DMAP-Catalyzed Annulation Approach for Modular Assembly of Furan-Fused Chromenes

Article abstract of DOI:10.1021/acs.orglett.0c03374

With a tandem DMAP-catalyzed reaction between o-AQM, in which it is generated in situ from propargylic amine, and acyl carbene surrogate (from pyridinium ylide), a variety of polyarylated chromenes are assembled in good yields. This process does not require transition-metal catalyst and exhibits easy manipulation of the arene group and good functional group compatibility, particularly the -Br group which can be further transformed to other functionalities by cross-coupling reactions. The modular feature of o-AQM substrates and the simple operation procedures add further advantages to this synthetic method.

Full text of DOI:10.1021/acs.orglett.0c03374

pubs.acs.org/OrgLett
Letter
DMAP-Catalyzed Annulation Approach for Modular Assembly of
Furan-Fused Chromenes
Xinwei He,* Ruxue Li, Pui Ying Choy, Tianyi Liu, Junya Wang, On Ying Yuen, Man Pan Leung,
Yongjia Shang, and Fuk Yee Kwong*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c03374
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: With a tandem DMAP-catalyzed reaction between
o-AQM, in which it is generated in situ from propargylic amine,
and acyl carbene surrogate (from pyridinium ylide), a variety of
polyarylated chromenes are assembled in good yields. This process
does not require transition-metal catalyst and exhibits easy
manipulation of the arene group and good functional group
compatibility, particularly the −Br group which can be further
transformed to other functionalities by cross-coupling reactions.
The modular feature of o-AQM substrates and the simple
operation procedures add further advantages to this synthetic
method.
eterocycles embodying a chromene framework are often
found in many natural products and pharmaceutically
aldehyde, terminal alkyne, and amine.16−18 Inspired by the rich
reactivity of o-AQM for annulation and the chemistry of
acylpyridinium methylides involving O-cyclization processes,19
we are intrigued whether these two substrates could be
combined to enable facile construction of structurally
diversified furan-fused chromenes. In continuing our research
interest in polycycle assembly20,21 and o-AQM chemistry,22−24
we here show our development of a tandem reaction between
propargylamine and pyridinium ylide catalyzed by DMAP
(Scheme 1d). This transition-metal-free procedure features
simple operation (can be performed without inert atmosphere
protection) and good functional group tolerance (e.g., −Br,
−Cl, −NO2, −CN, −OH, −SO2Me, and alkene).
We initially test the feasibility of this reaction by employing
propargylamine 1a and N-phenacylpyridinium bromide (2a) as
the exemplary substrates (Table 1). Upon surveying common
organic bases, DMAP delivered the best product yield (entries
1−5). The use of an inorganic base such as K2CO3 and KOH
or not led to decreased yields (entries 6−8). A screening of
several solvents revealed that MeCN is the best (entry 2 vs
entries 9−14). Lowering the reaction temperature to 60 °C
gave decreased product yield (entry 15). Increasing the
reaction temperature or catalyst loading failed to improve the
yield (entries 16 and 18). When the amine moiety of 1a was
H
useful intermediates.1 In particular, chromenes composed of a
furan moiety display a range of activities in biological
investigations and drug explorations,2 for example, antibacte-
rial,3 -fungal,4 -HIV,5 -inflammatory,6 and -osteoporotic
actions.7 There are two typical regioisomers of furochromene
with respect to the reciprocal orientation of fused furan,
namely furo[3,2-c]chromene and furo[2,3-c]chromene
(Scheme 1a). It is worth noting that the furo[2,3-c]chromene
isomer expresses exclusive activity in the treatment of liver
diseases.8 Recently, transition-metal-catalyzed strategies have
emerged targeting arene-substituted furo[3,2-c]chromenes
(Scheme 1b). By employing alkynylchromone as the key
starting material, Larock9 and Hu10 have independently
