Copper-catalyzed reaction of a-aryldiazoesters with terminal alkynes: A formal [3 + 2] cycloaddition route leading to indene derivatives

Full text of DOI:10.1021/ja808080h

Published on Web 11/26/2008
Copper-Catalyzed Reaction of r-Aryldiazoesters with Terminal Alkynes: A
Formal [3 + 2] Cycloaddition Route Leading to Indene Derivatives
Eun Ju Park, Seok Hwan Kim, and Sukbok Chang*
Department of Chemistry and School of Molecular Science (BK21), Korea AdVanced Institute of Science and
Technology (KAIST), Daejeon 305-701, Republic of Korea
Received October 14, 2008; E-mail: sbchang@kaist.ac.kr
Table 2. Catalytic Reaction of R-Aryldiazoesters with 1-Alkynesa
R-Diazocarbonyl compounds have long been used as a versatile
precursor of carbenes in organic synthesis leading to various
applications.1 Attributing to their ease of preparation and handling,
a diverse range of reactivities of R-diazocarbonyls has been
extensively investigated under thermolytic, photolytic, or transition
metal-employed conditions.2 Representative examples among those
are cyclopropanation, ylide transformation, or X-H insertion (X
) O, N, S, C, Si, etc.)3 which have been elegantly utilized in the
synthesis of complex molecules.4 Reaction of alkynes with car-
benoids normally affords cyclopropene compounds5 which are
versatile synthetic building blocks.6 However, we recently observed
a notable outcome from the Cu(NHC)-catalyzed [NHC: N-hetero-
cyclic carbene] reaction of terminal alkynes with R-aryldiazoesters
leading to indenes, representing the first example of Cu-catalyzed
formal [3 + 2] cycloaddition between those two components.7 Since
indene derivatives have received a great attention from pharma-
ceutical and materials chemistry,8 we further investigated the scope
and mechanistic details of the reaction, which are described herein.9
Table 1. Optimization of the Reaction Conditionsa
entry
catalyst system
solvent
yield (%)b
1
2
3
4
5
6
7
8
9
CuCl
CuCl/AgSbF6
Cu(IPr)Cl
Cu(IPr)Cl/AgSbF6
Cu(IPr)Cl/AgSbF6/NaB(ArF)4
Cu(IMes)Cl/AgSbF6/NaB(ArF)4
Cu(IPr)Br/AgSbF6/NaB(ArF)4
Cu(IPr)Cl/AgSbF6/NaB(ArF)4
Au(IPr)Cl/AgSbF6/NaB(ArF)4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
CH2Cl2
<1 (95)
44 (40)
<1 (<1)
75 (14)
90 (<1)
48 (8)
84 (10)
41 (27)
30 (10)
a 1a (0.2 mmol), 2a (0.6 mmol), catalyst (10 mol %), AgSbF6 (12
mol %), NaB(ArF)4 (12 mol %) in solvent (2.0 mL) at 25 °C for 30
min. b NMR yield of 3a and number in parenthesis is NMR yield of 4a.
a Conditions: R-aryldiazoester (0.5 mmol), 1-alkyne (1.5 mmol),
Cu(IPr)Cl (10 mol %), AgSbF6 (12 mol %), NaB(ArF)4 (12 mol %) in
CH2Cl2 (5.0 mL) at 25 °C for 30 min. b Isolated yield.
When methyl R-diazophenylacetate (1a) was reacted with (4-
methoxyphenyl)acetylene (2a) in the presence of CuCl catalyst, a
cyclopropene compound (4a) was exclusively obtained (Table 1,
entry 1).10 Quite surprisingly, upon the use of cationic copper
species, 3H-indene-1-carboxylate (3a) was produced along with 4a
in similar ratio (entry 2). Although a copper catalyst alone such as
Cu(IPr)Cl11 [IPr: 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]
was ineffective (entry 3), a silver additive significantly increased
conversion and selectivity, giving 3a as a major adduct (entry 4).
