Synthesis of chroman-4-one and indanone derivatives via silver catalyzed radical ring opening/coupling/cyclization cascade

Article abstract of DOI:10.1016/j.tet.2019.130490

A variety of chroman-4-one and indanone derivatives were conveniently synthesized from readily available cyclopropanols and alkenyl aldehydes via a silver catalyzed radical ring-opening/coupling/cyclization cascade. The reaction proceeded under mild and neutral conditions with broad substrate scope and afforded the desired products in moderate to good yields. A probable mechanism for the cascade reaction was also proposed.

Full text of DOI:10.1016/j.tet.2019.130490

Accepted Manuscript
Synthesis of chroman-4-one and indanone derivatives via silver catalyzed radical ring
opening/coupling/cyclization cascade
Qiang Liu, Guanqun Xie, Qiang Wang, Zhendong Mo, Chen Li, Shujiang Ding,
Xiaoxia Wang
PII:
S0040-4020(19)30817-8
DOI:
https://doi.org/10.1016/j.tet.2019.130490
Article Number: 130490
Reference:
TET 130490
To appear in: Tetrahedron
Received Date: 23 June 2019
Revised Date: 23 July 2019
Accepted Date: 27 July 2019
Please cite this article as: Liu Q, Xie G, Wang Q, Mo Z, Li C, Ding S, Wang X, Synthesis of chroman-4-
one and indanone derivatives via silver catalyzed radical ring opening/coupling/cyclization cascade,
Tetrahedron (2019), doi: https://doi.org/10.1016/j.tet.2019.130490.
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Synthesis of chroman-4-one and indanone
derivatives via silver catalyzed radical ring
opening/coupling/cyclization cascade
Leave this area blank for abstract info.
Qiang Liua,b, Guanqun Xiea, Qiang Wanga,b, Zhendong Moa, Chen Lia, Shujiang Dingb, Xiaoxia Wanga
aSchool of Materials Science and Engineering, Dongguan University of Technology, Dongguan, 523808, China
bDepartment of Applied Chemistry, School of Science, Xi’an Jiaotong University, Xi’an, 710049, China

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Graphical Abstract
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Synthesis of chroman-4-one and indanone
derivatives via silver catalyzed radical ring
opening/coupling/cyclization cascade
Leave this area blank for abstract info.
Qiang Liua,b, Guanqun Xiea, Qiang Wanga,b, Zhendong Moa, Chen Lia, Shujiang Dingb, Xiaoxia Wanga
aSchool of Materials Science and Engineering, Dongguan University of Technology, Dongguan, 523808, China
bDepartment of Applied Chemistry, School of Science, Xi’an Jiaotong University, Xi’an, 710049, China

1
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Tetrahedron
journal homepage: www.elsevier.com
S
ynthesis of chroman-4-one and indanone derivatives via silver catalyzed
radical ring opening/coupling/cyclization cascade
Qiang Liua,b, Guanqun Xiea, Qiang Wanga,b, Zhendong Moa, Chen Lia, Shujiang Dingb, Xiaoxia Wanga,
a School of Materials Science and Engineering, Dongguan University of Technology, Dongguan, 523808, China
b Department of Applied Chemistry, School of Science, Xi’an Jiaotong University, Xi’an, 710049, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A variety of chroman-4-one and indanone derivatives were conveniently synthesized from
readily available cyclopropanols and alkenyl aldehydes via a silver catalyzed radical ring-
opening/coupling/cyclization cascade. The reaction proceeded under mild and neutral conditions
with broad substrate scope and afforded the desired products in moderate to good yields. A
probable mechanism for the cascade reaction was also proposed.
Available online
2019 Elsevier Ltd. All rights reserved
.
Keywords:
Cyclopropanol
Ring opening reaction
Silver catalysis
Chroman-4-ones
Indanones
Corresponding author. e-mail: wangxx@dgut.edu.cn

2
Tetrahedron
1. Introduction
alkenyl aldehydes via the ring-opening/coupling cascade,
ACCEPTED MANUSCRIPT
providing chroman-4-one and indanone derivatives efficiently
under mild conditions (Scheme 1 (d)).
Cyclopropanols, readily available from the Kulinkovich
reaction or the Simmons-Smith reaction,[1] are important building
blocks in the field of organic synthesis and have emerged as
starting materials for the preparation of versatile multi-funcitional
compounds.[2,3]
Typically,
the
ring-opening
of
cyclopropanols/cross-coupling strategies have been used for the
synthesis of β-substituted carbonyl compounds or the related
structurally more complicated derivatives.[4] Dai group described
copper-catalyzed ring-opening/electrophilic trifluoromethylation
of cyclopropanols to form β-CF3-substituted carbonyl compounds,
which was applied in a concise synthesis glucagon receptor
antagonist LY2409021.[5a] Recently, Zhu group reported a
visible-light-induced cyclopropanols ring-opening coupling with
olefin-substituted cyanohydrins strategy for the synthesis of
unsymmetrical 1,8-diketones.[5b] Additionally, cyclopropanols
and their derivatives are often used to facilitate the total synthesis
of natural products as building blocks or intermediates.[6] For
instance, Zhang group developed a Cu-catalyzed cyclopropanol
ring-opening/cyclization
cascade
to
construct
the
azabicyclo[3.3.1]nonane framework, which was applied in the
total synthesis of (-)-suaveoline.[7] In short, cyclopropanols and
their derivatives can be converted into versatile structural
scaffolds due to the intrinsic strain in the three-membered ring
system and have found useful applications.
Scheme 1. Synthesis of chroman-4-one/indanone-containing compounds.
2. Results and Discussion
For the initial study, 2-(allyloxy)benzaldehyde 1a and 1-
phenylcyclopropanol 2a were selected as the model substrates
and a variety of conditions were screened to optimize the reaction
(Table 1). When the reaction was performed with potassium
persulfate alone as an oxidant at 55 °C under N2 atmosphere for
24 h, the desired product 3-(4-oxo-4-phenylbutyl)chroman-4-one
3aa was obtained only in 22% yield (entry 1). By contrast, the
yield of 3aa increased to 58% when silver nitrate was used as a
catalyst in combination with the oxidant (entry 2). It was found
that the transformation of 1-phenylcyclopropanol 2a into
propiophenone was inevitable as a side reaction, which may
account for the relatively low yield. Therefore, excess 2a was
used in subsequent studies so as to improve the yields of 3aa.
With the amount of 2a increased to 3 equiv., the yield of 3aa was
improved to 71% (entry 3). Adjusting the reaction temperature to
80 °C or room temperature did not bring about better yields as
compared with the reaction temperature of 55 °C (entries 4-5).
Subsequently, a variety of solvents were investigated to further
optimize the reaction (entries 6-11). DMF-H2O turned out to be a
fairly good solvent (entry 9), but other solvents, such as MeCN
and DCE (entries 10, 11), were not effective for this
transformation. The results showed that DMSO-H2O was still the
most suitable solvent. Other catalysts, including AgNO2, AgOAc
and CuBr, were examined, but they proved less efficient (entries
12-14). It was found other oxidants were inferior to K2S2O8 in
that (NH4)2S2O8 led to 38 % yield of 3aa, and TBHP (tert-butly
hydroperoxide), DTBP (di-tert-butly peroxide) resulted in no
product at all (entries, 15-17). Eventually, no 3aa was obtained in
the control experiment in the absence of K2S2O8 (entry 18).
Figure 1. Examples of chroman-4-one/indanone-containing
compounds.
On the other hand, chromanone and indanone frameworks are
privileged structural motifs found in numerous natural products
and pharmaceuticals (Figure 1) with extraordinary biological and
pharmaceutical activities.[8] For example, natural product
Liriopein B[9] has anti-breast cancer activity; Abyssinone II[10] is
an aromatase inhibitor; Donepezil[11] is an AchE inhibitor (Figure
1). Therefore, the preparation of functionalized chromanones and
indanones and their related derivatives have received
considerable synthetic attention over the last few years.[12] In
2017, Zhu group[13] developed a visible light induced tandem
radical addition/cyclization of alkenyl aldehydes with activated
bromides leading to indanones and related compounds (Scheme 1
(a)). In 2018, Yu group[14] reported a silver-catalyzed radical
cascade cyclization with 1,3-dicarbonyl compounds for the
preparation of 1,5-/1,3-dicarbonyl heterocycles containing a
chroman-4-one and indanone moiety (Scheme 1 (b)). In addition,
Table 1. Optimization of Reaction Conditions[a]
Tang and co-workers[15] demonstrated
a K2S2O8-mediated
selective trifluoromethylacylation of alkenes under transition
metal free condition using CF3SO2Na as the trifluoromethylation
reagent (Scheme 1 (c)).
Herein, we envisioned that the strained tertiary cycloalkanols
might be a suitable substrate to initiate the radical cyclization of

3
O
O
HO
AgNO3 (20 mol %)
K2S2O8 (3 equiv.)
CHO
ACCEYPieTldED MANUSCRIPT
R2
Entry
Cat.
Oxidant
Solvent
+
R2
(%)[b]
R3
O
R3
DMSO/H2O (1:1), 55°C
O
1a
2
3
1[c]
2[d]
3
-
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
(NH4)2S2O8
TBHP
DMSO-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
DMSO-H2O(2:1 v/v)
DMSO-H2O(1:2 v/v)
DMSO
22
58
71
60
58
52
46
32
64
6
CH3
O
O
O
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
AgNO2
AgOAc
CuBr
O
O
O
O
O
3ab, 78%
O
3ac, 62%
3aa, 71%
4[d]
5[e]
6
O
OMe
OMe
O
O
O
O
O
O
O
O
O
O
3ad, 58%
3af, 46%
3ae, 64%
O
OMe
OMe
OMe
F
S
O
O
7
O
O
O
O
O
O
O
O
O
3ah, 68%
8
3ag, 43%
3ai, 52%
O
O
O
9
DMF-H2O(1:1 v/v)
MeCN-H2O(1:1 v/v)
DCE-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
DMSO-H2O(1:1 v/v)
O
O
O
O
10
11
12
13
14
15
16
17
18
3ak, 48%
3al, 50%
3aj, 66%
OMe
O
O
O
21
23
54
15.
38
0
Me
O
O
O
O
3am, 58%
3an, 45% (dr 1:1)
3ao, 42% (dr 1:1)
O
O
O
3ap, 43% (dr 1.5:1)
AgNO3
AgNO3
AgNO3
AgNO3
Scheme 2. Substrate scope of cyclopropanols.
