Single and consecutive cyclization reactions of alkynyl carbene complexes and 8-azaheptafulvenes: direct access to poh cyclic pyrrole and indole derivatives

Article abstract of DOI:10.1002/chem.200901257

The reactivity of alkynyl and enynyl Fischer carbene complexes towards 8-azaheptafulvenes is examined. Alkynyl carbenes 1 a-f undergo regioselective [8+2] heterocyclization with 8-aryl-8-azaheptafulvenes 2a,b providing cycloheptapyrroles 3 and 4 with meta

Full text of DOI:10.1002/chem.200901257

DOI: 10.1002/chem.200901257
Single and Consecutive Cyclization Reactions of Alkynyl Carbene Complexes
and 8-Azaheptafulvenes: Direct Access to Polycyclic Pyrrole and Indole
Derivatives
Josꢀ Barluenga,* Jaime Garcꢁa-Rodrꢁguez, ꢂngel L. Suꢃrez-Sobrino, and Miguel Tomꢃs[a]
Abstract: The reactivity of alkynyl and
enynyl Fischer carbene complexes to-
wards 8-azaheptafulvenes is examined.
Alkynyl carbenes 1a–f undergo regio-
selective [8+2] heterocyclization with
8-aryl-8-azaheptafulvenes 2a,b provid-
ing cycloheptapyrroles 3 and 4 with
metal carbene or ester functionality at
C3. Moreover, consecutive cyclization
reactions are involved when enynyl car-
benes are used. Thus, the cyclopen-
ta[b]pyrrole framework 7 is formed by
the consecutive [8+2] cyclization and
cyclopentannulation reactions. The ini-
ophiles to afford increasing structural
complexity (compounds 8 and 9). More
importantly, the construction of the
indole skeleton is accomplished with a
high degree of substitution and func-
tionalization (compounds 11–15) by a
one-pot sequence that involves [8+2]
tially
formed
cyclopentannulation
adduct can be intercepted through a
Diels–Alder reaction with classic dien-
À
cyclization, R NC or CO insertion,
Keywords: carbenes · chromium ·
cyclization · heterocycles · indole ·
pyrrole
and ring closure.
Introduction
Despite the fact that much work has been devoted to car-
bocylization reactions, the cyclization of FCCs with heteroa-
tom-containing substrates leading to heterocyclic systems
has been studied to a lesser extent.[9] Thus, apart from some
examples of cycloaddition reactions with 1,3-dipoles through
the activated carbon–carbon bond,[3] imines and unsaturated
imines have been the substrates most-commonly reported
for heterocyclization of FCCs. Although simple imines un-
dergo diastereo- and enantioselective [3+2] cyclization with
Cyclization reactions involving a,b-unsaturated Fischer car-
bene complexes (FCCs) have been a focus of great attention
in the past years, mostly owing to their rich and versatile re-
activity that makes them interesting starting materials for
the construction of cyclic molecules of different types.[1]
First of all, the strong activation of the conjugated carbon–
carbon double and triple bond by the metal–carbene func-
tion has been exploited for selective [4+2][2] and [3+2][3]
cycloaddition reactions. Moreover, the resulting carbene cy-
cloadducts can occasionally undergo further cyclization, thus
increasing the structural complexity of the reaction prod-
uct.[4] On the other hand, when the metal–carbon bond is in-
volved in the cyclization process, the unsaturated carbene
ligand can participate as a one-[5], three-[6], and five-carbon[7]
synthesis equivalent.[8]
enantiopure alkenyl carbene complexes (3Ccarbene
+
C,Nimine) to provide pyrrolidinone derivatives,[10] the [4+2]
and the [4+3] cycloaddition reactions were observed in the
case of a,b-unsaturated imines and alkynyl carbenes afford-
[11]
ing dihydropyridines (3C,Nimine + 2Ccarbene
nones (3C,Nimine + 3Ccarbene),[12] respectively.
