Cobalt-mediated [2+2+2] cycloadditions of pyrimidine derivatives to alkynes

Article abstract of DOI:10.1002/(SICI)1521-3765(19991203)5:12<3549::AID-CHEM3549>3.0.CO;2-V

The scope and limitations of the cobalt-mediated [2+2+2] cycloaddition of pyrimidine derivatives to alkynes has been investigated. The 5,6-double bond of these heterocyclic nuclei has been found to participate in an entirely intermolecular fashion to generate chemo- and stereoselectively novel, fused and substituted 5,6-dihydropyrimidine cobalt complexes, which upon oxidative demetallation liberate the corresponding new heterocyclic ligand. On the other hand, 1-alkynyl pyrimidines have been found to be suitable partners in the cocyclization with disubstituted alkynes, such as bis(trimethylsilyl)acetylene (BTMSA) or dimethyl 2-butyn-1,4-dioate (DMAD), to allow the direct preparation of hitherto unknown dihydropyrido[3,2-ij]quinazoline cobalt complexes. Effects of the substitution on the pyrimidine nucleus, the cocyclization partner, the complex auxiliary, and the reaction conditions were examined, and in some cases competing pathways that lead to [CpCo(cyclobutadienes)], cyclopentadienone complexes, and compounds that arise from a C-H activation-type reaction were observed.

Full text of DOI:10.1002/(SICI)1521-3765(19991203)5:12<3549::AID-CHEM3549>3.0.CO;2-V

FULL PAPER
Cobalt-Mediated [2‡2‡2] Cycloadditions of Pyrimidine
Derivatives to Alkynes
HeÂleÁne Pelissier,[c] Jean Rodriguez,*[a] and K. Peter C. Vollhardt*[b]
Abstract: The scope and limitations of
the cobalt-mediated [2‡2‡2] cycloaddi-
tion of pyrimidine derivatives to alkynes
has been investigated. The 5,6-double
bond of these heterocyclic nuclei has
been found to participate in an entirely
intermolecular fashion to generate che-
mo- and stereoselectively novel, fused
and substituted 5,6-dihydropyrimidine
cobalt complexes, which upon oxidative
demetallation liberate the correspond-
ing new heterocyclic ligand. On the
other hand, 1-alkynyl pyrimidines have
been found to be suitable partners in the
cocyclization with disubstituted alkynes,
such as bis(trimethylsilyl)acetylene
(BTMSA) or dimethyl 2-butyn-1,4-dio-
ate (DMAD), to allow the direct prep-
aration of hitherto unknown dihydro-
pyrido[3,2-ij]quinazoline cobalt com-
plexes. Effects of the substitution on
the pyrimidine nucleus, the cocyclization
partner, the complex auxiliary, and the
reaction conditions were examined, and
in some cases competing pathways that
lead to [CpCo(cyclobutadienes)], cyclo-
pentadienone complexes, and com-
pounds that arise from a C H activa-
tion-type reaction were observed.
Keywords: alkynes ´ cobalt ´ cyclo-
oligomerizations ´ heterocycles
pyrimidine nucleus[9] and its presence in a multitude of
biologically important molecules, for example nucleic acids,
extensive synthetic attention has been given to this core
substrate.[10] More particularly, the selective modification of
nucleosides is a challenge in the quest for the development of
medicinal agents effective for the treatment of cancer and
viral infections, such as herpes and AIDS.[11] Part of this effort
has involved the utilization of the 5,6-double bond for
synthetic elaboration by means of inter- and intramolecular
electrophilic additions[12] or cycloaddition processes, such as
6p-electrocyclizations, [2‡2] cycloadditions, [3‡2] photoad-
ditions,[13] and [4‡2] Diels ± Alder reactions with appropri-
ately functionalized pyrimidones.[14] In this paper, we wish to
report the scope and limitations of our studies which are
directed towards the chemo-, regio-, and stereoselective
participation of pyrimidine derivatives in cobalt-mediated
[2‡2‡2] cycloaddition reactions as a new synthetic entry to
modified nucleosides.
Introduction
The cobalt-mediated [2‡2‡2] cycloaddition is a powerful
synthetic method to form carbon ± carbon bonds,[1] and
provides chemo-, regio- and stereoselective pathways to
various natural products and compounds of theoretical
interest.[2] Studies on heteroaromatic double bonds have
shown the ability of these systems to readily participate in the
cobalt-mediated cyclization with alkynes. This methodology
has been used for the rapid construction of complexed
dihydroindoles by the reaction of either the indole 2,3-double
bond[3] or the pyrrole 2,3-double bond.[4] Imidazoles,[5] furans,
and thiophenes[6] have also been found to be effective in this
process. The success of such heterocyclic olefins and partic-
ularly of enamides in these transformations,[7] led us to
consider pyrimidines as cyclization partners.[8] Because of the
extremely diverse physiological activity exhibited by the
[a] Dr. J. Rodriguez
Â
Â
Â
Á
Laboratoire ReSo, Reactivite en Synthese organique
 Ã
UMR au CNRS 6516, Centre de St Jerome, boîte D12
F-13397 Marseille cedex 20 (France)
Fax : ( ‡ 33)491-28-88-41
Results and Discussion
E-mail: jean.rodriguez@reso.u-3mrs.fr
Preparation of the cycloaddition partners: In order to
examine the feasibility of cobalt-mediated cycloadditions to
the pyrimidine nucleus, we prepared various derivatives by
adaptation or by the application of standard literature
procedures. In general, these substrates cannot be used in
their N H form in the [2‡2‡2] cycloaddition because of their
insolubility in common organic solvents. However, 1N,3N-
[b] Prof. K. P. C. Vollhardt
Department of Chemistry, University of California and
the Chemical Sciences Division
Lawrence Berkeley Laboratory, Berkeley, California 94720 (USA)
E-mail: vollhard@cchem.berkeley.edu
[c] Dr. H. Pelissier
Á
Laboratoire de Synthese Organique, ESA au CNRS 6009
F-13397 Marseille cedex 20 (France)
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J. Rodriguez, K. P. C. Vollhardt, H. Pelissier
FULL PAPER
dimethylated substrates 1a ± d,[15] imides 1e ± g,[16] imidates 2
and 4,[17] or enamines 3[16,18] show good solubility in most
organic solvents and can be readily prepared in good yields.
Similarly, permethylation (N and O)[19] or selective O-
acylation[20] of nucleosides allows the preparation of soluble
derivatives 1h ± l (Tables 1 ± 4). Compounds 1 ± 4 were em-
ployed as substrates in potential intermolecular [2‡2‡2]
cycloaddition to a,w-diynes.
Table 1. Preparation of pyrimidines 1a ± l.
Conversely, 1N-alkylation or acylation of pyrimidines 5
gives rise to suitable functionalized substrates 6 (Table 5) for
the study of the cocyclization with substituted alkynes, such as
BTMSA or DMAD. Since attempted direct selective alkyla-
tion at N1 of both uracil and thymine resulted in a mixture of
1,3-dialkylpyrimidinediones,[21] we chose a two-step sequence
through the readily available 3N-aroyl intermediates 5 (R1 ˆ
COAr; Table 5).[22]
Alkylation of pyrimidinediones 5 with NaOH in glyme,
KOH in acetone or, under phase-transfer catalysis, Et3N in
ethanol or diazabicyclononene (DBN), resulted in very poor
yields of 6 ( < 5%) and partial or complete hydrolysis of the
amide function. However, it was found that by the use of
anhydrous K2CO3 in a mixture of dry DMSO and dry THF in a
ratio of 1:8, the alkylation of 5 either with 4-iodo-1-butyne or
5-iodo-1-pentyne proceeded cleanly to give only the desired
1-alkylpyrimidines 6a ± d in acceptable yields. Compound 6e
could be obtained selectively in 32% yield with Et3N in a
mixture of EtOH/H2O (1:1). Direct acylation of uracil (5:
R1 ˆ R2 ˆ H) with 4-pentynoyl chloride[23] following a report-
ed procedure afforded 6 f in 60% yield.[13] The cyano
derivatives 6g (n ˆ 1) and 6h (n ˆ 1) have been prepared in
60% and 66% yields, respectively, by Michael addition of the
corresponding pyrimidinediones to acrylonitrile,[24] while 6i
(n ˆ 2, R1 ˆ R2 ˆ H) was obtained in 37% yield by direct
alkylation of 5 (R1 ˆ COPh, R2 ˆ H) with 4-chlorobutyroni-
Table 2. Preparation of pyrimidines 2a,b.
Abstract in French: Nous dØcrivons une Øtude dØtaillØe sur la
rØactivitØ de diverses pyrimidines vis-à-vis de la rØaction de
cycloaddition [2‡2‡2] induite par les complexes du cobalt(i).
Dans un premier temps, nous avons montrØ que la double
liaison C5 ± C6 de ces hØtØrocyles participe de mani›re inter-
molØculaire a une cycloaddition chimio- et stØrØosØlective avec
des a,w-diynes pour conduire aux complexes diØniques du
cobalt attendus. Ces dØrivØs organomØtalliques constituent des
prØcurseurs de nouveaux squelettes hØtØrocycles de type
quinazoline par simple dØcomplexation oxydante. Par ailleurs,
lꢀutilisation de 1-alcynyl pyrimidines permet de rØaliser des co-
cyclisations avec des dØrivØs acØtylØniques disubstituØs comme
le bis(trimethylsilyl)acetylene (BTMSA) ou le dimethyl 2-
butyn-1,4-dioate (DMAD) conduisant à la construction du
squelette dihydropyrido[3,2-ij]quinazoline sous forme de
complexe diØnique du cobalt. Nous avons ØtudiØ en dØtail les
diffØrents param›tres de ces cycloadditions en faisant varier la
substitution sur le noyau hØtØrocyclique, la nature du complexe
de cobalt et les conditions opØratoires afin d'Øviter la formation
parasite de complexes cyclobutadiØnyles, cyclopentadiØnones
et des sous-produits issus de reactions d'activation de liaisons
C H.
R1
R2
Yield[%]
2a
2b
Cl
OMe
Cl
OMe
75
64
Table 3. Preparation of pyrimidines 3a ± d.
R1
R2
R3
Yield[%]
3a
3b
3c
3d
H
Pr
Me
Me
H
H
Me
Me
Ac
Ac
H
59
72
80
98
Me
trile by the use of K2CO3 in THF and concomitant saponifi-
cation of the benzoyl protecting group at N3. Similarly,
alkylation of N-acetylcytosine (3a) gave the desired 1N-(1-
pentyne) derivative 7 in 88% yield (Scheme 1).
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Cyclooligomerizations
3549±3561
Table 4. Preparation of pyrimidines 4a ± d.
Table 6. Cycloaddition of la to a,w-diynes 8a ± c.
R1
R2
Yield[%]
n
T[8C]
Solvent
Complex
Yield[%][a]
4a
4b
4c
4d
Me
Me
Me
Et
Me
Et
nPr
Me
64
80
88
88
8a
8b
8c
8b
1
2
3
2
110
110
110
140
toluene
toluene
toluene
xylene
9a
10a
11a
10a
53 (96)
57 (89)
22 (94)
76
[a] Values in brackets are based on consumed 1a.
Table 5. Preparation of pyrimidines 6a ± i.
balt.[2,26] The observed anisotropic effect and the comparison
of the chemical shifts of the methine proton Ha at the ring
junction in 9a ± 11a with the corresponding carbocyclic
analogue 12[26] are consistent with the proposed stereochem-
istry (Table 7). In addition to the good agreement of the
Table 7. 1H NMR shifts (d) for Ha and DdHa between complexes and free
R1
R2
X
n
Y
Yield[%]
ligands.
6a
6b
6c
6d
6e
6 f
6g
6h
6i
COPh
COPh
COPh
COPhNO2-p
H
H
COPh
H
H
H
H
Me
H
H
H
H
H
H
H2
H2
H2
H2
H2
O
H2
H2
H2
2
1
2
2
2
2
1
1
2
C H
C H
C H
C H
C H
C H
N
81
33
76
35
32
60
60
66
37
n
Ha
DdHa
N
N
Scheme 1. Alkylation of acetylcytosine. Reagents and conditions:
a) K2CO3 (1.1 equiv), DMSO, 708C, 8 h.
Cyclization of pyrimidines 1 ± 4 with a,w-diynes: We first
examined the reaction of 1,3-dimethyluracil (1a) with a,w-
diynes 8a ± c in the presence of [CpCo(CO)2] in refluxing,
irradiated toluene (18h). The desired complexes 9a ± 11a
were formed only in fair yields owing to the incomplete
conversion of the starting materials. In an attempt to optimize
the reaction of 1a with 1,7-octadiyne (8b), the cyclization was
carried out in refluxing xylene for 20h, which resulted in the
complete conversion of 1a and a 76% isolated yield of
complex 10a (Table 6).
In contrast with the results obtained from the reaction of
the pyrrole and imidazole nuclei,[25] these results show that the
heterocyclic 5,6-double bond of uracil derivative 1a can be
engaged in an intermolecular fashion to give complexes 9a ±
11a, which have a syn configuration. Because of the lack of
reference compounds, the relative stereochemistry of the
ligand with respect to the CpCo fragment was assigned on the
basis of the well-documented magnetic anisotropy of co-
proposed stereochemistry, the deshielding (DdHa) of the
proton Ha in 10a by cobalt, relative to the free ligand 13,[27] is
almost equal to that found for the syn carbocyclic complex 14
relative to the corresponding free ligand 15[26] (Table 7).
Finally, unambiguous support for these assignments was
obtained by an X-ray structural determination of 10j (major
diastereomer, vide infra).[8]
Having shown the participation of the 5,6-double bond of
uracil derivatives in the [2‡2‡2] cycloaddition, we then
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J. Rodriguez, K. P. C. Vollhardt, H. Pelissier
FULL PAPER
turned our attention to the scope and limitations of this
reaction. The first finding was the high sensitivity of this
process to steric hindrance. Indeed, compounds 1b and 1c,
derived from thymine and 5-fluorothymine, respectively, were
not affected by prolonged irradiation in the presence of
[CpCo(CO)2] in refluxing toluene or xylene. Similarly, no
reaction was observed with dimethyluracil 1a and 1,8-
bis(trimethylsilyl)-1,7-octadiyne (16),[28] which gave rise to
the formation of the known cyclobutadiene and cyclopenta-
dienone complexes 17 and 18[29] (Scheme 2).
Scheme 3. Hydrolysis of 10e. Reagents and conditions: a) SiO2, MeOH or
Al2O3, H2O, RT.
the reactivity of substrates 1h ± l towards 1,7-octadiyne (8b)
was explored. It was gratifying that all derivatives gave the
expected [2‡2‡2] cycloadducts 10h ± l as mixtures of the four
possible diastereomers in ratios that depended on the nature
of the starting nucleoside (Table 9).
Table 9. Cyclization of nucleosides 1h ± l with 1,7-octadiyne (8b).
