Visible light mediated oxidative lactonization of 2-methyl-1,1′-biaryls for the synthesis of benzocoumarins

Article abstract of DOI:10.1039/c9ob00529c

A visible light mediated oxidative lactonization of 2-methyl-1,1′-biaryls was developed, giving benzocoumarins in good yields. The reaction features multiple C-H functionalization processes with oxygen as the final oxidant. The corresponding 2-aldehdyes, alcohols and carboxylic acids of the 1,1′-biaryls also worked well for the reaction.

Full text of DOI:10.1039/c9ob00529c

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Visible light mediated oxidative lactonization of 2-methyl-1,1’-
biaryls for the synthesis of benzocoumarins
Zhi Luoa,b Zhong-Hua Gao,a,b Zhi-Yong Song,a,b You-Feng Hana,b and Song Ye*,a,b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A visible light mediated oxidative lactonization of 2-methyl-1,1’- (Scheme 1). The lactonization of 2'-halo-1,1'-biaryl-2-carboxylic
biaryls was developed, giving benzocoumarins in good yields. The acids was reported under copper-catalyzed10 or base-mediated
reaction features multiple C-H functionalization with oxygen as conditions (path a).11 The dehydrogenative lactonization of 2-
the final oxidant. The corresponding 2-aldehdyes, alcohols and arylbenzoic acids was realized under transitional metals12, 5c or
carboxylic acids of the 1,1’-biaryls also worked well for the photocatalysis13 (path b). In addition, the metal-catalyzed
reaction.
oxidative aryl C–H lactonization of 2-arylbenzaldehyde was
successfully demonstrated (path c).14 Furthermore, the metal-
catalyzed oxidative carbonylation of 2-arylphenol was also
established (path d).15 Despite of these advances, two or one
functional group is required for the reaction (paths a-d). In this
Benzo-3,4-coumarin is the core structure of many natural
products with unique biological activities,1 such as Urolithin A2
Alternariol3 and Atenuisol4 (Fig. 1). In addition, benzocoumarin
can serve as key intermediate for the synthesis of various
natural products.5 Recently, these molecules have also found
applications in smart materials.6
communication, we report
a photocatalyzed oxidative
lactonization of 2-methyl-1,1'-biphenyls (path e), which
features metal-free C-H functionalization without the
requirement of functional groups.
Fig. 1 Selected bioactive benzocoumarins.
Many methods have been developed for the synthesis of
benzo-3,4-coumarin, including the classical intramolecular
esterification of 2'-hydroxy-[1,1'-biphenyl]-2-carboxylic acid,7
Baeyer-Villiger oxidation of fluorenones8 and oxidation of
benzylic C-H bonds in 6H-benzo[c]chromenes.9 Recently, the
transition metal-catalyzed coupling and C-H functionalized
reaction have been reported for the synthesis of benzo-3,4-
coumarins from readily available biphenyl compounds
Scheme 1 Synthesis of benzo-3,4-coumarins from biphenyl compounds.
Inspired by the photocatalyzed oxidative C(sp3)-H
functionalization by Fukuzumi16 and Cibulka,17 we were
interested in the synthesis of benzo-3,4-coumarins from 2-
methyl-1,1'-biphenes under photocatalysis. The reaction 5-
chloro-2-methyl-1,1'-biphenyl (1a) with O2 (balloon) as oxidant
was irradiated with blue LEDs in the presence of [Acr-Mes]ClO4
as the photocatalyst and HCl as co-catalyst (Table 1). We were
encouraged to find that the reaction in acetonitrile gave the
desired product benzocoumarin 2a in 33% yield without
chlorinated byproducts (Table 1, entry 1). Water as the co-
a.Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of
Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of
Sciences, Beijing 100190, China. E-mail: songye@iccas.ac.cn.
b.University of Chinese Academy of Sciences, Beijing 100049, China.
Electronic Supplementary Information (ESI) available: Experimental procedures
and spectroscopic data. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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solvent was then investigated, and the yield was improved to withdrawing group at either aryl ring worked weVlliewtoArgticivleeOntlhinee
DOI: 10.1039/C9OB00529C
50% when MeCN/H2O (2:1) was used as the mixed solvent desired benzo-3,4-coumarins (2b-2h) in good yields. The
(entries 2-5). Increasing the loading of HCl to 2 equivalents led reaction of 2-methyl-1,1'-biphenyl resulted in some loss of the
