Intramolecular Pauson-Khand reactions of α,β-unsaturated esters and related electron-deficient olefins

Article abstract of DOI:10.1021/jo026828g

The intramolecular Pauson-Khand (PK) reaction 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 substitution 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.

Full text of DOI:10.1021/jo026828g

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
2975

TABLE 1. Coba lt-Med ia ted Cycliza tion of En yn es 1a -d
only product detected under conditions B (entries 5, 9,
11 and 13; 74-79% yield), while the PK product 3 was
selectively formed under conditions C (entries 4, 6, 8, 10
and 14; 42-67% yield). In the latter cases, the PK
products 3 were isolated as mixtures of epimers at C-6
(endo- + exo-isomers),17 generally with low stereoselec-
tivity, except the PK reactions of enynes 1h (entry 8) and
especially 1k (entry 14), which occurred with high endo-
selectivity.18
yield(%)c
entry enyne
n
EWG
R
conditionsa
2:3b
2
3
1
2
3
4
5
6
7
8
9
1a
1a
1a
1b
1b
1b
1c
1c
1c
1d
1d
1d
1
1
1
1
1
1
1
1
1
2
2
2
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
PO(OEt)2
PO(OEt)2
PO(OEt)2
CO2Et
H
H
H
Me
Me
Me
H
H
H
A
B
C
A
B
C
A
B
C
A
B
C
84:16
67:33
<2:>98
51:49
82:18
<2:>98
66:34
35:65
<2:>98
84:16
>98:<2
34:66
45
27 13
31
27 26
41
8
It is interesting to note that the chemoselectivity
exhibited in the cyclization of the dicobalt hexacarbonyl
complexes of the electron-poor enynes 1a -k in refluxing
acetonitrile (major formation of the cyclopentenone prod-
uct) is in contrast to the results described by Krafft et
al. in the thermolysis of the dicobalt hexacarbonyl
complexes of unactivated enynes in refluxing toluene,
which afforded selectively the 1,3-diene product.9 To
check if this different behavior was due to a solvent effect,
we performed the reaction of the cobaltcarbonyl com-
plexes of the enynes 1b and 1g in refluxing toluene. In
the case of 1b, we found effectively a reversal of the
chemoselectivity with regard to the result obtained in
refluxing acetonitrile, the diene 2b now being the major
product formed in the reaction, which shows that the
solvent plays an important role in the selectivity of the
thermally induced cyclization. However, the efficiency of
this diene formation process in refluxing toluene was
lower than using TMANO as a promoter in toluene at
room temperature (conditions B) probably due to the
relative instability of dienes 2 at high temperatures. In
agreement with this belief, in the case of the thermally
more unstable diene 2g, the reaction of its precursor
enyne 1g in refluxing toluene only led to decomposition
mixtures.
9
54
40 18
14 27
37
40
57
10
11
12
CO2Et
CO2Et
CO2Et
6
CO2Et
CO2Et
13 25
a
Conditions A: (i) Co2(CO)8, CH2Cl2, rt; (ii) Me3NO‚2H2O (7
equiv). Conditions B: (i) Co2(CO)8, molecular sieves (4 Å), toluene,
rt; (ii) Me3NO‚2H2O (7 equiv). Conditions C: (i) Co2(CO)8, CH2Cl2,
rt; (ii) CH3CN, 80 °C. Determined by 1H NMR on the crude
b
mixtures. c Yield after separation by silica gel chromatography.
This substrate proved to be more prone to giving the 1,3-
diene than in the case of the 1,6-enynes 1a -c, especially
under conditions B (entry 11), which afforded exclusively
the 1,3-diene 2d . However, the PK bicyclic product 3d
could be again obtained as the major product under
thermal conditions C, although with moderate chemose-
lectivity (entry 12, 2d :3d ) 34:66). In all cases, the
products 2 and 3 were readily separated by silica gel
chromatography.
To expand the scope of this process, the γ-oxygenated
R,â-unsaturated esters 1e-j, having different substitu-