Scheme 2. Attempted cycloaddition of 1a to 1,8-bis(trimethylsilyl)-1,7-
octadiyne 16. Reagents and conditions: a) [CpCo(CO)2] (1.5 equiv), hn,
toluene, 408C, 30 h.
The presence of a sulfur atom in 1d also inhibited the
reaction, probably by deactivation of the cobalt complex.[30]
A
switch from the pyrimidinedione to the more aromatic
pyrimidine core, as in 2a and 2b, also suppressed the
[2‡2‡2] cycloaddition.
L
Solvent
Complex (ratio)[a]
Yield[%][b]
1h
1h
1i
1j
1j
1k
1l
CO
CO
CO
CO
C2H4
C2H4
CO
toluene
xylene
xylene
xylene
THF
10h[c]
45 (100)
71 (94)
33 (54)
76[c]
94
37 (59)
18 (23)
10h (7.5:4:1:1)
10i (2.4:1.8:1:1)
10j (45:4:1:1)
10j (45:4:1:1)
10k (1:1:1:1)
10l (1:1:1:1)
However, imides 1e and 1 f were successful in this reaction
to give, after chromatography on neutral alumina, acceptable
yields of the corresponding cobalt-complexed heterocycles,
while the tri-N-benzoyl derivative 1g failed to add to 1,7-
octadiyne (8b) under the same conditions (Table 8).
THF
toluene
[a] Determined by 1H NMR. [b] Values in brackets are based on consumed
1. [c] Not determined.
Table 8. Cyclization of le ± g with a,w-diynes.
This, like other related cyclizations,[25] is strongly affected
by changes in the reaction conditions. For example, the yield
of 10h was improved from 45 to 71% by changing the solvent
from toluene to boiling xylene. Even better, with
[CpCo(C2H4)2][31] as the reagent in refluxing THF, complexes
10j were obtained in almost quantitative yield. However, the
presence of the relatively acidic N H bond in 1k and 1l seems
to be detrimental, since 10k and 10l were obtained in low
yields (37% and 18%, respectively), even in the presence of
[CpCo(C2H4)2].
The observed diastereoselectivity also deserves some com-
ments. Interestingly, we observed a very high selectivity in
favor of one of the four possible isomers of 10j (45:4:1:1)
during the cycloaddition of deoxyuridine derivative 1j with
8b with either [CpCo(CO)2] in refluxing xylene or the more
efficient [CpCo(C2H4)2]. The corresponding uridines 1h and
1i gave only moderate diastereoselection, while no stereo-
selectivity and a very bad mass balance was observed in the
case of 1k and 1l, regardless of the reaction conditions. Our
results with regard to the diastereoselectvity observed for
1h ± j can be tentatively explained by changes in the
conformation as a result of puckering in the furanose ring.[32]
It is known that pyrimidine nucleosides generally exist in the
anti conformation; the 5,6-double bond lies more or less
above the sugar ring depending on the substitution.[33] As a
n
Complex
Yield[%][a]
1e
1e
1e
1 f
1 f
1 f
1g
1
2
3
1
2
3
2
9e
10e
11e
9 f
10 f
11 f
10g
46 (100)
79 (100)
21 (40)
40 (100)
55 (100)
22 (23)
0 (100)
[a] Values in brackets are based on consumed 1.
The behavior of 1e and 1 f was comparable to that of the
parent pyrimidinedione 1a and had the same regio- and
stereochemical outcome. Only the 5,6-double bond of the
heterocycle was involved in the cyclization, which gave only
the syn isomer, as shown by spectral data and, furthermore,
hydrolysis of 10e gave 10a (Scheme 3), which was identical
with the sample prepared directly from 1a (Table 6).
An extension of the method to nucleosides was of interest
as a contribution to the synthesis of modified nucleosides for
the development of new biologically active agents. Therefore,
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Cyclooligomerizations
3549±3561
Table 10. Cycloaddition of imidates 4 to a,w-diynes 8a ± c.
consequence, an increase in the substitution on the sugar
would probably make the two faces of the olefin more
accessible by the cobalt complex; this would result in a lower
selectivity. The assignment of the stereochemistry was first
deduced from NMR spectroscopic studies and was confirmed
by X-ray diffraction analysis of 10j (major isomer),[8] which
also supported the proposed configuration of complexes 9 and
11.
n
Complex
Yield[%][a]
In an effort to extend the method further, we turned our
attention to the use of enamines 3, derived from cytosine and
imidates 4. Although the enamide double bond has been
found to be compatible in the [2‡2‡2] cycloaddition,[7]
4a
4b
4c
4d
4a
4a
2
2
2
2
1
3
21 ‡ 25
22 ‡ 25
23 ‡ 25
37 ‡ 9 (89)
15 ‡ 7 (73)
20 ‡ 7 (93)
26
9 (56)
[b]
compounds
3
gave relatively disappointing results
±
±
[b]
(Scheme 4). N-Acetylcytosine (3a) failed to react with 8b in
[a] Values in brackets are based on consumed 4. [b] No reaction.
nometallic species isolated from the reaction mixture in 9%
yield. In sharp contrast to these results, 1,6-heptadiyne (8a,
n ˆ 1) and 1,8-nonadiyne (8c, n ˆ 3) failed to add to 4a under
the same experimental conditions.
Scheme 4. Cycloaddition of
conditions: a) [CpCo(CO)2] (2 equiv), hn, toluene, reflux 20 h.
3 with 1,7-octadiyne 8b. Reagents and
Cocyclization of pyrimidines 6 with disubstituted acetylenes:
In another extension of the scope of the cyclization, the
potential construction of tricyclic systems was explored by
appending one of the alkyne units to the pyrimidine nucleus,
as in 6 and 7. BTMSA[34] was chosen as the cocyclization
partner owing to its very low autocyclization rate in the
presence of [CpCoL2][35] (Table 11). In a preliminary experi-
ment, 1N-1-pentynylderivative 6a was photolyzed in a
refluxing mixture of THF/BTMSA in the ratio 1:2 for
solubility reasons. After all the starting material had been
consumed, removal of the solvent and flash chromatography
DMSO (perhaps for reasons of solubility, as 3a is only poorly
soluble in this and other solvents more typically employed in
these cyclizations, such as toluene) and only led to the
formation of complex 19[29] from the reaction of 8b with
[CpCo(CO)2]. In the case of 3b and 3c, which were soluble in
toluene, once again 19 was the only organometallic complex
obtained, while 9% of the desired tricyclic derivative 20d was
formed with 3d in refluxing toluene (Scheme 4).
Changing the solvent did not help, since
no reaction occurred in DME, only 6% of
Table 11. Cocyclization of 6a ± i with disubstituted acetylenes.
20d was obtained in THF, and in xylene
extensive decomposition was observed
without the generation of any isolable
desired product. While it is not obvious
why these cycloadditions were not success-
ful, it is possible that, for 3a ± c, it is again
the presence of an acidic N H bond that is
responsible, whereas for 3d it may be the
increased aromaticity of the system.
R
T[8C][a]
Complex
anti/syn[b]
Yield[%][c]
The results of the [2‡2‡2] cycloaddition
of imidates 4 (Table 10) were more gratify-
ing. Thus, 4a provided a moderate yield
(37%) of 21 with 1,7-octadiyne (8b, n ˆ 2)
together with 9% of the corresponding
pyrimidinedione 25 produced by the hy-
drolysis of the imidate function during
workup. Indeed, 21 was converted quanti-
tatively to 25 by treatment with wet silica
gel. Similarly, heterocycles 4b and 4c gave
the expected diene complexes 22 and 23,
when treated with 8b (n ˆ 2), in 15% and
20% yield, respectively, accompanied by
7% of 25. Finally, in the case of 4d, the
hydrolyzed complex 26 was the only orga-
[d]
6a
6a
6a
6a
6b
6c
6d
6e
6e
6 f
6 f
6g
6h
6i
TMS
TMS
TMS
COOMe
COOMe
TMS
TMS
TMS
COOMe
TMS
TMS
TMS
TMS
110
rt
27
27
5
23
5
5
anti
±
±
rt[e]
rt
27 ‡ 31
18 ‡ 21
28
61
±
[f]
rt
rt
rt
rt
rt
rt
65
85
40
65
32
18
±
35
73
±
±
±
±
±
[g]
±
29
10
anti
±
±
±
30
[f]
[g]
[f]
[f]
[f]
±
±
COOMe
[a] Unless otherwise noted, [CpCo(CO)2] was used as the reagent. [b] The designation syn and anti
indicates the position of the Co atom relative to the tertiary hydrogen atoms of the ring junction.
[c] Isolated. [d] Not determined.[e] L ˆ C2H4. [f] No reaction. [g] Decomposition.
Chem. Eur. J. 1999, 5, No. 12
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J. Rodriguez, K. P. C. Vollhardt, H. Pelissier
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Table 12. Chemical shifts (d) and coupling constants [Hz] in 27 ± 30.
allowed the isolation of the CpCo-complex 27 as a mixture of
two diastereomers in only 5% yield (Table 11). In an effort to
improve this outcome, the effects of the temperature, the
cocyclization partner, the cobalt auxiliary, and the structure of
the starting pyrimidines were examined.
Thus, at room temperature, the reaction of 6a provided 27
in 23%. Surprisingly, under these conditions addition of
[CpCo(C2H4)2][31] resulted not only in 27 but also in a new
addition product, the butadiene complex 31, derived by
formal C H activation.[36] A similar result was obtained with
cytosine derivative 7, which gave a 23% yield of a mixture of
the two cobalt complexes 33 and 34 after photolysis for 20 h at
room temperature in the presence of BTMSA and [CpCo-
(CO)2] (Scheme 5).
Major isomer (anti)
Minor isomer (syn)
R1
R
Ha
Hb
J(Ha,Hb) Ha Hb J(Ha,Hb)
27 COPh TMS
28 COPh COOMe
1.65 2.21 8.1
2.78 3.12 8.1
1.44 2.01 8.0
2.70 2.94 8.0
2.55 3.77 10.5
±
±
±
29
30
H
H
TMS
COOMe
2.37 3.69 10.3
±
±
±
caused by the cobalt in the exo position strongly suggests that
the major isomer of the reaction has the anti configuration.
The same conclusions can be drawn with respect to the
chemical shifts and the coupling constants of Ha and Hb in 29.
For compounds 28 and 30, the above comparison of the
chemical shift could not be made since they were obtained as
only one isomer; however, it is interesting to note that the
coupling constants for Ha and Hb were the same as in
complexes 27 and 29 (Table 12).
Scheme 5. Cycloaddition of 7 with BTMSA. Reagents and conditions:
a) [CpCo(CO)2] (2 equiv), BTMSA (6 equiv), hn, THF, RT, 20 h.
Interestingly, the observation of the important difference in
the coupling constants between anti and syn complexes seems
to be quite general and even proved to be consistent over a set
of 17 diene complexes prepared in this work. It also correlates
well with previous studies.[4] In short, the syn-diene-cobalt
complex has J(Ha,Hb) ˆ 10 ± 11 Hz, while in the anti isomer
has J(Ha,Hb) ˆ 7 ± 8 Hz (Figure 1).
Previous studies[3,5] have shown that DMAD was also a very
good partner in [2‡2‡2] cycloadditions and therefore its
potential in the present system was investigated. Photolysis of
6a and DMAD in the presence of [CpCo(CO)2] at room
temperature led to a 61% yield of complex 28 as only one
diastereomer (Table 11). Unfortunately, under the same
conditions 6b, which has a shorter tether length (n ˆ 1), failed
to react. In the case of the thymine derivative 6c, the
cyclobutadiene complex 32 was the only organometallic
species isolated from the reaction mixture in 18% yield. This
result shows, once again, the high sensitivity of the reaction to
steric hindrance (vide supra). Compound 6d proved to be
very unstable under the reaction conditions; it completely
degraded. In light of the failure of 3a ± c and 10k,l to undergo
cycloadditions, it is of interest that the N3-unprotected
pyrimidine 6e did react with BTMSA (35%) and DMAD
(73%) to assemble the tricyclic complexes 29 and 30,
respectively. It was thought that further activation of the
heteroarene on switching from a N-alkynyl to a N-alkynoyl
substituent, as in 6 f, would improve the yield of the cyclo-
addition. Unfortunately, 6 f remained unchanged, even after
15 h at 658C, and decomposed on prolonged heating. Finally,
unlike related successful [2‡2‡2] cycloadditions of alkyneni-
triles[37] to form annelated pyridines, the substrates 6g ± i are
stable under the reaction conditions and none of the desired
complexes were obtained.
Figure 1. Coupling constants of methine protons in syn and anti diene-
cobalt complexes.
Mechanistic discussion: Theoretical and experimental mech-
anistic investigations[38] have led to a proposed mechanism of
the [2‡2‡2] cycloaddition that involves cobaltacyclopenta-
diene or -cycloheptadiene intermediates, which are also
consistent with the byproducts, such as cyclobutadiene and
cyclopentadienone complexes, encountered in this study. In
accordance with these findings, one can formulate Schemes 6
and 7 for the two topological variants of the cycloaddition of
pyrimidines.[39]
The assignment of the stereochemistry of 27 ± 30 was made
A further competing pathway was observed with the
formation of diene complexes 31 and 33, which result from
formal C H activation.[36] The exact mechanism of this
process is not known; however, one can envisage direct
electrophilic aromatic substitution by the cobaltacyclopenta-
by comparison with related systems,[3,5] and utilized the effects
1
of the magnetic anisotropy of cobalt in H NMR spectro-
scopy.[2,26] In the major isomer, the protons Ha and Hb in 27
appeared at d ˆ 1.65 and 2.21, respectively, as two doublets
with a coupling constant of 8 Hz, whereas in the minor isomer,
Ha and Hb resonated at d ˆ 2.55 and 3.77 as two doublets with
a coupling constant of 10.5 Hz (Table 12). The deshielding
diene, oxidative addition to the C H bond to give a (rare[40]
)
CoV species, or a b-hydride/reductive elimination sequence
from the cobaltacycloheptadiene intermediate.
3554
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0947-6539/99/0512-3554 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 12

Cyclooligomerizations
3549±3561
and then brought to reflux for 30 min. After cooling, the mixture was
extracted with CHCl3 (3 Â 20 mL) and washed with saturated aqueous
NaHCO3 solution. The extract was dried over Na2SO4 and filtered, and the
solvent removed under reduced pressure to give the crude methylated
pyrimidines.
1,3-Dimethyluracil (1a): White crystals (EtOH); yield: 89%; m.p. 120 ±
1228C; 1H NMR (300 MHz, CDCl3): d ˆ 3.32 (s, 3H), 3.38 (s, 3H), 5.72 (d,
J ˆ 7.8 Hz, 1H), 7.11 (d, J ˆ 7.8 Hz, 1H); C6H8N202 (140.14): calcd C 51.39,
H 5.71, N 19.98; found C 51.21, H 5.63, N 19.95.
1,3-Dimethylthymine (1b): White crystals (EtOH); yield: 97%; m.p. 154 ±
1558C; 1H MNR (300 MHz, CDCl3): d ˆ 1.92 (s, 3H), 3.35 (s, 3H), 3.36 (s,
3H), 6.97 (m, 1H); C7H10N2O2 (154.17): calcd C 54.54, H 6.49, N 18.18;
found C 54.39, H 6.54, N 18.22.
