Cobalt-mediated [2 + 2 + 2] cycloaddition versus C-H and N-H activation of pyridones and pyrazinones with alkynes: An experimental study

Article abstract of DOI:10.1002/chem.200601823

The reactivity of a range of pyridone and pyrazinone derivatives towards alkynes in the presence of cyclopentadienylcobaltbis(ethene) has been investigated. Depending on the nature of the substrates, [2 + 2 + 2]- or [2 + 2] cycloaddition, C-H, or N-H activation may occur. In the case of pyridones, the first three predominated with N-protected derivatives, whereas substrates containing N-H bonds followed an N-H activation pathway. The [2 + 2 + 2] cycloaddition of an N-butynylisoquinolone was applied successfully to the total synthesis of anhydrolycorinone. Pyrazinone substrates showed similar patterns of reactivity.

Full text of DOI:10.1002/chem.200601823

FULL PAPER
DOI: 10.1002/chem.200601823
À
À
Cobalt-Mediated [2+2+2] Cycloaddition versus C H and N H Activation
of Pyridones and Pyrazinones with Alkynes: An Experimental Study
Corinne Aubert,[a] Patrick Betschmann,[b] Michael J. Eichberg,[b] Vincent Gandon,[a]
Thilo J. Heckrodt,[b] Jürg Lehmann,[b] Max Malacria,[a] Birgit Masjost,[b] Elisa Paredes,[b]
[b]
K. PeterC. Vollhardt,*
and Glenn D. Whitener[b]
À
Abstract: The reactivity of a range of
pyridone and pyrazinone derivatives
towards alkynes in the presence of
dones, the first three predominated
with N-protected derivatives, whereas
lowed an N H activation pathway. The
[2+2+2] cycloaddition of an N-buty-
nylisoquinolone was applied successful-
ly to the total synthesis of anhydroly-
À
substrates containing N H bonds fol-
cyclopentadienylcobaltbis(ethene) has
A
been investigated. Depending on the
nature of the substrates, [2+2+2]- or
corinone.
showed similar patterns of reactivity.
Pyrazinone
substrates
À
Keywords: C H activation · cobalt ·
À
cycloaddition · heterocycles · N H
À
À
[2+2] cycloaddition, C H, or N H ac-
tivation may occur. In the case of pyri-
activation
Introduction
methods. The success of these transformations led us to con-
sider, initially, pyridine and pyrazine as potential cyclization
partners and, eventually, their more reactive pyridone and
pyrazinone analogues. These nuclei play a key role in medic-
inal chemistry and are often incorporated in active pharma-
ceutical ingredients.[8] They are also present in a vast variety
of biologically active natural products.[9] Therefore, cycload-
ditions of the generic type illustrated in Scheme 1 promised
to provide not only access to novel azapolycycles, but also
further insights into the scope of the methodology.
Nitrogen-containing heterocycles are present in a multitude
of biologically important molecules with extremely diverse
physiological activity. They are also of great importance in
medicinal chemistry because of their pharmacological poten-
tial. Hence, the development of novel methods directed at
the synthesis of new azacycles is of great interest. We have
been engaged in the cobalt-mediated activation of double
bonds in aromatic heterocycles toward the [2+2+2] cyclo-
addition with alkynes.[1] Remarkably, even though resonance
stabilized, these systems participate readily in such cycliza-
tions. Thus, this methodology has been applied to furans,[2]
benzofurans,[3] thiophenes,[2] indoles,[4] pyrroles,[5] imida-
zoles,[6] and pyrimidines,[7] giving rise to fused dihydroheter-
oaromatics that are largely inaccessible by conventional
Moreover, pyridines (and pyridones) can themselves be
constructed by cobalt- (and other metal-) catalyzed alkyne
cooligomerizations with nitriles and isocyanates, respective-
[a] Dr. C. Aubert, Dr. V. Gandon, Prof. Dr. M. Malacria
UniversitØ Pierre et Marie Curie-Paris 6
Laboratoire de Chimie Organique (UMR CNRS 7611)
Institut de Chimie MolØculaire (FR 2769), case. 229
4 place Jussieu, 75252 Paris cedex 05 (France)
[b] Dr. P. Betschmann, Dr. M. J. Eichberg, Dr. T. J. Heckrodt,
Dr. J. Lehmann, Dr. B. Masjost, Dr. E. Paredes,
Prof. Dr. K. P. C. Vollhardt, Dr. G. D. Whitener
Department of Chemistry, University of California at Berkeley
and the Chemical Sciences Division, Lawrence Berkeley National
Laboratory, Berkeley, CA 94720–1460 (USA)
Fax : (+1)510-643-5208
Scheme 1. Generic cobalt-mediated [2+2+2] cycloadditions of ethyne to
E-mail: kpcv@berkeley.edu
pyridone [Eq. (1)] and pyrazinone [Eq. (2)].
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7443

ly,[10] opening an avenue to sequential cyclizations with even
greater changes in complexity. Herein, we report the results
of our initial forays into this chemistry, which revealed a
puzzling divergence in reactivity from the expected [2+2+
Table 1. Preparation of alkynyl-2-pyridones 1–5.
À
À
2] cycloaddition mode to one in which C H or N H bond
activation with simultaneous double alkyne insertion took
place, depending on the nature of the substrates.
Product
X
n
Yield [%]
2
3
4
5
TsO
I
TsO
TsO
5
22
3
4
85
46
50
Results and Discussion
5
Initial attempts: Early experiments revealed that pyridine
and pyrazine themselves do not enter into the cobalt-medi-
ated [2+2+2] cycloaddition, even under conditions that
have proven to be most favorable for these reactions in
other cases. It was hoped, however, that some type of activa-
tion might render the heterocycles more compliant. Un-
fortunately, focusing on the pyridine nucleus, neither modifi-
cation to pyridinium salts, nor precomplexation to
osmium[11] were productive. Inspired by previous findings
that the (formal) enamine double bond needs to be alkanoy-
lated to render it a successful cocyclization partner,[4,6,12] it
was decided to switch to the oxo derivatives of pyridine and
pyrazine as substrates. Such a change is known to attenuate
aromaticity,[13] which appears to play a role in the energetics
of the alkene metal-complexation and insertion steps of the
mechanism of the cobalt-mediated cyclization.[14] An experi-
mental indication of increased reactivity toward cycloaddi-
tions is given by numerous Diels–Alder reactions of pyri-
dones[15] and pyrazinones.[16]
Table 2. Preparation of diynyl-2-pyridones 6 and 7.
Product
n
Yield [%]
68
6
7
1
252
The problem of O-alkylation was pronounced with 4-pyri-
dones. Thus, treatment with alkynyl tosylates or iodides in
the presence of base in DMF or DMSO led to alkoxypyri-
dines in low overall yields. This difficulty was circumvented
by using the method of Guerry and Neier[19] and 4-trimethyl-
silyloxypyridine (8)[20] as the nucleophile (Table 3).
Preparation of starting materials: Alkynyl-2-pyridones 1–7
(only the first two of which were known)[17,18] were prepared
by adaptation or application of standard literature proce-
dures for such compounds (Table 1 and Table 2). The alkyla-
tion of pyridones is complicated by the possibility of attack
at either nitrogen or oxygen, as well as the further ability of
the products to isomerize by inter- or intramolecular trans-
fer of the alkyl or acyl group. Therefore, alkynyloxypyri-
dines resulting from O-alkylation were common side prod-
ucts which could, however, be readily separated by column
chromatography.
Table 3. Preparation of alkynyl-4-pyridones 9–12.
Product
X
n
Yield [%]
9
Br
I
I
1
2
3
4
85
17
85
60
10
11
12
I
Abstract in German: Eine Reihe von Pyridon- und Pyrazi-
N-Acylpyridones pose the additional dilemma of facile
acyl migration. For example N-acetyl-2-pyridone cannot be
isolated at room temperature and is in equilibrium with the
O-acetyl derivative at À408C.[21] In contrast, its 4-pyridone
isomer exists as the amide at room temperature in the solid
state, although equimolar equilibration with the ester form
occurs in solution.[22] Consequently, it was not surprising that
reaction of 4-pyridone with 4-pentynoyl chloride led to an
inseparable 2:3 mixture of the N- and O-acylated derivatives
13 and 14, respectively (Scheme 2).[23]
nonderivaten wurde auf ihre Reaktivität gegenüber Alkinen
in der Gegenwart von Cyclopentadienylcobaltbis(ethen) un-
A
tersucht. In Abhängigkeit vom Substrat traten zum einen [2+
2+2] oder [2+2] Cycloadditionen auf, zum anderen auch
À
À
C H oder N H Aktivierungsreaktionen. Die ersten drei
Fälle dominierten wenn N-geschützte Pyridone verwendet
À
À
wurden, wohingegen Substrate mit N H Bindungen eine N
H Aktivierung unterliefen. Die [2+2+2] Cycloaddition
eines N-Butinylisochinolons wurde erfolgreich in der Total-
synthese von Anhydrolycorinon eingesetzt. Pyrazinone zeigt-
en ein ähnliches Reaktionsverhalten.
The alkynylation of pyrazinones was achieved in
a
manner similar to that described for the pyridone systems
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Chem. Eur. J. 2007, 13, 7443 – 7465

Cobalt-Mediated Reactions
FULL PAPER
ducts.[7] Thus, treatment of excess N-methyl-2-pyridone
(6 equiv) and 1,7-octadiyne with [CpCo(C2H4)2] resulted in
A
a number of products arising from both single and double
[2+2+2] cycloaddition to the pyridone double bonds
(Scheme 3). These included five isomeric double adducts,
three of which (20a–c) were separable, two of which formed
an inseparable mixture (20d,e, 1:1), in a total yield of 23%.
In addition, single adducts to the enamine (21, 1.6%) and
enone (namely 22, 1.1%, and its aromatized congener 23,
1.8%) units were isolated. Finally, trimer 24 and diene com-
plex 25 were generated in 11% overall yield, based on the
(limiting) diyne starting material. The former arises from
catalytic cyclotrimerization of octadiyne and is a common
side product in reactions employing this substrate,[24] while
the latter is the result of a cocyclization of the diyne with a
cobalt ethene ligand (Scheme 3). In line with the explorato-
ry nature of these investigations (and those following in this
paper), systematic efforts to optimize yields were not under-
taken, but past experience has shown that improvements,
often substantial, are possible by variation of reaction condi-
tions.[3–7]
All five isomers of 20 displayed similar mass spectral char-
acteristics, including the expected molecular ion at m/z 569,
sequential loss of two CpCo moieties, and the presence of a
fragment peak at m/z 256, corresponding to CpCo-tetrahy-
dronaphthalene. Structural assignments of the isomers of 20
were hampered by the complexity of their NMR spectra and
the failure to produce X-ray quality crystals. Double activa-
tion of the pyridone core could generate eight distinct dia-
Scheme 2. Pentynoylation of 4-pyridone.
(Table 4). Precursors for all-intramolecular cyclizations were
obtained by double alkynylation of pyrazinediones
(Table 5).
Table 4. Preparation of N-alkynylpyrazinones 15–17.
Product
X
n
Yield [%]
15
16
17
TsO
TsO
I
241
3
4
52
60
Table 5. Preparation of dialkynylpyrazinediones 18 and 19.
À
stereomers of 20, reasonably assuming cis fusion of the C3
À
C4 and C5 C6 carbons of the lactam ring. For the major
1
product, 20a, the H NMR spectrum showed two signals for
the Cp peaks at d=4.50 and d=4.43 ppm (s, 5H), and one
for the N-methyl peak at d=3.01 ppm (s, 3H). In addition,
three resolved doublets and a broadened singlet were ob-
Product
n
Yield [%]
60
18
19
239
3
Cycloadditions of 1,7-octa-
diyne to N-methylpyridones:
First experiments investigated
the potential of 1,7-octadiyne
to cycloadd to the two N-meth-
ylpyridones in the presence of
[CpCo(C2H4)2]. The juxtaposi-
G
tion of these reagents was
chosen in order to establish the
basic feasibility of the pro-
posed chemistry on the N-pro-
tected heterocyclic core, to
probe for the possible occur-
rence of double additions as in
C (Scheme 1), and to compare
the stereochemistry of the
products with that obtained in
analogous cycloadditions, par-
ticularly that found in the most
closely related pyrimidine ad-
Scheme 3. Reaction of 1,7-octadiyne with N-methyl-2-pyridone (6 equiv). Reagents and conditions: a) [CpCo-
(C2H4)2], THF, reflux, 2.5 h.
AHCTREUNG
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7445

K. P. C. Vollhardt et al.
served at d=3.78 (J=2.7 Hz, 1H), 2.86 (J=4.2Hz, 1H),
2.54 (J=3.1 Hz, 1H), and 2.50 ppm (br s, 1H), and these
were assigned to the four complexed alkene protons shifted
upfield by the anisotropy of the cobalt. The only resolved
ring fusion proton signal was a doublet of doublets at d=
3.54 ppm (J=8.89, 4.2Hz, 1H), assigned to the methane-hy-
drogen atom Ha, a to the nitrogen atom. This characteristi-
cally large chemical shift (relative to those in related anti
complexes;[7] see also, e.g., 33 and 34) corresponds well to
those for closely related pyrimidinedione derivatives, in
which the CpCo moiety is syn to the ring fusion hydrogens
(for selected examples, see Table 6), suggesting the same ar-
(s, 5 H each), as well as the methyl resonance at d=
2.72 ppm (s, 3H) could also be identified. The 13C NMR
spectrum appeared similar to that of 20a. Stereochemical as-
signments of isomers 20c–20e were not possible.
The monoadducts 21 and 22 displayed similar mass spec-
tral patterns, including a molecular ion at m/z 339, a base
peak at m/z 337 due to loss of the two ring fusion hydro-
gens,[25] and peaks at m/z 271 and 215 corresponding to the
1
stepwise loss of Cp and Co. For 21, the H NMR spectrum
displayed two downfield, slightly broad doublets at d=5.69
(J=9.6 Hz, 1H) and d=5.58 ppm (J=9.6 Hz, 1H), assigned
to the uncomplexed vinyl hydrogen atoms. In keeping with
the chemical shift reasoning described above
(Table 6), a signal at d=3.44 ppm (JHaHb =10.0 Hz)
was assigned to the ring junction proton Ha, a to the
amide nitrogen. The adjacent methine hydrogen was
observed at d=2.31 ppm (br d, J=10.7 Hz, 1H).
These results indicate a syn relationship between the
ring junction hydrogens and the CpCo moiety. The
13C data were in accord with the structure. As expect-
ed, in this, as well as all subsequent CpCo diene com-
pounds reported here, the terminal diene carbons
appear at dramatically higher field than their internal
neighbors. Demetalation of 21 with CuII afforded the
free ligand 28, contaminated with a small amount of
the aromatized product 29 (4:1; Scheme 4). Most di-
Table 6. Chemical shifts [ppm] and vicinal coupling constants [Hz] for
the syn hydrogen Ha in pyridones 20a and 21, and pyrimidinediones 26
and 27.
20a
21
26[a]
27[a]
dHa
3.54
8.89
3.44
10.0
3.03–3.14
10.7–11.0
3.25–3.34
10.8–12.6
JHaHb
1
agnostically, the H NMR resonances of the hydrogen
[a] Ref. [7a].
rangement for at least this half of the molecule. The 13C-
DEPT NMR displayed the number and type of signals ex-
pected for this structure. A total of eight signals for the
methylene carbons appeared in two clusters at d=23.9–
24.3 ppm and d=29.3–29.7 ppm, the. Similarly, two groups
of peaks were observed for the eight methine carbon atoms
of the complexed cyclohexadiene rings at d=42.1–48.4 ppm
and d=53.0–57.1 ppm. Another series of peaks, identified as
the its four quaternary carbons, were seen at d=92.0–
95.1 ppm. Signals at d=169.5, 81.5, 81.3, and 32.8 were as-
signed to the carbonyl, two Cp rings, and the methyl carbon
atoms, respectively.
Thus, while the spectral data support the formulation of
20a as a double adduct, only the stereochemistry of the 3,4-
pyridone ring fusion, or the right half of the molecule, can
be assigned with reasonable certainty, and the orientation of
the cyclohexadiene with its attached CpCo moiety of the
left half remains unknown. Unfortunately, attempted oxida-
tive demetalation led to decomposition.
Scheme 4. Demetalation of the cyclization product 21. Reagents and con-
ditions: a) CuCl2·2H2O, Et3N, MeCN, 08C, 30 min.
atoms in the vicinity of the metal in the starting complex
are found at the expected higher d values. Crucial for the
confirmation of the regiochemistry of cycloaddition were
the chemical shifts of quinolone 29, which corresponded to
those of the parent N-methylquinolone.[26]
The structural assignment of the other monocyclization
product 22 was made in a similar manner, the syn stereo-
chemistry indicated by the methine signal next to the car-
bonyl, d=2.99 (dd, J=12.1, 4.2 Hz, 1H). This complex
probably gives rise to the aromatic 23, the structure of
1
which was confirmed by comparison of its H NMR spec-
Compound 20b appears to be a “left half” isomer of 20a.
It displayed all of the four olefinic hydrogen resonances in
trum with that of N-methylisoquinolone.[27]
To reduce the number of possible products and to probe
the scope of this cycloaddition, the more symmetrical N-
methyl-4-pyridone was subjected to the reaction conditions
described in Scheme 3. Disappointingly, only a 2% yield of
the monocyclized product 30 was isolated, diyne autooligo-
merization to 24 dominating the reaction path (Scheme 5).
For 30, the ring fusion methine hydrogen resonance a to the
nitrogen atom appeared at d=3.19 ppm (J=11.0 Hz), and
1
the H NMR spectrum distinctly, at d=3.53 (d, J=4.4 Hz,
1H), 2.84 (d, J=3.4 Hz, 1H), 2.78 (d, J=3.6 Hz, 1H), and
2.76 ppm (d, J=3.3 Hz, 1H). As with 20a, a signal assigned
to the ring junction hydrogen at C6 of the lactam moiety ap-
peared at d=3.17 ppm (dd, J=9.0, 3.6 Hz, 1H), again sug-
gesting a syn relationship to the metal at this (and the adja-
cent) position. The two Cp peaks at d=4.44 and 4.39 ppm
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Cobalt-Mediated Reactions
FULL PAPER
Scheme 5. Reaction of 1,7-octadiyne with N-methyl-4-pyridone (2equiv).
Reagents and conditions: a) [CpCo(C2H4)2], THF, reflux, 2.5 h.
A
Scheme 6. Cocyclotrimerization of 1 with BTMSA. Reagents and condi-
tions: a) BTMSA, [CpCo(C2H4)2], THF, room temperature, 2h.
A
the neighboring methine proton peak at d=2.93 ppm (J=
11.0 Hz) consistent with a CpCo moiety located syn to these
hydrogens.
Thus, while the preceding chemistry demonstrates the
À
possibility of using either or both C C double bonds of pyri-
dones as cocyclization partners with alkynes in the presence
of CpCo, the process is plagued by competitive alkyne aro-
matization. The diene complexes isolated appear to show a
preference for the syn stereochemistry noted in analogous
pyrimidinone cyclizations, but mixtures ensue.[7] Indeed,
DFT calculations described in the accompanying paper
attest to the similarity in the energetic requirements on
route to both syn and anti products.[28] Rather than tinkering
with reaction conditions to improve the outcome of these
transformations, the topology of the reaction partners was
modified such as to maximize the likelihood of heterocycle
incorporation in the products.
Cobalt-mediated [2+2+2] cycloadditions of alkyne-teth-
ered pyridones: Tethering one or both of the alkyne cyclo-
addition partners to the heteroaromatic core to lower the
entropic costs of the [2+2+2] cyclization has been a fre-
quent strategy to improve reaction yields.[1] In the case of
CpCo, this variant has generated a number of novel poly-
cycles,[2–7] some of which have been utilized in total synthe-
ses.[12,29] In this vein, the N-alkynylated pyridones 1–7 and 9–
13 were subjected to cocyclization with a large excess of
bis(trimethylsilyl)acetylene (BTMSA). The nature of the re-
sulting products—CpCo-complexed cyclobutadienes, cyclo-
hexadienes, and 3-butadienylpyridones—showed a remark-
able dependence on the length or nature of the tether. This
section will summarize examples of the first two modes,
while a subsequent part will describe the third type, which
Scheme 7. Cocyclotrimerization of 2 with BTMSA and oxidative demeta-
lation of product 33. Reagents and conditions: a) BTMSA, [CpCo-
A
N
the data for similar anti fused diene complexes.[7] Specifical-
ly, Ha and Hb give rise to relatively shielded signals at d=
2.36 ppm (d, J=8.0 Hz) and d=1.48 ppm (dd, J=8.0,
4.6 Hz). Further structural confirmation was derived by oxi-
dative demetalation (Scheme 7) to 34. In this free ligand,
the NMR resonance for Ha appears at d=4.75 ppm and Hb
at d=2.40 ppm, while the dienyl hydrogen singlet has expe-
rienced a shift from d=4.82to 5.86 ppm on decomplexation.
Solidification of these assignments rested on an X-ray crys-
tal structure analysis (Scheme 7). The molecule forms a pro-
nounced bowl, the metal located on its concave face. The
energetic preference for the observed stereochemistry in
this tethered system is also indicated by DFT calculations.[28]
As will be described in a later section, lengthening the
tether in 2 twice by increments of a methylene spacer (3 and
À
involves C H activation.
Simultaneous additions of separate solutions of N-2-pro-
pynylpyridone 1 and the cobalt reagent in THF to BTMSA
produced, perhaps not surprisingly, only cyclobutadiene
complex 31 and the ethene adduct 32, the latter in unusually
high yield (Scheme 6).[30]
However, extending the tether length by one carbon, as in
N-3-butynyl system 2, provided, under the same conditions,
the [2+2+2] product 33 in 35% yield almost exclusively,
only trace amounts of the cyclobutadiene isomer (see Exper-
imental Section) and none of the ethene adduct being de-
tectable (Scheme 7). The identity of 33, including its anti ste-
reochemistry, was clearly indicated by the NMR spectra,
which were characteristically distinct from those for related
syn complexes, in particular 21 (Table 6), and in line with
À
4, respectively) led to products of C H activation, to the
complete detriment of a [2+2+2] pathway. Finally, to com-
plete this series, the N-heptynyl derivative 5 was tested in
the process, to give, now as the sole new compound, the cy-
clobutadiene complex (see Experimental Section).
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K. P. C. Vollhardt et al.
Encouraged by the result depicted in Scheme 7, all-intra-
molecular variants of this cycloaddition were explored with
substrates 6 and 7. The former can be viewed as an extend-
ed version of 2, and, on the basis of Scheme 7, was thought
to be an excellent substrate for [2+2+2] cycloisomeriza-
tion. The homolog 7, on the other hand, when considered as
produced in all cases substantial amounts of bis(trimethylsi-
lyl)cyclobutadiene cobalt complexes (50, 25, 15, and 34%,
À
respectively), no products of C H activation, some spurious
side products in the case of 9 and 10 (see Experimental Sec-
tion), and, puzzlingly contrasting with the 2-pyridone series,
only with N-4-pentynylpyridone 11 the desired fused diene
36 (47%; Scheme 9). The structural proof of 36 rests on the
À
a derivative of 3, was anticipated to enter the C H activa-
tion manifold (vide infra). Contrary to these expectations,
adding 6 under high-dilution conditions to [CpCo(C2H4)2]
G
produced only an inseparable mixture of regioisomers re-
sulting from intermolecular cycloadditions, as indicated by
mass spectral analysis. On the other hand, 7 underwent
À
smooth cyclization (and not C H activation) to tetracycle
35 in quite acceptable yield (Scheme 8). The H NMR spec-
1
Scheme 9. Cocycloaddition of 11 to BTMSA and oxidative demetalation
of product 36. Reagents and conditions: a) BTMSA, [CpCo
ACHTREUNG
oxane, THF, room temperature, 4.5 h; b) Fe
ACHTREUNG
H2O, 0 8C, 10 min.
same accumulated evidence as that for 33 and 35: NMR
data [e.g., dHa =2.35 (J=8.8 Hz) and dHb =1.47 ppm (J=
8.8 Hz)], oxidative free ligand 37 generation, aromatization
of 37 to the corresponding 4-quinolone with DDQ (see Ex-
perimental Section), and an X-ray crystallographic analysis.
As mentioned above, N-acylated azaaromatics perform
frequently in a superior manner in this methodology com-
pared to their N-alkylated counterparts.[4,6,12] Therefore, un-
daunted by the lability of N-acylpyridones and their propen-
sity to equilibrate with their ester isomers,[21–23] 13 (admixed
Scheme 8. Cyclization of 7. Reagents and conditions: a) [CpCo(C2H4)2]
(1.1 equiv), THF, room temperature, 16 h. Yield based on recovered
starting material (27%).
A
trum of 35 reveals the complexed diene proton at d=2.40
(br s) ppm and the tertiary nuclei at dHa =2.37 (d, J=
8.0 Hz) and dHb =1.48 ppm (m). An X-ray structural deter-
mination confirmed the structural assignment. The complete
stereoselectivity of this transformation contrasts with related
intramolecular cycloadditions in the indole[4b] and pyrrole
series.[5] This array of atoms has not been reported in the lit-
erature, either as such or as a substructure.
Extending the above series to its 4-pyridone isomeric
counterpart was deemed again instructive, because symme-
try might lead to improved yields, the disappointing results
in the cycloadditions with external diynes (vide supra) not-
withstanding. Moreover, it was hoped that the changes in
the outcome of the cyclization of 2-pyridone substrates
might be affected in an intelligible manner by this switch. In
the event, cocyclization of the N-alkynyl-4-pyridones 9–12
with 14) was exposed to BTMSA and [CpCo(C2H4)2]
A
(Scheme 10).
The reaction furnished two products 38 and 39 of [2+2+2]
cocycloaddition in a poor 5.5% total yield and in the ab-
sence of any other tractable material. The “normal” product
38 was readily identified by spectral analysis, in particular
1H NMR spectroscopy, with the characteristic absorptions
for Ha [d=3.78 ppm (J=6.9 Hz), unusually deshielded rela-
tive to Ha of 37 due to the presence of the amide carbonyl],
and Hb [d=1.21 ppm (J=6.9 Hz)] and, ultimately, by an X-
ray structure.
The identity of the other cyclization product 39 was more
difficult to establish. While the incorporation of BTMSA
and CpCo was evident from resonances at d=0.32(s, 9H),
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Cobalt-Mediated Reactions
FULL PAPER
methodology, much of it devel-
oped toward arene couplings
that construct the embedded
biphenyl
unit.
A
retro-
AHCTREUNG
the C ring as a cyclohexadiene
suggests two feasible discon-
nections, a and b (Scheme 11).
Approach a, employing an en-
amide double bond as a cocyc-
lization partner in the cobalt-
mediated step has been exe-
cuted by us previously.[12] Ap-
proach b constitutes a benzo-
fused version of Scheme 7 and
was realized according to
Scheme 12.
Starting
methylenedioxy
with
isoquinoline
ACHTREUNG
(papraline) 40,[34] N-alkynyla-
tion with 3-butynyl-1-tosy-
late[35] gave the corresponding
isoquinolinium salt, which was
Scheme 10. Cocyclotrimerization of 13 with BTMSA. Reagents and conditions: a) BTMSA, [CpCo(C2H4)2],
G
1,4-dioxane, THF, room temperature, 1.5 h.
oxidized
hexacyanoferrate
with
potassium
(III) in a two-
1
0.38 (s, 9H), and 4.65 ppm (s, 5H) in the H NMR spectrum,
ACHTREUNG
the presence of an additional oxygen atom was suggested by
a molecular ion at m/z 485. Rather than the two doublets
for the ring fusion arrangement in 38, three singlets were
observed at d=3.11 (s, 1H), 3.50 (s, 1H), and 1.60 ppm (br
s, 1H). That the last of these corresponded to a hydroxy
proton was supported by a broad absorption in the IR spec-
trum at 3373 cmÀ1. The precise location of this function was
determined by an X-ray structural analysis, which revealed
39 to be a hydroxylated diene isomer of 38 (Scheme 10).
The structure is remarkable in as much as it constitutes a
novel 4-quinolone hydrate, kinetically protected from aro-
matization (by dehydration) by the attached metal unit. A
Scheme 11. Retro
galanthan core.
A
mechanism for this oxidation through enolization and one-
electron transfer to adventitious CoIII is suggested by recent
literature.[31]
In summary of the results described in this section, it is
À
clear that the pyridone nucleus bearing tethered C C triple
bonds is a relatively effective cocyclization partner with al-
kynes, but the reaction displays a subtle divergence in its
outcome, which seemingly is strongly dependent on the
length of the tether linking the nitrogen atom with the prox-
imal triple bond. In accord with previous findings in the pyr-
imidine series,[7] tethering one or both of the alkyne units
causes an inversion of the stereochemistry of the resulting
cobalt complex to anti.
Application to the total synthesis of anhydrolycorinone: The
successful execution of Scheme 7 inspired its extension to a
new approach to the synthesis of the galanthan (pyrrolophe-
nanthridine) alkaloid skeleton,[32] as exemplified by anhy-
drolycorinone 44.[33] This family of natural products has
been a frequent target on which to test the utility of new
Scheme 12. Total synthesis of anhydrolycorinone. Reagents and condi-
tions: a) 3-Butynyl tosylate, MeCN, 1608C (microwave), 3 h;
b) K3[Fe(CN)6], H2O, 0 8C, 1 h, then KOH, 08C, 0.5 h; c) [CpCo
BTMSA, room temperature, 1 h; d) Bu4NF, THF, room temperature, 2h,
then Fe(NO3)3·9H2O, THF, H2O, room temperature, 2min.
A
AHCTREUNG
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7449

