Synthesis of functionalized 1 H -indenes via copper-catalyzed arylative cyclization of arylalkynes with aromatic sulfonyl chlorides

Article abstract of DOI:10.1021/ja209300c

A variety of polysubstituted 1H-indenes can be prepared through the copper-catalyzed arylative cyclization of simple arylalkynes with commercially available aromatic sulfonyl chlorides that function as an aryl group donor. The reaction tolerates a broad r

Full text of DOI:10.1021/ja209300c

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Synthesis of Functionalized 1H-Indenes via Copper-Catalyzed
Arylative Cyclization of Arylalkynes with Aromatic Sulfonyl Chlorides
Xiaoming Zeng, Laurean Ilies, and Eiichi Nakamura*
Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
S Supporting Information
b
Scheme 1. Copper-Catalyzed Cyclization of Arylalkyne 1
with Naphthalenesulfonyl Chloride (2)
ABSTRACT: A variety of polysubstituted 1H-indenes can
be prepared through the copper-catalyzed arylative cycliza-
tion of simple arylalkynes with commercially available
aromatic sulfonyl chlorides that function as an aryl group
donor. The reaction tolerates a broad range of functional
groups, including bromide and iodide, nitrile, ketone, and
nitro groups. The reaction allowed the synthesis of poly-
cyclic aromatic hydrocarbons, such as a bis(indene), inda-
cene, and fused polyarene derivatives, some of them showing
strong fluorescence in solution and the solid state.
romatic sulfonyl chlorides, which are readily available com-
A
mercially by sulfonylation of arenes, have been widely
utilized for electrophilic arylsulfonylation1 but are little known
as an aryl group donor, except for some recent examples2 of their
use as an electrophilic aryl group, where SO2Cl acts as an
electrofugal group with SO2 expulsion. Our interest in the
catalytic activity of ubiquitous metals,3,4 including copper,5 and
in organic semiconductors converged into the discovery of a new
reaction. We report here a serendipitous finding of the Cu(I)-
catalyzed formation of indene and indacene derivatives6,7 by
arylative cyclization8 of an arylalkyne with an aromatic sulfonyl
chloride, where the latter formally acts as a donor of an aryl
radical group with loss of SO2Cl (Scheme 1). Indene derivatives
have found use in catalysis,9 materials science,10,11 and medicinal
chemistry.12 The present reaction tolerates a variety of functional
groups, including bromide and iodide, nitrile, ketone, and nitro
groups, and will be useful in obtaining functionalized indene
derivatives as illustrated below (see eq 2 and Scheme 2) for
organic electronic devices.13
reaction took place. The high temperature was also essential to
achieve conversion of the starting materials. The catalyst loading
could be decreased at the expense of a lower reaction rate (71%
yield with 5 mol % catalyst, 5 h of reaction). In the presence of
other metal salts, this reaction did not proceed at all (FeCl2,
CoBr2, NiCl2, and PtCl2) or gave a trace (4% yield) of the indene
product 3 [PdCl2(PPh3)2]. Other copper(I) catalysts (CuBr and
CuI) gave 3 in good yield (69 and 60%, respectively), whereas
copper(II) salts such as CuCl2 and Cu(OTf)2 performed poorly
(30 and 26%, respectively). Na2CO3 was found to be the best
base, and other inorganic or organic bases gave inferior results, in
some cases destroying the aromatic sulfonyl chloride (see the SI
for details). In the absence of the base, even when a stoichio-
metric amount of copper was used, the indene product was
formed in a trace amount.
To gain insight into the mechanism, we examined the reaction
of tolane under the same reaction conditions and found that
1-naphthalenesulfonyl chloride undergoes desulfitative addition
to diphenylacetylene to give a triarylvinyl chloride as a mixture of
stereoisomers through loss of the SO2 group (eq 1). This re-
sult contradicts some previous results that an organic sulfonyl
chloride adds across an alkyne to form arylvinylsulfones in the
presence of a copper catalyst.14 In light of the thermal behavior of
related palladium catalysis,2 we may consider that the first step of
the reaction is insertion of the metal into the SO2ÀCl bond, and
the thermal conditions employed here promote the loss of the
SO2 group from a SO2ÀCuÀCl intermediate, as illustrated at the
bottom of Scheme 1. On the other hand, a radical scavenger
(TEMPO) shut off the reaction, suggesting the involvement of
A typical example performed on a gram scale illustrates the
simplicity of the reaction (Scheme 1, top). A mixture of 1-iso-
propyl-2-(phenylethynyl)benzene (1; 1.00 g, 4.54 mmol),
1-naphthalenesulfonyl chloride (2; 2.57 g, 11.35 mmol),
Na2CO3 (1.20 g, 11.35 mmol), and CuCl (0.11 g, 1.14 mmol)
in m-xylene (0.1 mL) was heated under argon at 140 °C for 15 h.
Aqueous workup and silica gel purification gave 1.35 g of 1,1-
dimethyl-3-(1-naphthyl)-2-phenylindene (3; 86% yield). A small
amount of starting material 1 and most of the excess 2 were
recovered, and no other byproducts were detected. The reaction
proceeded with 1.0 equiv of 2, albeit more slowly. The reaction
also proceeded without solvent (61% yield) and slowed down in
a dilute xylene solution or in the presence of polar solvents, which
destroyed the aromatic sulfonyl chloride [see the Supporting
Information (SI) for details].
Both the copper catalyst and the mild inorganic base are
essential for this reaction, and in the absence of either, no
Received: October 3, 2011
Published: October 11, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/ja209300c J. Am. Chem. Soc. 2011, 133, 17638–17640
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radical species.14 We defer a mechanistic discussion until we
obtain further relevant experimental results.
Table 1. Copper-Catalyzed Reaction of 2-(Alkynyl)alkylbenzenes
with Various Aromatic Sulfonyl Chloridesa
As illustrated in Table 1, a variety of aromatic sulfonyl chlorides
reacted smoothly with 1-isopropyl-2-[(4-methoxyphenyl)ethynyl]-
benzene under the optimized conditions. Both electron-rich and
electron-deficient aromatic sulfonyl chlorides (entries 2À10)
gave the corresponding indene products in good yield. Ortho-
substituted aromatic sulfonyl chlorides (entries 9, 11, 12) reacted
cleanly, suggesting that steric effects do not significantly affect the
reaction. An important feature of this reaction is the functional
group tolerance in spite of the high-temperature conditions, as
illustrated by the tolerance of nitrile (entry 4), nitro (entry 10),
ketone (entry 5), fluoride (entry 6), chloride (entries 7 and 10),
bromide (entry 9), and even iodide (entry 8) groups. 2,3-
Dehydrobenzo[1,4]dioxine and thiophene molecules (entries
12 and 13) could also be introduced with good yield. Aliphatic
sulfonyl chlorides did not react under these conditions, suggest-
ing that the CÀS bond cleavage is a difficult step.
Various 2-(alkynyl)alkylbenzene derivatives could also be
utilized. Both electron-rich (entries 1À13) and electron-deficient
alkynes (entry 14) reacted well, although the reaction was slightly
slower for the latter. A heteroaromatic alkyne substrate (entry 15)
and an aliphatic alkyne (entry 16) could also be employed to
produce the corresponding indenes. The isopropyl group on the
benzene ring could be replaced with a diphenylmethyl group
(entry 17) or a benzyl group (entry 18) but not with a methyl
group (data not shown). These data indicate that the cleaving
CÀH bond must be labile, and combined with the high functional
group tolerance, they may be taken as support for a radical, cation,
or carbene mechanism for the ring-forming reaction.
A doublecyclization reaction ofdiacetylenic compounds creates
four new CÀC bonds to produce a bisindene (e.g., 5 in eq 2) or a
dibromoindacene (e.g., 7 in Scheme 2), both of which are of
considerable interest for the promising properties of structurally
related polybenzoheterole molecules.15 Indacene derivatives have
recently received attention as metal ligands16 and ambipolar
organic semiconductors,11 and therefore, we examined the cycliza-
tion of diyne 6 with 2-bromobenzenesulfonyl chloride to obtain
dibromo-1,7-dihydro-s-indacene 7 (Scheme 2). Utilizing the two
bromine groups, we could form two additional rings in excellent
yield to obtain nonacyclic compound 8 through formation of six
new CÀC bonds in two steps.
a Reaction conditions: 2-(alkynyl)alkylbenzene (0.50 mmol), aromatic
sulfonyl chloride (1.25 mmol), CuCl (0.125 mmol), Na2CO3 (1.25 mmol),
m-xylene (0.1 mL), 140 °C; see the SI for details. b Isolated yields.
showed especially strong blue (458 nm) fluorescence both in
solution (ΦF = 0.95) and in the solid state (ΦF = 0.83). A study
Interestingly, compounds 5 and 8 showed strong blue fluo-
rescence both in solution and in the solid state. Compound 5
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dx.doi.org/10.1021/ja209300c |J. Am. Chem. Soc. 2011, 133, 17638–17640

