
6H), 6.8 (s, 1H), 7.09 (br s, 1H), 7.28 (br s, 1H), 7.63 (t, 1H,
2318
asc.wiley-vch.de
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2315 – 2320

An Efficient and General Microwave-Assisted Copper-Catalyzed Conia-Ene Reaction
J=7 Hz), 8.58 (br s, 1H); 13C NMR (75 MHz, CDCl3): d=
25.2, 33.3, 36.2, 53.4, 66.4, 117.8, 121.8, 124.7, 126.9, 129.1,
136.8, 147.1, 171.6; ESI-HR-MS: m/z=276.1229, calcd. for
[C15H17NO4 +H]+: 276.1230.
Nakamura, J. Am. Chem. Soc. 2008, 130, 17161; Sn-cat-
alyzed reactions: l) O. Kitagawa, H. Fujiwara, T.
Suzuki, T. Tagushi, M. Shiro, J. Org. Chem. 2000, 65,
6819.
The product 4f (yield: 72%) was isolated as a white solid;
mp 60–618C. H NMR (300 MHz, CDCl3): d=1.84–1.93 (m,
[6] A Conia-ene type cyclization of nitrogen- and oxygen-
tethered acetylenic malonic esters was recently report-
1
2H), 2.41 (t, 2H, J=7 Hz), 2.71 (td, 2H, J=7, 2.5 Hz), 3.78
(s, 6H), 6.74 (s, 1H), 7.17 (d, 1H, J=5 Hz), 7.24 (br s),
ed using catalytic amounts of InACTHNUTRGENUN(G OTf)3 and DBU: K.
Takahashi, M. Midori, K. Kawano, J. Ishihara, S. Hata-
keyama, Angew. Chem. 2008, 120, 6340; Angew. Chem.
Int. Ed. 2008, 47, 6244. For other related metal-cata-
lyzed cyclization reactions leading to nitrogen and
oxygen heterocycles, see: a) X. Marat, N. Monteiro, G.
Balme, Synlett 1997, 845; b) B. Clique, N. Monteiro, G.
Balme, Tetrahedron Lett. 1999, 40, 1301; c) M. Cavic-
chioli, X. Marat, N. Monteiro, B. Hartmann, G. Balme
Tetrahedron Lett. 2002, 43, 2609; d) M. Nakamura, C.
Liang, E. Nakamura, Org. Lett. 2004, 6, 2015; e) S.
Morikawa, S. Yamazaki, Y. Furuzaki, N. Amano, K.
Zenke, K. Kakiuchi, J. Org. Chem. 2006, 71, 3540;
f) A. B. Leduc, T. P. Lebold, M. A. Kerr, J. Org. Chem.
2009, 74, 8414; g) T. P. Lebold, A. B. Leduc, M. A.
Kerr, Org. Lett. 2009, 11, 3770.
7.28–7.31ACHTUNGTRENNUNG
(m, 1H); 13C NMR (75 MHz, CDCl3): d=25.1,
32.8, 36.5, 53.4, 65.7, 122.0, 123.7, 125.5, 128.9, 139.6, 140.3,
171.9; ESI-HR-MS: m/z=303.0660, calcd. for [C14H16SO4 +
Na]+: 303.0662.
References
[1] For selected references, see: a) B. M. Trost, A. B. Pin-
kerton, J. Org. Chem. 2001, 66, 7714; b) D. F. Taber, H.
Yu, C. D. Incarvito, A. L. Rheingold, J. Am. Chem.
Soc. 1998, 120, 13285; c) G. A. Molander, E. D. Dowdy,
H. Schumann, J. Org. Chem. 1998, 63, 3386; d) A.
Hassner, E. Ghera, T. Yechezkel, V. Kleiman, T. Bala-
subramanian, D. Ostercamp, Pure Appl. Chem. 2000,
72, 1671; e) M. Mikolajczyk, M. Mikina, R. Zurawinski,
Pure Appl. Chem. 1999, 71, 473; f) S. Sakuda, Y. Su-
giyama, Z-Y. Zhou, H. Takao, H. Ikeda, K. Kakinuma,
Y. Yamada, H. Nagasawa, J. Org. Chem. 2001, 66,
3356; g) B. Heasley, Eur. J. Org. Chem. 2009, 10, 1477.