developed gold-catalyzed reaction systems for constructing
furo[3,2-c]chromenes. Ma has disclosed a Rh-catalyzed two-
step process by using diazochromanone and alkynes as starting
material.11
In conrast to furo[3,2-c]chromene, methods to access the
furo[2,3-c]chromene skeleton remain sporadically investigated:
The only examples were reported by Yan showing the reaction
between nitrochromene and acylacetonitrile (Scheme 1c).12 It
would be of high interest to explore a synthetic method for
assembling this unique furo[2,3-c]chromene bearing the
following features: (i) transition-metal-free; (ii) capable of
using modular substrates to allow broad product structure
diversity; (iii) requiring only simple organic catalyst; (iv)
operationally simple. o-Alkynyl quinone methide (o-
AQM)13−15 is a reactive intermediate generated in situ from
modular propargylamines, which can be straightforwardly
obtained via a three-component reaction between aromatic
Received: October 9, 2020
https://dx.doi.org/10.1021/acs.orglett.0c03374
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Scheme 1. Modern Approaches for Accessing
Furochromenes
Table 1. Evaluation of Reaction Parameters
b
entry
catalyst
solvent
yield (%)
1
2
3
4
5
6
7
8
Et3N
DMAP
DBU
DABCO
pyridine
K2CO3
KOH
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
toluene
DCE
48
84
24
62
61
25
16
36
60
43
66
58
74
68
37
83
70
83
64
68
62
15
45
53
40
42
9
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
DMF
EtOH
DMSO
THF
c
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
d
e
f
g
h
i
j
k
l
m
n
altered to piperidinyl, morpholinyl, or tetrahydroisoquinolinyl
in 1-piperidinyl, 1-morpholinyl, or 1-THIQ, respectively, yields
of the desired product were decreased (entries 20−22). Other
relevant acyl carbene surrogates such as 2-p-NMe2py, 2-imid,
2-quin, and 2-iso-quin were evaluated, and the pyridinium
methylide 2a was found to be the best choice (entry 2 vs
entries 23−26).
a
Reaction conditions: 2-(3-phenyl-1-(pyrrolidin-1-yl)prop-2-yn-1-
yl)phenol (1a) (0.3 mmol), N-phenacylpyridinium bromide (2a)
(0.36 mmol), and catalyst (20 mol %) in solvent (3 mL) at 80 °C for
With the optimized reaction conditions, we next investigated
the substrate scope of propargylamines 1 (Scheme 2).
Generally, the desired chromene products were obtained in
high yields. It is notable to show that the −Br and −Cl groups,
present at either the phenolic or the alkynyl arene moieties,
remained intact in the reaction (products 3ca, 3da, 3ga, 3ha,
3ka, 3la, 3pa, 3qa). This beneficial outcome offers us an
excellent opportunity to subsequently amend the product
functionality by established cross-coupling protocols.25 The
product structure of 3ga was characterized by single-crystal X-
ray crystallography. The electronic nature of the substituents
present at the phenolic and the alkynyl arene moieties showed
no obvious effect in the reaction. Multiple halogens located at
either the phenolic or the alkynyl arene rings were also
tolerable (products 3sa and 3va), though the highly electron-
deficient nitro group provided slightly lower yield (product
3ma). The steric hindrance of the substituents also showed a
negligible effect on the yield, and even the extremely steric
bulky tert-butyl group was also well-suited (product 3ta). The
b
c
5 h under air atmosphere. Isolated yields were reported. At 60 °C.
d
e
f
g
At 100 °C. For 2 h. The catalyst loading was 50 mol %. The
h
catalyst loading was 10 mol %. 1-Piperidinyl was used instead of 1a.
i
j
1-Morpholinyl was used instead of 1a. 1-THIQ was used instead of
1a. 2-p-NMe2py was used instead of 2a. 2-Imid was used instead of
2a. 2-Quin was used instead of 2a. 2-iso-Quin was used instead of
2a.
k
l
m
n
reaction with 3-bromo-2-(3-phenyl-1-(pyrrolidin-1-yl)prop-2-
yn-1-yl)phenol (1x) provided a relatively poor product yield
(product 3xa), which might be due to the 3-subsituted
phenolic moiety that is known to hinder the o-AQM
formation. Other than aromatic alkyne substituents, alkenyl-,
thienyl-, and alkyl-containing substrates were also examined.
