Fischer Carbene Pentannulation with Alkynes Having Adjacent Carbonate or Acyloxy Groups: Synthesis of 3-Substituted 1-Indanones

Article abstract of DOI:10.1021/acs.orglett.0c00901

Various aryl Fischer carbenes reacted with alkynes having adjacent acyloxy or carbonate groups to regioselectively deliver 3-substituted 1-indanones. The acyloxy or carbonate group probably coordinates with the Cr metal to give a tetra-coordinated chromium complex forming a six-membered ring that retards CO insertion for ketene formation, which is required for benzannulation. Alternatively, the ortho position aryl ring attack results in pentannulation, providing regioselectively 3-substituted 1-indanones. The method is extended to the synthesis of the core structure of 3-epi-mutisianthol.

Full text of DOI:10.1021/acs.orglett.0c00901

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Letter
Fischer Carbene Pentannulation with Alkynes Having Adjacent
Carbonate or Acyloxy Groups: Synthesis of 3-Substituted 1-
Indanones
Rodney A. Fernandes,* Sachin P. Gholap, Vijay P. Chavan, Akeel S. Saiyed,
and Shubhankar Bhattacharyya
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ABSTRACT: Various aryl Fischer carbenes reacted with alkynes having adjacent acyloxy or carbonate groups to regioselectively
deliver 3-substituted 1-indanones. The acyloxy or carbonate group probably coordinates with the Cr metal to give a tetra-
coordinated chromium complex forming a six-membered ring that retards CO insertion for ketene formation, which is required for
benzannulation. Alternatively, the ortho position aryl ring attack results in pentannulation, providing regioselectively 3-substituted 1-
indanones. The method is extended to the synthesis of the core structure of 3-epi-mutisianthol.
ischer carbenes are extensively used to synthesize various
the reaction.7b Barluenga’s work on controlling the reaction
results by the transmetalation of Fischer carbenes to Ni or Rh
to obtain cyclopentenones is also noteworthy.7c,d
Faromatic, aliphatic, and heterocyclic synthetic building
blocks and biologically active molecules.1,2 Dotz benzannula-
̈
tion is a well-established reaction involving the thermal [3 + 2
+ 1] benzannulation of α,β-unsaturated Fischer carbenes with
alkynes to provide the naphthalene moiety.2,3 Apart from the
We have been actively involved for over a decade in the
̈
application of the Dotz benzannulation reaction in the total
synthesis of various biologically active napthoquinone natural
products.3c,8 In our recent synthesis of (+)-kalafungin,
̈
normally explored Fischer carbene benzannulation by the Dotz
pathway,2b the competing pentannulation is less explored.
̈
(+)-frenolicin B, and related molecules, the Dotz benzannu-
̈
Initially, Dotz and coworkers reported the pentannulation
lation of Fischer carbene 1a with alkyne 2 provided the
naphthalene compound 3 in 51% yield (Scheme 1).8f This was
elaborated to 4 and then to the previously mentioned natural
products. We visualized that the use of alkyne 5a would
directly give product 4 (after phenolic OH methylation),
reaction of nucleophilic aminated alkynes with Fischer
carbenes to produce diaminated indanes and indanones in
moderate yields.4 Similarly, pentannulation was observed in
the reaction of pentacarbonyl chromium carbene with
diphenylacetylene in poorly coordinating solvent.5 The use
̈
thereby reducing the functionalization steps post Dotz
of aminocarbene complexes for the cyclopentannulation
benzannulation. This also appeared promising when using
the dimeric Fischer carbenes toward the synthesis of
actinorhodins.8h Alkyne 5a was prepared from D-glucono-δ-
6
̈
reaction was later separately explored by Dotz and Yamashita.
