High-efficiency α-benzoyloxylation and hydroxylation of β-keto amides by phase transfer catalysis

Article abstract of DOI:10.1016/j.tet.2018.06.026

A facile and efficient protocol for α-benzoyloxylation and α-hydroxylation of β-keto amides by phase-transfer catalysis is presented. This methodology provides mild and practical access to a variety ofα-oxygenated β-keto amides. Furthermore, α-benzoyloxyl

Full text of DOI:10.1016/j.tet.2018.06.026

Accepted Manuscript
High-efficiency α-benzoyloxylation and hydroxylation of β-keto amides by phase
transfer catalysis
Yakun Wang, Qinghe Gao, Nan Li, Yifan Chen, Jingwen Cui, Feiyu Gao, Qingwei
Meng
PII:
S0040-4020(18)30715-4
10.1016/j.tet.2018.06.026
TET 29622
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 April 2018
Revised Date: 5 June 2018
Accepted Date: 12 June 2018
Please cite this article as: Wang Y, Gao Q, Li N, Chen Y, Cui J, Gao F, Meng Q, High-efficiency α-
benzoyloxylation and hydroxylation of β-keto amides by phase transfer catalysis, Tetrahedron (2018),
doi: 10.1016/j.tet.2018.06.026.
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High-efficiency α-Benzoyloxylation and
Hydroxylation of β-keto Amides by
Phase Transfer Catalysis
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Yakun Wang,a* Qinghe Gaoa , Nan Lia, Yifan Chena, Jingwen Cuia, Feiyu Gaoa and Qingwei Meng*b
a School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, Henan, P. R.China
E-mail: 161072@xxmu.edu.cn; Fax: (+86)-0373-3029879
bSchool of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024,Liaoning,
P. R. China. E-mail: mengqw@dlut.edu.cn; Fax: +86-0411-84986201

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1
Tetrahedron
journal homepage: www.elsevier.com
High-efficiency α-Benzoyloxylation and Hydroxylation of β-keto Amides by
Phase Transfer Catalysis
Yakun Wang,a* Qinghe Gaoa , Nan Lia, Yifan Chena, Jingwen Cuia, Feiyu Gaoa and Qingwei Meng*b
a School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, Henan, P. R.China
E-mail: 161072@xxmu.edu.cn; Fax: (+86)-0373-3029879
bSchool of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024,Liaoning, P. R. China.
E-mail: mengqw@dlut.edu.cn; Fax: +86-0411-84986201
ARTICLE INFO
ABSTRACT
Article history:
Received
A facile and efficient protocol for the α-benzoyloxylation and α-hydroxylation of β-keto
amides by phase-transfer catalysis is presented. This methodology provides mild and
Received in revised form
Accepted
practical access to highly functionalized a variety of α-oxygenated β-keto amides.
Furthermore, the α-benzoyloxylation products can be easily converted into α-hydroxylation
Available online
compounds, which are useful synthetic precursors of biological targets.
2009 Elsevier Ltd. All rights reserved.
Keywords:
α-benzoyloxylation
phase-transfer catalysis
α- hydroxylation
β-keto amides
acyloxy-functionalization
dicarbonyl compounds by diacyl peroxides were rarely reported.
Thus, the development of green and highly efficient α-
benzoyloxylation of β-dicarbonyl compounds with broad
substrate scope is necessary and meaningful.
1. Introduction
The α-oxygenated β-dicarbonyl compounds are common
On the other hand, phase-transfer catalysis (PTC) is a well
knownrecognized as useful tool to develop sustainable
structural motifs in
a wide range of natural products and
pharmaceuticals.1 Because of this, the α-oxidations of β-
dicarbonyl compounds, leading to both α-hydroxy and α-oxo
derivatives, are important chemical transformations in synthetic
chemistry and pharmaceutical science.2 Over the past few
decades, the commonly used strategy is was the direct oxidation
of the corresponding β-dicarbonyl compounds with various
a
oxidation processes24. In 2016, Itoh reported the first
enantioselective α-benzoyloxylation of malonic diester 25, our
group independently reported the α-benzoyloxylation of β-keto
esters, by phase transfer catalysis26. Compared with the β-keto
esters, β-keto amides are still challenging substrates, possibly due
to the lower acidity of the α-hydrogen. Furthermore, the α-
hydroxy-β-keto amide structure could be widely found in natural
products and pharmaceuticals such as novel antimicrobial agent
Pramanicin27 and bioactive nature product Y224A28. Recently,
the α-oxygenated β-keto amides have been demonstrated to be
key-intermediates to access Brazilin-type compounds, which
showed antiproliferative activity against different human tumor
cell lines29 (Scheme 1). Although α-hydroxylations of β-keto
amides have been achieved by ROOH11d,e,30 and oxone10, a
highly efficient method for the α-oxidation of β-keto amides for a
broad scope of substrates, remains to be developed. Herein, we
reported the first efficient α-benzoyloxylation of β-keto amides
by phase-transfer catalysis, and the α-hydroxylation product
could be easily obtained by hydrolysis.
