One-pot cascade reactions of 1-arylpenta-3,4-dien-2-ones leading to 2-arylphenols and dibenzopyroanones

Article abstract of DOI:10.1039/c4cc06204c

A one-pot cascade reaction of 1-arylpenta-3,4-dien-2-ones with activated ketones allowed for an efficient and sustainable synthesis of 2-arylphenols. Moreover, this reaction was also found to be compatible and combinable with Pd-catalyzed C-H activation a

Full text of DOI:10.1039/c4cc06204c

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One-pot cascade reactions of 1-arylpenta-3,4-
dien-2-ones leading to 2-arylphenols and
dibenzopyroanones†
Cite this: Chem. Commun., 2014,
50, 14968
Received 8th August 2014,
Accepted 6th October 2014
Yan He, Xinying Zhang* and Xuesen Fan*
DOI: 10.1039/c4cc06204c
www.rsc.org/chemcomm
A one-pot cascade reaction of 1-arylpenta-3,4-dien-2-ones with
activated ketones allowed for an efficient and sustainable synthesis
of 2-arylphenols. Moreover, this reaction was also found to be
compatible and combinable with Pd-catalyzed C–H activation and
carbonylation of the in situ formed 2-aryl phenols, thus resulting in a
highly convenient and atom-economic synthesis of dibenzopyranones.
Cascade reactions are emerging as attractive tools in organic
chemistry since they combine two or more chemical steps in
one pot and enable the construction of complex molecules
from simple and easily available starting materials.1,2
Scheme 1 Michael addition/aldol condensation/C–H activation/carbo-
nylation leading to dibenzopyranones from allenic ketones.
The dibenzopyranone unit has been found in a wide range of
natural products, pharmaceuticals and functional materials.3 Due to More interestingly, this conjugate addition is often followed by
their importance, the search for novel and efficient synthesis of simultaneous cyclization(s) to afford various cyclic compounds.
dibenzopyranones remains a hot topic in the synthetic community.4 This has been well pioneered by Ma’s synthesis of a-pyrones from
Recently, Inamoto,5 Shi,6 and Chuang7 have independently devel- the tandem reaction of allenic ketones with diethyl malonate.9 Our
oped an elegant approach toward dibenzopyranones through metal- own effort has also resulted in some efficient synthesis of benzoic
catalyzed CO insertion of 2-arylphenols. While this C–H activation and heterocyclic compounds through reactions of allenic ketones
and carbonylation process itself was atom-economical compared with different nucleophiles.10 Inspired by these results, we found a
with classical coupling methods starting from pre-functionalized new synthesis of 2-arylphenols via a base-promoted Michael addi-
substrates, a retroactive look of this method revealed that the 2- tion of activated ketones onto the readily obtainable 1-arylpenta-
arylphenols used therein were in most cases prepared beforehand 3,4-dien-2-ones followed by an intramolecular aldol condensation,
by Pd-catalyzed coupling between o-iodo phenols and arylboronic a process that allows for the synthesis of a wide range of 2-arylated
acids (Scheme 1). The necessity of step-by-step operation and the phenols. Interestingly, this tandem process was found to be
pre-introduction and subsequent loss of the stoichiometric amounts compatible and combinable with a palladium-catalyzed C–H acti-
of boronic acid and iodide functions may compromise the sustain- vation and carbonylation of the in situ formed 2-arylphenol, thus
ability of this strategy.
resulting in a highly convenient one-pot process toward dibenzo-
Allene derivatives are valuable intermediates in synthetic pyranones featured with atom economy and operational simplicity
chemistry owing to their diverse reactivity.8 Among them, the as shown in Scheme 1.11
electron-deficient allenic ketones have been proved as good electro-
Initially, 1-phenylpenta-3,4-dien-2-one (1a) and ethyl 3-oxo
philes for conjugate addition with active methylene compounds. butanoate (2a) were selected as model substrates for our study
(Table 1). We found that the reaction of 1a and 2a proceeded
School of Environment, School of Chemistry and Chemical Engineering,
Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine
Chemicals, Henan Key Laboratory for Environmental Pollution Control,
Henan Normal University, Xinxiang, Henan 453007, P. R. China.
E-mail: xuesen.fan@htu.cn, xinyingzhang@htu.cn
smoothly under the promotion of 1 equiv. of K2CO3 in CH3CN
at 80 1C for 4 h to generate ethyl 6-hydroxy-2,4-dimethyl-[1,10-bi
phenyl]-3-carboxylate (3a) in 78% yield (Table 1, entry 1). Following
studies on the effect of different bases showed that Cs2CO3 gave
the best yield and its optimum dosage turned out to be 1 equiv.
(entries 2–8). In the absence of a base, no reaction was observed
† Electronic supplementary information (ESI) available: Experimental procedures,
characterisation data and NMR spectra. See DOI: 10.1039/c4cc06204c
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Table 1 Optimization studies for the formation of 3aa
Table 2 Synthesis of 2-arylphenols (3)a,b
Entry
Base
Solvent
T (1C)
Yieldb (%)
1
2
3
4
K2CO3
Cs2CO3
NaOH
Na2CO3
Et3N
Cs2CO3
Cs2CO3
Cs2CO3
—
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
EtOH
80
80
80
80
80
80
80
80
80
100
40
Reflux
80