de Meijere disclosed the [3 + 2] cycloadditions of β-amino-
α,β-unsaturated pentacarbonylcarbenechromium complexes
with alkynes to give substituted cyclopentadienes.7a Later,
Wulff et al. reported the interesting reaction of methoxy
pentacarbonyl chromium carbenes with alkynones to give the
pentannulated lactone products.7b The stereoelectronic effects
were found to determine the geometry of intermediate E or Z
isomers of the η1,η3-vinyl carbene complex, which further
influences the benzannulation or pentannulation outcome of
Received: March 10, 2020
https://dx.doi.org/10.1021/acs.orglett.0c00901
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

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̈
Scheme 1. Product Variation in Dotz Reaction
Figure 1. Indanone and indane core natural products.
were an inseparable mixture, indicating possible benzannulated
and furan products. After systematically varying the solvents,
alkyne concentration, and temperature, the optimum con-
ditions were found to be performing the reaction of 1b with
alkyne 5b (0.95 equiv) in benzene (calcd 0.032 M) at 55 °C.
With the optimized conditions in hand, the scope of this
Fischer carbene pentannulation reaction to 3-substituted 1-
indanones was next examined. As shown in Scheme 2, the
reaction of Fischer carbene 1b with carbonate-based alkynes
delivered the indanone products 6b−d as single diastereomers
in moderate to good yields (42−65%). Alkynes with acyloxy
group gave the indanones 6e−h in 22−61% yields. A dimer
alkyne (prepared from propargyl alcohol and 1,8-octanedi-
carboxylic acid) furnished the dimer indanone 6i in 36% yield.
The butyrolactone-based alkynes reacted with 1b to provide
the indanones 6j and 6a in 45 and 51% yields, respectively.
Similarly, the Fischer carbene 1a with an ortho-methoxy group
reacted with different alkynes to deliver the indanones 6k−p in
21−52% yields. The 4-methoxy-, 2,3-dimethoxy-, 2-methoxy-3-
benzyloxy-, 2-methoxy-4-TBSO-, and 2-benzyloxy-4-TBSO-
based Fischer carbenes reacted with different alkynes and gave
the indanones 6q−u, respectively, in 41−52% yields.
Interestingly, the dimeric biphenyl Fischer carbene8b reacted
with propargyl benzoate to give dimeric indanone 6v in 25%
yield. A reaction of Fischer carbene 1b on a 1.1 mmol scale
with alkyne 5h (1.046 mmol) resulted in indanone 6e in 46%
yield (Scheme 2). With alkynes having a stereocenter (and
being enantiopure), the indanones 6b−d, 6a, 6k, 6l, and 6p−u
were obtained as single enantiopure diastereomers, as inferred
by NMR data and the relative stereochemistry corroborated
from the X-ray structure of 6a. For racemic alkynes with a
stereocenter, the racemic indanones 6g, 6h, 6j, 6n, and 6o
were also obtained as single diastereomers, as analyzed from
the NMR data.
lactone in six steps.9 The former on reaction with Fischer
carbene 1b surprisingly furnished the cyclopentannulation
product 6a in 51% yield as a single diastereomer. The structure
was fully characterized by using spectroscopic methods and
unambiguously confirmed by single-crystal X-ray data. We
could not isolate any other product from the reaction mixture
because it showed a trail of spots on TLC, probably of the
competing inseparable minor benzannulated or furan com-
pounds for the remaining mass balance. Considering the
alkyne 5a to have a acyloxy group adjacent to the alkyne, we
considered that a carbonate group would also give a similar
reaction. Thus the reaction of Fischer carbene 1b with alkyne
5b also provided the indanone product 6b in 35% yield.
The indanone moiety has immense significance. First, it is
present in many natural products, for example, taiwaniaquinol
B (7a),10a−d dichroanal A (7b),10e jungianol (7c),10f
mutisianthol (7d),10g kinamycins A−J (7e),10h−j nakiterpiosin
(7f),10k,l veratramine (7g),10m and so on (Figure 1). Second,
the indanone derivatives are used in medicine and show
various bioactivities.11,12 Considering a few reports on the
Fischer carbene pentannulation reaction and the significance of
the indanone moiety in many natural products and bioactive
molecules, we considered exploring the scope and limitation of
this reaction.