oxidants such as MoOPH3, OsO4 , Pb(OAc)4 , m-CPBA6,
4
5
DMD7,
oxaziridines8,
IBX9,
oxone10,
ROOH11,
nitrosobenzene12, H2O2 or molecular oxygen14. However, the
13
oxyfunctionalizations of 1, 3-dicarbonyl compounds and their
hetero analogs were previously limited to hydroxy, peroxy15,
16
aminoxy
and oxygen-sulfonyl groups17. Thus, the
development of a novel simple and simple novel method for the
efficient oxyfunctionalization of the 1, 3-dicarbonyl group is
currently a desirable and timely task. In the past few years, the
acyloxy-functionalizations of 1, 3-dicarbonyl compouds were
realized by using hypervalent iodine compounds18, Bu4NI/t-
BuOOH19, manganese(III) acetate20 and iron(III) salts21. To
achieve the benzoyloxylation with the less reactive benzoyl
peroxide as oxidant, the dicarbonyl substrates had to be
previously activated by being transformed transformation into
enamines22 or metal complexes23. Unlike α-hydroxylation,
methods for intermolecular oxidative α-benzoyloxylation of 1, 3-
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Tetrahedron
Table 1. Optimization of the reaction conditions for the α-
benzoyloxylation and of β-keto amide 1a a.
Entry
Solvent
Base
t
Cat.
Yield
[h]
(2a/3a) [%]b
1
2
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
CH2Cl2
Et2O
/
48
48
12
2
/
trace/n.rd
23/ n.rd
67/23
30% K2CO3
30% K2CO3
DBU
/
3
TBABr
TBABr
TBABr
TBABr
TBABr
TBABr
TBABr
TBABr
TBABr
TBABr
TBABr
TBACl
TBAF
BTMAB
TBABr
Scheme 1. Direct α-oxidation of β-keto amides.
4
trace/21
trace/trace
34/trace
21/65
2. Results and discussions
5
Et3N
12
12
2
6c
7
K2CO3
In order toTo develop a new and convenient method of for the
α-oxidation of β-keto amides, we investigated the α-
benzoyloxylation of 1-indanone derived β-keto amide 1a using
benzoyl peroxide as the oxygen source. First, the reaction can not
proceed without base and catalyst (Table 1, entry 1). When 30%
K2CO3 aqueous solution was added in toluene, the α-
benzoyloxylation reaction was undertaken, but afforded 2a was
obtained with only 23% yield (Table 1, entry 2). Then
tetrabutylammonium bromide (TBABr) was used as the phase
transfer catalyst, and we were pleased to see that the yield of 2a
was improved to 67%, and the α-hydroxylation product 3a was
also observed (Table 1, entry 3). Then we tested the organic
10% KOH
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
10% KOH
78
9
6
71/20
2
91/trace
84/trace
71/23
10
11
12
13
14
15
16
17
MTBE
DMSO
THF
2
12
12
12
2
41/48
MeOH
Et2O
trace/65
81/trace
87/trace
65/21
bases
1,8-Diazabicyclo[5.4.0]undec-7-ene
(DBU)
and
triethylamine (Et3N), but only a trace amountthe yields of 2a was
were noticeably decreased formed (Table 1, entries 4-5). Solid
K2CO3 provided a low yield compared with 30% K2CO3 aqueous
solution, which indicated that the presence of H2O is necessary
for the reactivity (Table 1, entry 6). The use of 10% NaOH KOH
aqueous solution provided faster reaction rates, but the selectivity
of 2a was poor. We thought 2a might be undergoing hydrolysis
in the presence of stronger inorganic base aqueous solution
(Table 1, entry 7). In the solvent screening, we found that the
Et2O
2
Et2O
2
CH2Cl2/MeOH
4:1
6
trace/85
a
Unless otherwise specified, the reactions were performed with 1a (0.1
mmol), BPO (0.13 mmol, 97% dry wt., wet with 25% water), catalyst (0.005
Font: 8 pt
Formatted:
reaction medium had
a
significant effect on the α-
b
mmol), and base (0.5 mL) in solvent (2 mL). Yields shown are of isolated
benzoyloxylation and α-hydroxylation. Using CH2Cl2 as the
solvent resulted in an elevated yield of 2a, and the reaction time
was shortened to 6 h (Table 1, entry 8). Ether solvents such as
Et2O and MTBE can accelerate the reaction and 2a was obtained
with high yields (84-91%) (Table 1, entries 9-10). The more high
polar solvents (THF and DMSO) were also tested, and we can
not only obtain both the α-benzoyloxylation product 2a and but
also the α-hydroxylation product 3a (Table 1, entries 11-12). To
our surprise, when MeOH was used, we did not obtain the α-
benzoyloxylation product 2a, and only the α-hydroxylation
product 3a was observedobtaided in 65% yield. We thought not
only the ester group but also the amide group of 1a might be
partly hydrolysed in MeOH. Next we screened the phase transfer
products. cFive equivalents of the base was used.d n.r = no reaction
With the optimized conditions in hand, we next explored the
substrate scope to demonstrate the generality in α-
benzoyloxylation of β-keto amides. First, we investigated the
influence of substituents at the amide sides. Aniline-derived
substrates 1a-1e containing 4'-Me, 4'- MeO, 3', 5’-CF3, 4'-t-Bu
and Aryl aryl derivatives 1f-1g containing naphthyl and benzyl
groups could bewere nicely converted into the corresponding
products 2a-2g in good yields (78-94%). Compounds 1f-1k, with
aliphatic amido groups, resulted in lower reaction rate (4h),
affording and the corresponding product 2f-2k were obtaind in
excellent yields (89-94%). Next, we the reaction scope was
extended the procedure to substrates which have halogen atoms
and electron-donating groups on the aromatic ring of the indane
scaffold. Under mild conditions, Substrates 1l-1n with Cl or Br
on the aromatic rings, were nicely converted into the
corresponding products (2l-2n) in good yields (86-93%).
