Fluorenes as new molecular scaffolds for carbon-carbon σ-bond cleavage reaction: Acylfluorenylation of arynes

Article abstract of DOI:10.1039/b814597k

Acyl and fluorenyl moieties are facilely installed into neighbouring positions of aromatic skeletons via C-C bond cleavage reaction using arynes. The Royal Society of Chemistry.

Full text of DOI:10.1039/b814597k

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Fluorenes as new molecular scaffolds for carbon–carbon r-bond cleavage
reaction: acylfluorenylation of arynesw
Hiroto Yoshida,* Takeshi Kishida, Masahiko Watanabe and Joji Ohshita
Received (in Cambridge, UK) 21st August 2008, Accepted 11th September 2008
First published as an Advance Article on the web 8th October 2008
DOI: 10.1039/b814597k
Acyl and fluorenyl moieties are facilely installed into neighbour-
ing positions of aromatic skeletons via C–C bond cleavage
reaction using arynes.
ketones underwent the insertion of benzyne (entries 6–8).
Furthermore, the reaction was applicable to esters of fluorene-
carboxylic acid (2i or 2j), providing high yields of 3ai or 3aj
(entries 9 and 10). A fluorenyl moiety plays a vital role in
enabling the present C–C cleavage reaction to proceed, and
thus, no trace of the desired product was formed in the
reaction using ethyl diphenylacetate despite its structural
resemblance to 2i (eqn (1)).
Direct installation of two carbon units (C1 and C2) into
carbon–carbon unsaturated compounds via C1–C2 bond clea-
vage has gained much attention, because it provides new
organic transformations for constructing complex carbon
frameworks in a straightforward manner.1,2 In this context,
Stoltz’s3 and our groups4,5 have already disclosed insertion
reactions of arynes into a C–C bond of b-dicarbonyl or
a-cyanocarbonyl compounds, which offer facile approach to
highly functionalized arenes, being hardly available by con-
ventional methods, however, applicability of the reaction is
totally restricted to active methylene compounds bearing two
electron-withdrawing groups (EWG), to the best of our
knowledge.6 The key for the reaction to proceed would be
smooth formation of a carboanionic species ((EWG)2Cꢀ) via
rapid deprotonation induced by two EWGs,3,4 and thus we
envisaged that the use of another molecular scaffold having a
C–H moiety of suitable acidity would result in a new C–C
bond cleavage reaction. We report herein on acylfluorenyla-
tion of arynes using fluorene derivatives, where formation of a
key carboanionic species is facilitated by its aromatic stabili-
zation, allowing two carbon–carbon bond-forming processes
(aryl–acyl and aryl–fluorenyl bonds) to occur at neighbouring
positions of an aromatic skeleton all at once (Scheme 1).7,8
We initially conducted the reaction of benzyne (generated in
situ from 1a9 and KF–18-Crown-6) with 9-fluorenyl isopropyl
ketone (2a) in THF at room temperature and found that the
methine–carbonyl bond added across benzyne to give a 97%
yield of acylfluorenylation product 3aa (Table 1, entry 1). Aryl
fluorenyl ketones (2b or 2c) could also participate in the
reaction to give the products (3ab or 3ac) in 90 or 74% yield
(entries 2 and 3), and the reaction using cyclopropyl (2d) or
cyclobutyl (2e) ketone furnished 3ad or 3ae, whose strained
cyclic structure remained intact (entries 4 and 5). Although the
yields were somewhat lower than those described above, the
C–C bond of heteroaryl (2f) or sterically-congested (2g or 2h)
ð1Þ
The scope of the reaction was further examined by using
substituted arynes (Scheme 2). Such symmetrical arynes as
2,3-naphthalyne (from 1b) or 4,5-dialkylated arynes (from
1c–1e) smoothly reacted with 2a to give the respective inser-
tion products (3ba–3ea) in good yields. Perfect regioselec-
tivities were observed in the reaction of 1,2-naphthalyne
(from 1f) or 3-methoxybenzyne (from 1g), where the fluorenyl
moiety was attached to the less congested site exclusively. In
Department of Applied Chemistry, Graduate School of Engineering,
Hiroshima University, Higashi-Hiroshima 739-8527, Japan.
E-mail: yhiroto@hiroshima-u.ac.jp; Fax: +81-82-424-5494;
Tel: +81-82-424-7724