K. P. C. Vollhardt et al.
step sequence[36] to the desired precursor 41 for the key
step. The cobalt-mediated [2+2+2] cycloaddition delivered
the pentacycles 42 and 43 in an approximate 2:1 ratio in ad-
mirable combined 57% yield (67% based on recovered
starting material). It appears that the added benzofusion (in
comparison to 33) exerts a steric effect on the stereochemis-
try of insertion such that endo product formation becomes
competitive.[28] The NMR spectra of these two isomers show
the trends delineated above for the exo versus endo disposi-
tion of the metal (see Experimental Section). An indication
of the steric encumbrance exerted by the benzene ring is
hindered rotation of the trimethylsilyl groups in the bay
region of the dihydrophenanthridinone skeleton on the
NMR time scale at room temperature. In 43, this effect is
visible by the broadening of one of the silyl singlets; in 42 it
is more pronounced, leading to the appearance of three sin-
glets for the individual methyls. We have detected such be-
havior in other products of the cocyclization of
BTMSA.[4b,29g,37] Removal of the two silyl groups with fluo-
ride, followed by oxidative demetalation with Fe-
À
Scheme 13. C H activation in the cobalt-mediated reaction of 3 with
BTMSA. Reagents and conditions: a) BTMSA, [CpCo(C2H4)2], THF,
room temperature, 1 h; b) Fe(NO3)3·9H2O, MeCN, H2O (9:1), 08C.
A
AHCTREUNG
without the obtention of the intermediate cyclohexadiene
ligand. This material was identical with 44 prepared previ-
ously by route a in Scheme 11.[12]
AHCTREUNG
a second singlet at d=À0.64 ppm (br), pinpointing the pres-
ence of an internal, terminal diene hydrogen atom. The
13C NMR spectrum, in conjunction with 2D spectra, corro-
borated these assignments, cemented ultimately by an X-ray
crystal structure analysis (Scheme 13). The molecule is un-
usually deformed, such as to twist the essentially coplanar
complexed diene unit away from the pyridone ring (dihedral
angle around the alkylidene double bond=À558). This dis-
tortion places H5 exactly above the terminal diene carbon
centroid, the vector H5-centroid-Co deviating from linearity
by only 18. The switch from [2+2+2] chemistry (Scheme 7)
À
Dienylpyridones by C H activation reactions: As alluded to
in previous sections, [2+2]- and [2+2+2] cocycloadditions
are not the only pathways by which pyridones transform.
Alternative options for these substrates are C H, and, as we
shall describe in the next section, N H activation, with si-
multaneous double alkyne stitching to provide dienylated
heterocycles, isomeric to the [2+2+2] products. Such inser-
tions have been noted previously in cobalt-mediated cycliza-
tions of heterocycles, usually, but not always, as minor by-
products.[2,4a,7a,38,39] Experimental[40] and theoretical evi-
dence[14] support attack of the cobaltacyclopentadiene inter-
À
À
À
to C H activation on simple lengthening of the tether is
À
mediate (formed by alkyne oxidative coupling) on the C H
qualitatively in accord with DFT estimates, which reveal a
narrowing of energetic requirements for the two respective
pathways on going from 2 to 3, although the pronounced
switchover in mechanism is not reproduced computational-
ly.[28]
bond of the heterocycle. One notes that such ethynylogous
hydroheteroarylations of alkynes are rare, but of obvious
synthetic desirability.[41] In the present case, this process sur-
faces rather startlingly with 3-pentynylpyridone 3, which,
under the conditions that furnished only [2+2+2] products
from the lower homologue 2 (Scheme 7) and the all-intra
analogue 7 (Scheme 8), provided the fused dienylpyridone
complex 45 essentially quantitatively (1H NMR analysis of
crude product; 85% isolated yield; Scheme 13).
That 45 was different from the expected fused quinolone
complex was immediately evident in its NMR spectra. In
particular, the tertiary hydrogen signals typical of the cyclo-
hexadiene ring fusion, Ha,b, were missing and, instead, the
typical pattern for a 6-substituted pyridone was evident [d=
4.65 (dd, J=6.0, 1.5 Hz, 1H, H5), 6.47 (dd, J=9.1, 6.0 Hz,
1H, H4), 6.62ppm (dd, J=9.1, 1.5 Hz, 1H, H3)], H5 being
shielded by about 0.7 ppm from its normal position by the
anisotropy of the adjacent CpCodiene moiety (vide infra).
Moreover, in addition to the anticipated singlet for the inter-
nal complexed diene hydrogen (d=4.56 ppm, br), there was
Quantitative decomplexation of 45 was achieved with Fe-
(NO3)3 (Scheme 13), and the changes in the NMR spectra in
going from 45 to the unknown system 46 were exactly as ex-
pected. Significant with respect to the structural assignments
of related dienes (vide infra), the terminal diene signal ap-
pears as a doublet (J=2.0 Hz) at d=6.33 ppm, whereas its
internal counterpart produces a doublet of triplets [d=
6.06 ppm (J=1.8, 1.7 Hz)] due to additional allylic coupling.
With reasonable quantities of 46 in hand, its potential to un-
dergo thermal electrocyclic ring closure was tested. Butadie-
nylbenzene and 2-(butadienyl)pyridine have been shown to
follow such a pathway during gas-phase pyrolyses to furnish
1,2-dihydronaphthalene and 5,6-dihydroquinoline, respec-
tively.[42] Indeed, when 46 was heated to 1108C for 12h, aro-
matization with concomitant protodesilylation was the
result, yielding 47 quantitatively (NMR). Monitoring this re-
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Cobalt-Mediated Reactions
FULL PAPER
action revealed the intermediacy of two compounds, 48 and
49, both of which could be purified by HPLC and independ-
ently thermolyzed to 47, quantitatively (Scheme 14). It is
À
Scheme 15. Regioselective C H activation–insertion of 3 with unsymmet-
rical alkynes. Reagents and conditions: a) Phenyl(trimethylsilyl)acetylene
(100 equiv), [CpCo
(NO3)3·9H2O, MeCN/H2O (9:1), 08C; c) 1-trimethylsilylpropyne
(135 equiv), [CpCo(C2H4)2], THF, room temperature, 1 h; d) Fe-
(NO3)3·9H2O, MeCN/H2O (9:1), 08C.
C
AHCTREUNG
Scheme 14. Electrocyclic ring closure of the free ligand 46. a) Toluene,
1108C, 12h.
AHCTREUNG
likely that 48 is the precursor to 47, as the peri-silyl group
should be very prone to hydrolytic removal.[43] The structure
of 49, clearly an isomer of 48 on the basis of spectral data,
was assigned in analogy to similar isomerizations in the
furan and thiophene series[2] and the observation of substan-
tial deshielding of the signals for the methylene hydrogens
proximal to the butadienylidene substituent when going
from 46 to 49. Moreover, the internal diene hydrogen expe-
riences a downfield shift of about 0.4 ppm on moving syn to
the pyridone function. This isomer must be in equilibrium
with its precursor to be converted to 48 and eventually 47.
We suspect that this isomerization is catalyzed by adventi-
tious acid.
usually shielded H5 signal of the latter [d=4.53 ppm (d, J=
6.6 Hz)]. The identity of 54 was surmised on the basis of the
changes in the NMR data when compared to those of its
isomer 53, similar to those noted for 49 relative to 46.
While the examples above attest to the potentially re-
À
markable efficiency of a C H activation pathway in the
cobalt-mediated reaction of tethered 2-pyridones with cer-
tain alkynes, limitations were encountered with other sub-
strates. Thus, the reaction of 3 with ethyne, even at À708C,
in the presence of [CpCo(C2H4)2] supplied only N-(3-phe-
A
nylpropyl)-2-pyridone in 65% yield, derived by alkyne cotri-
merization of the triple bond of 3 with ethyne (see Experi-
mental Section).[44] Similarly, dimethyl butynedioate gave N-
[3-(2,3,4,5-tetramethyoxycarbonylphenyl)propyl]-2-pyridone
(56%, see Experimental Section). On the other hand, ho-
mologation of the tether as in 4 gave diene complex 55 in
26% yield, in addition to cyclobutadiene complex 56 (13%;
Scheme 16).
The high yielding conversion depicted in Scheme 13
stimulated a brief exploration of its scope with other sym-
metrical and unsymmetrical monoalkynes. Thus, the reaction
of a large excess phenyl(trimethylsilyl)acetylene with pyri-
done 3 gave 50 regioselectively in 79% yield (Scheme 15).
1
The H and 13C NMR spectral features of 50 were remarka-
bly similar to those of 45, except for the signal for the
carbon atom bearing the phenyl substituent and that of the
hydrogen next to it. The position of the phenyl group was
ascertained by 2D spectroscopy (HMQC). The observed re-
gioselectivity is in accord with the strong preference of silyl
groups to occupy the positions a to the metal center in the
intermediate cobaltacyclopentadienes.[1g,h] Removal of the
Scheme 16. Cobalt-mediated reaction of 4 with BTMSA. Reagents and
cobalt with Fe
G
conditions: a) BTMSA, [CpCo(C2H4)2], THF, room temperature, 1 h.
N
tively (Scheme 15). A similar result was observed with 1-tri-
methylsilylpropyne as the cocyclization partner, which gave
only regioisomer 52 (33%), admixed with the free ligand 53
and its isomer 54 (10:1, 47%) (Scheme 15). This mixture
could be converted quantitatively to 53 and 54 (4:1) with
FeIII. In these compounds, the regiochemical identity was
readily verified by the absence of coupling between the
methyl substituent on the butadienylidene fragment and the
terminal hydrogen. The syn disposition of this fragment with
respect to the pyridone nucleus is again manifest in the un-
À
In summary of this section, C H activation with simulta-
neous double alkyne stitching replaces [2+2+2] cycloaddi-
tions in the reactions of N-protected pyridones in a subtle
and unpredictable way. While products derived from both
options simultaneously were not found for any particular re-
action discussed so far, such direct competition is evident in
other systems.[4a,7a] Thus, it is clear that the two reaction
manifolds are close energetically, as corroborated by compu-
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7451

K. P. C. Vollhardt et al.
tational estimates.[28] In view of the above, the question
Execution of the same protocol with 4-pyridone also led
to N-H activation, albeit less efficiently and stereoselec-
tively, furnishing the two isomers 59 and 60 (2:1), separated
by HPLC, in 18% combined yield (Scheme 17). The differ-
ence in nature of the stereochemistry of these two com-
plexes is clearly evident in the chemical shifts of the diene
hydrogen atoms next to the pyridone substituent: d=0.92
(59) and 4.11 ppm (60). Both complexes delivered their free
ligands 61 and 62, respectively, on oxidation.
À
arose whether N H activation was another alternative, an-
swered in the next section.
À
N H activation reactions: The catalytic hydroamination of
alkynes to enamines is a subject of considerable current in-
terest.[45] Hydroamination occurring with simultaneous
alkyne coupling to furnish dienylamines is rare.[46] Wakatsuki
and Yamazaki have reported that thioacetanilide and thiour-
ea derivatives add to Cpcobaltacyclopentadienes in this
The above results are gratifying, albeit limited to the two
examples investigated, in as much as they indicate that,
indeed, in addition to the two modes of cycloaddition and to
[40b]
À
fashion, whereas pyrrole underwent C H activation.
On
consideration of these results, it appeared reasonable to
À
À
À
expect that the parent 2- and 4-pyridones would react by N
C H activation, N H activation is feasible and, considering
the other possible modes of reactivity, most facile for pyri-
dones in the presence of CpCo. Future experimentation is
warranted in order to explore the synthetic utility of this re-
action, as it generates valuable synthetic building blocks.
Having explored at some length the reactivity of pyridones
by variation of substituents, another attempt at delineating
the scope of this chemistry was made by replacing C4 in the
heterocycle by nitrogen, as in pyrazinone. The results are in-
structive in comparison to those collected in the pyridinone
(vide supra) and pyrimidinone series.[7]
H insertion, an expectation reinforced by a DFT appraisal
of the comparative energetics involved.[28]
Indeed, when excess 2-pyridone (53 equiv, to maximize
cocycloaddition) was treated with 1,7-octadiyne and [CpCo-
(C2H4)2], cobalt complex 57 was recovered with exclusive Z-
configuration in 45% yield, remarkably high in view of the
intermolecular nature of this heterocycle activation
(Scheme 17). The structure of 57 was indicated by the ab-
G
Cobalt-mediated activation of pyrazinones: Like pyridine,
pyrazine itself is left untouched by CpCo. Therefore, in anal-
ogy to Scheme 3 and in anticipation of a [2+2+2] cycload-
dition, N-methylpyrazinone 63 and 1,7-octadiyne were treat-
ed with [CpCo(C2H4)2]. Surprisingly, complex 64 was
G
formed regioselectively (22% yield; 29% based on convert-
ed 63) via C-H activation (Scheme 18). The NMR spectra of
Scheme 18. Reaction of pyrazinone 63 with 1,7-octadiyne (1.9 equiv). Re-
agents and conditions: a) [CpCo(C2H4)2], C6H6, D, 4 h. Yield based on re-
A
covered 63 (24%).
À
Scheme 17. N H activation of 2- and 4-pyridone. Reagents and condi-
tions: a) [CpCo
A
A
this compound showed the disappearance of the low field
peak associated with H-3 in pyrazinones, but the preserva-
tion of the characteristic doublets for the other hydrogen
atoms of the heterocycle. The presence of the cobalt-com-
plexed diene unit and its stereochemistry was evident in the
À
sence of an infrared band for an N H bond and the pres-
ence of a complete set of four pyridone protons, notably a
doublet characteristic of pyridone H-6 next to nitrogen [d=
7.27 ppm (J=5.5 Hz)]. In addition, there were three broad-
ened singlets assigned to CpCo-bound dienyl hydrogens at
d=À0.15, 1.71, and 3.08 ppm, the first two chemical shifts
typical of terminal Z and E positions, the third consistent
with an E-hydrogen atom appropriately shifted by the
neighboring enamido group.[47] Oxidative demetalation de-
livered free ligand 58, a novel array, in quantitative yield.
1
13C and H NMR spectra, the latter through three diagnostic
singlets at d=4.65 and 2.51 ppm, for the two E hydrogen
atoms, the former relatively deshielded by the adjacent het-
erocyclic substituent, and 0.37 ppm, for the Z hydrogen
atom at the terminus.
À
While C H activations of similar functions are unprece-
À
dented to our knowledge, it appears that the imine C H
bond in 63 is particularly reactive, obviating the expected
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Cobalt-Mediated Reactions
FULL PAPER
cycloaddition pathway. Tentative confirmation of this notion
was sought by removing this site, as in N,N’-dibenzylpyrazi-
nedione 65,[48] for which the relative propensity to enter the
À
[2+2+2] versus C H activation manifold could be properly
evaluated. In the event, the former wins out, as reaction
with 1,7-octadiyne formed linear tricycle 66 in 15% isolated
yield (Scheme 19). In this reaction, substantial quantities of
Scheme 19. Reaction of pyrazinedione 65 with 1,7-octadiyne (3.6 equiv).
Reagents and conditions: a) [CpCo(C2H4)2] (1.1 equiv), toluene, room
G
temperature, 18 h. Yield based on recovered 65: 54%.
unreacted 65 were recovered (72%), indicating that compet-
itive diyne cyclotrimerization is detrimental. Based on con-
verted heterocycle, the yield is an admirable 54%. The sym-
Scheme 20. Cobalt-mediated [2+2+2] cycloaddition of BTMSA to
alkyne tethered pyrazinone 15. Reagents and conditions: a) BTMSA,
1
metry in 66 is reflected in the simple H NMR spectrum and
its syn stereochemistry surmised by the position of the
peaks for the tertiary hydrogens [d=3.71 ppm (br s)]
(Table 6), in accord with related cyclizations in the pyridone
(Scheme 3–5) and pyrimidinone series.[7]
[CpCo(C2H4)2] (1.2equiv), THF, room temperature, 3 h; b) CuCl 2·H2O,
NEt3, THF, 08C to room temperature, 7 h.
A
À
To prevent the C H activation pathway of Scheme 18 and
improve the competitiveness of heterocycle incorporation at
the expense of external alkyne cyclotrimerization, recourse
was again taken to the attachment of one or both of the
triple bonds by
a tether. Gratifyingly, in analogy to
Scheme 7, the 3-butynyl substituted system 15 was trans-
formed to 67 (41%), in addition to a small amount of arom-
atized and partly desilylated 68 (10%). The NMR spectra
clearly indicated that [2+2+2] cycloaddition had occurred,
its stereopreference revealed by dHa =1.94 (d, J=8.4 Hz)
and dHb =3.20 (dd, J=8.4, 2.8 Hz), the latter showing a
small coupling to the imine hydrogen at d=7.88 (d, J=
2.8 Hz). An X-ray diffraction analysis confirmed these as-
signments and presented a molecule with a three-dimension-
al disposition almost identical to that of the pyridone analog
33 (Scheme 7). Curiously, attempted decomplexation of 67
with FeIII led to a complex mixture of unidentified products.
More successful was CuII, although it caused aromatization
to 69 (44%) together with some, presumably subsequent,
monodesilylation to 68 (5%; Scheme 20). The pyrroloquin-
À
Scheme 21. Cobalt-mediated C H activation of alkyne tethered pyrazi-
none 16. Reagents and conditions: a) BTMSA, [CpCo
A
room temperature, 2.5 h; b) Fe(NO3)3·9H2O, MeCN, H2O, 0 8C, 1.5 min.
A
Finally, in the spirit of Scheme 8, an all-intramolecular
isomerization of N,N’-dipentynylpyrazinedione 19 was exe-
cuted (Scheme 22), fully expecting a symmetrical structure
with the carbon tether emanating from the terminal diene
carbons in the anticipated cyclohexadiene cobalt complex,
such as found in the cycloisomerization of the all carbon an-
alogue tetradeca-7-ene-1,13-diyne.[50] Surprisingly, an unsym-
metrical molecule ensued, the puzzling spectral data of
which were demystified only by an X-ray structural analysis
(Scheme 22). It showed that one of the terminal triple bonds
had been incorporated in a way that was regioisomeric to
normal, the resulting bowl shaped ligand bearing the metal
on its convex face. Remarkably, the bond lengths and (dihe-
dral) angles around the metalated diene unit in this (for-
mally) anti-Bredt[51] molecule are unexceptional. The rela-
tively large chemical shifts of Ha [d=3.93 (d, J=7.9 Hz)]
and Hb [d=3.76 (dd, J=7.8, 5.5 Hz)] corroborate the stereo-
chemical assignments of 66 (syn) and 67 (anti). DFT compu-
tations of the system revealed that the pathway from 19 to
72 is not only perfectly feasible thermodynamically, but also
that it proceeds by a new mechanism.[28] Attempts to affect
A
In consonance with the pyridone (Scheme 13 and 15) and
pyrimidinone analogues,[7] extending the tether length by
À
one methylene group caused C H activation to resurface,
albeit in much poorer yield (70 in Scheme 21). Decomplexa-
tion of 70 under standard conditions furnished 71
(Scheme 21). The NMR data of these compounds were as
expected in comparison to those of 45 and 46, respectively.
An attempt to extend the series to the hexynylpyrazinone
17, by analogy to Scheme 16, was unsuccessful.
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7453

