Synthesis of Benzo[ b]furans by Intramolecular C-O Bond Formation Using Iron and Copper Catalysis

Article abstract of DOI:10.1021/acs.orglett.0c00754

One-pot processes for the synthesis of benzo[b]furans from 1-aryl- or 1-alkylketones using nonprecious transition metal catalysts have been developed. Regioselective iron(III)-catalyzed halogenation of the aryl ring, followed by iron- or copper-catalyzed O-arylation allowed the synthesis of various structural analogues, including the benzo[b]furan-derived natural products corsifuran C, moracin F, and caleprunin B.

Full text of DOI:10.1021/acs.orglett.0c00754

This is an open access article published under a Creative Commons Attribution (CC-BY)
License, which permits unrestricted use, distribution and reproduction in any medium,
provided the author and source are cited.
pubs.acs.org/OrgLett
Letter
Synthesis of Benzo[b]furans by Intramolecular C−O Bond Formation
Using Iron and Copper Catalysis
Martyn C. Henry and Andrew Sutherland*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c00754
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: One-pot processes for the synthesis of benzo[b]furans from
1-aryl- or 1-alkylketones using nonprecious transition metal catalysts have
been developed. Regioselective iron(III)-catalyzed halogenation of the aryl
ring, followed by iron- or copper-catalyzed O-arylation allowed the synthesis
of various structural analogues, including the benzo[b]furan-derived natural
products corsifuran C, moracin F, and caleprunin B.
preparation of benzo[b]furans by formation of the C7a−O bond
he benzo[b]furan ring system is a privileged structure,
Tfound in a wide range of natural products and pharmaceuti- has also been reported via metal-catalyzed cyclization of 1-(2-
haloaryl)ketones.5 A general process was reported by Willis and
co-workers, who showed that enolates of 1-(2-bromoaryl)-
ketones were effective substrates for palladium-catalyzed O-
heterocyclization and the preparation of 2,3-disubstituted
benzo[b]furans (Scheme 1b).5a Similar transformations that
use nonprecious transition metal catalysts have also been
described.5b−f Whereas high-temperature reactions, under basic
conditions involving copper(I) salts, are typically used, Bolm
and co-workers reported that this transformation could also be
catalyzed by iron(III) chloride.5f
Although several methods for the synthesis of benzo[b]furans
through C7a−O bond formation have been described, these
require prehalogenated 1-arylketone starting materials. We
recently reported the use of iron(III) triflimide as a super Lewis
acid for the activation of N-halosuccinimides and the subsequent
regioselective halogenation of arenes.6 This process could also
be combined with copper-catalyzed inter- and intramolecular
C−N and C−O bond forming reactions for the preparation of
anilines, aryl amides, and benzannulated heterocycles.7 Based on
this research program, we envisaged a one-pot approach for the
preparation of highly substituted benzo[b]furans from simple 1-
aryl- or 1-alkylketones, involving regioselective iron(III)-
catalyzed halogenation, followed by metal-mediated O-aryla-
tion. We now report the development of various one-pot
processes for the synthesis of benzo[b]furans. As well as
demonstrating the use of parts per million (ppm) copper loading
to perform C−O cyclization (Scheme 1c), we report that both
steps can also be catalyzed using a single iron salt.
cally active compounds.1 2-Substituted analogues, in particular,
have been isolated from various plant and marine sources, as well
as bacterial and fungal organisms and have been shown to have
activity as antimicrobial, antifungal, and anti-inflammatory
agents.
