Silver-Catalyzed Carbon Dioxide Fixation on Alkynylindenes

Article abstract of DOI:10.1021/acs.orglett.0c03250

The synthesis of polycyclic indene derivatives via silver-catalyzed carbon dioxide fixation on 2-alkynylindene derivatives was achieved by nucleophilic addition of the indenyl anion to carbon dioxide involving carbon-carbon bond formation and subsequent intramolecular cyclization to the alkyne part activated by a silver catalyst. This cascade process could be applied to various substrates to obtain the corresponding products in high yields. The endo/exo selectivity of the cyclization could be controlled by the steric or electronic effect of the substituents on the substrates, and 6-endo-selective cyclization was realized to afford α-pyrone-fused indenes.

Full text of DOI:10.1021/acs.orglett.0c03250

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Letter
Silver-Catalyzed Carbon Dioxide Fixation on Alkynylindenes
Akira Okumura, Po-Yao Chuang, Kodai Saito, and Tohru Yamada*
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ABSTRACT: The synthesis of polycyclic indene derivatives via silver-
catalyzed carbon dioxide fixation on 2-alkynylindene derivatives was
achieved by nucleophilic addition of the indenyl anion to carbon
dioxide involving carbon−carbon bond formation and subsequent
intramolecular cyclization to the alkyne part activated by a silver
catalyst. This cascade process could be applied to various substrates to
obtain the corresponding products in high yields. The endo/exo selectivity of the cyclization could be controlled by the steric or
electronic effect of the substituents on the substrates, and 6-endo-selective cyclization was realized to afford α-pyrone-fused indenes.
carboxylate intermediate, which could be followed by intra-
arbon dioxide is an attractive C1 source for molecular
Cconstruction in terms of nontoxicity, low-cost availability, molecular cyclization into the alkyne part activated by a silver
and easy handling.1 However, the thermodynamic stability of
catalyst and protonation of the vinylsilver intermediate to
afford the polycyclic indene (Scheme 1). We now report a new
method for the synthesis of polycyclic indenes by silver-
catalyzed CO2 incorporation into 2-alkynylindenes.
A catalyst screening was conducted using 2-alkynylindene
derivative 1a. The reaction was carried out using DBU as a
base in toluene under CO2 at a pressure of 2 MPa (Table 1).
Without a transition metal salt, no cyclized product was
obtained, and 1a was recovered (entry 1). Metal salts such as
CO2 has made it difficult to fix carbon dioxide into an organic
substrate, and thus, reactions with strong nucleophiles are
often required in order to suppress decarboxylation from a
CO2 adduct.2 For this problematic concern, the CO2
incorporation reaction based on base-mediated deprotonation
and subsequent nucleophilic addition to CO2sequential
intramolecular cyclization with an alkyne activated by
transition metal catalysts3is a reliable solution that has
been widely applied to various heterocycle syntheses.4 While
silver-catalyzed CO2 incorporation into propargyl alcohols and
alkynyl anilines based on this strategy has been reported,3a
carbon nucleophiles, such as alkynyl ketones5 and ynones,6
involving C−H carboxylation7 through generation of an
enolate were more recently achieved for these reactions.
Therefore, the achievement of carboxylative cyclization
involving carbon−carbon bond formation with CO2 is one of
the attractive tasks in CO2 chemistry and might allow for rapid
access to the target molecules.
Scheme 1. Background and Representative Concepts of the
Present Work
The development of efficient methods for the synthesis of
polycyclic indene derivatives has been considered an important
issue in organic synthesis because indenes have many
promising applications, such as pharmaceutical agents showing
unique biological activities, building blocks for functional
materials,8 and ligand precursors of indenyl−metal complexes.9
An interesting characteristic of indene is its relatively high
acidity (pKa = 20.1 in DMSO)10 originating from the
cyclopentadiene structure containing a benzylic position, and
a base-mediated deprotonation reaction can occur to generate
an indenyl anion, which can be applied for further reactions
with some electrophiles. However, the applicable electrophiles
have been limited because a strong base has been used for the
generation of the indenyl anion.11 We envisioned that the
indenyl anion generated from deprotonation of a 2-
alkynylindene could capture carbon dioxide to give the
Received: September 28, 2020
https://dx.doi.org/10.1021/acs.orglett.0c03250
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