K. P. C. Vollhardt et al.
al ethyne to generate benzene,
or by ethene to produce
[CpCo(h4-cyclohexadiene)], all
types of which are observed as
undesired products. The de-
sired intermediate is h2-pyri-
done complex C (in equilibri-
um with its various isomers).
This species (when N-protect-
ed) may undergo insertion to
cobaltacycloheptadiene
D,
giving rise to [2+2+2] adducts
F via E. Alternatively, it may
enter a proton transfer mani-
À
fold (C H activation) to fur-
Scheme 22. All-intramolecular [2+2+2] cycloaddition of 19. Reagents and conditions: a) [CpCo(C2H4)2], tol-
uene, room temperature, 3.5 h.
A
nish G, which subsequently
provides dienylpyridone H. Fi-
nally, for N-unprotected sys-
this process by shortening the tether, as in 18, failed to give
identifiable products.
tems, the metallotropomer I of C can undergo proton migra-
À
tion (N H activation) to J and, eventually, N-dienylpyridone
K.
General mechanistic considerations: While a more detailed
mechanistic discussion is relegated to an accompanying pub-
lication dealing with DFT computations of the specific path-
ways of reactivity encountered in this work,[28] this and a re-
cently published calculational appraisal[14] leads to the gener-
ic picture outlined in Scheme 23 for the reaction of 2-pyri-
done with ethyne. The key intermediate is the cobaltacyclo-
pentadiene B derived by oxidative coupling of two ethynes
in A. This intermediate may valence tautomerize to the cor-
responding cyclobutadiene complex, be trapped by addition-
Conclusion
In summary, we have extended the cobalt-mediated hetero-
cycle activation methodology to the nuclei of pyridone and
pyrazinone. The diversity of the resulting products attests to
the fact that the metal has several energetically close-lying
trajectories at its disposal, a finding that is corroborated by
DFT calculations in an accompanying study. Synthetically,
some potentially quite useful molecular alterations were un-
covered, namely, in addition to [2+2+2] cycloadditions, di-
enylations at carbon and nitrogen proceeding by alkyne
stitching. While it is, at present, difficult to predict the over-
all efficiency and relative preponderance of the former two
pathways, it appears that the latter mode prevails for N-un-
protected systems. Further experimentation should shed fur-
ther light on these issues.
Experimental Section
General methods: Unless otherwise stated, all starting materials were ob-
tained 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, respective-
ly, 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 via Hamilton gas tight syringes mounted on
a syringe pump. Column chromatography was performed on flash silica
gel (Merck Reagents silica gel 60, 230–400 mesh ASTM). Thin-layer
chromatography (TLC) was carried out on a 250 mm coating with fluores-
cent indicator. Melting points were observed in open Pyrex capillary
tubes with a Thomas-Hoover Unimelt apparatus and are uncorrected. In-
frared spectra were obtained either on neat compounds (NaCl plates), in
solution (solvent, NaCl cells), or with KBr pellets. 1H NMR assignments,
when given, were made on the basis of correlation spectroscopy. Low-
Scheme 23. Generic mechanisms of the cobalt-mediated reaction of
ethyne with 2-pyridone.
7454
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 7443 – 7465

Cobalt-Mediated Reactions
FULL PAPER
and high-resolution mass spectra were provided by the Mass Spectral
Service at the University of California at Berkeley. Elemental analyses
were executed by the Microanalytical Laboratory, UCB. Microwave-as-
sisted reactions were run in a Smith Synthesizer single-mode microwave
cavity, producing continuous radiation at 2450 MHz.
ed 4 (406 mg, 46%). Colorless oil; IR (film): n˜ =3445, 3296, 3230, 2944,
2115, 1660, 1583, 1539, 1465, 1435, 1145, 768 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d=7.33–7.25 (m, 2H), 6.56 (d, J=9.2Hz, 1H), 6.16 (td, J=6.7,
1.1 Hz, 1H), 3.95 (t, J=7.4 Hz, 2H), 2.25 (td, J=6.9, 2.7 Hz, 2H), 1.96 (t,
J=2.6 Hz, 1H), 1.88 (m, 2H), 1.58 ppm (m, 2H); 13C NMR (100 MHz,
CDCl3): d=162.6, 139.4, 137.5, 121.1, 106.1, 83.7, 68.9, 49.2, 28.4, 25.4,
18.1 ppm; MS (70 eV, EI): m/z (%): 175 (89) [M+], 136 (100), 133 (49),
109 (65), 95 (69), 80 (79), 67 (49); HRMS: Calcd for C11H13NO:
175.0997; found: 175.0994.
N-(3-Butynyl)-2-pyridone (2): This compound was prepared by an alter-
native route to that published.[18] A solution of 2-pyridone (freshly recrys-
tallized, washed with EtOAc, 98%, 2.49 g, 25.7 mmol), NaOH (1.05 g,
25.7 mmol), and 3-butynyl tosylate (96%, 5 g, 21.4 mmol)[52] in MeOH
(15 mL) was heated to reflux for 21 h, during which additional MeOH
(15 mL) was added to minimize foaming. The mixture was poured into
water and extracted with CH2Cl2. The organic phase was washed with
sat. Na2CO3, dried over MgSO4, and the solvent removed in vacuo. Chro-
matography (hexanes/EtOAc 1:1–1:2) gave first 2-(3-butynyloxy)pyridine
(121 mg, 4%). Colorless oil; IR (film): n˜3299, 2960, 2122, 1597, 1572,
N-(6-Heptynyl)-2-pyridone (5): A solution of 2-pyridone (freshly recrys-
tallized, washed with EtOAc, 98%, 1.227 g, 12.9 mmol), NaOH (0.52 g,
12.9 mmol), and 6-heptynyl tosylate (4.12 g, 15.5 mmol)[55] in MeOH
(15 mL) was heated to reflux for 22 h. It was then poured into water, ex-
tracted with CH2Cl2, the organic phase washed with sat. Na2CO3, dried
over Na2SO4, and the solvent removed in vacuo. Chromatography (hex-
anes/EtOAc 1:1–1:2) delivered 5 (1.226 g, 50%). Slightly reddish oil; IR
(film): n˜ =3449, 3297, 3230, 2940, 2862, 2115, 1659, 1584, 1539, 1465,
1477, 1434, 1250, 1143, 1046, 1017, 780, 644 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d=8.18 (dd, J=4.8, 1.2Hz, 1H), 7.57 (dd, J=6.4, 5.2Hz, 1H),
6.88 (dd, J=6.4, 5.2Hz, 1H), 6.77 (d, J=8.4 Hz, 1H), 4.44 (t, J=6.8 Hz,
2H), 2.69 (td, J=6.8, 2.8 Hz, 2H), 2.03 ppm (t, J=2.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d=163.2, 146.7, 138.5, 116.8, 111.1, 80.8, 69.5, 63.5,
19.2ppm; MS (70 eV, EI): m/z (%): 147 (52) [M+], 118 (8), 108 (19), 95
(100), 78 (53), 67 (40); HRMS: Calcd for C9H9NO: 147.0684; found:
147.0683. Subsequent fractions contained 2 (796 mg, 25%). Colorless
powder; m.p. 81–838C; IR (film): n˜ =3451, 3295, 3232, 2961, 2117, 1660,
1434, 1159, 1144, 768 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.32–7.23
;
(m, 2H), 6.56 (dd, J=9.0, 0.6 Hz, 1H), 6.16 (td, J=6.6, 1.3 Hz, 1H), 3.92
(t, J=7.4 Hz, 2H), 2.25 (td, J=6.9, 2.7 Hz, 2H), 1.93 (t, J=2.6 Hz, 1H),
1.79–1.71 (m, 2H), 1.59–1.50 (m, 2H), 1.50–1.40 ppm (m, 2H); 13C NMR
(100 MHz, CDCl3): d=162.6, 139.3, 137.5, 121.2, 105.9, 84.2, 68.5, 49.8,
28.8, 28.0, 25.7, 18.3 ppm; MS (70 eV, EI): m/z (%): 189 (84) [M+], 188
12
(100), 150 (69), 109 (61), 96 (48); HRMS: Calcd for
190.1187; found: 190.1187.
C
13CH15NO:
11
1582, 1539, 1438, 1353, 1168, 1147, 767 cmÀ1
;
1H NMR (400 MHz,
CDCl3): d=7.30–7.19 (m, 2H), 6.45 (d, J=9.2Hz, 1H), 6.17 (t, J=
6.6 Hz, 1H), 3.96 (t, J=6.4 Hz, 2H), 2.58 (m, 2H), 1.96 ppm (t, J=
2.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=162.3, 139.9, 138.4, 120.7,
105.6, 80.5, 71.1, 48.8, 18.5 ppm; MS (70 eV, EI): m/z (%): 147 (100) [M+
], 118 (6), 108 (7), 95 (99), 80 (30), 67 (28); elemental analysis calcd (%)
for C9H9NO: C 73.45, H 6.16, N 9.52; found: C 73.16, H 6.25, N 9.53.
N-(3,8-Nonadiynyl)-2-pyridone (6): To a solution of N-3-butynyl-2-pyri-
done (2) (1.21 g, 8.22 mmol) in dry THF (50 mL) was added BuLi (2.5m,
4.6 mL, 11.5 mmol) via syringe at À788C and the mixture stirred for 1 h
at À788C. Neat 5-iodo-1-pentyne (6.38 g, 32.9 mmol)[53] was added, the
solution allowed to warm to room temperature overnight, the mixture
poured into H2O (80 mL), and the aqueous layer extracted with Et2O
(4”50 mL). After drying over MgSO4, the volatiles were removed under
reduced pressure, and the crude product purified by column chromatog-
raphy (CHCl3) to yield 6 (1.21 g, 68%). Pale amber oil; IR (thin film):
N-(4-Pentynyl)-2-pyridone (3): 5-Iodo-1-pentyne (11.3 g, 52.0 mmol)[53]
was added to a solution of 2-pyridone (4.94 g, 52.0 mmol) and potassium
carbonate (7.16 g, 52.0 mmol) in DMSO (150 mL). The mixture was
heated to 1008C for 48 h, filtered, and solvent removed by distillation at
0.001 torr. The residue was extracted with chloroform (200 mL) and the
resulting solution washed with 1.00n HCl (2”50 mL), saturated NaCl
(2”50 mL), and dried over sodium sulfate. Chromatography (CHCl3/
MeOH 9:1) gave 3 (7.10 g, 85%). Light yellow liquid; IR (KBr) n˜ =3296,
3228, 3075, 2940, 2116, 1659, 1588, 1539, 1465, 1434, 1348, 1242, 1164,
n˜ =3274, 2858, 1660, 1582, 1531, 1424, 1180, 1131, 834 cmÀ1 1H NMR
;
(250 MHz, CDCl3): d=7.31–7.21 (m, 2H), 6.41 (d, J=8.6, 1H), 6.05 (d,
J=8.6, 1H), 3.95–3.86 (m, 2H), 2.59–2.48 (m, 2H), 2.19–2.08 (m, 4H),
1.85 (t, J=2.7 Hz, 1H), 1.61–1.47 ppm (m, 2H); 13C NMR (62.9 MHz,
CDCl3): d=165.2, 136.3, 134.4, 124.7, 103.2, 83.2, 79.5, 72.4, 68.6, 46.3,
23.4, 18.5, 17.9, 17.1 ppm; MS (70 eV, EI): m/z (%): 213 (18) [M+], 212
(79), 196 (56), 184 (61), 134 (31), 117 (100); HRMS: Calcd for
C14H15NO: 213.1118; found: 213.1153; elemental analysis calcd (%) for
C14H15NO: C 78.84, H 7.09, N 6.57; found: C 78.57, H 7.22, N 6.63.
1144, 846, 767 cmÀ1 1H NMR (300 MHz, CDCl3): d=7.30 (m, 2H), 6.46
;
(d, J=9.7 Hz, 1H), 6.15 (td, J=6.7, 1.0 Hz, 1H), 4.04 (t, J=6.8 Hz, 2H),
2.22 (td, J=6.8, 2.6 Hz, 2H), 2.02 (t, J=2.6 Hz, 1H), 1.97 ppm (quin, J=
6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=161.9, 139.4, 137.9, 121.0,
105.8, 82.7, 69.7, 48.6, 27.1, 15.4 ppm; MS (70 eV, EI): m/z (%): 161 (50)
[M+], 144 (8), 109 (100), 95 (19), 81 (36), 67 (32), 53 (15); HRMS: Calcd
for C10H11NO: 161.0841; found: 161.0842. Further elution furnished 2-(4-
pentynyloxy)pyridine (100 mg, 1%). 1H NMR (300 MHz, CDCl3): d=
2.28–2.20 (m, 3H), 2.38 (td, J=7.2, 2.6 Hz, 2H), 4.40 (t, J=6.2Hz, 2H),
6.75 (dd, J=8.4, 2.0 Hz, 1H), 6.88 (ddd, J=8.4, 5.2, 2.0 Hz, 1H), 7.59 (td,
J=8.4, 2.0 Hz, 1H), 8.15 ppm (dd, J=5.2, 2.0 Hz, 1H).
N-(4,9-Decadiynyl)-2-pyridone (7): To a solution of N-4-pentynyl-2-pyri-
done (3) (3.00 g, 18.6 mmol) in dry THF (120 mL) was added BuLi
(2.5m, 10.4 mL, 26 mmol) via syringe at À788C. The solution was stirred
for 1 h at À788C, neat 5-iodo-1-pentyne (16 g, 82.5 mmol) added and the
reaction mixture allowed to warm to room temperature overnight. The
mixture was poured into water (150 mL), extracted with ethyl ether (4”
60 mL), the organic layer dried over MgSO4, and solvents removed under
reduced pressure. Column chromatography (hexanes/EtOAc 2:1) gave 7
(2.20 g, 52%). Brown oil; IR (thin film): n˜ =3293, 2936, 2866, 1659, 1586,
N-(5-Hexynyl)-2-pyridone (4): A solution of 2-pyridone (freshly recrys-
tallized, washed with EtOAc, 98%, 485 mg, 5 mmol), NaOH (245 mg,
6 mmol), and 5-hexynyl tosylate (1.51 g, 6 mmol)[54] in MeOH (5 mL) was
heated to refluxed for two days, during which additional MeOH (5 mL)
was added after 18 h. The mixture was poured into water, extracted with
CH2Cl2, the organic phase washed with saturated Na2CO3, dried over
MgSO4, and the solvent removed in vacuo. Chromatography (hexanes/
EtOAc 1:1–1:2) eluted first 2-(5-hexynyloxy)pyridine (142 mg, 16%).
Colorless oil; IR (film) n˜ =3300, 2948, 2117, 1596, 1570, 1478, 1469, 1434,
1539, 1434, 1335, 1169, 1164, 1145, 846, 767 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d=7.12(m, 2H), 6.30 (d, J=10.0 Hz, 1H), 5.97 (t, J=7.0 Hz,
1H), 3.81 (t, J=7.0 Hz, 2H), 2.21 (m, 4H), 1.97 (td, J=6.4, 2.7 Hz, 2H),
1.82(t, J=2.7 Hz, 1H), 1.71 (q, J=6.6 Hz, 2H), 1.48 ppm (q, J=7.0 Hz,
2H); 13C NMR (400 MHz, CDCl3): d=162.6, 139.4, 137.9, 121.0, 105.8,
83.5, 80.4, 79.2, 60.3, 48.9, 27.9 (2C), 17.7, 17.4, 15.8 ppm; MS (70 eV, EI):
m/z (%): 227 (2) [M+], 226 (7) [M+-H], 132(52), 109 (100); HRMS:
Calcd for C15H17NO: 227.1310; found: 227.1303.
1252, 1049, 989, 781, 637 cmÀ1 1H NMR (400 MHz, CDCl3): d=8.15 (dt,
;
N-(2-Propynyl)-4-pyridone (9): To a mixture of 3-bromopropyne (80%
w/w in toluene, 300 mL, 2.69 mmol) in MeCN (9 mL) at reflux was added
4-trimethylsilyloxypyridine (8) (336 mg, 2.01 mmol)[20] in MeCN (3 mL)
via syringe pump over a period of 45 min. After a total of 3 h, the reac-
tion mixture was cooled to room temperature and treated with MeOH
(3.7 mL) and solid K2CO3 (750 mg). Following a further 30 min, the sus-
pension was filtered and concentrated in vacuo. The residue was purified
by chromatography (CH2Cl2/MeOH 8:1) to give compound 9 (229 mg,
J=4.3, 1.0 Hz, 1H), 7.56 (dd, J=2.0, 1.2 Hz, 1H), 6.85 (ddd, J=7.1, 5.1,
0.8 Hz, 1H), 6.77 (dt, J=8.4, 0.8 Hz, 1H), 4.31 (t, J=6.4 Hz, 2H), 2.28
(m, 2H), 1.97 (t, J=2.8 Hz, 1H), 1.91 (m, 2H), 1.72 ppm (m, 2H);
13C NMR (100 MHz, CDCl3): d=163.9, 146.8, 138.6, 116.6, 111.1, 84.2,
68.6, 65.3, 28.2, 25.1, 18.2 ppm; MS (70 eV, EI): m/z (%): 175 (22) [M]+,
147 (16), 146 (26), 96 (51), 95 (100), 79 (36), 78 (36), 67 (74); HRMS:
Calcd for C11H13NO: 175.0997. Found: 175.0995. Further fractions provid-
Chem. Eur. J. 2007, 13, 7443 – 7465
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7455