Due to the medical importance of benzo[b]furans, there has
been significant efforts in developing new synthetic methods for
their preparation,2 including transition-metal-catalyzed pro-
cesses.3−5 A common approach is the reaction of 2-halophenols
with alkynes via a Sonogashira reaction, followed by transition-
metal-catalyzed O-heterocyclization.2a Li and co-workers have
shown that these steps can be combined in a one-pot process
using a catalytic system composed of [Pd(η3-C3H5)Cl]2 and a
tetraphosphine ligand (Scheme 1a).4c Low catalyst loading
(<0.1 mol %) could be used with a wide range of 2-chloro-, 2-
bromo-, and 2-iodophenol substrates. Although less common,
Scheme 1. Selected Metal-Catalyzed Approaches for the
Synthesis of Benzo[b]furans
Received: February 27, 2020
https://dx.doi.org/10.1021/acs.orglett.0c00754
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
The 1-aryl- and 1-alkylketones used in this study were readily
accessed from commercially available phenylacetic acids. For
example, the synthesis of 1-arylketone 3a, used to optimize the
one-pot processes, was prepared in two steps (Scheme 2). 3-
O-arylation step (e.g., FeCl3 with 99.9% purity contains 31.1
ppm of Cu).8 However, this presented an opportunity to
develop a one-pot process using a single iron complex in which
the residual ppm levels of copper could be used to catalyze the
cyclization step. The one-pot process was repeated using only
FeCl3, with either 97 or 99.9% purity, which gave benzo[b]furan
4a in 48 and 44% yields, respectively (Table 1, entries 2 and 3).
To verify that ppm loading of copper could catalyze the
heterocyclization of 1-(2-haloaryl)ketones, we performed the
single-step cyclization with the iodide of 3a using CuI (0.001
mol %, 14 ppm).9 This gave benzo[b]furan 4a in 55% yield.
Thus, in the one-pot process, we believe that whereas iron(III)
performs the iodination step, the ppm loading of copper is
responsible for the intramolecular O-arylation step. To improve
the yield of this one-pot process, catalyst loading was next
investigated. Using FeCl3 (99.9% purity) at 5 mol % loading
gave 4a in 60% yield (entry 4). Increasing the catalyst loading
further (entry 5) did not lead to substantially higher yields, and
so 5 mol % was deemed the optimal amount for subsequent
studies.
To determine whether iron(III) could catalyze both
halogenation and cyclization steps, the one-pot process was
performed using an ultrapure iron(III) salt. As ultrapure
iron(III) chloride was not commercially available, iron(III)
nitrate nonahydrate (99.999% purity), which contains no
copper, was investigated. Initial trials demonstrated that in
combination with [BMIM]NTf2, Fe(NO3)3·9H2O was an
effective Lewis acid for regioselective halogenation, with
complete conversion to the iodide intermediate after 5 h.
Then, using only this complex (5 mol %) for the entire one-pot
process gave benzo[b]furan 4a in 55% yield (Table 1, entry 6).
To verify that iron(III) was responsible for catalysis of the
cyclization step, control reactions were performed. For example,
a reaction in which the iodide of 3a was treated with DMEDA
(10 mol %), Cs2CO3 in a mixture of toluene and water, under
standard cyclization conditions (130 °C) resulted in no
conversion to benzo[b]furan 4a. This result confirmed that
the C−O bond forming step (entry 6) is catalyzed by iron(III)
and not due to the introduction of ppm amounts of copper with
the addition of reagents and solvents (e.g., water) during the
second step.
a
Scheme 2. Synthesis of 1-Arylketone 3a
a
Isolated yields.
Methoxyphenylacetic acid (1) was converted to Weinreb amide
2 under standard conditions, and subsequent reaction with 4-
chlorophenylmagnesium bromide allowed the efficient, scalable
synthesis of 3a.