catalyst.
Tetrabutylammonium chloride (TBACl) and
Tetrabutylammonium fluoride (TBAF) were introduced but and
provided 2a in 81-87% yields (Table 1, entries 14-15). Finally,
benzyltrimethylammonium bromide (BTMAB) was tested, but it
still provided low yield compared with TBABr (Table 1, entryies
9, 16). It is worth mentioning that the yield of α-hydroxylation
product 3a was improved to 85% when 4:1 CH2Cl2/MeOH were
used as the components (Table 1, entry 17). After all, the two α-
oxygenated products of β-keto amide 1a the α-benzoyloxylation
product 2a and the α-hydroxylation product 3a could be
respectively obtained with good yield by phase-transfer catalysis.
1l-1n which have halogen substituents were nicely converted
into the corresponding products. Howerver, when methoxy
groups were introduced (1o and 1p), a longer reaction time (12 h)
was needed to afford the desired products with 71-78% yields.
Then the scope of 1-tetralone-derived β-keto amide 1q was

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examined, and the desired products 2q was obtained with 68%
yield. Interestingly, the six, five, four-membered acyclic
substrates 1r-1t could be converted into the α-benzoyloxylation
prodcuts with 81-89% yields. Interestingly, cCompound 1u
which has methyl and phenyl in the N-position,
afforded 2u in extremely low yield even 10% KOH was used as
the base. UltimatelyAfter all, these results constituted showed a
significant improvement in substrate scope on phase-transfer-
catalyzed α-benzoyloxylation of β-keto amides (Scheme 2).
Under phase-transfer catalysis conditions, we further examined
the α-hydroxylation of β-keto amides to explore the synthetic
utility. We were pleased to see that the indanone derived β-keto
amides 1a, 1h, 1p can be easily transformed into the α-
hydroxylation products with 78-91% yields. More challenging β-
keto amides 1q, 1v, 1w which were derived from 1-tetralone
were also examined. By using 25% KOH as the base, we can also
obtain the α-hydroxylation products with 65-77% yields.
Scheme 3. Substrate scope of the α-hydroxylation of β-keto
amides.
Ultimately, sSuch
a simple and efficient method for α-
The phase-transfer catalysed α-oxidations of β-keto amides
with mixed peroxide were carried out under standard reaction
conditions employing benzoyl pivaloyl peroxide, t-butyl
peroxybenzoate, dicumyl peroxide and cumyl hydroperoxide. 2a
was obtained in 45% yield by using benzoyl pivaloyl peroxide as
the oxidant, while the formation of the alkyl acyloxy product was
not observed. t-Butyl peroxybenzoate and dicumyl peroxide
could not promote the reaction. When cumyl hydroperoxide was
used, we can obtain the α-hydroxylation product 3a was obtained
in 35% yield. These results showed the unique structure of
benzoyl peroxide is was important for the high-efficiency α-
benzoyloxylation and hydroxylation of β-keto amides (Scheme
4).
hydroxylation showed good substrate tolerance for indanone and
1-tetralone-derived β-keto amides (Scheme 3), and all the new
compounds have been fully characterized with 1HNMR, 13CNMR
and HRMS.
Scheme 4. Reaction with mixed acyl peroxides and tert-butyl
hydroperoxide.
In order to understand the reaction mechanism, we conducted
some control experiments. First, We we added TEMPO as a
radical inhibitor, and but the results did not noticeably influenced,
which indicated a radical process was not occurring in this
reaction system. Then we use pure oxygen gas was used instead
of BPO as the oxidant, but very little productnearly no α-
hydroxylation product was obtained, which indicated that the
oxygen source for α-hydroxylation product 3a was BPO.
Furthermore, the α-benzoyloxylation product 2a can be
hydrolyzed under stronger inorganic base (10% KOH), and 3a
was obtained in 81% yield (Scheme 5).
Scheme 2. Substrate scope of the α-benzoyloxylation of β-
keto amides.