K. P. C. Vollhardt et al.
85%). Blue-green oil; IR (film): n˜ =3405, 3080, 2955, 2123, 1640, 1546,
1183, 853, 574 cmÀ1 1H NMR (500 MHz, CDCl3): d=7.72(d, J=7.5 Hz,
(C), 69.6 (CH), 33.5 (CH2), 14.3 ppm (CH2). No attempts were made to
obtain these compounds completely pure.
;
2H), 6.49 (d, J=7.6 Hz, 2H), 4.80 (d, J=2.5 Hz, 2H), 2.65 ppm (t, J=
2.6 Hz, 1H); 13C NMR (125 MHz, CDCl3): d=178.3, 140.3, 118.2(br),
77.4, 75.2, 45.9 ppm; MS (70 eV, EI): m/z (%): 133 (100) [M+], 105 (31),
104 (63), 78 (14), 52(16); HRMS: Calcd for C 8H7NO: 133.0528; found:
133.0526.
1-(3-Butynyl)-2-pyrazinone (15): A mixture of 2-pyrazinone (507 mg,
5.28 mmol), 3-butynyl tosylate (1.24 g, 5.6 mmol),[52] and K2CO3 (1.50 g,
11.7 mmol) in CH3CN (130 mL) was stirred under reflux for 6 h. The
mixture was then allowed to cool to room temperature, concentrated on
a rotary evaporator, and extracted with CH2Cl2 and H2O. The combined
organic phases were dried over MgSO4, filtered, and concentrated. Chro-
matography (CH2Cl2/MeOH 20:1) gave the known O-alkynylation side
product (224 mg, 29%) 2-(3-butynyloxy)pyrazine[57] and then 15 (322 mg,
41%). IR (KBr): n˜ =3225, 3075, 3050, 3020, 2960, 2920, 1650, 1585, 1500,
1455, 1445, 1430, 1365, 1355, 1310, 1185, 1125, 1060, 1000, 920, 810, 745,
N-(3-Butynyl)-4-pyridone (10): A solution of impure 4-iodo-1-butyne
(550 mg, 3.05 mmol) in MeCN (15 mL) was combined with 8 (540 mg,
3.23 mmol) in MeCN (6 mL). Treatment of the reaction mixture with
MeOH (6 mL) and K2CO3 (1.2g, 8.7 mmol) was followed by filtration
and concentration in vacuo to leave a white solid residue. Chromatogra-
phy (CH2Cl2/MeOH 10:1–8:1) gave 10 (76 mg, 17%). Colorless solid;
m.p. 97–1008C; IR (film): n˜ =3383, 3291, 2962, 2925, 2116, 1641, 1557,
710, 615, 595, 550, 525 cmÀ1 1H NMR (CDCl3, 300 MHz): d=8.15 (s,
;
1H), 7.32(d, J=4.4 Hz, 1H), 7.20 (dd, J=4.4, 1.2Hz, 1H), 4.01 (t, J=
6.3 Hz, 2H), 2.70 (td, J=6.3, 2.7 Hz, 2H), 2.04 ppm (t, J=2.7 Hz, 1H);
13C NMR (CDCl3, 100 MHz): d=156.0, 149.5, 129.5, 123.5, 79.7, 71.8,
48.5, 18.1 ppm; MS (70 eV, EI): m/z (%): 148 (92) [M+], 119 (19), 96
(100), 81 (50), 68 (30), 54 (18); HRMS: Calcd for C8H8N2O: 148.0637;
found: 148.0637.
1
1404, 1187, 854 cmÀ1; H NMR (500 MHz, CDCl3): d=7.34 (d, J=5.9 Hz,
2H), 6.34 (d, J=5.9 Hz, 2H), 3.90 (t, J=6.4 Hz, 2H), 2.63 (td, J=6.4,
2.6 Hz, 2H), 2.10 ppm (t, J=2.6 Hz, 1H); 13C-DEPT NMR (125 MHz,
CDCl3): d=178.7 (C), 140.1 (CH), 118.1 (CH), 78.8 (C), 72.4 (CH), 54.7
(CH2), 20.9 (CH2); MS (70 eV, EI): m/z (%): 147 (44) [M+], 118 (4), 109
(7), 108 (100), 95 (3), 82(19), 53 (6); HRMS: Calcd for C 9H9NO:
147.0684; found: 147.0682.
1-(4-Pentynyl)-2-pyrazinone (16): A mixture of 2-pyrazinone (154 mg,
1.60 mmol), 4-pentynyl tosylate (425 mg, 1.91 mmol),[58] and CsCO3
(1.06 g, 5.50 mmol) in CH3CN (40 mL) was stirred under reflux for 1 h.
The mixture was allowed to cool to room temperature, concentrated on a
rotary evaporator, and extracted with CH2Cl2 and H2O. The combined or-
ganic phases were dried over MgSO4, filtered, and concentrated. Column
chromatography (hexanes/CH2Cl2/EtOAc 3:1:1-CH2Cl2/MeOH 9:1) gave
16 (135 mg, 52%). Colorless oil; IR (KBr): n˜ =3220, 3080, 3060, 3015,
2960, 1655, 1585, 1490, 1460, 1435, 1340, 1270, 1215, 1165, 1125, 1075,
N-(4-Pentynyl)-4-pyridone (11): Following the procedure described
above, a solution of 5-iodo-1-pentyne (1.2g, 6.2mmol) in MeCN (10 mL)
was combined with 8 (795 mg, 4.75 mmol) in MeCN (4 mL). After 3.5 h,
the reaction mixture was treated with MeOH (4 mL) and K2CO3
(800 mg). Filtration and concentration in vacuo left a white solid residue.
Chromatography (CH2Cl2/MeOH 10:1) furnished 11 (655 mg, 85%).
Yellow oil; IR (film): n˜ =3291, 1640, 1548, 1194, 854 cmÀ1 1H NMR
;
1
1050, 915, 815, 760, 734, 690, 620, 575 cmÀ1; H NMR (CDCl3, 300 MHz):
(500 MHz, CDCl3): d=7.33 (d, J=7.2Hz, 2H), 6.38 (d, J=7.1 Hz, 2H),
3.95 (t, J=6.8 Hz, 2H), 2.23 (td, J=6.4, 2.6 Hz, 2H), 2.08 (t, J=2.6 Hz,
1H), 1.95 ppm (quin, J=6.6 Hz, 2H); 13C-DEPT NMR (125 MHz,
CDCl3): d=178.6 (C), 139.8 (CH), 118.4 (CH), 81.3 (C), 70.5 (CH), 54.6
(CH2), 28.7 (CH2), 14.8 ppm (CH2); MS (70 eV, EI): m/z (%): 161 (100)
[M+], 133 (19), 132 (49), 120 (16), 108 (96), 107 (30), 82 (25), 81 (41), 67
(13); HRMS: Calcd for C10H11N1O1: 161.0841; found: 161.0838.
d=8.13 (d, J=0.9 Hz, 1H), 7.31 (d, J=4.4 Hz, 1H), 7.16 (dd, J=4.4,
1.1 Hz, 1H), 4.02(t, J=6.9 Hz, 2H), 2.25 (td, J=6.6, 2.6 Hz, 2H), 2.05 (t,
J=2.6 Hz, 1H), 1.97 ppm (quin, J=6.5 Hz, 2H); 13C NMR (CDCl3,
100 MHz): d=156.0, 149.4, 129.1, 123.6, 82.1, 70.3, 48.3, 26.4, 15.4 ppm;
MS (70 eV, EI): m/z (%): 162(49) [ M+], 145 (9), 133 (8), 120 (33), 110
(100), 106 (8), 97 (28), 82 (47), 79 (10), 68 (28), 66 (17), 54 (13), 52 (6);
HRMS: Calcd for C9H10N2O: 162.0793; found: 162.0793. A subsequent
fraction gave 2-(4-pentynyloxy)pyrazine (110 mg, 42%). Colorless oil; IR
(KBr): n˜ =3625, 3060, 2965, 2945, 2905, 1585, 1535, 1470, 1420, 1375,
1310, 1295, 1200, 1155, 1075, 1060, 1035, 1010, 935, 845, 755, 690, 650,
N-(5-Hexynyl)-4-pyridone (12): Following the procedure described
above, a solution of 6-iodo-1-hexyne (501 g, 2.40 mmol)[56] in MeCN
(8 mL) was combined with compound 8 (357 mg, 2.13 mmol) in MeCN
(3 mL). After 3 h, the reaction mixture was treated with MeOH (2.5 mL)
and K2CO3 (550 mg) and then filtered and concentrated in vacuo. Chro-
matography (CH2Cl2/MeOH 10:1) gave compound 12 (222 mg, 60%).
White solid; m.p. 121–1248C; IR (KBr): n˜ =3192, 2942, 2862, 1675, 1639,
1
615 cmÀ1; H NMR (CDCl3, 300 MHz): d=8.22 (s, 1H), 8.10 (ABm, 2H),
4.42(t, J=6.9 Hz, 2H), 2.40 (td, J=7.1, 2.6 Hz, 2H), 2.02 ppm (quin, J=
6.9 Hz, 2H); 13C NMR (CDCl3, 100 MHz): d=160.2, 140.6, 136.6, 136.0,
83.2, 69.1, 64.7, 27.8, 15.3 ppm; MS (70 eV, EI): m/z (%):162 (22) [M+],
147 (9), 134 (79), 123 (9), 106 (5), 96 (100), 79 (27), 68 (66), 66 (24), 52
(18); HRMS: Calcd for C9H10N2O: 162.0793; found: 162.0792.
1553, 1520, 1510, 1190, 853, 722, 534 cmÀ1 1H NMR (500 MHz, CDCl3):
;
d=7.26 (d, J=7.6 Hz, 2H), 6.29 (d, J=7.5 Hz, 2H), 3.76 (t, J=7.3 Hz,
2H), 2.19 (td, J=6.8, 2.6 Hz, 2H), 1.94 (t, J=2.6 Hz, 1H), 1.85 (quin, J=
7.5 Hz, 2H), 1.48 ppm (quin, J=7.3 Hz, 2H); 13C-DEPT NMR
(125 MHz, CDCl3): d=178.7 (C), 139.5 (CH), 118.7 (CH), 82.8 (C), 69.4
(CH), 56.3 (CH2), 29.6 (CH2), 24.6 (CH2), 17.8 ppm (CH2); MS (70 eV,
EI): m/z (%): 175 (64) [M+], 146 (31), 121 (28), 120 (23), 108 (100), 82
(23), 67 (10), 53 (13); HRMS: Calcd for C11H13NO: 175.0997; found:
175.0998.
1-(5-Hexynyl)-2-pyrazinone (17): A mixture of 2-pyrazinone (216 mg,
2.23 mmol), 6-iodo-1-hexyne (521 mg, 2.50 mmol)[56] and K2CO3 (623 mg,
4.51 mmol) in CH3CN (50 mL) was stirred under reflux for 19 h. The
mixture was allowed to cool to room temperature, concentrated on a
rotary evaporator, and extracted with CH2Cl2 and H2O. The combined or-
ganic phases were dried over MgSO4, filtered, and concentrated. Chro-
matography (CH2Cl2/MeOH 20:1) furnished 17 (237 mg, 60%). Colorless
oil; IR (KBr): n˜ =3225, 3085, 2960, 2905, 1655, 1630, 1580, 1560, 1490,
1460, 1430, 1375, 1340, 1310, 1285, 1240, 1210, 1155, 1120, 1090, 1015,
N-(4-Pentynoyl)-4-pyridone (13) and pyridin-4-yl pent-4-ynoate (14): To
a solution of 4-pyridone (1.04 g, 10.9 mmol) in CH2Cl2 (20 mL) at room
temperature was added
a solution of 4-pentynoyl chloride (625 mg,
920, 820, 740, 720, 625, 585, 555, 525 cmÀ1 1H NMR (CDCl3, 300 MHz):
;
5.46 mmol) in CH2Cl2 (5 mL) over 3 min. After 30 min, the reaction mix-
ture was transferred via canula to a Schlenk flask fitted with a glass frit.
The mixture was filtered through the frit into another Schlenk flask and
concentrated in vacuo to give a solid consisting of 13 and 14 (545 mg,
58%) in an approximate ratio of 3:2( 1H NMR). White solid; 1H NMR
(300 MHz, CD2Cl2) signals attributable to 13: d=8.10 (dd, J=8.2Hz,
2H), 6.28 (d, J=8.3 Hz, 2H), 3.10 (t, J=6.9 Hz, 2H), 2.68 (td, J=7.3,
2.6 Hz, 2H), 2.08 ppm (t, J=2.6 Hz, 1H). Chromatography of the mix-
ture (MeOH) afforded only 14 contaminated with methyl 4-pentynoate.
Colorless oil; IR (film): n˜ =3298, 3061, 2943, 2118, 1763, 1593, 1470,
d=8.14 (d, J=1.2Hz, 1H), 7.32 (d, J=4.4 Hz, 1H), 7.09 (dd, J=4.4,
1.2Hz, 1H), 3.92(t, J=7.3 Hz, 2H), 2.27 (td, J=6.9, 2.6 Hz, 2H), 1.97 (t,
J=2.6 Hz, 1H), 1.95–1.85 (m, 2H), 1.63–1.53 ppm (m, 2H); 13C NMR
(CDCl3, 100 MHz): d=156.2, 149.7, 128.6, 124.0, 84.4, 69.3, 48.9, 27.8,
25.2, 18.0 ppm; MS (70 eV, EI): m/z (%): 176 (30) [M+], 175 (30), 159
(19), 147 (15), 137 (38), 134 (100), 120 (11), 110 (38), 96 (60), 79 (75), 68
(60), 53 (27); HRMS: Calcd for C10H12N2O: 176.0948; found: 176.0950. A
subsequent fraction gave 2-(5-hexynyloxy)pyrazine (103 mg, 26%). Col-
orless oil; IR (KBr): n˜ =3300, 3060, 2950, 2870, 2115, 1580, 1535, 1470,
1415, 1380, 1310, 1290, 1195, 1180, 1155, 1060, 1050, 1000, 950, 920, 840,
1434, 1196, 1128, 734, 647 cmÀ1 1H NMR (500 MHz, CDCl3): d=8.60 (d,
;
J=5.6 Hz, 2H), 7.10 (d, J=6.1 Hz, 2H), 2.80 (t, J=7.2Hz, 2H), 2.59 (td,
J=7.3, 2.6 Hz, 2H), 2.02 ppm (t, J=2.6 Hz, 1H); 13C NMR-DEPT
(125 MHz, CDCl3): d=168.9 (C), 157.2(C), 151.4 (CH), 116.8 (CH), 81.6
1
750, 735, 640, 610, 540 cmÀ1; H NMR (CDCl3, 300 MHz): d=8.22 (d, J=
1 Hz, 1H), 8.08 (ABm, 2H), 4.33 (t, J=6.4 Hz, 2H), 2.28 (td, J=7.1,
2.6 Hz, 2H), 1.96 (t, J=2.6 Hz, 1H), 1.96–1.87 (m, 2H), 1.75–1.65 ppm
7456
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 7443 – 7465

Cobalt-Mediated Reactions
FULL PAPER
(m, 2H); 13C NMR (CDCl3, 100 MHz): d=160.4, 140.6, 136.5, 136.1, 84.0,
68.9, 65.8, 27.9, 25.1, 18.2 ppm; MS (70 eV, EI): m/z (%): 176 (4) [M+],
175 (12), 147 (58), 135 (6), 120 (7), 107 (6), 96 (90), 79 (100), 68 (68), 53
(32); HRMS: Calcd for C10H12N2O: 176.0948; found: 176.0950.
(d, J=7.3 Hz, 1H), 6.37 (d, J=7.3 Hz, 1H), 3.57 (s, 3H), 2.92 (m, 2H),
2.88 (m, 2H), 1.83 ppm (m, 4H); 13C NMR-DEPT (125 MHz, CDCl3):
d=142.4 (C), 137.0 (C), 134.8 (C), 131.4 (CH), 127.4 (CH), 125.5 (CH),
105.7 (CH), 36.9 (CH3), 29.8 (CH2), 29.4 (CH2), 23.1 (CH2), 22.9 ppm
(CH2), signals for the carbonyl and one quaternary carbon not detected;
MS (70 eV, EI): m/z (%): 213 (100) [M+], 212 (72), 198 (12), 185 (26),
128 (12), 115 (17); HRMS: Calcd for C14H15NO: 213.1154; found:
213.1155.
N,N’-Di(3-butynyl)-2,3-pyrazinedione (18): To a solution of 1,4-dihydro-
2,3-pyrazinedione (300 mg, 2.68 mmol) in DMSO (50 mL) was added a
60% NaH dispersion (235 mg, 5.87 mmol) under H2 evolution. After
10 min, 3-butynyl tosylate (1.26 g, 5.632 mmol)[52] was added and the mix-
ture stirred at room temperature for 3.5 days. The DMSO was removed
under high vacuum, the brown residue transferred into a separatory
funnel, extracted with CH2Cl2/H2O, and the combined organic layers
dried over MgSO4, filtered and concentrated. Column chromatography
(CH2Cl2/MeOH 20:1) delivered compound 18 (227 mg, 39%). White
solid; IR (KBr): n˜ =3245, 3110, 2960, 2115, 1685, 1655, 1640, 1590, 1460,
Compound 20c: Orange oil; IR (film): n˜ =2928, 2855, 1615, 1435, 1265,
1
805, 335 cmÀ1; partial H NMR (300 MHz, C6D6): d=4.52(s, 5H), 4.46 (s,
5H), 3.99 (d, J=3.0 Hz, 1H), 3.15 (s, 3H), 2.92 (d, J=3.7 Hz, 1H), 2.75
(m, 1H), 2.50–1.40 (m, 19H), 0.80 (d, J=7.7 Hz, 1H), 0.68 ppm (d, J=
6.6 Hz, 1H); MS (70 eV, EI): m/z (%): 569 (100) [M+], 503 (8), 445 (33),
443 (23), 441 (32), 380 (41), 378 (67), 376 (30), 337 (11), 317 (10), 256
(25), 191 (23), 189 (52), 187 (33), 171 (12), 124 (39). HRMS: Calcd for
C32H37Co2NO: 569.1539; found: 569.1541.
1420, 1385, 1320, 1275, 1225, 1175, 1000, 815, 720, 685, 625, 575, 525 cmÀ1
;
1H NMR (CDCl3, 300 MHz): d=6.28 (s, 2H), 3.91 (t, J=6.5 Hz, 4H),
2.65 (td, J=6.5, 2.6 Hz, 4H), 2.02 (t, J=2.6 Hz, 2H); 13C NMR (CDCl3,
100 MHz): d=155.7, 113.4, 80.4, 71.2, 48.0, 18.1; MS (70 eV, EI): m/z
(%): 216 (100) [M+], 177 (11), 164 (94), 149 (31), 112(47), 97 (26), 83
(18), 69 (20); HRMS: Calcd for C12H12N2O2: 217.0932; found: 217.0933.
Fractions C were concentrated and rechromatographed (hexanes/EtOAc
2:1) to give 20a (48.3 mg, 12.4%). Orange waxy solid; m.p. 76–788C; IR
(KBr): n˜ =3091, 2927, 2852, 1623, 1432, 802 cmÀ1 1H NMR (500 MHz,
;
C6D6): d=4.50 (s, 5H), 4.43 (s, 5H), 3.78 (d, J=2.7 Hz, 1H), 3.54 (dd,
J=8.89, 4.2Hz, 1H), 3.01 (s, 3H), 2.86 (d, J=4.2Hz, 1H), 2.54 (d, J=
3.1 Hz, 1H), 2.50 (br s, 1H), 2.43 (dt, J=16.1, 6.4 Hz, 1H), 2.38 (dt, J=
8.8, 3.4 Hz, 1H), 2.26 (m, 2H), 2.13 (m, 3H), 1.97 (m, 3H), 1.87 (m, 4H),
1.73 (m, 1H), 1.67 (m, 1H), 1.57 (m, 2H), 0.60 ppm (br s, 1H);
13C NMR-DEPT (125 MHz, C6D6): d=169.5 (C), 95.1 (C), 93.3 (C), 93.0
(C), 92.0 (C), 81.5 (CH, Cp), 81.3 (CH, Cp), 57.1 (CH), 55.1 (CH), 54.1
(CH), 53.0 (CH), 48.4 (CH), 45.2 (CH), 43.6 (CH), 42.1 (CH), 32.8
(CH3), 29.7 (CH2), 29.63 (CH2), 29.59 (CH2), 29.3 (CH2), 24.3 (CH2), 24.2
(CH2), 24.0 (CH2), 23.9 ppm (CH2); MS (70 eV, EI): m/z (%): 569 (52)
[M+], 503 (8), 445 (10), 444 (10), 380 (10), 257 (17), 256 (100), 252 (10),
187 (10), 124 (7); HRMS: Calcd for C32H37Co2NO: 569.1539; found:
569.1536.
N,N’-Di(4-pentynyl)-2,3-pyrazinedione (19): To a solution of 1,4-dihydro-
2,3-pyrazinedione (349 mg, 3.11 mmol) in DMSO (50 mL) was added a
60% NaH dispersion (270 mg, 6.75 mmol) generating H2. After 10 min,
4-pentynyl tosylate (1.49 g, 6.24 mmol)[58] was added and the mixture
stirred at room temperature for 18 h. Purification as for 18 provided 19
(458 mg, 60%). White solid; IR (KBr): n˜ =3245, 2945, 1685, 1675, 1650,
1590, 1460, 1425, 1335, 1315, 1275, 1220, 1005, 860, 805, 765, 725, 680,
575, 540, 510 cmÀ1 1H NMR (CDCl3, 300 MHz): d=6.39 (s, 2H), 3.90 (t,
;
J=6.9 Hz, 4H), 2.26 (td, J=6.9, 2.6 Hz, 4H), 2.02 (t, J=2.6 Hz, 2H),
1.94 ppm (quin, J=6.9 Hz, 4H); 13C NMR (CDCl3, 100 MHz): d=155.8,
113.1, 82.5, 69.9, 47.8, 26.5, 15.7 ppm; MS (70 eV, EI): m/z (%): 244 (84)
[M+], 227 (9), 215 (5), 192 (100), 175 (10), 163 (18), 150 (20), 136 (22),
126 (54), 120 (35), 108 (22), 97 (21), 81 (18), 65 (35), 55 (22); HRMS:
Calcd for C14H16N2O2: 244.1212; found: 244.1217.
Fractions D were concentrated and rechromatographed (hexanes/EtOAc
1:1) to give a 1:1 mixture of 20d and 20e (29 mg, 7.5%) and pure 20b
(8.6 mg, 2.2%).
Cobalt-mediated cycloaddition of N-methyl-2-pyridone to 1,7-octadiyne:
To a refluxing solution of N-methyl-2-pyridone (985 mg, 9.03 mmol) in
dry THF (40 mL) was added 1,7-octadiyne (180 mL, 144 mg, 1.36 mmol)
Mixture 20d/e (1:1): Orange oil; 1H NMR (500 MHz, C6D6): d=4.44 (s,
5H, Cp), 4.39 (s, 5H, Cp), 4.32(s, 5H, Cp), 4.27 (s, 5H, Cp), 3.57 (br s,
2H), 3.52 (d, J=4.4 Hz, 1H), 3.44 (br s, 1H), 3.34 (br s, 1H), 3.16 (dd,
J=9.0, 3.6 Hz, 1H), 2.97 (m, 1H), 2.83 (d, J=3.6 Hz, 1H), 2.78 (d, J=
3.6 Hz, 1H), 2.76 (d, J=3.6 Hz, 1H), 2.71 (s, 3H, N-Me), 2.57 (s, 3H, N-
Me), 2.50–0.70 ppm (m, 38H); 13C NMR (125 MHz, C6D6): d=170.9,
170.5, 93.8, 93.1, 91.8, 91.5, 83.5 (Cp), 83.0 (Cp), 80.5 (2Cp), 73.8, 69.7,
67.4, 63.8, 61.6, 58.4, 56.7, 53.8, 52.4, 50.5, 50.4, 49.7, 48.0, 46.4, 45.0, 44.8,
43.1, 41.2, 37.1, 31.6, 30.0, 29.8, 29.5, 29.4, 29.2, 29.0, 28.9, 28.8, 28.7, 28.4,
27.5, 27.3, 23.60, 23.58, 23.5, 23.3, 23.2, 22.8 ppm; MS (70 eV, EI): m/z
(%): 569 (59) [M+], 501 (5), 445 (17), 378 (21), 376 (26), 339 (17), 257
(19), 256 (100), 252 (8), 189 (10), 187 (16), 124 (13).
in THF (8 mL) and [CpCo(C2H4)2] (268 mg, 1.49 mmol) in THF (8 mL)
R
via separate syringes over a period of 110 min. After a total of 2.5 h, the
mixture was concentrated in vacuo and the residue subjected to chroma-
tography (hexanes/EtOAc 3:1) to yield five sets of fractions A, B, C, D,
and E, in order of increasing polarity. Fractions A were rechromato-
graphed (hexanes/EtOAc 100:1–20:1) to afford trimer 24 (13 mg, 9%)[24]
preceded by diene complex 25 (7.1 mg, 2%). Red-brown oil; UV/Vis
(CH3OH): lmax (loge)=260 (4.00), 348 (2.90), 389 (2.78) nm; IR (thin
film): n˜ =2936, 2841, 1450, 1437, 1354, 1165, 1114, 1016, 806 cmÀ1
;
1H NMR (300 MHz, C6D6): d=4.59 (s, 5H), 2.98 (d, J=2.4 Hz, 2H), 2.42
(dt, J=16.2, 6.2 Hz, 2H), 2.17 (dt, J=16.0, 6.3 Hz, 2H), 2.03 (m, 2H),
1.71 (m, 2H), 1.62 (AA ’m, 2H), 0.97 ppm (BB’m, 2H); 13C NMR
(75 MHz, C6D6): d=93.8, 80.6, 50.4, 29.5, 26.2, 24.0 ppm; MS (EI, 70 eV):
m/z (%): 258 (100) [M+], 256 (70), 252 (58), 188 (73), 187 (80), 124 (12);
HRMS: Calcd for C15H19Co: 258.0819; found: 258.0818; elemental analy-
sis calcd (%) for C15H19Co: C 69.76, H 7.42; found C 69.66, H 7.48.
Compound 20b: Orange oil; IR (film): n˜ =2924, 2854, 1622, 1456, 1378,
802cm À1 1H NMR (500 MHz, C6D6): d=4.44 (s, 5H), 4.39 (s, 5H), 3.53
;
(d, J=4.4 Hz, 1H), 3.17 (dd, J=9.0, 3.6 Hz, 1H), 2.84 (d, J=3.4 Hz, 1H),
2.78 (d, J=3.6 Hz, 1H), 2.76 (d, J=3.3 Hz, 1H), 2.72 (s, 3H), 2.45 (dd,
J=6.0, 1.1 Hz, 1H), 2.40 (dt, J=16.2, 6.4 Hz, 1H), 2.28 (m, 3H), 2.22 (m,
1H), 2.10 (m, 2H), 1.98 (m, 2H), 1.89 (m, 3H), 1.81 (m, 4H), 1.60 ppm
(m, 2H); 13C NMR (125 MHz, C6D6): d=171.0, 94.3, 93.5, 92.2, 91.8,
80.91 (Cp), 80.89 (Cp), 58.7, 52.8, 51.0, 50.7, 48.3, 46.9, 45.5, 41.4, 32.0,
29.8, 29.33, 29.28, 29.2, 24.0, 23.9, 23.6, 23.5 ppm; MS (70 eV, EI): m/z
(%): 569 (36) [M+], 501 (7), 445 (29), 443 (19), 441 (19), 378 (26), 376
(23), 375 (23), 257 (17), 256 (100), 187 (8), 124 (6); HRMS: Calcd for
C32H37Co2NO: 569.1539; found: 569.1540.
Fractions B were concentrated and rechromatographed (hexanes/EtOAc
2:1) to give, in order, 22 (5.3 mg, 1.1%), the aromatic 23 (5.1 mg, 1.8%),
and impure complex 20c (3.7 mg, 1.0%).
Compound 22: Orange oil; IR (film): n˜ =2929, 2360, 1652, 1262, 1094,
1024, 801 cmÀ1 1H NMR (300 MHz, C6D6): d=5.06 (dd, J=8.0, 1.7 Hz,
;
1H), 4.56 (dd, J=8.0, 3.3 Hz, 1H), 4.41 (s, 5H), 3.62(d, J=4.2Hz, 1H),
2.99 (dd, J=12.1, 4.2 Hz, 1H), 2.83 (d, J=4.2 Hz, 1H), 2.59 (s, 3H), 2.32
(m, 3H), 1.99 (m, 2H), 1.77 (m, 2H), 1.53 ppm (m, 2H); 13C NMR
(125 MHz, C6D6): d=170.5, 125.0, 107.9, 93.4, 93.1, 81.4 (Cp), 54.1, 53.4,
45.2, 38.8, 34.1, 30.2, 29.5, 24.0, 23.9 ppm; MS (70 eV, EI): m/z (%): 339
(33) [M+], 338 (21), 337 (100), 271 (54), 269 (29), 267 (13), 215 (13), 214
(14), 187 (8), 172(9); HRMS: Calcd for C 19H22CoNO: 339.1033; found:
339.1034.
Fractions E were concentrated and rechromatographed (hexanes/EtOAc
1:4) to give compound 21 (7.5 mg, 1.6%). Orange oil; IR (film): n˜ =2928,
1663, 1608, 1108, 810 cmÀ1 1H NMR (500 MHz, C6D6): d=5.69 (d, J=
;
9.6 Hz, 1H), 5.58 (d, J=9.6 Hz, 1H), 4.35 (s, 5H), 3.44 (dd, J=10.0,
2.7 Hz, 1H), 2.93 (s, 3H), 2.49 (d, J=4.4 Hz, 1H), 2.31 (d, J=10.7 Hz,
1H), 2.12 (dt, J=16.2, 6.3 Hz, 1H), 2.01 (dt, J=16.3, 6.0 Hz, 1H), 1.94
(dt, J=16.1, 6.0 Hz, 1H), 1.76 (m, 4H), 1.52(m, 1H), 1.42ppm (m, 1H);
13C NMR-DEPT (125 MHz, C6D6): d=161.2(C), 140.4 (CH), 119.5
(CH), 94.1 (C), 93.0 (C), 81.3 (CH, Cp), 60.5 (CH), 50.5 (CH), 48.3
Compound 23: Yellow oil; IR (film): n˜ =2928, 2857, 1647, 1630, 1604,
1
794 cmÀ1; H NMR (500 MHz, CDCl3): d=8.12(s, 1H), 7.19 (s, 1H), 6.95
Chem. Eur. J. 2007, 13, 7443 – 7465
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7457

