Generation and reaction of metal-containing carbonyl ylides: Tandem [3+2]-cycloaddition-carbene insertion leading to novel polycyclic compounds [1]

Full text of DOI:10.1021/ja010478i

5814
J. Am. Chem. Soc. 2001, 123, 5814-5815
Scheme 1
Generation and Reaction of Metal-Containing
Carbonyl Ylides: Tandem
[3+2]-Cycloaddition-Carbene Insertion Leading to
Novel Polycyclic Compounds
Nobuharu Iwasawa,* Masahide Shido,† and Hiroyuki Kusama
Department of Chemistry, Tokyo Institute of Technology
O-okayama, Meguro-ku, Tokyo 152-8551, Japan
Department of Chemistry, Graduate School of Science
The UniVersity of Tokyo, Hongo, Bunkyo-ku
Tokyo 113-0033, Japan
ReceiVed February 22, 2001
In this paper, we report the generation of novel metal-containing
carbonyl ylides by the reaction of o-ethynylphenyl ketones with
W(CO)5‚THF, and the reaction of these ylides with electron-rich
alkenes to give polycyclic compounds through a [3+2]-cycload-
dition, followed by insertion of the resulting tungsten carbene
moiety into a neighboring C-H bond.
We have previously reported that benzopyranylidene complexes
can be prepared by the treatment of o-ethynylphenyl ketone
derivatives with W(CO)5‚THF through the electrocyclization of
vinylidene intermediates (see Scheme 2, path iii), and that these
complexes undergo Diels-Alder reaction with electron-rich
alkenes such as alkenyl ethers, ketene acetals, and enamines to
give substituted naphthalenes in good yield.1 To carry out this
reaction by a one-pot procedure, we examined the same com-
plexation reaction in the presence of a ketene acetal, which led
us to the discovery of the novel reaction pathways described
below.
When o-ethynylphenyl isopropyl ketone 1a was treated with a
stoichiometric amount of W(CO)5‚THF in the presence of 4 equiv
of 1,1-diethoxyethylene, the starting material was consumed
within 2 h at room temperature. To our great surprise, purification
of the crude product revealed that the expected 3-ethoxy-1-
isopropylnaphthalene1 had not been formed at all, but rather that
a novel polycyclic compound 2a had been obtained in 73% yield
as a single stereoisomer. Furthermore, the same product was also
obtained in nearly the same yield even with 20 mol % of W(CO)5‚
THF. The structure, including the relative stereochemistry, of this
compound was confirmed to be as shown in eq 1 by X-ray
analysis.
vinyltungsten species 5a to give a formal [3+2]-cycloaddition
product, an unstable carbene complex 6a.6 Finally, the W(CO)5-
carbene moiety thus generated inserts into a C-H bond of the
neighboring ethoxy group7 to give the product 2a while regenerat-
ing W(CO)5‚THF. This result is quite interesting because a
benzopyranylidene complex is produced when the same reaction
is carried out in the absence of the ketene acetal, suggesting the
presence of an equilibrium between the π-complex 3a8 and the
metal-containing 1,3-dipole 4a.
The generality of this reaction was examined employing several
o-ethynylphenyl ketone derivatives and electron-rich alkenes. As
summarized in Table 1, both vinyl ethers and ketene acetals can
be employed as the electron-rich alkene component to give the
corresponding polycyclic products in good yield with 10 or 20
mol % of W(CO)5‚THF. Several kinds of aryl ketone including
an aryl aldehyde can also be employed in this reaction. In most
cases, a single diastereomer is obtained, whose relative stereo-
chemistry is assigned to be the same as that of 2a based on the
1
similarity of the coupling constants in its H NMR spectrum.
(2) For reviews on the carbonyl ylides, see: (a) Padwa, A.; Weingarten,
M. D. Chem. ReV. 1996, 96, 223. (b) Do¨rwald, F. Z. Metal Carbenes in
Organic Synthesis; Wiley-VCH: Weinheim, 1999; p 206. For some recent
examples, see: (c) Pirrung, M. C.; Kaliappan, K. P. Org. Lett. 2000, 2, 353.
