Generation and reaction of tungsten-containing carbonyl ylides: [3 + 2]-Cycloaddition reaction with electron-rich alkenes

Article abstract of DOI:10.1021/ja044194k

Novel tungsten-containing carbonyl ylides 7, generated by the reaction of the o-alkynylphenyl carbonyl derivatives 1 with a catalytic amount of W(CO) ₅(thf), reacted with alkenes to give polycyclic compounds 5 through [3 + 2]-cycloaddition reaction followed by intramolecular C-H insertion of the produced nonstabilized carbene complex intermediates 8. In the presence of triethylsilane, these tungsten-containing carbene intermediates 8 were smoothly trapped intermolecularly by triethylsilane to give silicon-containing cycloadducts 17 with regeneration of the W(CO)₅ species. By this procedure, the scope of alkenes employable for this reaction was clarified. The presence of the tungsten-containing carbonyl ylide 7c was confirmed by direct observation of the mixture of o-ethynylphenyl ketone 1c and W(CO) ₅(thf-d₈). Careful analysis of the intermediate by 2D NMR, along with the observation of the direct coupling with tungsten-183 employing the ¹³C-labeled substrate, confirmed the structure of the ylide 7c. Examination using (E)- or (Z)- vinyl ether revealed that the [3 + 2]-cycloaddition reaction proceeded in a concerted manner and that the facial selectivity of the reaction differed considerably depending on the presence or absence of triethylsilane. These results clarified the reversible nature of this [3 + 2]-cycloaddition reaction.

Full text of DOI:10.1021/ja044194k

Published on Web 02/05/2005
Generation and Reaction of Tungsten-Containing Carbonyl
Ylides: [3 + 2]-Cycloaddition Reaction with Electron-Rich
Alkenes
Hiroyuki Kusama, Hideaki Funami, Masahide Shido, Yoshihiro Hara,
Jun Takaya, and Nobuharu Iwasawa*
Contribution from the Department of Chemistry, Tokyo Institute of Technology, O-okayama,
Meguro-ku, Tokyo 152-8551, Japan
Received September 24, 2004; E-mail: niwasawa@chem.titech.ac.jp
Abstract: Novel tungsten-containing carbonyl ylides 7, generated by the reaction of the o-alkynylphenyl
carbonyl derivatives 1 with a catalytic amount of W(CO)5(thf), reacted with alkenes to give polycyclic
compounds 5 through [3 + 2]-cycloaddition reaction followed by intramolecular C-H insertion of the
produced nonstabilized carbene complex intermediates 8. In the presence of triethylsilane, these tungsten-
containing carbene intermediates 8 were smoothly trapped intermolecularly by triethylsilane to give silicon-
containing cycloadducts 17 with regeneration of the W(CO)5 species. By this procedure, the scope of alkenes
employable for this reaction was clarified. The presence of the tungsten-containing carbonyl ylide 7c was
confirmed by direct observation of the mixture of o-ethynylphenyl ketone 1c and W(CO)5(thf-d8). Careful
analysis of the intermediate by 2D NMR, along with the observation of the direct coupling with tungsten-
183 employing the 13C-labeled substrate, confirmed the structure of the ylide 7c. Examination using (E)- or
(Z)- vinyl ether revealed that the [3 + 2]-cycloaddition reaction proceeded in a concerted manner and that
the facial selectivity of the reaction differed considerably depending on the presence or absence of
triethylsilane. These results clarified the reversible nature of this [3 + 2]-cycloaddition reaction.
copper,2e,f silver,5a gold,2a mercury,2g,5b and so on have been
employed for this purpose and applied for the synthesis of
Introduction
Transition-metal-catalyzed electrophilic activation of alkynes
toward intramolecular addition of heteronucleophiles has at-
tracted much attention as a useful method for the preparation
of heterocyclic compounds.1 In particular, construction of
heteroaromatic compounds by cyclization of o-alkynylphenyl
derivatives has emerged as a highly useful method for the
preparation of compounds such as indoles,2 isoquinolines,3
benzofurans,2g,4 isocoumarins, 2g,5 etc. Most extensively studied
is the formation of an indole nucleus by the reaction of
o-alkynylaniline derivatives through 5-endo cyclization. A
variety of transition-metal catalysts such as palladium,2a-e,3,4,5c
several natural products.2f,3a,4b
In these reactions, it is supposed that vinyl transition-metal
intermediates I and II are generated by the nucleophilic addition
of heteronucleophiles toward the transition-metal-activated
alkyne moiety (Scheme 1). However, the produced vinylmetallic
intermediates have been simply protonated in most cases and
have rarely been employed for further carbon-carbon bond
formation. One exception is the palladium-catalyzed reaction
originally reported by Utimoto2a and developed extensively by
Cacchi and co-workers,2b,c where cyclization-coupling reaction
of o-alkynylaniline derivatives with aryl halides occurs through
the electrophilic activation of the alkyne moiety by the arylpal-
ladium(II) species. By this procedure, a substituent could be
introduced on the 3-position of the indole nucleus. In recent
reports, similar tandem cyclization-Heck reactions to prepare
4-substituted isoquinolines from o-alkynylbenzaldimines have
been reported by Larock and co-workers.3c In these reactions,
the produced vinylpalladium species behaves as a vinylmetallic
species; that is, Heck-type coupling reaction with alkenes occurs
at the position R to the metal.