K. P. C. Vollhardt et al.
(CH), 36.3 (CH), 32.4 (CH3), 29.9 (CH2), 29.2 (CH2), 23.9 (CH2),
23.7 ppm (CH2); MS (70 eV, EI): m/z (%): 339 (52) [M+], 338 (21), 337
(100), 271 (22), 241 (10), 215 (13), 214 (14), 213 (12); HRMS: Calcd for
C19H22CoNO: 339.1033; found: 339.1032.
316 (51), 295 (25), 288 (36); elemental analysis calcd (%) for C23H34Co
NOSi2: C 60.63, H 7.52, N 3.07; found: C 60.35, H 7.64, N 3.18.
Complex 33 from the cocyclization of 2 with BTMSA: N-3-Butynyl-2-
pyridone (2) (147 mg, 1 mmol), [CpCo(C2H4)2] (180 mg, 1 mmol), and
A
Quinolone derivatives 28 and 29 by oxidative demetalation of 21: To a
solution of 21 (8.7 mg, 0.026 mmol) and Et3N (2 0mL, 0.14 mmol) in
MeCN (2mL) at 0 8C was added solid CuCl2·2H2O (23 mg, 0.14 mmol).
After 30 min, the mixture was diluted with CH2Cl2, washed with water
and brine, and dried over Na2SO4. Concentration left a residue which
was purified by chromatography (CH2Cl2/MeOH 20:1) to give a mixture
of 28 and 29 (5.4 mg, 96%) in a ratio of 4:1. Yellow oil; 1H NMR
(300 MHz, CDCl3) signals attributable to 29: d=7.56 (d, J=9.4 Hz, 1H),
7.23 (s, 1H), 7.04 (s, 1H), 6.60 (d, J=9.2Hz, 1H), 3.68 (s, 3H); GC-MS
for 29: m/z (%): 213 (100) [M+], 212 (45), 209 (30), 198 (10), 185 (79),
167 (12), 156 (21), 139 (20), 128 (16), 115 (20), 63 (20). Another run per-
formed as above [21 (5.1 mg, 0.015 mmol), Et3N (2 0mL, 0.14 mmol),
CuCl2·2H2O (24 mg, 0.14 mmol), MeCN (2 mL)] provided uncontaminat-
ed 28 (1 mg, 31%). Yellow oil; IR (film): n˜ =2931, 2858, 1662, 1609,
BTMSA (20 mL) were reacted as in the preceding preparation of 31 and
32 to give complex 33 (153 mg, 35%). Red solid; m.p. 124–1258C; IR
(film): n˜ =2952, 2896, 1666, 1606, 1248, 836, 811 cmÀ1
;
1H NMR
(300 MHz, C6D6): d=6.10 (dd, J=10.1, 4.6 Hz, 1H), 6.06 (d, J=9.0 Hz,
1H), 4.82(s, 1H), 4.52(s, 5H), 4.19 (dt, J=12.1, 8.9 Hz, 1H), 3.28 (quin,
J=5.9 Hz, 1H), 2.36 (d, J=8.9 0 Hz, 1H), 1.48 (dd, J=8.0, 4.6 Hz, 1H),
1.32–1.27 (m, 2H), 0.29 (s, 9H), 0.15 ppm (s, 9H); 13C NMR (125 MHz,
C6D6): d=161.0, 139.3, 124.3, 83.9, 81.6, 78.8, 77.2, 62.1, 60.0, 43.3, 41.0,
32.2, 4.21, 3.31 ppm; MS (70 eV, EI): m/z (%): 441 (38) [M+], 243 (55),
228 (100); elemental analysis calcd (%) for C22H32CoNOSi2: C 59.85, H
7.31, N 3.17; found: C 59.58, H 7.37, N 3.13. Shortening the mixing times
of the reagents to 30 min diminished the yield of 33 (18%) and led to the
detection of the faster eluting 1-[2-(N-2-oxopyridinyl)ethyl]-2,3-bis(trime-
thylsilyl)cyclobudadiene CpCo complex (2.4%). Colorless solid; m.p.
1435, 1398, 1247, 1108, 822 cmÀ1 1H (300 MHz, CDCl3): d=6.06 (dd, J=
;
110–1118C; IR (film): n˜ =2953, 1660, 1585, 1538, 1243, 836 cmÀ1
;
9.7, 2.8 Hz, 1H), 5.88 (dd, J=9.7, 2.6 Hz, 1H), 5.41 (d, J=6.1 Hz, 1H),
5.27 (m, 1H), 4.16 (m, 1H), 3.20 (m, 1H), 2.98 (s, 3H), 2.25 (m, 4H),
1.66 ppm (m, 4H); MS (70 eV, EI): m/z (%): 215 (69) [M+], 214 (100),
213 (22), 186 (72), 173 (28), 172 (48), 158 (20), 144 (18), 129 (22), 128
(22), 115 (29), 91 (16), 77 (12).
1H NMR (500 MHz, C6D6): d=6.66 (dd, J=8.7, 7.1 Hz, 1H), 6.53 (d, J=
9.2Hz, 1H), 6.47 (d, J=4.9 Hz, 1H), 5.45 (dd, J=6.3, 5.6 Hz, 1H), 4.77
(s, 5H), 3.97 (s, 1H), 3.62 (m, 2H), 2.28 (m, 1H), 2.12 (m, 1H), 0.16 (s,
9H), 0.13 ppm (s, 9H); 13C NMR (125 MHz, C6D6): d=161.8, 138.8,
137.8, 121.4, 104.2, 87.9, 79.4, 73.3, 68.8, 49.8, 30.0, 0.83, 0.27 ppm, one cy-
clobutadienylcarbon signal not detected; MS (70 eV, EI): m/z (%): 441
(13) [M+], 346 (100), 294 (32), 248 (23); HRMS: Calcd for
C22H32CoNOSi2: 441.1355; found: 441.1357.
Complex 30 from cocyclization of N-methyl-4-pyridone with 1,7-octa-
diyne: To a solution of N-methyl-4-pyridone (207 mg, 1.90 mmol) in de-
gassed, refluxing THF (25 mL) was added 1,7-octadiyne (120 mL, 96 mg,
0.91 mmol) in THF (4.5 mL) and [CpCo(C2H4)2] (164 mg, 0.91 mmol) in
T
Oxidative demetalation of 33 to 34:
A
solution of Fe(NO3)3·9H2O
A
THF (4.5 mL) via separate syringes over 75 min. After a further 70 min,
the reaction mixture was concentrated in vacuo and the residue purified
by chromatography (hexanes/EtOAc 1:0–1:1) to afford 24 (11.5 mg,
4.4%), 25 (63.5 mg, 60%), and an impure, polar fraction. This latter ma-
terial was rechromatographed (CH2Cl2/MeOH 20:1) to give complex 30
(100 mg, 0.25 mmol) in MeCN (1 mL) and H2O (1 mL) was added to a
solution of complex 33 (22 mg, 0.05 mmol) in MeCN (1 mL) and THF
(1 mL) at 08C. After stirring for 12min, the mixture was poured into ice
water and extracted with CH2Cl2. The combined organic layers were
washed with H2O, dried over Na2SO4, and the solvent was removed in
vacuo. Chromatography (hexanes/EtOAc 1:2) delivered the free ligand
34 (7.8 mg, 49%). White solid; m.p. 153–1548C; IR (film): n˜ =2957, 1656,
(7.3 mg, 2%). Orange oil; IR (film): n˜ =2927, 1575, 1319, 1241, 806 cmÀ1
;
1H NMR (300 MHz, C6D6): d=5.69 (d, J=7.5 Hz, 1H), 4.81 (d, J=
7.5 Hz, 1H), 4.37 (s, 5H), 3.63 (d, J=4.1 Hz, 1H), 3.19 (dd, J=11.4,
3.6 Hz, 1H), 2.93 (dd, J=10.7, 4.4 Hz, 1H), 2.79 (d, J=3.6 Hz, 1H), 2.39
(dt, J=16.5, 7.4 Hz, 1H), 2.17 (s, 3H), 1.94 (m, 2H), 1.72 (m, 2H), 1.53
(m, 2H), 1.33 ppm (m, 1H); 13C NMR (125 MHz, C6D6): d=150.8, 94.3,
92.4, 91.8, 81.0 (Cp), 59.2, 52.7, 47.8, 40.5, 29.1, 28.8, 23.3, 23.2 ppm, sig-
nals for the carbonyl and one alkenyl carbon not observed; MS (70 eV,
EI): m/z (%): 339 (18) [M+], 257 (17), 256 (100), 252 (11), 213 (35), 212
(19), 187 (14), 159 (6), 124 (8).
1608, 1420, 1249, 837 cmÀ1 1H NMR (500 MHz, C6D6): d=5.97 (dd, J=
;
10.1, 3.3 Hz, 1H), 5.86 (d, J=2.1 Hz, 1H), 5.69 (dd, J=10.1, 2.2 Hz, 1H),
4.76 (m, 1H), 3.62(dd, J=12.6, 2.2 Hz, 1H), 3.54 (d, J=12.6 Hz, 1H),
2.41 (m, 1H), 2.11 (m, 1H), 1.92 (dd, J=17.5, 8.0 Hz, 1H), 0.18 (s, 9H),
0.15 ppm (s, 9H); 13C NMR (100 MHz, C6D6): d=166.1, 146.9, 141.8,
139.7, 136.8, 123.4, 118.9, 58.3, 45.1, 36.1, 29.1, 2.2, 1.5 ppm; MS (70 eV,
EI): m/z (%): 317 (50) [M+], 316 (100), 302 (11), 274 (11), 244 (17), 228
(16), 73 (49); elemental analysis calcd (%) for C17H27NOSi2: C 64.29, H
8.57, N 4.41; found: C 64.06, H 8.81, N 4.10.
Complexes 31 and 32 from the reaction of 1, BTMSA, and [CpCo-
ACHTREUNG
Cocyclization of 5 with BTMSA: Heptynylpyridone 5 (189 mg, 1 mmol),
AHCTREUNG
[CpCo(C2H4)2] (180 mg, 1 mmol), and BTMSA (20 mL) were treated as
in the preparation of 31 and 32 to generate 1-[5-(N-2-oxopyridinyl)pen-
N
1 mmol) in dry, degassed THF (2mL) were added simultaneously over
1 h to degassed BTMSA (15 mL). Subsequently, the mixture was stirred
for 1 h, THF and excess BTMSA removed in vacuo, and the residue puri-
fied by chromatography (hexane/EtOAc 1:1) to give compounds 31
(32.9 mg, 7.7%) and 32 (134 mg, 29%).
tyl]-2,3-bis(trimethylsilyl)cyclobudadiene CpCo complex (132 mg, 27%).
Light yellow oil; IR (film): n˜ =2918, 1662, 1591, 1539, 1245, 837 cmÀ1
;
1H NMR (500 MHz, C6D6): d=6.66 (t, J=6.9 Hz, 1H), 6.53 (d, J=
9.2Hz, 1H), 6.35 (d, J=6.1 Hz, 1H), 5.45 (t, J=6.4 Hz, 1H), 4.78 (s,
5H), 4.17 (s, 1H), 3.53 (m, 2H), 1.79 (t, J=7.6, 2H), 1.49 (m, 2H), 1.36–
1.24 (m, 2H), 1.12 (m, 2H), 0.22 (s, 9H), 0.16 ppm (s, 9H); 13C NMR
(125 MHz, C6D6): d=162.0, 138.5, 137.5, 121.4, 104.2, 92.7, 79.3, 68.8,
66.7, 64.2, 49.2, 30.3, 29.5, 29.3, 26.7, 0.90, 0.34 ppm; MS (70 eV, EI): m/z
(%): 483 (100) [M+], 410 (9), 385 (6), 320 (11), 313 (15), 294 (12), 152
(12), 73 (22); elemental analysis calcd (%) for C25H38CoNOSi2: C 62.08,
H 7.92, N 2.90; found: C 61.90, H 7.85, N 2.58.
Complex 31: Yellow solid; m.p. 93–958C; IR (film): n˜ =2954, 1662, 1588,
1538, 1438, 1246, 839 cmÀ1 1H NMR (500 MHz, C6D6): d=6.90 (d, J=
;
6.2Hz, 1H), 6.62(dd, J=7.5, 6.8 Hz, 1H), 6.52(d, J=9.2Hz, 1H), 5.49
(dd, J=6.5, 6.4 Hz, 1H), 4.71 (s, 5H), 4.32(d, J=15.1 Hz, 1H), 4.21 (d,
J=15.1 Hz, 1H), 4.18 (s, 1H), 0.17 (s, 9H), 0.07 ppm (s, 9H); 13C NMR
(125 MHz, C6D6): d=161.7, 138.5, 136.3, 121.1, 104.3, 84.2, 79.5, 70.0,
69.1, 66.6, 47.1, 0.60, 0.17 ppm; MS (70 eV, EI): m/z (%): 427 (56) [M+],
333 (100), 163 (57), 152 (33), 147 (22); elemental analysis calcd (%) for
C21H30CoNOSi2: C 58.99, H 7.07, N 3.27; found: C 58.75, H 7.32, N 3.54.
Cyclization of 7 to 35: Decadiyne 7 (330 mg, 1.45 mmol) was dissolved in
dry, degassed THF (10 mL) and added during 4 h to a solution of [CpCo-
Complex 32: Dark red solid; m.p. 117–1188C; IR (film): n˜ =2955, 1736,
1659, 1588, 1538, 1438, 1246, 839 cmÀ1 1H NMR (400 MHz, C6D6): d=
;
(C2H4)2] (287 mg, 1.59 mmol) in THF (50 mL). The mixture was stirred
overnight at room temperature. The solvent was removed in vacuo and
the residue was purified by chromatography (hexane/EtOAc 2:1) to give
unreacted starting material (89 mg, 27%) and complex 35 (219 mg, 43%,
59% based on consumed starting material). Red crystals; m.p. 126–
1278C; IR (film): n˜ =2800, 2934, 1655, 1593, 1539, 1435, 1280, 1143, 868,
6.69 (d, J=5.8 Hz, 1H), 6.64 (d, J=6.9 Hz, 1H), 6.56 (d, J=8.9 Hz, 1H),
5.48 (dd, J=6.8, 6.2Hz, 1H), 5.41 (s, 1H), 4.57 (s, 5H), 3.94 (d, J=
13.3 Hz, 1H), 3.77 (d, J=13.3 Hz, 1H), 1.43–1.35 (m, 2H), 0.87 (m, 2H),
0.38 (s, 9H), 0.17 ppm (s, 9H); 13C NMR (100 MHz, C6D6): d=162.2,
138.4, 137.3, 121.7, 103.9, 87.7, 85.9, 80.8, 74.2, 67.2, 57.9, 30.3, 25.8, 2.46,
2.39 ppm; MS (70 eV, EI): m/z (%): 455 (41) [M+], 389 (100), 361 (78),
806 cmÀ1
;
7458
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 7443 – 7465