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4
Tetrahedron
Scheme 7. Gram scale reaction of α-benzoyloxylation and
hydroxylation.
Scheme 5. Control experiments.
In order to develop a convenient method for to obtain the chiral
On the basis of these experiments, we proposed a possible
mechanism for the α-benzoyloxylation and hydroxylation of β-
keto amides. Phase-transfer catalysis catalyst (PTC) such as
TBABr is an organic molecule incorporating a quarternary
nitrogen center with an ability to dissolve in both aqueous and
organic solvents. The catalyst thereby carries an inorganic base
(e.g., CO32-) into the organic phase where it deprotonates the β-
keto amides, then the chiral catalyst forms an ion-pair between
the positive quarternary amine and the enolate anion, which
attacks the electrophile BPO, thereby forming the α-
benzoyloxylation product. Then under stronger bases, the α-
hydroxylation product can bewas generated by hydrolysis of α-
benzoyloxylation product (Scheme 6).
α-benzoyloxylation product of β-keto amides, we further
investigated the asymmetric α-benzoyloxylation of 1-
indanone-derived β-keto amide 1a catalysed by cinchona
alkaloid derived phase-transfer catalyst. The simple PTC-1
provided 2a with 10% ee in toluene (Table 2, entry 2). The N-
oxide PTC-2 led to a slightly higher enantioselectivity (Table 2,
entry 3). PTC-3, which has hydroxy groups at both the C-9 and
C-6′ positions, showed poor results. Then we screened the doubly
quaternized catalyst PTC-3, but the enantioselectivity was poor
(Table 2, entry 4). C-2′-arylated PTC-5 and C-9 etherified PTC-
6 could not noticeably improve the enantioselectivity of 2a
(Table 2, entries 5-6). PTC-7, with electron-withdrawing groups
(-CF3) at the 3 and 5 positions, improved the enantioselectivity
(Table 2, entry 8). PTC-8, which the C-9 hydroxy was protected
by
a bulky 1-adamantyl group, afforded 2a in a higher
enantioselectivity (30 % ee). I think the bulky 1-adamantyl group
can act as a large space resistance group, and the anthracene ring
can be involved in stronger π-π stacking interactions with
substrate 1a than a benzene ring. Although the results of the
asymmetric α-benzoyloxylation of β-keto amides was were
not satisfying, we still developed an enantioselective
oxidative C-O coupling of β-keto amides by phase-transfer
catalysis, and this reaction provided an easy and rapid access
for potentially valuable precursors for the synthesis of
natural products and pharmaceuticals.
Table 2. Optimization of the reaction conditions for the
asymmetric α-benzoyloxylation of β-keto amide 1a a.
Scheme 6. Proposed mechanism for α-benzoyloxylation and
hydroxylation of β-keto amides.
To demonstrate the utility of this reaction, we scaled up the α-
benzoyloxylation and hydroxylation to the gram scale. Under
phase-transfer catalysis, 5 mmol of β-keto amides (1a) reacted
smoothly with 6.5 mol of BPO and gave 1.63 g (88% yield) of
2a after 4 h. It is worth mentioning that the α-hydroxylation
product can be respectivelyeasily obtained with in 81% yield by
simply using the different the solvent (CH2Cl2/MeOH= 4:1) and
the base (10% KOH) (Scheme 7).
Entry
1
Solvent
Et2O
Base
Cat. Yieldb [%]
PTC-1 86
eec [%]
0
30% K2CO3

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5
concentrated in vacuo. The residue was purified by
2
3
4
5
6
7
8
9
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
PhCH3
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
30% K2CO3
PTC-1
PTC-2
PTC-3
PTC-4
PTC-5
PTC-6
PTC-7
PTC-8
73
78
51
46
78
82
81
84
10
flash chromatography (silica gel; petroleum ether/ethyl
acetate 20:1-5:1) to afford the α-benzoyloxylation
products 2a-2u
23
5
=
.
4.2.1.
2-benzoyloxy-1-oxo-N-phenyl-2,3-dihydro-1H-
5
indene-2-carb-oxamide (2a). Brown solid, 34 mg, 91% yield;
mp:190-192 °C. 1H NMR (400 MHz, CDCl3) δ 8.36 (s, 1H), 8.18
– 8.03 (m, 2H), 7.87 (d, J = 7.7 Hz, 1H), 7.77 – 7.64 (m, 2H),
7.63 – 7.45 (m, 6H), 7.41 – 7.32 (m, 2H), 7.18 (d, J = 7.4 Hz,
14
18
25
30
1H), 4.37 (d, J = 16.9 Hz, 1H), 3.49 (d, J = 16.8 Hz, 1H). 13
C
NMR (101 MHz, CDCl3) δ 197.74, 164.57, 163.35, 151.65,
137.07, 136.38, 134.19, 133.51, 130.02, 129.07, 128.84, 128.40,
128.12, 126.37, 125.11, 125.01, 120.07, 86.33, 36.23. HRMS
(ESI-TOF) m/z: [M+Na]+ Calcd for [C23H17NO4+Na]+ requires
m/z 394.1055, found m/z 394.1052.
a
Unless otherwise specified, the reactions were performed with 1a (0.1
mmol), BPO (0.13 mmol), catalyst (0.005 mmol), and base (0.5 mL) in
b
c
solvent (2 mL). Yields shown are of isolated products. Ee values were
determined by HPLC analysis on Chiralpak AD-H.