The conjugated enyne moiety was well-compatible in this
reaction (product 3ya) and so was the heterocyclic thienyl-
bearing substrate (product 3za). Nevertheless, only a single
ring-closure step was observed when the alkyl-containing
B
https://dx.doi.org/10.1021/acs.orglett.0c03374
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Scheme 2. Scope of Propargylamine 1
Scheme 3. Scope of Aryl-Containing Pyridinium Methylide
2
a
a
Reaction conditions: propargylamines 1a (0.3 mmol), pyridinium
methylides 2 (0.36 mmol), and DMAP (20 mol %) in MeCN (3 mL)
at 80 °C for 5 h under benchtop air atmosphere. Isolated yields were
reported.
a
Reaction conditions: propargylamines 1 (0.3 mmol), pyridinium
methylide 2a (0.36 mmol), and DMAP (20 mol %) in MeCN (3 mL)
at 80 °C for 5 h under benchtop air atmosphere. Isolated yields were
b
reported. A gram-scale synthesis; 1.18 g of product 3aa was
delivered.
Scheme 4. Three-Component Strategy for Assembling the
a
Furan-Fused Chromene 3aa
alkyne substrate was employed (product 4).26 A gram-scale
experiment was performed to show the practicability of the
new reaction system, and the product 3aa was obtained in 73%
yield.
Subsequently, we explored the scope of pyridinium
methylides 2 in this reaction (Scheme 3). Substituents of
both electron-withdrawing and electron-donating nature at the
Ar group of 2 were well-tolerated in the reaction (products
3ab−3af). Functional groups such as bromo, nitro, nitrile,
methanesulfonyl, and hydroxyl moieties were all compatible
(products 3ae, 3ag, 3ah, 3aj, and 3ak, respectively). 2-
Naphthyl substrate delivered the desired product in 89% yield
(product 3ap). Notably, alkyl- and alkoxyl-containing
pyridinium methylides were tolerated, and the corresponding
products were afforded in fair to good yields (products 3aq
and 3ar).
In order to put forward of this synthetic strategy, we test the
feasibility of a direct three-component assembly of the product
(Scheme 4). To our delight, the reaction of α-bromoaceto-
phenone, pyridine, and 1a gave the intended product 3aa in
60% yield.
a
Reaction conditions: 2-(3-phenyl-1-(pyrrolidin-1-yl)prop-2-yn-1-yl)-
phenol (1a) (0.2 mmol), 2-bromo-1-phenylethan-1-one (0.24 mmol),
pyridine (0.24 mmol), and DMAP (20 mol %) in MeCN (2 mL) at
80 °C for 5 h under benchtop air atmosphere. Isolated yield was
reported.
(Scheme 5a). The H/D exchange experiment of 2a was
performed in the presence of D2O. Spectroscopic data showed
that almost all H atoms on the methylene group of 2a were
exchanged with deuterium in 10 min. The deuterated product
d2-3ga was obtained in 80% yield. A proposed mechanism is
presented in Scheme 5b. With reference to literature
precedents,13 we presume that this one-pot tandem reaction
involves the initial deamination of the propargylic amine 1′ to
generate the o-AQM intermediate under thermal conditions.