We next examined the alkyne selectivity toward pentannu-
lation versus the benzannulation of Fischer carbene, as shown
in Scheme 3. Ethyl propiolate (8) reacted with Fischer carbene
1b to deliver the known naphthol 9 in 46% yield.13 No
pentannulation product could be isolated in this reaction from
the trail of other minor reaction products. Similarly, the
acyloxy alkyne 10 from homopropargyl alcohol reacted with 1b
to provide naphthol 11 in 55% yield. The acetonide-based
alkyne 5b′ reacted with 1b to give naphthol 12 in 51% yield.
As previously discussed, acetonide alkyne 2 reacted with
The reaction of Fisher carbene 1b with alkyne 5b as model
substrates was considered for optimization. (See Table S1 for
details.) The reaction of 1b with 5b (1.5 equiv) in benzene at
50 °C gave indanone 6b in 35% yield. An inseparable trail of
spots was observed on TLC for the reaction mixture. We could
isolate compound 6b as the major product, whereas others
B
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a
Scheme 2. Substrate Scope for Indanone Synthesis
Scheme 3. Alkyne Selectivity for Benzannulation
Scheme 4. Plausible Mechanism
a
Optimum conditions: Fischer carbene 1 (0.32 mmol), alkyne 5
b
(0.304 mmol, 0.95 equiv), benzene (10 mL), 55 °C. Fischer carbene
(0.64 mmol) used. Alkyne (0.608 mmol) used.
c
probably prevents the CO insertion required for benzannula-
tion. On the contrary, the direct loss of the CO group from this
complex results in aryl ring attack at the ortho position, leading
to pentannulation product 13c. Similarly, in our work, the
reaction of Fischer carbene 1b with the alkyne having the
acyloxy or carbonate group gives the 18-electron chromium
complex 14a (Scheme 4B). Furthermore, the insertion of
alkyne to carbene furnishes the metallotriene 14b. If the CO
insertion occurs, then this would give the ketene 14f required
Fischer carbene 1a and gave naphthol product 3 (Scheme 1).
From these experiments, we concluded that the acyloxy or
carbonate group adjacent to the alkyne has a role to play in
deciding the pentannulation reaction. It is also inferred from
4
̈
the previous Dotz work (Scheme 4A) using diaminoalkyne
that the amine group on the styryl bond of 13a intra-
molecularly displaces the CO ligand, giving the tetracarbonyl
chromium complex 13b having the four-membered ring. This
C
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̈
for the Dotz benzannulation. However, in this work, the
acyloxy or carbonate carbonyl group adjacent to the alkyne
probably coordinates with the Cr metal, giving the
tetracarbonyl chromium complex 14c or 14c′ involving a six-
membered ring. This possibly prevents the CO insertion, and
hence the intramolecular ortho attack of the aryl ring results in
the indanone enol-ether 14d, which hydrolyzes to the
indanone 14e.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00901.