)
and azepi-
Looking for a different heteroatom substrate, for instance
the unusual two-carbon, one-nitrogen synthon (2C,N), we
have recently found that the 8-azaheptafulvene system rep-
resents an appropriate model towards high-order cyclization
reactions of Fischer alkenyl carbene complexes to provide
fused pyrrolidine and piperidine derivatives ([8+2] and
[8+3] cyclization reactions, respectively; Scheme 1).[13]
Keeping these precedents in mind as well as 1) alkynyl
carbene complexes are very prone to react through the acti-
[a] Prof. Dr. J. Barluenga, Dr. J. Garcꢀa-Rodrꢀguez,
Dr. ꢁ. L. Suꢂrez-Sobrino, Prof. Dr. M. Tomꢂs
Instituto Universitario de Quꢀmica Organometꢂlica “Enrique Moles”
Unidad Asociada al CSIC
Universidad de Oviedo
Juliꢂn Claverꢀa 8, 33006 Oviedo (Spain)
Fax : (+34)985-103-450
E-mail: barluenga@uniovi.es
ꢀ
vated C C bond, 2) the known ability of alkenyl-conjugated
alkynyl carbene complexes to develop consecutive cycliza-
tion reactions, 3) a sole cycloaddition of 8-azaheptafulvenes
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200901257.
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FULL PAPER
Scheme 1. Cyclization reactions of 8-azaheptafulvenes with alkenyl and
alkynyl Fischer carbene complexes.
with a strongly activated alkyne has been described as
yet,[14] we have studied the reaction of Fischer alkynyl and
enynyl carbene complexes with N-aryl-8-azaheptafulvenes.
Herein, we report on the construction of the pyrrole unit by
the single [8+2] cyclization as well as of fused pyrroles, for
example, the indole framework by consecutive [8+2] cycli-
zation/benzoannulation reactions (Scheme 1). The structure
of all the metal–carbene complexes 1 (alkynyl carbenes 1a–
f; enynyl carbenes 1g–k) and 8-azaheptafulvenes 2a,b em-
ployed are depicted in Scheme 2.
Scheme 2. Carbene complexes 1 and 8-azaheptafulvenes 2 used in this
work.
Results and Discussion
ACHTUNGTRENNUNG[8+2] Cycloaddition of alkynyl carbene complexes 1a–f
with 8-aryl-8-azaheptafulvenes 2: First, chromium alkynyl
carbene 1a (R1 =Ph) was mixed with 8-azaheptafulvene 2a
(R2 =pMe-C6H4; 1:1 molar ratio) in THF and the mixture
was stirred for 3 h at room temperature. Removal of the sol-
vent and purification of the residue by column chromatogra-
phy (SiO2, hexanes/EtOAc 50:1) allowed the isolation of the
1,3a-dihydrocyclohepta[b]pyrrole carbene complex 3a in
84% yield (Scheme 3; Table 1, entry 1).[15] The scope of this
[8+2] cycloaddition reaction was studied by using chromi-
um–carbene complexes with representative substitution pat-
Scheme 3. The [8+2] cycloaddition of Fischer carbene complexes 1a–f
and 8-azaheptafulvenes 2.
Abstract in Spanish: Se ha estudiado la reactividad de alqui-
nil y eninil complejos carbeno de Fischer frente a 8-azahepta-
fulvenos. Los alquinil carbenos 1a–f experimentan una hete-
rociclaciꢀn [8 + 2] frente a 8-aril-8-azaheptafulvenos 2a–b
dando lugar a cicloheptapirroles 3 y 4 conteniendo en C-3
una funciꢀn metal carbeno o ꢁster. Ademꢂs, cuando se usan
eninilcarbenos se producen reacciones consecutivas de cicla-
ciꢀn. Asꢃ, mediante reacciones consecutivas de ciclaciꢀn [8 +
2] y ciclopentanulaciꢀn, se forma el esqueleto de ciclopen-
ta[b]pirrol 7. El aducto de ciclopentanulaciꢀn formado ini-
cialmente puede ser atrapado mediante una reacciꢀn Diels–
Alder con dienꢀfilos clꢂsicos, dando lugar a una mayor com-
plejidad estructural (compuestos 8 y 9). De mayor interꢁs es
el hecho de que se pueda llevar a cabo la construcciꢀn del es-
queleto de indol con alto grado de sustituciꢀn y funcionaliza-
ciꢀn (compuestos 11–15) mediante una secuencia “one-pot”
que implica una ciclaciꢀn [8 + 2], inserciꢀn de R-NC o CO
y cierre de anillo.
Table 1. Carbene cycloadducts 3 and esters 4 from carbenes 1 and aza-
heptafulvenes 2.