DTBP
0
-
0
aReaction conditions: 1a (0.3 mmol, 1 equiv.), 2a (3.0 equiv.), catalyst (20
mol %), oxidant (3.0 equiv.), solvent (v/v, 6 mL), N2 atmosphere, at 55 °C,
24 h.
bIsolated yields.
c2a (1.5 equiv.).
d80 °C.
eRoom temperature.
With the optimized condition described in Table 1, entry 3, we
further explored the generality and scope of the substrates for this
cascade reaction, and the representative results were listed in
Scheme 2. A variety of cyclopropanols 2 substituted by the aryl
with electron-donating groups such as -Me, -t-Bu (2b, 2c), -Ph
(2d) and -OMe (2e-2g), or with electron-withdrawing group such
as -F (2h) at the para position reacted smoothly with the 2-
(allyloxy)benzaldehyde 1a, delivering the corresponding
chroman-4-one derivatives 3ab-3ah in moderate to good yields.
It is noteworthy the cyclopropanol with the heteroaryl
substitution, such as thienyl (2i), was tolerated in the reaction
condition affording 3ai in 52% yield. In addition, aliphatic
substituted cyclopropanols (2j-2m) also reacted with 1a
successfully to furnish the corresponding products (3aj-3am)
with 48% - 66% yields. Furthermore, three disubstituted
cyclopropanols 2n-2p were tested under the standard conditions.
Products 3ao, 3an were obtained as mixture of diastereomers
with 1:1 ratio in 42%, 45% yield, respectively. Product 3ap was
obtained as a mixture of diastereomers with 1.5:1 ratio in 43%
yield. The ratio of diastereomers is determined by 1H NMR. The
formation of 3an-3ap illustrated the cleavage of the more
substituted C-C bond of the cyclopropanol 2n-2p, which is
consistent with the formation of a thermodynamically more
stable secondary alkyl radical intermediate.
Scheme 3. Substrate scope of 2-(allyloxy)benzaldehydes.
Next, the scope of the 2-(allyloxy)benzaldehyde derivatives 1
for this cascade reaction was investigated. As shown in Scheme 3,
substrates 1 with the phenyl ring bearing electron-donating
groups, such as -Me (1b - 1d), -OMe (1f), reacted smoothly with
the 1-phenylcyclopropanol 2a, delivering the corresponding
chroman-4-one derivatives (3ba - 3fa) in moderate to good yields.
It is notable that substrate 1e with a bulky t-Butyl ortho to the
phenol hydroxyl group gave product 3ea in 32% yield. Generally,
substrates 1 that bear the aryl with electron-withdrawing groups,
such as -F (1g - 1i), -Br (1j, 1k), -Cl (1m - 1o), coupled with 2a

4
Tetrahedron
ACCEPTED MANUSCRIPT
in slightly less efficiency than the substrates substituted with
electron-donating aryl, affording 3ag-3oa in moderate to good
yields. In addition, 1-(allyloxy)-2-naphthaldehyde (2p), which
contains
a naphthyl ring, also worked well with this
transformation, affording 3pa in 53% yield.
Scheme 5. Control Experiments.
Scheme 4. The synthesis of indanone derivatives.
Scheme 6. Plausible mechanism.
We further turned to explore the possibility of employment of
2-allylbenzaldehyde derivatives 4 as the starting materials to
couple with a series of cyclopropanols 2 for the synthesis of
indanones derivatives 5 using the same strategy. As exemplified
in Scheme 4, a range of structurally diverse cyclopropanols 2,
which are substituted by the aryl with -t-Bu (2c), -Ph (2d) or -
OMe (2e, 2f) attached on the para position, were coupled readily
with 2-allylbenzaldehyde 4a to provide their corresponding
products (5aa-5af) in moderate to good yields. In addition, the
alkyl substituted cyclopropanols (2j, 2m) also reacted with 4a
successfully to furnish 5aj and 5am in 56% and 66% yields
respectively. Moreover, substrate 4b with the aryl substituted by
strong electron-withdrawing group such as -F was also successful
for this reaction, allowing direct access to the desired products
5ba, 5bc in 62% and 50% yields respectively.
Based on the results of the control experiments (Scheme 5)
and the previous reports,[17,18] a plausible mechanism (Scheme 6)
was
proposed
for
this
silver-catalyzed
ring-
opening/coupling/cyclization cascade. Initially, a cyclopropanol
radical (I) is produced via oxidation of the cyclopropanol 2,
either by Ag2+ species or sulfate radical (SO4 ) (path a or path b),
•-
both of which can be generated from the reaction of AgNO3 and
K2S2O8.[18] Then the cyclopropanol radical (I) undergoes a ring
opening rearrangement to provide a β-ketone radical (II)
followed by an intermolecular addition to the C-C double bond of
1 or 4, leading to the formation of a new radical intermediate
(III). Sequential radical attack on the aldehyde moiety forms an
oxygen radical (IV) followed by a formal 1,2-H shift to deliver
the benzyl radical (V).[19] Finally, the sulfate radical (SO4 )
•-
Several control experiments were conducted to probe into the
reaction mechanism. Firstly, 5.0 equiv. of free-radical scavenger
(2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl (TEMPO) was added
to the cascade reaction in the standard reaction condition, only to
find the reaction was completely inhibited (Scheme 5, eq. 1).[16]
The results implied the reactions may proceed through a radical
pathway. The reaction of benzaldehyde 6 with 1a under the
standard condition (Scheme 5, eq. 2) was examined, but the
desired product 7 was not observed, which revealed that the
aldehydic group in either of 1a or 6 could not produce the
carbonyl radical to make the cascade reaction proceed. Finally,
cyclopropanol 8[17] was used as an additional substrate to
examine this cascade reaction. In this case, compound 9 was
obtained in 45% yield (Scheme 5, eq. 3), which also indicated
that the radical was mainly initiated from the ring-opening of
cyclopropanols rather than from substrates 1.
would abstract a hydrogen from the benzyl radical (V) to give the
final products 3 or 5.[19]
3. Conclusions
In summary, a facile synthesis of chroman-4-one and indanone
derivatives was developed from readily available starting
[20]
materials under mild conditions.
A probable mechanism was
proposed which indicate the involvement of a silver-catalyzed
radical ring-opening of cyclopropanols followed by an
intermolecular coupling with alkenyl aldehydes and the
subsequent cyclization cascade. Further studies concerning the
ring-opening/coupling reactions of cyclopropanols for the
construction of structurally more versatile molecules are
underway in our lab.
4. Experimental Section
4.1. General Information
1H NMR (600 MHz) and 13C NMR (150 MHz) spectra were
obtained in CDCl3 with TMS as internal standard. HRMS (ESI)
spectra were recorded on a 1200-6520 Q-TOF/Agilent mass

5
25.9, 21.5. LRMS (ESI): [M + Na]+ 317.1; HRMS (ESI-TOF) m/z
spectrometer using electrospray ionization. Low-resolution Mass
spectra were obtained from GC-MS system. The starting
materials were purchased from Aldrich, Energy Chemical
Chemicals used without further purification. Flash column
chromatography was performed using 200-300 mesh silica gel.
Substrates 1[21], 2[18, 22] and 4[23] were synthesized according to the
reported procedures.
ACCEPTED MANUSCRIPT
calcd for C19H18O3Na, 317.1154, [M + Na]+, found 317.1158.
3-(4-oxo-4-(p-tolyl)butyl)chroman-4-one (3ab). Yield 72 mg,
78%; white solid, mp 99-100 °C; Rf = 0.50 (PE/EA = 5:1 v/v). H
1
NMR (600 MHz, CDCl3) δ 7.89 (dd, J = 7.9, 1.7 Hz, 1H), 7.85 (d, J
= 8.2 Hz, 2H), 7.56 – 7.40 (m, 1H), 7.25 (d, J = 7.9 Hz, 2H), 7.05 –
6.98 (m, 1H), 6.96 (dd, J = 8.3, 0.5 Hz, 1H), 4.57 (dd, J = 11.5, 4.5
Hz, 1H), 4.31 (dd, J = 11.4, 8.9 Hz, 1H), 3.01 (t, J = 7.1 Hz, 2H),
2.87 – 2.60 (m, 1H), 2.41 (s, 3H), 2.03 – 1.88 (m, 2H), 1.88 – 1.73
(m, 1H), 1.66 – 1.54 (m, 1H). 13C NMR (150 MHz, CDCl3) δ 199.3,
194.3, 161.5, 143.8, 135.8, 134.3, 129.3, 128.1, 127.4, 121.3, 120.5,
117.7, 70.4, 45.8, 38.1, 25.9, 21.67, 21.65. LRMS (ESI): [M + Na]+
333.1; HRMS (ESI-TOF) m/z calcd for C20H20O3Na, 331.1310, [M +
Na]+, found 331.1314.
4.2. General Procedure for the Preparation of Substrates 1[20]
and 2[18, 22]
A solution of salicylaldehyde (5 mmol) in dry DMF (10.0 mL)
was treated with K2CO3 (7.0 mmol) and allyl bromide (6.0
mmol). The mixture was stirred 2 hours at 70 °C. Then it was
cooled to room temperature and poured into saturated aqueous
NH4Cl and extracted 4 times with EtOAc. The organic phases
were evaporated and then subjected to column chromatography
to afford the starting materials 1. General Procedure for the
Preparation of Substrates 2[18, 22]: Ethyl magnesium bromide (2.8
equiv., 3M in Et2O) in THF was added drop wise over 30
minutes at 0 °C to a solution of ester (1 equiv.) and titanium
isopropoxide (1.4 equiv.) in THF. The mixture was warmed to
room temperature and stirred overnight. Then the mixture was
quenched with water and the precipitated solid was removed by
filtration. The filtrate was extracted with ether (3 × 30 mL),
washed with water and dried over Na2SO4 followed by filtration
and concentration. The residue was subjected to column
chromatography to afford the cyclopropanols 2.
3-(4-(4-(tert-butyl)phenyl)-4-oxobutyl)chroman-4-one
(3ac).