4.2.2.
2-benzoyloxy-1-oxo-N-(4-methyl-phenyl)-2,3-dihydro-
1H-indene-2-carboxamide (2b). Brown solid, 36 mg, 94% yield;
mp:183-187 °C. 1H NMR (400 MHz, CDCl3) δ 8.31 (s, 1H), 8.15
– 8.05 (m, 2H), 7.87 (d, J = 7.6 Hz, 1H), 7.77 – 7.63 (m, 2H),
7.61 – 7.42 (m, 6H), 7.16 (d, J = 8.3 Hz, 2H), 4.35 (d, J = 16.8
Hz, 1H), 3.49 (d, J = 16.8 Hz, 1H), 2.34 (s, 3H). 13C NMR (101
MHz, CDCl3) δ 197.80, 164.56, 163.21, 151.66, 136.32, 134.69,
134.52, 134.16, 130.02, 129.54, 128.82, 128.44, 128.08, 126.36,
125.09, 120.09, 86.33, 36.26, 20.92. HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for [C24H19NO4+Na]+ requires m/z 408.1212,
found m/z 408.1208.
3. Conclusion
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In conclusion, we developed the facile and efficient α-
benzoyloxylation of β-keto amides under phase-transfer
catalysis with commercially available benzoyl peroxide.
Under mild conditions, good yields (up to 94%) were
obtained for a range of substituted indanone, 1-tetralone,
cyclohexanone and cyclopentanone derivatives. Moreover,
the α-hydroxylation products can alsocould be easily
obtained by hydrolysis under strong inorganic base. This
new methodology was also successfully used for a gram-
scale reaction. Further investigations on expanding this α-
benzoyloxylation to other useful compounds are currently
underway.
4.2.3. 2-benzoyloxy-1-oxo-N-(4-methoxy-phenyl)-2,3-dihydro-
1H-indene-2-carboxamide (2c). Yellow solid, 37 mg, 93% yield;
mp:181-183 °C. 1H NMR (400 MHz, CDCl3Chloroform-d) δ 8.32
(s, 1H), 8.14 – 8.00 (m, 2H), 7.80 – 7.60 (m, 3H), 7.62 – 7.44 (m,
5H), 7.33 (t, J = 7.9 Hz, 2H), 7.14 (t, J = 7.4 Hz, 1H), 4.28 (d, J =
17.1 Hz, 1H), 3.44 (d, J = 17.1 Hz, 1H).δ 8.34 (s, 1H), 8.16 –
8.07 (m, 2H), 7.87 (dd, J = 7.7, 1.1 Hz, 1H), 7.76 – 7.42 (m, 9H),
6.89 (d, J = 9.1 Hz, 2H), 4.35 (d, J = 16.9 Hz, 1H), 3.81 (s, 3H),
3.49 (d, J = 16.9 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 197.96,
164.59, 163.19, 156.85, 151.72, 136.34, 134.14, 133.71, 133.57,
130.19, 130.02, 128.80, 128.46, 128.42, 128.08, 126.35, 125.10,
121.85, 114.16, 86.34, 55.50, 36.32. HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for [C24H19NO5+Na]+ requires m/z 424.1161,
found m/z 424.1155.
4. Exprimental
4.1. General
Unless otherwise stated, all commercial reagents and solvents
were used without further additional purification. Analytical TLC
was visualized with UV light at 254 nm. Thin layer
chromatography was carried out on TLC aluminum sheets with
silica gel 60 F254. Purification of reaction products was carried
out with chromatography on silica gel 60 (200-300 mesh). 1H
NMR (400 MHz) spectra was obtained at 25 °C; 13C NMR (126
MHz) were recorded on
a VARIAN INOVA-400M and
AVANCE II 400 spectrometer at 25 °C. Chemical shifts are
reported as δ (ppm) values relative to TMS as internal standard.
Mass spectra are reported by using electron ionization and
electrospray ionization techniques. Melting points were
determined with a hot plate apparatus. HPLC analyses were
performed on equipped with Diacel Chiralpak AD-H chiral
4.2.4 .2-benzoyloxy-1-oxo-N-(3,5-ditrifluoromethyl-phenyl)-2,3-
dihydro-1H-indene-2-carboxamide (2d). White solid, 40 mg,
78% yield; mp:227-230 °C. 1H NMR (400 MHz, CDCl3) δ 8.79
(d, J = 12.1 Hz, 1H), 8.08 (dt, J = 7.6, 4.4 Hz, 4H), 7.86 (d, J =
7.7 Hz, 1H), 7.80 – 7.47 (m, 7H), 4.38 (d, J = 17.0 Hz, 1H), 3.48
(d, J = 17.0 Hz, 1H).13C NMR (101 MHz, CDCl3) δ 197.51,
197.48, 164.60, 164.58, 164.12, 151.65, 138.52, 136.85, 134.41,
133.04, 130.11, 130.09, 128.84, 128.83, 128.38, 127.97, 126.43,
125.23, 119.83, 118.20, 86.24, 36.20, 36.17. HRMS (ESI-TOF)
m/z: [M+Na]+ Calcd for [C25H15F6NO4+Na]+ requires m/z
530.0803, found m/z 530.0810.
