Synthesis of Benzoaryl-5-yl(2-hydroxyphenyl)methanones via Photoinduced Rearrangement of (E)-3-Arylvinyl-4H-chromen-4-ones

Article abstract of DOI:10.1021/acs.orglett.7b03007

A concise and efficient photoinduced rearrangement of (E)-3-arylvinyl-4H-chromen-4-ones for the synthesis of benzoaryl-5-yl(2-hydroxyphenyl)methanones is described. Benzoaryl-5-yl-(2-hydroxyphenyl)methanones were obtained in 77-95% yields via the irradiation of (E)-3-arylvinyl-chromones in the 95% EtOH with a high-pressure mercury lamp at room temperature under Ar atmosphere. The reported method provides a novel procedure for the synthesis of α,α′-diaryl ketone derivatives without addition of any transition metals and oxidants or other additives. A plausible mechanism was proposed, and the rearrangement product was characterized by NMR, HRMS, and X-ray.

Full text of DOI:10.1021/acs.orglett.7b03007

Letter
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
pubs.acs.org/OrgLett
Synthesis of Benzoaryl-5-yl(2-hydroxyphenyl)methanones via
Photoinduced Rearrangement of (E)‑3-Arylvinyl‑4H‑chromen-4-ones
Jinming Fan, Tao Wang, Chenchen Li, Rui Wang, Xiaoyu Lei, Yong Liang,† and Zunting Zhang*
Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering
Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, and School of Chemistry and Chemical
Engineering, Shaanxi Normal University, Xi’an 710119, People’s Republic of China
*
S Supporting Information
ABSTRACT: A concise and efficient photoinduced rearrange-
ment of (E)-3-arylvinyl-4H-chromen-4-ones for the synthesis
of benzoaryl-5-yl(2-hydroxyphenyl)methanones is described.
Benzoaryl-5-yl-(2-hydroxyphenyl)methanones were obtained
in 77−95% yields via the irradiation of (E)-3-arylvinyl-
chromones in the 95% EtOH with a high-pressure mercury
lamp at room temperature under Ar atmosphere. The reported
method provides a novel procedure for the synthesis of α,α′-
diaryl ketone derivatives without addition of any transition metals and oxidants or other additives. A plausible mechanism was
proposed, and the rearrangement product was characterized by NMR, HRMS, and X-ray.
ight, as a clean, convenient energy, usually needs short
reaction time with high atom efficiency in many reactions.
Scheme 1. Reported Synthesis of (2-
Hydroxyphenyl)(naphthalen-2-yl)-methanone
1
L
After the photon was absorbed by the substrates, electrons transit
from the ground state to the excited state, and as a result, the
structure and properties of the molecule were changed. Since
there is no requirement for additional additives or reagents for
the photochemical reaction, it demonstrates the meaning of
2
green chemistry. Nowadays, photochemical reaction has been
used as a practical synthetic method in various areas of organic
3
4
chemistry, such as total synthesis, asymmetric synthesis and
5
6
temperature to give ortho-hydroxyl-substituted diaryl ketone
metal catalysis, green organic synthesis, photolabile protecting
15b
7
8
product in better yield 98% (path c).
In our group, various complicated fused-polyheterocyclics,
groups, and so on. Photoinduced rearrangement is a common
9
phenomenon in photochemistry. Rearrangement of diary-
16
e.g., 2H-phenanthro[9,10-c]pyrazoles, dibenzo [f,h][1,2,4]-
lethenes, which usually involves photoinduced cyclization,
sigmatropic hydrogen shift, opening of an aromatic ring, and
formation of rearrangement products, is one of the typical
1
7
triazolo[3,4-b]quinazolines, 7a-phenyl-1a,7a-dihydrobenzo-
1
8
19
pyrano[2,3-b]azirin-7-ones, polybenzoquinazolines, benzo-
2
0
10
[c]furo[2,3-a]xanthenone, 14H-dibenzo[a,c]-xanthen-14-
photoinduced rearrangements and has been recently reviewed.
21 22
one, benzo[e]-chromeno[2,3-g]indol-13(1H)-one, and C5-
Due to its biological activity, α,α′-diaryl ketone skeleton was
23
modified pyrimidine and pyrimidine nucleoside derivatives
usually considered a biologically active moiety in pharmaceutical
1
1
were synthesized via photochemical process. In 1996, Silva et al.
reported that the photo-oxidative cyclization of (E)-2-styryl-
chromones at ambient temperature for 30−50 days in the open
air gave 12H-benzo[a]xanthene-12-ones in moderate yields
chemistry. The ortho-hydroxyl-substituted diaryl ketone
12
moiety has been found in some natural products, and potential
13
biological activity was observed as well. However, only a few
1
4
methods have been reported, and either elevated temperature
24
15
(Scheme 2). In this Letter, interestingly, when (E)-3-styryl-
chromone 1a was irradiated by UV light, the rearrangement
product (2-hydroxyphenyl)(naphthalen-2-yl)methanone 2a was
obtained. We demonstrated a simple and efficient protocol for
the synthesis of benzoaryl-5-yl-(2-hydroxyphenyl)methanones 2
via the photoinduced rearrangement of (E)-3-arylvinyl-chro-
menes 1 with irradiation by a high-pressure mercury lamp at
room temperature under Ar atmosphere (Scheme 3).
or transition-metal catalyst was required for the reaction to
proceed smoothly.