[2] a) R. Bloch, P. Le Perchec, F. Rouessac, J.-M. Conia,
Tetrahedron 1968, 24, 5971; b) P. Le Perchec, J.-M.
Conia, Synthesis 1975, 1; c) J. Drouin, F. Leyendecker,
J.-M. Conia, Tetrahedron 1980, 36, 1203.
[7] a) N. Monteiro, G. Balme, J. Gorꢁ, Tetrahedron Lett.
1991, 32, 1645; b) N. Monteiro, J. Gorꢁ, G. Balme, Tet-
rahedron 1992, 48, 10103.
[8] D. Bouyssi, N. Monteiro, G. Balme, Tetrahedron Lett.
1999, 40, 1297.
[9] C.-L. Deng, T. Zou, Z.-Q. Wang, R.-J. Song, S.-M. Guo,
J.-H. Li, J. Org. Chem. 2009, 74, 412. In this Cu/Ag co-
catalyzed Conia-ene reaction, 2-(pent-4-ynyl)malono-
AHCTUNGTREGnNNNU itrile remained unaffected while 2-(pent-4-ynyl)malo-
nate gave moderate yields of the corresponding cy-
clized product having the double bond in the endocy-
clic position.
[3] J. Boaventura, J. Drouin, J.-M. Conia, Synthesis 1983,
801.
[10] This copper complex is commercially available or
easily prepared using known procedures: a) C. G.
Bates, P. Saejueng, M. Q. Doherty, D. Venkataraman,
Org. Lett. 2004, 6, 5005; for the use of this copper cata-
lyst in coupling reactions see: b) C. G. Bates, P. Sae-
jueng, J. M. Murphy, D. Venkataraman, Org. Lett. 2002,
4, 4727; c) S. Cacchi, G. Fabrizi, L. M. Parisi, Org. Lett.
2003, 5, 3843.
[11] For recent reviews on microwave-assisted organic syn-
thesis, see: a) C. O. Kappe, Angew. Chem. 2004, 116,
6408; Angew. Chem. Int. Ed. 2004, 43, 6250; b) A. de
La Hoz, A. Diaz-Ortiz, A. Moreno, Chem. Soc. Rev.
[4] a) R. Stammler, M. Malacria, Synlett 1994, 92; b) P.
Cruciani, C. Aubert, M. Malacria, Tetrahedron Lett.
1994, 35, 6677; c) P. Cruciani, C. Aubert, M. Malacria,
J. Org. Chem. 1995, 60, 2664; d) P. Cruciani, R. Stamm-
ler, C. Aubert, M. Malacria, J. Org. Chem. 1996, 61,
2699; e) J-L. Renaud, M. Petit, C. Aubert, M. Malacria,
Synlett 1997, 931; f) J.-L. Renaud, C. Aubert, M. Malac-
ria, Tetrahedron 1999, 55, 5113; g) C. Aubert, O. Bui-
sine, M. Petit, F. Slowinski, M. Malacria, Pure Appl.
Chem. 1999, 71, 1463.
[5] For Mo-catalyzed Conia-ene reactions: a) F. E. McDo-
nald, T. C. Olson, Tetrahedron Lett. 1997, 38, 7691; Re-
catalyzed reactions: b) Y. Kuninobu, A. Kawata, K.
Takai, Org. Lett. 2005, 7, 4823; Ni/Yb-catalyzed reac-
tions: c) Q. Gao, B.-F. Zheng, J.-H. Li, D. Yang, Org.
Lett. 2005, 7, 2185; Au-catalyzed reactions: d) J. J. Ken-
nedy-Smith, S. T. Staben, F. D. Toste, J. Am. Chem.