(1) (a) Zeni, G.; Larock, R. C. Chem. ReV. 2004, 104, 2285. (b) Li, J. J.; Gribble,
G. W. Palladium in Heterocyclic Chemistry; Pergamon: New York, 2000.
(2) (a) Iritani, K.; Matsubara, S.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1799.
(b) Arcadi, A.; Cacchi, S.; Marinelli, F. Tetrahedron Lett. 1989, 30, 2581.
(c) Cacchi, S.; Fabrizi, G.; Pace, P. J. Org. Chem. 1998, 63, 1001. (d)
Kamijo, S.; Yamamoto, Y. J. Org. Chem. 2003, 68, 4764. (e) Ezquerra, J.;
Pedregal, C.; Lamas, C. J. Org. Chem. 1996, 61, 5804. (f) Hiroya, K.;
Itoh, S.; Sakamoto, T. J. Org. Chem. 2004, 69, 1126 and references therein.
(g) Larock, R. C.; Harrison, L. W. J. Am. Chem. Soc. 1984, 106, 4218.
(3) (a) Roesch, K. R.; Larock, R. C. J. Org. Chem. 2002, 67, 86. (b) Dai, G.;
Larock, R. C. Org. Lett. 2001, 3, 4035. (c) Huang, Q.; Larock, R. C. J.
Org. Chem. 2003, 68, 980 and references therein. (d) Ohtaka, M.;
Nakamura, H.; Yamamoto, Y. Tetrahedron Lett. 2004, 45, 7339.
(4) (a) Torii, S.; Xu, L. H.; Okumoto, H. Synlett 1992, 515. (b) Lu¨tjens, H.;
Scammells, P. J. Synlett 1999, 1079. (c) Hu, Y.; Yang, Z. Org. Lett. 2001,
3, 1387. (d) Houpis, I. N.; Choi, W. B.; Reider, P. J.; Molina, A.; Churchill,
H.; Lynch, J.; Volante, R. P. Tetrahedron Lett. 1994, 35, 9355. (e) Nan,
Y.; Miao, H.; Yang, Z. Org. Lett. 2000, 2, 297 and references therein.
(5) (a) Bellina, F.; Ciucci, D.; Vergamini, P.; Rossi, R. Tetrahedron 2000, 56,
2533 and references therein. (b) Sakamoto, T.; An-naka, M.; Kondo, Y.;
Yamanaka, H. Chem. Pharm. Bull. 1986, 34, 2754. (c) Sashida, H.;
Kawamukai, A. Synthesis 1999, 1145.
As a heteronucleophile, the amino group of aniline derivatives
has most frequently been employed along with the imino
nitrogen of benzaldimine derivatives. On the contrary, the
hydroxy or alkoxy group of phenol or benzyl alcohol deriva-
tives6 has been studied less commonly, and the use of the
9
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J. AM. CHEM. SOC. 2005, 127, 2709-2716
2709

A R T I C L E S
Scheme 1
Kusama et al.
Scheme 3
Scheme 2
Scheme 4
carbonyl oxygen of aryl aldehydes or aryl ketones has rarely
been studied. Yamamoto reported one of these few examples,
say, the cyclization of o-alkynylbenzaldehydes to 1-alkoxy-1H-
isochromenes catalyzed by Pd(OAc)2, which behaved both as
a Lewis acid and as a transition metal,7 and also developed a
synthesis of substituted naphthalene derivatives through Lewis
acid-catalyzed benzannulation between o-alkynylphenyl carbo-
nyl derivatives and alkynes.8 As a related reaction, iodine-
promoted cyclization of o-alkynylphenyl carbonyl derivatives
has recently been reported to give 1H-isochromenes.9
naphthalenes 4 in good yield. To carry out these two reactions
by a one-pot procedure, we examined the same complexation
reaction in the presence of a ketene acetal, which led us to the
discovery of the novel reaction pathways described below.13
We have recently been developing synthetic reactions utilizing
the electrophilic nature of pentacarbonyltungsten (W(CO)5)
species for the effective activation of alkynes through the
formation of an alkyne-π-complex or its isomerized vinylidene
complex (Scheme 2).10 For example, endo-selective cyclization
of 6-siloxy-5-en-1-ynes or 5-siloxy-5-en-1-ynes and solvent-
dependent exo- or endo-selective cyclization of 7-siloxy-6-en-
1-ynes have been developed utilizing this electrophilic property.
We also reported that benzopyranylidene complexes 3 can
be prepared by the treatment of o-ethynylphenyl ketone deriva-
tives 1 with W(CO)5(thf) through the electrocyclization of
vinylidene intermediates 2 (Scheme 3).11,12 These complexes
undergo a Diels-Alder reaction with electron-rich alkenes such
as vinyl ethers, ketene acetals, and enamines to give substituted
Results and Discussion
Generation and Reaction of Tungsten-Containing Car-
bonyl Ylides and Their Tandem [3 + 2]-Cycloaddition-
Carbene Insertion, Leading to Novel Polycyclic Compounds.