Entry
1
2
Cr R1
R2
Product Yield
[%][a]
1
2
3
4
1a 2a Cr Ph
pMe-C6H4
pMe-C6H4
pMe-C6H4
pMe-C6H4
pMe-C6H4
3a
84
72
75
69
69
70
78
80
80
88
64
87
4a[b]
3b
1b 2a Cr cyclopropyl
4b[b]
3c
1c
2a Cr TMS
4c[b]
3d
1d 2a Cr tBu
4d
3e
3 f
5
6
7
1e 2a
1 f 2a
1e 2b
W
W
W
Ph
pMeO-C6H4 pMe-C6H4
Ph
pMeO-C6H4 3g
4g
[a] Overall yields after purification with column chromatography (silica
gel, hexanes/EtOAc 50:1). [b] Obtained as major compound along with
the 1,4-dihydrocyclohepta[b]pyrrole isomer
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J. Barluenga et al.
terns, such as carbenes 1b–d (R1 =cyclopropyl, trimethylsilyl
(TMS), tBu). In this way, the new carbene complexes 3b–d
were obtained in good yields (69–78%) after purification by
chromatography (Scheme 3; Table 1, entries 2–4). On the
other hand, the [8+2] cycloaddition by using tungsten–car-
bene complexes 1e and 1 f took place under the same reac-
tion conditions to produce the tungsten–carbene complexes
3e–f (80–88% yield; Table 1, entries 5 and 6). Moreover,
the cyclization between the 8-azaheptafulvene with a remov-
able substituent (2b; R2 =pMeO-C6H4)[16] and the carbene
1e led to the 1,6-dihydrocyclohepta[b]pyrrole carbene
isomer 3g albeit in a lower yield (64%; Table 1, entry 7).[15]
The course of this [8+2] cyclization can be rationalized by
the nucleophilic conjugate addition through the lone pair on
the nitrogen atom to the electrophilic alkynylcarbene to
form the zwitterionic intermediate I, which cyclizes though
attack of the metal allenyl metallate to the tropilium cation.
Next, the oxidation of the resulting carbenes 3a–d,g to
the corresponding esters 4 was achieved in good yield (69–
87%) with pyridine oxide (THF, 258C, 1 h; Scheme 3;
Table 1, entries 1–4,7). Notably, the 1,3a-dihydrocyclohep-
ta[b]pyrrole skeleton of the starting metal carbenes 3a–d
undergoes isomerization during chromatographic purifica-
tion to the more stable 1,6-dihydrocyclohepta[b]pyrrole
esters 4a–d (SiO2, hexanes/EtOAc 50:1). In addition, minor
amounts of the isomeric 1,4-dihydrocyclohepta[b]pyrrole
esters (<15%) were formed and separated in most cases.[15]
Finally, compound 4a was aromatized by hydride abstrac-
tion with trityl tetrafluoroborate to provide the pyrrole-
fused tropylium salt 5 (99% yield; Scheme 4).
the expected tungsten–carbene cycloadduct 6a was obtained
in 84% yield after removal of solvent and column chroma-
tography
purification
(SiO2,
hexanes/EtOAc
10:1;
Scheme 5).
Scheme 5. Consecutive [8+2] cycloaddition and cyclopentannulation of
carbene 1k and azaheptafulvene 2a.
Compound 6a was then subjected to thermal cyclization
(refluxing THF, 3 h) to furnish the tetracyclic ketone 7 in
82% yield after column chromatography (SiO2, hexanes/
EtOAc 10:1). This cyclopentannulation most probably in-
volves electrocyclization of the metallatriene fragment and
reductive metal elimination (intermediate II), followed by
SiO2-promoted hydrolysis of the enol ether (Scheme 5).[15]
On the other hand, the chromium cycloadduct carbene 6b
was formed from carbene 1i under the above reaction con-
1
ditions as established by H NMR spectroscopy of the crude
(Scheme 6). However, unlike the analogous tungsten car-
bene 6a, this chromium carbene was too unstable to be puri-
fied. Moreover, attempts to induce the thermal cyclopentan-
nulation reaction by stirring crude 6b failed owing to de-
Scheme 4. Aromatization of 4a to the tropilium salt 5.
