Two-Step Access to β-Substituted o-Hydroxyphenyl Ethyl Ketones from 4-Chromanone and its Application in Preparation of a Silica-Supported Cobalt(II) Salen Complex

Article abstract of DOI:10.1002/adsc.202100705

The o-hydroxyphenyl ethyl ketone skeleton is prevalent in many biologically active natural products and active pharmaceutical ingredients. Herein, a two-step protocol has been developed for synthesis of various β-substituted o-hydroxyphenyl ethyl ketones.

Full text of DOI:10.1002/adsc.202100705

RESEARCH ARTICLE
doi.org/10.1002/adsc.202100705
Two-Step Access to β-Substituted o-Hydroxyphenyl Ethyl Ketones
from 4-Chromanone and its Application in Preparation of a
Silica-Supported Cobalt(II) Salen Complex
Luxia Guo,a Meng Ye,a Luigi Vaccaro,b Minghao Li,a,* and Yanlong Gua, c,*
a
Key Laboratory for Large-Format Battery Materials and System
Ministry of Education
Huazhong University of Science and Technology (HUST)
1037 Luoyu road, Hongshan District, Wuhan 430074, People’s Republic of China
E-mail: liminghaochem@hust.edu.cn; klgyl@hust.edu.cn
b
Laboratory of Green S.O.C.
Dipartimento di Chimica, biologia e Biotecnologie
Università degli Studi di Perugia
Via Elce di Sotto 8, 06123 Perugia, Italy.
State Key Laboratory for Oxo Synthesis and Selective Oxidation
c
Lanzhou Institute of Chemical Physics
Lanzhou, 730000, People’s Republic of China
Manuscript received: June 7, 2021; Revised manuscript received: July 27, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100705
Abstract: The o-hydroxyphenyl ethyl ketone skeleton is prevalent in many biologically active natural products
and active pharmaceutical ingredients. Herein, a two-step protocol has been developed for synthesis of various
β-substituted o-hydroxyphenyl ethyl ketones. A base-mediated ring opening of 4-chromanone was used to
introduce the β-ethoxyl o-hydroxyphenyl ethyl ketone intermediary, followed by nucleophile substitution under
BF3 ·Et2O assisted conditions to give the desired β-carbon, nitrogen, or thiol substituted o-hydroxyphenyl ethyl
ketones. With the aid of this protocol, a silica-supported cobalt(II) salen complex was successfully prepared
and its structure was confirmed by FTIR, 13C MAS NMR, UV-Vis absorption, and XPS spectra. The
immobilized cobalt(II) salen catalyst not only displayed comparable catalytic activity in the synthesis of
several heterocycles including 1,3-oxazolidine, benzimidazole, and benzoxazole as compared with their
homogeneous counterparts, but also could be recycled for several times without obvious loss of its catalytic
activity.
Keywords: β-Substituted o-hydroxyphenyl ethyl ketones; Supported cobalt(II) salen complex; 4-Chromanone;
Nucleophiles; Heterocycles
Introduction
pentamidine.[2] Flavaspidic acid AB isolated from the
rhizomes of Dryopteris crassirhizoma has been shown
Several biologically active natural products and active to exhibit radical scavenging and antibacterial
pharmaceutical ingredients feature a peculiar o-hydrox- activity.[3] Malabaricone C has been recently found to
yphenyl ethyl ketone skeleton (Figure 1). For example, be a suitable candidate in the treatment and prevention
Phloridzin, a naturally occurring compound extracted of obesity as a sphingomyelin synthase inhibitor.[4]
from the bark of pear, apple, cherry and other fruit Therefore, the construction of molecules with o-
trees, is a non-selective SGLT inhibitor and a Na+/K+ hydroxyphenyl ethyl ketone framework has attracted
-ATPase inhibitor.[1] Methylene-bis-aspidinol isolated the interest of the chemistry community.