As mentioned in the Introduction, we examined the complex-
ation reaction of an o-ethynylphenyl carbonyl compound in the
presence of a ketene acetal to carry out both the formation of
the benzopyranylidene complex and the successive Diels-Alder
reaction by a one-pot procedure. When o-ethynylphenyl iso-
propyl ketone (1a) was treated with a stoichiometric amount of
W(CO)5(thf) in the presence of 4 equiv of 1,1-diethoxyethene,
the starting material was consumed within 2 h at room
temperature. Surprisingly, purification of the crude product
revealed that the expected 3-ethoxy-1-isopropylnaphthalene, the
product of the Diels-Alder reaction between benzopyranylidene
complex 3 and 1,1-diethoxyethene, had not been formed at all,
but that a novel compound, 5a, had been obtained in 73% yield
as a single stereoisomer (Scheme 4).13 Furthermore, the same
product was obtained in nearly the same yield even with 10
(6) Gabriele, B.; Salerno, G.; Fazio, A.; Pittelli, R. Tetrahedron 2003, 59, 6251.
(7) (a) Asao, N.; Nogami, T.; Takahashi, K.; Yamamoto, Y. J. Am. Chem.
Soc. 2002, 124, 764. (b) Patil, N. T.; Yamamoto, Y. J. Org. Chem. 2004,
69, 5139.
(8) (a) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.; Yamamoto, Y. J. Am.
Chem. Soc. 2002, 124, 12650. (b) Asao, N.; Nogami, T.; Lee, S.;
Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 10921. (c) Asao, N.; Kasahara,
T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2003, 42, 3504. (d) Asao, N.;
Aikawa, H.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 7458. (e) For a
mechanistic study of the reaction described in ref 8a,b, see: Straub, B. F.
Chem. Commun. 2004, 1726.
(11) (a) Iwasawa, N.; Shido, M.; Maeyama, K.; Kusama, H. J. Am. Chem. Soc.
2000, 122, 10226. (b) Kusama, H.; Shiozawa, F.; Shido, M.; Iwasawa, N.
Chem. Lett. 2002, 31, 124. See also: (c) Ohe, K.; Miki, K.; Yokoi, T.;
Nishino, F.; Uemura, S. Organometallics 2000, 19, 5525. (d) Miki, K.;
Yokoi, T.; Nishino, F.; Ohe, K.; Uemura, S. J. Organomet. Chem. 2002,
645, 228. (e) Miki, K.; Yokoi, T.; Nishino, F.; Kato, Y.; Washitake, Y.;
Ohe, K.; Uemura, S. J. Org. Chem. 2004, 69, 1557. (f) Miki, K.; Ohe, K.;
Uemura, S. Tetrahedron Lett. 2003, 44, 2019.
(9) (a) Barluenga, J.; Va´zquez-Villa, H.; Ballesteros, A.; Gonza´lez, J. M. J.
Am. Chem. Soc. 2003, 125, 9028. (b) Yue, D.; Ca`, N. D.; Larock, R. C.
Org. Lett. 2004, 6, 1581.
(10) (a) Miura, T.; Murata, H.; Kiyota, K.; Kusama, H.; Iwasawa, N. J. Mol.
Catal. A 2004, 213, 59. (b) Miura, T.; Kiyota, K.; Kusama, H.; Lee, K.;
Kim, H.; Kim, S.; Lee, P. H.; Iwasawa, N. Org. Lett. 2003, 5, 1725. (c)
Iwasawa, N.; Miura, T.; Kiyota, K.; Kusama, H.; Lee, K.; Lee, P. H. Org.
Lett. 2002, 4, 4463. (d) Kusama, H.; Yamabe, H.; Iwasawa, N. Org. Lett.
2002, 4, 2569. (e) Iwasawa, N.; Maeyama, K.; Kusama, H. Org. Lett. 2001,
3, 3871. (f) Maeyama, K.; Iwasawa, N. J. Org. Chem. 1999, 64, 1344. (g)
Maeyama, K.; Iwasawa, N. J. Am. Chem. Soc. 1998, 120, 1928. (h) Miura,
T.; Iwasawa, N. J. Am. Chem. Soc. 2002, 124, 518.
(12) For a review of vinylidene complexes, see: (a) McDonald, F. E. Chem.s
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.
(13) Iwasawa, N.; Shido, M.; Kusama, H. J. Am. Chem. Soc. 2001, 123, 5814.
9
2710 J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005

Generation of Tungsten-Containing Carbonyl Ylides
A R T I C L E S
Scheme 5
philes at the â-position of the metal, generating the nonstabilized
carbene complex, which further undergoes typical carbene
reaction such as C-H bond insertion. Thus, the zwitterionic
intermediate 7 could be regarded as a tungsten-containing
carbonyl ylide, a novel bifunctional metal-containing reactive
species, and behaves both as a carbonyl ylide and as a carbene
complex to realize construction of a polycyclic carbon skeleton
in a single operation.
The scope of this reaction was examined employing several
o-(1-alkynyl)phenyl ketone derivatives and electron-rich alkenes
(Table 1). Not only ketene acetal but also n-butyl vinyl ether
can be employed as an electron-rich alkene component to give
the corresponding polycyclic products in good yield even with
10 mol % W(CO)5(thf). Several kinds of aryl ketones including
an aryl aldehyde are suitable for this reaction. Furthermore, an
aryl aldehyde derivative, 1e, containing an internal alkyne
moiety also reacts smoothly with the vinyl ether (entry 8).20 In
most cases, a single diastereomer is obtained, whose relative
stereochemistry is assigned to be the same as that of 5a on the
basis of the similarity of the coupling constants in its 1H NMR
spectrum.