(d) Kitagaki, S.; Anada, M.; Kataoka, O.; Matsuno, K.; Umeda, C.; Watanabe,
N.; Hashimoto, S. J. Am. Chem. Soc. 1999, 121, 1417.
(3) We have not yet been successful in confirming the presence of metal-
containing carbonyl ylides such as 4. Direct observation of a mixture of
o-ethynylphenylbutyrophenone 1c and W(CO)5‚THF-d8 in THF-d8 by NMR
revealed the appearance of small amounts of two kinds of unknown species,
one of which could be the carbonyl ylide 4c. They disappear gradually along
with the formation of the benzopyranylidene complex 12c. We are currently
investigating to determine the exact structure of these two species.
(4) For the attack of oxygen nucleophile onto a π-complexed alkyne, see:
Hegedus, L. S. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.;
Pergamon Press: Oxford, England, 1991; Vol. 4, p 551.
(5) No reaction occurred when a mixture of acetophenone and 1,1-
diethoxyethylene was treated with a stoichiometric amount of W(CO)5‚THF.
(6) We are not certain whether the reaction proceeds in a stepwise or a
concerted manner. In the reaction with the ketene silyl acetal, we observed
the formation of the product derived from the first addition step as shown
below. (Yields were not optimized.)
The mechanism of formation of this compound is thought to
be as follows (Scheme 1). Treatment of W(CO)5‚THF with
o-ethynylphenyl ketone 1a gives a metal-containing carbonyl ylide
4a2,3 through the endo-mode of attack of the carbonyl oxygen
onto the W(CO)5-π-complexed alkynyl part of the molecule.4,5
Then, the ketene acetal attacks the C1 carbon of this complex
followed by intramolecular nucleophilic attack by the resulting
(7) For examples of this type of reaction, see: (a) Fischer, H.; Schmid, J.;
Ma¨rkl, R. J. Chem. Soc., Chem. Commun. 1985, 572. (b) Wang, S. L. B.;
Wulff, W. D.; Hoogsteen, K. J. Am. Chem. Soc. 1992, 114, 10665. (c)
Barluenga, J.; Rodr´ıguez, F.; Vadecard, J.; Bendix, M.; Fan˜ana´s, F. J.; Lo´pez-
Ortiz, F.; Rodr´ıguez, M. A. J. Am. Chem. Soc. 1999, 121, 8776. (d) Takeda,
K.; Okamoto, Y.; Nakajima, A.; Yoshii, E.; Koizumi, T. Synlett 1997, 1181.
(e) Barluenga, J.; Aznar, F.; Ferna´ndez, M. Chem. Eur. J. 1997, 3, 1629. See
also: Sulikowski, G. A.; Cha, K. L.; Sulikowski, M. M. Tetrahedron:
Asymmetry 1998, 9, 3145.
* Address correspondence to this author at the Tokyo Institute of Technol-
ogy.
† The University of Tokyo.
(1) Iwasawa, N.; Shido, M.; Maeyama, K.; Kusama, H. J. Am. Chem. Soc.
2000, 122, 10226. See also: Ohe, K.; Miki, K.; Yokoi, T.; Nishino, F.; Uemura,
S. Organometallics 2000, 19, 5525.
(8) For a review of π-complexes of group 6 metals, see: Whiteley, M. W.
In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone, F. G.
A., Wilkinson, G., Eds.; Pergamon: Oxford, 1995; Vol. 5, p 331.
10.1021/ja010478i CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/25/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 24, 2001 5815
Scheme 2
Table 1. Reaction of Various o-Ethynylphenyl Ketones with
Electron-Rich Alkenes
R1 ) OC2H5, R2 ) CH3
R1 ) H, R2 ) n-C3H7
a
b
R )
i-Pr (1a)
Me (1b)
n-Pr (1c)
H (1d)
76 (2a)
78 (2b)
75 (2c)
50 (2d)
74 (2e)
74 (2f)
94c (2g)
a 20 mol % of W(CO)5‚THF and about 5 equiv of the ketene acetal
were employed. b 10 mol % of W(CO)5‚THF and about 10 equiv of
the vinyl ether were employed. c Including about 5% yield of an
isomeric product.