The 1,4-conjugate addition of pyridinium methylide 2a′ to o-
AQM occurs to give species A. Subsequent elimination
In order to have more insight toward the reaction
mechanism, we carried out the deuterium-labeling experiment
C
https://dx.doi.org/10.1021/acs.orglett.0c03374
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Kong, Shatin, New Territories, Hong Kong, China; Key
Scheme 5. Deuterium-Labeling Experiment and a Proposed
Mechanism
Laboratory of Functional Molecular Solids, Ministry of
Education, Anhui Laboratory of Molecule-Based Materials
(State Key Laboratory Cultivation Base), College of
Chemistry and Materials Science, Anhui Normal University,
Wuhu 241002, China; orcid.org/0000-0002-1974-2464;
Email: xinweihe@mail.ahnu.edu.cn
Fuk Yee Kwong − State Key Laboratory of Synthetic
Chemistry and Department of Chemistry and Shenzhen
Municipal Key Laboratory of Chemical Synthesis of
Medicinal Organic Molecules, Shenzhen Research Institute,
The Chinese University of Hong Kong, Shatin, New
Territories, Hong Kong, China; orcid.org/0000-0001-
9105-1740; Email: fykwong@cuhk.edu.hk
Authors
Ruxue Li − Key Laboratory of Functional Molecular Solids,
Ministry of Education, Anhui Laboratory of Molecule-Based
Materials (State Key Laboratory Cultivation Base), College
of Chemistry and Materials Science, Anhui Normal
University, Wuhu 241002, China
Pui Ying Choy − State Key Laboratory of Synthetic Chemistry
and Department of Chemistry and Shenzhen Municipal Key
Laboratory of Chemical Synthesis of Medicinal Organic
Molecules, Shenzhen Research Institute, The Chinese
University of Hong Kong, Shatin, New Territories, Hong
Kong, China
Tianyi Liu − State Key Laboratory of Synthetic Chemistry and
Department of Chemistry and Shenzhen Municipal Key
Laboratory of Chemical Synthesis of Medicinal Organic
Molecules, Shenzhen Research Institute, The Chinese
University of Hong Kong, Shatin, New Territories, Hong
Kong, China
Junya Wang − Shenzhen Municipal Key Laboratory of
Chemical Synthesis of Medicinal Organic Molecules,
Shenzhen Research Institute, The Chinese University of Hong
Kong, Shenzhen 518507, China
On Ying Yuen − State Key Laboratory of Synthetic Chemistry
and Department of Chemistry and Shenzhen Municipal Key
Laboratory of Chemical Synthesis of Medicinal Organic
Molecules, Shenzhen Research Institute, The Chinese
University of Hong Kong, Shatin, New Territories, Hong
Kong, China
proceeds to afford intermediate B. The intermediate C is then
formed under thermal conditions. The next cyclization and
rearomatization occur to form the desired product 3.
In summary, we have demonstrated that the pyridinium
ylide, an acyl carbene surrogate, was able to react with modular
o-alkynyl quinone methide (o-AQM) via two ring-closure steps
to give a diversity of arene-containing furochromenes in good
yields. A three-component strategy was also demonstrated
based on this reaction. This transition-metal-free process does
not require inert atmosphere protection and shows good
functional group tolerance (for instance, −Br, −Cl, −NO2,
−CN, −OH, −SO2Me, alkenyl, and thienyl). We anticipate
that this method would be a useful synthetic tool for
chromene-related studies in related fields such as organic and
medicinal chemistry.
ASSOCIATED CONTENT
* Supporting Information
■
Man Pan Leung − State Key Laboratory of Synthetic
Chemistry and Department of Chemistry and Shenzhen
Municipal Key Laboratory of Chemical Synthesis of
Medicinal Organic Molecules, Shenzhen Research Institute,
The Chinese University of Hong Kong, Shatin, New
Territories, Hong Kong, China
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c03374.
Experimental procedures and spectroscopic data for all
compounds (PDF)
Yongjia Shang − Key Laboratory of Functional Molecular
Solids, Ministry of Education, Anhui Laboratory of Molecule-
Based Materials (State Key Laboratory Cultivation Base),
College of Chemistry and Materials Science, Anhui Normal
University, Wuhu 241002, China; orcid.org/0000-0001-
9873-9150
Accession Codes
CCDC 1996084 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.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c03374
AUTHOR INFORMATION
Corresponding Authors
■
Notes
Xinwei He − State Key Laboratory of Synthetic Chemistry and
Department of Chemistry, The Chinese University of Hong
The authors declare no competing financial interest.