Initial development of a one-pot synthesis of benzo[b]furans
focused on iron(III)-catalyzed halogenation and copper(I)-
catalyzed cyclization of 1-arylketone 3a (Table 1). Iron
Table 1. Optimization Studies for the Iron- and Copper-
a
Catalyzed Synthesis of Benzo[b]furan 4a
catalyst loading
(mol %)
catalyst purity
(%)
yield
b
entry
catalyst
(%)
c
1
FeCl3 + CuI
FeCl3
FeCl3
FeCl3
FeCl3
2.5 + 10
97
97
99.9
99.9
99.9
99.999
59
48
44
60
63
55
2
3
4
5
2.5
2.5
5
10
5
Having developed three different one-pot processes involving
various copper loadings (zero, ppm, and 10 mol %), the scope of
these with a range of 1-arylketones was next studied. Initially, the
one-process involving Fe(NO3)3·9H2O that uses iron(III) to
catalyze both steps was performed with electron-deficient (p-
CF3Ph, 3e) and electron-rich (p-MeOPh, 3j) 1-arylketone
substrates (Scheme 3). This gave benzo[b]furan 4e and the
natural product, corsifuran C (4j) (from Corsinia coriandrina),10
in 55 and 41% yields, respectively. These results confirm that a
single iron complex can be used to catalyze both steps and access
various benzo[b]furans. However, due to the moderate yields
(also, 55% for 4a), the requirement of an ultrapure metal salt,
and the avoidance of copper contaminants, we felt that the other
one-pot processes that use standard grades of iron(III) chloride
would be more synthetically useful.
d
6
Fe(NO3)3·9H2O
a
All reactions used [BMIM]NTf2 (3 times the amount of Fe catalyst).
b
c
Isolated yields. Conducted using CuI (10 mol %) and DMEDA (20
d
mol %). Reaction times for each step was 5 and 20 h.
triflimide (2.5 mol %), generated from iron(III) chloride and
the ionic liquid, [BMIM]NTf2, was used for activation of N-
iodosuccinimide (NIS) and subsequent iodination of 3a (entry
1). 1H NMR studies confirmed that despite the meta-
arylethanone substituent, iron(III)-catalyzed iodination pro-
ceeded exclusively at the position para to the methoxy activating
group. The second stage of the one-pot process was conducted
using copper(I) iodide (10 mol %) and DMEDA (20 mol %),
which gave benzo[b]furan 4a in 59% yield.
The one-pot process involving FeCl3 (99.9% purity) to
catalyze the iodination step and then residual copper (31.1 ppm)
to catalyze the O-heterocyclization was next investigated for the
preparation of biologically important 2-arylbenzo[b]furans
(Scheme 3). 1-Arylketone substrates bearing electron-deficient
and electron-rich aryl groups, as well as various o-, m-, and p-
substituents were found to be effective substrates, allowing the
As Bolm and co-workers reported that iron(III) could be used
for the O-cyclization of 1-(2-bromoaryl)ketones,5f we next
investigated whether a single iron salt could be used to perform
both iodination and cyclization steps during a one-pot process.
This goal became more challenging when we were made aware
that most grades of commercial FeCl3 contain various levels of
metal contaminants, including sufficient copper to catalyze the
B
https://dx.doi.org/10.1021/acs.orglett.0c00754
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
a,b
Scheme 3. Scope of One-Pot Synthesis of Benzo[b]furans
4
Scheme 4. One-Pot Synthesis of Benzo[b]furans 4j and 6
a,b
a
b
Iron(III) chloride with 97% purity was used. Isolated yields.
c
d
Iodination step was performed at 50 °C for 6 h. Iodination step
done separately using [BMIM]NTf2 as solvent and at 70 °C for 16 h.
the use of CuI (10 mol %) resulted in a more efficient reaction
with the isolation of corsifuran C (4j) in 84% yield. It should be
noted that this C7a−O bond forming approach does have
limitations,11 as shown by the synthesis of benzo[b]furan 6i. Our
previous studies have shown that electron-rich arenes are
required for regioselective and efficient iron(III)-catalyzed
halogenations.6,7 Iodination of unactivated 3-methylphenyl-
substituted 1-arylketone 5i required forcing conditions (70 °C
for 16 h), yielding a 4:1 mixture of desired 6-iodo and undesired
4-iodo regioisomers. Copper-catalyzed cyclization of the
mixture led to the isolation of 6i in 26% yield, over the two steps.