tion at the γ-position, alkyne terminus, and ester moiety,
were readily prepared by piperidine-promoted condensa-
tion of the corresponding aldehyde with ethyl p-tolyl-
sulfinyl acetate13 (SPAC condensation, 81-83% yield) and
further hydroxyl protection.14 Following the same pro-
cedure, but using p-tolylsulfinyl acetonitrile15 in the
SPAC condensation step, we also prepared the R,â-
unsaturated nitrile 1k (68% overall yield). The results
obtained in the reaction of their dicobalt hexacarbonyl
complexes under both refluxing acetonitrile (conditions
C) and TMANO-promoted conditions (conditions B) are
collected in Table 2.
Except for the free alcohol 1e, which proved to be
unreactive (entries 1 and 2), in every case, the selectivity
of the reaction was generally high and again quite
sensitive to the reaction conditions. Interestingly, in the
case of the enynes 1g,i-k a complete shift in the reaction
selectivity was achieved. Thus, the 1,3-diene 216 was the
The reactivity and the potential synthetic interest of
dienes 2 in Diels-Alder reactions were also briefly
studied.19 Due to the relative instability of dienes 2, we
found it more efficient to perform a one-pot cobalt
cyclization/Diels-Alder process (Schemes 1 and 2). After
N-oxide-promoted cyclization of the cobalt complexes of
enynes 1g,i,j (conditions B), the crude dienes 2 were
treated in toluene at 100 °C with methyl maleimide as a
dienophile. In all cases, the reaction was completely
stereoselective, affording a single endo-cycloadduct 420
(42-51% overall yield from enynes 1). A similar result
was obtained in the one-pot cobalt cyclization of the R,â-
unsaturated nitrile 1k and Diels-Alder reaction with
methyl triazoline, which afforded the adduct 5k as a
single diastereomer in 39% overall yield.
(17) In the stereochemical assignment of the endo/ exo products
3f-k the values of J 5,6 constitute a very useful diagnostic criteria: J 5,6
is significantly lower in the endo isomer (J 5,6 ) 3.8-4.0 Hz, H5/H6 in
cis arrangement) than in the exo isomer (J 5,6 ) 8.9-9.3 Hz, H5/H6 in
trans arrangement).
(18) Intramolecular PK reactions of enynes substituted at the allylic
and propargylic position tend to be highly exo-selective. See, for
instance: (a) Mukai, C.; Sonobe, H.; Kim, J . S.; Hanoka, M. J . Org.
Chem. 2000, 65, 6654-6659. (b) Mukai, C.; Kim, J . S.; Sonobe, H.;
Hanaoka, M. J . Org. Chem. 1999, 64, 6822-6832. (c) Magnus, P.;
Principe, L. M.; Slater, M. J . J . Org. Chem. 1987, 52, 1483-1486. (d)
Magnus, P.; Principe, L. M. Tetrahedron Lett. 1985, 26, 4851-4854.
For endo-selective intramolecular PK reactions of R,â-unsaturated
sulfones, see ref 8.
(19) For Diels-Alder reactions of related dienylesters, see: Grigg,
R.; Stevenson, P.; Worakun, T. Tetrahedron 1988, 44, 2033-2048.
(20) Stereochemical assignment of products 4i,j and 3j,n was based
on NMR spectroscopic analysis (NOESY experiments).
(13) (a) Tanikaga, R.; Nozaki, Y.; Tamura, T.; Kaji, A. Synthesis
1983, 134-135. (b) Tanikaga, R.; Nozaki, Y.; Tamura, T.; Kaji, A.
Chem. Lett. 1980, 781-784.
(14) Enyne 1j was preferably prepared by Sonogashira reaction of
the terminal alkyne 1e [PhI, Pd(OAc)2, CuI, PPh3, Et3N, C6H6, 80 °C;
72% yield] and further OH protection.
(15) Nokami, J .; Mandai, T.; Imakura, Y.; Nishiuchi, K.; Kawada,
M.; Wakabayashi, S. Tetrahedron Lett. 1981, 22, 4489-4490.
(16) (E)-Configuration of dienes 2 was established by comparison
with related compounds, see: Nishida, M.; Adachi, N.; Onozuka, K.;
Matsumura, H.; Mori, M. J . Org. Chem. 1998, 63, 9158-9159.
2976 J . Org. Chem., Vol. 68, No. 7, 2003