from the leaves of Mallotus oppositifolius, has
O-hydroxyphenyl ethyl ketones are typically pre-
exhibited trypanocidal activity against Trypanosoma pared by the Fries rearrangement of phenol ester albeit
brucei brucei trypomastigotes similar to drug in some cases, with moderate regioselectivity
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Michael addition of o-hydroxyphenyl vinyl ketone
with a nucleophile is greatly appealing to furnish o-
hydroxyphenyl ethyl ketones because of the structural
diversity of nucleophile (Scheme 1e). However, the
lack of simple, cost-effective, and scalable method to
prepare o-hydroxyphenyl vinyl ketone[12] and its high
reactivity to undergo intramolecular cyclization (Sche-
me 1f) hamper its utilization.[13]
The ring-opening reactions of heterocycles have
gained a great prominence, as it not only opens
avenues for the creation of structurally novel mole-
cules with multiple functional groups but also enriches
the connotation of heterocyclic reactivities. Generally
the destruction of heterocycles can be classified into
three major categories: (i) the ring opening of highly
strained heterocycles, such as aziridines, epoxyethanes
etc.;[14] (ii) the gas evolution induced ring opening of
Figure 1. Representative bioactive molecules containing 2-
hydroxyphenyl alkyl ketones.
(Scheme 1a).[5] The condensation of o-acetylphenol medium-sized heterocycles such as denitrogenation of
with aromatic aldehyde followed by noble-metal- triazoles, decarboxylation of carbamate etc.;[15] (iii) the
catalysed hydrogenation provided an alternative way to ring opening of heterocycles containing labile frag-
generate β-aryl o-hydroxyphenyl ethyl ketones ments such as acetal, benzyl ether etc.[16] 4-Chroma-
(Scheme 1b).[6] In addition the hydroacylation of none was commercially available and also easily
salicylaldehyde with olefins,[7] oxidation of o-hydrox- prepared by the tandem oxa-Michael addition/cycliza-
ybenzyl alcohols,[8] electrophilic addition of o-hydrox- tion of phenol and acrylonitrile[17] or by tandem adol
ybenzamide or its congeners with organometallic condensation/oxa-Michael addition of o-acetylphenol
compounds,[9] hydration of o-ethynylphenols[10] (Sche- and paraformaldehyde.[18] The 4-chromanone was
me 1c) and CÀ H hydroxylation aryl alkyl ketone labile under either acidic or basic conditions.[19] The
(Scheme 1d),[11] have also been used to synthesize direct electrophilic ring opening of 4-chromanone with
some specific o-hydroxyphenyl ethyl ketones. From a nucleophile would be an ideal route to synthesize
the view of generation of molecular diversity, the various β-substituted o-hydroxyphenyl ethyl ketones.
However, it suffered from intramolecular cyclization
(Scheme 1f).[19a,b] Herein, we report our results on an
effective two-step protocol that allows synthesis of β-
substituted o-hydroxyphenyl ethyl ketones starting
from 4-chromanone and consisting in i) the base
promoted ring opening of 4-chromanone to give β-
ethoxyl o-hydroxyphenyl ethyl ketone 1a and ii) a
BF3·Et2O mediated substitution through the in situ
generation of boron difluoride complex 1b[20] followed
by releasing one molecular ethanol to form boron
difluoride complex 1c[21] that undergoes intermolecular
Michael addition to provide the desired β-substituted
o-hydroxyphenyl ethyl ketones (Scheme 1g). Notably,
the first step can be scalable while the second step
features a broad substrate scope, in which various C-,
N-, and S-based nucleophiles can be employed. With
the aid of this two-step protocol, a novel method to
prepare silica-supported cobalt(II) salen complexes has
also been developed, and the resulting heterogeneous
system showed excellent catalytic activities in the
oxidative synthesis of several heterocycles.
Results and Discussion
Initially, a base promoted electrophilic ring-opening
reaction with EtOH was explored. As shown in
Scheme 2a, the NaOH promoted ring opening of 4-
Scheme 1. General methods to furnish the o-hydroxyphenyl
ethyl ketone skeleton.
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Scheme 2. The synthesis of β-indolyl o-hydroxyphenyl ethyl
ketone.