to slight improvement of the yield (entry 6). Better yield (65%) yield (2i). Unfortunately, the reaction of 2-methyl-1,1'-biaryls
was realized when the loading of photocatalyst was increased with electron-donating groups, such as methoxyl, gave only
to 4 mol% (entry 7).
trace or no product under current condition.
Table 1 Reaction optimization.a
PC
(x mol%).
2.5
2.5
2.5
2.5
2.5
2.5
4.0
HCl
(y equiv.)
0.2
0.2
0.2
0.2
0.2
2.0
2.0
entry
solvent
yield (%)b
MeCN (1 mL)
33
36
42
50
33
55
65
1
2
3
4
5
6
7
MeCN/H2O (10:1 )
MeCN/H2O (5:1 )
MeCN/H2O (2:1 )
MeCN/H2O (1:1 )
MeCN/H2O (2:1 )
MeCN/H2O (2:1 )
a Reaction conditions: 1a (0.3 mmol), PC (x mol %), HCl (4M in 1,3-dioxane, y
equiv.), oxygen (balloon), blue LEDs, solvent (1 mL), RT, 48 h. b Isolated yield.
Scheme 3 Investigation on the scope of the reaction.
The success of photocatalyzed oxidative lactonization of 2-
methyl-1,1'-biphenyls under mild condition promoted us to
investigate the reaction of corresponding 2-aldehyde, alcohol
and carboxylic acid (scheme 3). It was found that the reaction
of 2-aldehyde-biaryls
smoothly to give the products (2d and 2g
Interestingly, the one with electron-donating group (methyl)
worked as well 2j). Notably, the reaction of 3'-
(trifluoromethyl)-[1,1'-biphenyl]-2-carbaldehyde showed
3
with electron-withdrawing group went
,
2d) in good yields.
(
perfect regioselectivity to give the oxidative lactonization
product (2k) exclusive at the para-position. The reaction of 2-
alcohol-biaryls
4 gave the desired products (2g and 2i) in
reasonable yields. Finally, the reaction of 2-phenylbenzoic acid
(5
) gave benzocoumarin 2b in high yield (85%).
To classify the mechanism of the photocatalyzed
dehydrogenative lactonization reaction, some control
experiments were carried out (Scheme 4). It was found that no
reaction occurred when light or photocatalyst was absent
(reactions a & b). The yield of product was dramatically
decreased without the addition of hydrochloride (reaction c).
The reaction was totally prohibited when two equivalence of
Scheme 2 Reaction of 2-methyl-1,1'-biaryls.
With the optimized reaction conditions in hand, a series of
2-methyl-1,1'-biaryls was then investigated for the reaction
(Scheme 2). It was found that biaryls with electron-
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TEMPO was added as the radical inhibit (reaction d). Finally,
the oxidation of benzaldehyde and benzyl alcohol under the
standard conditions afforded benzoic acid in good yields
(reactions e & f).
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DOI: 10.1039/C9OB00529C
Fig. 2 Plausible catalytic cycle.
In conclusion, the visible-light photocatalytic tandem
multiple C-H oxidation and dehydrogenative lactonization of 2-
methyl-1,1'-biaryls was developed to give benzocoumarins in
good yields. This methodology features multiple C-H
functionalization using O2 as the final oxidant under mild
conditions. In addition, the corresponding aldehydes, alcohol
and acid of the 1,1'-biaryls also worked for the reaction.
Scheme 4 Control experiments.
Acknowledgements
Financial support from the National Natural Science
Foundation of China (Nos 21425207, 21521002 and 21702208),
and the Chinese Academy of Sciences is greatly acknowledged.
Based on the experimental results and literature
18
reports,16b-d,
a plausible mechanism of the reaction is
described in Fig. 2. Irradiation of the photocatalyst gives its
electron-transfer state (Acr•–Mes•+)19 that can oxidize Cl¯ to
Cl•. A hydrogen of the methyl group of 1,1'-biphenyl is
abstracted by Cl• to afford benzyl radical
I
. It should be noted Conflicts of interest
that the benzyl radical I can also be directly generated via the
The authors declare no conflicts of interest
single electron transfer with excited photocatalyst when no
hydrochloride is added according to control experiment
(Scheme 4, reaction c). The oxidation of benzyl radical by
oxygen affords peroxyl radical II, which is decomposed under
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DOI: 10.1039/C9OB00529C
Mes
O
N
O
X
ClO4
Me
PC (4.0 mol%)
Ar
Ar'
Ar
Ar'
HCl (2.0 equiv.)
O2 (balloon), blue LEDs
MeCN/H2O (2:1), RT, 48-72 h
X = Me, CH2OH,
CHO, COOH
48-85% yield
A visible light mediated C-H lactonization of 2-methyl-1,1’-biaryls with oxygen as the
oxidant was developed, giving benzocoumarins in good yields.