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a
Table 1. Examination of the Reaction Conditions
Scheme 2. Substrate Scope of Silver-Catalyzed CO2
a
Fixation
b
yields (%)
entry
catalyst
none
AuCl
Pt(acac)2
Pd(OAc)2
AgOBz
AgOBz
AgF
RSM (%)
2a 3a
1
2
3
4
5
97
97
97
97
11
0
83
23
10
0
0
0
0
0
0
0
0
0
74
86
10
62
68
58
62
53
9
10
2
c
6
7
8
9
AgO
6
AgNO3
AgOBz
AgOBz
AgOBz
13
11
10
12
d
10
e
11
f
0
0
12
a
Conditions: 1a (0.1 mmol) and the catalyst (20 mol %) in toluene
b
(1.0 mL) at 25 °C under CO2 at a pressure of 2 MPa. NMR yields.
c
d
e
f
The reaction time was 3 h. In DMF. In CH3CN. In DMSO.
Au, Pt, and Pd, which were expected to activate the alkyne
moiety, were proved not to be effective for this reaction
(entries 2−4). Interestingly, silver benzoate was employed for
this reaction and gave the 6-endo-cyclized product 2a in 74%
yield along with the 5-exo-cyclized product 3a in 9% yield
(entry 5). The yield of 2a was further improved by a longer
reaction time (entry 6). Although other silver salts were
evaluated to improve the yield and the selectivity, no catalyst
surpassed AgOBz (entries 7−9). The reaction solvent was also
investigated, and it was found that the use of polar solvents
such as DMF, CH3CN, and DMSO did not have a positive
effect on the yield of 2a (entries 10−12).12 The optimal
reaction conditions were established as follows: AgOBz (20
mol %), DBU (4 equiv), CO2 (2.0 MPa), toluene, 25 °C, 3 h.
The substrate scope was explored. The catalyst loading for
the reaction of 1a could be reduced to 2 mol % without any
decreased yield of 2a. Investigation of the effect of the R1
substituent (Scheme 2) showed an increase in the yield of 2
with 1b and 1c, which contained an electron-donating group
(EDG) on the benzene ring, to afford 2b/3b and 2c/3c in 80%
and 85% yield, respectively. On the other hand, an electron-
withdrawing group (EWG) on R1 (1d, 1e) resulted in
decreased yields (2d/3d, 76% yield; 2e/3e, 79%) and 5-exo/
6-endo selectivity. The use of a 2-tolyl group (1f) and a 1-
naphthyl group (1g), which could have a larger steric influence
around the alkyne moiety, showed a positive effect, and
selective 6-endo cyclization was realized to afford 2f and 2g in
63% and 68% yield, respectively. Substrates bearing other
aromatics at the alkyne terminus, such as 3,5-xylyl (1h), 2-
naphthyl (1i), and 2-pyridyl (1j), were also suitable for this
method and gave the corresponding 6-endo-cyclized products.
Substrate 1k containing the cyclohexene unit at R1 was
selectively converted into the 6-endo-cyclized product 2k in
64% yield. Next, the reactions of alkyl-substituted substrates
a
Conditions: starting material 1 (0.1 mmol) and AgOBz (20 mol %)
in toluene (1.0 mL) at 25 °C under CO2 at a pressure of 2 MPa
(details in the Supporting Information). Isolated yields are shown.
b
MTBD = 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene. 1m (1
mmol) was used.
were examined. Substitution with primary (n-butyl (2l),
phenethyl (2m)), secondary (cyclohexyl (2n)), and tertiary
(tert-butyl (2o)) alkyl groups realized the 6-endo-selective
cyclization to afford the corresponding products in good yields.
Next, the effect of substituents on the indene was
investigated (Scheme 3). Substrates having a 5,6-dimethylin-
dene structure (4a and 4b) were employed for this reaction to
B
https://dx.doi.org/10.1021/acs.orglett.0c03250
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Scheme 3. Substrate Scope of Silver-Catalyzed CO2
Fixation
Scheme 4. Plausible Reaction Mechanism
a
former case, it could be considered that the repulsion between