1,3-Dimethyl-5-fluorouracil (1c): White crystals (EtOH); yield: 88%; m.p.
128 ± 1308C; 1H NMR (300 MHz, CDCl3): d ˆ 3.29 (s, 3H), 3.33 (s, 3H),
7.25 (d, J ˆ 5.1 Hz, 1H).
Preparation of 1,3-dimethyl-4-thiouracil (1d):[14] 1,3-Dimethyluracil (1a)
(0.840 g, 6.0 mmol) and phosphorus pentasulfide (1.05 g, 4.72 mmol) were
refluxed in dry pyridine (18 mL) for 3 d. After evaporation of the pyridine
under vacuum, water (50 mL) was added, and the mixture was extracted
with CHCl3 (4 Â 20 mL). The organic layer was washed with water (2 Â
20 mL) and dried over Na2SO4. Filtration and evaporation of the solvent
gave an orange solid, which was chromatographed (silica gel, pentane/
acetone 1:1) to give a yellow solid. Yield: 92%; m.p. 1838C; IR (CDCl3):
Scheme 6. Proposed mechanism for intramolecular cycloadditions.
1
nÄ ˆ 1725, 1660, 1360, 1140 cm 1; H NMR (300 MHz, CDCl3): d ˆ 6.90 (d,
J ˆ 8.3 Hz, 1H), 6.60 (d, J ˆ 8.3 Hz, 1H), 3.76 (s, 3H), 3.42 (s, 3H); MS
‡
(70 eV): m/z (%): 156 (100) [M ], 123 (24), 100 (26), 86 (7), 82 (8), 77 (9), 72
(18).
Preparation of imides (1e ± g): These compounds were obtained with a
reported procedure.[15]
1,3,N4-trimethyliminouracil (1e): White crystals (Et2O); yield: 66%; m.p.
798C; 1H NMR (300 MHz, CDCl3): d ˆ 6.74 (d, J ˆ 8.3 Hz, 1H), 5.75 (d,
J ˆ 8.3 Hz, 1H), 3.25 (s, 3H), 3.23 (s, 3H), 2.01 (s, 3H).
1,3-Dimethyl-N4-ethyliminouracil (1 f): Pale yellow solid; yield: 54%; m.p.
1
88 ± 898C; IR (CDCl3): nÄ ˆ 2970, 1670, 1610, 1460, 1400 cm
;
1H NMR
(300 MHz, CDCl3): d ˆ 5.96 (d, J ˆ 8.1 Hz, 1H), 3.60 (m, 9H), 1.31 (t, J ˆ
7.2 Hz, 3H); 13C NMR (75.8 MHz, CDCl3): d ˆ 151.71, 150.59, 137.33, 92.83,
‡
42.71, 35.91, 28.31, 16.34; MS (70 eV): m/z (%): 167 (57) [M ], 166 (22), 111
(9), 109 (21), 96 (33), 95 (52), 83 (8), 82 (10), 81 (22); C8H13N3O (167.21):
calcd C 57.46, H 7.84, N 25.13; found C 56.80, H 7.72, N 24.65.
1,3-Dibenzoyl-N4-benzyliminouracil (1g): White crystals (EtOH); yield:
48%; m.p. 140 ± 1428C; 1H NMR (300 MHz, CDCl3): d ˆ 8.73 (d, J ˆ
6.1 Hz, 1H), 8.08 (d, overlapping, J ˆ 6.1 Hz, 2H), 7.77 (m, 4H), 7.43 (m,
Scheme 7. Proposed mechanism for intermolecular cycloadditions.
‡
10H); MS (70 eV): m/z (%): 423 (60) [M ], 395 (61), 394 (100), 366 (34),
318 (59), 291 (55), 105 (98).
Experimental Section
Preparation of nucleosides (1h ± j): These compounds were obtained with a
reported procedure.[18]
General methods: Unless otherwise stated, all starting materials were
obtained from commercial suppliers and used without further purification.
DME, THF, and Et2O were freshly distilled from sodium benzophenone;
toluene and xylene were distilled from potassium and sodium, respectively,
and DMSO was stored over 4 Š molecular sieves. Unless otherwise
specified, all reactions that involved air- or moisture-sensitive materials
were carried out under an atmosphere of dry nitrogen or argon with
glassware that was oven-dried overnight at 1308C. In these experiments,
reagents were usually added from Hamilton gastight syringes mounted on a
syringe pump. Column chromatography was performed on flash silica gel
(Merck Reagents silica gel60, 230 ± 400 mesh ASTM). Thin-layer chroma-
tography (TLC) was carried out on a 250 m coating with fluorescent
indicator. Melting points were observed in open Pyrex capillary tubes with
a Thomas ± Hoover Unimelt apparatus and are uncorrected. Infrared
spectra were obtained either on neat compounds (NaCl plates), in solution
(solvent, NaCl cells), or with KBr pellets. Low- and high-resolution mass
spectra were provided by the Mass Spectral Service at the University of
California, Berkeley. Elemental analyses were determined by the Micro-
analytical Laboratory, UCB.
Tetramethyluridine (1h): White crystals from flash chromatography
(hexanes/Et2O 1:1); yield: 99%; m.p. 1028C; 1H NMR (300 MHz, CDCl3):
d ˆ 7.90 (d, J ˆ 8 Hz, 1H), 5.91 (m, 1H), 5.72 (d, J ˆ 8 Hz, 1H), 4.16 (m,
1H), 3.84 (m, 2H), 3.78 (dd, J ˆ 11.2, 2.1 Hz, 1H), 3.59 (s, 3H), 3.55 (dd, J ˆ
11.2, 2.2 Hz, 1H), 3.41 (s, 3H), 3.40 (s, 3H), 3.29 (s, 3H).
2',3'-O-Isopropylidene dimethyluridine (1i): Prepared by the methylation
of 2',3'-O-isopropylidene uridine[41] following a reported procedure.[18]
Yield: 100%; colorless thick oil; IR (CDCl3): nÄ ˆ 3000, 1710, 1670, 1470,
1
1080 cm 1; H NMR (300 MHz, CDCl3): d ˆ 7.44 (d, J ˆ 8.1 Hz, 1H), 5.80
(d, J ˆ 1.4 Hz, 1H), 5.72 (d, J ˆ 8.1 Hz, 1H), 4.75 (m, 2H), 4.40 (m, 1H),
3.56 (m, 2H), 3.42 (s, 3H), 3.26 (s, 3H), 1.55 (s, 3H), 1.32 (s, 3H); 13C NMR
(75.8 MHz, CDCl3): d ˆ 162.47, 150.57, 138.87, 137.98, 113.51, 100.51, 93.61,
85.26, 80.89, 72.35, 58.88, 27.08, 25.14, 24.72; MS (70 eV): m/z (%): 312 (4)
‡
[M ], 297 (17), 237 (45), 209 (13), 187 (76), 151 (20), 129 (100), 128 (18), 127
(19), 101 (42), 100 (41), 97 (20), 92 (16), 87 (21), 85 (24), 85 (27), 84 (23), 83
(41), 71 (52).
Trimethyldeoxyuridine (1j): Colorless oil; yield: 85%; 1H NMR (300 MHz,
CD2Cl2): d ˆ 7.71 (d, J ˆ 8.1 Hz, 1H), 6.23 (dd, J ˆ 7.8, 5.9 Hz, 1H), 5.71 (d,
J ˆ 8.1 Hz, 1H), 4.12 (q, J ˆ 2.7 Hz, 1H), 3.96 (dt, J ˆ 5.7, 2.4 Hz, 1H), 3.63
(dd, J ˆ 10.6, 3.0 Hz, 1H), 3.51 (dd, J ˆ 10.6, 3.0 Hz, 1H), 3.38 (s, 3H), 3.32
(s, 3H), 3.25 (s, 3H), 2.41 (ddd, J ˆ 13.7, 5.9, 2.4 Hz, 1H), 2.05 (ddd, J ˆ 13.7,
7.8, 5.9 Hz, 1H).
Preparation of 1,3-dimethylpyrimidinediones (1a ± c):[14] General proce-
dure: The pyrimidinedione (10 mmol) was suspended in an aqueous NaOH
solution (13%, 8 mL) and cooled to 08C. Dimethyl sulfate (2.5 mL) was
added slowly, the reaction mixture was left for 30 min at room temperature
Chem. Eur. J. 1999, 5, No. 12
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0512-3555 $ 17.50+.50/0
3555

J. Rodriguez, K. P. C. Vollhardt, H. Pelissier
FULL PAPER
Preparation of acetylnucleosides (1k) and (1l): These compounds were
organic extracts were washed successively with 5% aqueous HCl (10 mL)
and brine (20 mL), and then dried over Na2SO4. Filtration and evaporation
of the solvent gave a pale yellow oil. Purification by flash chromatography
(SiO2, MeOH/CHCl3 1:99) gave pure 6a as white crystals. Yield: 0.95 g
prepared according to a reported procedure.[19]
2',3',5'-Tri-O-acetyluridine (1k): White crystals (EtOH); yield: 80%; m.p.
1308C; 1H NMR (300 MHz, C6D6): d ˆ 7.16 (m, 2H), 6.13 (d, J ˆ 5 Hz,
1H), 5.61 (d, J ˆ 8.1 Hz, 1H), 5.54 (overlapping dd, J ˆ 5.5 Hz, 5.3, 1H),
5.44 (overlapping dd, J ˆ 5.5 Hz, 5.3, 1H), 4.22 (m, 2H), 4.10 (m, 1H), 1.752
(s, 3H), 1.749 (s, 3H), 1.70 (s, 3H); 13C NMR (75.8 MHz, C6D6): d ˆ 183.01,
169.93, 169.59, 169.44, 163.41, 150.87, 139.42, 103.39, 88.11, 80.09, 73.34,
70.54, 63.21, 20.08, 20.05.
(81%); m.p. 1018C; IR (C6D6): nÄ ˆ 3300, (3100 ± 2950, weak), 1755, 1715,
1
1675, 1635, 1600, 1435, 1250 cm
;
1H NMR (300 MHz, CDCl3): d ˆ 7.92
(dd, J ˆ 7.8, 0.7 Hz, 2H), 7.64 (t, J ˆ 7.4 Hz, 1H), 7.49 (t, J ˆ 7.8 Hz, 2H), 7.32
(d, J ˆ 8.0 Hz, 1H), 5.80 (d, J ˆ 8.0 Hz, 1H), 3.91 (t, J ˆ 6.8 Hz, 2H), 2.30
(td, J ˆ 6.8, 2.6 Hz, 2H), 2.07 (t, J ˆ 5.0 Hz, 1H), 1.94 (q, J ˆ 6.8 Hz, 2H);
13C NMR (75.8 MHz, C6D6): d ˆ 169.73, 162.46, 149.95, 144.36, 134.74,
132.43, 130.38, 129.21, 101.53, 82.64, 70.27, 47.79, 27.14, 15.49; MS (70 eV):
3',5'-Di-O-acetyldeoxyuridine (1l): White solid; yield: 94%; m.p. 108 ±
1098C; 1H NMR (300 MHz, CDCl3): d ˆ 7.47 (d, J ˆ 10.5 Hz, 1H), 6.28
(dd, J ˆ 10.5, 7.4 Hz, 1H), 5.74 (d, J ˆ 10.5 Hz, 1H), 5.22 (m, J ˆ 7.0 Hz,
1H), 4.26 (m, 3H), 2.50 (ddd, J ˆ 7.4, 6.1, 2.0 Hz, 1H), 2.20 (m, 1H), 2.08 (s,
3H), 2.06 (s, 3H).
‡
m/z (%): 282 (1) [M ], 254 (3), 212 (3), 177 (13), 105 (100), 77 (81);
C16H14N2O3 (282.30): calcd C 68.08, H 4.96, N 9.93; found C 68.07, H 4.98, N
9.95.
1-(1-Butynyl)-3-benzoyluracil (6b): This compound was prepared as above
Preparation of pyrimidines (2): 2,6-Dichloropyrimidine (2a) was prepared
according to a reported procedure and used for the preparation of 2,6-
dichloropyrimidine (2b).[16]
2,6-Dichloropyrimidine (2a): Pale yellow solid; yield: 75%; m.p. 558C; 1H
NMR (300 MHz, CDCl3): d ˆ 8.53 (d, J ˆ 8.2 Hz, 1H), 7.46 (d, J ˆ 8.2 Hz,
1H).
2,6-Dimethoxypyrimidine (2b): Pale yellow oil; yield: 64%; 1H NMR
(300 MHz, CDCl3): d ˆ 8.19 (d, J ˆ 7.8 Hz, 1H), 6.38 (d, J ˆ 7.8 Hz, 1H),
3.99 (s, 3H), 3.95 (s, 3H).
from 4-iodo-1-butyne.[42] Flash chromatography (silica gel, MeOH/CHCl3
(1:99) gave white crystals. Yield: 33%; m.p. 142 ± 1458C; IR (CHCl3): nÄ ˆ
1
3305, 2930, 1755, 1710, 1670, 1600, 1390, 1180 cm
;
1H NMR (300 MHz,
CDCl3): d ˆ 7.74 (m, 5H), 7.38 (d, J ˆ 7.9 Hz, 1H), 5.79 (d, J ˆ 7.9 Hz, 1H),
3.90 (t, J ˆ 2.6 Hz, 2H), 2.11 (t, J ˆ 2.6 Hz, 1H); 13C NMR (75.8 MHz,
CDCl3): d ˆ 168.61, 162.40, 149.42, 144.97, 135.11, 131.16, 130.31, 129.09,
‡
101.42, 79.66, 71.98, 47.80, 18.53; MS (70 eV): m/z (%): 268 (3) [M ], 240
(26), 188 (8), 106 (25), 105 (100), 82 (23), 78 (15), 77 (94), 76 (9), 70 (8).
1-(1-Pentynyl)-3-benzoylthymine (6c): This compound was prepared as
above from 3-benzoylthymine (5c).[22] Flash chromatography (silica gel,
MeOH/CHCl3 0.5:99.5) gave 6c as a colorless oil. Yield: 76%; IR (C6D6):
Preparation of enamines (3): These compounds were prepared according to
a reported procedure.[16,17]
Acetylcytosine (3a): White solid; yield: 59%; m.p. > 3108C; 1H NMR
(300 MHz, [D6]DMSO): d ˆ 7.80 (d, J ˆ 10.8 Hz, 1H), 7.10 (d, J ˆ 10.8 Hz,
1H), 2.10 (s, 3H); C6H7N3O2 (153.14): calcd C 47.06, H 4.61, N 27.44; found
C 47.14, H 4.64, N 27.79.
1-Propylacetylcytosine (3b): White solid; yield: 72%; m.p. 1628C; 1H
NMR (300 MHz, CDCl3): d ˆ 7.70 (d, J ˆ 8.4 Hz, 1H), 7.41 (d, J ˆ 8.4 Hz,
1H), 3.81 (t, J ˆ 6.9 Hz, 2H), 2.35 (s, 3H), 1.75 (m, 2H), 0.98 (t, J ˆ 7.1 Hz,
3H).