■
sı
Experimental procedures, characterization data, and
NMR spectra of all compounds and X-ray data for 6a
(PDF)
We further considered synthetic modifications of indanone
compound 6e and also elaborated it to the core structure of
mutisianthol 7d (Scheme 5). The latter is an indane natural
Accession Codes
CCDC 1945347 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Scheme 5. Synthetic Transformations of Indanone 6e and
Synthesis of the Core Structure of Mutisianthol
AUTHOR INFORMATION
Corresponding Author
■
Rodney A. Fernandes − Department of Chemistry, Indian
Institute of Technology Bombay, Powai, Mumbai 400076,
Maharashtra, India; orcid.org/0000-0001-8888-0927;
Email: rfernand@chem.iitb.ac.in
Authors
Sachin P. Gholap − Department of Chemistry, Indian Institute
of Technology Bombay, Powai, Mumbai 400076,
Maharashtra, India
Vijay P. Chavan − Department of Chemistry, Indian Institute of
Technology Bombay, Powai, Mumbai 400076, Maharashtra,
India
Akeel S. Saiyed − Department of Chemistry, Indian Institute of
Technology Bombay, Powai, Mumbai 400076, Maharashtra,
India
Shubhankar Bhattacharyya − Department of Chemistry, Indian
Institute of Technology Bombay, Powai, Mumbai 400076,
Maharashtra, India
product isolated from the roots of Mutisia homoeantha.10g The
indanone 6e on Baeyer−Villiger oxidation furnished dihy-
drocoumarin 15 in 69% yield. Here transesterification occurred
with the generated m-chlorobenzoic acid. The NaBH4
reduction of 6e gave the known cis isomer of diol 16
(87%).14 One-carbon Wittig olefination on 6e provided the
exomethylene compound, which on subsequent hydrogena-
tion, furnished the single cis diastereomer that on in situ
benzoate ester hydrolysis gave alcohol 17 in 72% yield (from
6e). Further oxidation of alcohol 17 with Dess−Martin
periodinane (DMP) to the aldehyde and Wittig olefination
with the ylide from Z furnished core structure 1815 of 3-epi-
mutisianthol.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c00901
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Department of Science and Technology New
Delhi for financial support (grant no. SB/S1/OC-42/2013).
S.P.G., V.P.C., and A.S.S. thank the University Grants
Commission of India (UGC), CSIR New Delhi, and IIT-
Bombay, respectively, for research fellowships.
In summary, in this Letter, we have developed Fischer
carbene pentannulation with alkynes having the adjacent
acyloxy or carbonate groups. Various 3-substituted 1-
indanones (22 examples) have been prepared by this method.
In the case of chiral enantiopure alkynes, the reaction afforded
single enantiopure diastereomers. The acyloxy or carbonate
carbonyl group probably coordinates with the Cr metal,
retarding the CO insertion to give the ketene intermediate
required for benzannulation. The diverted reaction results in
an aryl ring giving an ortho attack, resulting in pentannulation
leading to indanone compounds. The method has been
elaborated to complete the synthesis of the core structure of
3-epi-mutisianthol.
REFERENCES
■
̈
(1) (a) Fischer, E. O.; Maasbol, A. Zur Frage eines Wolfram-
Carbonyl-Carben-Komplexes. Angew. Chem. 1964, 76, 645. (b) Dotz,
̈
K. H. Carbene Complexes in Organic Synthesis. Angew. Chem., Int.
Ed. Engl. 1984, 23, 587. (c) Wulff, W. D. Metal-Carbene
Cycloadditions. In Comprehensive Organic Synthesis; Wiley-Inter-
science: New York, 1988. (d) Hegedus, L. S. Transition Metals in
the Synthesis of Complex Organic Molecules; University Science Books,
1994. (e) de Meijere, A.; Schirmer, H.; Duetsch, M. Fischer Carbene
Complexes as Chemical Multitalents: The Incredible Range of
Products from Carbenepentacarbonylmetal α,β-Unsaturated Com-
̈
plexes. Angew. Chem., Int. Ed. 2000, 39, 3964. (f) Dotz, K. H.; Stendel,
J., Jr. Fischer Carbene Complexes in Organic Synthesis: Metal-
D
https://dx.doi.org/10.1021/acs.orglett.0c00901
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Assisted and Metal-Templated Reactions. Chem. Rev. 2009, 109,
3227. (g) Barluenga, J.; Aguilar, E. Group 6 Metal Fischer Carbene
Complexes: Versatile Synthetic Building Blocks. Adv. Organomet.
Chem. 2017, 67, 1.