Furthermore, when o-ethynylphenyl methyl ketone 1b (R )
Me) was treated with W(CO)5‚THF in the presence of 5 equiv of
water, o-acetylacetophenone 10b (R ) Me) was obtained in about
50% yield. Direct observation of the reaction mixture in THF-d8
clearly showed the formation of a methyleneisobenzofuran
derivative 9b (R′ ) H) at room temperature. This compound is
produced by the exo-mode of attack of the carbonyl oxygen onto
the W(CO)5-π-complexed alkyne to give 7b (R ) Me), followed
by protonation of the C-W bond and deprotonation from the
methyl group (see Scheme 2). To account for the various
phenomena observed, we propose the following overall picture
of the dynamic equilibria involved in this reaction, which can be
partially controlled by the order of addition of the reagents.
The reaction of o-ethynylphenyl ketones and W(CO)5‚THF can
proceed through the following three pathways: (i) exo-attack of
the carbonyl oxygen to the π-complexed alkyne to give 7, which
might be in equilibrium with its tautomer 8,9 (ii) endo-attack of
the carbonyl oxygen to the π-complexed alkyne to give carbonyl
ylide 4, and (iii) 1,2-H shift to give vinylidene complex 11, which
then undergoes irreversible electrocyclization to give pyranylidene
complex 12. We currently suppose that reactions i and ii are faster
than reaction iii, but that pathways i and ii are under rapid
equilibrium. Thus, in the presence of a reagent capable of trapping
intermediate 4 or 7 such as H2O or electron-rich alkenes, the
reaction proceeds through either pathway i or ii to give the
corresponding hydrolysis product 10 (path i) or [3+2]-cycload-
dition product 2 (path ii).10 However, in the absence of such
trapping reagents, an equilibrium exists between 4, 7, and the
π-complex 3, and formation of the vinylidene complex 11 occurs
as a relatively slower process,11 which gives benzopyranylidene
complex 12 through an irreversible unimolecular electrocycliza-
tion.
In conclusion we have developed a novel method for the
generation of metal-containing carbonyl ylides and their [3+2]-
cycloaddition followed by carbene insertion for the construction
of complex cyclic carbon frameworks. The dynamic equilibrium
of the system has also been clarified.
Acknowledgment. This research was partly supported by the Toray
Science Foundation and a Grant-in-Aid for Scientific Research from the
Ministry of Education, Science, Sports and Culture of Japan. We would
like to thank Ms. Sachiyo Kubo for performing X-ray analysis.
(9) When we examined the reaction of cyclohexene derivative A with
W(CO)5‚THF, formation of a rather unstable, blue-colored complex was
observed by TLC. We suppose this complex to be B, as DMSO oxidation of
the mixture gave an aldehyde C in moderate yield. Isolation of the complex
B and its oxidation to the aldehyde C were also presented by Ohe, Uemura,
and their co-workers (Kyoto University) at the 79th Annual Meeting of the
Chemical Society of Japan, Kobe, March 31, 2001. We thank them for
informing us of their unpublished results.
Supporting Information Available: Preparative methods and spectral
and analytical data of compounds 2 and X-ray data for 2a (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
JA010478I
(10) The reason for the difference in the reaction pathways between H2O
and electron-rich alkenes is not obvious.
(11) It is not certain whether there is an equilibrium between the π-complex
and the vinylidene complex, although it is generally accepted that there is.
For a review of vinylidene complexes, see: (a) McDonald, F. E. Chem. Eur.
J. 1999, 5, 3103. (b) Bruneau, C.; Dixneuf, P. H. Acc. Chem. Res. 1999, 32,
311. (c) Bruce, M. I. Chem. ReV. 1991, 91, 197. (d) Bruce, M. I.; Swincer, A.
G. AdV. Organomet. Chem. 1983, 22, 59.