Scheme 3. Substrate scope of BF3 ·Et2O promoted reactions
ofβ-ethoxyl o-hydroxyphenyl ethyl ketones and indoles.
chromanone was undemanding. The β-ethoxyl o-
hydroxyphenyl ethyl ketone 1a could be obtained in yl ethyl ketones 2 in good yields. The strong electron-
95% yield in a gram scale. With compound 1a in deficient β-ethoxyl 2-hydroxy-5-nitrophenyl ethyl ke-
hand, we started to explore the substitution of 1a with tone did not give the desired product, indicating the
a nucleophile. Indole is a well-known privileged electronic influence on the reaction. The reaction was
structure occurring in numerous natural products such sensitive to the substituents at the alpha position of 1a.
as alkaloids, peptides and it is also a natural carbon- β-ethoxyl o-hydroxyphenyl propyl ketone furnished
based nuclophile. Thus the simple indole was chosen the product (2s) in a high yield. But, the α-dimethyl β-
to react with 1a. However, the reaction was distress- ethoxyl o-hydroxyphenyl ethyl ketone could not be
ing. In the presence of a common acid such as PTSA, employed in this reaction (2t), implied 1c was the
TfOH, ZnCl2, and Sc(OTf)3 as catalyst, the desired reaction intermediate.
product was obtained in a poor yield due to the poor
Besides indole, other nucleophiles were also ex-
chemoselectivity detected by TLC (Table S1 in the plored as a reaction partner. As shown in Scheme 4,
supporting information). O-hydroxyacetophenone can electron-rich arenes such as sesamol, and 1,2,4-
react with BF3·Et2O to form boron difluoride acetyl- trimethoxybenzene, or electron-rich alkene such as
phenolate chelate easily.[20] Therefore, we envisioned 1,1-diphenylethylene were all applicable in this reac-
that the solid skeleton of boron difluoride complex tion (3a–c). Surprisingly, the pyrrole could not be
might be helpful to suppress aforementioned intra-
molecular cyclization. Accordingly, we tried to prepare
boron difluoride complex 1b, but unfortunately, only
the formation of compound 1a could be observed
(Scheme 2b). Then, the direct addition of 1.1 equiv-
alent of BF3·Et2O to the mixture of 1a and indole
through the generation of 1b in situ was investigated.
To our delight, the desired β-indolyl o-hydroxyphenyl
ethyl ketone 2a was obtained in a good 79% yield
(Scheme 2c).
The substrate scope was then explored. As shown
in Scheme 3, there was no significant electronic effect
on indole for this reaction. Both electron-rich and
electron-deficient indole participated in the reaction
smoothly, affording the desired products in the yields
of 50–81% under identical conditions. The scope of
the reaction with respect to β-ethoxyl o-hydroxyphenyl
ethyl ketone 1a was next investigated. 1a featuring an
alkyl, alkoxy, or halogen on the aromatic ring reacted
readily with indole to deliver β-indoly o-hydroxyphen-
Scheme 4. The substitution reactions of 1a with other nucleo-
philes.
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employed in this protocol and only complex mixtures acceptor, or a bisnucleophile to participate in synthesis
were obtained under standard reaction conditions, of substituted quinolone, cyclohexenone, coumarin,
although it is a typical electron-rich heteroarene. The and 3-benzofuranone (Scheme 5).
acetophenone, a Csp3-based nucleophile afforded the
To demonstrate the applicability of synthetic strat-
desired 1,5-dicarbonyl compound in 65% yield (3d). egy, a silica-immobilized cobalt(II) salen complex was
The nitrogen-based nucleophile, aniline, participated in prepared through BF3 ·Et2O promoted substitution of β-
the reaction smoothly affording the desired product 3e ethoxyl o-hydroxyphenyl ethyl ketone 1a with sulf-
in 54% yield. It is worth mentioning that 3e has been hydryl functionalized silica gel followed by condensa-
proved to be a potential antimicrobial agent.[22] tion with ethylenediamine that coordinated with Co-
Although a three-component Mannich reaction of (OAc)2·H2O to furnish the heterogeneous catalyst
formaldehyde, 2-hydroxyacetophenone and aniline has (Figure 2).
been reported to synthesize 3e, the yield is rather low
The FTIR spectra were collected to evaluate the
(less than 40%).[23] The reactions of 1a and sulfur- above process. As shown in Figure 3a, the HMS-SH
based nucleophiles, such as p-toluenethiol and benzyl showed a characteristic peak of À SH group at
mercaptan, proceeded also smoothly, giving products 2439 cmÀ 1.[24] After it reacted with 1a promoted by
3f and 3g in 89% and 82% yields, respectively.