(2) (a) Wulff, W. D.; Yang, D. C.; Murray, C. K. Cyclopropanations
and Cycloadditions of Transition Metal Carbene Complexes. Pure
Approach to the Synthesis of Regioisomeric Core of Cardinalin 3.
Synlett 2010, 2010, 2667. (c) Fernandes, R. A.; Mulay, S. V. Total
Synthesis of (+)-Demethoxycardinalin 3. J. Org. Chem. 2010, 75,
7029. (d) Fernandes, R. A.; Ingle, A. B. A Concise Stereoselective
Synthesis of Tetracyclic Naphthoquinone, (−)-Isagarin. Eur. J. Org.
Chem. 2011, 2011, 6624. (e) Fernandes, R. A.; Ingle, A. B.; Chavan,
V. P. Stereoselective Synthesis of (−)-1-epi-Ventiloquinone L and
(+)-Ventiloquinone L, the Monomeric Unit of Cardinalin 3. Org.
Biomol. Chem. 2012, 10, 4462. (f) Fernandes, R. A.; Chavan, V. P.;
Mulay, S. V.; Manchoju, A. A Chiron Approach to the Total Synthesis
of (−)-Juglomycin A, (+)-Kalafungin, (+)-Frenolicin B and
(+)-Deoxyfrenolicin. J. Org. Chem. 2012, 77, 10455. (g) Fernandes,
R. A.; Mulay, S. V.; Chavan, V. P. A Concise Total Synthesis of
Arizonins B1 and C1. Tetrahedron: Asymmetry 2013, 24, 1548.
(h) Mulay, S. V.; Fernandes, R. A. Synthetic Studies on Actinorhodin
and γ-Actinorhodin: Synthesis of Deoxyactinorhodin and Deoxy-γ-
Actinorhodin/Crisamicin A Isomer. Chem. - Eur. J. 2015, 21, 4842.
(i) Mulay, S. V.; Bhowmik, A.; Fernandes, R. A. Synthetic Studies
Toward Actinorhodin and γ-Actinorhodin by Homo-coupling
Strategy: Synthesis of Hemiactinorhodin and Hemi-γ-actinorhodin.
Eur. J. Org. Chem. 2015, 2015, 4931.
̈
Appl. Chem. 1988, 60, 137. (b) Dotz, K. H.; Tomuschat, P.
Annulation Reactions of Chromium Carbene Complexes: Scope,
Selectivity and Recent Developments. Chem. Soc. Rev. 1999, 28, 187.
(c) Barluenga, J. Fischer Carbene Complexes. A New Tool for
Heterocyclic Synthesis. Pure Appl. Chem. 2002, 74, 1317. (d) Minatti,
̈
A.; Dotz, K. H. Chromium-Templated Benzannulation Reactions.
Top. Organomet. Chem. 2004, 13, 123. (e) Barluenga, J.; Martínez, S.
New Heterocyclization Reactions with Fischer Carbene Complexes.
ARKIVOC 2006, vii, 129. (f) Fernandes, R. A.; Mulay, S. V. Chiral
̈
Cups (Calixarenes) via Dotz Benzannulation. Synthesis 2014, 46,
1836. (g) Santamaría, J.; Aguilar, E. Beyond Fischer and Schrock
Carbenes: Non-heteroatom-stabilized Group 6 Metal Carbene
Complexes − a General Overview. Org. Chem. Front. 2016, 3, 1561.
̈
(3) (a) Dotz, K. H. Synthesis of the Naphthol Skeleton from
Pentacarbonyl[Methoxy(phenyl)carbene]Chromium (O) and Tolan.
Angew. Chem., Int. Ed. Engl. 1975, 14, 644. (b) Waters, M. L.; Wulff,
W. D. The Synthesis of Phenols and Quinones via Fischer Carbene
Complexes. Org. React. 2008, 70, 121. (c) Fernandes, R. A.; Kumari,
(9) The synthesis of alkyne 5a required six steps from D-glucono-δ-
lactone. The preparation of precursor 2 for 5a is reported by us. (See
ref 8f.) The last steps of lactonization and TBS protection are given in
the Supporting Information.
