Low-valent niobium-mediated synthesis of indenes: Intramolecular coupling reaction of CF3 group with alkene C-H bond

Article abstract of DOI:10.1246/cl.2007.24

CF₃ group of o-alkenyl-α,α,α-trifluorotoluenes underwent intramolecular coupling reaction with the alkene C-H bond under NbCl₅/LiAlH₄ system. Substituted indenes were obtained in good yields. Copyright

Full text of DOI:10.1246/cl.2007.24

24
Chemistry Letters Vol.36, No.1 (2007)
Low-valent Niobium-mediated Synthesis of Indenes:
Intramolecular Coupling Reaction of CF3 Group with Alkene C–H Bond
Kohei Fuchibe, Ken Mitomi, and Takahiko AkiyamaÃ
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588
(Received September 7, 2006; CL-061037; E-mail: takahiko.akiyama@gakushuin.ac.jp)
CF3 group of o-alkenyl-ꢀ,ꢀ,ꢀ-trifluorotoluenes underwent
Table 1. Optimization of reagents
intramolecular coupling reaction with the alkene C–H bond
under NbCl5/LiAlH4 system. Substituted indenes were obtained
in good yields.
CF3
Reagents
Ph
1,4-dioxane, reflux, 1.5 h
Ph
1a
2a
F
Indene is a ubiquitous component of organic molecules and
plays important roles in various fields of chemistry. For instance,
substituted indene derivatives frequently occur in natural prod-
ucts and exhibit biological activity.1 Anions prepared from in-
dene derivatives and appropriate bases are representative varia-
tions of Cp ligands, and the ꢁ-coordinated indenyl complexes
sometimes exhibit remarkable catalytic activities.2 In recent
years, indene skeletons have attracted much attention as core
parts of functional materials such as conducting polymers3 and
discotic liquid crystals.4 Development of novel synthetic method
of the indene derivatives is, thus, extremely important to these
areas of research.
A number of methods have been reported for the construc-
tion of the five-membered carbocycles. Cation-mediated reac-
tions such as the Nazarov-type ꢁ-cyclization and intramolecular
electrophilic aromatic substitution are one of the most familiar
methods.5 Intramolecular nucleophilic attack of carbanion
equivalents to carbonyl groups affords the indene or its related
compounds.6 Insertions of alkynes to aryl metals also give in-
dene derivatives.7,8
On the other hand, we have previously reported a low-valent
niobium-mediated synthesis of substituted fluorenes from o-
aryl-ꢀ,ꢀ,ꢀ-trifluorotoluenes.9 In this protocol, the CF3 group
is activated by the low-valent niobium,10 and coupled with the
neighboring aromatic C–H bond.11 Keeping this success in
mind, we planned to synthesize indene derivatives from o-alken-
yl-ꢀ,ꢀ,ꢀ-trifluorotoluenes (Scheme 1).
At the outset, we attempted a reaction of o-styryl-ꢀ,ꢀ,ꢀ-tri-
fluorotoluene (1a) (Table 1). To a dioxane solution of 1a and an
equimolar amount of NbCl5, dioxane suspension of LiAlH4 was
added over a period of 1.5 h. During the addition, the reaction
mixture was allowed to reflux. When the addition was complet-
ed, the reaction was quenched with water. The desired indene 2a
was obtained in 64% yield and conventional reduction products
(hydrodefluorination products) 4 and 5 were obtained in 22%
yield (Entry 1).
CH3
CF3
+
+
+
Ph
Ph
Ph
4 (styryl)
5 (phenethyl)
3
6
Yield/%
Entry Reagentsa
2a
3
4 + 5 (ratio)
6
1a
b
1
2
3
4
5
6
7
NbCl5, LiAlH4
TaCl5, LiAlH4
WCl6, LiAlH4
PdCl2, LiAlH4
NbCl5, Red-Al
64
—
42 11
16 18
22 (55:45)
23 (56:44)
12 (83:17)
16 (76:24)
71 (18:82)
—
—
—
—
44
—
—
—
—
—
39
7
—
86
97
b
b
b
4
7
6
—
—
11
—
—
NbCl5, DIBAL
NbCl5, NaBH4
—
a100 mol % of metal salt and 10 molar amounts of reducing
agent were used for each entries. bDioxane suspension of
LiAlH4 was added over 1.5 h.
of the starting material 1a (Entry 3). In the case of PdCl2, the al-