BF3 ·Et2O, that peak disappeared, while it was accom-
It was noted that the β-ethoxyl o-hydroxyphenyl
ethyl ketone contained several functional groups,
which could also act as a biselectrophile, a 1,4-donor-
Scheme 5. Synthesis of cyclic compounds from 1a.
Figure 3. Catalyst characterization. (a) FTIR spectra, (b) 13
C
Figure 2. Schematic diagram of the procedure to immobilize
salen-type cobalt(II) schiff base complex.
MAS NMR spectra, (c) UV-Vis absorbtion spectra, (d–g) XPS
spectra, (h) TEM image of the HMS-Co-Salen.
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panied by the presence of the characteristic peaks of specific surface areas (BET) of HMS-Keto was almost
phenyl group (1400 cmÀ 1 to 1600 cmÀ 1) and C=O one half that of HMS-SH although their morphologies
group (1646 cmÀ 1), proving the successful immobiliza- were similar (Table S3). The specific surface areas of
tion of salicylaldehyde fragment.[25] The appearance of HMS-Co-Salen was 605 m2 gÀ 1 similar to that of HMS-
characteristic peak of C=N group at 1639 cmÀ 1 in the Keto.
FTIR spectrum of HMS-Salen implied the formation
The catalytic activity of HMS-Co-Salen was
of the salen ligand.[26] The FTIR spectrum of HMS-Co- evaluated in the representative cobalt(II)-catalysed
Salen slightly shifted toward bluer wavelengths com- oxidative cyclization reactions. As shown in Sche-
pared with HMS-Salen, suggesting the coordination of me 6a, The HMS-Co-Salen catalysed tandem CÀ N and
salen ligand with cobalt salt.[27] This process was also CÀ O bond formation of N-methylanilines with styrene
confirmed by the 13C MAS NMR spectra. As shown in oxides in the presence of TBHP via a one-pot sequence
Figure 3b, the peaks of HMS-Keto at 162 ppm and of SN2 ring opening of the epoxide, CÀ H functionaliza-
206 ppm could be assigned to the aromatic carbon tion and cyclization furnished 1,3-oxazolidines in
connected with the hydroxyl group and carbonyl yields of 52–72%, which was comparable with the
carbon, respectively. After HMS-Keto reacted with reported homogeneous protocol[32] and represented the
ethylenediamine, a peak at 154 ppm appeared, indica- first heterogeneous catalytic system to synthesis of 1,3-
tive of the formation of C=N bond. In the 13C MAS oxazolidines from N-methylanilines and styrene. The
NMR spectrum of HMS-Salen, the peak at 206 ppm HMS-Co-Salen catalyst could be recovered by filtra-
still existed suggesting the incomplete conversion of tion after the reaction and reused for 9 consecutive
HMS-Keto. The elemental analysis showed that the cycles without obvious loss of activity (Figure S3).