̈
A.; Pathare, R. S. A Decade with Dotz Benzannulation in the
Synthesis of Natural Products. Synlett 2020, 31, 403.
(10) (a) Lin, W.-H.; Fang, J.-M.; Cheng, Y.-S. Uncommon
Diterpenes with the Skeleton of Six-five-six Fused-rings from
Taiwania cryptomerioides. Phytochemistry 1995, 40, 871. (b) Lin, W.-
H.; Fang, J.-M.; Cheng, Y.-S. Diterpenes and Related Cycloadducts
from Taiwania cryptomerioides. Phytochemistry 1996, 42, 1657.
(c) Chang, C.-I.; Chien, S.-C.; Lee, S.-M.; Kuo, Y.-H. Three Novel
5(6→7)Abeoabietane-type Diterpenes from the Bark of Taiwania
cryptomerioides. Chem. Pharm. Bull. 2003, 51, 1420. (d) Chang, C.-I.;
Chang, J.-Y.; Kuo, C.-C.; Pan, W.-Y.; Kuo, Y.-H. Four New 6-Nor-
5(6→7)abeo-abietane Type Diterpenes and Antitumoral Cytotoxic
Diterpene Constituents from the Bark of Taiwania cryptomerioides.
Planta Med. 2005, 71, 72. (e) Kawazoe, K.; Yamamoto, M.; Takaishi,
Y.; Honda, G.; Fujita, T.; Sezik, E.; Yesilada, E. Rearranged Abietane-
type Diterpenes from Salvia Dichroantha. Phytochemistry 1999, 50,
̈
(4) (a) Dotz, K. H.; Kreiter, C. G. Zum Reaktionsverhalten von
̈
̈
Bis(diathylamino)acetylene Gegenuber Pentacarbonyl-
(methoxyphenylcarben)chrom(0) und -Wolfram(0). Chem. Ber.
̈
1976, 109, 2026. (b) Dotz, K. H.; Neugebauer, D. Template
Reactions on Chromium(0): Synthesis of a Functionalized Indene
from Pentacarbonyl[methoxy-(phenyl)carbene]chromium and Bis-
(diethylamino)acetylene. Angew. Chem., Int. Ed. Engl. 1978, 17, 851.
̈
̈
(c) Dotz, K. H.; Pruskil, I. Stereoselektivitat der Einschiebung von
Inaminen in die ChromCarbenkohlenstoff-Bindung: erster Schritt
einer Zweistufigen Synthese von Indanon- und Indenon-Derivaten.
Chem. Ber. 1978, 111, 2059.
̈
(5) Dotz, K. H. Reaktionen von Komplexliganden IX. Carbenli-
ganden, Carbonylliganden und Alkine als Bausteine fur Isocyclische
und Heterocyclische Systeme. J. Organomet. Chem. 1977, 140, 177.
̈
̈
493. (f) Bohlmann, F.; Zdero, C. Uber Inhaltsstoffe der Tribus
̈
(6) (a) Dotz, K. H.; Erben, H.-G.; Harms, K. Aminocarbene
Annulation by Alkynes: a Regio- and Diastereoselective Route to
Mutisieae. Phytochemistry 1977, 16, 239. (g) Bohlmann, F.; Zdero, C.;
Le Van, N. Neue Geranyl-cumarin-derivate und Weitere Inhaltsstoffe
aus der Tribus Mutisieae. Phytochemistry 1979, 18, 99. (h) Ito, S.;
Matsuya, T.; Omura, S.; Otani, M.; Nakagawa, A.; Takeshima, H.;
Iwai, Y.; Ohtani, M.; Hata, T. A New Antibiotic, Kinamycin. J.
