Synthesis of: Cis / trans -dihydrochromenones via a photoinduced rearrangement of 4-phenyl-3-aryl/cyclohexenylcoumarins

Article abstract of DOI:10.1039/d1ob01058a

A concise and environmentally friendly protocol has been developed for the synthesis of cis-dihydrochromenones and trans-dihydrochromenones in EtOH at room temperature. Irradiation of 4-phenyl-3-arylcoumarins in EtOH with 313 nm UV light under an argon atmosphere at room temperature gave cis-4b,15c-dihydro-16H-benzofuro[3′,2′:7,8]phenanthro[9,10-c]chromen-16-ones and cis-8c,14b-dihydro-9H-benzo[11,12]chryseno[5,6-c]chromen-9-ones in good yields. And an analogous treatment of 4-phenyl-3-alkenylcoumarins as 4-phenyl-3-arylcoumarins provided trans-1,2,3,4,4a,14b-hexahydro-5H-phenanthro[9,10-c]chromen-5-ones. The described photorearrangement proceeded smoothly without the addition of any transition metals and additives. The photorearrangement of 4-phenyl-3-arylcoumarins is believed to proceed via 6π-electrocyclization, a [1,3]-hydrogen shift and keto-enol isomerization.

Full text of DOI:10.1039/d1ob01058a

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Synthesis of cis/trans-dihydrochromenones via a
photoinduced rearrangement of 4-phenyl-
3-aryl/cyclohexenylcoumarins†
Cite this: DOI: 10.1039/d1ob01058a
Wangxi Gao, Lixin Niu, Tao Wang,
Zunting Zhang
Yong Liang, ‡ Ding Wang * and
*
A concise and environmentally friendly protocol has been developed for the synthesis of cis-dihydrochro-
menones and trans-dihydrochromenones in EtOH at room temperature. Irradiation of 4-phenyl-3-aryl-
coumarins in EtOH with 313 nm UV light under an argon atmosphere at room temperature gave cis-
4b,15c-dihydro-16H-benzofuro[3’,2’:7,8]phenanthro[9,10-c]chromen-16-ones and cis-8c,14b-dihydro-
9H-benzo[11,12]chryseno[5,6-c]chromen-9-ones in good yields. And an analogous treatment of 4-
phenyl-3-alkenylcoumarins as 4-phenyl-3-arylcoumarins provided trans-1,2,3,4,4a,14b-hexahydro-5H-
phenanthro[9,10-c]chromen-5-ones. The described photorearrangement proceeded smoothly without
the addition of any transition metals and additives. The photorearrangement of 4-phenyl-3-arylcoumarins
is believed to proceed via 6π-electrocyclization, a [1,3]-hydrogen shift and keto–enol isomerization.
Received 1st June 2021,
Accepted 27th July 2021
DOI: 10.1039/d1ob01058a
rsc.li/obc
ment of trans-2,3,3a,11b-tetrahydro-1H-cyclopenta[l]phenan-
threnes with n-BuLi yielded cis-2,3,3a,11b-tetrahydro-1H-cyclo-
Introduction
According to the number of electrons involved in a given π penta[l]phenanthrenes in 75% yield (Scheme 1b).8
system, electrocyclic reactions can be summarized mainly into Photochemical syntheses of a few other cis-polyheterocyclic
4, 6 and 8π-electron electrocyclization reactions.1 They are compounds have been reported. In 2020, Jon D. Rainier
effective and predictable methods with excellent regio- and reported cis-fused dihydrophenanthrenes via irradiation of tri-
stereocontrol explained by Woodward–Hoffmann’s rules.2 In substituted cyclopentenones in the presence of TFA with a
recent years, 6π-electrocyclization reactions have been playing sig- 350 nm UV lamp in CHCl3 and trans-fused dihydrophenan-
nificant roles in the synthesis of complex target molecules,3 threnes were also obtained without TFA (Scheme 1c).9
especially in the synthesis of polyheterocyclic compounds and
stereochemical compounds.4 This reaction offers a diastereo selec-
tive method for the synthesis of fused polyheterocyclic com-
pounds.5
Irradiation
of
stilbene
analogues
through
6π-electrocyclization is one of the good strategies to synthesize
trans-polyheterocyclic compounds.6 For example, irradiation of
biphenyldihydropyridones in CH2Cl2 at room temperature with a
350 nm UV light gave trans-dihydrophenanthrenes (Scheme 1a).7
Photoinduced cyclization of 2-vinylbiphenyls gave trans-2,3,3a,11b-
tetrahydro-1H-cyclopenta[l]phenanthrenes. Subsequent treat-
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,
China. E-mail: zhangzt@snnu.edu.cn
†Electronic supplementary information (ESI) available. CCDC 2047431 (4b). For
ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
d1ob01058a
‡Present address: Department of Molecular Medicine, Beckman Research
Institute of City of Hope, Duarte, California 91010, USA.