loading of salen ligand was 0.42 mmol/g (Table S2). In More importantly, there was no leached cobalt detected
the UV-Vis absorbtion spectrum of HMS-Salen (Fig- by ICP-AAS in the filtrate. The comparison between
ure 3c), there was an obvious absorption band at the fresh and recoverable catalysts in Co 2p XPS
415 nm, which was the characteristic absorption peak profile and FTIR spectrum had shown no obvious
of schiff base.[28] After HMS-Salen coordinated with differences (Figure S4). In addition, the HMS-Co-
cobalt, a new absorption peak at 600 nm appeared, Salen catalyst could also used in aerobic oxidative
which was attributed to the d-d electron transition of synthesis of benzimidazole and benzoxazole (Sche-
metal. The surface composition and chemical state me 6b). It is worth mentioning that the HMS-Co-Salen
were then investigated using X-ray photoelectron featured a long alkyl chain which made the Co-salen
spectroscopy (XPS). The wide survey spectrum of complex more flexible compared with conventional
HMS-Co-Salen (Figure 3d) showed that all of the heterogenerous Co-salen complexes prepared by chem-
essential elements could be detected, consistent with ical grafting that might account for its high catalytic
the result of EDX elemental maps (Figure S1). The N activities in above oxidative cyclization reactions.[33]
1s spectrum clearly evidenced the presence of nitrogen
atoms with three kinds of chemical environments: the
peaks at 399.2 and 400.8 eV were attributed to C=N…
Co and C=N groups, respectively, while the peak at
402.8 eV was attributed to À NH2 (Figure 3e).[29] These
results indicated that the cobalt ion mainly coordinated
with salen ligand instead of the ONN tridentate pincer
type schiff base ligand (Figure 2). In the spectrum of O
1s (Figure 3f), besides two predominant peaks
(533.4 eV for OÀ Si and 532.8 eV for OÀ H), there was
a small peak at 531.1 eV, which was attributed to
OÀ Co group.[30] The Co 2p XPS profile (Figure 3g)
displayed two main peaks centered at 781.8 and
796.9 eV, which were assigned to the Co 2p 3/2 orbital
energy level and Co 2p 1/2 orbital energy level,
indicative of the existence of Co(II) species.[31] The
loading of Co(II) measured by ICP-AAS was
0.21 mmol/g. TEM images showed that the morpholo-
gies of HMS-SH and HMS-Keto were spherical
sponge-like (Figure S2a,b). However, the morphology
of HMS-Salen changed towards to amorphous form
(Figure S2c). The HMS-Co-Salen was mainly com-
posed of block-shaped particles and a few spherical
particles (Figure 3h). It should be noted that the
Scheme 6. Synthesis of heterocycles catalyzed by the immobi-
lized salen-type cobalt(II) schiff base complex.
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was obtained (55.4 mg, 71% yield) by isolation with preparative
thin-layer chromatography (eluting solution: petroleum ether/
ethyl acetate=6/1 (v/v)).
Conclusion
We had developed a two-step protocol whereby 4-
chromanone underwent ring destruction with ethanol
under basic condition to give β-ethoxyl o-hydroxy-
phenyl ethyl ketone that reacted effectively with a
The procedure for synthesis of substituted coumarin 6a: In
a 10 mL of V-type flask equipped with triangle magnetic
stirring, 1a (0.3 mmol), Ph3P-CHCO2Et (0.45 mmol), and 4-
nucleophile to deliver the target β-substituted o- DMAP (0.018 mmol) were added in toluene (1.0 mL). The
mixture was refluxing for 10 h. After the reaction was
completed, the mixture was cooled to room temperature, and
the product was obtained (52.3 mg, 80% yield) by isolation
with preparative thin-layer chromatography (eluting solution:
petroleum ether/ethyl acetate=4/1 (v/v)).
hydroxyphenyl ethyl ketones. Various nucleophiles
including indole, 1,2,4-trimethoxybenzene, 1,1-diphe-
nylethylene, acetophenone, p-toluenethiol, and benzyl
mercaptan all participated smothly in the substitution
reaction. In addition, this protocol was applicable to
prepare the silica-immobilized cobalt salen complex,
The procedure for synthesis of substituted coumarin 7a: In
which showed excellent catalytic activities in synthesis a 10 mL of V-type flask equipped with triangle magnetic
stirring, 1a (0.3 mmol), PhI(OAc)2 (0.9 mmol), Bu4NI
(0.75 mmol), and NaOAc (0.3 mmol) were added in CH3CN
of 1,3-oxazolidine, benzimidazole, and benzoxazole.
°
(1.0 mL). The mixture was stirred at 30 C for 12 h. After the
Experimental Section
reaction was completed, the mixture was cooled to room
temperature, and the product was obtained (46.5 mg, 62%) by
isolation with preparative thin-layer chromatography (eluting
solution: petroleum ether/ethyl acetate=5/1 (v/v)).
General procedure for the synthesis of 1a:chroman-4-one
(2.96 g, 20 mmol) was mixed with ethanol (100 mL) in a
250 mL of round bottomed flask equipped with magnetic
stirring. NaOH (1.60 g, 40 mmol) was added to the system after
4-chromanone dissolved completely. The mixture was then
stirred at room temperature for 1.5 h. After completion of the
reaction monitored by TLC the mixture was neutralized with
HCl (1 M/L). The solvents were removed under vacuum and
the aqueous phase was extracted by ethyl acetate (30 mL×3).