Antibiot. 1970, 23, 315. (i) Hata, T.; Omura, S.; Iwai, Y.; Nakagawa,
A.; Otani, M.; Ito, S.; Matsuya, T. A New Antibiotic, Kinamycin:
Fermentation, Isolation, Purification and Properties. J. Antibiot. 1971,
24, 353. (j) Omura, S.; Nakagawa, A.; Yamada, H.; Hata, T.; Furusaki,
A.; Watanabe, T. Structures and Biological Properties of Kinamycin A,
B, C, and D. Chem. Pharm. Bull. 1973, 21, 931. (k) Gao, S.; Wang, Q.;
Chen, C. Synthesis and Structure Revision of Nakiterpiosin. J. Am.
Chem. Soc. 2009, 131, 1410. (l) Gao, S.; Wang, Q.; Huang, L. J.-S.;
Lum, L.; Chen, C. Chemical and Biological Studies of Nakiterpiosin
and Nakiterpiosinone. J. Am. Chem. Soc. 2010, 132, 371. (m) Saito, K.
Veratramine, a New Alkaloid of White Hellebore (Veratrum
grandifiorum Loes. fil.). Bull. Chem. Soc. Jpn. 1940, 15, 22.
(11) (a) Finkielsztein, L. A.; Castro, E. F.; Fabian, L. E.; Moltrasio,
G. Y.; Campos, R. H.; Cavallaro, L. V.; Moglioni, A. G. New 1-
Indanone Thiosemicarbazone Derivatives Active Against BVDV. Eur.
J. Med. Chem. 2008, 43, 1767. (b) Sugimoto, H.; Iimura, Y.;
Yamanishi, Y.; Yamatsu, K. Synthesis and Structure-Activity Relation-
ships of Acetylcholinesterase Inhibitors: l-Benzyl-4-[(5,6-dimethoxy-l-
oxoindan-2-yl)methyl]piperidine Hydrochloride and Related Com-
pounds. J. Med. Chem. 1995, 38, 4821. (c) Huang, L.; Miao, H.; Sun,
Y.; Meng, F.; Li, X. Discovery of Indanone Derivatives as Multi-target-
directed Ligands Against Alzheimer’s Disease. Eur. J. Med. Chem.
2014, 87, 429. (d) DeSolms, S. J.; Woltersdorf, O. W., Jr.; Cragoe, E.
J., Jr.; Watson, L. S.; Fanelli, G. M., Jr. (Acylaryloxy)acetic Acid
Indanone Complexes. J. Chem. Soc., Chem. Commun. 1989, 692.
(b) Grotjahn, D. B.; Dotz, K. H. Carbene Complexes of Chromium
Bearing Nitrogen Substituents. Synlett 1991, 1991, 381. (c) Yamashita,
A. Synthesis of Indenes from Alkynes and Phenyl Amino Chromium
Carbene Complexes. Tetrahedron Lett. 1986, 27, 5915.
(7) (a) Flynn, B. L.; Funke, F. J.; Silveira, C. C.; de Meijere, A.
Selective [3 + 2] Cycloadditions of β-Amino-α,β-unsaturated
Pentacarbonylchromium Complexes to Alkynes − A New Approach
to Functionally Substituted Cyclopentadienes. Synlett 1995, 1995,
1007. (b) Waters, M. L.; Brandvold, T. A.; Isaacs, L.; Wulff, W. D.;
Rheingold, A. L. Stereoelectronic Effects on Product Formation from
the E- and Z-Isomers of η1η3-Vinyl Carbene Complexed Intermediates
in the Reactions of Fischer Carbene Complexes with Alkynes.
̈
́
Organometallics 1998, 17, 4298. (c) Barluenga, J.; Vicente, R.; Lopez,
́
́
L. A.; Rubio, E.; Tomas, M.; Alvarez-Rua, C. New Fischer Carbenes
Complexes of Rhodium(I): Preparation and 2-Cyclopentenone Ring
Synthesis by Annelation to Alkynes. J. Am. Chem. Soc. 2004, 126, 470.