Consecutive [8+2] cyclization/cyclopentannulation reac-
tions of enynyl carbene complexes 1i and 1k with 8-azahep-
tafulvene 2a: Frequently, the cyclization of alkynylcarbenes
can be extended beyond a single cyclization if a conjugated
alkenyl substituent is present in the starting metal car-
bene.[17] In such a case, the corresponding cycloadducts 3
would feature the 1-metalla-1,3,5-hexatriene function (see
Scheme 3; R1 =alkenyl in compounds 3) amenable for fur-
ther diverse cyclizations. First, it was noted that running the
reaction of azaheptafulvene 2a with the tungsten cyclohexe-
nylethynyl carbene 1k under the reaction conditions de-
scribed above (THF, room temperature) led to a complex
mixture of unidentified compounds. Satisfactorily, the reac-
tion worked well if the reagents were mixed at À508C and
the resulting mixture slowly warmed up to 08C. In this way,
Scheme 6. Formation and Diels–Alder reaction of the cyclopentannula-
tion intermediate II with dimethyl acetylenedicarboxylate.
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Cyclization Reactions of Alkynyl Carbene Complexes
FULL PAPER
composition even at room temperature. At this point, we
were interested to know whether the cyclopentannulation to
the intermediate II had occurred prior to decomposition. To
prove this, the carbene 1i and the azaheptafulvene 2a were
allowed to form 6b (THF, À50 to 08C) and then dimethyl
acetylenedicarboxylate was added to the reaction mixture
and heated at 608C for 12 h. Removal of the solvent and pu-
rification through column chromatography of the resulting
mixture (SiO2, hexanes/EtOAc 3:1) afforded compound 8 in
62% overall yield (Scheme 6). Therefore, the initial carbene
cycloadduct 6b does undergo the cyclopentannulation reac-
tion to generate the cyclopentadiene structure II, which in
turn yields the [4+2] cycloadduct 8 upon reaction with di-
methyl acetylenedicarboxylate (Scheme 6).The structure of
8 was elucidated by NMR analysis and confirmed by X-ray
diffraction analysis (Figure 1).[18]
Consecutive [8+2] cyclization/benzoannulation reactions of
chromium enynyl carbene complexes 1g–j with 8-azahepta-
fulvenes 2: Synthesis of substituted indoles: The usefulness
of the [8+2] cyclization of alkynyl Fischer carbenes and 8-
azafulvenes can be extended to the synthesis of heteropoly-
cyclic compounds containing the indole framework by using
a one-pot [8+2]/
in Scheme 8. Thus, chromium enynyl carbene 1 g and N-(4-
[5+1] cyclization sequence,[20] as is depicted
ACHTUNGTRENNUNG
Scheme 8. One-pot [8+2]/ACTHNUTRGNE[NUG 5+1] cyclization of chromium carbene 1g.
methoxyphenyl)-8-azaheptafulvene 2b were mixed in THF
at À508C and the solution allowed to warm to 08C. tBuNC
(2 equiv) was added to the resulting [8+2]-cycloadduct-con-
taining mixture and then stirred at 708C for 2 h to give,
after solvent removal and column chromatography purifica-
tion (SiO2, hexanes/EtOAc 5:1), the cycloadduct 11 in 78%
yield. In this case, the primary [8+2] cycloadduct carbene
(see cycloadducts 6a,b in Scheme 5 and Scheme 6) would
undergo isocyanide insertion to the non-isolated metal het-
erocumulene species III, followed by metal-promoted elec-
trocyclic ring closure to the dihydroindole adduct 10. Upon
chromatographic purification, the latter compound com-
pletely isomerizes to the aromatic dihydrocyclohepta[b]in-
dole structure 11.
Figure 1. X-ray structure for compound 8 in the crystal. Thermal ellip-
soids at the 50% probability level.
In the same way, the one-pot multicyclization process
with maleinimide as the dienophile afforded compound 9 in
74% yield, wherein five stereogenic centers were created
consecutively
with
complete
diastereoselectivity
(Scheme 7).[19] The structure of 9 was determined by NMR
spectroscopic experiments and the relative configuration as-
signed by NOESY experiments.