column
(0.46 cm × 25 cm), using mixtures of n-
hexane/isopropyl alcohol as mobile phase, at 25 °C.
4.2. General Proceduce for the α-benzoyloxylation
of β-keto amides (2a-2u).
The reaction was conducted with β-keto amides 1a-1u
(0.1 mmol) in the presence of TBABr (0.005 mmol)
and benzoyl peroxide (0.13 mmol) in a mixture containing
Et2O (2mL) and 30% K2CO3 (0.5 mL). The reaction was
stirred at this temperature for 2 h. After the reaction was
completed (confirmed by TLC analysis), the mixture was
diluted with EtOAc (30 mL), washed with water (3 × 10
mL), dried over anhydrous Na2SO4, filtered, and
4.2.5. 2-benzoyloxy -1-oxo-N-(4-tert-butyl-phenyl)-2,3-dihydro-
1H-indene -2-carboxamide (2e).Brown solid, 37 mg, 87% yield;
mp:150-153 °C. 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 8.17
– 8.01 (m, 2H), 7.86 (dt, J = 7.7, 0.9 Hz, 1H), 7.74 – 7.65 (m,
2H), 7.61 – 7.44 (m, 7H), 7.40 – 7.35 (m, 2H), 4.48 – 4.21 (m,
2H), 3.49 (d, J = 16.8 Hz, 1H), 1.32 (s, 9H). 13C NMR (101 MHz,
CDCl3)
δ 197.78, 164.57, 163.18, 151.65, 148.03, 136.33,

ACCEPTED MANUSCRIPT
6
Tetrahedron
134.49, 134.15, 133.54, 130.93, 130.02, 128.85, 128.81,
4.2.11.
2-benzoyloxy-1-oxo-N-(tert-butyl)-2,3-dihydro-1H-
128.45, 128.08, 126.37, 125.88, 125.07, 119.79, 86.32, 65.59,
36.19, 34.44, 31.34, 30.59, 19.21, 13.76. HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for [C25H15NO4+Na]+ requires m/z 530.0803,
found m/z 530.0810.
indene-2-carboxamide (2k). White solid, 33 mg, 93% yield;
mp:136-139 °C. 1H NMR (400 MHz, CDCl3) δ 8.12 – 7.98 (m,
2H), 7.85 (dt, J = 7.7, 1.0 Hz, 1H), 7.74 – 7.62 (m, 2H), 7.56 –
7.48 (m, 3H), 7.44 (td, J = 7.5, 1.0 Hz, 1H), 6.51 (s, 1H), 4.17 (d,
J = 16.8 Hz, 1H), 3.38 (dd, J = 16.7, 1.2 Hz, 1H), 1.41 (s, 9H).
13C NMR (101 MHz, CDCl3) δ 198.08, 164.78, 164.42, 151.77,
135.98, 133.98, 129.84, 128.77, 127.86, 126.20, 124.93, 86.13,
51.89, 36.60, 28.58. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
[C21H21NO4+Na]+ requires m/z 374.1368, found m/z 374.1361.
4.2.6.
2-benzoyloxy-1-oxo-N-(1-naphthyl)-2,3-dihydro-1H-
indene-2-carboxamide (2f) Brown solid, 35 mg, 84% yield;
mp:153-156 °C. 1H NMR (400 MHz, CDCl3) δ 8.86 (s, 1H), 8.23
– 8.13 (m, 2H), 8.09 – 7.87 (m, 4H), 7.80 – 7.65 (m, 3H), 7.64 –
7.43 (m, 7H), 4.48 (d, J = 17.0 Hz, 1H), 3.56 (d, J = 17.0 Hz,
1H). 13C NMR (101 MHz, CDCl3) δ 198.13, 164.77, 163.96,
151.87, 136.46, 134.23, 134.05, 133.52, 131.53, 130.07, 128.86,
128.75, 128.48, 128.15, 127.08, 126.73, 126.46, 126.22, 126.18,
125.64, 125.18, 120.54, 120.51, 86.55, 36.22. HRMS (ESI-TOF)
m/z: [M+Na]+ Calcd for [C27H19NO4+Na]+ requires m/z
444.1212, found m/z 444.1217.