(d) Barluenga, J.; Barrio, P.; Riesgo, L.; Lopez, L. A.; Tomas, M. A
General and Regioselective Synthesis of Cyclopentenone Derivatives
through Nickel(0)-Mediated [3 + 2] Cyclization of Alkenyl Fischer
Carbene Complexes and Internal Alkynes. J. Am. Chem. Soc. 2007,
129, 14422.
(8) For selected examples, see: (a) Fernandes, R. A.; Chavan, V. P. A
Highly Enantioselective Synthesis of (−)- and (+)-Juglomycin A
through Dotz Benzannulation and Asymmetric Dihydroxylation.
Tetrahedron Lett. 2008, 49, 3899. (b) Fernandes, R. A.; Mulay, S.
V. Dimeric Fischer Carbenes: a Bidirectional Dotz Benzannulation
́
́
̈
̈
E
https://dx.doi.org/10.1021/acs.orglett.0c00901
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Diuretics. 2. (2-Alkyl-2-aryl-1-oxo-5-indanyloxy)acetic Acids. J. Med.
Chem. 1978, 21, 437.
(12) (a) Turek, M.; Szczesna, D.; Koprowski, M.; Bałczewski, P.
Synthesis of 1-Indanones with a Broad Range of Biological Activity.
Beilstein J. Org. Chem. 2017, 13, 451. (b) Nagle, D. G.; Zhou, Y.-D.;
Park, P. U.; Paul, V. J.; Rajbhandari, I.; Duncan, C. J. G.; Pasco, D. S.
A New Indanone from the Marine Cyanobacterium Lyngbya
majuscula That Inhibits Hypoxia-induced Activation of the VEGF
Promoter in Hep3B Cells. J. Nat. Prod. 2000, 63, 1431. (c) Cossy, J.;
Belotti, D.; Maguer, A. Synthesis of Indatraline Using a Suzuki Cross-
Coupling Reaction and a Chemoselective Hydrogenation: A Versatile
Approach. Synlett 2003, 1515. (d) Yu, H.; Kim, I. J.; Folk, J. E.; Tian,
X.; Rothman, R. B.; Baumann, M. H.; Dersch, C. M.; Flippen-
Anderson, J. L.; Parrish, D.; Jacobson, A. E.; Rice, K. C. Synthesis and
Pharmacological Evaluation of 3-(3,4-Dichlorophenyl)-1-indanamine
Derivatives as Nonselective Ligands for Biogenic Amine Transporters.
J. Med. Chem. 2004, 47, 2624. (e) Ahmed, N. Synthetic Advances in
the Indane Natural Product Scaffolds as Drug Candidates: A Review.
Stud. Nat. Prod. Chem. 2016, 51, 383−434.
(13) Yamashita, A.; Toy, A. Regioselectivity of the Reaction of a
Chromium-carbene Complex with Alkynes: Examination of Steric and
Electronic Factors. Tetrahedron Lett. 1986, 27, 3471.
́
(14) Fernandez, F.; García-Mera, X.; Morales, M.; Vilarin
Caamano, O.; De Clercq, E. Synthesis of New 6-Substituted Purinyl-
̃
o, L.;
̃
5′-nor-1′-homocarbanucleosides Based on Indanol. Tetrahedron 2004,
60, 9245.
(15) Bianco, G. G.; Ferraz, H. M. C.; Costa, A. M.; Costa-Lotufo, L.
V.; Pessoa, C.; de Moraes, M. O.; Schrems, M. G.; Pfaltz, A.; Silva, L.
F., Jr. (+)- and (−)-Mutisianthol: First Total Synthesis, Absolute
Configuration, and Antitumor Activity. J. Org. Chem. 2009, 74, 2561.
F
https://dx.doi.org/10.1021/acs.orglett.0c00901
Org. Lett. XXXX, XXX, XXX−XXX