Scheme 1 Synthesis of cis/trans compounds via 6π-electrocyclization.
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Table 1 Optimization of reaction conditionsa
Irradiation of 2,2′-diphenyl-3,3′-bibenzofurans with 300 nm UV
light under an oxygen atmosphere in the presence of
tetracyanoethylene (TCNE) yielded cis-phenyl[1-b]-hydroxy[2-b]-
naphthalenylidene-[1,2-b:4,3-b′]bisbenzofuran in 32% yield
(Scheme 1d).10
Our group has been focussing on the synthesis of aromatic
fused heterocyclic compounds via the photocyclic dehydro-
genation reaction without any oxidants or additives,11 such as
synthesizing polycyclic heteroaromatic coumarin derivatives
via the photoinduced dehydrogenative annulation of 4-phenyl-
3-heteroarylcoumarins (Scheme 2).11g Encouraged by our pre-
vious work, 3-(dibenzo[b,d]-furan-4-yl)-4-phenyl-2H-chromen-2-
ones (1) were irradiated in EtOH with UV light (313 nm) at
room temperature under an argon atmosphere. To our sur-
prise, cis-4b,15c-dihydro-16H-benzofuro[3′,2′:7,8]phenanthro
[9,10-c]chromen-16-ones (2) were obtained. In this paper, we
would like to report a strategy for the synthesis of cis/trans-
dihydrochromenones via irradiation of 4-phenyl-3-aryl/cyclo-
hexenylcoumarins in EtOH with UV light (313 nm) at room
temperature under an argon atmosphere (Scheme 3).
C
Timeb
(h)
Yieldc
(%)
Entry
Solvent (v/v)
(mol L−1
)
1
2
3
4
5
6
7
8
Acetonitrile
Dichloromethane
Acetone
N,N-Dimethylformamide
Toluene
Methanol
Ethanol
95% ethanol
Ethanol
Ethanol
Ethanol
Ethanol
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.020
0.010
0.004
0.002
0.005
5
5
4.5
6
6
4
4
5
6
5
4
4
4
35
38
43
28
27
49
58
55
43
45
48
46
32
9
10
11
12
13d
Ethanol
a Substrate 1a (0.25 m mol) was dissolved in various solvents (50 mL,
5 mM) and irradiated with a lamp (64 W, 313 nm) at room temperature
under Ar. b Reaction time was determined by the complete consump-
tion of 1a as indicated by thin layer chromatography (TLC). c Isolated
yields were based on 1a. d Performed under an open air atmosphere.
Results and discussion
3-(Dibenzo[b,d]furan-4-yl)-4-phenyl-2H-chromen-2-one 1a was
chosen as the substrate to optimize reaction conditions, and
the selected reaction conditions are summarized in Table 1.
Initially, irradiation of 1a (0.25 mmol) in CH3CN (50 mL) with
a lamp (313 nm) at room temperature for 5 h gave the photo-
rearrangement product 2a in 35% yield (Table 1, entry 1).