TABLE 2. Coba lt-Med ia ted Cycliza tion of En yn es 1e-k
2:3
yield
(%)c
entry
enyne
EWG
R1
R2
conditionsa
(endo:exo)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1e
1e
1f
1f
1g
1g
1h
1h
1i
1i
1j
1j
1k
1k
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
H
H
H
H
H
H
H
H
Me
Me
Ph
Ph
H
H
H
B
C
B
C
B
C
B
C
B
C
B
C
B
C
d
d
CH2OEt
CH2OEt
TIPS
TIPS
TIPS
TIPS
TIPS
TIPS
TIPS
64:36 (34:66)
<2:>98 (40:60)
>98:<2
<2:>98 (59:41)
26:74 (62:38)
<2:>98 (85:15)
>98:<2
<2:>98 (51:49)
>98:<2
59
61
79
66
54
67
79
61
75
85
74
42
t
CO2 Bu
t
CO2 Bu
CO2Et
CO2Et
CO2Et
CO2Et
CN
TIPS
TIPS
TIPS
55:45 (41:59)
>98:<2
<2:>98 (96:4)
CN
H
a
b
Conditions B and C as described in Table 1. Determined by 1H NMR on crude mixtures. c In isolated products after silica gel
d
chromatography. No reaction was observed.
TABLE 3. Coba lt-Med ia ted Cycliza tion of En yn es 1l-n
SCHEME 1
SCHEME 2
entry
1
R1
R2
conditionsa 2:3 (endo:exo)b yield (%)c
1
2
3
4
5
6
1l
1l
1m
1m
H
H
H
H
CH2OEt
CH2OEt
TIPS
B
C
B
C
B
C
17:83 (85:15)
<2:>98 (89:11)
<2:>98 (86:14)
<2:>98 (95:5)
<2:>98 (55:45)
<2:>98 (80:20)
59
60
80
88
62
82
TIPS
1n Ph TIPS
1n Ph TIPS
We next examined the effect of a higher substitution
pattern at the enyne framework on the cyclization
process. The R,â-unsaturated esters 1l-n , having sub-
stitution at both γ- and δ-positions (Table 3), were
prepared by SPAC condensation with 3,3-dimethyl-5-
hexynal, eventual phenylation of the alkyne terminus in
the case of enyne 1n [PhI, Pd(OAc)2, CuI, PPh3, Et3N],
and hydroxyl protection.
Unlike the previous cases, the cyclization of enynes
1l-n was much more selective, giving rise predominantly
(entry 1) or exclusively to the PK product 3 regardless of
the reaction conditions used (entries 2-6). In these cases,
the difficulty in the formation of the exocyclic diene
a
b
Conditions B and C as described in Table 1. Determined by
1H NMR on the crude mixtures. c In isolated products after silica
gel chromatography.
product 2 may be attributed to its high steric congestion
resulting from the hindrance between the gem-dimethyl
group and the OTIPS, as well as the allylic OTIPS/CO2-
Et interaction. In agreement with the importance of
minimizing the steric effects between the OR group and
the gem-dimethyl and ester moieties, the PK reactions
of the enynes 1l-n occurred in most cases with a much
higher endo-selectivity17 (up to 95:5 endo/exo ratio, entry
J . Org. Chem, Vol. 68, No. 7, 2003 2977