Because of the great significance of the indole nucleus,[21]
this direct indole-ring-construction procedure was extended
to the cyclic enynyl carbene complexes 1h–j and azahepta-
fulvenes 2a,b (Scheme 9). Following the above protocol,
carbenes 1h–j and azaheptafulvene 2a (R2 =pMe-C6H4)
were combined and the resulting mixture treated with
tBuNC to provide an inseparable mixture of isomeric cyclo-
heptaindoles 12 and 13 in high overall yields after chromato-
graphic purification (Table 2, entries 1–3). On the contrary,
the use of azaheptafulvene 2b (R2 =pMeO-C6H4) resulted
in the formation of a single isomer 12d (82% yield) on reac-
tion with 1i (Table 2, entry 4). Furthermore, this sequence
could be carried out successfully by using carbon monoxide
instead of tert-butyl isocyanide, as the third component
(Table 2, entries 5–7). Thus, after reacting carbenes 1h,i and
azaheptafulvenes 2a,b, the flask containing the reaction
Scheme 7. One-pot formation of 9 from 1i and 2a by a [8+2] cycloaddi-
tion/cyclopentannulation/ACTHNUTRGENUGN[4+2] cycloaddition sequence.
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J. Barluenga et al.
(trityl tetrafluoroborate, CH2Cl2, 258C, 1 h) permitted to iso-
late the expected indole-fused tropylium cation 15 in 97%
yield. The X-ray diffraction structure of 15 is depicted in
Figure 2.[18] Therefore, both the pyrrole and the arene rings
of the indole framework were built in a one-pot process by
consecutive [8+2] and [5+1] cyclization steps. Notably,
most general methods to synthesize the indole ring are
based on the annulation of the pyrrole ring onto a pre-exist-
ing arene nucleus.[22] Moreover, the presence of the indole
skeleton in innumerable natural and bioactive compounds
enhances the synthetic interest in this last reaction se-
quence.
Scheme 9. ACHTUNGTRENNUNG[8+2]/ACHTUNGTRENNUNG[5+1] Cyclization process to cycloheptaindoles 12 and
13.
ꢀ
Table 2. Cycloheptaindoles 12 and 13 from carbenes 1, azaheptafulvenes 2, and C Y (CNtBu/CO).
Conclusions
Entry
1
2
n
X
R2
C Y
Products (12:13)
Yield
[%][a]
ꢀ
The [8 +2] heterocyclization re-
action of alkynyl Fischer car-
benes with 8-azaheptafulvenes
described herein represents an
efficient and simple access to
cycloheptadiene-fused pyrroles
with a versatile functionality at
1
2
3
4
5
6
7
1h
1i
1j
1i
1i
1h
1i
2a
2a
2a
2b
2a
2b
2b
1
2
2
2
2
1
2
CH2
CH2
O
CH2
CH2
CH2
CH2
pMe-C6H4
pMe-C6H4
pMe-C6H4
pMeO-C6H4
pMe-C6H4
pMeO-C6H4
pMeO-C6H4
CNtBu
CNtBu
CNtBu
CNtBu
CO
12a, 13a (1:10)
12b, 13b (1:4)
12c, 13c (1:2)
12d
12e, 13e (1:1)
12 f
81
89
86
82
75
79
71
CO
CO
12g
[a] Overall yields after purification with column chromatography (silica gel, hexanes/EtOAc 5:1).
mixture was filled with CO (1 atm), irradiated under a UV
lamp (400 W pressure mercury lamp) for 30 min, and the
mixture stirred at room temperature for 12 h. Following this
protocol, a 1:1 mixture of 12e and 13e resulted from aza-
heptafulvene 2a and carbene 1i (Table 2, entry 5), whereas
single isomers 12 f,g were again exclusively isolated from
azaheptafulvene 2b and carbenes 1h,i (Table 2, entries 6
and 7).
Furthermore, the mixtures 12a–c,e/13a–c,e were hydro-
genated (H2, 1 bar, C/Pd, 258C, 1 h) to the single cyclohep-
taindoles 14a–c,e in nearly quantitative yields (Scheme 10).
Moreover, hydride extraction from the mixture of 12e/13e
Figure 2. X-ray structure for compound 15 in the crystal. Thermal ellip-
soids at the 50% probability level.