1
nÄ ˆ 3300, 3100, 3070, 3040, 1755, 1710, 1670, 1250, 1040 cm
;
1H NMR
(300 MHz, CDCl3): d ˆ 8.05 (d, J ˆ 7.5 Hz, 2H), 7.74 (t, J ˆ 6.6 Hz, 1H), 7.63
(t, J ˆ 5.6 Hz, 2H), 7.28 (s, 1H), 4.00 (t, J ˆ 6.2 Hz, 2H), 2.44 (m, 2H), 2.16
(m, 1H), 2.09 (m, 2H), 2.09 (s, 3H); 13C NMR (75.8 MHz, C6D6): d ˆ
170.02, 163.37, 149.99, 140.96, 134.93, 132.33, 130.47, 129.30, 109.86, 82.93,
‡
70.35, 47.73, 27.50, 15.67, 12.32; MS (70 eV): m/z (%): 297 (6) [M ], 296 (28),
268 (13), 251 (1), 191 (24), 149 (24), 121 (29), 105 (100), 96 (21), 77 (94), 51
(50).
1,N4-Dimethylcytosine (3c): White solid; yield: 80%; m.p. 1798C; 1H NMR
(300 MHz, CDCl3): d ˆ 7.00 (d, J ˆ 8.4 Hz, 1H), 5.60 (m, 2H), 3.35 (s, 3H),
2.80 (s, 3H).
1,N4,N4-Trimethylcytosine (3d): White solid; yield: 98%; m.p. 1758C; 1H
NMR (300 MHz, CDCl3): d ˆ 7.60 (d, J ˆ 7.5 Hz, 1H), 5.70 (d, J ˆ 7.5 Hz,
1H), 3.48 (s, 3H), 3.20 (m, 6H).
1-(1-Pentynyl)-3-(p-nitrobenzoyl)uracil (6d): This compound was prepared
as above from 3-p-nitrobenzoylthymine (5d).[22] Flash chromatography
(silica gel, MeOH/CHCl3 1:99) gave 6d as a colorless oil. Yield: 35%; IR
(CDCl3): nÄ ˆ 3310, (3120 ± 2950, weak), 2260, 1765, 1715, 1675, 1610, 1535,
1350, 1250 cm 1; 1H NMR (300 MHz, CDCl3): d ˆ 8.31 (d, J ˆ 9.0 Hz, 2H),
8.08 (d, J ˆ 9.0 Hz, 2H), 7.36 (d, J ˆ 8.1 Hz, 1H), 5.81 (d, J ˆ 8.1 Hz, 1H),
3.92 (t, J ˆ 7.0, 2H), 2.30 (td, J ˆ 7.0, 2.6 Hz, 2H), 2.07 (t, J ˆ 2.6 Hz, 1H),
1.94 (q, J ˆ 7.0 Hz, 2H); 13C NMR (75.8 MHz, C6D6): d ˆ 168.87, 162.44,
151.13, 149.84, 145.05, 136.52, 131.21, 124.28, 101.47, 82.69, 70.50, 48.05,
Preparation of imidates (4): These compounds were prepared by alkylation
of the corresponding 2,6-dialkylpyrimidines.[16]
‡
1-Methyl-4-methoxypyrimidine-2-one (4a): Pale yellow solid; yield: 64%;
m.p. 1458C; 1H NMR (300 MHz, [D6]DMSO): d ˆ 7.98 (d, J ˆ 6.6 Hz, 1H),
5.98 (d, J ˆ 6.6 Hz, 1H), 3.73 (s, 3H), 3.56 (s, 3H).
27.17, 15.54; MS (70 eV): m/z (%): 327 (3) [M ], 275 (8), 257 (7), 177 (37),
150 (100), 104 (85), 76 (61); C16H13N3O5 (327.30): calcd C 58.72, H 4.00, N
12.84; found C 57.35, H 4.09, N 11.98.
1-Methyl-4-ethoxypyrimidine-2-one (4b): Pale yellow solid; yield: 80%;
m.p. 1368C; 1H NMR (300 MHz, CDCl3): d ˆ 7.50 (d, J ˆ 8.3 Hz, 1H), 5.51
(d, J ˆ 8.3 Hz, 1H), 4.00 (q, J ˆ 6.7 Hz, 2H), 3.10 (s, 3H), 0.98 (t, J ˆ 6.7 Hz,
3H).
1-(1-Pentynyl)uracil (6e): Et3N (8 mL) and 5-iodo-1 pentyne[42] (1.46 g,
7.5 mmol) was added to a solution of 3-benzoyluracil (5a)[22] (1.08 g,
5 mmol) in a mixture of EtOH and H2O (1:1, 20 mL). The mixture was
heated at 508C for 21 h. Most of the solvent was evaporated under reduced
pressure, and CHCl3 (60 mL) was added to the residue, which was then
filtered through a short pad of Celite. The filtrate was washed with H2O
(3 Â 20 mL), and the organic layer dried over Na2SO4. Evaporation of the
solvent gave a yellow oil which was purified by flash chromatography (SiO2,
1-Methyl-4-propoxypyrimidine-2-one (4c): Pale yellow solid; yield: 88%;
1
m.p. 108 ± 1108C; IR (CDCl3): nÄ ˆ 2975, 1670, 1640, 1310 cm
;
1H NMR
(300 MHz, CDCl3): d ˆ 7.38 (d, J ˆ 7.1 Hz, 1H), 5.82 (d, J ˆ 7.2 Hz, 1H),
4.29 (t, J ˆ 6.8 Hz, 2H), 3.48 (s, 3H), 1.72 (m, 2H), 0.95 (t, J ˆ 7.4 Hz, 3H);
13C NMR (75.8 MHz, CDCl3): d ˆ 171.08, 158.60, 147.38, 95.00, 67.98, 37.35,
CHCl3/MeOH 98:2). Yield: 0.28 g (32%); white crystals; m.p. 128 ± 1308C;
‡
1
IR (CHCl3): nÄ ˆ 3400, 3320, 3010, 1700, 1460, 1230 cm
;
1H NMR
21.31, 9.78; MS (70 eV): m/z (%): 168 (23) [M ], 139 (22), 138 (31), 127
(70), 126 (100), 110 (56), 109 (15), 84 (88), 83 (96), 82 (35), 82 (29); for
C8H12N2O2: C 57.13, H 7.19, N 16.65; found C 56.56, H 6.79, N 16.61.
(300 MHz, [D6]acetone): d ˆ 7.55 (d, J ˆ 8.0 Hz, 1H), 5.54 (dd, J ˆ 8.0,
1.7 Hz, 1H), 3.84 (t, J ˆ 7.0 Hz, 2H), 2.41 (t, J ˆ 2.5 Hz, 1H), 2.27 (td, J ˆ
7.0, 2.5 Hz, 2H), 1.89 (q, J ˆ 7.0 Hz, 2H); 13C NMR (75.8 MHz, [D6]ace-
tone): d ˆ 164.38, 151.75, 146.10, 101.82, 83.54, 70.72, 48.11, 28.29, 15.91; MS
1-Ethyl-4-methoxypyrimidine-2-one (4d): Pale yellow solid; yield: 88%;
1
m.p. 908C; H NMR (300 MHz, CDCl3): d ˆ 7.48 (d, J ˆ 7.2 Hz, 1H), 5.88
‡
(70 eV): m/z (%): 178 (6) [M ], 150 (15), 133 (31), 113 (72), 107 (90), 82
(d, J ˆ 7.2 Hz, 1H), 3.93 (s, 3H), 3.89 (q, J ˆ 7.3 Hz, 2H), 1.33 (t, J ˆ 7.3 Hz,
(100); C9H10N2O2 (178.19): calcd C 60.66, H 5.66: N, 15.79; found C 60.443,
H 5.70, N 15.61.
3H).
Preparation of pyrimidines (6): 1-(1-Pentynyl)-3-benzoyluracil (6a). An-
hydrous K2CO3 (0.889 g, 4.58 mmol) and 5-iodo-1-pentyne[42] (0.893 g,
4.58 mmol) was added to a solution of 3-benzoyluracil (5: R1 ˆ COPh, R2 ˆ
H)[22] (0.90 g, 4.16 mmol) in dry DMSO (5 mL) and dry THF (40 mL). The
mixture was stirred under nitrogen at room temperature for 22 h, filtered
through a short pad of Celite, and then rinsed with CHCl3 (50 mL). The
solvent was evaporated under reduced pressure. Water (50 mL) was added,
and the mixture then extracted with CHCl3 (3 Â 60 mL). The combined
1-(4-Pentynoyl)uracil (6 f): 4-Pentynoyl chloride[23] (1.4 g, 12 mmol) was
added in one portion to a magnetically stirred suspension of powdered
uracil (1.12 g, 10 mmol) in CH3CN (10 mL) and pyridine (2 mL) at room
temperature. The resulting brown mixture remained heterogeneous
throughout. After 3.5 h, the suspension was filtered and washed with
CH3CN and hexanes. Recrystallization from THF gave pure 6 f. Yield:
1.15 g (60%); white crystals; m.p. 1878C (decomp); IR (KBr): nÄ ˆ 3450,
3556
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0512-3556 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 12

Cyclooligomerizations
3549±3561
1
3290, 3040, 2845, 1730, 1635, 1405, 1265, 1160 cm
;
1H NMR (300 MHz,
filtered through a short pad of Celite and rinsed with the reaction solvent
until the filtrate was clear. The solvent was then removed in vacuo and the
residue subjected to flash chromatography (silica gel or neutral alumina).
Note that when the reactions were carried out with [CpCo(C2H4)2],[31] THF
was used as solvent and nitrogen replaced by argon. Simultaneous addition
of the cocyclizing alkyne in THF (5 mL) and [CpCo(C2H4)2] in THF (5 mL)
was performed with two syringe pumps. No irradiation was used under
these conditions.
[D6]acetone): d ˆ 8.22 (d, J ˆ 8.5 Hz, 1H), 5.83 (dd, J ˆ 8.5, 2.0 Hz, 1H),
3.38 (t, J ˆ 7.0 Hz, 2H), 2.56 (td, J ˆ 7.0, 2.6 Hz, 2H), 2.39 (t, J ˆ 2.6 Hz,
1H); 13C NMR (300 MHz, [D6]DMSO): d ˆ 171.44, 162.92, 149.47, 137.56,
‡
104.47, 83.24, 71.60, 37.89, 13.53; MS (70 eV): m/z (%): 192 (4) [M ], 164
(5), 113 (54), 81 (81), 69 (64), 53 (100); C9H8N2O3 (192.17): calcd C 56.22, H
4.16, N 14.57; found C 56.00, H 4.26, N 14.79.
1-Cyanoethyl-3-benzoyluracil (6g): 3-Benzoyluracil (5a)[22] (0.432 g,
2 mmol) was suspended in H2O (5 mL) and EtOH (95%, 5 mL). Et3N
(2 mL) was added, and the solid dissolved. Acrylonitrile (2.5 mL) was
added, and the mixture was allowed to stand at room temperature for 21 h.
After this time, a white precipitate formed. The mixture was then cooled to
08C and filtered. The white precipitate was washed with cold water and
dried in vacuo for 24 h to give 6g. Yield: 0.356 g (60%): white solid; m.p.
168 ± 1708C; IR (KBr): nÄ ˆ 3100, 2250, 1740, 1700, 1660, 1600, 1435, 1260,
1230 cm 1; 1H NMR (300 MHz, CDCl3): d ˆ 7.94 (d, J ˆ 7.4 Hz, 2H), 7.71 (t,
J ˆ 7.4 Hz, 1H), 7.54 (m, 2H), 7.39 (d, J ˆ 8.0 Hz, 1H), 5.84 (d, J ˆ 8.0 Hz,
1H), 4.01 (t, J ˆ 6.3 Hz, 2H), 2.84 (t, J ˆ 6.3 Hz, 2H); 13C NMR (75.8 MHz,
[D6]DMSO): d ˆ 169.43, 162.23, 149.39, 146.31, 135.59, 131.02, 130.33,
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,8a,9-h)-1,3-dimethyl-1,2,3,4,4a-endo,
9a-endo-hexahydro-2,4-dioxo-cyclopenta[g]quinazoline]cobalt (9a): From
1a (0.145 g, 1.035 mmol), [CpCo(CO)2] (0.373 g, 2.07 mmol), and 8a
(0.191 g, 2.07 mmol) in toluene (10 mL), with irradiation under reflux for
19 h. Flash chromatography (SiO2, hexanes/Et2O 20:80) gave orange
crystals. Yield: 0.194 g (53%); m.p. 152 ± 1548C; IR (C6D6): nÄ ˆ 3100. 2960,
1700, 1665, 1665, 1420, 1295, 755 cm 1; 1H NMR (300 MHz, C6D6): d ˆ 4.25
(s, 5H), 3.47 (d, J ˆ 4.9 Hz, 1H), 3.19 (s, 3H), 3.14 (dd, J ˆ 10.7, 3.4 Hz, 1H),
2.99 (d, J ˆ 3.4 Hz, 1H), 2.74 (s, 3H), 2.71 (dd, J ˆ 10.7, 4.9 Hz, 1H), 2.27
(m, 1H), 2.02 (m, 3H), 1.85 (m, 1H), 1.74 (m, 1H); 13C NMR (75.8 MHz,
C6D6): d ˆ 171.08, 151.20, 100.15, 99.51, 80.56, 56.15, 45.55, 43.97, 42.29,
‡
‡
129.49, 118.28, 101.07, 43.79, 16.94; MS (70 eV): m/z (%): 269 (2) [M ], 242
33.28, 31.84, 31.77, 27.75, 24.06; MS (70 eV): m/z (%): 356 (0.13) [M ], 355
(0.5), 241 (30), 105 (100), 77 (89), 53 (43), 51 (50); C14H11N3O3 (269.26):
calcd C 62.45, H 4.12, N 15.60; found C 62.26, H 4.12, N, 15.41.
(0.12), 354 (0.73), 232 (6), 231 (9), 204 (8), 175 (73), 145 (100), 117 (83), 115
(88), 91 (48), 77 (17), 65 (20); C18H21CoN2O2 (356.31): calcd C 60.68, H 5.94,
N 7.86; found C 60.42, H 5.96, N 7.77.