analysis showed that formation of the complex was complete,
and Me3NO‚2H2O (140 mg, 1.26 mmol) was added in one portion.
The resulting solution was stirred at room temperature until
the complete disappearance of the complex and filtered through
a pad of Celite. The combined solvents were evaporated, and
the residue was purified by flash chromatography to afford 2a
(8 mg, 27%) and 3a (5 mg, 13%).
SCHEME 3
Th er m a l Rea ction in Aceton itr ile (Meth od C). A solution
of 1a (30 mg, 0.18 mmol) in CH2Cl2 (5 mL) was added to a flask
containing solid Co2(CO)8 (80 mg, 0.23 mmol). The resulting
solution was stirred until TLC analysis showed that formation
of the complex was complete, and the solvent was then removed
under reduced pressure. The residue was diluted with CH3CN
(7 mL), and the resulting solution was heated at reflux until
the complete disappearance of the complex. The solvent was
evaporated, and the residue was diluted with ethyl ether and
filtered through a pad of Celite. The combined solvents were
evaporated, and the residue was purified by flash chromatog-
raphy to afford 3a (11 mg, 31%).
E t h yl (E)-2-(Met h ylid en e)cyclop en t ylid en eet h a n oa t e
(2a ): 1H NMR (300 MHz, CDCl3) δ 6.14 (t, J ) 2.8 Hz, 1H),
5.57 (t, J ) 2.4 Hz, 1H), 5.12 (t, J ) 2.2 Hz, 1H), 4.17 (m, 2H),
2.93 (td, J ) 2.4, 7.3 Hz, 2H), 2.43 (tt, J ) 2.4, 7.3 Hz, 2H), 1.77
(m, 2H), 1.30 (t, J ) 7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
167.3, 160.2, 127.5, 109.0, 108.0, 59.4, 34.5, 33.1, 23.9, 14.4;
HRMS (EI+) calcd for (C10H14O2)[M]+ 166.0994, found 166.0989.
4-(Eth oxyca r bon yl)bicyclo[3.3.0]oct-1-en -3-on e (3a ): 1H
NMR (300 MHz, CDCl3) δ 5.86 (m, 1H), 4.24 (q, J ) 7.3 Hz,
2H), 3.33 (m, 1H), 3.08 (d, J ) 4.1 Hz, 1H), 2.61 (m, 2H), 2.29-
1.98 (m, 4H), 1.31 (t, J ) 7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3)
δ 203.7, 190.4, 169.4, 122.6, 61.4, 59.4, 50.4, 30.2, 26.2, 25.3,
14.2; HRMS (EI+) calcd for (C11H14O3)[M]+ 194.0943, found
194.0936.
Typ ica l P r oced u r e for th e On e-P ot Coba lt Cycliza tion /
Diels-Ald er Rea ction : Diels-Ald er Ad d u ct of Dien e 2g
a n d N-Meth ylm a leim id e (4g). A solution of enyne 1g (45 mg,
0.13 mmol) in toluene (8 mL) was added to a flask containing
solid Co2(CO)8 (59 mg, 0.17 mmol) and molecular sieves (4 Å,
360 mg). The resulting solution was stirred for 30 min, and Me3-
NO‚2H2O (103 mg, 0.93 mmol) was added in one portion. After
the mixture was stirred at room temperature for 4 h, N-
methylmaleimide (44 mg, 0.40 mmol) was added. The reaction
mixture was stirred at reflux for 24 h and then filtered through
a pad of Celite, which was washed with ethyl ether. The
combined solvents were evaporated, and the residue was purified
by flash chromatography (hexane/ethyl acetate 3:1) to afford 4g
(30 mg, 51%, white solid): mp 91-93 °C; 1H NMR (300 MHz,
CDCl3) δ 5.00 (m, 1H), 4.00 (m, 3H), 3.08 (m, 2H), 3.00 (s, 3H),
2.66 (dd, J ) 8.1, 16.7 Hz, 1H), 2.42-2.23 (m, 4H), 1.75 (m, 1H),
1.16 (t, J ) 7.3 Hz, 3H), 1.10 (m, 21H); 13C NMR (75 MHz,
CDCl3) δ 179.9, 178.6, 170.7, 141.9, 134.8, 77.6, 61.1, 41.7, 39.4,
38.5, 34.2, 33.2, 24.8, 23.8, 18.1, 14.0, 12.4. Anal. Calcd for
4), likely due to the presumed higher stability of the
cobaltacycle intermediate I (OTIPS and CO2Et groups in
an anti relationship) compared to the diastereomer II
(Scheme 3).
In summary, electron-poor 1,6-enynes having an ester,
cyano, or phosphonate moiety bonded to the alkene
terminus are appropriate substrates in cobalt-mediated
enyne cyclizations. Two competitive reaction pathways
operate in the cyclization of their dicobalt hexacarbonyl
complexes: the formation of the exocyclic 1,3-diene and
the formation of the cyclopentenone PK product. The
chemoselectivity of the reaction proved to be highly
dependent on the substitution at the enyne and especially
on the reaction conditions. In general, the PK product is
selectively formed in refluxing acetonitrile, while in many
cases the 1,3-diene can be isolated as the major product
under TMANO-promoted conditions.
Exp er im en ta l Section
Typ ica l P r oced u r es for Coba lt-Med ia ted Cycliza tion s:
Cycliza tion of En yn e 1a . Am in e N-Oxid e-P r om oted Rea c-
tion (Meth od A). A solution of 1a (30 mg, 0.18 mmol) in CH2-
Cl2 (5 mL) was added to a flask containing solid Co2(CO)8 (80
mg, 0.23 mmol). The resulting solution was stirred until TLC
analysis showed that formation of the complex was complete,
and Me3NO‚2H2O (140 mg, 1.26 mmol) was added in one portion.
The resulting solution was stirred at room temperature until
the complete disappearance of the complex. The solvent was
evaporated, and the residue was diluted with ethyl ether and
filtered through a pad of Celite. The combined solvents were
evaporated, and the residue was purified by flash chromatog-
raphy (hexane/ethyl acetate 10:1) to afford 2a (13 mg, 45%,
colorless oil) and 3a (3 mg, 8%, colorless oil).
C
24H39NO5Si (449.6): C, 64.11; H, 8.74; N, 3.11. Found: C, 63.55;
H, 9.07; N, 3.10.
Ack n ow led gm en t. Financial support of this work
by the M.C.Y.T is gratefully acknowledged (Project
BQU2000-0266). M.R.R. also thanks the M.E.C. for a
predoctoral fellowship.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Am in e N-Oxid e/Molecu la r Sieves-P r om ot ed R ea ct ion
(Meth od B). A solution of 1a (30 mg, 0.18 mmol) in toluene (5
mL) was added to a flask containing solid Co2(CO)8 (80 mg, 0.23
mmol) and powdered molecular sieves (4 Å, oven dried at 80 °C
for 4 h, 240 mg). The resulting solution was stirred until TLC
J O026828G
2978 J . Org. Chem., Vol. 68, No. 7, 2003