Soc. 2004, 126, 4526; e) S. T. Staben, J. J. Kennedy-
Smith, F. D. Toste, Angew. Chem. 2004, 116, 344;
Angew. Chem. Int. Ed. 2004, 43, 340; f) A. Ochida, H.
Ito, M. Sawamura, J. Am. Chem. Soc. 2006, 128, 16486;
g) J.-H. Pan, M. Yang, Q. Gao, N.-Y. Zhu, D. Yang,
Synthesis 2007, 2539; h) H. Ito, Y. Makida, H. Ohmiya,
M. Sawamura, Org. Lett. 2008, 10, 5051; i) F. Gagosz,
Org. Lett. 2005, 7, 4133; Pd/Yb-catalyzed reactions:
j) B. K. Corkey, F. D. Toste, J. Am. Chem. Soc. 2005,
127, 17168; In-catalyzed reactions: k) Y. Itoh, H. Tsuji,
K.-I. Yamagata, K. Endo, I. Tanaka, M. Nakamura, E.
2005, 34, 164; c) A. Loupy, ACTHNUTRGNEUGN(Ed. ), in: Microwaves in
Organic Synthesis, 2nd edn., Wiley-VCH, Weinheim,
2006.
[12] Copper iodide can promote the cyclization of 1g, but
stoichiometric quantities of copper salt, base and proto-
nating species are needed, see: a) N. Monteiro, G.
Balme, J. Gorꢁ, Synlett 1992, 227; b) N. Monteiro, J.
Gorꢁ, B. Van Hemelryck, G. Balme, Synlett 1994, 447.
[13] P. Lin, G. H. Whitman, J. Chem. Soc. Chem. Commun.
1983, 1102.
[14] The required internal alkynes were easily prepared
using conventional Sonogashira coupling method: K.
Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett.
1975, 4467.
[15] For some rare examples of Conia-ene cycloisomeriza-
tion of internal alkynes see: a) ref.[5h]; b) C.-L. Deng,
Adv. Synth. Catal. 2010, 352, 2315 – 2320
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2319

Sonia Montel et al.
UPDATE
R.-J. Song, Y.-L. Liu, J.-H. Li, Adv. Synth. Catal. 2009,
351, 3096.
cording to a procedure reported by us earlier: G. Four-
net, G. Balme, J. Gorꢁ, Tetrahedron 1991, 47, 6293.
[18] Five types of mechanisms have been previously pro-
posed for the metal-mediated Conia-ene cyclization of
alkyne bearing an active methylene group see ref.[5k]
and references cited therein.
[19] Examples of the cycloisomerization of 2-propynyl-1,3-
dicarbonyl derivatives leading to the corresponding 5-
methylene-4,5-dihydrofurans are relatively scarce.
Among them, a paper describing a cyclization catalyzed
[16] A similar unexpected beneficial effect of CaH2 was re-
cently observed during a Pd-catalyzed coupling reac-
tion: F. Yu, X. Lian, S. Ma, Org. Lett. 2007, 9, 1703. In
our case, the role of CaH2 is still not fully understood.
It is noteworthy that when the same reaction was per-
formed in the presence of NaH in place of CaH2, 4a
was obtained in only 55% along with 5% of the 6-endo
decarboxylated product.
[17] The stereochemistry of the exocyclic double bond in 4a
was found to be E by comparison of its spectral and an-
alytical data with those of the compound prepared
from the reaction of 1a with methyl 4-iodobenzoate ac-
by CuACTHGUNRETNNU(G OTf)2, PPh3, in basic media was published
during the preparation of this manuscript, see: Y.-F.
Chen, H.-F. Wang, Y. Wang, Y.-C. Luo, H.-L. Zhu, P.-F.
Xu, Adv. Synth. Catal. 2010, 352, 1163.
2320
asc.wiley-vch.de
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2315 – 2320