Interestingly, when o-ethynylphenyl methyl ketone (1b) (R1
) Me) was treated with W(CO)5(thf) in the presence of 5 equiv
of water, 1,2-bis(acetyl)benzene (13b) was isolated in about 50%
yield. Direct observation of the reaction mixture in THF-d8
clearly showed the formation of a methyleneisobenzofuran
derivative, 12b, at room temperature. This compound is
produced by the exo-mode of attack of the carbonyl oxygen21
onto the W(CO)5-π-complexed alkyne to give 11b, followed
by deprotonation from the methyl group and protonation of the
tungsten-carbon bond (Scheme 6).
mol % W(CO)5(thf) by carrying out the reaction in the presence
of a smaller amount (3 equiv) of 1,1-diethoxyethene. The
structure, including the relative stereochemistry, of this com-
pound was confirmed to be as shown in Scheme 4 by X-ray
analysis.14
The mechanism of this reaction is considered to be the
following (Scheme 5). The alkyne moiety of o-ethynylphenyl
ketone 1 is activated by W(CO)5 electrophilically through
π-complex formation.15 The 6-endo-mode of the nucleophilic
attack of the carbonyl oxygen onto the activated alkyne moiety
generates a zwitterionic intermediate, 7,16-18 which readily
undergoes [3 + 2]-cycloaddition with the electron-rich alkene
to give an unstabilized tungsten carbene complex, 8. Finally,
the tungsten carbene moiety thus generated inserts into a
carbon-hydrogen bond of the neighboring ethoxy group19 to
give the product 5 with regeneration of the W(CO)5 species.
The noteworthy feature of this reaction is that the alkenyltung-
sten species, produced by the addition of the carbonyl oxygen
onto the tungsten-activated alkyne moiety, reacts with electro-
Furthermore, Ohe, Uemura, and their co-workers succeeded
in isolating complexes 15 which were generated by reaction of
cyclohexene derivative 14 with M(CO)5(L) (M ) Cr, W) in
THF (Scheme 7).11d
To account for these phenomena, 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 (Scheme 8). The reaction of o-
ethynylphenyl ketones with W(CO)5(thf) can proceed through
the following three pathways: (i) exo-attack of the carbonyl
oxygen on the π-complexed alkyne to give 11, which might be
in equilibrium with its tautomer 16, (ii) endo-attack of the
carbonyl oxygen on the π-complexed alkyne to give carbonyl
ylide 7, and (iii) 1,2-hydrogen shift to give vinylidene complex
2. 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 11 or 7 such as water or alkenes, the
reaction proceeds through either pathway i or pathway ii to give
the corresponding product 12 (path i) or tungsten-carbene
(14) See the Supporting Information.
(15) 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.
(16) For generation of tungsten-containing azomethine ylides, see: (a) Kusama,
H.; Takaya, J.; Iwasawa, N. J. Am. Chem. Soc. 2002, 124, 11592. (b)
Takaya, J.; Kusama, H.; Iwasawa, N. Chem. Lett. 2004, 33, 16. For
generation of platinum-containing carbonyl ylides, see: (c) Kusama, H.;
Funami, H.; Takaya, J.; Iwasawa, N. Org. Lett. 2004, 6, 605.
(17) 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, Germany, 1999; p 206. (c) Padwa, A.;
Pearson, W. H. Synthetic Applications of 1,3-Dipolar Cycloaddition
Chemistry Toward Heterocycles and Natural Products; Wiley-Inter-
science: Hoboken, NJ, 2003; p 253. For some recent examples, see: (d)
Hodgson, D. M.; Labande, A. H.; Pierard, F. Y. T. M.; Expo´sito Castro,
M. AÄ . J. Org. Chem. 2003, 68, 6153. (e) Nakamura, S.; Hirata, Y.; Kurosaki,
T.; Anada, M.; Kataoka, O.; Kitagaki, S.; Hashimoto, S. Angew. Chem.,
Int. Ed. 2003, 42, 5351.
(20) The same reaction of 1d with ketene acetal did not give the corresponding
cycloadduct, but aldol-type products 9 and 10 were produced in 85% yield.
(18) For formation of metal-containing ylides, see: Padwa, A.; Gasdaska, J. R.
J. Am. Chem. Soc. 1986, 108, 1104.
(19) 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.;
Su, J.; 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.sEur. J.
1997, 3, 1629. See also: Sulikowski, G. A.; Cha, K. L.; Sulikowski, M.
M. Tetrahedron: Asymmetry 1998, 9, 3145.
(21) Casey, C. P.; Strotman, N. A.; Guzei, I. A. Organometallics 2004, 23, 4121.
9
J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005 2711

A R T I C L E S
Kusama et al.
yield/%
Table 1. Reaction of Various o-(1-Alkynyl)phenyl Ketones with Electron-Rich Alkenesa
entry
R1
R2
R3
R4
time
1
2
3
4
5
6
7b
8
i-Pr
i-Pr
Me
Me
n-Pr
n-Pr
H
H
H
H
H
H
H
H
Me
1a
1a
1b
1b
1c
1c
1d
1e
OC2H5
H
OC2H5
H
CH3
n-C3H7
CH3
n-C3H7
CH3
n-C3H7
n-C3H7
n-C3H7
5a
5b
5c
5d
5e
5f
23 h
75
50
84
74
81
77
94
69
1 week
4 days
2 days
2 days
8 h
OC2H5
H
H
H
5g
5h
4 h
16 h
H
a 10 equiv of n-butyl vinyl ether and 3 equiv of 1,1-diethoxyethene were used. b Including an about 5% yield of an isomeric product concerning the
substituent R4.