Yield 65 mg, 62%; white solid, mp 85-86 °C; Rf = 0.58 (PE/EA =
5:1 v/v). H NMR (600 MHz, CDCl3) δ 8.17 – 7.75 (m, 3H), 7.74 –
1
7.35 (m, 3H), 7.01 (t, J = 7.5 Hz, 1H), 6.96 (d, J = 8.3 Hz, 1H), 4.57
(dd, J = 11.5, 4.5 Hz, 1H), 4.31 (dd, J = 11.4, 8.9 Hz, 1H), 3.02 (t, J
= 7.0 Hz, 2H), 2.86 – 2.44 (m, 1H), 2.02 – 1.80 (m, 3H), 1.62 (m,
1H), 1.34 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 199.3, 194.3,
161.5, 156.8, 135.7, 134.3, 128.0, 127.4, 125.5, 121.3, 120.6, 117.7,
70.4, 45.8, 38.2, 35.1, 31.1, 25.9, 21.6. LRMS (ESI): [M + Na]+
373.0; HRMS (ESI-TOF) m/z calcd for C23H26O3Na, 373.1780, [M +
Na]+, found 373.1784.
3-(4-([1,1'-biphenyl]-4-yl)-4-oxobutyl)chroman-4-one
(3ad).
Yield 64 mg, 58%; white solid, mp 112-113 °C; Rf = 0.32 (PE/EA =
5:1 v/v). H NMR (600 MHz, CDCl3) δ 8.03 (d, J = 8.3 Hz, 2H),
1
4.3. General Procedure for the Preparation of Substrates 4[23]
:
7.90 (dd, J = 7.9, 1.7 Hz, 1H), 7.69 (d, J = 8.3 Hz, 2H), 7.65 – 7.59
(m, 2H), 7.53 – 7.44 (m, 3H), 7.40 (t, J = 7.4 Hz, 1H), 7.02 (dd, J =
11.0, 4.0 Hz, 1H), 6.97 (d, J = 8.3 Hz, 1H), 4.58 (dd, J = 11.5, 4.5
Hz, 1H), 4.33 (dd, J = 11.4, 8.9 Hz, 1H), 3.07 (t, J = 7.0 Hz, 2H),
2.83 – 2.66 (m, 1H), 2.04 – 1.91 (m, 2H), 1.91 – 1.82 (m, 1H), 1.72 –
1.59 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 199.2, 194.3, 161.5,
145.7, 139.8, 135.8, 135.5, 128.9, 128.6, 128.2, 127.4, 127.2, 127.2,
121.4, 120.5, 117.7, 70.4, 45.8, 38.3, 25.9, 21.6. LRMS (ESI): [M +
Na]+ 393.1; HRMS (ESI-TOF) m/z calcd for C25H22O3Na, 393.1467,
[M + Na]+, found 393.1468.
To a solution of the 2-formylphenylboronic acid and
corresponding allyl halide (1.5 equiv.) in THF (0.2 M) in a
round-bottom flask were added PdCl2(PPh3)2 (2.5 mol %). The
reaction mixture was heated to 50 °C, then aq Na2CO3 (1 M, 2
equiv.) solution was added drop wise over a period of 1 h and the
heating continued in reflux for 3-4 h. The reaction mixture was
quenched with H2O and extracted with DCM (three times). The
combined organic layer was washed with brine, dried over
MgSO4, and concentrated in vacuum. The residue was purified
by column chromatography on silica gel (EtOAc/PE = 1:50) to
afford the desired yellow product 4.
3-(4-(4-methoxyphenyl)-4-oxobutyl)chroman-4-one (3ae). Yield
62 mg, 64%; white solid, mp 77-78°C; Rf = 0.38 (PE/EA = 5:1 v/v).
1H NMR (600 MHz, CDCl3) δ 7.94 (d, J = 8.8 Hz, 2H), 7.89 (dd, J =
7.8, 1.5 Hz, 1H), 7.51 – 7.41 (m, 1H), 7.01 (t, J = 7.5 Hz, 1H), 6.96
(d, J = 8.3 Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), 4.57 (dd, J = 11.4, 4.5
Hz, 1H), 4.31 (dd, J = 11.4, 8.9 Hz, 1H), 3.87 (s, 3H), 2.98 (t, J = 7.1
Hz, 2H), 2.71 (td, J = 8.6, 4.6 Hz, 1H), 2.00 – 1.89 (m, 1H), 1.86 –
1.80 (m, 1H), 1.68 – 1.58 (m, 1H). 13C NMR (150 MHz, CDCl3) δ
198.2, 194.3, 163.4, 161.5, 135.8, 130.3, 129.9, 127.4, 121.3, 120.5,
117.7, 113.7, 70.4, 55.4, 45.8, 37.9, 25.9, 21.7. LRMS (ESI): [M +
Na]+ 347.1 HRMS (ESI-TOF) m/z calcd for C20H20O4Na, 347.1259,
[M + Na]+, found 347.1264.
4.4. General procedures for the silver nitrate catalyzed ring-
opening/coupling/cyclization cascade between cyclopropanols
and alkenyl aldehydes
A reaction tube protected by the nitrogen equipped with a
magnetic stir bar was charged with alkenyl aldehyde (1 or 4, 0.30
mmol), cyclopropanol (2, 0.9 mmol), AgNO3 (10.2 mg, 0.06
mmol), K2S2O8 (243.0 mg, 0.9 mmol), and DMSO/H2O (1:1, 6.0
mL), respectively. The mixtures were allowed to react at 55 °C
for 24h. When the reaction was completed, the mixture was
charged in 30 mL water and extracted with CH2Cl2 (15 mL x 3
times). The CH2Cl2 layers were combined and dried over
Na2SO4, which was further was purified by column
chromatography on silica gel (eluent, petroleum ether/ethyl
acetate = 25:1 to 10:1) to afford the desired product 3 or 5.
3-(4-(3,4-dimethoxyphenyl)-4-oxobutyl)chroman-4-one
(3af).
Yield 48 mg, 46%; white solid, mp 97-98 °C; Rf = 0.22 (PE/EA =
3:1 v/v). H NMR (600 MHz, CDCl3) δ 7.89 (dd, J = 7.9, 1.7 Hz,
1
1H), 7.59 (dd, J = 8.4, 1.9 Hz, 1H), 7.53 (d, J = 1.9 Hz, 1H), 7.47
(ddd, J = 8.7, 7.2, 1.7 Hz, 1H), 7.07 – 6.99 (m, 1H), 6.96 (d, J = 8.3
Hz, 1H), 6.89 (d, J = 8.4 Hz, 1H), 4.58 (dd, J = 11.5, 4.4 Hz, 1H),
4.32 (dd, J = 11.5, 8.8 Hz, 1H), 3.95 (s, 3H), 3.94 (s, 3H), 3.01 (t, J =
7.1 Hz, 2H), 2.73 (ddd, J = 10.0, 8.7, 5.2 Hz, 1H), 2.06 – 1.88 (m,
2H), 1.84 (m, 1H), 1.71 – 1.56 (m, 1H). 13C NMR (150 MHz,
CDCl3) δ 198.3, 194.3, 161.4, 153.2, 148.9, 135.8, 130.0, 127.3,
122.7, 121.3, 120.5, 117.7, 109.99,109.97, 70.3, 56.0, 55.9, 45.7,
37.8, 25.9, 21.8. LRMS (ESI): [M + Na]+ 377.1; HRMS (ESI-TOF)
m/z calcd for C21H22O5Na, 377.1365, [M + Na]+, found 377.1366.
4.5. Characterization of compounds 3 and 5
3-(4-oxo-4-phenylbutyl)chroman-4-one (3aa). Yield 62 mg, 71%;
1
white solid, mp 92-93 °C; Rf = 0.27 (PE/EA = 10:1 v/v). H NMR
(600 MHz, CDCl3) δ 7.96 (dd, J = 8.2, 1.0 Hz, 2H), 7.89 (dd, J = 7.9,
1.6 Hz, 1H), 7.56 (t, J = 7.4 Hz, 1H), 7.50 – 7.39 (m, 3H), 7.09 –
6.99 (m, 1H), 6.96 (d, J = 8.4 Hz, 1H), 4.58 (dd, J = 11.5, 4.5 Hz,
1H), 4.32 (dd, J = 11.4, 8.9 Hz, 1H), 3.05 (t, J = 7.0 Hz, 2H), 2.73
(tt, J = 8.9, 5.1 Hz, 1H), 2.06 – 1.76 (m, 3H), 1.75 – 1.38 (m, 1H).
13C NMR (150 MHz, CDCl3) δ 199.6, 194.2, 161.5, 136.8, 135.8,
133.1, 128.6, 128.0, 127.4, 121.4, 120.5, 117.7, 70.4, 45.8, 38.3,
3-(4-oxo-4-(3,4,5-trimethoxyphenyl)butyl)chroman-4-one (3ag).
1
Yield 49 mg, 43%; white solid; Rf = 0.11 (PE/EA = 5:1 v/v). H
NMR (600 MHz, CDCl3) δ 7.88 (dd, J = 7.9, 1.5 Hz, 1H), 7.47 (ddd,
J = 8.7, 7.2, 1.7 Hz, 1H), 7.22 (s, 2H), 7.01 (t, J = 7.5 Hz, 1H), 6.96

6
Tetrahedron
(d, J = 8.4 Hz, 1H), 4.58 (dd, J = 11.5, 4.4 Hz, 1H), 4.32 (dd, J =
21.0. LRMS (ESI): [M + Na]+ 345.1; HRMS (ESI-TOF) m/z calcd
ACCEPTED MANUSCRIPT
11.4, 8.8 Hz, 1H), 4.05 – 3.87 (m, 9H), 3.02 (dd, J = 13.5, 6.3 Hz,
2H), 2.80 – 2.65 (m, 1H), 2.02 – 1.81 (m, 3H), 1.63 (tdd, J = 9.6, 7.5,
4.8 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 198.4, 194.2, 161.4,
153.0, 142.5, 135.8, 132.1, 127.3, 121.3, 120.5, 117.7, 105.4, 70.3,
60.9, 56.2, 45.7, 38.0, 25.9, 21.7. LRMS (ESI): [M + Na]+ 407.1;
HRMS (ESI-TOF) m/z calcd for C22H24O6Na, 407.1471, [M + Na]+,
found 407.1471.
for C21H22O3Na, 345.1467, [M + Na]+, found 345.1462.