Although these one-pot processes are most effective for the
preparation of electron-rich benzo[b]furans, this type of
benzannulated system is widely found in pharmaceutically
important compounds and natural products (e.g., corsifuran C,
4j). To further demonstrate this, a number of benzo[b]furans
prepared in this study were converted to target compounds
(Scheme 5). For example, the nitro group of analogue 4g was
reduced with tin dichloride in 90% yield to give amine 7, a
nanomolar affinity agent of amyloid plaque.12 Removal of the
silyl protecting groups of benzo[b]furan 4m with TBAF, under
standard conditions, gave moracin F (8), an antifungal
phytoalexin, isolated from the tissue of mulberry shoots infected
with Fusarium solani.13,14 Finally, allylic oxidation of benzo[b]-
furan 6d with selenium dioxide gave caleprunin B (9), a natural
2-acetylbenzo[b]furan, isolated from both Eupatorium sternber-
gianum and Calea berteriana.15,16
a
b
Iron(III) chloride with 99.9% purity was used. Isolated yields.
c
Isolated yields using Fe(NO3)3·9H2O (5 mol %).
synthesis of a range of structural analogues 4a−4n in 55−75%
yields. This included the efficient preparation of corsifuran C 4j
in 74% yield.
This one-pot process was also used to investigate the synthesis
of more challenging benzo[b]furan targets. This included less
reactive 1-arylketones with amino-substituted aryl rings or
bearing alkylketone side chains (Scheme 4). Although some of
the benzo[b]furans were formed using this one-pot process, the
cyclization step with ppm loading of copper required a longer
reaction time (>48 h), resulting in low yields (<40%). For this
reason, the synthesis of these targets was investigated using the
one-pot process involving CuI (10 mol %). Following a brief
optimization study of the original one-pot process (Table 1,
entry 1), the use of FeCl3 (97% purity) at 5 mol % loading,
followed by CuI (10 mol %), proved most effective for these
substrates. Amino-substituted benzo[b]furans 6a and 6b with
synthetically useful protecting groups were prepared in 48 and
65% yields, respectively. Substrates with alkylketone (5c and
5d) or aldehyde (5e) side chains were also tolerated and gave
the corresponding benzo[b]furans in moderate to good yields.
Cyclic ketones (5f−5h) were also found to be substrates for this
one-pot process, allowing the effective preparation of polycyclic
benzo[b]furans 6f−6h. This one-pot process was also used for
the gram-scale synthesis of corsifuran C (4j). Whereas the use of
ppm loading of copper for the heterocyclization step on a small
scale gave 4j in 74% yield (Scheme 3), for a larger-scale reaction,
In summary, we have developed new one-pot processes for
the synthesis of benzo[b]furans from 1-aryl- or 1-alkylketones,
using earth-abundant, nonprecious transition metal catalysts for
C
https://dx.doi.org/10.1021/acs.orglett.0c00754
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
for Antimicrobial Agents. RSC Adv. 2015, 5, 96809−96828.
(c) Radadiya, A.; Shah, A. Bioactive Benzofuran Derivatives: An
Insight on Lead Developments, Radioligands and Advances of the Last
Decade. Eur. J. Med. Chem. 2015, 97, 356−376.
Scheme 5. Synthesis of Biologically Active Benzo[b]furans
and Natural Products
a
(2) For general reviews of benzo[b]furan synthesis, see: (a) Godoi, B.;
Schumacher, R. F.; Zeni, G. Synthesis of Heterocycles via Electrophilic
Cyclization of Alkynes Containing Heteroatom. Chem. Rev. 2011, 111,
2937−2980. (b) Katritzky, A. R.; Rachwal, S. Synthesis of Heterocycles
Mediated by Benzotriazole. 2. Bicyclic Systems. Chem. Rev. 2011, 111,
7063−7120. (c) Heravi, M. M.; Zadsirjan, V.; Hamidi, H.; Tabar Amiri,
P. H. Total Synthesis of Natural Products Containing Benzofuran
Rings. RSC Adv. 2017, 7, 24470−24521. (d) Miao, Y.-h.; Hu, Y.-h.;
Yang, J.; Liu, T.; Sun, J.; Wang, X.-j. Natural Source, Bioactivity and
Synthesis of Benzofuran Derivatives. RSC Adv. 2019, 9, 27510−27540.