Scheme 6
Scheme 8
Scheme 7
intermediate 8 (path ii). However, in the absence of such
trapping reagents, an equilibrium exists among 11, 7, and the
π-complex 6, and formation of vinylidene complex 2 occurs
from the π-complex 6 as a relatively slower process, which gives
a benzopyranylidene complex, 3, through an irreversible uni-
molecular electrocyclization. It should be noted that in this
o-ethynylphenyl ketone-W(CO)5(L) system exist three different
reaction pathways, which are under rapid equilibrium through
the π-complex, and that these pathways could be controlled with
appropriate choice of the reaction parameters to give three
different types of carbon frameworks.
Scheme 9
Investigation with Various Alkenes: Reaction in the
Presence of Silanes as Trapping Agents of Tungsten-
Carbene Complex Intermediates. Since it had become clear
that the reactions of several o-(1-alkynyl)phenyl ketone deriva-
tives with a ketene acetal or a vinyl ether proceeded smoothly,
we further continued our study to extend the scope of the
reaction using various alkenes. Since all alkenes do not have a
suitable insertable carbon-hydrogen bond and since carbene
intermediate 8 is not stable, we needed to develop a method to
trap intermediate 8 to allow the study of the reactivity with
different alkenes. It is well-known that metal carbenoids or free
carbenes can readily insert into a silicon-hydrogen bond of
silanes.22 Therefore, we decided to examine a reaction in the
presence of 10 equiv of triethylsilane under the same conditions
to capture the intermediates 8 intermolecularly. Thus, a mixture
of o-ethynylbenzaldehyde (1d) and n-butyl vinyl ether was
treated with 10 mol % W(CO)5(thf) in the presence of
triethylsilane in THF at room temperature, and the reaction was
found to proceed as expected, giving the desired silicon-
containing compound 17a in 78% yield with a small amount
of polycyclic compound 5g (17% yield) (Scheme 9). The
formation of this silicon-containing product 17a clearly proved
the existence of the tungsten-carbene intermediate 8d. This
major product 17a was obtained as a single stereoisomer, the
(22) (a) Connor, J. A.; Rose, P. D.; Turner, R. M. J. Organomet. Chem. 1973,
55, 111. (b) Connor, J. A.; Day, J. P.; Turner, R. M. J. Chem. Soc., Dalton
Trans. 1976, 108.
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Generation of Tungsten-Containing Carbonyl Ylides
A R T I C L E S
Table 2. Reaction of 1d with Various Alkenes in the Presence of
Silanesa
yield/%
entry
R
R′
3SiH
17
5g
ratio 17:5g
1
2
3
4
5
6
7
8
9
O-n-Bu
Et3SiH
t-BuMe2SiH
Ph3SiH
i-Pr3SiH
EtMe2SiH
Et3SiH
Et3SiH
Et3SiH
Et3SiH
78, 17a
40, 17b
4, 17c
<3 17d
85, 17e
74, 17f
70, 17g
59, 17h
44, 17i
17
53
84
93
6
82:18
43:57
5:95
<3:>97
93:7
O-t-Bu
OSiMe3
CH2SiMe3
Ph
a Except 17i, all products were obtained as a single stereoisomer, the
structure of which was confirmed to be as shown above by the measurement
of NOE. In the case of entry 9, a diastereomer concerning the substituent
R was produced in a ratio of 98:2.
structure of which was confirmed to be as shown in Scheme 9
by measurement of the nuclear Overhauser effect (NOE).14
Although the tungsten-containing carbene intermediate was
found to be easily trapped intermolecularly by triethylsilane,
intramolecular insertion of the carbene part into the neighboring
carbon-hydrogen bond slightly competes with the insertion into
a silicon-hydrogen bond (Scheme 9). Thus, we further exam-
ined reactions employing various silanes to improve the
efficiency of the carbene-trapping reaction.
The influence of the substituents on silicon for one chosen
peculiar reaction is summarized in Table 2 (entries 1-5). The
use of tert-butyldimethylsilane gave 17b in lower yield than
triethylsilane (93%, ratio 17b:5g ) 43:57, entry 2). Furthermore,
the reactions in the presence of triphenylsilane or triisopropyl-
silane gave the corresponding silylated product 17c or 17d in
very low yield, and intramolecular insertion of the carbene
moiety into the neighboring C-H bond occurred predominantly
(entries 3 and 4). As the larger size of the substituent of silane
strongly hindered Si-H insertion of the carbene intermediate,
we expected that a smaller silane would effectively trap the
carbene intermediate. Indeed, by the use of ethyldimethylsilane,
the ratio of the products 17e and 5g was improved to 93:7 (entry
5). All cycloadducts 17a-e were obtained as a single stereo-
isomer, the structure of which was confirmed to be the same as
that of compound 17a by the similarity of the coupling pattern
Figure 1. Energy level of the HOMO and LUMO of carbonyl ylides A
and D (calculated by B3LYP/6-31G*).
compound 17f was obtained in high yield as a single stereo-
isomer (entry 6). This reaction could also be carried out with
silyl enol ether and allylsilane to give the corresponding silylated
product in good yield (entries 7 and 8). Furthermore, even
styrene could be employed successfully (entry 9); however,
1-octene and methyl acrylate could not be reacted. Thus, by
carrying out the reaction in the presence of silane, the scope of
the alkenes employable for this [3 + 2]-cycloaddition was
expanded to a great extent, and not only electron-rich alkenes
such as ketene acetal and vinyl ethers but even styrene could
be employed for this reaction.