w Electronic supplementary information (ESI) available: Experimental
procedure including spectroscopic and analytical data. See DOI:
10.1039/b814597k
Scheme 1 Insertion reaction of arynes into C–C s-bond.
Chem. Commun., 2008, 5963–5965 | 5963
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Table 1 Acylfluorenylation of benzynea
Entry
R0
2
t/h
Yield (%)b
3
1
2
3
i-Pr
Ph
2a
2b
2c
18
26
10
97
90
74
3aa
3ab
3ac
4
5
2d
2e
15
13
71
69
3ad
3ae
6
7
2f
20
17
58
63
3af
2g
3ag
8
t-Bu
EtO
2h
2i
2j
48
12
15
52
93
88
3ah
3ai
3aj
9
10
a
i-PrO
The reaction was carried out in THF (10 mL) at rt using 1a
(0.30 mmol), 2 (0.20 mmol), KF (0.60 mmol) and 18-crown-6
b
(0.60 mmol). Isolated yield based on 2.
marked contrast, the reaction of 4-methylbenzyne (from 1h)
produced a mixture of two regioisomers in ca. 50 : 50 ratio.
In addition, ethyl fluorene-9-carboxylate having phenyl-
ethynyl (2k)10 or tert-butyl 2l) substituent on its 2,7 positions
also underwent the reaction facilely, whereas the use of
2,7-dibromofluorene 2m resulted in a lower yield of the
product.
Formation of fluorenyl anion 4 via deprotonation of 2 by a
fluoride ion would trigger the acylfluorenylation as depicted in
Scheme 3. Subsequent nucleophilic attack of 4 to an aryne that
generates aryl anion 5, followed by intramolecular nucleo-
philic substitution at a carbonyl moiety, gives acylfluorenyl-
ation product 3. Owing to the aromatic stabilization of 4,
deprotonation of 2 takes place with greater facility than that of
ethyl diphenylacetate, which would be responsible for the
smooth reaction with 2. The exclusive formation of 3fa or
3ga is ascribable to steric effects,11 which prevent 4 from
approaching the more congested site of 1,2-naphthalyne or
3-methoxybenzyne.12
Scheme 2 Acylfluorenylation of arynes.
synthesized readily under extremely mild conditions.
Further studies on constructing complex carbon frame-
works of aromatic compounds via insertion reactions of
In conclusion, we have demonstrated that a fluorene
is an excellent molecular scaffold for C–C bond cleavage–dual
C–C bond formation sequence, where the facile generation
of a fluorenyl anion, being attributable to its aromatic
stabilization, is the key to smooth progress. Based upon
the present reaction, diverse multi-substituted arenes,
which would otherwise be difficult to obtain, can be
arynes into
laboratories.
a
C–C bond are in progress in our
We thank Central Glass Co. Ltd. for a generous gift of
trifluoromethanesulfonic anhydride. H.Y. also acknowledges
JGC-S Scholarship Foundation and The 2007 Hiroshima
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6 There has been no report on direct C–C bond insertion reactions of
arynes using neutral C–CH compounds, except for refs. 3 and 4.
For examples on the C–C bond insertion reactions of arynes using
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7 Introduction of two carbon functional groups into arynes via
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Scheme 3 Plausible pathway for acylfluorenylation.
8 For a review on insertion reactions of arynes into element–element
s-bonds, see: D. Pena, D. Perez and E. Guitian, Angew. Chem.,
´ ´
Int. Ed., 2006, 45, 3579.
9 Y. Himeshima, T. Sonoda and H. Kobayashi, Chem. Lett., 1983,
1211.
University Fujii Research Promotion Fund for financial
support.
10 A 15% yield of ethyl 2,7-bis(phenylethynyl)-9-phenylfluorene-9-
carboxylate was also produced as a by-product via a formal C–H
bond cleavage reaction.
11 Inductive electron-withdrawing effect of a methoxy group in
3-methoxybenzyne also prefers nucleophilic attack at a meta
position of the methoxy group.
Notes and references
1 For reviews, see: M. Murakami and Y. Ito, in Topics in Organo-
metallic Chemistry, ed. S. Murai, Springer, Berlin, 1999, vol. 3,
pp. 97–129C.-H. Jun, Chem. Soc. Rev., 2004, 33, 610.
2 For recent examples on insertion reactions of alkynes into C–C
s-bonds, see: M. Murakami, S. Ashida and T. Matsuda, J. Am.
Chem. Soc., 2005, 127, 6932; Y. Kuninobu, A. Kawata and
12 Similar regioselectivities have been observed in the reaction of
active methylene compounds. See ref. 4.
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