1-Cyanoethyluracil (6h): This compound was prepared by Michael addition
of uracil to acrylonitrile following the reported procedure.[24] Yield: 66%;
white crystals; m.p. 2308C; IR (DMSO): nÄ ˆ 3010, 2800, 1700, 1635, 1460,
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,8a,9-h)-1,3-dimethyl-1,2,3,4,4a-endo,
9a-endo-hexahydro-2-oxo-4-methylimino-cyclopenta[g]quinazoline]cobalt
(9e): From 1e (0.128 g, 0.83 mmol), 8a (173 mL, 1.33 mmol), and [CpCo-
(CO)2] (186 mL, 1.33 mmol) in toluene (16 mL), with irradiation under
reflux for 18 h. Flash chromatography on neutral alumina (pentane/AcOEt
1:9) gave an orange oil. Yield: 0.141 g (46%). Cooling in pentane gave
orange crystals; m.p. 93 ± 958C; IR (CH2Cl2): nÄ ˆ 2940, 1660, 1630, 1480,
1150 cm 1; 1H NMR (300 MHz, C6D6): d ˆ 4.35 (s, 5H), 3.35 (s, 3H), 3.18 (s,
3H), 3.10 (m, 1H), 3.07 (m, 2H), 3.02 (m, 1H), 2.78 (s, 3H), 2.20 (m, 1H),
1.97 (m, 3H), 1.80 (m, 1H); 13C NMR (75.8 MHz, C6D6): d ˆ 158.20, 154.08,
100.01, 99.56, 80.53, 57.18, 45.29, 42.14, 39.40, 36.52, 33.33, 31.98, 31.87,
1
1
1240 cm ; H NMR (300 MHz, [D6]DMSO): d ˆ 7.67 (d, J ˆ 7.9 Hz, 1H),
5.60 (d, J ˆ 7.9 Hz, 1H), 3.93 (t, J ˆ 6.5 Hz, 2H), 2.89 (t, J ˆ 6.5 Hz, 2H); 13
C
NMR (75.8 MHz, [D6]DMSO): d ˆ 163.61, 150.69, 145.28, 118.33, 101.27,
‡
43.27, 16.87; MS (70 eV): m/z (%): 165 (29) [M ], 125 (36), 82 (100), 53
(39); C7H7N3O2 (165.15): calcd C 50.90, H 4.20, N 25.40; found C 50.67, H
4.02, N 25.18.
1-Cyanopropyluracil (6i): 4-Chlorobutyronitrile (0.11 mL, 1.2 mmol) and
K2CO3 (0.152 g, 1.1 mmol) were successively added to a solution of 3-
benzoyluracil (5a)[22] (0.261 g, 1 mmol) in a mixture dry THF and dry
DMSO (10:1, 10 mL). The solution was heated at 608C for 12 h. Cooling,
filtration, and evaporation of the solvents in vacuo gave a crude solid,
which was purified by flash chromatography (silica gel, CHCl3/CH3OH
4:1). Yield: 37%; white crystals; m.p. 1578C; IR (CHCl3): nÄ ˆ 3400, 2975,
2260, 1700, 1630, 1240, 1053, 1010 cm 1; 1H NMR (300 MHz, [D6]DMSO):
d ˆ 8.21 (d, J ˆ 7.8 Hz, 1H), 6.15 (d, J ˆ 7.8 Hz, 1H), 4.33 (t, J ˆ 6.9 Hz,
2H), 3.10 (m, 4H); 13C NMR (75.8 MHz, CDCl3): d ˆ 164.95, 150.73,
147.29, 125.95, 101.61, 47.20, 31.67, 27.06; MS (70 eV): m/z (%): 179 (26)
‡
30.64, 24.22; MS (70 eV): m/z (%): 369 (52) [M ], 354 (20), 312 (26), 289
(47), 288 (23), 287 (35), 244 (29), 243 (21), 242 (71), 239 (21), 215 (92), 188
(21), 187 (100), 158 (92), 144 (27), 124 (68), 121 (41), 117 (20), 115 (45), 71
(20); HRMS: calcd for C19H24CoN3O 369.125; found 369.125.
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,8a,9-h)-1,3-dimethyl-1,2,3,4,4a-endo,
9a-endo-hexahydro-2-oxo-4-ethylimino-cyclopenta[g]quinazoline]cobalt
(9 f): From 1 f (0.167 g, 1 mmol), 8a (209 mL, 1.8 mmol), and [CpCo(CO)2]
(240 mL, 1.9 mmol) in toluene (16 mL), with irradiation under reflux for
20 h. Flash chromatography (neutral alumina, pentane/AcOEt 1:99) gave
orange crystals. Yield: 0.150 g (40%); m.p. 127 ± 1298C; IR (CH2Cl2): nÄ ˆ
‡
[M ], 139 (18), 126 (31), 125 (20), 113 (29), 112 (47), 108 (16), 96 (26), 83
(12), 82 (100), 70 (15).
1
2950, 1680, 1640, 1490 cm 1; H NMR (300 MHz, C6D6): d ˆ 4.30 (s, 5H),
1-(1-Pentynyl)-N4-acetylcytosine (7): This compound was prepared from
acetylcytosine (3a) and 5-iodo-1-pentyne[42] with the procedure described
for 6a (vide supra). Flash chromatography (silica gel, CHCl3/CH3OH
85:15) gave 7 as a white solid. Yield: 88%; m.p. 1718C; IR (CDCl3): nÄ ˆ
3400, 1725, 1665, 1490, 1230 cm 1; 1H NMR (300 MHz, CDCl3): d ˆ 7.84 (d,
J ˆ 7.2 Hz, 1H), 7.41 (d, J ˆ 7.2 Hz, 1H), 4.03 (t, J ˆ 6.8 Hz, 2H), 2.32 (s,
3H), 2.25 (m, 2H), 2.02 (m, 3H); 13C NMR (75.8 MHz, CDCl3): d ˆ 171.48,
163.02, 155.51, 148.96, 96.73, 82.14, 69.92, 49.62, 26.54, 24.56, 15.22; MS
3.39 (m, 2H), 3.38 (s, 3H), 3.18 (m, 2H), 3.09 (m, 1H), 3.01 (m, 1H), 2.76 (s,
3H), 2.20 (m, 2H), 1.90 (m, 4H), 1.34 (t, J ˆ 7.2 Hz, 3H); 13C NMR
(75.8 MHz, C6D6): d ˆ 156.37, 154.25, 100.05, 99.40, 80.40, 57.35, 45.22,
43.72, 42.69, 39.86, 33.26, 31.94, 31.84, 31.60, 24.19, 17.67; MS (70 eV): m/z
‡
(%): 383 (46) [M ], 326 (30), 273 (36), 258 (36), 256 (34), 242 (40), 239 (42),
175 (27), 174 (36), 158 (25), 124 (100), 121 (33), 115 (34); HRMS: calcd for
C20H26CoN3O 383.141; found 383.141.
‡
(70 eV): m/z (%): 219 (78) [M ], 204 (88), 176 (19), 167 (95), 161 (17), 148
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1,3-dimethyl-1,2,3,4,4a-endo,
6,7,8,9,10a-endo-decahydro-2,4-dioxo-benzo[g]quinazoline]cobalt (10a):
From 1a (0.40 g, 2.85 mmol), [CpCo(CO)2] (1.03 g, 5.71 mmol), and 8b
(0.606 g, 5.71 mmol) in xylene (20 mL), with irradiation under reflux for
20 h. Flash chromatography (SiO2, hexanes/AcOEt 65:35) gave orange
crystals. Yield: 0.804 g (76%); m.p. 130 ± 1318C; IR (neat): nÄ ˆ 3100, 2940,
1700, 1660, 1485, 1300, 1005, 815 cm 1; 1H NMR (300 MHz, C6D6): d ˆ 4.32
(s, 5H), 3.24 (s, 3H), 3.23 (d overlapping, 1H), 3.13 (dd, J ˆ 11.0, 3.3 Hz,
1H), 2.80 (s, 3H), 2.78 (d overlapping, 1H), 2.67 (dd, J ˆ 11.0, 4.9 Hz, 1H),
2.34 (m, 1H), 1.99 (m, 2H), 1.72 (m, 3H), 1.43 (m, 2H); 13C NMR
(75.8 MHz, C6D6): d ˆ 170.63, 151.17, 93.73, 93.17, 81.16, 56.53, 48.69, 46.69,
41.67, 33.44, 28.90, 28.83, 27.68, 23.49, 23.35; MS (70 eV): m/z (%): 370 (27)
(9), 138 (100), 125 (64), 111 (66), 95 (41), 81 (94), 67 (88), 54 (36);
C11H13N3O2 (219.24): calcd C 60.01, H 5.78, N 18.77; found C 60.18, H 5.78,
N 18.62.
General Procedure for [CpCoL2] Cyclizations: The pyrimidine (1 mmol)
was dissolved in the appropriate solvent (10 mL) in a round bottom flask
(50 mL) equipped with a coil condenser. This mixture was then degassed
under nitrogen by three freeze-pump-thaw cycles on a vacuum line and
then brought to the required temperature. The diyne (1.5 to 2 mmol) was
dissolved in the same solvent (7 mL) and degassed as before, then
[CpCo(CO)2] (1.5 to 2 mmol) was added by means of a syringe. The
resulting solution was loaded into a gastight syringe (10 mL) and added to
the pyrimidine by means of a syringe pump over a period of 18 ± 22 h.
During the addition, the flask was irradiated with a slide projector lamp
(sylvania ELH 300W) at a distance of 5 cm from the center of the flask with
an applied potential of 65 V. Note that for reactions carried out at room
temperature, it was necessary to blow air across the surface of the flask. The
mixture was then cooled at room temperature and the black solution was
‡
[M ], 369 (22), 368 (100), 302 (30), 187 (26), 172 (12), 124 (76), 91 (20), 57
(20); C19H23CoN2O2 (370.34): calcd C 61.62, H 6.26, N 7.56; found C 60.96,
H 6.17, N 7.66.
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1,3-dimethyl-1,2,3,4,4a-endo,
6,7,8,9,10a-endo-decahydro-2-oxo-4-methylimino-benzo[g]quinazoline]co-
balt (10e): From 1e (0.153 g, 1 mmol), 8b (240 mL, 1.8 mmol), and
Chem. Eur. J. 1999, 5, No. 12
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0512-3557 $ 17.50+.50/0
3557

J. Rodriguez, K. P. C. Vollhardt, H. Pelissier
FULL PAPER
[CpCo(CO)2] (224 mL, 1.8 mmol) in toluene (16 mL), with irradiation
under reflux for 20 h. Flash chromatography (neutral alumina, pentane/
acetone (7:3) gave a thick orange oil. Yield: 0.383 g (79%); IR (CH2Cl2):
nÄ ˆ 2930, 1660, 1630, 1475, 805 cm 1; 1H NMR (300 MHz, C6D6): d ˆ 4.35 (s,
5H), 3.41 (s, 3H), 3.18 (s, 3H), 3.10 (m, 2H), 2.84 (m, 1H), 2.79 (s, 3H), 2.62
(m, 1H), 2.10 (m, 1H), 1.67 (m, 7H); 13C NMR (75.8 MHz, CDCl3): d ˆ
159.00, 154.33, 93.83, 93.49, 81.18, 57.48, 48.15, 44.72, 39.28, 36.77, 33.51,
Compound 10ib: orange crystals; m.p. 59 ± 638C; 1H NMR (300 MHz,
C6D6): d ˆ 5.10 (brd, J ˆ 8.9 Hz, 3H), 4.58 (m, 1H), 4.46 (s, 5H), 3.80 (m,
2H), 3.37 (m, 2H), 3.32 (s, 3H), 3.18 (s, 3H), 3.15 (m, 1H), 2.16 (m, 3H),
2.02 (m, 1H), 1.91 (m, 1H), 1.75 (m, 2H), 1.50 (m, 2H), 1.49 (s, 3H), 1.23 (s,
3H); 13C NMR (75.8 MHz, C6D6): d ˆ 169.31, 113.19, 98.06, 93.38, 91.01,
87.50, 85.35, 83.39, 81.11, 74.45, 58.83, 56.39, 52.73, 51.57, 45.27, 28.68, 28.67,
‡
27.48, 27.26, 25.37, 23.62, 23.54; MS (70 eV): m/z (%): 542 (72) [M ], 187
(76), 172 (48), 159 (38), 129 (100), 124 (36), 101 (37), 71 (8).
‡
30.38, 29.55, 29.08, 23.61, 23.60; MS (70 eV): m/z (%): 383 (100) [M ], 381
(29), 326 (38), 303 (58), 301 (36), 272 (52), 258 (47), 256 (86), 229 (60), 187
(35), 172 (35), 128 (34), 124 (47), 97 (32), 85 (29), 83 (30), 71 (46); HRMS:
calcd for C20H26CoN3O 383.141; found; 383.140. When the flash chroma-
tography was performed on neutral Al2O3 deactivated with 3% H2O or
SiO2 and eluted with a mixture of MeOH/CHCl3, 10e was completely
transformed to the cobalt complex 10a.
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1,3-dimethyl-1,2,3,4,4a-endo,
6,7,8,9,10a-endo-decahydro-2-oxo-4-ethylimino-benzo[g]quinazoline]co-
balt (10 f): From 1 f (0.117 g, 0.7 mmol), 8b (157 mL, 1.26 mmol), and
[CpCo(CO)2] (168 mL, 1.33 mmol) in toluene (12 mL), with irradiation
under reflux for 22 h. Flash chromatography (neutral alumina, pentane/
Compound 10ic: orange crystals; m.p. 47 ± 508C; 1H NMR (300 MHz,
C6D6): d ˆ 5.45 (d, J ˆ 2.0 Hz, 1H), 5.31 (dd, J ˆ 6.5, 2.0 Hz, 1H), 5.06 (dd,
J ˆ 6.6, 4.4 Hz, 1H), 4.50 (m, 1H), 4.36 (s, 5H), 3.68 (m, 2H), 3.38 (m, 1H),
3.36 (s, 3H), 3.13 (m, 1H), 3.12 (s, 3H), 2.83 (m, 1H), 2.22 (dd, J ˆ 7.4,
1.2 Hz, 1H), 2.10 (m, 2H), 1.80 (m, 3H), 1.55 (s, 3H), 1.50 (m, 3H), 1.14 (s,
3H); 13C NMR (75.8 MHz, C6D6): d ˆ 168.99, 152.08, 113.70, 96.54, 96.13,
93.46, 90.82, 85.63, 85.30, 82.76, 81.12, 73.81, 58.85, 54.01, 52.14, 51.37, 45.19,
‡
28.55, 27.79, 27.35, 27.31, 25.41, 23.50; MS (70 eV): m/z (%): 542 (62) [M ],
231 (59), 187 (68), 172 (46), 159 (68), 129 (100), 124 (38), 101 (33), 71 (13).