4.2.12. 5-chloro-2-benzoyloxy-1-oxo-N-phenyl-2,3-dihydro-1H-
indene-2-carboxamide (2l). White solid, 38 mg, 93% yield;
mp:195-198 °C. 1H NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 8.18
– 8.05 (m, 2H), 7.79 (d, J = 8.2 Hz, 1H), 7.74 – 7.65 (m, 1H),
7.61 – 7.51 (m, 5H), 7.45 (dd, J = 8.3, 1.8 Hz, 1H), 7.40 – 7.34
(m, 2H), 7.21 – 7.14 (m, 1H), 4.31 (d, J = 17.0 Hz, 1H), 3.47 (d,
J = 17.0 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 196.30, 164.54,
163.11, 152.93, 142.95, 136.91, 134.32, 132.02, 130.02, 129.11,
128.96, 128.89, 128.20, 126.65, 126.16, 125.14, 120.10, 86.20,
36.02. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
[C23H16ClNO4+Na]+ requires m/z 428.0666, found m/z 428.0668.
4.2.7. 2-benzoyloxy-1-oxo-N-(benzyl)-2,3-dihydro-1H-indene-2-
carbox-amide (2g). Colorless oil, 30 mg, 78% yield; 1H NMR
(400 MHz, CDCl3) δ 8.05 – 7.98 (m, 2H), 7.87 (d, J = 7.7 Hz,
1H), 7.73 – 7.60 (m, 2H), 7.56 (dd, J = 7.7, 1.0 Hz, 1H), 7.47 (td,
J = 7.8, 3.8 Hz, 3H), 7.41 – 7.26 (m, 5H), 7.06 (s, 1H), 4.69 –
4.45 (m, 2H), 4.29 (d, J = 16.9 Hz, 1H), 3.46 (d, J = 16.9 Hz,
1H). 13C NMR (101 MHz, CDCl3) δ 197.75, 165.84, 164.58,
151.74, 137.62, 136.17, 134.04, 133.74, 129.95, 128.79, 128.73,
128.46, 128.01, 127.62, 127.47, 126.35, 125.02, 86.07, 43.90,
36.72. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
[C24H19NO4+Na]+ requires m/z 408.1206, found m/z 408.1210.
4.2.13. 5-bromine-2-benzoyloxy -1-oxo-N-phenyl-2,3-dihydro-
1H-indene-2-carboxamide (2m). White solid, 41 mg, 91% yield;
mp:194-196 °C. 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 8.11
– 8.00 (m, 2H), 7.77 – 7.63 (m, 3H), 7.61 – 7.46 (m, 5H), 7.33 (t,
J = 7.9 Hz, 2H), 7.14 (t, J = 7.4 Hz, 1H), 4.28 (d, J = 17.1 Hz,
1H), 3.44 (d, J = 17.1 Hz, 1H).13C NMR (101 MHz, CDCl3) δ
196.56, 164.53, 163.07, 152.97, 136.90, 134.33, 132.41, 131.90,
131.80, 130.03, 129.72, 129.12, 128.89, 128.17, 126.19, 125.15,
120.09, 86.11, 35.95. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
[C23H16BrNO4+Na]+ requires m/z 472.0160, found m/z 472.0158.
4.2.8. 2-benzoyloxy -1-oxo-N-(n-butyl)-2,3-dihydro-1H-indene-
2-carboxamide (2h). White solid, 33 mg, 93% yield; mp:102-105
°C. 1H NMR (400 MHz, CDCl3) δ 8.05 (dd, J = 8.4, 1.4 Hz, 2H),
7.84 (dt, J = 7.7, 0.9 Hz, 1H), 7.73 – 7.61 (m, 2H), 7.57 – 7.40
(m, 4H), 6.66 (s, 1H), 4.23 (d, J = 16.8 Hz, 1H), 3.54 – 3.24 (m,
3H), 1.65 – 1.48 (m, 2H), 1.48 – 1.31 (m, 2H), 0.95 (t, J = 7.3
Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 197.93, 165.57, 164.54,
151.76, 136.07, 134.01, 133.75, 129.92, 128.74, 128.59, 127.92,
126.30, 124.94, 86.07, 39.81, 36.59, 31.46, 19.98, 13.74. HRMS
(ESI-TOF) m/z: [M+Na]+ Calcd for [C21H21NO4+Na]+ requires
m/z 374.1363, found m/z 374.1370.
4.2.14. 4-bromine-2-benzoyloxy -1-oxo-N-phenyl-2,3-dihydro-
1H-indene-2-carboxamide (2n). Brown solid, 37 mg, 86% yield;
mp:178-182 °C. 1H NMR (400 MHz, CDCl3) δ 8.41 (s, 1H), 8.10
(dd, J = 8.3, 1.4 Hz, 2H), 7.85 (ddd, J = 24.2, 7.8, 1.0 Hz, 2H),
7.73 – 7.50 (m, 5H), 7.37 (ddd, J = 8.5, 7.6, 1.8 Hz, 3H), 7.24 –
7.12 (m, 1H), 4.30 (d, J = 17.4 Hz, 1H), 3.40 (d, J = 17.4 Hz,
1H). 13C NMR (101 MHz, CDCl3) δ 197.24, 164.51, 163.17,
151.33, 138.94, 136.89, 135.60, 134.37, 130.04, 129.78, 129.13,
128.91, 128.10, 125.19, 123.80, 121.64, 120.14, 85.86, 37.66.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for [C23H16BrNO4+Na]+
requires m/z 472.0160, found m/z 472.0156.