3-(4-oxoundecyl)chroman-4-one (3am). Yield 55 mg, 58%; white
solid, mp 42-43 °C; Rf = 0.51 (PE/EA = 5:1 v/v). H NMR (600
1
MHz, CDCl3) δ 7.88 (dd, J = 7.9, 1.6 Hz, 1H), 7.55 – 7.38 (m, 1H),
7.01 (t, J = 7.5 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 4.54 (dd, J = 11.4,
4.5 Hz, 1H), 4.28 (dd, J = 11.4, 8.9 Hz, 1H), 2.72 – 2.58 (m, 1H),
2.46 (t, J = 7.2 Hz, 2H), 2.39 (t, J = 7.5 Hz, 2H), 1.85 (ddt, J = 13.6,
11.1, 5.6 Hz, 1H), 1.80 – 1.71 (m, 1H), 1.70 – 1.62 (m, 1H), 1.60 –
1.47 (m, 3H), 1.27 (s, 8H), 0.88 (t, J = 6.9 Hz, 3H). 13C NMR (150
MHz, CDCl3) δ 210.7, 194.2, 161.4, 135.8, 127.4, 121.3, 120.5,
117.7, 70.3, 45.8, 42.9, 42.4, 31.6, 29.2, 29.0, 25.8, 23.8, 22.6, 21.1,
14.0. LRMS (ESI): [M + Na]+ 339.2; HRMS (ESI-TOF) m/z calcd
for C20H28O3Na, 339.1936, [M + Na]+, found 339.1940.
3-(4-oxo-4-phenylbutyl)chroman-4-one (3ah). Yield 63mg, 68%;
white solid, mp 100-102 °C; Rf = 0.27 (PE/EA = 10:1 v/v). 1H NMR
(600 MHz, CDCl3) δ 8.03 – 7.94 (m, 2H), 7.89 (dd, J = 7.9, 1.6 Hz,
1H), 7.57 – 7.40 (m, 1H), 7.13 (dd, J = 11.8, 5.4 Hz, 2H), 7.05 – 6.98
(m, 1H), 6.96 (d, J = 8.4 Hz, 1H), 4.57 (dd, J = 11.5, 4.5 Hz, 1H),
4.31 (dd, J = 11.4, 8.9 Hz, 1H), 3.01 (t, J = 7.0 Hz, 2H), 2.84 – 2.50
(m, 1H), 2.01 – 1.88 (m, 2H), 1.88 – 1.76 (m, 1H), 1.68 – 1.49 (m,
1H). 13C NMR (150 MHz, CDCl3) δ 198.0, 194.2, 165.7 (d, J =
254.7 Hz), 161.5, 135.8, 133.3 (d, J = 2.9 Hz), 130.6 (d, J = 9.3 Hz),
127.4, 121.4, 120.5, 117.7, 115.7 (d, J = 21.8 Hz), 70.4, 45.8, 38.2,
25.9, 21.5. 19F NMR (565 MHz, CDCl3) δ -105.2. LRMS (ESI): [M
+ Na]+ 335.0; HRMS (ESI-TOF) m/z calcd for C19H17O3FNa,
335.1059, [M + Na]+, found 335.1061.
3-(4-(4-methoxyphenyl)-2-methyl-4-oxobutyl)chroman-4-one
(3an). Yield 46 mg, 45%; oil; Rf = 0.39 (PE/EA = 5:1 v/v). 1H NMR
(600 MHz, CDCl3) δ 7.94 (t, J = 9.3 Hz, 2H), 7.90 – 7.78 (m, 1H),
7.54 – 7.35 (m, 1H), 7.01 (t, J = 7.5 Hz, 1H), 6.98 – 6.67 (m, 3H),
4.58 (m, 1H), 4.28 (ddd, J = 13.8, 11.6, 9.1 Hz, 1H), 3.88 (t, J = 8.5
Hz, 3H), 2.96 (m, 1H), 2.86 – 2.67 (m, 2H), 2.44 – 2.24 (m, 1H),
1.93 (m, 1H), 1.55 – 1.36 (m, 1H), 1.03 (dd, J = 12.3, 6.6 Hz, 3H).
13C NMR (150 MHz, CDCl3) δ 198.1, 194.5, 163.4, 161.5, 135.7,
130.3, 127.4, 121.3, 120.5, 117.7, 113.7, 70.5, 55.4, 45.3, 43.8, 33.3,
27.2, 20.1. LRMS (ESI): [M + Na]+ 361.1; HRMS (ESI-TOF) m/z
calcd for C21H22O4Na, 361.1416, [M + Na]+, found 361.1420.
3-(4-oxo-4-(thiophen-3-yl)butyl)chroman-4-one (3ai). Yield 47
1
mg, 52%; oil; Rf = 0.43 (PE/EA = 5:1 v/v). H NMR (600 MHz,
CDCl3) δ 8.11 – 8.03 (m, 1H), 7.89 (dd, J = 7.8, 1.6 Hz, 1H), 7.70 –
7.52 (m, 1H), 7.50 – 7.43 (m, 1H), 7.32 (dd, J = 5.0, 2.9 Hz, 1H),
7.01 (t, J = 7.5 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 4.57 (dd, J = 11.5,
4.5 Hz, 1H), 4.31 (dd, J = 11.4, 8.8 Hz, 1H), 2.95 (t, J = 7.1 Hz, 2H),
2.79 – 2.56 (m, 1H), 2.01 – 1.87 (m, 2H), 1.84 (ddd, J = 16.3, 11.2,
5.7 Hz, 1H), 1.62 (ddd, J = 13.1, 9.2, 6.6 Hz, 1H). 13C NMR (150
MHz, CDCl3) δ 194.29, 194.04, 161.5, 142.2, 135.8, 131.9, 127.4,
126.9, 126.4, 121.4, 120.5, 117.7, 70.4, 45.8, 39.5, 25.9, 21.6. LRMS
(ESI): [M + Na]+ 323.0; HRMS (ESI-TOF) m/z calcd for
C17H16O3SNa, 323.0718, [M + Na]+, found 323.0716.
3-(2-isopropyl-4-oxo-4-phenylbutyl)chroman-4-one (3ao). Yield
42 mg, 42%; colorless oil. H NMR (600 MHz, CDCl3) δ 8.01 –
1
7.80 (m, 3H), 7.57 (td, J = 7.3, 1.3 Hz, 1H), 7.50 – 7.40 (m, 3H),
6.99 (m, 2H), 4.61 (m, 1H), 4.30 (m, 1H), 3.05 (m, 1H), 2.86 (dt, J =
15.8, 7.5 Hz, 1H), 2.82 – 2.53 (m, 1H), 2.37 – 2.16 (m, 1H), 2.08 –
1.85 (m, 1H), 1.85 – 1.73 (m, 1H), 1.61 – 1.23 (m, 1H), 1.05 – 0.85
(m, 6H). 13C NMR (150 MHz, CDCl3) δ 200.0, 194.7, 161.5, 137.2,
135.7, 133.0, 128.6, 128.0, 127.3, 121.2, 120.5, 117.7, 70.3, 44.1,
40.4, 36.3, 31.3, 28.0, 20.3, 18.6. HRMS (ESI-TOF) m/z calcd for
C22H25O3, 337.1798, [M + H]+, found 337.1795.
3-(4-cyclohexyl-4-oxobutyl)chroman-4-one (3aj). Yield 59 mg,
1
66%; white solid, mp 63-64 °C; Rf = 0.47 (PE/EA = 5:1 v/v). H
NMR (600 MHz, CDCl3) δ 7.88 (dd, J = 7.9, 1.6 Hz, 1H), 7.58 –
7.28 (m, 1H), 7.01 (t, J = 7.5 Hz, 1H), 6.95 (d, J = 8.3 Hz, 1H), 4.54
(dd, J = 11.4, 4.5 Hz, 1H), 4.28 (dd, J = 11.4, 9.0 Hz, 1H), 2.66 (m,
1H), 2.50 (t, J = 7.1 Hz, 2H), 2.40 – 2.23 (m, 1H), 1.91 – 1.70 (m,
6H), 1.69 – 1.56 (m, 1H), 1.50 (m, 1H), 1.37 – 0.98 (m, 6H). 13C
NMR (150 MHz, CDCl3) δ 213.5, 194.2, 161.4, 135.7, 127.3, 121.3,
120.5, 117.7, 70.3, 50.8, 45.8, 40.2, 28.4, 25.83, 25.82, 25.6, 21.0.
LRMS (ESI): [M + Na]+ 323.2; HRMS (ESI-TOF) m/z calcd for
C19H24O3Na, 323.1623, [M + Na]+, found 323.1628.
3-(2-(2-oxo-2-phenylethyl)pentyl)chroman-4-one (3ap). Yield 43
mg, 43%; colorless oil. 1H NMR (600 MHz, CDCl3) δ 8.02 – 7.78 (m,
3H), 7.67 – 7.39 (m, 4H), 7.09 – 6.78 (m, 2H), 4.59 (m, 1H), 4.28 (m,
1H), 3.15 – 2.88 (m, 2H), 2.86 – 2.56 (m, 1H), 2.40 – 2.15 (m, 1H),
1.93 (m, 1H), 1.55 – 1.19 (m, 5H), 0.89 (td, J = 6.9, 4.1 Hz, 3H). 13C
NMR (150 MHz, CDCl3) δ 199.8, 194.6, 161.5, 137.2, 135.7, 133.0,
128.6, 128.0, 127.3, 121.3, 120.5, 117.7, 70.5, 43.9, 43.2, 37.5, 31.2,
30.5, 19.7, 14.2. HRMS (ESI-TOF) m/z calcd for C22H25O3,
337.1798, [M + H]+, found 337.1796.
3-(4-oxo-5-phenylpentyl)chroman-4-one (3ak). Yield 44 mg,
1
48%; oil; Rf = 0.33 (PE/EA = 5:1 v/v). H NMR (600 MHz, CDCl3)
δ 7.86 (dd, J = 7.9, 1.5 Hz, 1H), 7.50 – 7.41 (m, 1H), 7.32 (t, J = 7.5
Hz, 2H), 7.26 (dd, J = 9.0, 5.6 Hz, 1H), 7.19 (d, J = 7.4 Hz, 2H),
7.00 (t, J = 7.5 Hz, 1H), 6.94 (d, J = 8.3 Hz, 1H), 4.48 (dd, J = 11.5,
4.4 Hz, 1H), 4.22 (dd, J = 11.4, 8.9 Hz, 1H), 3.68 (s, 2H), 2.60 (tt, J
= 8.6, 5.6 Hz, 1H), 2.55 – 2.38 (m, 2H), 1.79 (ddt, J = 13.3, 11.1, 5.6
Hz, 1H), 1.72 – 1.57 (m, 2H), 1.44 (dddd, J = 13.0, 10.6, 7.7, 5.3 Hz,
1H). 13C NMR (150 MHz, CDCl3) δ 207.8, 194.2, 161.4, 135.8,
134.1, 129.4, 128.7, 127.3, 127.0, 121.3, 120.5, 117.7, 70.3, 50.2,
45.6, 41.6, 25.6, 21.0. LRMS (ESI): [M + Na]+ 331.1; HRMS (ESI-
TOF) m/z calcd for C20H20O3Na, 331.1310, [M + Na]+ , found
331.1314.