The combined organic phase was washed with brine (30 mL)
and dried over Na2SO4. After removing volatile components,
the organic residue was subjected to an isolation with silica
column chromatography (eluting solution: petroleum ether/ethyl
acetate=20/1 (v/v)). A light yellow transparent liquid was
obtained (3.69 g, 95% yield).
The procedure for synthesis of heterogeneous HMS-Co-
Salen: In a 100 mL of round bottomed flask equipped with
triangle magnetic stirring, 1-hexadecylamine (13 mmol, 3.2 g)
was dissolved in EtOH/H2O (50 ml, V/V=7/9), tetraethyl
orthosilicate (39 mmol, 8.3 g) and trimethoxysilylpropanethiol
(10 mmol, 1.97 g) were added in sequence at room temperature.
After stirring for 20 h at room temperature, a large amount of
white solid was obtained and then filtered. Soxhlet extraction
was carried out for 72 h to remove impurities. The material was
dried under vacuum, affording an organic/inorganic hybrid
material,[28] which was named HMS-SH. Next, HMS-SH
(2 mmol, 0.92 g) and compound 2a (2 mmol, 0.39 g) were
added to the flask, followed by BF3 ·Et2O (2.2 mmol, 0.31 g),
General procedure for the reaction of 1a and indole: In a
10 mL of V-type flask equipped with triangle magnetic stirring,
1a (0.3 mmol) and indole (0.3 mmol) were dissolved in CH3CN
(1 mL), then BE3 ·Et2O (1.1 equiv., 0.33 mmol) was added. The
°
which were reacted in acetonitrile at 80 C for 12 h. The solid
was filtered out, washed with ethanol and distilled water, and
then dried under vacuum conditions to give HMS-Keto. After
that, HMS-Keto was reacted with ethylenediamine (0.5 mmol,
°
mixture was stirred at 80 C for 12 h. After the reaction was
°
0.03 g) in ethanol solution at 80 C for 6 h. After filtration, the
completed, the mixture was cooled to room temperature, and
the product was obtained by isolation through preparative thin-
layer chromatography (eluting solution: petroleum ether/ethyl
acetate=8/1 (v/v)). Tests for other nucleophiles were all
performed with an analogous procedure.
HMS-Salen was obtained by washing with ethanol and drying
under vacuum conditions. Finally, the obtained HMS-Salen and
Co(OAc)·4H2O (0.25 mmol, 0.07 g) were refluxed in ethanol
solution for 6 h, followed by filtration, washing with ethanol
and distilled water, and drying in vacuum drying oven for 24 h
to give HMS-Co-Salen.
The procedure for synthesis of substituted quinolone 4a: In
a 10 mL of V-type flask equipped with triangle magnetic
stirring, 1a (0.3 mmol) and 4-aminoveratrole (0.3 mmol) were
dissolved in CH3CN (1.0 mL), then BE3 ·Et2O (1.1 equiv.,
General procedure for the reaction of N-methylaniline and
styrene oxide: In a 10 mL of V-type flask equipped with
triangle magnetic stirring, N-methylaniline (0.3 mmol), styrene
oxide (0.6 mmol) and HMS-Co-Salen (0.03 mmol) were added
in DCE (2 mL). The mixture was stirred at 60 C for 2 h, and
then TBHP (0.6 mmol) was added to the mixture. The mixture
°
0.33 mmol) was added. The mixture was stirred at 80 C for 8 h.
After the reaction was completed, the mixture was cooled to
room temperature, and the product was obtained (57.4 mg, 68%
yield) by isolation by preparative thin-layer chromatography
(eluting solution: petroleum ether/ethyl acetate=2/1 (v/v)).
°
°
was stirred at 60 C for additional 2 h and then cooled to room
temperature. The product was obtained by preparative thin-layer
chromatography (eluting solution: petroleum ether/ethyl
acetate=10/1 (v/v)).
