PK reactions. On the other hand, regarding the selectivity
cyclopentenone vs diene formation in intramolecular PK
reactions of unactivated enynes, Krafft et al. have
reported that the thermolysis of their dicobalt hexacar-
bonyl complexes in refluxing toluene affords the exocyclic
1,3-dienes instead of the cyclopentenone products.9
In this context, we describe here the behavior of
electron-deficient 1,6- (and 1,7-) enynes having an ester,
cyano, or phosphonate function at the alkene terminus
in cobalt-mediated cyclizations,10 as well as the applica-
tion of this process to the controlled formation of either
the exocyclic 1,3-diene 2 or the PK bicyclo[3.3.0]octenone
3.
First, to explore the viability of R,â-unsaturated esters
in intramolecular PK reactions, the model 1,6-enynes 1a
and 1b, readily prepared by Wadsworth-Emmons ole-
fination of the corresponding alkynyl aldehyde, were
converted into their hexacarbonyldicobalt complexes
[Co2(CO)8, CH2Cl2] and treated under trimethylamine
N-oxide (TMANO) promoted conditions11 (conditions A
or B) and thermal conditions (CH3CN, 80 °C; conditions
C), which proved to be the best experimental conditions
in the case of the intramolecular PK reactions of R,â-
unsaturated sulfones.8 The results are summarized in
Table 1.
In tr a m olecu la r P a u son -Kh a n d Rea ction s
of r,â-Un sa tu r a ted Ester s a n d Rela ted
Electr on -Deficien t Olefin s
Marta Rodr´ıguez Rivero and J uan Carlos Carretero*
Departamento de Quı´mica Orga´nica, Facultad de Ciencias,
Universidad Auto´noma de Madrid, 28049 Madrid, Spain
juancarlos.carretero@uam.es
Received December 10, 2002
Abstr a ct: The intramolecular Pauson-Khand (PK) reac-
tion of a variety of electron-poor enynes having an ester,
cyano, or phosphonate group at the olefin terminus is
described. Depending on the reaction conditions and sub-
stitution at the enyne, their dicobalthexacarbonyl complexes
led preferentially to the exocyclic 1,3-diene or to the PK
cyclopentenone product. In general, the 1,3-diene was
obtained as the major product under N-oxide-promoted
conditions, while the PK product was selectively formed in
refluxing acetonitrile.
Today, the cobalt-mediated carbonylative cocyclization
of an alkyne and an alkene, known as the Pauson-
Khand (PK) reaction, has become one of the most
powerful methods for the synthesis of cyclopentenones.1
Concerning the structural scope of this reaction, although
its high tolerance to electronically different functional
groups at the alkyne moiety is well-known, this func-
tional group compatibility has been much less studied
in the case of the alkene partner. Particularly, since the
pioneering work of Pauson and Khand,2 it was generally
assumed that π-conjugated electron-deficient olefins such
as R,â-unsaturated esters and nitriles were not appropri-
ate substrates in Pauson-Khand reactions because the
key cobaltacycle intermediate underwent preferably an
elimination process to give a conjugated 1,3-diene3 rather
than the carbonyl insertion step required in the formation
of the cyclopentenone product. Unlike this belief, several
cases of successful cobalt-mediated PK reactions of
electron-poor olefins, without formation of 1,3-dienes,
have been described in recent years.4 Thus, Smit et al.
reported some examples of intramolecular PK reactions
of conformationally restricted enones,5 Cazes et al.
described that sterically uncongested electron-deficient
olefins, like methyl acrylate and acrylonitrile, are suitable
substrates in N-oxide-promoted intermolecular PK reac-
tion,6 and our group has recently reported the use of R,â-
unsaturated sulfoxides7 and sulfones8 in intramolecular
Synthetically interesting, the outcome of the reaction
of the enynes 1a ,b was very dependent on the reaction
conditions. Thus, in refluxing acetonitrile, only the PK
bicyclic product 3 could be detected and isolated (entries
3 and 6), whereas the use of N-oxide-promoted conditions
in toluene or CH2Cl2 at room temperature led to the
exocyclic 1,3-diene 2 as the major product12 (entries 1, 2,
and 5). A similar product selectivity was observed in the
case of the R,â-unsaturated phosphonate ester 1c: major
formation of the 1,3-diene 2c under N-oxide-promoted
conditions A (entry 7) and exclusive formation of the PK
product 3c under thermal conditions (entry 9). This study
was next applied to the 1,7-enyne 1d (entries 10-12).