C3 (metal carbene, ester). By starting from readily available
enynylcarbenes in which the alkenyl appendage is attached
at the C3 position, new processes that involve consecutive
cyclization reactions can be designed. Thus, the formation of
the cyclopenta[b]pyrrole framework by the consecutive
[8+2] cyclization/cyclopentannulation reactions is illustrat-
ed. More importantly, the construction of both rings of the
indole skeleton is easily accomplished in a regioselective
manner by the one-pot sequence that involves [8+2] cycli-
zation/R-NC or CO insertion/ring closure. The high degree
of substitution and functionalization of the resulting benzo
Scheme 10. Hydrogenation and hydride abstraction in 12 and 13.
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Cyclization Reactions of Alkynyl Carbene Complexes
FULL PAPER
(m, 1H), 5.45ACTHNUTRGNEUG(N s, 1H), 5.4 (m, 1H), 3.97 (s, 3H), 3.91 (s, 3H), 2.96–2.90
moiety should be noted. Finally, it is shown that pyrrole-
containing cycloadducts with increasing structural complexi-
ty can be accessed if the cyclopentannulation intermedi-
ate—1,3-cyclopentadiene system—is intercepted by classic
dienophiles.
(m, 2H), 2.52–2.50 (m, 2H), 2.40–2.35 (m, 2H), 2.06–1.96 ppm (m, 2H);
13C NMR (75 MHz, CDCl3, 258C, TMS): d=159.2 (C), 139.0 (C), 138.9
(C), 137.8 (C), 131.2 (C), 130.2 (CH), 129.8 (C), 128.8 (C), 123.6 (CH),
122.4 (C), 121.1 (CH), 119.1 (CH), 118.1 (C), 115.4 (C), 114.3 (CH),
113.8 (CH), 61.3 (CH3), 55.4 (CH3), 31.1 (CH2), 29.2 (CH2), 27.3 (CH2),
25.5 ppm (CH2); HRMS: m/z: calcd for C24H23NO3: 373.1678; found:
373.1670.
Experimental Section
Acknowledgements
Typical preparation of compound 3a: A solution of alkynyl carbene 1a[23]
(168.1 mg, 0.5 mmol) and 8-para-tolyl-8-azaheptafulvene 2a[24] (97.6 mg,
0.5 mmol) in THF (2 mL) was stirred under nitrogen at room tempera-
ture for 3 h. Then, the solvent was removed and the crude product puri-
fied by column chromatography (SiO2, hexanes/EtOAc 50:1) to give 3a
(223.2 mg, 84%). 1H NMR (300 MHz, CDCl3, 258C, TMS): d=7.34–6.92
(m, 9H), 6.59–6.41 (m, 2H), 6.28–6.20 (m, 1H), 5.50–5.42 (m, 1H), 5.30–
5.22 (m, 1H), 4.38 (brs, 1H), 4.14 (s, 3H), 2.31 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3, 258C, TMS): d =317.6 (C), 230.5 (C), 223.6 (C), 146.8
(C), 142.5 (C), 138.0 (C), 136.1 (C), 133.2 (C), 132.6 (C), 130.4 (CH),
129.3 (CH), 128.8 (CH), 128.4 (CH), 127.8 (CH), 126.3 (CH), 125.0
(CH), 114.4 (CH), 100.2 (CH), 64.1 (CH3), 49.3 (CH), 21.0 ppm (CH3);
HRMS: m/z: calcd for C29H21NO6Cr:. 531.0774; found: 531.0777.
This research was partially supported by the Governments of Spain
(CTQ2007–61048) and Principado de Asturias (IB08–088).
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S. R. Gilbertson, Tetrahedron 1985, 41, 5813–5832; c) J. Bao, W. D.
Wulff, V. Dragisich, S. Wenglowsky, R. G. Ball, J. Am. Chem. Soc.
1994, 116, 7616–7630; d) J. Barluenga, F. Aznar, A. Martin, S. Bar-
luenga, Tetrahedron 1997, 53, 9323–9340; e) J. Barluenga, R. M.
Canteli, J. Flꢄrez, S. Garcꢀa-Granda, A. Gutiꢅrrez-Rodrꢀguez, E.