D
https://dx.doi.org/10.1021/acs.orglett.0c03374
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(10) Hu, F.; Chen, T.; Yan, J.; Cheng, M.; Huang, L.; Hu, Y. Au-
catalyzed cascade addition/cyclization/H-transfer reactions of 3-(1-
alkynyl)chromones to construct 4H-Furo[3,2-c]pyrans scaffold. RSC
Adv. 2012, 2, 11238−11241.
(11) Gong, J.; Zhao, Z.; Zhang, F.; Wu, S.; Yan, G.; Quan, Y.; Ma, B.
One-Pot Novel Regioselective Cycloisomerization Synthesis of 2-
Substituted or 3-Substituted 4H-Furo[3,2-c]chromene through the
Intermediate Cyclopropenes of 3-Diazochroman-4-one and Phenyl-
acetylene. Org. Lett. 2014, 16, 5524−5527.
(12) Jiang, W.; Sun, J.; Liu, R.-Z.; Yan, C.-G. Molecular diversity of
the domino annulation reaction of 2-aryl-3-nitrochromenes with
pivaloylacetonitriles. Org. Biomol. Chem. 2018, 16, 5816−5822.
(13) For a review, see: (a) Bai, W.-J.; David, J. G.; Feng, Z.-G.;
Weaver, M. G.; Wu, K.-L.; Pettus, T. R. R. The Domestication of
ortho-Quinone Methides. Acc. Chem. Res. 2014, 47, 3655−3664.
(b) Nachtsheim, B. J. Mild map to quinone methides. Nat. Chem.
2020, 12, 326−328. (c) Hopf, H.; Jones, P. g.; Nicolescu, A.; Bicu, E.;
Birsa, L. M.; Belei, D. A Facile Synthesis of Pechmann Dyes. Chem. -
Eur. J. 2014, 20, 5565−5568. (d) Walden, D. N.; Jaworski, A. A.;
Johnston, R. C.; Hovey, M. t.; Baker, H. V.; Meyer, M. P.; Scheidt, K.
A.; Cheong, P. H.-Y. Formation of Aza-ortho-quinone Methides
Under Room Temperature Conditions: Cs2CO3 Effect. J. Org. Chem.
2017, 82, 7183−7189.
ACKNOWLEDGMENTS
■
We thank the Science, Technology and Innovation Commis-
sion of Shenzhen Municipality (JCYJ20180307150641423)
and Research Grants Council of Hong Kong (GRF: 14304519-
19P), the CUHK Direct Fund (4053388), and the Anhui
Provincial Natural Science Foundation (no. 1808085MB41)
for financial support. We are thankful for the financial support
from the Innovation and Technology Commission (HKSAR,
China) to the State Key Laboratory of Synthetic Chemistry.
DEDICATION
■
Dedicated to Prof. Henry N. C. Wong on the occasion of his
70th birthday.
REFERENCES
■
(1) (a) Eicher, T.; Hauptmann, S.; Speicher, A. Chemistry of
Heterocycles: Structure, Reaction, Synthesis, and Applications; Wiley,
̆
Somerset, NJ, 2013. (b) Casar, Z. Synthesis of Heterocycles in
Contemporary Medicinal Chemistry; Springer: Switzerland, 2016. For
the most recent review, see: (c) Yang, Q.; Guo, R.; Wang, J. Catalytic
Asymmetric Syntheses of 2-Aryl Chromenes. Asian J. Org. Chem.
2019, 8, 1742−1765. See also references cited therein.
(14) For a review, see: Yang, B.; Gao, S. Recent advances in the
application of Diels-Alder reactions involving o-quinodimethanes, aza-
o-quinone methides and o-quinone methides in natural product total
synthesis. Chem. Soc. Rev. 2018, 47, 7926−7953.