7-methyl-3-(4-oxo-4-phenylbutyl)chroman-4-one (3ba). Yield 67
mg, 73%; white solid, mp 89-90 °C; Rf = 0.40 (PE/EA = 5:1 v/v). 1H
NMR (600 MHz, CDCl3) δ 7.95 (dt, J = 8.5, 1.5 Hz, 2H), 7.78 (d, J
= 8.0 Hz, 1H), 7.62 – 7.52 (m, 1H), 7.50 – 7.42 (m, 2H), 6.83 (ddd, J
= 8.0, 1.5, 0.5 Hz, 1H), 6.76 (s, 1H), 4.54 (dd, J = 11.4, 4.4 Hz, 1H),
4.28 (dd, J = 11.4, 8.7 Hz, 1H), 3.03 (t, J = 7.0 Hz, 2H), 2.77 – 2.59
(m, 1H), 2.35 (s, 3H), 1.99 – 1.88 (m, 2H), 1.87 – 1.81 (m, 1H), 1.64
– 1.58 (m, 1H). 13C NMR (150 MHz, CDCl3) δ 199.6, 194.0, 161.5,
147.3, 136.8, 133.0, 128.6, 128.0, 127.3, 122.8, 118.3, 117.7, 70.4,
45.7, 38.3, 26.0, 21.9, 21.6. LRMS (ESI): [M + Na]+ 331.1; HRMS
(ESI-TOF) m/z calcd for C20H20O3Na, 331.1310, [M + Na]+, found
331.1314.
3-(4-oxo-6-phenylhexyl)chroman-4-one (3al). Yield 50 mg, 50%;
1
white solid, mp 53-54 °C; Rf = 0.42 (PE/EA = 5:1 v/v). H NMR
8-methyl-3-(4-oxo-4-phenylbutyl)chroman-4-one (3ca). Yield 59
mg, 64%; white solid, mp 104-105 °C; Rf = 0.51 (PE/EA = 5:1 v/v).
1H NMR (600 MHz, CDCl3) δ 8.10 – 7.84 (m, 2H), 7.85 – 7.68 (m,
1H), 7.56 (ddd, J = 8.6, 2.5, 1.2 Hz, 1H), 7.51 – 7.42 (m, 2H), 7.33
(ddd, J = 7.2, 1.6, 0.8 Hz, 1H), 6.91 (t, J = 7.6 Hz, 1H), 4.60 (dd, J =
11.4, 4.5 Hz, 1H), 4.32 (dd, J = 11.4, 8.9 Hz, 1H), 3.05 (t, J = 6.9
Hz, 2H), 2.84 – 2.56 (m, 1H), 2.24 (s, 3H), 2.00 – 1.79 (m, 3H), 1.67
– 1.49 (m, 1H). 13C NMR (150 MHz, CDCl3) δ 199.7, 194.7, 159.7,
136.9, 136.6, 133.0, 128.6, 128.0, 127.0, 124.9, 120.7, 120.2, 70.3,
(600 MHz, CDCl3) δ 7.90 (dd, J = 7.9, 1.6 Hz, 1H), 7.62 – 7.41 (m,
1H), 7.29 (dd, J = 10.2, 5.0 Hz, 2H), 7.20 (t, J = 7.5 Hz, 3H), 7.08 –
7.00 (m, 1H), 6.98 (d, J = 8.4 Hz, 1H), 4.54 (dd, J = 11.4, 4.5 Hz,
1H), 4.28 (dd, J = 11.4, 8.9 Hz, 1H), 2.92 (t, J = 7.6 Hz, 2H), 2.84 –
2.70 (m, 2H), 2.70 – 2.59 (m, 1H), 2.46 (t, J = 7.2 Hz, 2H), 1.84 (m,
1H), 1.76 (m, 1H), 1.71 – 1.61 (m, 1H), 1.50 (m, 1H). 13C NMR (150
MHz, CDCl3) δ 209.5, 194.2, 161.4, 141.0, 135.8, 128.5, 128.3,
127.4, 126.1, 121.4, 120.5, 117.7, 70.3, 45.7, 44.3, 42.7, 29.7, 25.7,

7
45.6, 38.3, 25.9, 21.6, 15.5. LRMS (ESI): [M + Na]+ 331.1; HRMS
(ESI-TOF) m/z calcd for C20H20O3Na, 331.1310, [M + Na]+, found
331.1314
8-fluoro-3-(4-oxo-4-phenylbutyl)chroman-4-one (3ia). Yield 50
ACCEPTED MANUSCRIPT
mg, 54%; white solid, mp 83-84 °C; Rf = 0.40 (PE/EA = 5:1 v/v). 1H
NMR (600 MHz, CDCl3) δ 7.96 (d, J = 7.3 Hz, 2H), 7.67 (d, J = 8.0
Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.7 Hz, 2H), 7.28 (ddd,
J = 7.9, 7.1, 1.3 Hz, 1H), 6.95 (td, J = 8.0, 4.4 Hz, 1H), 4.67 (dd, J =
11.5, 4.5 Hz, 1H), 4.41 (dd, J = 11.5, 8.9 Hz, 1H), 3.05 (t, J = 7.0
Hz, 2H), 2.78 (ddd, J = 10.1, 8.9, 5.4 Hz, 1H), 2.01 – 1.90 (m, 2H),
1.89 – 1.81 (m, 1H), 1.67 – 1.60 (m, 1H). 13C NMR (150 MHz,
CDCl3) δ 199.5, 193.2, 151.5 (d, J = 248.5 Hz), 149.7 (d, J = 11.5
Hz), 136.8, 133.1, 128.6, 128.0, 122.6, 122.4 (d, J = 3.9 Hz), 121.6
(d, J = 17.4 Hz), 120.7 (d, J = 6.4 Hz), 71.0, 45.8, 38.2, 25.8, 21.4.
19F NMR (565 MHz, CDCl3) δ -135.56. LRMS (ESI): [M + Na]+
335.1; HRMS (ESI-TOF) m/z calcd for C19H17O3FNa, 335.1059, [M
+ Na]+, found 335.1064.
6-methyl-3-(4-oxo-4-phenylbutyl)chroman-4-one (3da). Yield 46
mg, 50%; white solid, mp 57-58 °C; Rf = 0.48 (PE/EA = 5:1 v/v). 1H
NMR (600 MHz, CDCl3) δ 7.95 (d, J = 7.6 Hz, 2H), 7.68 (s, 1H),
7.57 (dd, J = 12.8, 5.4 Hz, 1H), 7.51 – 7.38 (m, 2H), 7.34 – 7.09 (m,
1H), 6.86 (d, J = 8.4 Hz, 1H), 4.54 (dd, J = 11.4, 4.4 Hz, 1H), 4.29
(dd, J = 11.4, 8.7 Hz, 1H), 3.04 (t, J = 7.0 Hz, 2H), 2.83 – 2.58 (m,
1H), 2.30 (s, 3H), 2.01 – 1.88 (m, 2H), 1.84 (m, 1H), 1.69 – 1.47 (m,
1H). 13C NMR (150 MHz, CDCl3) δ 199.6, 194.5, 159.5, 136.8,
133.0, 130.8, 128.7, 128.6, 128.0, 126.9, 120.1, 117.5, 70.4, 45.9,
38.3, 26.0, 21.6, 20.4. LRMS (ESI): [M + Na]+ 331.1; HRMS (ESI-
TOF) m/z calcd for C20H20O3Na, 331.1310, [M + Na]+, found
331.1314
6-bromo-3-(4-oxo-4-phenylbutyl)chroman-4-one (3ja). Yield 53
mg, 48%; white solid, mp 103-104 °C; Rf = 0.45 (PE/EA = 5:1 v/v).
1H NMR (600 MHz, CDCl3) δ 8.16 – 7.76 (m, 3H), 7.65 – 7.51 (m,
2H), 7.51 – 7.34 (m, 2H), 6.87 (d, J = 8.8 Hz, 1H), 4.57 (dd, J =
11.5, 4.5 Hz, 1H), 4.31 (dd, J = 11.5, 8.9 Hz, 1H), 3.04 (dd, J = 8.5,
5.4 Hz, 2H), 2.72 (ddt, J = 8.9, 5.5, 4.9 Hz, 1H), 2.03 – 1.87 (m, 2H),
1.88 – 1.74 (m, 1H), 1.70 – 1.53 (m, 1H). 13C NMR (150 MHz,
CDCl3) δ 199.5, 193.0, 160.4, 138.4, 136.8, 133.1, 129.8, 128.6,
128.0, 121.84, 119.8, 114.0, 70.5, 45.5, 38.2, 25.8, 21.4. LRMS
(ESI): [M + Na]+ 395.0; HRMS (ESI-TOF) m/z calcd for
C19H17O3BrNa, 395.0259, [M + Na]+, found 395.0264.
8-(tert-butyl)-3-(4-oxo-4-phenylbutyl)chroman-4-one (3ea). Yield
1
33 mg, 32%; oil; Rf = 0.60 (PE/EA = 5:1 v/v). H NMR (600 MHz,
CDCl3) δ 7.96 (dd, J = 8.2, 1.1 Hz, 2H), 7.80 (dd, J = 7.8, 1.7 Hz,
1H), 7.56 (t, J = 7.4 Hz, 1H), 7.46 (ddd, J = 7.6, 4.8, 3.0 Hz, 3H),
6.95 (t, J = 7.7 Hz, 1H), 4.61 (dd, J = 11.3, 4.5 Hz, 1H), 4.32 (dd, J =
11.3, 9.0 Hz, 1H), 3.05 (dd, J = 10.5, 3.8 Hz, 2H), 2.73 (ddd, J =
13.4, 8.8, 5.2 Hz, 1H), 2.02 – 1.90 (m, 2H), 1.90 – 1.82 (m, 1H), 1.66
– 1.58 (m, 1H), 1.39 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 199.7,
194.9, 160.7, 138.8, 136.9, 133.0, 132.7, 128.6, 128.0, 125.5, 121.3,
120.8, 69.9, 45.5, 38.3, 34.9, 29.6, 25.9, 21.5. LRMS (ESI): [M +
Na]+ 373.2; HRMS (ESI-TOF) m/z calcd for C23H26O3Na, 373.1780,
[M + Na]+, found 373.1784
7-bromo-3-(4-oxo-4-phenylbutyl)chroman-4-one (3ka). Yield 63
mg, 57%; white solid, mp 112-113 °C; Rf = 0.42 (PE/EA = 5:1 v/v).