The procedure for synthesis of substituted cyclohexenone
5a: In a 10 mL of V-type flask equipped with triangle magnetic
stirring, 1a (0.3 mmol), ethyl acetoacetate (0.6 mmol), and
NaOH (0.6 mmol) were added in EtOH (1 mL). The mixture
The procedure for the reaction of o-phenylenediamine and
benzaldehyde: In a 10 mL of V-type flask equipped with
triangle magnetic stirring, o-phenylenediamine (0.2 mmol,
°
was stirred at 80 C for 5 h. After the reaction was completed,
the mixture was cooled to room temperature, and the product
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21.6 mg), benzaldehyde (0.2 mmol, 21.2 mg) and HMS-Co-
Salen (0.002 mmol, 9.6 mg) were added in EtOH (1 mL). The
mixture was stirred at room temperature for 0.5 h. After the
reaction was completed, the mixture was cooled to room
temperature and the product was obtained (36.9 mg, 95% yield)
by isolation with preparative thin-layer chromatography (eluting
solution: petroleum ether/ethyl acetate=5/1 (v/v)).
cyclohexene peroxodisulfate promoted oxidation of o-
allylphenol ( Badri, M. Soleymani, Synth. Commun.
2002, 32, 2385); b) electrophilic substitution of salicyl-
hydroxamic acid with vinyl Grignard reagent (X. Li, W.
Song, W. Tang, J. Am. Chem. Soc. 2013, 135, 16797).
[13] According to literature surveys, there is only one
protocol of the Michael addition o-hydroxyphenyl vinyl
ketone with malonate derivatives catalyzed by NaB
(OMe)4 and the yields haven’t been noted: L. Huang, J.-
S. Lin, B. Tan, X.-Y. Liu, ACS Catal. 2015, 5, 2826.
[14] J. Xuan, X.-K. Hea, W.-J. Xiao, Chem. Soc. Rev. 2020,
49, 2546.
The procedure for the reaction of 2-aminophenol and tert-
butyl isocyanide: In a 10 mL of V-type flask equipped with
triangle magnetic stirring and oxygen balloon, 2-aminophenol
(0.3 mmol, 32.7 mg), tert-butyl isocyanide (0.3 mmol, 24.9 mg)
and HMS-Co-Salen (0.03 mmol, 142.8 mg) were added in THF
°
(6 mL), the mixture was stirred at 65 C for 24 h. The mixture
[15] For selected examples: a) Y. Wang, Y. Wu, Y. Li, Y.
Tang, Chem. Sci. 2017, 8, 3852; b) Y. Gao, X. Zhang, X.
Zhang, Z. Miao, Org. Lett. 2021, 23, 2415.
[16] For selected examples: a) M. Li, C. Tang, J. Yang, Y. Gu,
Chem. Commun. 2011, 47, 4529; b) M. Li, H. Li, T. Li,
Y. Gu, Org. Lett. 2011, 13, 1064.
was cooled to room temperature, and the product was obtained
(47.3 mg, 90% yield) by isolation with preparative thin-layer
chromatography (eluting solution: petroleum ether/ethyl
acetate=5/1 (v/v)).
[17] Y.-L. Zhong, D. T. Borut, D. R. Gauthier Jr., D. Askin,
Tetrahedron Lett. 2011, 52, 4824.
Acknowledgements
[18] Y. Kang, Z. Pang, N. Xu, F. Chen, Z. Jin, X. Xu, J.
Agric. Food Chem. 2020, 68, 11077.
The National Natural Science Foundation of China (No.
21872060, 21902054, 21761132014, and 22072049) and
Fundamental Research Funds for the Central Universities of
China (2019kfyXJJS072) are gratefully acknowledged for the
financial support. This work was also supported by the
Innovation and Talent Recruitment Base of New Energy
Chemistry and Device and the Hubei Key Laboratory of
Material Chemistry and Service Failure.
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Adv. Synth. Catal. 2021, 363, 1–8
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These are not the final page numbers!

RESEARCH ARTICLE
Two-Step Access to β-Substituted o-Hydroxyphenyl Ethyl
Ketones from 4-Chromanone and its Application in Prepara-
tion of a Silica-Supported Cobalt(II) Salen Complex
Adv. Synth. Catal. 2021, 363, 1–8
L. Guo, M. Ye, L. Vaccaro, M. Li*, Y. Gu*