(3) For selected reviews of benzo[b]furan synthesis using metal
catalysis, see: (a) Wu, X.-F.; Neumann, H.; Beller, M. Synthesis of
Heterocycles via Palladium-Catalyzed Carbonylations. Chem. Rev.
a
Isolated yields.
́
́
2013, 113, 1−35. (b) Blanc, A.; Beneteau, V.; Weibel, J.-M.; Pale, P.
Silver and Gold-Catalyzed Routes to Furans and Benzofurans. Org.
Biomol. Chem. 2016, 14, 9184−9205. (c) Agasti, S.; Dey, A.; Maiti, D.
Palladium-Catalyzed Benzofuran and Indole Synthesis by Multiple C-H
Functionalizations. Chem. Commun. 2017, 53, 6544−6556.
aryl C−H halogenation and then intramolecular O-arylation.
Although, in principle, iron(III) can be used to perform each
step in a tandem catalytic process, the use of copper at either
ppm or 10 mol % loading was found to be more effective, leading
to the synthesis of a wide range of structural analogues, including
a number of pharmaceutically active targets and natural
products. Work is currently underway to discover new one-
pot, transition-metal-catalyzed processes for the preparation of
other benzannulated heterocycles.
(4) For recent, selected examples of benzo[b]furan synthesis using
metal catalysis, see: (a) Wang, J.-R.; Manabe, K. Hydroxyterphenyl-
phosphine-Palladium Catalyst for Benzo[b]furan Synthesis from 2-
Chlorophenols. Bifunctional Ligand Strategy for Cross-Coupling of
Chloroarenes. J. Org. Chem. 2010, 75, 5340−5342. (b) Yang, J.; Shen,
G.; Chen, D. Iron-Catalyzed Synthesis of 2-Arylbenzo[b]furans. Synth.
Commun. 2013, 43, 837−847. (c) Zhou, R.; Wang, W.; Jiang, Z.-j.;
Wang, K.; Zheng, X.-l.; Fu, H.-y.; Chen, H.; Li, R.-x. One-Pot Synthesis
of 2-Substituted Benzo[b]furans via Pd-Tetraphosphine Catalyzed
Coupling of 2-Halophenols with Alkynes. Chem. Commun. 2014, 50,
6023−6026. (d) Bosiak, M. J. A. Convenient Synthesis of 2-
Arylbenzo[b]furans from Aryl Halides and 2-Halophenols by Catalytic
One-Pot Cascade Method. ACS Catal. 2016, 6, 2429−2434.
(e) Yamaguchi, M.; Akiyama, T.; Sasou, H.; Katsumata, H.; Manabe,
K. One-Pot Synthesis of Substituted Benzo[b]furans and Indoles from
Dichlorophenols/Dichloroanilines Using a Palladium-Dihydroxyter-
phenylphosphine Catalyst. J. Org. Chem. 2016, 81, 5450−5463.
(f) Rehan, M.; Nallagonda, R.; Das, B. G.; Meena, T.; Ghorai, P.
Synthesis of Functionalized Benzo[b]furans via Oxidative Cyclization
of o-Cinnamyl Phenols. J. Org. Chem. 2017, 82, 3411−3424.
(g) Alonso-Maranon, L.; Martinez, M. M.; Sarandeses, L. A.; Gomez-
Bengoa, E.; Perez Sestelo, J. Indium(III)-Catalyzed Synthesis of
Benzo[b]furans by Intramolecular Hydroxyalkoxylation of ortho-
Alkynylphenols: Scope and Mechanistic Insights. J. Org. Chem. 2018,
83, 7970−7980. (h) Rong, Z.; Gao, K.; Zhou, L.; Lin, J.; Qian, G. Facile
Synthesis of 2-Substituted Benzo[b]furans and Indoles by Copper-
Catalyzed Intramolecular Cyclization of 2-Alkynyl Phenols and
Tosylanilines. RSC Adv. 2019, 9, 17975−17978.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00754.