1H NMR (600 MHz, CDCl3) δ 8.03 – 7.84 (m, 2H), 7.74 (d, J = 8.4
Hz, 1H), 7.66 – 7.51 (m, 1H), 7.46 (dd, J = 10.7, 4.9 Hz, 2H), 7.24 –
7.05 (m, 2H), 4.57 (dd, J = 11.5, 4.5 Hz, 1H), 4.31 (dd, J = 11.5, 8.9
Hz, 1H), 3.04 (t, J = 6.9 Hz, 2H), 2.86 – 2.53 (m, 1H), 2.00 – 1.88
(m, 2H), 1.88 – 1.77 (m, 1H), 1.65 – 1.49 (m, 1H). 13C NMR (150
MHz, CDCl3) δ 199.5, 193.4, 161.7, 136.8, 133.1, 130.1, 128.67,
128.65, 128.0, 125.0, 120.9, 119.4, 70.7, 45.7, 38.2, 25.8, 21.4.
LRMS (ESI): [M + Na]+ 395.0; HRMS (ESI-TOF) m/z calcd for
C19H17O3BrNa, 395.0259, [M + Na]+, found 395.0264.
7-methoxy-3-(4-oxo-4-phenylbutyl)chroman-4-one (3fa). Yield 64
mg, 66%; white solid, mp 96-97 °C; Rf = 0.32 (PE/EA = 5:1 v/v). 1H
NMR (600 MHz, CDCl3) δ 8.08 – 7.88 (m, 2H), 7.83 (d, J = 8.8 Hz,
1H), 7.56 (dd, J = 10.6, 4.2 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 6.58
(dd, J = 8.8, 2.3 Hz, 1H), 6.40 (d, J = 2.3 Hz, 1H), 4.55 (dd, J = 11.4,
4.4 Hz, 1H), 4.30 (dd, J = 11.3, 8.5 Hz, 1H), 3.83 (s, 3H), 3.04 (t, J =
7.0 Hz, 2H), 2.66 (ddd, J = 12.9, 8.3, 4.8 Hz, 1H), 1.99 – 1.89 (m,
2H), 1.87 – 1.80 (m, 1H), 1.62 (m, 1H). 13C NMR (150 MHz,
CDCl3) δ 199.7, 193.0, 165.8, 163.4, 136.8, 133.0, 129.1, 128.6,
128., 114.4, 110.0, 100.5, 70.7, 55.6, 45.4, 38.3, 26.1, 21.6. LRMS
(ESI): [M + Na]+ 347.2; HRMS (ESI-TOF) m/z calcd for
C20H20O4Na, 347.1259, [M + Na]+, found 347.1264.
5-bromo-3-(4-oxo-4-phenylbutyl)chroman-4-one (3la). Yield 51
mg, 46%; white solid, mp 72-73 °C; Rf = 0.40 (PE/EA = 5:1 v/v). 1H
NMR (600 MHz, CDCl3) δ 8.01 – 7.88 (m, 2H), 7.61 – 7.53 (m, 1H),
7.46 (dd, J = 10.5, 4.9 Hz, 2H), 7.31 – 7.25 (m, 1H), 7.22 (t, J = 8.0
Hz, 1H), 6.94 (dd, J = 8.3, 1.2 Hz, 1H), 4.57 (dd, J = 11.4, 4.6 Hz,
1H), 4.29 (dd, J = 11.4, 9.2 Hz, 1H), 3.04 (td, J = 7.2, 1.5 Hz, 2H),
2.77 (tdd, J = 7.6, 6.6, 5.2 Hz, 1H), 2.01 – 1.78 (m, 3H), 1.66 – 1.45
(m, 2H). 13C NMR (150 MHz, CDCl3) δ 199.6, 192.5, 162.8, 136.8,
134.8, 133.1, 128.6, 128.3, 128.0, 121.7, 118.7, 117.5, 69.9, 46.1,
38.2, 25.8, 21.5. LRMS (ESI): [M + Na]+ 395.0; HRMS (ESI-TOF)
m/z calcd for C19H17O3BrNa, 395.0259, [M + Na]+ , found 395.0264.
6-fluoro-3-(4-oxo-4-phenylbutyl)chroman-4-one (3ga). Yield 45
mg, 48%; white solid, mp 102-103 °C; Rf = 0.40 (PE/EA = 5:1 v/v).
1H NMR (600 MHz, CDCl3) δ 8.09 – 7.87 (m, 2H), 7.67 – 7.51 (m,
2H), 7.46 (dd, J = 10.6, 4.8 Hz, 2H), 7.19 (ddd, J = 9.0, 7.7, 3.2 Hz,
1H), 6.95 (dd, J = 9.1, 4.2 Hz, 1H), 4.56 (dd, J = 11.5, 4.5 Hz, 1H),
4.30 (dd, J = 11.5, 9.0 Hz, 1H), 3.05 (t, J = 7.0 Hz, 2H), 2.72 (ddd, J
= 13.4, 8.8, 5.3 Hz, 1H), 2.04 – 1.88 (m, 2H), 1.88 – 1.76 (m, 1H),
1.67 – 1.48 (m, 1H). 13C NMR (150 MHz, CDCl3) δ 199.5, 193.5,
157.7 (d, J = 1.7 Hz), 157.2 (d, J = 241.8 Hz), 136.8, 133.1, 128.6,
128.0, 123.3 (d, J = 24.8 Hz), 120.9 (d, J = 6.5 Hz), 119.4 (d, J = 7.3
Hz), 112.3 (d, J = 23.2 Hz), 70.5, 45.6, 38.2, 25.8, 21.4. 19F NMR
(565 MHz, CDCl3) δ -121.4. LRMS (ESI): [M + Na]+ 335.1; HRMS
(ESI-TOF) m/z calcd for C19H17O3FNa, 335.1059, [M + Na]+, found
335.1064.
5-chloro-3-(4-oxo-4-phenylbutyl)chroman-4-one (3ma). Yield 39
mg, 40%; oil; Rf = 0.47 (PE/EA = 5:1 v/v). H NMR (600 MHz,
1
CDCl3) δ 7.96 (dd, J = 8.3, 1.2 Hz, 2H), 7.62 – 7.53 (m, 1H), 7.46
(dd, J = 10.8, 4.7 Hz, 2H), 7.31 (t, J = 8.1 Hz, 1H), 7.03 (dd, J = 7.9,
1.0 Hz, 1H), 6.90 (dd, J = 8.4, 1.0 Hz, 1H), 4.56 (dd, J = 11.4, 4.6
Hz, 1H), 4.30 (dd, J = 11.4, 9.1 Hz, 1H), 3.05 (td, J = 7.2, 1.7 Hz,
2H), 2.76 (tdd, J = 7.6, 6.6, 4.7 Hz, 1H), 1.99 – 1.89 (m, 2H), 1.88 –
1.79 (m, 1H), 1.68 – 1.61 (m, 1H). 13C NMR (150 MHz, CDCl3) δ
199.6, 192.5, 162.8, 136.8, 134.5, 134.4, 133.1, 128.6, 128.0, 124.6,
117.8, 116.8, 69.9, 46.5, 38.2, 25.8, 21.5. LRMS (ESI): [M + Na]+
351.1; HRMS (ESI-TOF) m/z calcd for C19H17O3ClNa, 351.0764,
[M + Na]+, found 351.0768.
7-fluoro-3-(4-oxo-4-phenylbutyl)chroman-4-one (3ha). Yield 36
mg, 38%; white solid, mp 99-100 °C; Rf = 0.47 (PE/EA = 5:1 v/v).
1H NMR (600 MHz, CDCl3) δ 7.98 – 7.93 (m, 2H), 7.90 (dd, J = 8.7,
6.7 Hz, 1H), 7.56 (dd, J = 10.6, 4.2 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H),
6.73 (td, J = 8.5, 2.4 Hz, 1H), 6.65 (dd, J = 9.8, 2.3 Hz, 1H), 4.58
(dd, J = 11.5, 4.5 Hz, 1H), 4.33 (dd, J = 11.4, 8.9 Hz, 1H), 3.04 (t, J
= 6.9 Hz, 2H), 2.71 (ddd, J = 17.0, 8.8, 5.0 Hz, 1H), 1.99 – 1.88 (m,
2H), 1.88 – 1.82 (m, 1H), 1.63 – 1.58 (m, 1H). 13C NMR (150 MHz,
CDCl3) δ 199.5, 192.8, 167.33 (d, J = 255.8 Hz), 163.14 (d, J = 13.6
Hz), 136.8, 133.1, 129.9 (d, J = 11.4 Hz), 128.6, 128.0, 117.5 (d, J =
2.3 Hz), 109.8 (d, J = 22.7 Hz), 104.4 (d, J = 24.5 Hz), 70.8, 45.5,
38.2, 25.8, 21.4. 19F NMR (565 MHz, CDCl3) δ -100.8. LRMS
(ESI): [M + Na]+ 335.1; HRMS (ESI-TOF) m/z calcd for
C19H17O3FNa, 335.1059, [M + Na]+, found 335.1064.
7-chloro-3-(4-oxo-4-phenylbutyl)chroman-4-one (3na). Yield 47
mg, 48%; white solid, mp 108-109 °C; Rf = 0.40 (PE/EA = 5:1 v/v).
1H NMR (600 MHz, CDCl3) δ 8.01 – 7.91 (m, 2H), 7.89 – 7.75 (m,
1H), 7.64 – 7.50 (m, 1H), 7.52 – 7.39 (m, 2H), 6.99 (td, J = 4.5, 1.9
Hz, 2H), 4.58 (dd, J = 11.5, 4.5 Hz, 1H), 4.44 – 4.12 (m, 1H), 3.04 (t,
J = 7.0 Hz, 2H), 2.81 – 2.57 (m, 1H), 2.01 – 1.87 (m, 2H), 1.88 –
1.78 (m, 1H), 1.65 – 1.59 (m, 1H). 13C NMR (150 MHz, CDCl3) δ
199.5, 193.2, 161.8, 141.6, 136.8, 133.1, 128.67, 128.65, 128.0,

8
Tetrahedron
ACCEPTED MANUSCRIPT
122.2, 119.1, 117.8, 70.7, 45.6, 38.2, 25.8, 21.4. LRMS (ESI): [M
Hz, 2H), 7.75 (d, J = 7.6 Hz, 1H), 7.59 (t, J = 7.1 Hz, 1H), 7.47 (d, J
+ Na]+ 351.1; HRMS (ESI-TOF) m/z calcd for C19H17O3ClNa,
351.0764, [M + Na]+, found 351.0768.