To gain insight into the reactivity of the tungsten-containing
carbonyl ylide, we searched the energy levels of the HOMO
and LUMO of the tungsten-containing carbonyl ylide A and of
a simple carbonyl ylide, D, by ab initio calculations as shown
in Figure 1.24 The LUMO of the ylide A is considerably lower
1
of their H NMR spectra.
Since an efficient method for capturing the nonstabilized
carbene intermediate had been established, we next investigated
the reaction with various alkenes for [3 + 2]-cycloaddition with
the tungsten-containing carbonyl ylide 7 by carrying out the
reaction in the presence of triethylsilane (Table 2, entries 6-9).
By this procedure, we can examine the reaction with alkenes
containing no reactive C-H bond for intramolecular carbene
insertion.23 For example, when tert-butyl vinyl ether was
employed in this reaction, the corresponding silicon-containing
(23) It is well-known that C-H insertion is facilitated by the electron donation
from R-oxygen. For the electronic factor of carbene insertion into C-H
bonds, see: (a) Seyferth, D.; Mai, V. A.; Gordon, M. E. J. Org. Chem.
1970, 35, 1993. (b) Adams, J.; Poupart, M.-A.; Grenier, L.; Schaller, C.;
Ouimet, N.; Frenette, R. Tetrahedron Lett. 1989, 30, 1749.
(24) The calculations were performed with Gaussian 03 using the B3LYP hybrid
density functional method. The lanl2dz basis set was used for the W atom,
and the 6-31G* basis sets were used for the other atoms.
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J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005 2713

A R T I C L E S
Kusama et al.
than that of ylide D, which suggests that a strong interaction
between the LUMO of ylide A and the HOMO of an electron-
rich alkene is more favorable than with ylide D. The normal
carbonyl ylides react in general preferentially with electron-
deficient alkenes such as methyl acrylate,17 and there are few
examples for the reaction with electron-rich alkenes.25 On the
contrary, the reactivity of the tungsten-containing ylide A is
reversed and readily reacts with electron-rich alkenes. These
results are in good agreement with the above calculation, and
such a unique property of the metal-containing ylide A is thought
to be derived from the strong electron-withdrawing nature of
the tungsten carbonyl moiety.
Observation of the Tungsten-Containing Carbonyl Ylide.
In this reaction, the tungsten-containing carbonyl ylide 7 was
thought to be the key intermediate generated by treatment of
W(CO)5(thf) with o-(1-alkynyl)phenyl carbonyl compound 1
(Scheme 5). Commonly, carbonyl ylides are unstable and highly
reactive species, and thus, it was expected to be difficult to
isolate the ylide 7.26 Therefore, we first tried to detect such
species directly by NMR measurements. For that matter, 1-(2-
ethynylphenyl)butan-1-one (1c) was treated with 1.7 equiv of
W(CO)5(thf-d8) in THF-d8, and changes in the 1H NMR spectra
at 300 K with time were observed in the absence of Vinyl ether
(Figure 2). At t ) 5 min, the formation of a set of signals derived
from a new species (*, compound X) was observed at δ 8.92,
8.67, 8.56, 8.30, and 7.88 ppm. The signal at δ 8.92 was a
singlet, and the coupling pattern of the latter four signals
indicated that compound X was an ortho-disubstituted aryl
compound with much lower electron density than the starting
ketone 1c as deduced from the explicit lower field shift of these
signals. It could be considered that the singlet at 8.92 ppm could
be assigned to be the hydrogen of the terminal alkyne.
Furthermore, three new signals derived from the propyl group
were also observed at higher field. At t ) 1.5 h, these signals
still appear with a weak intensity, and another set of signals
(2, compound Y) was observed, which coincided with those
of the isolated benzopyranylidene complex 3c.11a Finally, at t
) 3.5 h, the signals corresponding to compound X mostly
disappeared and the benzopyranylidene complex 3c became the
major product.
1
Figure 2. Change of the H NMR spectra at 300 K.
As already mentioned, the reaction of o-ethynylphenyl
ketones and W(CO)5(thf) in the absence of alkenes is thought
to proceed through the following three pathways: (i) π-complex
6 undergoes a reversible endo-mode of attack of the carbonyl
oxygen onto the π-complexed alkyne to give the tungsten-
containing carbonyl ylide 7, (ii) exo-attack of the carbonyl
oxygen onto the π-complexed alkyne to give 11, and (iii) 1,2-
migration of the hydrogen of the π-complex 6 to give the
vinylidene intermediate 2, which then undergoes irreversible
6π-electrocyclization to give the pyranylidene complex 3c
(Scheme 8). Thus, at this point, intermediate X could be the
endo-cyclized tungsten-containing carbonyl ylide 7c, the exo-
cyclized ylide 11c, or the vinylidene complex 2c. To obtain
Figure 3. endo- and exo-cyclized carbonyl ylide 7c, 11c, and vinylidene
complex 2c.
further information on the structure of the compound X, the
same reaction was carried out at room temperature for 30 min
and then cooled to 233 K to hinder advancement of the reaction
during the measurement of the HMBC spectrum. As the 13C
signal at δ 184.6 ppm was found to have a correlation with
H(e) and H(f) of the propyl group, this signal was assigned as
C(3) derived from the carbonyl carbon. A noteworthy correlation
was observed between C(3) and the singlet at δ 8.92 derived
from the hydrogen of the alkyne (H(a)), which strongly suggests
that this intermediate is neither the exo-cyclized tungsten-
containing ylide 11c nor the vinylidene complex 2c but the endo-
cyclized carbonyl ylide 7c (Figure 3).