Reflux
80
78
85
50
56
Trace
71
48
29
—
83
58
76
80
81
83
80
5
6c
7d
8e
9
10
11
12
13
14
15
16
DMF
THF
DCE
Toluene
80
a
Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), base (0.5 mmol),
b
c
d
solvent (5 mL), 4 h. Isolated yield. 1 mmol of base. 0.25 mmol of
base. 0.1 mmol of base.
e
(entry 9). In following studies, we found temperature higher or lower
than 80 1C did not improve the yield of 3a (entries 10 and 11).
Furthermore, changing CH3CN to EtOH, DMF, THF, DCE or toluene
as the reaction medium gave a slightly decreased yield (entries 12–16).
In summary of the optimization, treatment of 1a and 2a with 1 equiv.
of Cs2CO3 in CH3CN at 80 1Cfor4hgave3a in a yield of 85% (entry 2).
To confirm the generality of this one-pot synthesis of 2-aryl-
phenols (3), we examined a variety of 1-arylpenta-3,4-dien-2-ones (1)
under the optimized reaction conditions. The results in Table 2
showed that 1 with either electron-donating or electron-withdrawing
group(s) on the aryl ring underwent this cascade process smoothly to
give 3 in good to excellent yields. Notably, fluoride was compatible
a
Reaction conditions: 0.5 mmol of 1, 0.6 mmol of 2, 0.5 mmol of
b
Cs2CO3, 5 mL of CH3CN, 80 1C, 4 h. Isolated yield.
with the reaction conditions (3d). In addition, reactions of 1 bearing have an adverse effect on the formation of 4a, anhydrous Na2SO4
a methyl, ethyl or aryl group on the internal or terminal position of was added as a dehydrating agent. In this case, the yield could be
the allene moiety proceeded effectively to afford 2-arylphenols with improved to 68%. Notably, the two phases of this cascade process
diverse substitution patterns (3e–3u). As a further aspect, with were well compatible in that not only was it unnecessary to isolate
1-thioenyl allenic ketone, 3k was obtained successfully. Next, the the intermediate 2-phenylphenol, but also was it needless to change
scope of the ketone substrates (2) was studied. In addition to or remove the solvent or the base promoter.
b-ketoester, b-diketone or b-cyanoketone reacted with 1 smoothly
Encouraged by the above results, we then studied the generality
to give 3k–3u in good yields. Interestingly, from the reactions of cyclo- of this novel synthesis of dibenzopyranone. The results listed in
hexane-1,3-dione, dibenzochromenones (3k–3n)wereobtained.With Table 3 showed that all the substrates tested could be successfully
pentane-2,4-dione as a substrate, on the other hand, the reactions converted into the corresponding products in good yields (4a–4r).
went through a more sophisticated process to give the corresponding The R1 unit of 1 could be neutral H, or an electron-donating methyl,
deacetylated 2-arylphenols (3o–3s).12
methoxy or electron-withdrawing fluoro group and the R2 and R3
With the establishment of a simple and sustainable synthesis units could be H, or an alkyl or aryl group. Meanwhile, the R5
of 2-arylphenols, their compatibility and combinability with the fragment of 2 could be an ester, keto or cyano group. The inclusion
Pd-catalyzed C–H activation and carbonylation required for the of these versatile functional groups makes further structural mani-
formation of dibenzopyranones were studied. Thus, 1a and 2a pulations of 4 easy to implement. Interestingly, starting from a
was treated with 1 equiv. of Cs2CO3 in CH3CN at 80 1C for 4 h. 1-thioenyl allenic ketone, thieno[3,2-c]pyran-4-one (4h) with potential
To the resulting mixture were added Pd(OAc)2 (10 mol%) and anti-cancer activity could be conveniently obtained.13 It is worth
AgOAc (3 equiv.). It was then stirred at 80 1C under a CO atmo- noting that this cascade reaction was regio-selective and favored the
sphere.7 From this one-pot reaction, the desired ethyl 1,3-dimethyl- formation of less sterically hindered products 4c, 4j and 4o.
6-oxo-6H-benzo[c]chromene-2-carboxylate (4a) was obtained in a
Based on the above observations and previous reports, plausible
yield of 36%. Considering that water formed along with 3a could pathways to account for the formation of 3a and 4a were proposed
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Table 3 One-pot syntheses of dibenzopyranones (4)a,b
good efficiency. These novel methodologies are complementary to
previously reported synthetic procedures and enable easy and sustain-
able access to poly-substituted phenols and dibenzopyranones.
We are grateful to the National Natural Science Foundation
of China (21172057, 21272058), RFDP (20114104110005),
PCSIRT (IRT1061) and 2012IRTSTHN006 for financial support.
Notes and references
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a
Reaction conditions: 0.2 mmol of 1, 0.24 mmol of 2, 0.2 mmol of Cs2CO3,
0.2 mmol of anhydrous Na2SO4, 4 mL of CH3CN, 80 1C, 4 h; then, CO (1 atm),
0.02 mmol of Pd(OAc)2, 0.6 mmol of AgOAc, 80 1C, 48 h. b Isolated yield.
in Scheme 2. Initially, the base triggers the cascade process by
deprotonating 2a to give anion A, which then undergoes a Michael
addition onto 1a to afford the second anion B. Tautomerization of B
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Scheme 2 Plausible mechanisms for the formation of 3a and 4a.
14970 | Chem. Commun., 2014, 50, 14968--14970
This journal is ©The Royal Society of Chemistry 2014