R3 and the silver coordinated to the alkyne causes a bias in
coordination to the alkyne, and as a result, the 6-endo
cyclization proceeds selectively. In the latter case, the alkyl
substitution induces a polarization between the two alkyne
carbons, and the 6-endo cyclization occurs at the positively
charged alkyne carbon substituted by the alkyl group.14
In summary, the synthesis of polycyclic indenes was
accomplished by carbon dioxide fixation and sequential
silver-catalyzed intramolecular cyclization of 2-alkynylindene
derivatives as substrates. It is worth noting that this process
involves carbon−carbon bond formation with CO2 based on
C−H functionalization under mild reaction conditions.
Various substrates were suitable for this method, and the 6-
endo cyclization mainly proceeded to give α-pyrone-fused
indenes in good yields. Further investigation of the reaction
mechanism and application of the reaction to the synthesis of
more complex molecules are underway.
a
Conditions: starting material 4 (0.1 mmol) and AgOBz (20 mol %)
in toluene (1.0 mL) at 25 °C under CO2 at a pressure of 2 MPa
(details in Supporting Information). Isolated yields are shown.
give the corresponding products 5a and 5b in 89% and 63%
yield, respectively, without the 5-exo-cyclized product. Cyclo-
hexyl- and tert-butyl-substituted 4c and 4d were also converted
into 5c and 5d in 54% and 62% yield, respectively. Substrates
containing a 5,6-dimethoxyindene moiety (4e−h) were found
to form the corresponding products bearing phenethyl (5e),
cyclohexyl (5f), and cyclohexenyl (5g) groups in good yields.
A plausible reaction mechanism is shown in Scheme 4. CO2
is incorporated onto substrate 1 in the presence of the silver
catalyst with DBU by means of carbon−carbon bond
formation to afford π complex 7.13Sequential intramolecular
cyclization of the carboxylate on the activated alkyne part
occurs to give the six- and five-membered vinylsilver
intermediates 8 and 9, respectively. Finally, the polycyclic
indenes are obtained through protonation and isomerization of
the vinylsilver intermediates. Although the 6-endo cyclization
pathway proceeds mainly, the selectivity of the cyclization
could be perfectly controlled by the introduction of a
substituent at the ortho position of the benzene ring and
alkyl groups at the alkyne terminus, giving only 2. In the
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c03250.
■
sı
Experimental procedures, characterization details, NMR
spectra of new compounds and reaction products (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Tohru Yamada − Department of Chemistry, Keio University,
Yokohama 223-8522, Japan; orcid.org/0000-0002-4177-
5019; Email: yamada@chem.keio.ac.jp
Authors
Akira Okumura − Department of Chemistry, Keio University,
Yokohama 223-8522, Japan
Po-Yao Chuang − Department of Chemistry, Keio University,
Yokohama 223-8522, Japan
C
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Letter
60, 1204−1206. (d) Iritani, K.; Yanagihara, N.; Utimoto, K.
Carboxylative Coupling of Propargylic Alcohols with Allyl Chloride.
J. Org. Chem. 1986, 51, 5499−5501. (e) Inoue, Y.; Ohuchi, K.;
Imaizumi, S. A new and facile synthesis of 3(2H)-furanones via
carboxylation-decarboxylation sequence. Tetrahedron Lett. 1988, 29,
5941−5942.
Kodai Saito − Department of Chemistry, Keio University,
Yokohama 223-8522, Japan; orcid.org/0000-0001-5867-
2713
Complete contact information is available at:
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Notes
The authors declare no competing financial interest.
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