Cobalt-Mediated Reactions
FULL PAPER
1H NMR (500 MHz, C6D6, assignments according
to the numbering in the structure shown): d=6.07
(d, J=10.0 Hz, 1H, H3), 5.62(dd, J=10.0, 4.0 Hz,
2.44, 1.24 ppm, signal for carbonyl not observed; MS (70 eV, EI): m/z
(%): 469 (52) [M+], 467 (19), 385 (32), 344 (17), 330 (16), 133 (19), 124
(12), 108 (37), 84 (100), 73 (77); HRMS: Calcd for C24H36CoNOSi2:
469.1668; found: 469.1671.
1H, H4), 5.19 (d, J=10.8 Hz,1H, H11), 4.25 (s,
5H, Cp), 2.40 (br s, 1H, H10), 2.37 (d, J=8.0 Hz,
1H, H6), 2.28(m, 1H, H16), 2.22–2.06 (m, 4H,
H11, H13, H14, H16), 2.05–1.85 (m, 2H, H13,
H14), 1.64 (m, 1H, H12), 1.50–1.46 (m, 2H, H5,
Complex 36: In a manner similar to the conversion of 9 described above,
compound 11 (140 mg, 0.864 mmol) in 1,4-dioxane (7 mL) and [CpCo-
A
(10 mL) over 2h. After a total of 2.5 h, the mixture chromatographed
(CH2Cl2/MeOH 20:1) to provide 36 (192mg, 47%) and 1-[3-( N-4-oxopyr-
idyl)propyl]-2,3-bis(trimethylsilyl)cyclobutadiene CpCo (70 mg, 15%).
H15), 1.38 (m, 1H, H12), 1.27 ppm (m, 1H, H15); 13C NMR (500 MHz,
C6D6): d=161.5 (C2), 140.2 (C4), 122.2 (C3), 98.5 (C9 or C8), 97.0 (C8 or
C9), 80.7 (5C, Cp), 64.8 (C7), 61.1 (C6), 50.1 (C10), 42.9 (C11), 36.3 (C5),
Complex 36: Red crystals (from CH2Cl2/hexanes); m.p. 168–1698C; IR
33.1 (C15), 32.5(C16), 29.8 (C14), 24.8 (C12), 24.5 ppm (C13); MS
U
(KBr): n˜ =2961, 1595, 1244, 1230, 1173, 837, 730 cmÀ1
;
1H NMR
(70 eV, EI): m/z (%): 351 (98) [M+], 349 (100), 281 (44), 254 (51), 227
(20), 225 (32), 198 (35); elemental analysis calcd (%) for C20H22CoNO: C
68.37, H 6.31, N 3.99; found: C 68.94, H 6.38, N 3.95.
(300 MHz, C6D6): d=6.06 (d, J=7.6 Hz, 1H), 4.94 (d, J=7.7 Hz, 1H),
4.68 (s, 5H), 4.48 (s, 1H), 2.58 (dd, J=12.6, 5.0 Hz, 1H), 2.35 (d, J=
8.8 Hz, 1H), 2.24 (td, J=10.4, 2.0 Hz, 1H), 1.56 (m, 1H), 1.47 (d, J=
8.8 Hz, 1H), 1.08 (m, 3H), 0.57 (s, 9H), 0.41 ppm (s, 9H); 13C NMR-
DEPT (125 MHz, C6D6): d=191.6 (C), 150.7 (CH), 97.7 (CH), 87.6 (C),
82.9 (CH), 81.9 (CH, Cp), 70.5 (C), 66.2 (CH), 63.5 (C), 53.4 (CH2), 50.0
(CH), 34.8 (CH2), 24.9 (CH2), 5.66 (CH3), 3.59 ppm (CH3); MS (70 eV,
EI): m/z (%): 455 (97) [M+], 440 (9), 390 (8), 362(10), 331 (31), 330
(100), 316 (46), 314 (35), 242 (33), 124 (7), 73 (17); HRMS: Calcd for
C23H34CoNOSi2: 455.1511; found: 455.1515.
Reaction of 9, BTMSA, and [CpCo
BTMSA (15 mL) at room temperature was added 9 (149 mg, 1.12mmol)
in 1,4-dioxane (6 mL) and EtOH (3 mL), and [CpCo(C2H4)2] (220 mg,
A
AHCTREUNG
1.22 mmol) in THF (8.5 mL) via separate syringes over a period of 2.5 h.
After a total of 4 h, the solvent was removed and the residue subjected
to chromatography (CH2Cl2/MeOH 20:1) to afford 1-(N-4-oxopyridyl)-
methyl-2,3-bis(trimethylsilyl)cyclobutadiene CpCo (232 mg) and a mixed
fraction, purified by HPLC (C18, 100% MeOH), containing more of this
complex (7 mg, for a total of 239 mg, 50%) and 1Z,3E-5-(N-4-oxopyrid-
yl)-1,2-bis(trimethylsilyl)-1,3-pentadiene (8 mg, 2.4%).
Cyclobutadiene complex: Yellow crystals (from Et2O); m.p. 155–1578C;
IR (KBr): n˜ =3060, 2952, 1638, 1562, 1244, 1188, 851, 835, 808 cmÀ1
;
1H NMR (500 MHz, CDCl3) d=7.23 (d, J=6.9 Hz, 2H), 6.38 (d, J=
6.9 Hz, 2H), 4.81 (s, 5H), 4.14 (s, 1H), 3.75 (m, 2H), 1.95 (m, 2H), 1.84
(m, 2H), 0.082 (s, 9H), 0.061 ppm (s, 9H); 13C NMR (125 MHz, CDCl3)
d=139.4, 118.9, 89.4, 79.0 (Cp), 68.0, 67.0, 65.0, 56.5, 30.8, 26.9, 0.66,
0.039 ppm, carbonyl signal not observed; MS (70 eV, EI): m/z (%): 455
(55) [M+], 430 (25), 358 (39), 357 (28), 322 (100), 314 (29), 285 (27), 175
(36), 149 (29), 108 (72), 69 (41), 57 (52); elemental analysis calcd (%) for
C23H34CoNOSi2: C 60.63, H 7.52, N 3.07; found: C 60.32, H 7.51, N 3.10.
Cyclobutadiene complex. Yellow crystals; m.p. 148–1508C; IR (KBr): n˜ =
2955, 2898, 2192, 1638, 1560, 1248, 1156, 840, 814, 727 cmÀ1 1H NMR
;
(500 MHz, CDCl3): d=7.22 (d, J=7.3 Hz, 2H), 6.26 (d, J=7.4 Hz, 2H),
4.82 (s, 5H), 4.25 (s, 1H), 4.21 (d, J=14.8 Hz, 1H), 4.16 (d, J=14.8 Hz,
1H), 0.013 (s, 9H), 0.0024 ppm (s, 9H); 13C NMR (125 MHz, CDCl3): d=
178.8 (br), 138.8, 118.3 (br), 80.9, 79.1 (Cp), 69.2, 68.8, 67.8, 55.7, 0.31,
À0.23 ppm; MS (70 eV, EI): m/z (%): 427 (20) [M+], 354 (11). 334 (17),
333 (54), 163 (28), 124 (32), 108 (22), 73 (100); elemental analysis calcd
(%) for C21H30CoNOSi2: C 58.99, H 7.07, N 3.28; found: C 58.60, H 7.20,
N 3.25.
Reaction of 12, BTMSA, and [CpCo
conversion of 9 described above, 12 (177 mg, 1.00 mmol) in 1,4-dioxane
(8 mL) and EtOH (1 mL) and [CpCo(C2H4)2] (198 mg, 1.10 mmol) in
(C2H4)2]: In a manner similar to the
AHCTREUNG
Pentadienylpyridone: Colorless oil; IR (film): n˜ =3365, 2954, 2898, 1641,
THF (9 mL) were added to BTMSA (20 mL) over 2.25 h. After a total of
3.25 h, the mixture was (CH2Cl2/MeOH 15:1) to deliver 1-[4-(N-4-oxopyr-
idyl)butyl]-2,3-bis(trimethylsilyl)cyclobutadiene CpCo (158 mg, 34%).
Yellow-black crystals (from Et2O); m.p. 151–1538C; IR (KBr): n˜ =3078,
1557, 1249, 1180, 837 cmÀ1 1H NMR (300 MHz, C6D6): d=6.59 (s, 1H),
;
6.34 (d, J=7.4 Hz, 2H), 6.27 (d, J=7.8 Hz, 2H), 6.00 (d, J=15.2Hz,
1H), 5.14 (dt, J=15.3, 6.3 Hz, 1H), 3.16 (dd, J=6.2, 1.2 Hz, 2H), 0.19 (s,
9H), 0.14 ppm (s, 9H); MS (70 eV, EI): m/z (%): 305 (24) [M+], 290 (5),
225 (9), 168 (47), 123 (48), 73 (100).
3036, 2947, 2897, 1637, 1570, 1244, 1194, 856, 807 cmÀ1
;
1H NMR
(500 MHz, CDCl3): d=7.34 (d, J=6.9 Hz, 2H), 6.51 (d, J=6.9 Hz, 2H),
4.80 (s, 5H), 4.12(s, 1H), 3.80 (m, 2H), 1.92(m, 2H), 1.78 (m, 2H), 1.38
(m, 2H), 0.89 (s, 9H), 0.048 ppm (s, 9H); 13C NMR (125 MHz, CDCl3:
d=178.8, 139.5, 118.8, 90.9, 78.9 (Cp), 73.0, 68.2, 64.7, 50.8, 30.7, 29.6,
26.1, 0.65, 0.046 ppm; MS (70 eV, EI): m/z (%): 469 (100) [M+], 454 (7),
371 (51), 299 (51), 294 (16), 272 (12), 124 (30), 108 (14), 73 (83); elemen-
tal analysis calcd (%) for C24H36CoNOSi2: C 61.38, H 7.73, N 2.98;
found: C 60.90, H 7.59, N 2.98.
Reaction of 10, BTMSA, and [CpCo
conversion of 9 described above, compound 10 (87.5 mg, 0.591 mmol) in
1,4-dioxane (5 mL) and [CpCo(C2H4)2] (112mg, 0.623 mmol) in THF
A
AHCTREUNG
(5 mL) were added to BTMSA (7 mL) over 1.5 h. After a total of 3 h,
the mixture was chromatographed (CH2Cl2/MeOH 10:1) to afford 1-[2-
(N-4-oxopyridyl)ethyl]-2,3-bis(trimethylsilyl)cyclobutadiene
CpCo
(50.3 mg) and mixed fractions, purified by HPLC (C18, CH3CN/MeOH
1:4), containing more of this complex (15 mg, for a total of 65.3 mg,
25%) and 1-[2-(N-4-oxopyridyl)ethyl]-3,4-bis(trimethylsilyl)cyclohexa-
diene CpCo (15 mg, 3.3%).
Oxidative demetalation of 36 to 37: To a solution of complex 36 (55 mg,
0.12mmol) in MeCN (1 mL) and THF (1 mL) at 0 8C was added drop-
wise a cooled solution of Fe(NO3)3·9H2O (240 mg, 0.590 mmol) in H2O
G
Cyclobutadiene complex: Yellow crystals (from Et2O); m.p. 138–1418C;
IR (film): n˜ =3229, 2955, 2897, 1640, 1549, 1401, 1244, 1193, 836, 811,
(0.5 mL). After 10 min, the mixture was poured onto H2O (5 mL) and ex-
tracted with CH2Cl2 (3”5 mL). The organic layers were dried over
MgSO4 and concentrated in vacuo, and the residue was chromatographed
(CH2Cl2/MeOH 20:1) to furnish compound 37 (34 mg, 85%). Yellow
solid; m.p. 122–1238C; IR (KBr): n˜ =3439, 2951, 2898, 1624, 1578, 1247,
734 cmÀ1 1H NMR (500 MHz, CDCl3): d=7.15 (d, J=6.4 Hz, 2H), 6.24
;
(d, J=6.6 Hz, 2H), 4.84 (s, 5H), 3.98 (s, 1H), 3.79 (ddd, J=12.8, 5.7,
5.7 Hz, 1H), 3.66 (ddd, J=14.4, 7.7, 7.7 Hz, 1H), 2.34 (m, 2H), 0.13 (s,
9H), 0.41 ppm (s, 9H); 13C NMR (125 MHz, CDCl3): d=139.6, 118.6
(br), 85.2, 79.1 (Cp), 69.0, 67.1, 66.3, 56.9, 32.5, 0.75, À0.11 ppm, signal
for carbonyl not observed; MS (70 eV, EI): m/z (%): 441 (100) [M+], 343
(41), 333 (58), 294 (23), 271 (43), 167 (9), 163 (24), 149 (25), 124 (11), 73
(20); HRMS: Calcd for C22H32CoNOSi2: 441.1354; found: 441.1356.
1197, 858, 833, 758 cmÀ1 1H NMR (500 MHz, CDCl3): d=6.82(d, J=
;
7.7 Hz, 1H), 5.99 (d, J=1.6 Hz, 1H), 5.01 (d, J=7.8 Hz, 1H), 4.30 (dd,
J=10.1, 1.9 Hz, 1H), 3.55 (d, J=10.1 Hz, 1H), 3.44 (dt, J=12.0, 5.3 Hz,
1H), 3.35 (ddd, J=13.6, 8.7, 5.0 Hz, 1H), 2.32 (m, 2H), 1.75 (m, 2H),
0.22 (s, 9H), 0.20 ppm (s, 9H); 13C NMR-DEPT (125 MHz, CDCl3): d=
192.7 (C), 152.9 (CH), 146.2 (C), 144.8 (C), 130.6 (C), 127.1 (CH), 100.9
(CH), 59.7 (CH), 53.6 (CH2), 45.8 (CH), 28.2 (CH2), 23.9 (CH2), 1.63
(CH3), 1.28 ppm (CH3); MS (70 eV, EI): m/z (%): 331 (18) [M+], 316
(43), 242 (23), 83 (100), 73 (33), 55 (9); elemental analysis calcd (%) for
C18H29NOSi2: C 65.20, H 8.81, N 4.22; found: C 65.10, H 8.82, N 4.30.
Cyclohexadiene complex: Red oil; IR (film): n˜ =2954, 2901, 2838, 1641,
1564, 1246, 1191, 841 cmÀ1 1H NMR (500 MHz, C6D6): d=6.38 (d, J=
;
5.7 Hz, 2H), 6.33 (d, J=6.9 Hz, 2H), 4.52 (s, 5H), 4.24 (s, 1H), 2.85 (m,
2H), 1.61 (dt, J=13.7, 5.8 Hz, 1H), 1.43 (m, 1H), 1.33 (m, 1H), 1.25 (dt,
J=13.7, 8.4 Hz, 1H), 0.90 (dd, J=14.9, 7.5 Hz, 1H), 0.35 (s, 9H), 0.21 (s,
9H), À0.009 ppm (dt, J=13.2, 7.6 Hz, 1H); 13C NMR (125 MHz, C6D6):
d=139.4, 119.1 (br), 85.6, 85.3, 81.0 (Cp), 66.9, 58.7, 53.5, 43.0, 31.7, 25.4,
Aromatization of 37: To a solution of 37 (12.8 mg, 0.039 mmol) in toluene
(1 mL) at 708C was added solid 2,3-dichloro-5,6-dicyano-1,4-benzoqui-
Chem. Eur. J. 2007, 13, 7443 – 7465
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7459

K. P. C. Vollhardt et al.
none (DDQ, 12.5 mg, 0.055 mmol). After 10 min, the mixture was con-
centrated in vacuo and the residue chromatographed (CH2Cl2/MeOH
30:1) to give the aromatized product (1.8 mg, 14%). Orange oil; IR
another 1 h, THF and excess BTMSA removed in vacuo, and the residue
purified by chromatography (hexane/EtOAc 1:2) to return some 41
(16.4 mg, 14%), the exo complex 42 (98.4 mg, 37%, 43% based on con-
verted starting material), and the endo complex 43 (54.6 mg, 20%, 24%
based on converted starting material).
(film): n˜ =2950, 1623, 1590, 1533, 1470, 1240, 1165, 844 cmÀ1 1H NMR
;
(500 MHz, CDCl3): d=7.56 (s, 1H), 7.40 (d, J=7.4 Hz, 1H), 6.23 (d, J=
7.4 Hz, 1H), 4.07 (t, J=5.7 Hz, 2H), 3.01 (t, J=6.2Hz, 2H), 2.19 (quin,
J=6.0 Hz, 2H), 0.38 (s, 9H), 0.37 ppm (s, 9H); 13C NMR-DEPT
(125 MHz, CDCl3): d=179.5 (C), 151.1 (C), 144.6 (C), 141.2(CH), 137.6
(C), 137.1 (CH), 132.2 (C), 124.1 (C), 109.6 (CH), 52.2 (CH2), 27.0
(CH2), 21.3 (CH2), 5.00 (CH3), 2.43 ppm (CH3); MS (FAB): m/z (%): 330
(41) [MH+], 314 (100); HRMS (FAB): Calcd for C18H28NOSi2: 330.1710;
found: 330.1719.
Complex 42: Red solid; m.p. 110–1128C; IR (film): n˜ =2954, 2895, 2849,
1645, 1609, 1473, 1248, 1038, 836 cmÀ1 1H NMR (500 MHz, CDCl3): d=
;
7.60 (s, 1H), 6.65 (s, 1H), 6.03 (AB, 2H), 5.21 (s, 1H), 4.72 (s, 5H), 4.32
(m, 1H), 3.49 (m, 1H), 2.85 (d, J=7.3 Hz, 1H), 2.08 (d, J=7.5 Hz, 1H),
2.04 (m, 1H), 1.90 (m, 1H), 0.41 (s, 9H), 0.29 (s, 3H), 0.08 (s, 3H),
À0.57 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): d=162.3, 149.4, 147.1,
132.5, 127.7, 125.7, 111.1, 108.4, 101.4, 85.1, 82.1 (Cp), 78.4, 64.8, 61.7,
43.7, 43.2, 33.7, 6.21, 5.73, 3.16, 2.22 ppm; MS (70 eV, EI): m/z (%): 535
(100) [M+], 533 (40), 460 (16), 73 (16); HRMS: Calcd for
C27H34CoNO3Si2: 535.1409; found: 535.1407.
Complexes 38 and 39: To stirring, degassed BTMSA (12mL) at room
temperature was added a mixture of 13 and 14 (150 mg, 0.85 mmol) in
1,4-dioxane (7 mL) and [CpCo(C2H4)2] (160 mg, 0.89 mmol) in THF
G
(7 mL) via separate syringes over 80 min. After a total of 1.5 h, the mix-
ture was concentrated in vacuo and the residue chromatographed on alu-
mina (activity III; hexanes/EtOAc 100:1–1:100, then CH2Cl2-CH2Cl2/
MeOH 10:1) to give 38 (10.6 mg, 2.7%) and 39 (11.7 mg, 2.8%).
Complex 43: Brown solid; m.p. 145–1468C; IR (film): n˜ =3449, 2955,
2896, 1649, 1474, 1261, 1037, 834 cmÀ1 1H NMR (500 MHz, CDCl3): d=
;
8.13 (s, 1H), 7.22 (s, 1H), 5.41 (s, 1H), 5.30 (s, 2H), 4.38 (s, 5H), 4.00 (m,
1H), 3.87 (d, J=10.9 Hz, 1H), 3.85 (m, 1H), 1.81 (d, J=10.9 Hz, 1H),
1.31 (m, 2H), 0.44 (br s, 9H), 0.41 ppm (s, 9H); 13C NMR (125 MHz,
CDCl3): d=162.9, 149.4, 145.8, 139.4, 128.3, 109.6, 104.3, 101.3, 93.6, 81.7
(Cp), 77.4, 66.9, 62.9, 62.5, 55.5, 44.6, 32.1, 5.43 (br), 2.65 ppm; MS
(70 eV, EI): m/z (%): 535 (34) [M+], 462(100), 410 (10), 395 (16), 73
(11); elemental analysis calcd (%) for C27H34NO3Si2Co: C 60.48, H 6.35,
N 2.61; found: C 60.38, H 6.41, N 2.65.
Complex 38: Red needles (from THF/pentane); m.p. 157–1608C; IR
(KBr): n˜ =3443, 2948, 1677, 1649, 1612, 1348, 1243, 1225, 855, 832, 810,
735 cmÀ1 1H NMR (500 MHz, CDCl3): d=8.15 (d, J=8.4 Hz, 1H), 5.27
;
(d, J=8.4 Hz, 1H), 4.90 (s, 1H), 4.76 (s, 5H), 3.78 (d, J=6.9 Hz, 1H),
2.93 (ddd, J=18.1, 9.9, 5.6 Hz, 1H), 2.80 (ddd, J=18.1, 10.9, 4.7 Hz, 1H),
2.08 (ddd, J=5.6, 10.9, 15.7 Hz, 1H), 1.81 (ddd, J=14.9, 10.0, 4.7 Hz,
1H), 1.21 (d, J=6.9 Hz, 1H), 0.40 (s, 9H), 0.16 ppm (s, 9H); 13C NMR-
DEPT (125 MHz, CDCl3): d=195.1 (C), 171.0 (C), 138.1 (CH), 107.8
(CH), 88.5 (C), 82.9 (CH), 81.5 (CH, Cp), 67.2 (C), 62.2 (CH), 60.1 (C),
48.6 (CH), 30.9 (CH2), 30.5 (CH2), 4.02(CH 3), 2.90 ppm (CH3); MS
(70 eV, EI): m/z (%): 469 (100) [M+], 454 (10), 404 (23), 376 (29), 330
(94), 256 (49), 124 (9), 84 (42), 73 (34); HRMS: Calcd for
C23H32CoNO2Si2: 469.1304; found: 469.1302.
Anhydrolycorinone 44: A mixture of 42 and 43 (2:1, 29.5 mg, 0.55 mmol)
in THF (1 mL) was treated with Bu4NF (28.8 mg, 1.10 mmol) for 2 h,
before the addition of Fe(NO3)3·9H2O (66.7 mg, 0.165 mmol) in THF
R
(2mL) and H 2O (1 mL). After 2min, the mixture was subjected to aque-
ous work up, dried (MgSO4), and chromatographed (ether/hexane 4:1) to
give 44 (5.9 mg, 41%).[12]
Cocyclization of 3 with BTMSA to give 45: Pentynylpyridone 3 (161 mg,
Complex 39: Red plates (from Et2O); m.p. 1958C (decomp); IR (KBr):
1.00 mmol) and [CpCo(C2H4)2] (180 mg, 1.00 mmol), both dissolved in
C
n˜ =3373, 2957, 1698, 1622, 1245, 846, 810 cmÀ1 1H NMR (500 MHz,
;
degassed THF (2mL each), were added through separate syringes to de-
gassed BTMSA (20 mL) under argon over 1 h at room temperature. Sub-
sequently, solvents were removed in vacuo and the resulting residue chro-
matographed (EtOAc/hexanes 8:2) under N2 to give complex 45 (387 mg,
85%). Dark violet crystals (from pentane/EtOAc); m.p. 198–1998C; IR
(KBr): n˜ =2955, 2897, 1651, 1570, 1538, 1456, 1300, 1245, 1138, 1064, 961,
CDCl3): d=8.07 (d, J=8.4 Hz, 1H), 5.48 (d, J=8.4 Hz, 1H), 4.65 (s,
5H), 3.50 (s, 1H), 3.11 (s, 1H), 2.56 (m, 2H), 2.44 (ddd, J=13.3, 10.1,
6.5 Hz, 1H), 1.98 (dt, J=13.4, 3.8 Hz, 1H), 1.60 (br s, 1H), 0.38 (s, 9H),
0.32ppm (s, 9H); 13C NMR-DEPT (125 MHz, CDCl3): d=193.9 (C),
172.1 (C), 137.3 (CH), 110.0 (CH), 95.0 (C), 87.6 (C), 82.8 (CH, Cp), 82.6
(CH), 77.8 (C), 68.85 (CH), 68.78 (C), 34.0 (CH2), 29.1 (CH2), 4.31
(CH3), 1.59 ppm (CH3); MS (70 eV, EI): m/z (%): 485 (3) [M+], 470 (49),
412 (9), 346 (17), 328 (60), 300 (16), 286 (24), 270 (22), 256 (14), 228 (14),
214 (10), 198 (14), 124 (100), 73 (99); elemental analysis calcd (%) for
C23H32CoNO3Si2: C 56.89, H 6.64, N 2.88; found: C 56.56, H 6.62, N 2.99.
834 cmÀ1 1H NMR (300 MHz, C6D6, assignments
;
according to the numbering in the structure
shown): d=6.62(dd, J=9.1, 1.5 Hz, 1H, H3), 6.47
(dd, J=9.1, 6.0 Hz, 1H, H4), 5.60 (dd, J=13.5,
6.2Hz, 1H, H11), 4.65 (dd, 6.0, 1.5 Hz, 1H, H5),
Isoquinolone 41: A solution of 40 (173 mg, 1 mmol) and 3-butynyl tosy-
late (500 mg, 2.2 mmol) in MeCN (2 mL) in a sealed tube was heated to
1608C for 3 h by microwave irradiation. The mixture was diluted with
Et2O and extracted three times with water (15 mL total). A solution of
K3[Fe(CN)6] (3.29 g, 10 mmol) in H2O (10 mL) was added over 1 h at
08C to the aqueous phase containing the crude isoquinolinium salt, fol-
lowed by a solution of KOH (841 mg, 15 mmol) in H2O (2mL) over
30 min at 08C. After the addition of toluene (20 mL), the mixture was
stirred for 30 min at 408C and extracted three times with CH2Cl2. The
combined organic phases were dried with MgSO4 and the solvent re-
moved in vacuo, yielding isoquinolone 41 (230 mg, 95%). White solid;
m.p. 177–1788C; IR (film): n˜ =3226, 2774, 2391, 1974, 1654, 1611, 1466,
4.56 (br s, 1H, H8), 4.49 (s, 5H, Cp), 3.80 (td, J=
12.7, 5.5 Hz, 1H, H11), 1.55–1.28 (m, 2H, H12),
1.19 (m, 2H, H13), 0.25 (s, 9H, TMS), 0.06 (s,
9H, TMS), À0.64 ppm (br s, 1H, H10); 13C NMR
(100 MHz, C6D6): d=162.7 (C2), 149.8 (C6), 136.4 (C4), 115.9 (C3), 101.2
(C5), 90.2(C9), 80.8 (C8), 80.7 (Cp), 56.9 (C7), 48.1 (C10), 37.7 (C11),
33.7 (C13), 20.6 (C12), 1.98 (TMS), 1.13 ppm (TMS); MS (70 eV, EI): m/
z (%): 455 (40) [M+], 382 (10), 330 (52), 316 (18), 258 (100), 242 (39),
228 (7), 184 (7), 170 (9), 73 (100), 59 (9); HRMS: Calcd for
C23H34CoNOSi2: 455.1511; found: 455.1506; elemental analysis calcd (%)
for C23H34CoNOSi2: C 60.63, H 7.52, N 3.07; found: C 60.83, H 7.48, N
3.26.
1253, 839, 788 cmÀ1 1H NMR (500 MHz, CDCl3): d=7.77 (s, 1H), 7.09
;
Oxidative demetalation of 45 to 46: Complex 45 (199 mg, 0.438 mmol) in
MeCN (10 mL) and THF (10 mL) at 08C was treated with Fe-
(d, J=7.3 Hz, 1H), 6.86 (s, 1H), 6.38 (d, J=7.3, 1H), 6.08 (s, 2H), 4.12
(t, J=6.6 Hz, 2H), 2.72 (td, J=6.6, 2.7 Hz, 2H), 2.02 ppm (t, J=2.7 Hz,
1H); 13C NMR (125 MHz, CDCl3): d=161.1, 151.8, 147.8, 134.4, 131.1,
121.6, 105.6, 105.6, 103.6, 101.7, 80.9, 70.6, 48.4, 18.7 ppm; MS (70 eV,
EI): m/z (%): 241 (73) [M+], 202 (20), 189 (100), 172 (60); elemental
analysis calcd (%) for C14H11NO3: C 69.70, H 4.60, N 5.81; found: C
69.43, H 4.67, N 5.67.
A
15 min. The mixture was poured into ice water (50 mL), extracted with
CH2Cl2 (3”50 mL), the combined organic layers washed with H2O
(50 mL), dried over sodium sulfate, and the solvent removed under re-
duced pressure. Column chromatography (EtOAc/hexanes) furnished 46
(145 mg, 100%). Colorless crystals; m.p. 59–608C; IR (KBr): n˜ =2960,
Complexes 42 and 43: A solution of isoquinolone 41 (121 mg, 0.5 mmol)
1652, 1574, 1526, 1447, 1260, 1152, 1024, 914, 800, 693 cmÀ1 1H NMR
;
in dry, degassed THF (4 mL) and a solution of [CpCo
0.5 mmol) in dry, degassed THF (4 mL) were added simultaneously over
1 h to a mixture of degassed BTMSA (6 mL). The mixture was stirred for
A
(300 MHz, C6D6): d=6.62(dd, J=9.1, 6.9 Hz, 1H, H4), 6.49 (dd, J=9.1,
1.4 Hz, 1H, H3), 6.33 (d, J=2.0 Hz, 1H, H10), 6.15 (dd, J=6.9, 1.4 Hz,
1H, H5), 6.06 (q, J=1.9 Hz, 1H, H8), 3.84 (t, J=6.8 Hz, 2H, H11), 1.85
7460
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 7443 – 7465