Compound 10id: orange crystals; m.p. 52 ± 558C; 1H NMR (300 MHz,
C6D6): d ˆ 5.23 (d, J ˆ 1.1 Hz, 1H), 5.16 (dd, J ˆ 6.4, 1.3 Hz, 1H), 5.08 (dd,
J ˆ 6.3, 4.0 Hz, 1H), 4.61 (dd, J ˆ 6.5, 1.9 Hz, 1H), 4.28 (s, 5H), 3.74 (dd,
J ˆ 5.6, 2.0 Hz, 1H), 3.43 (dd, J ˆ 10.7, 3.0 Hz, 1H), 3.22 (d, J ˆ 3.1 Hz, 1H),
3.17 (s, 3H), 3.10 (dd, J ˆ 5.2, 2.3 Hz, 1H), 3.06 (s, 3H), 2.59 (dd, J ˆ 10.8,
5.2 Hz, 1H), 2.15 (m, 2H), 1.90 (m, 1H), 1.70 (m, 2H), 1.57 (s, 3H), 1.50 (m,
3H), 1.25 (s, 3H); 13C NMR (75.8 MHz, C6D6): d ˆ 171.18, 151.01, 113.25,
97.45, 94.35, 92.54, 87.23, 85.23, 83.39, 81.14, 74.33, 58.81, 58.27, 51.35, 45.93,
41.07, 29.11, 28.51, 27.55, 27.32, 25.37, 23.59, 23.43; MS (70 eV): m/z (%): 542
AcOEt (1:9) gave orange crystals. Yield: 0.153 g (55%); m.p. 92 ± 948C; IR
1
(CH2Cl2): nÄ ˆ 2980, 2940, 1670, 1640, 1490, 1470, 820 cm
;
1H NMR
(300 MHz, C6D6): d ˆ 4.34 (s, 5H), 3.41 (s, 3H), 3.37 (m, 2H), 3.12 (m, 2H),
2.83 (d, J ˆ 2.7 Hz, 1H), 2.77 (s, 3H), 2.72 (d, J ˆ 3.3 Hz, 1H), 2.12 (m, 2H),
1.82 (m, 2H), 1.69 (m, 2H), 1.82 (m, 2H), 1.69 (m, 2H), 1.50 (m, 2H), 1.34
(t, J ˆ 7.2 Hz, 3H); 13C NMR (75.8 MHz, C6D6): d ˆ 156.34, 154.47, 93.71,
92.70, 80.96, 57.83, 48.34, 45.51, 43.81, 39.37, 33.51, 30.52, 29.11, 28.83, 23.63,
‡
23.54, 17.72; MS (70 eV): m/z (%): 397 (51) [M ], 340 (37), 287 (36), 272
‡
(54) [M ], 356 (22), 256 (30), 187 (64), 172 (37), 159 (32), 129 (100), 124
(32), 270 (33), 256 (46), 229 (63), 188 (28), 187 (66), 172 (22), 128 (54), 124
(100); HRMS: calcd for C21H28CoN3O 397.156; found 397.156.
(37), 101 (34), 71 (7).
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1-(1'-b-2'-deoxyribofuranose-
3',5'-dimethoxy)-3-methyl-1,2,3,4,4a-endo,6,7,8,9,10a-endo-decahydro-2,4-
dioxobenzo[g]quinazoline]cobalt (10j) (major isomer): From 1j (0.20 g,
0.74 mmol), [CpCo(C2H4)2] (0.266 g, 1.48 mmol), and 8b (0.157 g,
1.48 mmol) in THF (14 mL) at reflux without irradiation for 2 h. Flash
chromatography (SiO2, hexanes/AcOEt 1:1) gave an orange oil (yield:
0.349 g, 94%) of a mixture of four diastereomers in the ratio 45:4:1:1. 10j
was obtained after a second flash chromatography (SiO2, hexanes/AcOEt
55:45) as yellow crystals; m.p. 156 ± 1588C; IR (C6D6): nÄ ˆ 2980, 2930, 2820,
1705, 1670, 1460, 1200, 1100, 1060 cm 1; 1H NMR (400 MHz, CD2Cl2): d ˆ
5.89 (dd, J ˆ 8.3, 6.1 Hz, 1H), 4.71 (s, 5H), 3.98 (m, 2H), 3.92 (dt, J ˆ 6.1,
3.2 Hz, 1H), 3.59 (overlapping dd, 2H), 3.46 (s, 3H), 3.33 (s, 3H), 3.29 (d,
J ˆ 2.8 Hz, 1H), 3.03 (d, J ˆ 5.7 Hz, 1H), 2.88 (s, 3H), 2.69 (dd, J ˆ 10.0,
5.7 Hz, 1H), 2.33 (m, 1H), 2.28 (m, 1H), 2.24 (m, 1H), 2.03 (m, 5H), 1.76
(m, 1H), 1.67 (m, 1H); 13C NMR (75.8 MHz, C6D6): d ˆ 171.78, 151.71,
95.01, 92.18, 87.02, 82.26, 81.68, 81.07, 73.59, 58.94, 56.50, 53.54, 52.49, 44.55,
39.80, 35.20, 29.17, 27.63, 28.81, 23.67, 23.51; MS (70 eV): m/z (%): 500 (15)
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1-(1'-b-ribofuranose-2',3',5'-tri-
methoxy)-3-methyl-1,2,3,4,4a-endo,6,7,8,9,10a-endo-decahydro-2,4-dioxo-
benzo[g]quinazoline]-cobalt (10h) (major isomer): From 1h (0.20 g,
0.666 mmol), [CpCo(CO)2] (0.18 g, 0.999 mmol), and 8b (0.106 g,
0.999 mmol) in xylene (10 mL), with irradiation under reflux for 18 h.
Another addition of [CpCo(CO)2] (0.18 g, 0.999 mmol) and 8b (0.106 g,
0.999 mmol) in xylene (3 mL), and irradiation at reflux for additional 20 h.
Flash chromatography (SiO2, hexanes/AcOEt 3:2) gave an orange oil.
Yield: 0.249 g (71%). This oil was a mixture of four diastereomers in the
ratio 7.5:4:1:1. Compound 10h was obtained as a 5:1 mixture by preparative
TLC (hexanes/AcOEt, 45:55). Orange crystals; m.p. 75 ± 778C; IR (C6D6):
nÄ ˆ 3090, 3085, 3040, 2930, 1700, 1670, 1480, 1125, 1090, 680 cm 1; 1H NMR
(300 MHz, CD2Cl2): d ˆ 5.48 (d, J ˆ 4.6 Hz, 1H), 4.71 (s, 5H), 4.01 (m, 2H),
3.92 (dd, overlapping, J ˆ 5.2 Hz, 1H), 3.82 (dd, overlapping, J ˆ 5.4 Hz,
1H), 3.68 (dd, J ˆ 10.6, 3.1 Hz, 1H), 3.54 (dd, J ˆ 10.6, 4.5 Hz, 1H), 3.46 (s,
3H), 3.44 (s, 3H), 3,42 (s, 3H), 3.26 (d, J ˆ 2.5 Hz, 1H), 3.06 (overlapping d,
1H), 2.89 (s, 3H), 2.75 (dd, J ˆ 10.4, 5.7 Hz, 1H), 2.28 (m, 3H), 2.01 (m,
3H), 1.71 (m, 2H); 13C NMR (125.8 MHz, C6D6): d ˆ 171.54, 151.77, 94.74,
92.20, 91.36, 81.09, 80.30, 79.17, 72.62, 58.89, 58.11, 57.74, 53.92, 52.60, 44.78,
‡
[M ], 356 (15), 354 (20), 256 (9), 159 (33), 145 (14), 124 (25), 113 (35), 87
(20), 59 (5), 45 (100); C25H33CoN2O5 (500.48): calcd C 59.99, H 6.65, N 5.60;
found C 59.78, H 6.67, N 5.65. For details of the X-ray crystallographic data
of 10j, see ref. [8].
‡
39.78, 29.04, 28.84, 27.39, 23.61, 23.46; MS (70 eV): m/z (%): 530 (42) [M ],
464 (12), 356 (37), 256 (21), 187 (13), 175 (23), 159 (23), 143 (55), 124 (33),
115 (34), 101 (51), 71 (37), 45 (100); C26H35CoN2O6 (530.51): calcd C 58.84,
H 6.60, N 5.28; found C 57.94, H 6.50, N 5.10.
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1-(1'-b-ribofuranose-2',3',5'-tri-
acetate)-3-methyl-1,2,3,4,4a-endo,6,7,8,9,10a-endo-decahydro-2,4-dioxo-
benzo[g]quinazoline]cobalt (10k): From 1k (0.20 g, 0.595 mmol),
[CpCo(C2H4)2] (0.161 g, 0.893 mmol), and 8b (0.126 g, 1.19 mmol) in
THF (10 mL) at reflux without irradiation for 16 h. Addition of
[CpCo(C2H4)2] and diyne was carried out at reflux within 1 h and the was
refluxed for a further 15 h. Flash chromatography (SiO2, hexanes/EtOAc,
45:55) gave an inseparable mixture of four diastereomers in a ratio of
1:1:1:1 as an orange oil. Yield: 0.133 g (37%); IR (C6D6): nÄ ˆ 3100, 3040,
2940, 1760, 1720, 1680, 1370, 1225 cm 1; 1H and 13C NMR spectra were too
complicated to be described; however, they clearly showed the presence of
four diastereomers, for example: four Cp signals at d ˆ 4.76, 4.75, 4.74 and
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1-(-2',3'-isopropylidene-5'-
methyluridine)-3-methyl-1,2,3,4,4a-endo,6,7,8,9,10a-endo-decahydro-2,4-
dioxo-benzo[g]quinazoline]cobalt (10i). From 1i (0.312 g, 1 mmol), 8b
(270 mL, 2 mmol), and [CpCo(CO)2] (224 mL, 1.8 mmol) in xylene (18 mL),
with irradiation under reflux for 19 h. Flash chromatography (SiO2,
pentane/Et2O 9:1) allowed the separation of the four diastereomers 10ia
(0.067 g), 10ib (0.050 g), 10ic (0.031 g), 10id (0.027 g) with a total yield of
33%.
Compound 10ia: orange crystals; m.p. 44 ± 468C; IR (CH2Cl2): nÄ ˆ 2920,
1
1700, 1660, 1460 cm 1; H NMR (300 MHz, C6D6): d ˆ 5.58 (d, J ˆ 1.6 Hz,
‡
4.72 with equal integration values; MS (70 eV): m/z (%): 600 (2) [M ], 354
1H), 5.21 (dd, J ˆ 6.4, 1.6 Hz, 1H), 5.05 (dd, J ˆ 6.5, 4.4 Hz, 1H), 4.54 (m,
1H), 4.24 (s, 5H), 3.70 (m, 2H), 3.14 (s, 3H), 3.11 (m, 1H), 3.08 (s, 3H), 3.02
(d, J ˆ 3.1 Hz, 1H), 2.56 (dd, J ˆ 10.8, 5.2 Hz, 1H), 2.33 (m, 1H), 2.32 (m,
1H), 2.12 (m, 1H), 1.70 (m, 6H), 1.56 (s, 3H), 1.27 (s, 3H); 13C NMR
(75.8 MHz, C6D6): d ˆ 170.70, 151.32, 113.54, 95.38, 93.86, 92.89, 86.13,
85.87, 82.88, 81.54, 73.85, 58.81, 55.89, 50.78, 45.76, 40.98, 28.97, 28.74, 27.62,
(16), 259 (10), 189 (26), 139 (29), 124 (17), 105 (17), 97 (21), 66 (13), 43
(100); C28H33CoN2O9 (600.51): calcd C 56.00, H 5.50, N 4.67; found C 55.74,
H 5.52, N 4.52.
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1-(1'-b-2'-deoxyribofuranose-
3',5'-diacetate)-1,2,3,4,4a-endo,6,7,8,9,10a-endo-deca-2,4-dioxo-benzo[g]-
quinazoline]cobalt (10l): From 1l (0.312 g, 1 mmol), 8b (270 mL, 2 mmol),
and [CpCo(CO)2] (224 mL, 1.8 mmol) in toluene (21 mL), with irradiation
under reflux for 20 h. Flash chromatography (SiO2, hexane/AcOEt 1:9)
‡
27.50, 25.54, 23.55, 23.40; MS (70 eV): m/z (%): 542 (70) [M ], 356 (25), 256
(30), 187 (69), 172 (42), 159 (34), 129 (100), 128 (19), 124 (37), 101 (33), 71
(9); HRMS: calcd for C27H35CoN2O6 542.183; found 542.183.
3558
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0512-3558 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 12

Cyclooligomerizations
3549±3561
‡
gave an inseparable mixture of four diastereomers in a ratio of 1:1:1:1 as
[M ], 245 (95), 244 (17), 229 (9), 218 (28), 217 (40), 188 (20), 159 (28), 132
(34), 104 (76), 91 (69); C14H18N2O2 (246.31): calcd C 68.21, H 7.31, N 11.37;
found C 67.94, H 7.39, N 10.80.
red crystals. Yield: 0.091 g (18%); m.p. 60 ± 628C; IR (CH2Cl2): nÄ ˆ 2940,
1
1740, 1705, 1665, 1370, 1240, 810 cm 1; H and 13C NMR spectra were too
complicated to be described; however they showed the presence of four
diastereomers; MS (70 eV): m/z (%): 542 (2) [M ], 281 (16), 160 (13), 159
(100), 129 (21), 113 (52), 106 (18), 105 (20), 91 (37), 81 (80), 79 (13);
C26H31CoN2O7 (542.47): calcd C 57.57, H 5.76, N 5.16; found C 57.34, H 5.76,
N 4.99.
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,10a,11-h)-1,3-dimethyl-1,2,3,4,4a-endo,
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1-methyl-1,2,4a-endo,6,7,8,9,10a-
endo-octahydro-2-oxo-4-N,N'-dimethylamino-benzo[g]quinazoline]cobalt
(20d): From 3d (0.153 g, 1 mmol), 8b (260 mL, 2 mmol), and [CpCo(CO)2]
(248 mL, 2 mmol) in toluene (27 mL), with irradiation under reflux for 20 h.
Flash chromatography (SiO2, CHCl3/CH3OH, 7:3) gave a brown oil of 20d.
‡
‡
Yield: 0.028 g (9%); MS (70 eV): m/z (%): 383 (100) [M ], 381 (41), 317
11a-endo-hexahydro-2,4-dioxo-cyclohepta[g]quinazoline]cobalt
(11a):
(33), 316 (22), 315 (81), 300 (21), 259 (136), 258 (48), 256 (25), 230 (22), 229
(79), 217 (32), 201 (29), 189 (76), 187 (29), 172 (25), 158 (46), 157 (58), 156
(19), 142 (20), 130 (25), 129 (83), 128 (29), 124 (64), 116 (39).
From 1a (0.14 g, 0.999 mmol), [CpCo(CO)2] (0.36 g, 2mmol), and 8c
(0.24 g, 2 mmol) in toluene (10 mL), with irradiation under reflux for 20 h.