Treatment of β-naphthoic acid with 2-(trimethylsilyl)phenyl
trifluoromethanesulfonate in the presence of cesium fluoride at
1
25 °C for 24 h gave the corresponding product in 44% yield via
the rearrangement of a four-membered ring intermediate
1
4
(Scheme 1, path a). Alternatively, Pd-catalyzed direct arylation
of salicylaldehyde with 2-naphthaleneboronic acid in DMF under
O atmosphere afforded (2-hydroxyphenyl)(naphthalen-2-yl)-
2
15a
methanone in 65% yield (path b). Later on, [Cp*RhCl ] was
Received: September 25, 2017
2
2
successfully applied to the same substrates with slightly elevated
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b03007
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Synthesis of 12H-benzo[a]xanthen-12-one by
Photochemical Reaction of (E)-2-Styryl-4H-chromen-4-one
entry 8). Notably, lower or higher reaction concentration or
open air condition decreased the yields of 2a (entries 9−11).
Thus, the irradiation of 1a (5 mM) in 95% EtOH at ambient
temperature under Ar atmosphere for 1 h was determined to be
the optional conditions.
With the optimized condition determined, the scope of and
generality for rearrangement of (E)-3-arylvinyl-4H-chromen-4-
ones 1 were subsequently explored (Scheme 4). Thus, a wide
Scheme 3. Synthesis of Benzoaryl-5-yl(2-
hydroxyphenyl)methanones 2 via the Photoinduced
Rearrangement of (E)-3-Arylvinyl-4H-chromen-4-ones 1
a
Scheme 4. Scope of the Reaction
The substrate (E)-3-styryl-chromone 1a was synthesized on
25
the basis of the literature report. The photoinduced rearrange-
ment of 1a was performed at ambient temperature under the UV
irradiation with Ar atmosphere (Table 1). Initially, irradiation of
a
Table 1. Optimization of the Reaction Conditions
concn
(mM)
time
b
yield
c
entry
solvent
atmosphere
(h)
(%)
1
2
3
4
5
6
7
8
9
ACE
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
air
5
5
5
5
5
5
5
5
3
7
5
12
4
6
1
1
1
1
1
1
1
1
40
64
53
83
80
70
84
91
80
DCM
ACN
EtOH
MeOH
EtOH/H O (5:1)
2
EtOH/H O (7:1)
2
95% EtOH
95% EtOH
95% EtOH
95% EtOH
d
10
1
81
a
Irradiation of 1a (5 mM) in 95% EtOH (50 mL) with high-pressure
1
83
mercury lamp (500 W) at room temperature under Ar atmosphere.
The ratios of 2f/2f* and 2g/2g* were determined by H NMR.
a
Irradiation of 1a (0.25 mmol) in various solvents (50 mL, 5 mM)
1
with high-pressure mercury lamp (500 W) at room temperature.
b
Reaction time was determined by complete consumption of 1a.
c
d
1
range of substrates 1 with different functional groups were
subjected to the optimal condition to give corresponding
rearrangement products 2 in moderate to high yields (77−
95%). Although slightly longer reaction time was required, higher
yields of 2 were obtained for the substrates bearing an electron
withdrawing group (EWG) at the para-position of the phenyl
group compared to those with an electron donating group
(EDG) (2b−2e, 2i). The presence of m-Me or m-OMe in the
substrates led to the formation of 2 in a mixture of two
regioisomers with the ratio of ∼5:4 (2f−2g), which could
probably be explained by the steric hindrance. Various di- and
trisubstituted substrates have also been explored (2j−2n).
The effect of the various substituents on the chromen-4-one
ring was also investigated. Although the presence of EWG
significantly shortened reaction time compared to those bearing
EDG, the rearrangement products were still obtained in excellent
Isolated yields. 5% 1a was left by H NMR determination.
1
a in acetone with a high-pressure mercury lamp (500 W) at
room temperature for 12 h yielded (2-hydroxyphenyl)-
naphthalen-2-yl)methanone 2a in 40% yield (Table 1, entry
). Yields of 2a increased slightly in dichloromethane or
acetonitrile (53−64%) with shorter reaction time 4−6 h, (entries
−3). It is surprising to find out that protic solvents could
(
1
2
significantly improve the rearrangement efficiency to give 2a in
over 80% within 1 h (entries 4−5). Inspired by the interesting
result, a significant amount of water was added to alcohol.