(2) (a) Goel, A.; Kumar, A.; Raghuvanshi, A. Synthesis, Stereo-
chemistry, Structural Classification, and Chemical Reactivity of
Natural Pterocarpans. Chem. Rev. 2013, 113, 1614−1640. See also
references cited therein. For the most recent reference concerning the
related chromene/flavone-type skeleton in natural/pharmaceutical
products, see: (b) Ciesielski, P.; Metz, P. Asymmetric one-pot
transformation of isoflavones to pterocarpans and its applications in
phytoalexin synthesis. Nat. Commun. 2020, 11, 3091−3098.
(3) Feng, Z.-G.; Bai, W.-J.; Pettus, T. R. R. Unified Total Syntheses
of (−)-Medicarpin, (−)-Sophoracarpan A, and ( )-Kushecarpin A
with Some Structural Revisions. Angew. Chem., Int. Ed. 2015, 54,
1864−1867.
(15) For the most recent representative literature, see: Uyanik, M.;
Nishioka, K.; Kondo, R.; Ishihara, K. Chemoselective oxidative
generation of ortho-quinone methides and tandem transformations.
Nat. Chem. 2020, 12, 353−362.
(16) Yoo, W.-J.; Zhao, L.; Li, C.-J. The A3-Coupling (Aldehyde-
Alkyne-Amine) Reaction: A Versatile Method for the Preparation of
Propargylamines. Aldrichimica Acta 2011, 44, 43−51.
(17) Peshkov, V. A.; Pereshivko, O. P.; Van der Eycken, E. V. A. A
walk around the A3-coupling. Chem. Soc. Rev. 2012, 41, 3790−3807.
(18) Rokade, B. V.; Barker, J.; Guiry, P. J. Development of and
recent advances in asymmetric A3-coupling. Chem. Soc. Rev. 2019, 48,
4766−4790.
(19) For the most recent review describing pyridinium salts in
organic synthesis, see: (a) He, F.-S.; Ye, S.; Wu, J. Recent Advances in
Pyridinium Salts as Radical Reservoirs in Organic Synthesis. ACS
Catal. 2019, 9, 8943−8960. For selected publication describing
pyridinium methylides in synthesis of furan derivatives, see:
(b) Osyanin, V. A.; Osipov, D. V.; Klimochkin, Y. N. Reactions of
o-Quinone Methides with Pyridinium Methylides: A Diastereoselec-
tive Synthesis of 1,2-Dihydronaphtho[2,1-b]furans and 2,3-Dihydro-
benzofurans. J. Org. Chem. 2013, 78, 5505−5520.
(20) For our recent work on polycycle assembly, see: Fu, W. C.;
Wang, Z.; Chan, W. T. K.; Lin, Z.; Kwong, F. Y. Regioselective
Synthesis of Polycyclic and Heptagon-embedded Aromatic Com-
pounds through a Versatile π-Extension of Aryl Halides. Angew.
Chem., Int. Ed. 2017, 56, 7166−7170.
(21) Zhao, Q.; Fu, W. C.; Kwong, F. Y. Palladium-Catalyzed
Regioselective Aromatic Extension of Internal Alkynes through a
Norbornene-Controlled Reaction Sequence. Angew. Chem., Int. Ed.
2018, 57, 3381−3385.
(22) For our recent research on o-AQM, see: He, X.; Choy, P. Y.;
Leung, M. P.; Yuen, O. Y.; Liu, T.; Shang, Y.; Kwong, F. Y. ZnI2-
catalyzed regioselective cascade 1,4-conjugate addition/5-exo-dig
annulation pathway for one-pot access to heterobiaryl frameworks.
Chem. Commun. 2019, 55, 15069−15072.
(23) He, X.; Xie, M.; Li, R.; Choy, P. Y.; Tang, Q.; Shang, Y.;
Kwong, F. Y. Organocatalytic Approach for Assembling Flavanones
via a Cascade 1,4-Conjugate Addition/oxa-Michael Addition between
Propargylamine with Water. Org. Lett. 2020, 22, 4306−4310.