(5) (a) Gybin, A. S.; Smit, W. A.; Caple, R.; Veretenov, A. L.;
Shashkov, A. S.; Vorontsova, L. G.; Kurella, M. G.; Chertkov, V. S.;
Carapetyan, A. A.; Kosnikov, A. Y.; Alexanyan, M. S.; Lindeman, S.
V.; Panov, V. N.; Maleev, A. V.; Struchkov, Y. T.; Sharpe, S. M. J . Am.
Chem. Soc. 1992, 114, 5555-5566. (b) Veretenov, A. L.; Smit, W. A.;
Vorontsova, L. G.; Kurella, M. G.; Caple, R.; Gybin, A. S. Tetrahedron
Lett. 1991, 32, 2109-2112. See also: (c) Thommen, M.; Keese, R.
Synlett 1997, 231-240. (d) Son, S. U.; Park, K. H.; Chung, Y. K. J .
Am. Chem. Soc. 2002, 124, 6838-6839.
(6) (a) Ahmar, M.; Antras, F.; Cazes, B. Tetrahedron Lett. 1999, 40,
5503-5506. See also: (b) Costa, M.; Mor, A. Tetrahedron Lett. 1995,
36, 2867-2870.
(7) Carretero, J . C.; Adrio, J . Synthesis 2001, 1888-1896.
(8) Adrio, J .; Rodr´ıguez Rivero, M.; Carretero, J . C. Chem. Eur. J .
2001, 7, 2435-2448.
(9) (a) Krafft, M. E.; Wilson, A. M.; Dasse, O. A.; Bon˜aga, L. V. R.;
Cheung, Y. Y.; Fu, Z.; Shao, B.; Scott, I. L. Tetrahedron Lett. 1998, 39,
5911-5914. See also: (b) Krafft, M. E.; Bon˜aga, L. V. R.; Wright, J .
A.; Hirosawa, C. J . Org. Chem. 2002, 67, 1233-1246.
(10) For tungsten-mediated intramolecular PK reactions of R,â-
unsaturated esters and nitriles, see: (a) Shiu, Y.-T.; Madhushaw, R.
J .; Li, W.-T.; Lin, Y.-C.; Lee, G.-H.; Peng, S.-M.; Liao, F. L.; Wang,
S.-L.; Liu, R. S. J . Am. Chem. Soc. 1999, 121, 4066-4067. (b) Hoye, T.
R.; Suriano, J . A. J . Am. Chem. Soc. 1993, 115, 1154-1156.
(11) (a) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetrahedron
Lett. 1990, 31, 5289-5292. (b) Pe´rez-Serrano, L.; Casarrubios, L.;
Dom´ınguez, G.; Pe´rez-Castells, J . J . Org. Chem. 2000, 65, 3513-3519.
(12) Unlike this behavior, Cazes et al. have reported some successful
N-oxide-promoted intermolecular PK reactions (see ref 6a).
(1) For some reviews, see: (a) Sugihara, T.; Yamaguchi, M.; Nish-
izawa, M. Chem. Eur. J . 2001, 7, 3315-3318. (b) Brummond, K. M.;
Kent, J . L. Tetrahedron 2000, 56, 3263-3283. (c) Chung, Y. K. Coord.
Chem. Rev. 1999, 188, 297-341. (d) Schore, N. E. Org. React. 1991,
40, 1-90. (e) Schore, N. E. Chem. Rev. 1988, 88, 1081-1119.
(2) (a) Khand, I. U.; Pauson, P. L. Heterocycles 1978, 11, 59-67. (b)
Khand, I. U.; Pauson, P. L. J . Chem. Soc., Chem. Commun. 1974, 379.
(3) For a recent review on metal-mediated cyclization of enynes to
give dienes, see: Aubert, C.; Buisine, O.; Malacria, M. Chem. Rev. 2002,
102, 813-834.
(4) For a review, see: Rodr´ıguez Rivero, M.; Adrio, J .; Carretero, J .
C. Eur. J . Org. Chem. 2002, 2881-2889.
10.1021/jo026828g CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/05/2003
J . Org. Chem. 2003, 68, 2975-2978
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