(25) (a) Savinov, S. N.; Austin, D. J. Chem. Commun. 1999, 1813. (b) Kotera,
M.; Ishii, K.; Tamura, O.; Sakamoto, M. J. Chem. Soc., Perkin Trans. 1
1998, 313. (c) Koyama, H.; Ball, R. G.; Berger, G. D. Tetrahedron Lett.
1994, 35, 9185.
(26) (a) Do¨rwald, F. Z. Metal Carbenes in Organic Synthesis; Wiley-VCH:
Weinheim, Germany, 1999; p 75. (b) Winter, M. J. ComprehensiVe
Organometallic Chemistry II; Pergamon: New York, 1995; p 168. For
isolation of carbonyl ylides, see: (c) Hamaguchi, M.; Ibata, T. Tetrahedron
Lett. 1974, 15, 4475. (d) Janulis, E. P., Jr.; Arduengo, A. J., III. J. Am.
Chem. Soc. 1983, 105, 5929.
Since it was suggested that the intermediate X could be
identified as the ylide 7c, we next tried to confirm the presence
of the direct bonding between tungsten and C(1) by carrying
out the reaction employing 13C-labeled 1c27 (Scheme 10). As
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2714 J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005

Generation of Tungsten-Containing Carbonyl Ylides
A R T I C L E S
Scheme 10 a
Scheme 11
a The asterisk indicates the 13C-labeled position.
Scheme 12
Figure 4. Selected correlations in the HMBC spectrum.
tungsten-183 (natural abundance 14.3%) has 1/2 nuclear spin
while other isotopes of tungsten have no nuclear spin, a set of
satellite peaks should be observed in the 13C NMR spectrum at
the carbon directly bonded to tungsten due to the coupling with
tungsten-183.28 Although a peak at δ 155.5 ppm was observed
as a very weak signal in the case of the nonlabeled substrate,
by using the 13C-enriched substrate 1c (20% 13C), this peak had
medium strength. In the HMBC spectrum, this carbon has a
correlation with an ortho proton, H(c), of the benzene ring,
which suggests that this carbon is surely C(1). Most importantly,
this peak had a set of satellite peaks with a coupling constant
of 76.4 Hz (1JC-W).29,30 This result indicates that the labeled
C(1) is indeed directly connected to the tungsten. Additionally,
1
the singlet at δ 8.92 in the H NMR spectra showed a set of
satellite peaks due to the JC-H coupling (2JC-H ) 17.2 Hz)
2
reoisomer in 84% yield (Scheme 11). On the other hand, the
same reaction carried out in the presence of triethylsilane gave
a mixture of two diastereomers, 17j and 17k, in nearly equal
amounts in 84% yield. The stereochemistry of cycloadducts 17j
and 17k was confirmed to be as shown in Scheme 11 by NOEs.
Thus, facial selectivity of these two reactions differs dramati-
cally depending on the presence or absence of the carbene-
trapping reagent, and these results clearly indicate the presence
of an equilibrium in the [3 + 2]-cycloaddition reaction step.
Two mechanisms may explain these phenomena, that is, (i) a
concerted and reversible cycloaddition of the carbonyl ylide 7d
with the alkene (Scheme 12a) and (ii) a stepwise cycloaddition
via a zwitterionic intermediate, 18, and equilibrium existing
through ring opening and reclosing of the carbene intermediates
(Scheme 12b).16b
To discriminate between these two possibilities, we further
examined the reaction with stereochemically well-defined
trisubstituted vinyl ethers. The reaction of 1d with (E)- or (Z)-
2-methoxybut-2-ene in the presence of triethylsilane was carried
out using a catalytic amount of W(CO)5(thf) in THF at room
temperature. As shown in Scheme 13, both reactions gave a
mixture of two diastereomeric silylated compounds, which differ
in the facial selectivity of [3 + 2]-cycloaddition. All products
with the labeled carbon. Other correlations of compound X in
the HMBC spectrum also agreed well with the structure of
tungsten-containing carbonyl ylide 7c (Figure 4). Thus, we have
succeeded in observing directly the key reactive species,
tungsten-containing carbonyl ylide 7, which exists in a small
amount during the reaction and is slowly converted to the
benzopyranylidene complex 3 through the π-complex 6, when
the electron-rich alkene is not added to the mixture.
Concerted and Reversible Nature of the [3 + 2]-Cycload-
dition Reaction. Since the above results clearly indicate that
the tungsten-containing carbonyl ylide is indeed generated, we
next studied the mechanism of [3 + 2]-cycloaddition reaction
of the carbonyl ylide with alkenes. When 2-methoxypropene, a
1,1-disubstituted vinyl ether, was employed, we found an
intriguing phenomenom concerning the stereoselectivity of the
cycloadducts. The reaction of 1d and 2-methoxypropene with
a catalytic amount of W(CO)5(thf) proceeded smoothly to afford
the corresponding polycyclic compound 5i as a single diaste-
(27) For the preparation of 1c, see the Supporting Information.