Experimental procedures, characterization data, NMR
spectra of all compounds (PDF)
AUTHOR INFORMATION
■
Corresponding Author
Andrew Sutherland − WestCHEM, School of Chemistry,
University of Glasgow, Glasgow G12 8QQ, United Kingdom;
orcid.org/0000-0001-7907-5766;
Email: andrew.sutherland@glasgow.ac.uk
Author
Martyn C. Henry − WestCHEM, School of Chemistry, University
of Glasgow, Glasgow G12 8QQ, United Kingdom
Complete contact information is available at:
(5) For examples of benzo[b]furan synthesis by metal-catalyzed O-
arylation of 1-(2-haloaryl)ketones, see: (a) Willis, M. C.; Taylor, D.;
Gillmore, A. T. Palladium-Catalyzed Intramolecular O-Arylation of
Enolates: Application to Benzo[b]furan Synthesis. Org. Lett. 2004, 6,
4755−4757. (b) Chen, C.-y.; Dormer, P. G. Synthesis of Benzo[b]-
furans via CuI-Catalyzed Ring Closure. J. Org. Chem. 2005, 70, 6964−
6967. (c) Carril, M.; SanMartin, R.; Tellitu, I.; Dominguez, E. On-
Water Chemistry: Copper-Catalyzed Straightforward Synthesis of
Benzo[b]furan Derivatives in Neat Water. Org. Lett. 2006, 8, 1467−
1470. (d) Fang, Y.; Li, C. O-Arylation versus C-Arylation: Copper-
Catalyzed Intramolecular Coupling of Aryl Bromides with 1,3-
Dicarbonyls. J. Org. Chem. 2006, 71, 6427−6431. (e) Ackermann, L.;
Kaspar, L. T. TiCl4-Catalyzed Indirect Anti-Markovnikov Hydration of
Alkynes: Application to the Synthesis of Benzo[b]furans. J. Org. Chem.
2007, 72, 6149−6153. (f) Bonnamour, J.; Piedrafita, M.; Bolm, C. Iron
and Copper Salts in the Synthesis of Benzo[b]furans. Adv. Synth. Catal.
2010, 352, 1577−1581.
https://pubs.acs.org/10.1021/acs.orglett.0c00754
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from EPSRC (Ph.D. studentship to M.C.H.,
EP/M508056/1) and the University of Glasgow is gratefully
acknowledged.
REFERENCES
■
(1) For reviews of biologically active benzo[b]furans, see:
(a) Simonetti, S. O.; Larghi, E. L.; Bracca, A. B. J.; Kaufman, T. S.
Angular Tricyclic Benzofurans and Related Natural Products of Fungal
Origin. Isolation, Biological Activity and Synthesis. Nat. Prod. Rep.
2013, 30, 941−969. (b) Hiremathad, A.; Patil, M. R.; Chethana, K. R.;
Chand, K.; Santos, M. A.; Keri, R. S. Benzofuran: An Emerging Scaffold
(6) (a) Racys, D. T.; Warrilow, C. E.; Pimlott, S. L.; Sutherland, A.
Highly Regioselective Iodination of Arenes via Iron(III)-Catalyzed
D
https://dx.doi.org/10.1021/acs.orglett.0c00754
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Activation of N-Iodosuccinimide. Org. Lett. 2015, 17, 4782−4785.
(b) Racys, D. T.; Sharif, S. A. I.; Pimlott, S. L.; Sutherland, A. Silver(I)-
Catalyzed Iodination of Arenes: Tuning the Lewis Acidity of N-
Iodosuccinimide Activation. J. Org. Chem. 2016, 81, 772−780.
(c) Mostafa, M. A. B.; Bowley, R. M.; Racys, D. T.; Henry, M. C.;
Sutherland, A. Iron(III)-Catalyzed Chlorination of Activated Arenes. J.
Org. Chem. 2017, 82, 7529−7537.
(7) (a) Mostafa, M. A. B.; Calder, E. D. D.; Racys, D. T.; Sutherland, A.
Intermolecular Aryl C-H Amination Through Sequential Iron and
Copper Catalysis. Chem. - Eur. J. 2017, 23, 1044−1047. (b) Henry, M.