Higher yields of 2a were obtained in DCM or ACE (38–43%,
entries 2 and 3) compared with those in DMF and toluene
(27–28%, entries 4 and 5). Since the aprotic solvents did not
give acceptable results, polar protic solvents were further exam-
ined. To our delight, the yields of 2a were significantly elevated
in MeOH and EtOH (49% and 58%, entries 6 and 7). A slightly
worse result was obtained in 95% EtOH (55%, entry 8), which
indicated that the presence of water might inhibit the reactiv-
ity of the radical intermediate. Furthermore, various substrate
concentrations were explored. It was disappointing to observe
that either higher or lower substrate concentration led to
worse yields (entries 9–12). The worst yield of 2a was observed
when the reaction was performed in the open air (32%, entry
13). As a result, irradiation of 1a (5 mM) in EtOH at room
temperature under an Ar atmosphere was determined to be the
optimal conditions for the synthesis of 2a.
Scheme 2 Photoinduced dehydrogenative annulation of 4-phenyl-3-
heteroarylcoumarins.
With the optimized conditions in hand, the scope of 3-aryl-
4-phenyl-2H-chromen-2-ones 1 was explored and the results
are listed in Table 2. Generally, substrates 1 with electron-with-
drawing groups (CN or CF3) at the R1 or R3 position gave
photoinduced rearrangement products 2 in higher yields com-
pared to the substrates bearing an electron-donating group
(OMe). It could be further proved that substrates with two elec-
tron-withdrawing groups (CF3) led to even higher yields of 2f
and 2g (67%, 64%). It is worth noting that when a phenyl
group is present at the 3-position (R4 = Ph) of 1, only a trace
amount of the corresponding intramolecular rearranged
product was detected by 1H NMR.
It is surprising to find out that the treatment of 3-(cyclohex-
1-en-1-yl)-4-phenyl-2H-chromen-2-ones 3 under the optimized
Scheme 3 Synthesis of cis/trans-dihydrochromenones 2 and 4.
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Table 2 Synthesis of cis-dihydrochromenones 2 via irradiation of 1a,b
Table 3 Synthesis of trans-dihydrochromenones 4 via irradiation of 3a,b
a Irradiation of 1 (5 mM) in EtOH (50 mL) with a lamp (313 nm, 64 W)
at room temperature under an argon atmosphere. b Reaction time was
determined by the complete consumption of 1 as indicated by TLC.
Isolated yield.
a Irradiation of 3 (5 mM) in EtOH (50 mL) with a lamp (313 nm) at
room temperature under an argon atmosphere. b Reaction time was
determined by the complete consumption of 3 as indicated by TLC.
Isolated yield.
conditions yielded trans-1,2,3,4,4a,14b-hexahydro-5H-phenan-
thro[9,10-c]chromen-5-ones
4 in good yields (79%–93%)
(Table 3). Substrates 3 with electron-withdrawing groups (Ac, F
or CF3) at the R1, R2 or R3 positions gave photoinduced
rearrangement products 4 in higher yields compared to the
substrates bearing an electron-donating group (OMe or OEt). It
is important to note that only the trans-dihydro isomer was
obtained for 3-(cyclohex-1-en-1-yl)-4-phenyl-2H-chromen-2-one
3, whereas, the sole cis-dihydro isomer was isolated for 3-aryl-4-
phenyl-2H-chromen-2-one substrates 1. The crystal structure of
4b was characterized by single crystal X-ray diffraction, and
Scheme 4 Irradiation of 1b in CD3OD. The yields of 2b-2D, 2b-D, and
2b were determined by 1H NMR.