(28) Mann, B. E.; Taylor, B. F. 13C NMR Data for Organometallic Compounds;
Academic Press: London, 1981.
(29) (a) Iwasawa, N.; Ochiai, T.; Maeyama, K. J. Org. Chem. 1998, 63, 3164.
(b) Iwasawa, N.; Ochiai, T.; Maeyama, K. Organometallics 1997, 16, 5137.
(30) For NMR charts, see the Supporting Information.
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J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005 2715

A R T I C L E S
Scheme 13
Kusama et al.
temperature between the two cycloadducts 8x and 8y through
the carbonyl ylide 7d in a concerted [3 + 2]-cycloaddition-
retrocycloaddition pathway (Scheme 12a). In the presence of
triethylsilane, each of the two isomeric carbene intermediates
was readily trapped to give diastereomeric silicon-containing
cycloadducts, while in the case of the reaction without the silane,
the polycyclic compound was obtained only from the isomer
suitable for intramolecular C-H insertion by the equilibration
of the two isomeric carbene intermediates.
It is known that [3 + 2]-cycloaddition of carbonyl ylides with
alkenes is usually irreversible, and only a few specific cases
were reported for the retrocycloaddition reactions.31 Therefore,
the facile equilibrium observed here is a very rare example of
the retro-[3 + 2]-cycloaddition reaction of carbonyl ylide species
and is the characteristic feature of the tungsten-containing
carbonyl ylide.
Scheme 14
Conclusion
In conclusion, a new type of bifunctional reactive species,
tungsten-containing carbonyl ylide, is generated by the reaction
of o-alkynylphenyl carbonyl compounds 1 with W(CO)5(thf).
This novel species undergoes [3 + 2]-cycloaddition reaction
with electron-rich alkenes to give tungsten-containing carbene
complex intermediates 8, the carbene moiety of which inserts
into a neighboring C-H bond intramolecularly to give the
polycyclic compounds 5. In the presence of triethylsilane, the
same reaction provides the silicon-containing compounds 17,
intermolecular insertion products, in good yields. All these
reactions proceed with a catalytic amount of W(CO)5(thf) as
the catalyst is regenerated at the insertion steps. The presence
of the tungsten-containing carbonyl ylide 7c is directly con-
firmed by NMR measurement using a 13C-labeled substrate. The
concerted and reversible nature of this [3 + 2]-cycloaddition
reaction between tungsten-containing carbonyl ylide 7 and
alkenes is disclosed by these studies. We believe the concept
of the metal-containing 1,3-dipoles will find abundant applica-
tion in organic chemistry and provide new opportunities to
develop useful synthetic methods of various heterocyclic
compounds.
17l-o retained the stereochemistry of the vinyl ethers employed,
which clearly suggested that the [3 + 2]-cycloaddition proceeded
in a concerted manner. The stereochemistry of the cycloadducts
17l-o was confirmed by NOEs.14
Next, we examined reactions in the absence of triethylsilane
under similar conditions (Scheme 14). When the reaction using
(E)-2-methoxybut-2-ene was carried out, two isomeric insertion
products, 5j and 5k, were obtained in a ratio of 98:2, while the
reaction with (Z)-isomer gave the same mixture in a ratio of
17:83. Thus, in these cases, the minor products did not retain
the geometrical integrity of the vinyl ethers employed. Direct
1
observation of the H NMR spectra of both vinyl ethers in the
Acknowledgment. This research was partly supported by a
Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science, and Technology of Japan.
J.T. has been granted a Research Fellowship of the Japan Society
for the Promotion of Science for Young Scientists. We thank
Ms. Sachiyo Kubo for performing X-ray analysis.
presence of W(CO)5(thf-d8) in THF-d8 revealed that isomer-
ization of the geometry of the double bond hardly occurred in
the presence of triethylsilane, while considerable isomerization
was observed in the absence of triethylsilane, in particular, in
the case of the (Z)-alkene. These results suggest that diastere-
omers 5k (in the case of (E)-alkene) and 5j (in the case of (Z)-
alkene) were obtained from the reaction between substrate 1d
and in situ isomerized starting alkenes (in the absence of
triethylsilane) through a still concerted mechanism in these cases
also.
Comparison of the facial selectivity of the reactions in the
presence or absence of triethylsilane clearly indicates that the
selectivity differs considerably from one case to the other, and
in particular, the selectivity is reversed for the reaction using
the (Z)-alkene. Thus, there should be a rapid equilibrium at room
Supporting Information Available: Preparative methods and
spectral and analytical data of compounds 5 and 17, 13C NMR
spectra for the reaction shown in Scheme 10, and X-ray data
for 5a (PDF, CIF). This material is available free of charge via
the Internet at http://pubs.acs.org.
JA044194K
(31) For examples, see: (a) Hamaguchi, M.; Ibata, T. Chem. Lett. 1975, 4, 499.
(b) Gonza´lez, R.; Knight, B, W.; Wudl, F.; Semones, M. A.; Padwa, A. J.
Org. Chem. 1994, 59, 7949.
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2716 J. AM. CHEM. SOC. VOL. 127, NO. 8, 2005