= 7.7 Hz, 1H), 7.37 (t, J = 7.4 Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), 3.87
(s, 3H), 3.37 (dd, J = 17.2, 7.9 Hz, 1H), 3.05 – 2.93 (m, 2H), 2.90
(dd, J = 17.2, 3.8 Hz, 1H), 2.71 (ddt, J = 12.2, 8.2, 4.2 Hz, 1H), 2.14
– 1.95 (m, 1H), 1.95 – 1.79 (m, 2H), 1.67 – 1.47 (m, 1H). 13C NMR
(150 MHz, CDCl3) δ 208.7, 198.5, 163.4, 153.8, 136.7, 134.7, 130.3,
130.0, 127.3, 126.6, 123.9, 113.7, 55.4, 47.3, 38.0, 32.7, 31.1, 22.2.
LRMS (ESI): [M + Na]+ 331.1; HRMS (ESI-TOF) m/z calcd for
C20H20O3Na, 331.1310, [M + Na]+, found 331.1314
8-chloro-3-(4-oxo-4-phenylbutyl)chroman-4-one (3oa). Yield 54
mg, 55%; white solid, mp 116-117°C; Rf = 0.43 (PE/EA = 5:1 v/v).
1H NMR (600 MHz, CDCl3) δ 7.95 (d, J = 7.4 Hz, 2H), 7.81 (dd, J =
7.9, 1.5 Hz, 1H), 7.60 – 7.54 (m, 2H), 7.47 (t, J = 7.7 Hz, 2H), 6.97
(t, J = 7.8 Hz, 1H), 4.70 (dd, J = 11.5, 4.5 Hz, 1H), 4.42 (dd, J =
11.5, 9.0 Hz, 1H), 3.05 (t, J = 7.0 Hz, 2H), 2.78 (ddd, J = 13.4, 8.6,
5.2 Hz, 1H), 2.01 – 1.89 (m, 2H), 1.90 – 1.81 (m, 1H), 1.68 – 1.59
(m, 1H). 13C NMR (150 MHz, CDCl3) δ 199.5, 193.3, 156.9, 136.8,
135.8, 133.1, 128.6, 128.0, 126.0, 122.5, 121.8, 121.5, 71.0, 45.5,
38.2, 25.7, 21.4. LRMS (ESI): [M + Na]+ 351.1;HRMS (ESI-TOF)
m/z calcd for C19H17O3ClNa, 351.0764, [M + Na]+, found 351.0768.
2-(4-(3,4-dimethoxyphenyl)-4-oxobutyl)-2,3-dihydro-1H-inden-
1-one (5af). Yield 51 mg, 51%; colorless oil; Rf = 0.18 (PE/EA = 5:1
1
v/v). H NMR (600 MHz, CDCl3) δ 7.75 (d, J = 7.6 Hz, 1H), 7.64 –
7.56 (m, 2H), 7.53 (d, J = 1.9 Hz, 1H), 7.48 (t, J = 5.6 Hz, 1H), 7.37
(t, J = 7.4 Hz, 1H), 6.89 (d, J = 8.4 Hz, 1H), 3.95 (s, 3H), 3.94 (s,
3H), 3.38 (dd, J = 17.2, 7.9 Hz, 1H), 3.10 – 2.94 (m, 2H), 2.90 (dd, J
= 17.2, 3.9 Hz, 1H), 2.71 (ddt, J = 9.6, 8.2, 4.2 Hz, 1H), 2.11 – 1.98
(m, 1H), 1.98 – 1.81 (m, 2H), 1.67 – 1.43 (m, 1H). 13C NMR (150
MHz, CDCl3) δ 208.7, 198.5, 153.7, 153.2, 149.0, 136.7, 134.7,
130.2, 127.3, 126.6, 123.9, 122.7, 110.1, 110.03, 56.07, 55.98, 47.3,
37.8, 32.7, 31.1, 22.3. LRMS (ESI): [M + Na]+ 361.1; HRMS (ESI-
TOF) m/z calcd for C21H22O4Na, 361.1416, [M + Na]+, found
361.1420.
3-(4-oxo-4-phenylbutyl)-2H-benzo[h]chromen-4(3H)-one (3pa).
Yield 54 mg, 53%; white solid, mp 116-117 °C; Rf = 0.42 (PE/EA =
5:1 v/v). H NMR (600 MHz, CDCl3) δ 8.29 (d, J = 8.3 Hz, 1H),
1
7.98 – 7.92 (m, 2H), 7.87 (d, J = 8.7 Hz, 1H), 7.78 (d, J = 8.1 Hz,
1H), 7.61 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 7.58 – 7.50 (m, 2H), 7.46
(dd, J = 10.7, 5.0 Hz, 2H), 7.40 (d, J = 8.7 Hz, 1H), 4.80 (dd, J =
11.4, 4.5 Hz, 1H), 4.53 (dd, J = 11.3, 8.8 Hz, 1H), 3.06 (t, J = 7.1
Hz, 2H), 2.80 (ddd, J = 10.2, 8.5, 5.0 Hz, 1H), 2.11 – 1.93 (m, 2H),
1.93 – 1.80 (m, 1H), 1.77 – 1.63 (m, 1H). 13C NMR (150 MHz,
CDCl3) δ 199.7, 193.9, 159.7, 137.3, 136.8, 133.1, 129.5, 128.6,
128.0, 127.8, 126.2, 124.7, 123.4, 122.1, 121.0, 114.9, 71.2, 45.2,
38.3, 26.2, 21.6. LRMS (ESI): [M + Na]+ 367.1; HRMS (ESI-TOF)
m/z calcd for C23H20O3Na, 367.1310, [M + Na]+, found 367.1315.
2-(4-cyclohexyl-4-oxobutyl)-2,3-dihydro-1H-inden-1-one (5aj).
Yield 47 mg, 56%; white solid, mp 70-71 °C; Rf = 0.61 (PE/EA =
5:1 v/v). H NMR (600 MHz, CDCl3) δ 7.74 (d, J = 7.6 Hz, 1H),
1
7.69 – 7.53 (m, 1H), 7.46 (d, J = 7.7 Hz, 1H), 7.36 (t, J = 7.4 Hz,
1H), 3.35 (dd, J = 17.2, 7.9 Hz, 1H), 2.87 (dd, J = 17.2, 3.9 Hz, 1H),
2.65 (ddd, J = 13.7, 8.2, 4.2 Hz, 1H), 2.58 – 2.43 (m, 2H), 2.33 (tt, J
= 11.2, 3.4 Hz, 1H), 1.91 (tdd, J = 10.6, 8.3, 5.1 Hz, 1H), 1.79 (ddd,
J = 11.8, 7.8, 5.0 Hz, 4H), 1.74 – 1.65 (m, 3H), 1.50 – 1.40 (m, 1H),
1.37 – 1.14 (m, 5H). 13C NMR (150 MHz, CDCl3) δ 213.8, 208.7,
153.8, 136.7, 134.7, 127.3, 126.6, 123.9, 50.9, 47.3, 40.3, 32.7, 31.0,
28.5, 25.8, 25.6, 21.4. LRMS (ESI): [M + Na]+ 307.2; HRMS (ESI-
TOF) m/z calcd for C19H24O2Na, 307.1674, [M + Na]+, found
307.1678.
2-(4-oxo-4-phenylbutyl)-2,3-dihydro-1H-inden-1-one (5aa). Yield
59 mg, 60%; white solid, mp 66-67 °C; Rf = 0.50 (PE/EA = 5:1 v/v).
1H NMR (600 MHz, CDCl3) δ 7.96 (dd, J = 5.1, 3.3 Hz, 2H), 7.75
(d, J = 7.6 Hz, 1H), 7.66 – 7.52 (m, 2H), 7.46 (dd, J = 11.0, 4.7 Hz,
3H), 7.37 (t, J = 7.4 Hz, 1H), 3.38 (dd, J = 17.2, 7.9 Hz, 1H), 3.20 –
2.95 (m, 2H), 2.91 (dd, J = 17.2, 3.9 Hz, 1H), 2.71 (ddd, J = 13.7,
8.2, 4.2 Hz, 1H), 2.15 – 1.98 (m, 1H), 1.98 – 1.81 (m, 2H), 1.67 –
1.50 (m, 1H). 13C NMR (150 MHz, CDCl3) δ 208.7, 199.9, 153.7,
136.9, 136.7, 134.7, 133.0, 128.6, 128.0, 127.4, 126.6, 123.9, 47.3,
38.4, 32.7, 31.0, 21.9. LRMS (ESI): [M + Na]+ 301.1; HRMS (ESI-
TOF) m/z calcd for C19H18O2Na, 301.1204, [M + Na]+, found
301.1208.
2-(4-oxoundecyl)-2,3-dihydro-1H-inden-1-one (5am). Yield 59
mg, 66%; colorless oil; Rf = 0.73 (PE/EA = 5:1 v/v). H NMR (600
1
MHz, CDCl3) δ 7.79 – 7.71 (m, 1H), 7.59 (td, J = 7.5, 1.2 Hz, 1H),
7.52 – 7.44 (m, 1H), 7.40 – 7.33 (m, 1H), 3.35 (dd, J = 17.2, 7.9 Hz,
1H), 2.86 (dd, J = 17.1, 3.9 Hz, 1H), 2.65 (ddt, J = 9.4, 8.3, 4.2 Hz,
1H), 2.52 – 2.43 (m, 2H), 2.40 – 2.36 (m, 2H), 1.92 (dddd, J = 13.4,
10.5, 6.2, 4.5 Hz, 1H), 1.76 – 1.63 (m, 2H), 1.60 – 1.52 (m, 2H), 1.51
– 1.41 (m, 1H), 1.32 – 1.16 (m, 8H), 0.87 (t, J = 7.1 Hz, 3H). 13C
NMR (150 MHz, CDCl3) δ 211.0, 208.6, 153.7, 136.7, 134.7, 127.3,
126.6, 123.8, 47.3, 42.9, 42.4, 32.7, 31.6, 30.9, 29.2, 29.0, 23.8, 22.6,
21.4, 14.0. LRMS (ESI): [M + Na]+ 323.2; HRMS (ESI-TOF) m/z
calcd for C20H28O2Na, 323.1987, [M + Na]+, found 323.1991.