On the basis of literature reports12 and experimental evi-
detailed information is provided in the ESI. As illustrated in dence, a plausible mechanism for the formation of 2a is pro-
Fig. S2,† the molecule of 4b includes two benzene rings [A (C9, posed and illustrated in Scheme 5. Irradiation of 1a generates
C10, C11, C15, C21, C22) and D (C1, C3, C5, C12, C14, C17)], intermediate A via an intramolecular 6π-electrocyclization.12
one 2H-pyran-2-one ring B (C4, O1, C6, C7, C9, C10), one cyclo- Second, intermediate B is formed via a suprafacial [1,3]-H shift
hexa-1,3-diene ring C (C1, C2, C4, C5, C7, C8), and one cyclo- of intermediate A occurring twice. It is apparent that polar
hexane ring E (C2, O8, C16, C18, C19, C20). In the chair confor- protic solvent is beneficial for the process of [1,3]-H shift and
mation of cyclohexane, the two dihedral angles are P1[C(8), keto–enol isomerization; this accounts for the irradiation of 1b
C(16), C(20), C(18)]/P2 [C(8), C(2), C(18)] 128.61° and P1[C(8), in CD3OD, and 2b-2D and 2b-D were obtained. Third, the
C(16), C(20), C(18)]/P3 [C(16), C(19), C(20)] −129.93°. The keto–enol tautomerization of B led to the formation of inter-
twisted chair configuration of the formed cyclohexane and steric mediate C, and C was converted to the more stable 2a. The
hindrance might be responsible for the trans-configuration.
theoretical calculations results indicated that the energy of
In order to further examine and validate the mechanism for trans-4b,15c-dihydro-16H-benzofuro[3′,2′:7,8]phenanthro[9,10-
the formation of 2, irradiation of 1b in CD3OD with a lamp c]chrom-en-16-one (2a′) is higher than that of 2a (Fig. 1),
(313 nm) at room temperature under an Ar atmosphere led to which explains why trans 2a′ is easily converted to cis 2a.
the formation of 4b,15c-dideuterium of 2b (2b-2D, 88%), 15c-
A plausible mechanism for the formation of 4a is also pro-
deuterium of 2b (2b-D, 8%) and 2b (2b, 4%), separately posed and illustrated in Scheme 6. Irradiation of 3a with a
(Scheme 4).
313 nm lamp led to the formation of intermediate D, and this
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atom efficiency without any additives. The mechanism for the
photo- rearrangement of 4-phenyl-3-arylcoumarin to cis-dihydro-
chromenones involves 6π-electrocyclization, a [1,3]-hydrogen shift
occurring twice and keto–enol isomerization.
Experimental
General procedure for the preparation of 2 and 4
Substrate
3-(cyclohex-1-en-1-yl)-4-phenyl-2H-chromen-2-one
(3a) (150 mg, 0.5 mmol) was dissolved in EtOH (100 mL) at
ambient temperature in a quartz tube (100 mL). The solution
was degassed (ultrasound) for 30 min, deaerated by bubbling
argon for 30 min, irradiated with a lamp (30 W, 313 nm) at
room temperature until the reactant was consumed completely
as indicated by thin-layer chromatography (TLC). Then, the
volatiles were removed under reduced pressure, and the
residue was purified by column chromatography (ethyl acetate/
petroleum ether, 1 : 70) to give 4a (135 mg, 90%). Analogously,
compounds 2 were synthesized using the same methodology
described above, with 33–93% yields.
Scheme 5 Proposed possible mechanism for the formation of 2a.
Conflicts of interest
The authors declare no conflict of interest.
Acknowledgements
Fig. 1 The energy of 2a and 2a’: B3LYP/6-31G(d,p).
We are grateful for financial support from the National Natural
Science Foundation of China (No: 21672132).
Notes and references
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Conclusions
In conclusion, we have successfully demonstrated an approach for
the synthesis of cis-4b,15c-dihydro-16H-benzofuro[3′,2′:7,8] phenan-
thro[9,10-c]chromen-16-ones, cis-8c,14b-dihydro-9H-benzo[11,12]
chryseno[5,6-c]chromen-9-ones, and trans-1,2,3,4,4a,14b-hexahydro-
5H-phenanthro[9,10-c]chromen-5-ones by the irradiation of
4-phenyl-3-aryl/cyclohexenyl coumarin in EtOH with a lamp (64 W,
313 nm) at room temperature under an argon atmosphere. The
described method proceeded under mild conditions with high
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