Flash chromatography (SiO2, hexanes/Et2O 25:75) gave yellow-orange
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1-methyl-1,2,4a-endo,6,7,8,9,10a-
endo-octahydro-2-oxo-4-methoxy-benzo[g]quinazoline]cobalt (21): From
4a (0.140 g, 1 mmol), 8b (200 mL, 1.5 mmol), and [CpCo(CO)2] (186 mL,
1.5 mmol) in toluene (16 mL), with irradiation under reflux for 17 h. Flash
chromatography (SiO2, pentane/acetone, 1:4) gave 21 (0.358 mmol) and 25
(0.097 mmol, vide infra). The total yield of the reaction was 46%. 21:
orange crystals; m.p. 128 ± 1308C; IR (CHCl3): nÄ ˆ 2980, 1630, 1435, 1250,
1075, 1015 cm 1; 1H NMR (300 MHz, C6D6): d ˆ 4.28 (s, 5H), 3.54 (s, 3H),
3.25 (dd, J ˆ 12.6, 3.2 Hz, 1H), 2.91 (s, 3H), 2.87 (m, 2H), 2.38 (dd, J ˆ 11.3,
4.8 Hz, 1H), 2.12 (m, 1H), 1.93 (m, 2H), 1.66 (m, 3H), 1.45 (m, 2H); 13C
NMR (75.8 MHz, C6D6): d ˆ 173.61, 155.12, 93.95, 92.76, 81.07, 58.65, 53.70,
50.03, 45.34, 36.78, 33.12, 28.91, 28.68, 23.39, 23.28; MS (70 eV): m/z (%):
crystals. Yield: 0.85 g (22%); m.p. 129 ± 1328C; IR (C6D6): nÄ ˆ 3090, 3000,
1
2930, 2850, 1700, 1665, 1470, 1420, 1360, 1295, 1110, 1000, 755 cm
;
1H
NMR (300 MHz, C6D6): d ˆ 4.37 (s, 5H), 3.23 (s, 3H), 3.14 (d, J ˆ 4.7 Hz,
1H), 3.03 (dd, J ˆ 10.9, 3.0 Hz, 1H), 2.73 (s, 3H), 2.71 (d overlapping J ˆ
3.0 Hz, 1H), 2.62 (dd, J ˆ 10.9, 4.7 Hz, 1H), 2.28 (m, 1H), 2.16 (m, 1H),
2.01 (m, 1H), 1.76 (m, 1H), 1.45 (m, 6H); 13C NMR (75.8 MHz, C6D6): d ˆ
171.29, 151.34, 97.24, 95.87, 80.67, 56.77, 52.93, 51.79, 42.17, 35.20, 35.08,
‡
33.52, 32.49, 29.60, 29.04, 27.75; MS (70 eV): m/z (%): 384 (28) [M ], 383
(23), 382 (100), 380 (13), 317 (2), 316 (11), 314 (12), 258 (2), 253 (7), 200 (7),
186 (10), 124 (29); C20H25CoN2O2 (384.36): calcd C 62.49, H 6.56, N 7.29;
found C 61.95, H 6.68, N 6.86.
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,10a,11-h)-1,3-dimethyl-1,2,3,4,4a-endo,
11a-endo-hexahydro-2-oxo-4-methylimino-cyclohepta[g]quinazoline]co-
balt (11e): From 1e (0.153 g, 1 mmol), 8c (271 mL, 1.8 mmol), and
[CpCo(CO)2] (224 mL, 1.8 mmol) in toluene (16 mL), with irradiation
under reflux for 20 h. Flash chromatography (neutral alumina, pentane/
‡
370 (100) [M ], 367 (55), 363 (20), 304 (63), 301 (55), 288 (18), 245 (15), 187
(18), 124 (27); C19H23CoN2O2 (370.34): calcd C 61.62, H 6.26, N7.56; found
C 61.83, H 6.08, N 7.49.
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1-methyl-1,2,4a-endo,6,7,8,9,10a-
endo-octahydro-2-oxo-4-ethoxy-benzo[g]quinazoline]cobalt (22): From 4b
(0.140 g, 1 mmol), 8b (200 mL, 1.5 mmol), and [CpCo(CO)2] (186 mL,
1.5 mmol) in toluene (16 mL), with irradiation under reflux for 17 h. Flash
chromatography (SiO2, pentane/acetone, 1:4) gave 22 (0.037 g) and 25
(0.013 g). The total yield of the reaction was 22%. Compound 22: Orange
crystals; m.p. 111 ± 1138C; IR (C6D6): nÄ ˆ 2990, 2940, 1690, 1660, 1630,
AcOEt 1:99) gave orange crystals. Yield: 0.084 g (21%); m.p. 158 ± 1618C;
1
IR (CH2Cl2): nÄ ˆ 2940, 2870, 1665, 1635,1480, 1460, 1435, 1150, 813 cm
;
1H NMR (300 MHz, C6D6): d ˆ 4.45 (s, 5H), 3.42 (s, 3H), 3.18 (s, 3H), 3.08
(m, 2H), 2.82 (m, 1H), 2.77 (s, 3H), 2.75 (m, 1H), 2.30 (m, 2H), 1.87 (m,
2H), 1.50 (m, 6H); 13C NMR (75.8 MHz, C6D6): d ˆ 158.71, 153.93, 97.05,
95.80, 80.73, 57.39, 52.75, 49.60, 38.75, 36.52, 35.60, 35.24, 33.58, 32.67, 31.06,
1
1610, 1430, 1380, 1240, 1020 cm 1; H NMR (300 MHz, C6D6): d ˆ 4.30 (s,
‡
29.73, 29.20; MS (70 eV): m/z (%): 397 (40) [M ], 340 (29), 317 (34), 272
5H), 4.27 (m, 1H), 4.07 (m, 1H), 3.26 (dd, J ˆ 11.0, 2.7 Hz, 1H), 2.92 (m,
4H), 2.88 (d, J ˆ 2.7 Hz, 1H), 2.40 (dd, J ˆ 11.0, 4.8 Hz, 1H), 2.20 (m, 1H),
1.97 (m, 2H), 1.70 (m, 3H), 1.48 (m, 2H), 1.05 (t, J ˆ 7.1 Hz, 3H); 13C NMR
(75.8 MHz, C6D6): d ˆ 173.18, 155.16, 94.02, 92.58, 81.70, 62.36, 58.63, 50.83,
45.44, 36.69, 33.17, 29.04, 28.72, 23.76, 23.63, 14.35; MS (70 eV): m/z (%):
(25), 270 (40), 340 (29), 317 (34), 272 (25), 270 (40), 243 (47), 200 (25), 186
(33), 141 (34), 135 (35), 124 (100), 91 (21); HRMS: calcd for C21H28CoN3O
397.156; found 397.157.
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,10a,11-h)-1,3-dimethyl-1,2,3,4,4a-endo,
11a-endo-hexahydro-2-oxo-4-ethylimino-cyclohepta[g]quinazoline]cobalt
(11 f): From 1 f (0.167 g, 1 mmol), 8c (271 mL, 1.8 mmol), and [CpCo(CO)2]
(240 mL, 1.9 mmol) in toluene (16 mL), with irradiation under reflux for
22 h. Flash chromatography (neutral alumina, pentane/AcOEt 1:9) gave
orange crystals. Yield: 0.062 g (22%); m.p. 117 ± 1198C; IR (CH2Cl2): nÄ ˆ
2960, 2930, 1680, 1650, 1440, 813 cm 1; 1H NMR (300 MHz, C6D6): d ˆ 4.42
(s, 5H), 3.40 (s, 3H), 3.38 (m, 2H), 3.08 (m, 2H), 2.82 (d, J ˆ 2.7 Hz, 1H),
2.76 (s, 3H), 2.71 (d, J ˆ 3.5 Hz, 1H), 2.28 (m, 2H), 1.88 (m, 2H), 1.59 (m,
6H), 1.36 (t, J ˆ 7.2 Hz, 3H); 13C NMR (75.8 MHz, C6D6): d ˆ 156.56,
154.35, 97.12, 95.59, 80.50, 57.67, 52.66, 50.20, 43.83, 39.13, 35.47, 35.24, 33.44,
‡
384 (57) [M ], 354 (29), 288 (100), 230 (23), 189 (44), 187 (36), 186 (32), 160
(21), 159 (24), 158 (23), 131 (23), 129 (26), 128 (25), 116 (21), 115 (21), 91
(44), 77 (12); HRMS: calcd for C20H25CoN2O2 384,125; found 384.125.
(h5-2,4-Cyclopentadien-1-yl)[(5,5a,9a,10-h)-1-methyl-1,2,4a-endo,6,7,8,9,10a-
endo-octahydro-2-oxo-4-propoxy-benzo[g]quinazoline]cobalt (23): From
4c (0.168 g, 1 mmol), 8b (240 mL, 1.8 mmol), and [CpCo(CO)2] (224 mL,
1.8 mmol) in toluene (16 mL), with irradiation under reflux for 18 h. Flash
chromatography (SiO2, hexanes/acetone, 1.5:4.5) gave 23 (0.093 g) and 25
(0.014 g). The total yield of the reaction was 27%. 23: Orange crystals; m.p.
1
76 ± 778C; IR (CH2Cl2): nÄ ˆ 2900, 1630, 1620, 1320, 1280 cm
;
1H NMR
‡
32.66, 30.69, 29.20, 28.66, 17.71; MS (70 eV): m/z (%): 411 (56) [M ], 354
(300 MHz, C6D6): d ˆ 4.30 (s, 5H), 4.20 (m, 1H), 4.02 (m, 1H), 3.26 (dd, J ˆ
11.2, 3.3 Hz, 1H), 2.95 (d, J ˆ 4.8 Hz, 1H), 2.92 (s, 3H), 2.88 (d, J ˆ 3.2 Hz,
1H), 2.42 (dd, J ˆ 11.2, 4.7 Hz, 1H), 2.22 (m, 1H), 1.97 (m, 2H), 1.68 (m,
3H), 1.50 (m, 4H), 0.79 (t, J ˆ 7.4 Hz, 3H); 13C NMR (75.8 MHz, C6D6):
d ˆ 173.34, 155.16, 94.00, 92.62, 81.11, 68.08, 58.59, 50.09, 45.63, 36.83, 33.17,
(51), 303 (25), 301 (46), 286 (49), 285 (23), 284 (59), 270 (58), 243 (98), 230
(33), 229 (100), 200 (35), 186 (83), 172 (69), 141 (36), 135 (72), 124 (89), 84
(83); HRMS: calcd for C22H30CoN3O 411.172; found 411.172.
(5,5a,9a,10-h)-1,3-dimethyl-1,2,3,4,4a-endo,6,7,8,9,10a-endo-decahydro-
2,4-dioxo-benzo[g]quinazoline (13): An ice-cold solution of CuCl2 (0.368 g,
2.16 mmol) and Et3N (0.066 g, 0.648 mmol) in H2O (15 mL) was added
slowly To a cold (08C) solution of complex 10a (0.20 g, 0.54 mmol) in THF
(30 mL). The reaction was monitored by TLC and after 2 min all the
starting material had disappeared. The mixture was concentrated by rotary
evaporation, the residue ( ꢀ 10 mL) extracted with CHCl3 (3x30 mL),
successively washed with water (2 Â 30 mL) and saturated aqueous NaCl
(20 mL), and then dried over MgSO4. Filtration and evaporation of the
solvent gave a pale yellow oil. Preparative TLC (hexanes/AcOEt, 2:3) gave
‡
29.02, 28.71, 23.43, 23.32, 22.31, 10.65; MS (70 eV): m/z (%): 398 (65) [M ],
354 (39), 288 (74), 272 (59), 243 (24), 231 (44), 230 (100), 229 (36), 202 (33),
189 (77), 187 (22), 187 (21), 186 (40), 160 (32), 159 (53), 131 (27), 129 (31),
128 (23), 124 (70), 116 (22), 91 (37); HRMS: calcd for C21H27CoN2O2
398.140; found 398.139.
(h5-2,4-Cyclopentadien-1-yl)-[(5,5a,9a,10-h)-1-methyl-1,2,3,4,4a-endo,
6,7,8,9,10a-endo-decahydro-2,4-dioxo-benzo[g]quinazoline]cobalt
(25):
From hydrolysis of the corresponding imidates. For example, 22 (10 mg,
0.026 mmol) was added to a suspension of flash SiO2 (3 g) in acetone
(4 mL), which contained H2O (1 mL) and was then left to stand at room
temperature for 20 h. After filtration through a short pad of Celite and
drying over Na2SO4, evaporation of the solvent gave 25 with a very high
13. Yield: 0.12 g (91%); white crystals; m.p. 112 ± 1148C; IR (C6D6): nÄ ˆ
1
2940, 2860, 1715, 1675, 1480, 1415, 1280, 1100 cm
;
1H NMR (300 MHz,
C6D6): d ˆ 5.83 (brd, J ˆ 1.7 Hz, 1H), 5.50 (d, J ˆ 6.0 Hz, 1H), 3.33 (m,
1H), 3.24 (s, 3H), 2.69 (s, 3H), 2.54 (dd, J ˆ 7.6, 6.6 Hz, 1H), 2.17 (m, 1H),
1.91 (m, 3H), 1.33 (m, 2H), 1.16 (m, 2H); 13C NMR (75.8 MHz, C6D6): d ˆ
24.36 (2 CH2), 170.03, 153.17, 138.33, 136.22, 118.38, 117.70, 52.87, 39.67,
33.47, 30.98, 30.83, 27.72, 24.36 (2CH2); MS (70 eV): m/z (%): 246 (100)
purity (90%). Orange crystals; m.p. 1978C (decomp); IR (CH2Cl2): nÄ ˆ
1
2368, 2312, 1692, 780 cm
;
1H NMR (300 MHz, C6D6): d ˆ 4.28 (s, 5H),
3.13 (d, J ˆ 4.5 Hz, 1H), 3.08 (dd, J ˆ 9.4, 2.8 Hz, 1H), 2.72 (d, J ˆ 2.8 Hz,
Chem. Eur. J. 1999, 5, No. 12
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0512-3559 $ 17.50+.50/0
3559

J. Rodriguez, K. P. C. Vollhardt, H. Pelissier
FULL PAPER
1H), 2.70 (s, 3H), 2.50 (dd, J ˆ 11.0, 4.5 Hz, 1H), 2.46 (m, 1H), 2.30 (m,
1H), 1.95 (m, 2H), 1.70 (m, 3H), 1.42 (m, 2H); 13C NMR (75.8 MHz, C6D6):
d ˆ 171.55, 150.50, 94.25, 93.79, 81.42, 58.54, 48.12, 45.20, 41.47, 32.62, 29.12,
orange-red crystals. Yield: 0.235 g (73%); m. p. 2108C (decomp); IR
1
(CDCl3): nÄ ˆ 3390, 2950, 1710, 1485, 1450, 1430, 1265 cm
;
1H NMR
(300 MHz, CDCl3): d ˆ 7.49 (s, 1H), 5.56 (s, 1H), 4.90 (s, 5H), 4.51 (m, 1H),
3.81 (s, 3H), 3.74 (s, 3H), 2.94 (d, J ˆ 8.0 Hz, 1H), 2.78 (m, 1H), 2.70 (d, J ˆ
8.0 Hz, 1H), 1.83 (m, 4H); 13C NMR (75.8 MHz, CD2Cl2): d ˆ 172.22,
170.88, 168.45, 151.60, 83.51, 78.90, 78.15, 72.27, 61.19, 55.01, 52.79, 52.11,
‡
29.02, 23.52, 23.40; MS (70 eV): m/z (%): 356 (26) [M ], 355 (19), 353 (100),
350 (12), 288 (13), 187 (15), 159 (9), 128 (12), 124 (54); HRMS: calcd for
C18H21CoN2O2 356.093; found 356.093.