Martꢀn, J. Am. Chem. Soc. 1998, 120, 2514–2522; f) M. A. Vꢂzquez,
L. Cessa, J. L. Vega, R. Miranda, R. Herrera, H. A. Jimꢅnez-
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1927; g) M. A. Vꢂzquez, L. Reyes, R. Miranda, J. J. Garcꢀa, H. A. Ji-
mꢅnez-Vꢂzquez, J. Tamariz, F. Delgado, Organometallics 2005, 24,
3413–3421; h) J. Barluenga, S. Martꢀnez, A. L. Suꢂrez-Sobrino, M.
Tomꢂs, Organometallics 2006, 25, 2337–2343.
Typical preparation of compound 8: Carbene 1i[7b] (170.1 mg, 0.5 mmol)
and 8-para-tolyl-8-azaheptafulvene 2a (97.6 mg, 0.5 mmol) were mixed in
THF (2 mL) at - 508C and the solution allowed to slowly warm to 08C.
Then, dimethyl acetylenedicarboxilate (184 mL, 1.5 mmol) was added and
the mixture warmed at 708C for 2 h. After solvent removal, the crude
mixture was purified by column chromatography (hexanes/EtOAc 3:1) to
give compound 8 (150.5 mg, 62%): 1H NMR (300 MHz, CDCl3, 258C,
3
3
TMS): d=7.28 (s, 4H), 6.70 (d, JACTHNUGRTENNUG(H,H)=9.5 Hz, 1H), 6.11 (d, JACHTUNGTRNE(NUGN H,H)=
9.8 Hz, 1H), 5.39–5.31 (m, 1H), 5.22–5.13 (m, 1H), 3.82 (s, 3H), 3.75 (s,
3H), 3.61 (s, 3H), 3.31–3–26 (m, 1H), 2.87–2.72 (m, 1H), 2.46 (s, 3H),
2.32–2.24 (m, 2H), 1.81–1.72 (m, 1H), 1.69–1.58 (m, 2H), 1.54–1.43 (m,
1H), 1.38–1.34 (m, 2H), 1.20–1.16 (m, 1H), 0.93–0.87 ppm (m, 1H);
13C NMR (75 MHz, CDCl3, 258C, TMS): d=164.8 (C), 162.0 (C), 150.2
(C), 146.7 (C), 137.7 (C), 135.2 (C), 133.1 (C), 130.4 (C), 130.0 (C), 129.4
(CH), 127.0 (CH), 122.8 (CH), 121.8 (C), 119.9 (CH), 115.5 (CH), 110.0
(CH), 97.3 (C), 85.1 (CH), 56.8 (CH3), 55.2 (C), 52.2 (CH3), 51.8 (CH3),
27.2 (CH2), 25.0 (CH2), 24.6 (CH2), 23.4 (CH2), 22.8 (CH2), 21.2 ppm
(CH3); HRMS: m/z: calcd for C30H31NO5: 485.2197; found: 485.2199.
Typical preparation of compound 11: Enynyl carbene 1g[7b] (168.1 mg,
0.5 mmol) and 8-para-methoxyphenyl-8-azaheptafulvene 2b[24] (105.6 mg,
0.5 mmol) were mixed in THF (2 mL) under nitrogen at À508C and the
mixture allowed to slowly warm to 08C, then tert-buthylisocianate
(115 mL, 1 mmol) was added and the mixture warmed at 708C for 2 h.
After solvent removal, the resulting crude mixture was purified (SiO2,
hexanes/EtOAc 5:1) to give 11 (181.2 mg, 78%): 1H NMR (300 MHz,
[3] a) C. A. Merlic, A. Baur, C. C. Aldrich, J. Am. Chem. Soc. 2000,
122, 7398–7399; b) J. Barluenga, M. A. Fernꢂndez-Rodrꢀguez, E.
Aguilar, F. Fernꢂndez-Marꢀ, A. Salinas, B. Olano, Chem. Eur. J.
2001, 7, 3533–3544.
[4] J. Barluenga, F. Aznar, M. A. Palomero, Angew. Chem. 2000, 112,
4514–4516; Angew. Chem. Int. Ed. 2000, 39, 4346–4348.