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Scheme 2. Applications of the Copper-Catalyzed Arylative
Cyclization to the Synthesis of Indacene Derivative 7 and
Nonacyclic Fused Hydrocarbon 8
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In summary, we have developed a new synthesis of polysub-
stituted indene derivatives by exploiting aromatic sulfonyl chlor-
ides as an aryl group donor. Several new indene derivatives are
accessible from alkynylarenes17 that can be synthesized in a few
steps from commercially available compounds by the Sonogashira
reaction and commercially available aromatic sulfonyl chlorides.
The new dibromide 7 provided access to the new nonacyclic
compound 8. Given the variety of accessible indene derivatives
and the high functional group tolerance, we anticipate that the
present reaction will serve as a useful tool in the development of
functional materials.18
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’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures, op-
b
timization of the reaction conditions, and physical properties of
the compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
(16) Adams, C.; Morales-Verdejo, C.; Morales, V.; MacLeod-Carey,
D.; Manríquez, M.; Chꢀavez, I.; Mun~oz-Castro, A.; Delpech, F.; Castel,
A.; Gornitzka, H.; Riviꢁere-Baudet, M.; Riviꢁere, P.; Molins, E. Eur. J. Inorg.
Chem. 2009, 784–791.
Corresponding Author
nakamura@chem.s.u-tokyo.ac.jp
(17) Yang, S.; Li, Z.; Jian, X.; He, C. Angew. Chem., Int. Ed. 2009,
48, 3999–4001.
(18) Matsuo, Y.; Sato, Y.; Niinomi, T.; Soga, I.; Tanaka, H.;
Nakamura, E. J. Am. Chem. Soc. 2009, 131, 16048–16050.
’ ACKNOWLEDGMENT
We thank MEXT (KAKENHI Specially Promoted Research
22000008 to E.N., 23750100 to L.I.) and the Global COE
Program for Chemistry Innovation. X.Z. thanks the Japan
Society for the Promotion of Science for a Research Fellowship
for Young Scientists (P10033).
’ REFERENCES
(1) Morrison, R. T.; Boyd, R. N. Organic Chemistry, 5th ed.; Allyn
and Bacon, Boston, 1987.
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