C.; Senn, H. M.; Sutherland, A. Synthesis of Functionalized Indolines
and Dihydrobenzofurans by Iron and Copper Catalyzed Aryl C−N and
C−O Bond Formation. J. Org. Chem. 2019, 84, 346−364. (c) Henry, M.
C.; McGrory, R.; Faggyas, R. J.; Mostafa, M. A. B.; Sutherland, A. One-
Pot ortho-Amination of Aryl C-H Bonds using Consecutive Iron and
Copper Catalysis. Org. Biomol. Chem. 2019, 17, 4629−4639.
(8) The amount of copper stipulated in the batch analysis of
commercial samples of FeCl3 was verified by us, using inductively
coupled plasma analysis.
(9) Previous work by the Bolm group (ref 5f) showed that copper (at
ppm loading) is more catalytically active than iron for O-arylation of 1-
(2-bromoaryl)ketones. See also: (a) Buchwald, S. L.; Bolm, C. On the
Role of Metal Contaminants in Catalyses with FeCl3. Angew. Chem., Int.
Ed. 2009, 48, 5586−5587. (b) Larsson, P.-F.; Correa, A.; Carril, M.;
Norrby, P.-O.; Bolm, C. Copper-Catalyzed Cross-Couplings with Part-
per-Million Catalyst Loadings. Angew. Chem., Int. Ed. 2009, 48, 5691−
5693.
̈
(10) von Reuβ, S. H.; Konig, W. A. Corsifurans A−C, 2-
Arylbenzofurans of Presumed Stilbenoid Origin from Corsinia
coriandrina (Hepaticae). Phytochemistry 2004, 65, 3113−3118.
(11) This study also briefly investigated the synthesis of
benzothiophenes and indoles from thioketones and imines, respec-
tively, using similar one-pot processes. However, attempted preparation
of an aryl thioketone from ketone 3a using P2S5 or Lawesson’s reagent
resulted in decomposition. An imine was prepared from the reaction of
ketone 3a and p-toluidine, but this was not compatible with the
iodination step of the one-pot process, resulting in imine hydrolysis.
(12) Ono, M.; Kawashima, H.; Nonaka, A.; Kawai, T.; Haratake, M.;
Mori, H.; Kung, M.-P.; Kung, H. F.; Saji, H.; Nakayama, M. Novel
Benzofuran Derivatives for PET Imaging of β-Amyloid Plaques in
Alzheimer’s Disease Brains. J. Med. Chem. 2006, 49, 2725−2730.
(13) Takasugi, M.; Nagao, S.; Masamune, T.; Shirata, A.; Takahashi,
K. Structures of Moracins E, F, G and H, New Phytoalexins from
Diseased Mulberry. Tetrahedron Lett. 1979, 20, 4675−4678.
(14) Naik, R.; Harmalkar, D. S.; Xu, X.; Jang, K.; Lee, K. Bioactive
Benzofuran Derivatives: Moracins A−Z in Medicinal Chemistry. Eur. J.
Med. Chem. 2015, 90, 379−393.
́
(15) (a) Gonzalez, A. G.; Fraga, B. M.; Hernandez, M. G.; García, V. P.
Eupatarone, A 2-Acetylbenzofuran from Eupatorium Sternbergianum.
Phytochemistry 1982, 21, 1826−1827. (b) Ober, A. G.; Fronczek, F. R.;
Fischer, N. H. Three Benzofurans and a 1,4-Dioxin Derivative from
Calea Species: The Molecular Structures of Calebertin and Caleteucrin.
J. Nat. Prod. 1985, 48, 242−248.
(16) del Carmen Cruz, M.; Tamariz, J. An Efficient Synthesis of
Benzofurans and their Application in the Preparation of Natural
Products of the Genus Calea. Tetrahedron 2005, 61, 10061−10072.
E
https://dx.doi.org/10.1021/acs.orglett.0c00754
Org. Lett. XXXX, XXX, XXX−XXX