kene moiety was affected prior to the CF3 group (Entry 4) to give
6.13 Use of Red-Al [sodium bis(methoxyethoxy)aluminum hy-
dride], DIBAL, and NaBH4 resulted in formation of the conven-
tional reduction products 4 and 5 (Entry 5), or recovery of 1a
(Entries 6 and 7). The intramolecular coupling reaction was thus
accomplished by the NbCl5/LiAlH4 system.
Solid LiAlH4, in place of the dioxane suspension of the re-
ducing agent, decreased the yield of 2a and increased the yield of
4 and 5 (Scheme 2). Excess amount of the reducing agent in the
reaction medium likely promoted conventional reduction proc-
ess, leading to the formation of 4 and 5.9a
The use of a catalytic amount (30 mol %) of NbCl5 was
found to be effective for the present coupling reactions. As
shown in Table 2, arylvinyl-ꢀ,ꢀ,ꢀ-trifluorotoluenes gave arylin-
denes in good yields (Entries 1–11). It is worth noting that this
reaction smoothly gave aminoindene 2i and fused 2k, which
are potentially inaccessible by existing acid-promoted cycliza-
tions5a,5b or the Heck-type arylations of parent indenes.14
Use of other reagent in place of NbCl5 or LiAlH4 gave infe-
rior results: TaCl5 partially gave fluoroindene 3,12 in which one
fluorine atom survived (Entry 2). WCl6 gave significant amount
NbCl5 100 mol%
Solid LiAlH4 10 mol. amt.
CF3
H
NbCl5, LiAlH4
+
+
1a
2a
4
5
R2
R1
R1
1,4-dioxane, reflux, 3 h
R2
19%
34%
17%
Scheme 1. Our approach to indene skeletons.
Scheme 2.
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.1 (2007)
Table 2. Low-valent niobium-mediated synthesis of substituted indenesa
25
Entry
Alkenyltrifluorotoluene
(R)
1a (H)
Product(s)
Yield/%b
64, 2a
61, 2b
64, 2c
66, 2d
62, 2e
57, 2f
CF3
1
2
3
4
5
6
7
1b (p-Me)
1c (p-NMe2)
1d (p-OMe)
1e (m-OMe)
1f (o-OMe)
1g
R
R
CF3
62, 2g
CF3
64, 2h
1h
8
9c
Me2N
CF3
Me2N
Me2N
61, 2i
61, 2j
1i
1j
+
Ph
Ph
(32:68)
Ph
CF3
10
Ph
Ph
+
Ph
(80:20)
CF3
68, 2k
1k
11
b
aConditions: NbCl5 30 mol %, LiAlH4 5 mol. amt. (dioxane suspension, over 1.5 h), 3 h. NMR yield. Conventional reduction
products corresponding to 4 and 5 were obtained in 19–24% yields. NbCl5 100 mol %, LiAlH4 10 mol. amt., 10 h.
c
Chem. 1999, 64, 1733.
We now surmise that this reaction proceeds as we have
previously described for our fluorene synthesis.9a Further studies
on mechanistic aspects are in progress.
In summary, we have developed a novel low-valent niobi-
um-mediated synthetic method of indenes. We could obtain var-
ious substituted indenes in good yields, starting from o-alkenyl-
ꢀ,ꢀ,ꢀ-trifluorotoluenes via intramolecular coupling reaction of
the CF3 group and the alkene C–H bond.
6
7
a) R. L. Halterman, C. Zhu, Tetrahedron Lett. 1999, 40, 7445. b) V. G.
Nenajdenko, D. I. Denisenko, E. S. Balenkova, Russ. Chem. Bull.
2002, 51, 2090.
a) L. G. Quan, V. Gevorgyan, Y. Yamamoto, J. Am. Chem. Soc. 1999,
121, 3545. b) K.-J. Chang, D. K. Rayabarapu, C.-H. Cheng, J. Org.
Chem. 2004, 69, 4781. c) A. A. Pletnev, Q. Tian, R. C. Larock, J.
Org. Chem. 2002, 67, 9276. d) Y. Kuninobu, A. Kawata, K. Takai,
J. Am. Chem. Soc. 2005, 127, 13498.
See also: a) H. Yamabe, A. Mizuno, H. Kusama, N. Iwasawa, J. Am.
Chem. Soc. 2005, 127, 3248. b) R. Shintani, K. Okamoto, T. Hayashi,
J. Am. Chem. Soc. 2005, 127, 2872. c) M. F. Semmelhack, S. Ho, D.
Cohen, M. Steigerwald, M. C. Lee, G. Lee, A. M. Gilbert, W. D. Wulff,
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8
This work was supported in part by Grant-in-Aid for Scien-
tific Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan (No. 18750036).
Dedicated to Professor Teruaki Mukaiyama on the occasion
of his 80th birthday.
9
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Published on the web (Advance View) December 2, 2006; doi:10.1246/cl.2007.24