However, the corresponding product 2a was obtained in either
lower yield (entry 6) or comparable yield with extended reaction
time (entry 7). Interestingly, the yield of 2a was successfully
boosted to 91% by limiting the added water to 5% (95% ethanol,
B
DOI: 10.1021/acs.orglett.7b03007
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
yields (Scheme 4, 2o−2aa). Replacement of phenyl with
naphthalene and heteroaromatics require extended reaction
time to give 2 in desired yields, especially for 2ad and 2ae. In
summary, a wide range of functional groups (halogen and NO2)
could be successfully tolerated, which provide possibility for
further modification.
with a high-pressure mercury lamp led to the formation of 1a-(Z)
via photoisomerization, followed by a 6π-electron-cyclization to
give intermediate A. This is a typical well-known cyclization for
28
diarylethenes and has been recently well reviewed. Due to the
presence of hydrogens at C1/C2, the rearomatization of the core
(naphthalene ring) was proposed to proceed via sigmatropic
The structure of 2 was established via H NMR, 13C NMR,
1
rearrangement along with the C1−O bond cleavage. Thus,
27b
HRMS, IR, and X-ray structure of 2h. The molecular structure of
intermediate B was proposed to be generated via a thermal
suprafacial [1,9]-H shift. It was believed that the presence of a
26
2
h was depicted in Figure 1. The ortho-hydroxyl-substituted
27b
carbonyl group
significantly facilitates the rearrangement
process. As a result of proton migration and the opening of the
heterocyclic pyran ring, rearrangement product 2a was isolated
as the only product via the restoration of aromaticity. The
presence of an intramolecular hydrogen bond between the
hydroxyl group and the carbonyl group might further stabilize 2a.
To the best of our knowledge, only few similar examples for the
9
,27,29
described rearrangement were reported.
In summary, we have successfully investigated the photo-
chemical property of (E)-3-arylvinyl-4H-chromen-4-ones, which
provided access to the rearrangement product benzoaryl-5-yl(2-
hydroxyphenyl)methanones in high yields under Ar atmosphere
with the irradiation of a high-pressure mercury lamp at room
temperature. The advantages of the demonstrated method
include (a) excellent functional group tolerance, (b) nontoxic
solvent (95% EtOH), (c) no requirement of transition metal/
additives, (d) good to excellent yields, and (e) high atom
efficiency. The rearrangement is believed to proceed via trans−
cis photoisomerization, electron-cyclization, [1,9]-sigmatropic
shift, and rearomatization, which led to the pyran ring-opening to
Figure 1. ORTEP (30%) diagram of compound 2h.
diaryl ketone moiety of 2h included three benzene rings [A (C1−
C6), B (C8−C10, C15−C17), and C (C10−C15)]. An
intramolecular O−H···O hydrogen bond was observed, and
the bond length was 2.593 Å. The dihedral angle of the benzene
ring (A) and naphthalene ring (BC) was 45.9°. It was worthy to
note that the π−π stacking was not observed in the X-ray
structure of 2h.
The UV absorption spectra of 1a and 2a are shown in Figure 2.
Due to the formation of a carbonyl group and expansion of
27a
give a more stable product.
ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b03007.
Experimental procedures and detailed characterization
data of all new compounds (PDF)
X-ray data of 2h (CIF)
AUTHOR INFORMATION
Corresponding Author
■
Figure 2. UV absorption spectra of 1a and 2a in ethanol.
*
E-mail: zhangzt@snnu.edu.cn.
aromatic rings, the typical π → π* absorption was observed at
ORCID
−1
−1
2
92 nm (ε = 28200 L·mol ·cm ) and 312 nm (ε = 23200 L·
−1
−1
Jinming Fan: 0000-0001-5187-4136
Tao Wang: 0000-0002-1494-5297
Chenchen Li: 0000-0002-2956-7639
Yong Liang: 0000-0002-7225-7062
Zunting Zhang: 0000-0003-0806-2452
Present Address
mol ·cm ) in 1a, which were nearly in accordance with the
excited 297 and 313 nm light of a high-pressure mercury lamp.
The absorption of 2a was 267, 301, and 350 nm.
9
,10,27
On the basis of experimental data and literature reports,
a
plausible mechanism for the formation of 2a was proposed and
presented in Scheme 5. It is believed that irradiation of 1a-(E)
†
Department of Molecular Medicine, Beckman Research
Scheme 5. Proposed Mechanism for Rearrangement of 1a
Institute of City of Hope, Duarte, California 91010, United
States.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for financial support from the National Natural
Science Foundation of China (Nos: 21672132 and 21502110)
and the Fundamental Funds Research for the Central
Universities (No: GK201503034).
C
DOI: 10.1021/acs.orglett.7b03007
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(
26) Crystallographic data have been submitted to the Cambridge
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DOI: 10.1021/acs.orglett.7b03007
Org. Lett. XXXX, XXX, XXX−XXX