Cobalt-Mediated Reactions
FULL PAPER
(td, J=7.0, 1.6 Hz, 2H, H13), 1.29 (quin, J=6.9 Hz, 2H, H12), 0.09 (s,
9H, TMS), 0.001 ppm (s, 9H, TMS); 13C NMR (100 MHz, C6D6): d=
162.2 (C2), 160.2 (C6), 148.3 (C10), 145.9 (C9), 138.9 (C8), 137.1 (C4),
127.9 (C7), 118.7 (C3), 107.4 (C5), 41.4 (C11), 29.6 (C13), 22.9 (C12),
1.22 (TMS), 0.84 ppm (TMS); MS (70 eV, EI): m/z (%): 331 (48) [M+],
330 (64), 316 (20), 258 (100), 242 (65), 73 (74); HRMS: Calcd for
C18H29NOSi2: 331.1788; found: 331.1789; elemental analysis calcd (%)
for C18H29NOSi2: C 65.20, H 8.81, N 4.22; found: C 65.02, H 9.02, N 3.96.
7.0 Hz, 1H, H4), 6.59 (dd, J=9.0, 1.2Hz, 1H, H3), 6.22 (d, J=1.5 Hz,
1H, H10), 6.10 (dd, J=7.1, 1.2Hz, 1H, H5), 3.70 (t, J=6.0 Hz, 2H,
H11), 1.77 (td, J=6.6, 1.8 Hz, 2H, H13), 1.03 (quin, J=6.2Hz, 2H, H12),
0.29 ppm (s, 9H, TMS); 13C NMR (300 MHz, C6D6): d=161.1 (C2), 152.2
(Phquat), 146.8 (C6), 142.1 (C9), 137.8 (C4), 134.5 (C7), 131.8 (C10), 129.5
(C8), 127.9 (p-Ph), 128.9 (o-Ph), 126.6 (m-Ph), 118.9 (C3), 101.6 (C5),
42.1 (C11), 25.1 (C13), 21.7 (C12), 1.35 ppm (TMS); MS (70 eV, EI): m/z
(%): 335 (100) [M+], 320 (20), 262 (58), 73 (36); HRMS: Calcd for
C21H25NOSi: 335.1705; found: 335.1697.
Thermolysis of 46 to 47, 48, and 49: Dienylpyridone 46 (100 mg,
0.30 mmol) in toluene (30 mL) was heated at 1108C for 1.5 h. The tolu-
ene was removed and the mixture subjected to HPLC (EtOAc/hexanes
7:3) to separate 47 (65%), 48 (25%), and 49 (10%). Species 48 degraded
to 47 within 12h, while 49 converted to 47 quantitatively on heating.
More simply, heating 46 (100 mg) in toluene at 1108C for 12h gave 47
(73.0 mg, 95%).
Cocyclization of 3 with 1-trimethylsilylpropyne to give 52–54: Pentynyl
pyridone 3 (161 mg, 1.00 mmol) and [CpCo(C2H4)2] (180 mg, 1.00 mmol),
A
both dissolved in degassed THF (5 mL each), were added through sepa-
rate syringes to degassed 1-(trimethylsilyl) propyne (20 mL, 135 mmol)
under argon over 1 h at room temperature. Subsequently, solvents were
removed in vacuo and the resulting residue chromatographed (EtOAc/
hexanes 9:1) under N2 to give a mixture of 52 (33% by 1H NMR), ad-
Quinolone 47: Colorless solid; IR (KBr): n˜ =2954, 2896, 1660, 1651, 1645,
1
1574, 1479, 1423, 1313, 1251, 1143, 914, 838, 754 cmÀ1
;
1H NMR
mixed with the free ligand 53 and its isomer 54 (10:1, 47% by H NMR),
as a brown oil. The identity of 52 was ascertained by the diagnostic sig-
nals in the 1H NMR spectrum (C6D6, 300 MHz): selected d=4.53 (d, J=
6.6 Hz, 1H, H5), 4.48 (br s, 1H, H8), 4.36 (s, 5H, Cp), 1.89 (s, 3H, CH3),
0.03 (s, 9H, TMS), À0.59 ppm (br s, 1H, 10H), and a mass spectrum of
the mixture: MS (70 eV, EI): m/z (%): 397 (95) [M+]. The identity of 53
and 54 in the mixture was confirmed by oxidative demetalation of the
crude cyclization mixture and chromatography (EtOAc/hexanes 9:1) to
elute 53 (175 mg, 64%), then 54 (44 mg, 16%).
(300 MHz, CDCl3): d=7.68 (d, J=9.5 Hz, 1H, H4), 7.52(d, J=1.0 Hz,
1H, H10), 7.41 (d, J=1.0 Hz, 1H, H8), 6.68 (d, J=9.4 Hz, 1H, H3), 4.19
(t, J=6.0 Hz, 2H, H11), 2.99 (t, J=6.1 Hz, 2H, H13), 2.09 (quin, J=
6.1 Hz, 2H, H12), 0.29 ppm (s, 9H, TMS); 13C NMR (100 MHz, CDCl3):
d=161.0 (C2), 139.0 (C4), 137.2 (C6), 134.5 (C8), 133.3 (C9), 131.9
(C10), 124.1 (C7), 121.2 (C3), 120.0 (C5), 42.2 (C11), 27.6 (C13), 20.7
(C12), À1.10 ppm (TMS); MS (70 eV, EI): m/z (%): 257 (60) [M+], 242
(100), 113 (5); HRMS: Calcd for C15H19NOSi: 257.1236; found: 257.1238.
Diene 53: Colorless oil; IR (KBr): n˜ =2956, 1660, 1652, 1575, 1539, 1408,
Quinolone 48: Colorless solid; IR (KBr): n˜ =2954, 2896, 1660, 1651,
1
1248, 1141, 1071, 1038, 839, 801 cmÀ1; H NMR (300 MHz, C6D6): d=6.68
1645, 1574, 1479, 1423, 1313, 1251, 1143, 914, 838, 754 cmÀ1 1H NMR
;
(dd, 1H, J=9.12, 6.8 Hz, 1H, H4), 6.56 (dd, J=9.1, 1.3 Hz, 1H, H3), 5.94
(dd, J=6.8, 1.3 Hz, 1H, H5), 5.89 (br s, 1H, H8), 5.54 (s, 1H, H10), 3.84
(t, J=6.0 Hz, 2H, H11), 1.82 (td, J=6.6, 1.5 Hz, 2H, H13), 1.17 (s, 3H,
CH3), 1.28 (quin, J=6.3 Hz, 2H, H12), 0.12ppm (s, 9H, TMS); 13C NMR
(100 MHz, C6D6): d=161.9 (C2), 149.8 (C9), 145.9 (C6), 137.3 (C4), 136.5
(C8), 132.4 (C10), 129.9 (C7), 119.1 (C3), 105.9 (C5), 40.4 (C11), 29.4
(C13), 22.5 (C12), 21.2 (CH3), 1.34 ppm (TMS); MS (70 eV, EI): m/z
(%): 273 (100) [M+], 256 (90), 199 (100), 184 (60), 73 (43); HRMS:
Calcd for C16H23NOSi: 273.1549; found: 273.1546.
(300 MHz, CDCl3): d=8.08 (d, J=9.9 Hz, 1H, H4), 7.53 (s, 1H, H8),
6.64 (d, J=9.9 Hz, 1H, H3), 4.21 (t, J=6.0 Hz, 2H, H11), 2.96 (t, J=
6.0 Hz, 2H, H13), 2.09 (quin, J=6.0 Hz, 2H, H12), 0.47 (s, 9H, TMS),
0.39 ppm (s, 9H, TMS); 13C NMR (100 MHz, CDCl3): d=161.0 (C2),
139.7 (C4), 138.9 (C6), 136.5 (C8), 134.4 (C9), 128.1 (C10), 125.0 (C7),
121.3 (C5), 119.2 (C3), 42.5 (C11), 27.6 (C13), 20.7 (C12), 4.08 (TMS),
2.80 ppm (TMS); MS (70 eV, EI): m/z (%): 329 (13) [M+], 314 (10), 257
(55), 242 (100), 113 (5); HRMS: Calcd for C18H27NOSi2: 329.1631; found:
329.1632.
Diene 49: Colorless oil; 1H NMR (300 MHz, CDCl3): d=7.19 (dd, J=
9.0, 7.0 Hz, 1H), 6.50 (dd, J=9.0, 2.0 Hz, 1H), 6.46 (q, J=1.8 Hz, 1H),
6.34 (dd, J=7.0 Hz, 2.0 Hz, 1H), 6.33 (d, J=2.1 Hz, 1H), 4.05 (t, J=
6.2Hz, 2H), 2.48 (td, J=6.9, 1.5 Hz, 2H), 2.01 (quin, J=6.3 Hz, 2H),
0.12(s, 9H), 0.09 ppm (s, 9H); MS (70 eV, EI): m/z (%): 331 (58) [M+],
330 (40), 316 (20), 258 (100), 244 (65), 73 (69); HRMS: Calcd for
C18H29NOSi2: 331.1788; found: 331.1793.
Diene 54: Colorless oil; IR (KBr): n˜ =2956, 1660, 1652, 1575, 1539, 1408,
1
1248, 1141, 1071, 1038, 839, 801 cmÀ1; H NMR (300 MHz, C6D6): d=6.76
(dd, J=8.8, 7.1 Hz, 1H, H4), 6.62(d, J=8.8 Hz, 1H, H3), 6.24 (br s, 1H,
H8), 5.91 (d, J=6.9 Hz, 1H, H5), 5.49 (br s, 1H, H10), 3.77 (t, J=6.0 Hz,
2H, H11), 2.10 (td, J=6.9, 1.5 Hz, 2H, H13), 1.13 (quin, J=6.1 Hz, 2H,
H12), 0.30 ppm (s, 9H, TMS); 13C NMR (100 MHz, C6D6): d=161.0
(C2), 149.5 (C9), 137.9 (C4), 134.9 (C8), 133.0 (C10), 128.2 (C7), 118.3
(C3), 101.9 (C5), 46.1 (C11), 24.8 (C13), 22.4 (CH3, C12), 1.35 ppm
(TMS); the signal for C6 could not be detected; MS (70 eV, EI): m/z
(%): 273 (100) [M+], 258 (90), 199 (100), 184 (60), 73 (43).
Cocyclization of 3 with 1-trimethylsilyl-2-phenylacetylene to give 50: N-
(4-Pentynyl)-2-pyridone (3) (161 mg, 1.00 mmol) and [CpCo(C2H4)2]
G
(180 mg, 1.00 mmol) in degassed THF (5 mL each) were added through
separate syringes to degassed 1-trimethylsilyl-2-phenylacetylene (20 mL)
over 1 h at room temperature. The volatiles were removed by distillation
at 0.001 torr and the residue chromatographed (EtOAc/hexanes 9:1)
under N2 to give 50 (362mg, 79%). Dark-brown crystals (from pentane/
EtOAc); m.p. 209–2108C; IR (KBr): n˜ =3448, 2950, 1655, 1561, 1535,
N-(3-Phenylpropyl)-2-pyridone: Pentynylpyridone 3 (161 mg, 1.00 mmol)
in THF (50 mL) was degassed with argon, cooled to À708C, and purged
with ethyne for 1 h. A solution of [CpCo(C2H4)2] (180 mg, 1.00 mmol) in
A
THF (15 mL) was then added via a syringe pump over 1 h and the mix-
ture allowed to warm to room temperature slowly, while maintaining a
continuous flow of ethyne. Solvents were removed in vacuum and the
crude product chromatographed (EtOAc/hexanes 9:1) to give the prod-
uct (138 mg, 65%). Yellow resin; IR (KBr): n˜ =3392, 3027, 2957, 2930,
1
1384, 835 cmÀ1; H NMR (300 MHz, C6D6): d=7.62(br s, 2H, PhH), 7.26
(m, 3H, PhH), 6.62(dd, J=9.1, 1.5 Hz, 1H, H3), 6.45 (dd, J=9.1, 6.0 Hz,
1H, H4), 5.59 (m, 1H, H11), 4.73 (d, J=6.0 Hz, 1H, H5), 4.64 (br s, 1H,
H8), 4.45 (s, 5H, Cp), 3.72 (m, 1H, H11), 1.73–1.53 (m, 2H, H12), 1.32–
1.10 (m, 2H, H13), À0.10 (s, 9H, TMS), À0.32ppm (br s, 1H, H10);
13C NMR (100 MHz, C6D6): d=162.9 (C2), 149.2 (C6), 136.8 (C4), 130.4
(Ph), 128.1 (Ph), 127.8 (Ph), 115.8 (C3), 106.6 (Phquat), 101.0 (C5), 81.8
(Cp), 79.7 (C8), 69.8 (C9), 52.1 (C7), 48.4 (C10), 37.7 (C11), 33.3 (C13),
20.8 (C12), 1.28 ppm (TMS); MS (70 eV, EI): m/z (%): 459 (35) [M+],
386 (25), 335 (55), 320 (24), 73 (100); HRMS: Calcd for C26H30CoNOSi:
459.1429; found: 459.1430; elemental analysis calcd (%) for
C26H30CoNOSi: C 67.95, H 6.59, N 3.05; found: C 68.06, H 6.32, N 3.35.
2861, 1658, 1580, 1540, 1497, 1455, 1275, 1074, 768, 700 cmÀ1 1H NMR
;
(300 MHz, C6D6): d=7.08 (m, 3H), 6.94 (d, J=7.5 Hz, 2H), 6.69 (br t,
J=6.9 Hz, 1H), 6.55 (br d, J=9.1 Hz, 1H), 6.29 (br d, J=6.8 Hz, 1H),
5.44 (br t, J=6.8 Hz, 1H), 3.51 (t, J=7.4 Hz, 2H), 2.34 (t, J=7.2Hz,
2H), 1.76 ppm (quin, J=7.5 Hz, 2H); 13C NMR (100 MHz, C6D6): d=
167.5, 141.3, 138.9, 137.7, 130.8, 128.6, 126.2, 121.2, 104.9, 49.3, 32.9,
30.8 ppm; MS (70 eV, EI): m/z (%): 213 (39) [M+], 109 (100), 91 (60);
HRMS: Calcd for C13H15NO: 213.1154; found: 213.1153.
N-[3-(2,3,4,5-Tetramethyoxycarbonylphenyl)propyl]-2-pyridone: [CpCo-
Oxidative demetalation of 50 to 51: Complex 50 (100 mg, 0.220 mmol)
was treated according to the procedure that led to 46 to provide 51
(74.0 mg, 99%). Colorless oil; IR (KBr): n˜ =2964, 1652, 1575, 1539, 1417,
A
in degassed THF (10 mL each) were added through separate syringes
over 75 min to pentynylpyridone 3 (161 mg, 1.00 mmol) dissolved in de-
gassed THF (15 mL). After evaporation of solvents, the residue was chro-
matographed (EtOAc/MeOH 8:2) under N2 to give the tetraester
1261, 1020, 799 cmÀ1 1H NMR (300 MHz, C6D6): d=7.29 (m, 2H, o-
;
PhH), 7.13 (m, 3H, PhH), 6.79 (q, J=1.8 Hz, 1H, H8), 6.76 (dd, J=9.0,
Chem. Eur. J. 2007, 13, 7443 – 7465
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7461