(24) He, X.; Li, R.; Choy, P. Y.; Liu, T.; Yuen, O. Y.; Leung, M. P.;
Shang, Y.; Kwong, F. Y. Rapid Access of Alkynyl and Alkenyl
́
́
́
(4) Jimenez-Gonzalez, L.; Alvarez-Corral, M.; Munoz-Dorado, M.;
̃
Rodríguez-García, I. Pterocarpans: interesting natural products with
antifungal activity and other biological properties. Phytochem. Rev.
2007, 7, 125−154.
(5) Engler, T. A.; Lynch, K. O.; Reddy, J. P.; Gregory, G. S.
Synthetic pterocarpans with anti-HIV activity. Bioorg. Med. Chem. Lett.
1993, 3, 1229−1232.
(6) Njamen, D.; Talla, E.; Mbafor, J. T.; Fomum, Z. T.; Kamanyi, A.;
́
́
Mbanya, J.-C.; Cerda-Nicolas, M.; Giner, R. M.; Recio, M. C.; Rios, J.
L. Anti-inflammatory activity of erycristagallin, a pterocarpene from
Erythrina mildbraedii. Eur. J. Pharmacol. 2003, 468, 67−74.
(7) Tyagi, A. M.; Srivastava, K.; Kureel, J.; Kumar, A.; Raghuvanshi,
A.; Yadav, D.; Maurya, R.; Goel, A.; Singh, D. Premature T cell
senescence in Ovx mice is inhibited by repletion of estrogen and
medicarpin: a possible mechanism for alleviating bone loss.
Osteoporosis Int. 2012, 23, 1151−1161.
(8) (a) Clark, D.; Cramp, S. M.; Dyke, H. J.; Pallin, T. D.; Zahler, R.
Preparation of benzenesulfonylaminofurochromenecarboxylic acid
derivatives and analogs for use as methionyl aminopeptidase 2
modulators. PCT Int. Appl. WO 2012012642, 2012. (b) Cramp, S.
M.; Dyke, H. J.; Pallin, T. D.; Zahler, R. Preparation of partially
saturated tricyclic compounds as inhibitors of methionyl amino-
peptidase 2. PCT Int. Appl. WO 2012154676, 2012. (c) Hughes, T.
E.; Vath, J. E. Preparation of benzenesulfonylaminotetrahydrofur-
ochromenecarboxylic acid derivatives and analogs for use as in the
treatment of liver diseases. PCT Int. Appl. WO 2014071368, 2014.
(9) (a) Yao, T.; Zhang, X.; Larock, R. C. AuCl3-Catalyzed Synthesis
of Highly Substituted Furans from 2-(1-Alkynyl)-2-alken-1-ones. J.
Am. Chem. Soc. 2004, 126, 11164−11165. (b) Yao, T.; Zhang, X.;
Larock, R. Synthesis of Highly Substituted Furans by the Electrophile-
Induced Coupling of 2-(1-Alkynyl)-2-alken-1-ones and Nucleophiles.
J. Org. Chem. 2005, 70, 7679−7685.
E
https://dx.doi.org/10.1021/acs.orglett.0c03374
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Coumarins via a Dipyridinium Methylide and Propargylamine
Cascade Reaction. Org. Lett. 2020, 22, 7348−7352.
̈
(25) (a) de Meijere, A.; Brase, S.; Oestreich, M., Eds. Metal-
Catalyzed Cross-Coupling Reactions and More; Wiley-VCH: Weinheim,
2013. (b) Colacot, T., Ed. New Trends in Cross-Coupling: Theory and
Applications; RSC Publishing: Cambridge, U.K., 2015.
(26) For a similar structure of compound 4 to determine the E/Z-
configuration, see: Sashidhara, K. V.; Kumar, A.; Agarwal, S.; Kumar,
M.; Kumar, B.; Sridhar, B. A Simple and Efficient Access to New
Functionalized 4-Phenylacylideneflavenes. Adv. Synth. Catal. 2012,
354, 1129−1140.
F
https://dx.doi.org/10.1021/acs.orglett.0c03374
Org. Lett. XXXX, XXX, XXX−XXX