Interestingly, certain additives such as NaB(ArF)4 [ArF: 3,5-
bis(trifluoromethyl)phenyl] offered further improvement of the
reaction efficiency and selectivity under the mild conditions (entry
5).12 Catalysts having NHC ligands other than IPr were less
effective (entry 6). Modification of the copper species or change
of solvent resulted in detrimental effects (entries 7-8). In addition,
Au(IPr)Cl catalyst displayed lower efficiency when compared to
that of the corresponding Cu species (entry 9).
To explore the substrate scope, a range of alkynes and R-diaz-
oesters bearing various functional groups were then examined
(Table 2). It was found that electronic property of alkynes has
9
17268 J. AM. CHEM. SOC. 2008, 130, 17268–17269
10.1021/ja808080h CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Mechanistic Proposal of the Formal [3 + 2] Cyclization
profound effects on the reaction efficiency, consistent with the
mechanistic proposal that alkyne initially inserts onto carbenoid.
In fact, phenylacetylenes bearing electron-donating groups react
more readily, in general, with R-aryldiazoesters under the optimized
conditions as compared to electron-deficient alkynes. Structure of
the obtained indenes was confirmed by an X-ray crystallographic
analysis of one product (entry 6).13
Although aliphatic alkynes were inert under the conditions,
alkynes conjugated with vinyl or bearing a thienyl moiety readily
participated in the reaction (entries 7-8).14 Variation of alkoxy
groups in diazoesters did not affect the reaction efficiency (entries
9-10). Interestingly, electronic alternation on R-diazoesters showed
little effects on the reaction efficiency when compared to the alkyne
counterpart (entries 12-17). In addition, the reaction was highly
regioselective (entry 18), in that an unsymmetric aryldiazoester
reacts exclusively at the less hindered site.
between terminal alkynes and R-aryldiazoesters, thus allowing for
selective synthesis of indene derivatives under mild conditions.
Acknowledgment. This research was supported by the Korea
Research Foundation Grant (KRF-2006-312-C00587) and the
EEWS program at KAIST. We thank Dr. Junseung Lee for the
X-ray crystal structure analysis.
Interestingly, when the reaction was carried out in the presence
of a base such as potassium acetate, regioisomeric 1H-indene
compounds could be isolated, which can be attributed to the base-
mediated rearrangement of initially formed 3H-isomers (eq 1).15
Supporting Information Available: Experimental procedures,
analytical data, copies of NMR spectra of products, and a CIF file.
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
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To gain insight into the reaction mechanism, we performed
kinetic isotope effect studies (eq 2). Experiments revealed that this
cyclization exhibits no intermolecular kinetic isotope effects (kH/
kD ) 0.97). When phenylacetylene-d was allowed to react, the
deuterium atom was exclusively incorporated with high extent
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On the basis of the above experiments and precedent reports,2 a
plausible mechanistic pathway is presented in Scheme 1. Electron-
rich acetylene is proposed to insert into an initially formed copper
carbenoid (I) to afford zwitterionic species II.16 Subsequent
intramolecular electrophlic attack on the aromatic ring of II leads
to isoindene IV via III upon the release of copper species.17
Isomerization of IV to a more favorable structure will provide 3H-
indene product V. When an isolated cyclopropene species 4a was
subjected to the reaction conditions of copper catalysts, the cor-
responding indene 3a was not generated, but 4a was recovered
quantitatively. Thus, the possibility of Cu-catalyzed isomerization
of arylcyclopropenes to indenes can be clearly excluded although
the rearrangement was revealed to proceed by rhodium catalysts.18
In summary, we have developed the first example of a novel
type of Cu-catalyzed intermolecular formal [3 + 2] cycloaddition
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P. J. Organometallics 2006, 25, 2237.
(13) See the Supporting Information for details.
(14) Employment of 1,2-disubstituted acetylenes afforded only cyclopropene
compounds in high yields under the optimized conditions.
(15) Pettit, W. A.; Wilson, J. W. J. Am. Chem. Soc. 1977, 99, 6372.
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