K. P. C. Vollhardt et al.
(250 mg, 56%). Red resin; IR (KBr): n˜ =2954, 1733, 1659, 1582, 1541,
1441, 1374, 1248, 1212, 1161, 1114, 1047, 1000, 888, 811, 770 cmÀ1
(C3), 110.4 (C10), 103.8 (C5), 41.7 (C11), 34.9 (C14), 26.6 (C12),
25.7 ppm (C13); MS (70 eV, EI): m/z (%): 201 (100) [M+], 184 (24), 172
(42); HRMS: Calcd for C13H15NO: 201.1154; found: 201.1153; elemental
analysis calcd (%) for C13H15NO: C 77.58, H 7.51, N 6.96; found: C
77.45, H 7.25, N 6.98.
;
1H NMR (300 MHz, C6D6): d=7.59 (s, 1H), 6.64 (ddd, J=9.1, 6.6,
2.1 Hz, 1H), 6.49 (br d, J=9.1 Hz, 1H), 6.27 (dd, J=6.8, 2.1 Hz, 1H),
5.45 (td, J=6.8, 2.0 Hz, 1H), 3.66 (s, 3H), 3.53 (s, 3H), 3.42 (s, 3H), 3.40
(s, 3H), 2.36 (t, J=8.4 Hz, 2H), 1.62 (quin, J=7.5 Hz, 2H), 0.91 ppm (t,
J=7.1 Hz, 2H); 13C NMR (100 MHz, C6D6): d=167.4, 167.3, 166.4, 165.3,
162.4, 141.9, 139.1, 137.9, 136.6, 133.5, 133.5, 131.4, 131.2, 120.9, 105.1,
52.8, 52.7, 52.6, 52.5, 49.0, 30.6, 30.4 ppm; MS (70 eV, EI): m/z (%): 445
(20) [M+], 415 (20), 122 (38), 108 (100), 94 (42); HRMS: Calcd for
C22H23NO9: 445.1373; found: 445.1371.
Reaction of 4-pyridone with 1,7-octadiyne to give 59 and 60: [CpCo-
A
both dissolved in THF (2mL each), were added through separate syring-
es over 1 h to a solution of 4-pyridone (5.04 g, 53.0 mmol) in dry and de-
gassed MeOH (30 mL) at room temperature. Evaporation of the solvents
and chromatography (EtOAc/hexanes 8:2) provided a mixture, which
was separated by HPLC (silica gel, EtOAc/MeOH 9:1) to access 59
(40.0 mg, 12%) and 60 (20.0 mg, 6%).
Compound 59: Orange resin; 1H NMR (300 MHz, C6D6): d=6.65 (m,
2H), 6.41 (m, 2H), 4.25 (s, 5H, Cp), 1.68 (br s, 1H), 1.99–1.59 (m, 4H),
1.29–1.14 (m, 4H), 0.92 (br s, 1H), À0.72ppm (br s, 1H); 13C NMR
(100 MHz, C6D6): d=140.3, 101.5, 90.2, 86.0, 82.0 (Cp), 63.8, 35.2, 31.2,
29.6, 25.4, 23.2 ppm, signal for carbonyl carbon not detected; MS (70 eV,
EI): m/z (%): 325 (80) [M+], 219 (15), 200 (75), 172 (100), 144 (20);
HRMS: Calcd for C18H20CoNO: 325.0877; found: 325.0874.
Cocyclization of 4 with BTMSA to give 55 and 56: A solution of hexynyl-
pyridone 4 (175 mg, 1 mmol) in dry, degassed THF (2mL) and a solution
of [CpCo(C2H4)2] (180 mg, 1 mmol) in dry, degassed THF (2mL) were
N
added simultaneously over 1 h to degassed BTMSA (10 mL). The mix-
ture was stirred for another h, the volatiles removed in vacuo, and the
residue purified by chromatography (hexane/EtOAc 1:1–7:3–3:1) to de-
liver 55 (123 mg, 26%) and 56 (60.3 mg, 13%).
Complex 55: Dark red solid; m.p. 130–1318C (decomp); IR (film): n˜ =
2950, 1652, 1536, 1246, 833 cmÀ1 1H NMR (300 MHz, C6D6): d=7.10 (d,
;
J=7.0 Hz, 1H), 6.89 (dd, J=9.0, 7.0 Hz, 1H), 6.50 (d, J=7.9 Hz, 1H),
5.24 (m, 1H), 4.84 (s, 1H), 4.58 (s, 5H), 3.33 (m, 1H), 1.37–1.10 (m, 6H),
0.30 (s, 9H), 0.02(s, 9H), À0.41 ppm (s, 1H); 13C NMR (125 MHz,
C6D6): d=161.8, 155.5, 138.2, 116.9, 110.4, 92.4, 85.0, 81.5, 65.1, 48.0, 43.6,
41.7, 27.6, 26.5, 1.73, 1.11 ppm; MS (70 eV, EI): m/z (%): 469 (100) [M+],
396 (7), 358 (13), 73 (17); HRMS: Calcd for C24H36CoNOSi2: 469.1667;
found: 469.1673; elemental analysis calcd (%) for C24H36CoNOSi2: C
61.38, H 7.73, N 2.98; found: C 61.13, H 8.06, N 2.82.
Compound 60: Orange resin; 1H NMR (300 MHz, C6D6): d=6.37 (m,
2H), 6.29 (m, 2H), 4.24 (s, 5H, Cp), 4.12 (br s, 1H), 2.19 (dt, J=13.6,
4.1 Hz, 1H), 1.96 (m, 1H), 1.81 (s, 1H), 1.80–1.60 (m, 6H), À0.37 ppm
(br s, 1H); 13C NMR (100 MHz, C6D6): d=144.8, 101.4, 86.1, 81.9 (Cp),
81.8, 63.6, 35.2, 30.9, 29.7, 23.2, 23.0 ppm, signal for carbonyl carbon not
detected.
Oxidative demetalation of 59 to 61: Complex 59 (40 mg, 0.123 mmol) was
treated according to the procedure that led to 46, resulting in 61
(24.0 mg, 100%). Colorless oil; 1H NMR (300 MHz, C6D6) d=6.36 (d,
J=7.8 Hz, 2H), 6.19 (d, J=7.8 Hz, 2H), 5.70 (br s, 1H), 4.66 (br s, 1H),
4.56 (br s, 1H), 1.97 (t, J=6.0 Hz, 2H), 1.62 (t, J=6.0 Hz, 2H), 1.28 ppm
(m, 4H).
Complex 56: Light yellow oil; IR (film): n˜ =2952, 1661, 1591, 1538, 1245,
837 cmÀ1 1H NMR (500 MHz, CDCl3): d=7.31 (ddd, J=9.0, 6.7, 2.1 Hz,
;
1H), 7.25 (d, J=6.7 Hz, 1H), 6.57 (d, J=9.0 Hz, 1H), 6.16 (t, J=6.6 Hz,
1H), 4.80 (s, 5H), 4.15 (s, 1H), 3.92(t, J=7.3 Hz, 2H), 1.91 (m, 2H),
1.75 (quin, J=7.2Hz, 2H), 1.42 (m, 2H), 0.10 (s, 9H), 0.05 ppm (s, 9H);
13C NMR (125 MHz, CDCl3): d=162.6, 139.2, 137.4, 121.1, 105.8, 91.9,
78.9, 68.2, 66.8, 64.3, 49.6, 29.7, 29.2, 26.4, 0.60, 0.04 ppm; MS (70 eV, EI):
m/z (%): 469 (100) [M+], 396 (13), 306 (19), 299 (18), 294 (24), 152 (19),
73 (23); elemental analysis calcd (%) for C24H36CoNOSi2: C 61.38, H
7.73, N 2.98; found: C 61.56, H 7.96, N 2.95.
Oxidative demetalation of 50 to 62: Complex 60 (20.0 mg, 0.06 mmol)
was treated according to the procedure that led to 46, resulting in 62
(12mg, 100%).Colorless oil; 1H NMR (300 MHz, C6D6): d=6.37 (br s,
4H), 5.28 (br s, 1H), 4.56 (br s, 1H), 4.30 (br s, 1H), 1.77 (m, 2H), 1.69
(m, 2H), 1.32ppm (m, 4H); MS (70 eV, EI): m/z (%): 201 (62) [M+],
200 (100), 172 (96).
Reaction of 2-pyridone with 1,7-octadiyne to give 57: [CpCo(C2H4)2]
T
Reaction of 1-methyl-2-pyrazinone (63) with 1,7-octadiyne to give 64: A
solution of 1-methyl-2-pyrazinone (63) (90.1 mg, 0.82mmol) in C 6H6
(180 mg, 1.00 mmol) and 1,7-octadiyne (106 mg, 1.00 mmol), both in de-
gassed THF (2mL each), were added through separate syringes over 1 h
to a solution of 2-pyridone (5.04 g, 53.0 mmol) in dry and degassed
MeOH (30 mL) at room temperature. Removal of solvents and chroma-
tography (EtOAc/hexanes 8:2) resulted in complex 57 (146 mg, 45%).
Orange resin; IR (KBr): n˜ =3083, 2932, 2858, 1652, 1581, 1532, 1447,
(5 mL) and of [CpCo
ACHTREUNG
syringe-pumped separately into
a
(164 mg, 1.54 mmol) in C6H6 (3 mL) over a period of 4 h. After solvent
removal, column chromatography (EtOAc/MeOH 1:0–10:1) of the black
residue gave complex 64 (61.3 mg, 22%) and starting 63 (21.5 mg, 24%).
Orange oil; IR (KBr): n˜ =3080, 2930, 2865, 2830, 1645, 1590, 1485, 1435,
1405, 1355, 1325, 1275, 1255, 1205, 1165, 1140, 1110, 1040, 1010, 925, 900,
1354, 1275, 1138, 899, 848, 817, 766 cmÀ1 1H NMR
;
(300 MHz, C6D6, assignments according to the
numbering in the structure shown): d=7.27 (br d,
860, 835, 810, 730, 705, 650, 620, 600, 575 cmÀ1
;
1H NMR (C6D6,
J=5.5 Hz, 1H, H6), 6.74 (br t, J=9.0 Hz, 1H, H4),
300 MHz): d=6.61 (d, J=4.3 Hz, 1H), 5.78 (d, J=4.3 Hz, 1H), 4.75 (s,
5H), 4.65 (s, 1H), 2.71 (s, 3H), 2.51 (s, 1H), 2.50–2.32 (m, 3H), 2.24 (m,
1H), 1.99–1.71 (m, 2H), 1.58–1.48 (m, 2H), 0.37 ppm (s, 1H); 13C NMR
(C6D6, 100 MHz): d=160.3, 157.0, 123.5, 122.4, 99.4, 94.4, 81.7, 42.5, 39.3,
36.4, 32.6, 32.2, 24.2, 24.1 ppm; MS (70 eV, EI): m/z (%): 340 (74) [M+],
272 (29), 259 (9), 242 (18), 215 (100); HRMS: Calcd for C18H21CoN2O:
340.0990; found: 340.0988.
6.59 (d, J=9.0 Hz, 1H, H3), 5.61 (br t, J=6.1 Hz,
1H, H5), 4.23 (s, 5H, Cp), 3.08 (br s, 1H, H7), 2.21
(m, 2H), 1.83–1.55 (m, 4H), 1.71 (br s, 1H, H10),
1.20 (m, 2H), À0.15 ppm (br s, 1H, H10); 13C NMR (100 MHz, C6D6):
d=162.9 (C2), 137.7 (C6), 137.4 (C4), 120.7 (C3), 102.8 (C5), 90.4 (C8 or
C9), 86.8 (C8 or C9), 81.7 (Cp), 60.0 (C7), 31.3 (C10), 30.7, 25.7, 23.7,
22.9 ppm (C11–14); MS (70 eV, EI): m/z (%): 325 (100) [M+], 257 (45),
201 (44), 153 (34); HRMS: Calcd for C18H20CoNO: 325.0877; found:
325.0873.
N,N’-Dibenzyl-2,3-pyrazinedione (65):[44] A solution of 1,4-dihydro-2,3-
pyrazinedione (104.1 mg, 0.93 mmol) in DMSO (15 mL) was treated with
a 60% NaH dispersion (83 mg, 2.08 mmol). After 10 min, benzylbromide
(360 mg, 0.21 mmol) was added and the mixture stirred at room tempera-
ture for 2h. DMSO was removed under high vacuum, the brown residue
extracted with CH2Cl2/H2O, and the extract dried over MgSO4, and chro-
matographed (CH2Cl2/MeOH 20:1) to give 65 (236 mg, 87%). White
solid; IR (KBr): 3100, 3065, 3030, 2945, 1685, 1640, 1585, 1495, 1445,
1420, 1395, 1360, 1355, 1320, 1225, 1200, 1150, 1080, 1020, 945, 835, 755,
Oxidative demetalation of 57 to 58: Complex 57 (100 mg, 0.31 mmol)
was treated according to the procedure that led to 46 to provide 58
(63.0 mg, 100%). Colorless oil; IR (KBr): n˜ =3079, 2934, 2858, 1668,
1586, 1532, 1447, 1275, 1145, 896, 841, 771 cmÀ1 1H NMR (300 MHz,
;
C6D6): d=6.86 (s, 1H, H7), 6.64 (ddd, J=9.0, 6.4, 1.5 Hz, 1H, H4), 6.52
(dd, J=8.8, 1.4 Hz, 1H, H3), 6.45 (dd, J=6.5, 1.5 Hz, 1H, H6), 5.41 (td,
J=6.5, 1.4 Hz, 1H, H5), 4.91 (br s, 1H, H10), 4.64 (br s, 1H, H10), 2.07
(t, J=6.3 Hz, 2H, H11), 1.91 (t, J=6.1 Hz, 2H, H14), 1.33 (AA’m, 2H,
H12), 1.19 ppm (BB’m, 2H, H13); 13C NMR (100 MHz, C6D6): d=161.9
(C2), 147.2 (C8), 138.8 (C4), 138.2 (C9), 137.9 (C6), 122.3 (C7), 121.9
730, 695, 635, 620, 605, 555 cmÀ1 1H NMR (CDCl3, 300 MHz): d=7.46–
;
7.28 (m, 10H), 6.08 (s, 2H), 4.96 ppm (s, 4H); 13C NMR (CDCl3,
125 MHz): d=155.9, 135.0, 128.9, 128.5, 128.4, 112.1, 51.3 ppm; MS
7462
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 7443 – 7465

Cobalt-Mediated Reactions
FULL PAPER
(70 eV, EI): m/z (%): 292 (50) [M+], 281 (9), 207 (32), 201 (21), 91 (100),
65 (26); HRMS: Calcd for C18H16N2O2 292.1212; found: 292.1212.
Oxidative demetalation of 67 to 69: A solution of CuCl2·2H2O (60.5 mg,
0.35 mmol) in THF (2mL) and H 2O (0.5 mL) was added to an ice-cooled
solution of complex 67 (32.1 mg, 0.073 mmol) and NEt3 (20 mL,
0.143 mmol) in THF (2mL). After 5 min of stirring at 0 8C, TLC analysis
(EtOAc) showed only starting material, therefore, the ice bath was re-
moved and the solution was stirred at room temperature. After 7 h, the
starting material had disappeared, and the deep red solution was diluted
with H2O/CH2Cl2 and extracted with CH2Cl2. Column chromatography
(hexane/EtOAc 1:1) gave 69 (10 mg, 44%) and some 68 (1 mg, 5%). Col-
orless oil; 1H NMR (CDCl3, 300 MHz): d=8.23 (s, 1H), 7.68 (t, J=
1.1 Hz, 1H), 4.42(br t, J=7.8 Hz, 2H), 3.41 (dt, J=7.8, 1.1 Hz, 2H), 0.48
(s, 9H), 0.41 ppm (s, 9H); MS (70 eV, EI): m/z (%): 316 (28) [M+], 301
(100), 285 (27), 243 (18), 229 (7), 143 (14), 73 (16).
Reaction of 65 with 1,7-octadiyne to give 66: 1,7-Octadiyne (65.0 mg,
0.61 mmol) and [CpCo(C2H4)2] (71.0 mg, 0.39 mmol) in toluene (3 mL
R
each) were syringe-pumped separately to 1,4-dibenzyl-1,4-dihydropyra-
zine-2,3-dione (65) (107 mg, 0.37 mmol) in toluene (10 mL) over a period
of 3 h. TLC analysis (CH2Cl2/MeOH 20:1) showed mainly starting mate-
rial, therefore, the red solution was stirred for another 2h under reflux.
Subsequently, more 1,7-octadiyne (75.0 mg, 0.71 mmol) dissolved in tolu-
ene (5 mL) was added to the boiling solution by syringe pump over a
period of approximately 15 h. The solvent was removed and the black
mixture purified by column chromatography (CH2Cl2/MeOH 20:1) to
yield 66 (29 mg, 15%) and recovered starting material 65 (77 mg, 72%).
Red oil; 1H NMR (CDCl3, 300 MHz): d=7.38–7.24 (m, 10H), 5.21 (d, J=
14.8 Hz, 2H), 4.59 (s, 5H), 4.24 (d, J=14.8 Hz, 2H), 3.71 (br s, 2H), 3.03
(br s, 2H), 2.36–2.20 (m, 2H), 2.2.-1.92 (m, 4H), 1.80 ppm (m, 2H); MS
(70 eV, EI): m/z (%): 522 (36) [M+], 456 (18), 236 (30), 91 (100);
HRMS: Calcd for C31H31CoN2O2: 522.1718; found: 522.1714.
Reaction of 16 with BTMSA and [CpCo
ACHTREUNG
azinone 16 (101 mg, 0.62mmol) and [CpCo
AHCTREUNG
0.638 mmol) in THF (3 mL each) were added separately by syringe pump
to BTMSA (10 mL) at room temperature over a period of 2.5 h. After re-
moval of the volatiles, column chromatography (EtOAc/hexane 3:1) pro-
vided 70 (43.0 mg, 15%). Thick, red-green oil; IR (KBr): n˜ =3095, 3010,
2960, 2900, 1655, 1560, 1475, 1460, 1425, 1400, 1325, 1300, 1260, 1245,
1180, 1160, 1140, 1105, 1015, 965, 855, 830, 750, 685, 655, 623, 595,
Cocyclization of 15 with BTMSA to give 67 and 68: Butynylpyrazinone
15 (98.3 mg, 0.66 mmol) and [CpCo(C2H4)2] (145 mg, 0.805 mmol) in
N
THF (3 mL each) were added separately by syringe pump to BTMSA
(10 mL) at room temperature over a period of 3 h. The solvents were re-
moved, and column chromatography (EtOAc/hexane 1:1) of the black
residue provided 67 (119 mg, 41%) and compound 68 (15.8 mg, 10%).
552cm À1 1H NMR (C6D6, 300 MHz): d=8.40 (br s, 1H), 6.17 (br s, 1H),
;
5.26 (dd, J=12.7, 5.5 Hz, 1H), 4.57 (s, 1H), 4.45 (s, 5H), 3.65 (td, J=
12.5, 5.5 Hz, 1H), 1.37–1.06 (m, 4H), 0.20 (s, 9H), 0.03 (s, 9H),
À0.60 ppm (br s, 1H); 13C NMR (C6D6, 100 MHz): d=157.7, 143.3, 142.7,
119.6, 91.5, 81.0, 84.0, 53.0, 49.1, 37.7, 33.6, 20.5, 2.31, 1.45 ppm; MS
(70 eV, EI): m/z (%): 456 (100) [M+], 383 (35), 332(24), 317 (36), 73
(88); HRMS: Calcd for C22H33CoN2OSi2: 456.1463; found: 456.1459.
Complex 67: Red solid; IR (KBr): n˜ =3110, 2955, 2900, 2845, 1670, 1630,
1475, 1445, 1330, 1280, 1245, 1215, 1205, 1170, 1110, 1085, 1035, 1015,
970, 925, 860, 820, 810, 760, 680, 660, 635, 615 cmÀ1 1H NMR (C6D6,
;
300 MHz): d=7.88 (d, J=2.8 Hz, 1H), 4.86 (s, 1H), 4.49 (s, 5H), 4.13 (dt,
J=12.3, 8.7 Hz, 1H), 3.20 (dd, J=8.4, 2.8 Hz, 1H), 3.00 (dt, J=12.3,
6.0 Hz, 1H), 1.94 (d, J=8.4 Hz, 1H), 1.17 (t, J=8.3 Hz, 2H), 0.35 (s,
9H), 0.34 ppm (s, 9H); 13C NMR (CDCl3, 100 MHz): d=154.5, 153.3,
84.8, 81.8, 78.8, 77.0, 66.7, 64.1, 58.1, 43.7, 31.4, 4.7, 3.7 ppm; MS (70 eV,
EI): m/z (%): 442(100) [ M+], 427 (7), 317 (24), 229 (6), 124 (14), 73
(31); elemental analysis calcd (%) for C21H31CoN2OSi2: C 56.99, H 7.06,
N 6.33; found: C 57.03, H 7.22, N 6.30.
Oxidative demetalation of 70 to 71: To
(46.1 mg, 0.101 mmol) in THF (2mL) and CH 3CN (2mL) at 0 8C was
added Fe(NO3)3?9H2O (210 mg, 0.520 mmol) dissolved in CH3CN (2mL)
a solution of complex 70
AHCTREUNG
and H2O (0.5 mL). The dark green solution turned orange. After 1.5 min,
the mixture was poured into ice water and extracted three times with
CH2Cl2. The combined organic layers were dried (MgSO4), filtered and
concentrated in vacuo. Column chromatography (hexanes/EtOAc 1:1)
furnished 71 (25.0 mg, 75%). White solid; 1H NMR (CDCl3, 300 MHz):
d=7.97 (s, 1H), 7.53 (s, 1H), 6.55 (q, J=1.6 Hz, 1H), 6.38 (d, J=2.1 Hz,
1H), 3.97 (t, J=6.4 Hz, 2H), 2.49 (td, J=6.6, 1.5 Hz, 2H), 2.05 (quin, J=
6.6 Hz, 2H), 0.14 (s, 9H), 0.11 ppm (s, 9H); HRMS: Calcd for
C17H28N2OSi2: 332.1740; found: 332.1743.
Compound 68: White solid; IR (KBr): n˜ =3045, 2950, 2895, 1670, 1615,
1575, 1480, 1430, 1400, 1330, 1310, 1255, 1245, 1110, 1095, 1045, 990, 925,
880, 835, 755, 690, 625, 595, 580, 550 cmÀ1 1H NMR (CDCl3, 300 MHz):
;
d=8.26 (s, 1H), 7.37 (ABq, 2H), 4.46 (t, J=2.6 Hz, 2H), 3.42 (t, J=
2.6 Hz, 2H), 0.39 ppm (s, 9H); 13C NMR (CDCl3, 100 MHz): d=151.0
(2C), 138.3, 135.9, 134.7, 132.4, 130.7, 125.3, 47.3, 27.2, À0.20 ppm; MS
(70 eV, EI): m/z (%): 244 (20) [M+], 229 (100), 201 (7). HRMS: Calcd
for C13H16N2OSi: 244.1032; found: 244.1031.
Cyclization of 19 to 72: To dipentynylpyrazinedione 19 (106.1 mg,
0.43 mmol) in toluene (25 mL) was added [CpCo
A
0.479 mmol) in toluene (6 mL). The mixture was stirred at room temper-
Table 7. Crystal data and structure refinement for complexes 33, 35, 36, 38, 39, 45, 67, and 72.
33 35 36 38 39
C22H32CoNOSi2 C20H22CoNO C23H34CoNOSi2 C23H32CoNO2Si2 C23H32CoNO3Si2 C23H34CoNOSi2 C21H31CoN2OSi2 C19H21CoN2O2
45
67
72
formula
Fw
temperature
[K]
441.59
293(2)
351.43525.62469.13
485.61
146(2)
.54955.62442
155(2)
368.31
153(2)
157(2)
440(2)
135(2)
132(2)
wavelength
[Š]
0.71073
0.71073
0.71073
0.71073
0.71073
0.71073
0.71073
0.71073
crystal system triclinic
triclinic
P1
monoclinic
P21/c
19.9466(13)
14.1688(9)
18.0408(12)
90
116.1060(10)
90
4578.5(5)
8
monoclinic
C2/c
23.2021(18)
17.7971(14)
13.6060(10)
90
118.9050(10)
90
4918.4(7)
8
monoclinic
C2/c
29.458(3)
monoclinic
P21/n
18.3427(4)
7.41830(10)
19.8862(3)
90
117.0160(10)
90
2410.67(7)
4
triclinic
P1
triclinic
P1
¯
¯
¯
¯
space group
a [Š]
b [Š]
c [Š]
a [8]
P1
7.7555(6)
9.5294(7)
16.6462(12)
89.549(2)
78.700(2)
68.163(2)
1116.97(14)
2
7.802(4)
9.424(5)
12.258(6)
73.603(6)
87.129(6)
65.985(5)
787.6(7)
2
7.5467(8)
9.0865(10)
16.8965(18)
82.937(2)
77.934(2)
73.230(2)
1082.4(2)
2
9.3495(3)
9.7539(3)
19.7948(5)
99.923(2)
101.4510(10)
94.22
1731.88(9)
4
1.522
10.1754(9)
16.5627(15)
90
105.9150(10)
90
4774.4(7)
8
1.351
b [8]
g [8]
V [Š3]
Z
1calcd [gcmÀ3
]
1.340
1.481
1.093
1.322
0.868
1.362
0.820
1.255
0.824
1.358
0.917
m [mmÀ1
]
0.890
0.843
1.012
R1 [I > 2s(I)] 0.0679
wR2 (all data) 0.1715
0.0364
0.0806
0.0276
0.0764
0.0286
0.0722
0.0317
0.0696
0.0642
0.1480
0.0504
0.1213
0.0527
0.1493
Chem. Eur. J. 2007, 13, 7443 – 7465
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7463

K. P. C. Vollhardt et al.
ature for 3.5 h, the solvent removed, and the black residue purified by
column chromatography (CH2Cl2/MeOH 15:1) to give 72 (84.0 mg,
53%). Red oil; IR (KBr): n˜ =3085, 2900, 2910, 2850, 2230, 1655, 1600,
1465, 1435, 1410, 1390, 1350, 1330, 1305, 1290, 1255, 1175, 1150, 1120,
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Int. Ed. Engl. 1991, 30, 993.
1
1045, 1010, 930, 905, 860, 825, 810, 735, 725, 645, 620, 565 cmÀ1; H NMR
(CDCl3, 500 MHz): d=4.68 (s, 5H), 4.46 (m, 1H), 4.19 (m, 1H), 4.10 (br
s, 1H), 3.93 (d, J=7.9 Hz, 1H), 3.76 (dd, J=7.8, 5.5 Hz, 1H), 2.83 (t, J=
12.6 Hz, 1H), 2.75–2.70 (m, 2H), 2.43 (td, J=13.5, 4.8 Hz, 1H), 2.33 (dd,
J=5.4, 1.0 Hz, 1H), 2.01–1.89 (m, 2H), 1.82 (m, 1H), 1.67–1.44 ppm (m,
3H); 13C NMR (CDCl3, 125 MHz): d=154.5, 153.3, 92.1, 81.5, 74.0, 69.3,
61.6, 48.4, 45.5, 43.3, 36.5, 33.6, 31.5, 30.0, 29.2 ppm; MS (70 eV, EI): m/z
(%): 368 (100) [M+], 340 (7), 302 (7), 244 (11), 124 (17); HRMS: Calcd
for C19H21CoN2O2: 368.0935; found: 368.0939.
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Crystal structure determinations: X-ray intensity data were recorded on
a Bruker SMART 1000 CCD area detector[59] with monochromated MoKa
radiation (l=0.71073 Š). Data collection strategies were assigned based
on the apparent Laue symmetry obtained from a preliminary examina-
tion of the unit cell (full sphere for a triclinic setting and an arbitrary
hemisphere for higher symmetries). Data were integrated with the
SAINT software package[60] and corrected for Lorentz polarization ef-
fects and an empirical absorption correction applied within SADABS.[61]
The space group for each compound was assigned based on systematic
absences observed within the data.[62] Structures were solved by direct
methods[63] and expanded using Fourier methods and refined routinely.[64]
Except where disorder is indicated, all non-hydrogen atoms were refined
with anisotropic thermal motion parameters. Hydrogen atoms were in-
cluded in geometrically calculated positions with thermal parameters tied
to the atom to which they are bonded. The water hydrogens in 33 and 72
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À
were included in their observed positions but were restrained to have O
H distances of 0.86 Š. A summary of the crystal and structure refinement
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CCDC-630383–CCDC-630390 contain the supplementary crystallograph-
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Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data
request/cif.
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This work was supported by CNRS, MRES, and the NSF (CHE
0451241). We thank the Swiss National Science Foundation and the
Roche Research Foundation (J. L., P.B.), the Humboldt Foundation
(T.H.), the Studienstiftung des deutschen Volkes (B.M.), the NSF predoc-
toral program (M. J.E.), and OAS-LASPAU (E.P.).
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7465