2-(4-(4-(tert-butyl)phenyl)-4-oxobutyl)-2,3-dihydro-1H-inden-1-
one (5ac). Yield 55 mg, 55%; colorless oil; Rf = 0.61 (PE/EA = 5:1
v/v). 1H NMR (600 MHz, CDCl3) δ 8.07 – 7.80 (m, 2H), 7.75 (d, J =
7.6 Hz, 1H), 7.59 (td, J = 7.6, 1.1 Hz, 1H), 7.52 – 7.41 (m, 3H), 7.36
(t, J = 7.2 Hz, 1H), 3.37 (dd, J = 17.2, 7.9 Hz, 1H), 3.18 – 2.96 (m,
2H), 2.91 (dd, J = 17.2, 3.9 Hz, 1H), 2.70 (ddd, J = 13.7, 8.2, 4.2 Hz,
1H), 2.15 – 1.96 (m, 1H), 1.96 – 1.80 (m, 2H), 1.57 (tdd, J = 15.0,
9.9, 5.3 Hz, 1H), 1.34 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 208.7,
199.6, 156.7, 153.8, 136.7, 134.7, 134.3, 128., 127.3, 126.6, 125.5,
123.9, 47.3, 38.2, 35.1, 32.7, 31.14, 31.10, 22.1. LRMS (ESI): [M +
Na]+ 357.2; HRMS (ESI-TOF) m/z calcd for C23H26O2Na, 357.1830,
[M + Na]+, found 357.1835.
5-fluoro-2-(4-oxo-4-phenylbutyl)-2,3-dihydro-1H-inden-1-one
(5ba). Yield 55 mg, 62%; white solid, mp 65-66 °C; Rf = 0.42
(PE/EA = 5:1 v/v). H NMR (600 MHz, CDCl3) δ 7.96 (d, J = 7.3
1
Hz, 2H), 7.74 – 7.50 (m, 2H), 7.47 (t, J = 7.7 Hz, 2H), 7.24 (d, J =
7.5 Hz, 1H), 6.97 (t, J = 8.6 Hz, 1H), 3.38 (dd, J = 17.4, 8.0 Hz, 1H),
3.17 – 2.98 (m, 2H), 2.92 (dd, J = 17.4, 4.0 Hz, 1H), 2.73 (ddd, J =
13.6, 8.5, 4.2 Hz, 1H), 2.19 – 1.97 (m, 1H), 1.97 – 1.79 (m, 2H), 1.71
– 1.38 (m, 1H). 13C NMR (150 MHz, CDCl3) δ 204.7, 199.8, 159.0
(d, J = 263.9 Hz), 155.8 (d, J = 2.1 Hz), 136.9, 136.6 (d, J = 8.1 Hz),
133.0, 128.6, 128.0, 124.5 (d, J = 12.4 Hz), 122.4 (d, J = 4.2 Hz),
114.2 (d, J = 19.7 Hz), 47.8, 38.3, 32.7, 31.0, 21.8. 19F NMR (565
MHz, CDCl3) δ -114.6. LRMS (ESI): [M + Na]+ 319.1; HRMS (ESI-
TOF) m/z calcd for C19H17O2FNa, 319.1110, [M + Na]+, found
319.1114.
2-(4-([1,1'-biphenyl]-4-yl)-4-oxobutyl)-2,3-dihydro-1H-inden-1-
one (5ad). Yield 48 mg, 48%; white solid, mp 117-118 °C; Rf = 0.
(PE/EA = 5:1 v/v). H NMR (600 MHz, CDCl3) δ 8.13 – 7.96 (m,
1
2H), 7.76 (d, J = 7.7 Hz, 1H), 7.71 – 7.66 (m, 2H), 7.63 (dd, J = 8.2,
1.0 Hz, 2H), 7.59 (td, J = 7.6, 1.1 Hz, 1H), 7.48 (dd, J = 10.5, 4.4
Hz, 3H), 7.43 – 7.33 (m, 2H), 3.39 (dd, J = 17.2, 7.9 Hz, 1H), 3.23 –
2.97 (m, 2H), 2.92 (dd, J = 17.2, 3.9 Hz, 1H), 2.72 (ddd, J = 13.6,
8.3, 4.2 Hz, 1H), 2.17 – 1.99 (m, 1H), 2.01 – 1.81 (m, 2H), 1.60 (m,
1H). 13C NMR (150 MHz, CDCl3) δ 208.7, 199.5, 153.8, 145.7,
139.8, 136.7, 135.6, 134.8, 128.9, 128.6, 128.2, 127.4, 127.2, 126.6,
123.9, 47.3, 38.4, 32.8, 31.1, 22.0. LRMS (ESI): [M + Na]+ 377.2;
HRMS (ESI-TOF) m/z calcd for C25H22O2Na, 377.1517, [M + Na]+,
found 377.1523.
2-(4-(4-(tert-butyl)phenyl)-4-oxobutyl)-5-fluoro-2,3-dihydro-1H-
inden-1-one (5bc). Yield 52 mg, 50%; colorless oil; Rf = 0.47
(PE/EA = 5:1 v/v). H NMR (600 MHz, CDCl3) δ 8.09 – 7.79 (m,
1
2H), 7.55 (td, J = 7.9, 5.0 Hz, 1H), 7.51 – 7.37 (m, 2H), 7.24 (dd, J =
7.6, 0.5 Hz, 1H), 6.97 (t, J = 8.6 Hz, 1H), 3.38 (dd, J = 17.4, 8.0 Hz,
1H), 3.11 – 2.96 (m, 2H), 2.92 (dd, J = 17.4, 4.1 Hz, 1H), 2.73 (ddd,
2-(4-(4-methoxyphenyl)-4-oxobutyl)-2,3-dihydro-1H-inden-1-one
(5ae). Yield 49 mg, 54%; white solid, mp 67-68 °C; Rf = 0.35
1
(PE/EA = 5:1 v/v). H NMR (600 MHz, CDCl3) δ 7.94 (d, J = 8.8

9
7.
Tan, Q.; Yang, Z.; Jiang, D.; Cheng, Y.; Yang, J.; Xi, S.; Zhang, M.
Angew. Chem. Int. Ed. 2019, 58, 6420−6424.
J = 13.8, 8.4, 4.3 Hz, 1H), 2.12 – 1.97 (m, 1H), 1.97 – 1.79 (m, 2H),
ACCEPTED MANUSCRIPT
1.58 (dtd, J = 13.4, 10.2, 5.1 Hz, 1H), 1.34 (s, 9H). 13C NMR (151
MHz, CDCl3) δ 204.8, 199.5, 159.0 (d, J = 263.8 Hz), 156.8, 155.8
(d, J = 2.1 Hz), 136.6 (d, J = 7.9 Hz), 134.3, 128.0, 125.5, 124.5 (d, J
= 12.3 Hz), 122.4 (d, J = 3.5 Hz), 114.2 (d, J = 19.2 Hz), 47.8, 38.2,
35.1, 32.7, 31.0, 31.0, 21.9. 19F NMR (565 MHz, CDCl3) δ -114.6.
LRMS (ESI): [M + Na]+ 375.1; HRMS (ESI-TOF) m/z calcd for
C23H25O2FNa, 375.1736, [M + Na]+, found 375.1736.
8.
(a) Varghese, L.; Agarwal, C.; Tyagi, A.; Singh, R. P.; Agarwal, R.
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2-((6-oxo-4-(2-oxo-2-phenylethyl)heptyl)oxy)benzaldehyde
(9).
Yield 48 mg, 45%; colorless oil, mp 77-78°C; Rf = 0.38 (PE/EA =
10. Maiti, A.; Cuendet, M.; Croy, V. L.; Endringer, D. C.; Pezzuto, J. M.;
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1
5:1 v/v). H NMR (600 MHz, CDCl3) δ 10.47 (s, 1H), 7.98 (d, J =
7.6 Hz, 2H), 7.82 (dd, J = 7.6, 1.4 Hz, 1H), 7.57 (t, J = 7.3 Hz, 1H),
7.54 – 7.50 (m, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.01 (t, J = 7.5 Hz,
1H), 6.95 (d, J = 8.4 Hz, 1H), 4.06 (t, J = 6.3 Hz, 2H), 3.09 (dd, J =
16.5, 6.5 Hz, 1H), 2.97 (dd, J = 16.5, 6.4 Hz, 1H), 2.67 (dt, J = 12.8,
6.4 Hz, 1H), 2.61 – 2.54 (m, 2H), 2.17 (s, 3H), 1.96 – 1.82 (m, 2H),
1.67 – 1.53 (m, 2H).13C NMR (150 MHz, CDCl3) δ 208.1, 199.5,
189.8, 161.3, 136.9, 135.9, 133.2, 128.6, 128.3, 128.1, 124.8, 120.6,
112.4, 68.2, 47.8, 42.6, 30.6, 30.4, 30.1, 26.5. LRMS (ESI): [M +
Na]+ 375.1; HRMS (ESI-TOF) m/z calcd for C22H24O4Na, 375.1572,
[M + Na]+, found 375.1576.
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Acknowledgements
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This work was financially supported by Science Foundation for
Distinguished Scholars of Dongguan University of Technology
(Nos. GC200906-10), Postdoctor Foundation of Dongguan
University of Technology (No. 196100040006), leading talents
of innovation and entrepreneurship of the Dongguan City D2017
(16), National Natural Science Foundation of China (No.
51773165) and Young Talent Support Plan of Xi´an Jiaotong
University.
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Appendix A. Supplementary data
Supplementary data to this article can be found online at
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ACCEPTED MANUSCRIPT
Synthesis of chroman-4-one and indanone derivatives via silver
catalyzed radical ring opening/coupling/cyclization cascade
Qiang Liua,b, Guanqun Xiea, Qiang Wanga,b, Zhendong Moa, Chen Lia, Shujiang Dingb,
Xiaoxia Wanga,
a School of Materials Science and Engineering, Dongguan University of Technology, Dongguan, 523808, China
b Department of Applied Chemistry, School of Science, Xi’an Jiaotong University, Xi’an, 710049, China
Highlights
1. The research provided an efficient route for the construction of
chroman-4-one and indanone derivatives via silver-catalyzed radical ring
opening/coupling/cyclization cascade reactions.
2. The reaction proceeds under mild and neutral conditions with broad substrate
scope and affords the desired products starting from readily available
cyclopropanols and alkenyl aldehydes.
3. A probable mechanism for the cascade reaction was proposed based on
several elegantly designed control experiments.
Corresponding author. e-mail: wangxx@dgut.edu.cn