‡
45.92, 43.55, 34.24, 23.91; MS (70 eV): m/z (%): 444 (28) [M ], 442 (2), 383
(h5-2,4-Cyclopentadien-1-yl)-[(5,5a,9a,10-h)-1-ethyl-1,2,3,4,4a-endo,
(2), 378 (4), 318 (42), 288 (34), 287 (100), 246 (26), 229 (17), 215 (13), 158
(11), 124 (15), 118 (3); C20H21CoN2O6 (444.33): calcd C 54.05, H 4.73, N
6.30; found C 53.29, H 4.71, N 5.99.
6,7,8,9,10a-endo-decahydro-2,4-dioxo-benzo[g]quinazoline]cobalt
(26):
From 4d (0.154g, 1 mmol), 8b (240 mL, 1.8 mmol), and [CpCo(CO)2]
(224 mL, 1.8 mmol) in toluene (16 mL), with irradiation under reflux for
19 h. Flash chromatography (SiO2, hexanes/acetone, 1:9) gave an orange
oil. Yield: 0.028 g (9%); 1H NMR (300 MHz, C6D6): d ˆ 4.27 (s, 5H), 3.45
(m, 1H), 3.34 (dd, J ˆ 10.8, 3.1 Hz, 1H), 3.11 (d, J ˆ 5.0 Hz, 1H), 3.05 (m,
1H), 2.73 (d, J ˆ 3.0 Hz, 1H), 2.40 (m, 2H), 1.95 (m, 2H), 1.68 (m, 3H), 1.45
(m, 2H), 1.04 (t, J ˆ 7.0 Hz, 3H).
(h5-2,4-Cyclopentadien-1-yl)[5-(1,2,3,4-h)-2,3-bis(trimethylsilyl)-propene-
diyl]-2-benzoyl-1,2,3,5,6,7,8,9-octahydro-1,3-dioxopyrido[1,2-c]pyrimidine]-
cobalt (31): From 6a (0.28 g, 0.709 mmol), [CpCo(C2H4)2] (0.191g,
1.06 mmol) in THF (5 mL), and BTMSA (5 mL) at room temperature
with irradiation (lamp at about 15 cm from the flask, power on Variac set to
40) for 2 h. Flash chromatography (SiO2; hexanes/AcOEt 55:45) gave
orange-red crystals. Yield: 88 mg (21%); m.p. 1438C (decomp); IR
(CD2Cl2): nÄ ˆ 2960, 2900, 1740, 1685, 1655, 1600, 1450, 1265, 1255, 900,
855, 840 cm 1; 1H NMR (300 MHz, C6D6): d ˆ 8.05 (m, 2H), 6.93 (m, 3H),
4.57 (s, 5H), 4.39 (m, 1H), 3.29 (s, 1H), 2.59 (m, 1H), 2.30 (m, 1H), 2.29 (s,
1H), 1.65 (m, 1H), 1.48 (m, 1H), 1.35 (m, 1H), 0.98 (s, 1H), 0.47 (s, 9H),
0.10 (s, 9H); 13C NMR (75.8 MHz, C6D6): d ˆ 172.33, 171.67, 150.49, 134.19,
134.04, 130.63, 128.85, 91.15, 87.69, 83.85, 80.77, 71.54, 62.31, 50.77, 31.92,
Anti
and
syn-(h5-2,4-cyclopentadien-1-yl)[(7a,8,9,10-h)-2-benzoyl-
1,2,3,4,6,7,10a,10b-octahydro-9,10-bis-(trimethylsilyl)-5H-1,3-dioxopyrido-
[3,2-ij]quinazoline]cobalt complexes (27): From 6a (0.10 g, 0.355 mmol),
[CpCo(CO)2] (0.115 g, 0.638 mmol), in THF (3 mL), and BTMSA (6 mL),
with irradiation at room temperature for 17 h. The two diastereomers were
inseparable by flash chromatography (SiO2, hexanes/Et2O 2:3) and frac-
tional recrystallization (Et2O/hexanes). 27: Yield: 0.058 g (23%); anti/
syn ˆ 5, orange crystals; m.p. 103 ± 1058C; IR (C6D6): nÄ ˆ 2950, 1755, 1705,
1675, 1600, 1250, 970, 850 cm 1; 1H NMR (400 MHz, C6D6): d ˆ 8.00 (d, J ˆ
7.4 Hz, 2H), 4.48 (s, 1H), 4.06 (s, 5H), 2.26 (m, 1H), 2.21 (d, J ˆ 8.0 Hz,
1H), 1.65 (m,d overlapping J ˆ 8.0 Hz, 2H), 1.20 (m, 4H), 0.45 (s, 9H), 0.35
(s, 9H); 13C NMR (125.8 MHz, C6D6): d ˆ 170.33, 169.43, 150.63, 133.83,
133.70, 130.56, 128.77, 87.58, 84.18, 81.70, 71.01, 61.50, 59.84, 45.54, 44.07,
‡
38.08, 17.31, 3.85, 1.54; MS (70 eV): m/z (%): 576 (2) [M ], 575 (4), 574 (10),
508 (2), 469 (5), 404 (3), 329 (12), 179 (24), 142 (84), 124 (32), 115 (42), 105
(100), 77 (65); C29H37CoN2O3Si2 (576.73): calcd C 60.34, H 6.42, N 4.86;
found C 60.29, H 6.45, N 4.53.
(h5-2,4-Cyclopentadien-1-yl){1-{3-[(1,2,3,4-h)-2,3-bis(trimethylsilyl)-1,3-
cyclobuta-dien-1-yl]-propyl}-3-benzoyl-5-methylthymine}cobalt
(32):
‡
34.74, 23.57, 4.89, 3.41; MS (70 eV): m/z (%): 576 (4) [M ], 437 (2), 332 (7),
From 6c (0.20 g, 0.676 mmol), [CpCo(CO)2] (0.182 g, 1.014 mmol) in
THF (7 mL), and BTMSA (10 mL) at room temperature, with irradiation
for 18 h. Flash chromatography (SiO2, hexanes/Et2O 3:7) gave an orange-
yellow oil. Yield: 71 mg (29%); IR (CH2Cl2): nÄ ˆ 2960, 1755, 1705, 1660,
1600, 1440, 1250, 845, 815 cm 1; 1H NMR (300 MHz, C6D6): d ˆ 7.92 (d, J ˆ
7.0 Hz, 2H), 7.01 (m, 1H), 6.93 (m, 2H), 6.01 (s, 1H), 4.73 (s, 5H), 4.15 (s,
1H), 3.27 (m, 1H), 3.12 (m, 1H), 1.71 (m, overlapping, 1H), 1.69 (s, 3H),
1.50 (m, 2H), 0.18 (s, 9H), 0.89 (m, 1H), 0.14(s, 9H); MS (70 eV): m/z (%):
179 (17), 142 (62), 124 (14), 115 (32), 107 (87), 80 (100), 74 (55);
C29H37CoN2O3Si2 (576.73): calcd C 60.34, H 6.42, N 4.86; found C 60.02, H
6.65, N 4.87.
(h5-2,4-Cyclopentadien-1-yl)[(7a,8,9,10-h)-2-benzoyl-1,2,3,4,6,7,10a,10b-
octahydro-9,10-dicarboxylate-5H-1,3-dioxopyrido[3,2-ij]quinazoline]-
cobalt (28): From 6a (0.10 g, 0.355 mmol), [CpCo(CO)2] (0.115 g,
0.64 mmol), and DMAD (0.252 g, 1.78 mmol) in THF (10 mL), with
irradiation at room temperature for 21 h. Flash chromatography (SiO2,
hexanes/Et2O 1:9) gave anti-28 as orange crystals which sublimed without
melting at 848C. Yield: 0.119 g (61%); IR (CD2Cl2): nÄ ˆ 2950, 1750, 1725,
1700, 1675, 1600, 1450, 1255, 1200 cm 1; 1H NMR (300 MHz, CD2Cl2): d ˆ
7.97 (m, 2H), 7.69 (t, J ˆ 7.3 Hz, 1H), 7.55 (t, J ˆ 7.5 Hz, 2H), 5.62 (s, 1H),
4.99 (s, 5H), 4.42 (m, 1H), 3.81 (s, 3H), 3.60 (s, 3H), 3.12 (d, J ˆ 8 Hz, 1H),
2.86 (m, 1H), 2.78 (d, J ˆ 7.4 Hz, 1H), 1.91 (m, 4H); 13C NMR (75.8 MHz,
CD2Cl2): d ˆ 172.11, 170.67, 170.52, 167.59, 150.04, 135.04, 132.78, 130.46,
129.31, 83.76, 79.57, 78.30, 72.06, 60.01, 54.27, 52.86, 52.12, 46.50, 43.75,
‡
590 (9) [M ], 486 (3), 420 (3), 294 (5), 205 (8), 179 (14), 105 (100), 77 (62);
HMRS: calcd for C30H39CoN2O3Si2 590.754; found 590.685.
(h5-2,4-Cyclopentadien-1-yl){5-[(1,2,3,4-h)-2,3-bis(trimethylsilyl)-propene-
diyl]-1,2,3,5,6,7,8,9-hexahydro-1-oxo-3-N-acetylaminopyrido[1,2-c]-pyrimi-
dine}cobalt (33) and (h5-2,4-cyclopentadien-1-yl){1-{3-[(1,2,3,4-h)-2,3-bis-
(trimethylsilyl)-1,3-cyclobutadien-1-yl]-propyl}-N-acetylcytosine}cobalt
(34): From 7 (0.109 g, 0.5 mmol), BTMSA (3 mL, 3 mmol), and [CpCo-
(CO)2] (124 mL, 1 mmol) in THF (19 mL), with irradiation at room
temperature for 20 h. Flash chromatography (SiO2, pentane/AcOEt 3:7)
gave 33 (32 mg, 20%) and 34 (7 mg, 3%).
‡
33.98, 23.74; MS (70 eV): m/z (%): 548 (3) [M ], 246 (3), 218 (3), 142 (83),
141 (77), 124 (61), 115 (47), 105 (81), 78 (100), 77 (86), 66 (45);
C27H25CoN2O7 (584.44): calcd C 59.12, H 4.56, N 5.11; found C 58.85, H
4.81, N 4.82.
Compound 33: Red oil; 1H NMR (300 MHz, C6D6): d ˆ 4.50 (m, 1H), 4.37
(s, 5H), 3.38 (s, 1H), 2.55 (m, 1H), 2.30 (m, 1H), 2.10 (s, 3H), 2.06 (s, 1H),
‡
1.50 (m, 4H), 0.48 (s, 3H); MS (70 eV): m/z (%): 514 (44) [M ], 511 (29),
Anti and syn-(h5-2,4-cyclopentadien-1-yl)[(7a,8,9,10-h)-1,2,3,4,6,7,10a,10b-
octahydro-9,10-bis-(trimethylsilyl)-5H-1,3-dioxopyrido[3,2-ij]quinazoline]-
cobalt complexes (29): From 6e (0.146 g, 0.82 mmol), [CpCo(CO)2]
(0.266 g, 1.476 mmol) in THF (8 mL), and BTMSA (6 mL), with irradiation
at room temperature for 17 h. The two diastereomers were inseparable by
flash chromatography (SiO2, CHCl3/MeOH 99:1) and fractional recrystal-
lization (Et2O/hexanes). 29: Yield: 0.135 g (35%); anti/syn ˆ 10; orange
crystals; m.p. 1688C (decomp); IR (C6D6): nÄ ˆ 3380, 3190, 2950, 1700, 1675,
373 (30), 372 (28), 314 (19), 298 (20), 124 (24), 114 (23), 75 (36), 74 (24), 73
(100), 57 (23).
1
Compound 34: Yellow oil; H NMR (300 MHz, C6D6): d ˆ 7.46 (d, J ˆ 7.2,
1H), 6.47 (d, J ˆ 7.2 Hz, 1H), 4.70 (s, 5H), 4.20 (s, 1H), 3.38 (m, 2H), 2.26
(s, 3H), 1.65 (m, 4H), 0.15 (s, 3H), 0.10 (s, 3H); MS (70 eV): m/z (%): 514
‡
(48) [M ], 382 (25), 294 (18), 196 (14), 182 (15), 168 (17), 167 (18), 149 (18),
124 (24), 116 (24), 83 (20), 81 (19), 75 (64), 74 (41), 73 (100), 69 (16), 59 (28),
57 (18).
1
1260, 1250, 855, 830 cm 1; H NMR (300 MHz, C6D6): d ˆ 9.47 (brs, 1H),
6.18 (s, 1H), 4.62 (s, 5H), 4.41 (m, 1H), 2.16 (m, 1H), 2.01 (d, J ˆ 8.0 Hz,
1H), 1.64 (m, 1H), 1.41 (d, J ˆ 8.0 Hz, 1H), 1.12 (m, 3H), 0.47 (s, 9H), 0.32
(s, 9H); 13C NMR (75.8 MHz, C6D6): d ˆ 170.66, 151.83, 86.89, 83.73, 81.66,
72.48, 61.54, 60.39, 44.87, 43.46, 34.85, 23.71, 4.49, 3.29; MS (70 eV): m/z
Acknowledgments
‡
(%): 474 (4), 473 (13), 472 (38) [M ], 457 (7), 399 (26), 347 (13), 331 (44),
259 (53), 146 (13), 124 (23), 84 (99), 73 (100); C22H33CoN2O2Si2 (472.62):
calcd C 55.91, H 7.04, N 5.93; found C 57.76, H 6.87, N 5.93.
This work was supported by the National Institute of Health (GM22479)
and NSF (CHE 9610430). J.R. and H.P. acknowledge awards of postdoc-
toral fellowships by the Fonds de Bourse de Recherche Scientifique et
Technique de lꢁOTAN and the National Science Foundation, respectively.
We also gratefully acknowledge the twinning committee between the
(h5-2,4-Cyclopentadien-1-yl)[(7a,8,9,10-h)-1,2,3,4,6,7,10a,10b-octahydro-
9,10-dicarboxylate-1,3-dioxopyrido[3,2-ij]quinazoline]cobalt (30): From
6e (0.147 g, 0.82 mmol), [CpCo(CO)2] (0.266 g, 1.476 mmol), and DMAD
(0.583g, 4.1 mmol) in THF (10 mL), with irradiation at room temperature
for 21 h. Flash chromatography (SiO2, CHCl3/MeOH 99.5:0.5) gave
Ã
Region Provence Alpes Cote dꢁAzur and the State of California for the
provision of a special grant (CR 91-112). Finally we are indebted to Dr.
3560
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0512-3560 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 12

Cyclooligomerizations
3549±3561
Jacques Viala (UMR 6516, University of Marseille III) who saved for us
many computer files which had serious problems.
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49)7247-808-666; e-mail: crysdata@fiz.karlsruhe.de) on quoting the
depository number CSD-320197.
Ä
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Â
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Received: March 18, 1999 [F1683]
Chem. Eur. J. 1999, 5, No. 12
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