CDCl3, 258C, TMS): d=7.53–7.21 (m, 8H), 7.02 (d, 3J
2H), 6.90 (s, 1H), 6.46 (d, 3J
(H,H)=7.2 Hz, 1H), 5.61–5.58 (m, 1H),
5.48–5.41(m, 1H), 4.11 (s, 3H), 3.85 (s, 3H), 2.61–2.47 (m, 2H), 1.03 ppm
ACHTUNGTREN(NUNG H,H)=8.8 Hz,
AHCTUNGTRENNUNG
[5]
ACHTUNGTREN[NUNG 2+1]: a) J. Barluenga, S. Lꢄpez, A. A. Trabanco, A. Fernꢂndez-
ACHTUNGTRENNUNG
Acebes, J. Flꢄrez, J. Am. Chem. Soc. 2000, 122, 8145–8154; b) J.
Barluenga, M. A. Fernꢂndez-Rodrꢀguez, P. Garcꢀa-Garcꢀa, E. Agui-
lar, I. Merino, Chem. Eur. J. 2006, 12, 303–313.
(s, 9H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=159.8 (C), 151.1
(C), 149.1 (C), 142.5 (C), 136.7 (C), 135.4 (C), 131.3 (C), 130.5 (C), 130.1
(CH), 129.1(C), 128.9 (CH), 128.7 (CH), 128.1 (C), 126.6 (CH), 124.2
(CH), 121.4 (CH), 119.4 (CH), 114.8 (CH), 114.6 (CH), 107.4 (CH), 59.6
(CH3), 55.5 (CH3), 54.8 (C), 30.5 (CH3), 27.5 ppm (CH2); HRMS: m/z:
calcd for C31H32N2O2: 464.2464; found: 464.2468.
[6]
AHCTUNGTREG[NNUN 3+2]: a) R. Aumann, M. Kçssmeier, A. Jꢆntti, Synlett 1998, 1120–
1122; b) M. Hoffmann, M. Buchert, H. U. Reissig, Chem. Eur. J.
1999, 5, 876–882; c) J. Barluenga, S. Lꢄpez, J. Flꢄrez, Angew. Chem.
2003, 115, 241–243; Angew. Chem. Int. Ed. 2003, 42, 231–233; d) J.
Barluenga, J. Alonso, F. J. FaÇanꢂs, J. Am. Chem. Soc. 2003, 125,
2610–2616; e) J. Barluenga, R. Vicente, P. Barrio, L. A. Lꢄpez, M.
Tomꢂs, J. Am. Chem. Soc. 2004, 126, 5974–5975; f) Y.-T. Wu, D. Vi-
dovic, J. Magull, A. de Meijere, Eur. J. Org. Chem. 2005, 1625–
1636; [3+3]: g) J. Barluenga, A. Ballesteros, J. Santamarꢀa, R. B. de
La Rffla, E. Rubio, M. Tomꢂs, J. Am. Chem. Soc. 2003, 125, 1834–
1842; [4+3]: h) J. Barluenga, J. Alonso, F. Rodrꢀguez, F. J. FaÇanꢂs,
Angew. Chem. 2000, 112, 2555–2558; Angew. Chem. Int. Ed. 2000,
39, 2459–2462; i) J. Barluenga, S. Martꢀnez, A. L. Suꢂrez-Sobrino,
M. Tomꢂs, J. Am. Chem. Soc. 2002, 124, 5948–5949; j) J. Barluenga,
Typical preparation of compound 12 f: Enynyl carbene 1h[7b] (163.1 mg,
0.5 mmol) and 8-para-methoxyphenyl-8-azaheptafulvene 2b (105.6 mg,
0.5 mmol) were mixed in THF (2 mL) under nitrogen at À508C and the
mixture allowed to slowly warm to 08C. Then, the flask was filled with
CO (1 atm) and the mixture irradiated (400 W pressure mercury lamp)
for 30 min and stirred for an additional 12 h at room temperature. After
solvent removal, the crude product was purified (SiO2, hexanes/EtOAc
5:1) to give 12 f (147.4 mg, 79%): 1H NMR (300 MHz, CDCl3, 258C,
3
3
TMS): d=7.30 (d, J
N
ACHTUNGTREN(NUGN H,H)=8.7 Hz, 2H),
7.01 (d, 3J(H,H)=8.7 Hz, 2H), 6.27 (d, 3J
A
ACHTUNGTRENNUNG
Chem. Eur. J. 2009, 15, 8800 – 8806
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8805

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charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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Received: May 12, 2009
Published online: July 23, 2009
8806
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ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 8800 – 8806