4.2.9.
2-benzoyloxy-1-oxo-N-(isopropyl)-2,3-dihydro-1H-
indene-2-carboxamide (2i) Light yellow solid, 33 mg, 94%
yield; mp:103-106 °C. 1H NMR (400 MHz, CDCl3) δ 8.10 – 7.98
(m, 2H), 7.84 (d, J = 7.7 Hz, 1H), 7.71 – 7.61 (m, 2H), 7.58 –
7.48 (m, 3H), 7.44 (t, J = 7.5 Hz, 1H), 6.47 (s, 1H), 4.22 (d, J =
16.8 Hz, 1H), 4.10 (dt, J = 8.0, 6.6 Hz, 1H), 3.40 (d, J = 16.8 Hz,
1H), 1.30 - 1.19 (m, 6H). 13C NMR (101 MHz, CDCl3) δ 197.90,
164.76, 164.52, 151.75, 136.04, 134.00, 133.78, 129.89, 128.76,
128.62, 127.90, 126.28, 124.93, 85.95, 42.25, 36.56, 22.66,
22.34. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
[C20H19NO4+Na]+ requires m/z 360.1206, found m/z 360.1203.
4.2.15. 5-methoxyl-2-benzoyloxy -1-oxo-N-phenyl-2,3-dihydro-
1H-indene-2-carboxamide (2o). Yellow solid, 31 mg, 78% yield;
mp:149-153 °C. 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 8.18
– 8.00 (m, 2H), 7.79 (d, J = 8.4 Hz, 1H), 7.66 (s, 1H), 7.61 – 7.49
(m, 4H), 7.35 (dd, J = 8.5, 7.4 Hz, 2H), 7.19 – 7.11 (m, 1H), 6.99
(d, J = 8.6 Hz, 2H), 4.36 (d, J = 16.9 Hz, 1H), 3.93 (s, 3H), 3.44
(d, J = 16.9 Hz, 1H).13C NMR (101 MHz, CDCl3) δ 195.52,
166.70, 164.66, 163.61, 154.87, 137.21, 134.10, 130.03, 129.03,
128.79, 128.56, 126.95, 126.56, 124.89, 120.06, 116.51, 109.46,
86.62, 55.86, 36.12. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
[C24H19NO5+Na]+ requires m/z 424.1161, found m/z 424.1153.
4.2.10.
2-benzoyloxy-1-oxo-N-(cyclohexyl)-2,3-dihydro-1H-
1
indene-2-carboxamide (2j). Colorless oil, 33 mg, 89% yield; H
NMR (400 MHz, CDCl3) δ 8.11 – 7.97 (m, 2H), 7.83 (d, J = 7.7
Hz, 1H), 7.74 – 7.59 (m, 2H), 7.57 – 7.39 (m, 4H), 6.53 (d, J =
8.1 Hz, 1H), 4.23 (d, J = 16.8 Hz, 1H), 3.86 – 3.78 (m, 1H), 3.40
(d, J = 16.7 Hz, 1H), 2.06 – 1.84 (m, 2H), 1.84 – 1.55 (m, 3H),
1.51 – 1.16 (m, 5H). 13C NMR (101 MHz, CDCl3) δ 197.93,
164.68, 164.51, 151.76, 136.02, 133.99, 129.88, 128.76, 127.88,
126.28, 124.92, 85.99, 48.88, 36.54, 32.87, 32.50, 25.46, 24.73,
24.61. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
[C23H23NO4+Na]+ requires m/z 400.1525, found m/z 400.1530.
4.2.16. 5,6-dimethoxyl-2-benzoyloxy -1-oxo-N-phenyl-2,3-
dihydro-1H-indene-2-carboxamide (2p). Yellow solid, 30 mg,
71% yield; mp:223-226 °C. 1H NMR (400 MHz, CDCl3) δ 8.35
(s, 1H), 8.09 (s, 2H), 7.63 (d, J = 7.5 Hz, 1H), 7.61 – 7.46 (m,
4H), 7.38 – 7.22 (m, 4H), 7.13 (s, 1H), 4.27 (d, J = 16.5 Hz, 1H),
4.00 (s, 3H), 3.91 (s, 3H), 3.38 (d, J = 16.5 Hz, 1H).
13C NMR (101 MHz, CDCl3) δ 195.88, 164.64, 163.61, 156.93,
149.98, 147.61, 137.20, 134.10, 130.02, 129.04, 128.79, 128.57,

ACCEPTED MANUSCRIPT
7
124.89, 120.02, 107.35, 105.25, 86.73, 56.46, 56.16, 35.84.
203.14, 168.30, 153.06, 136.89, 136.54, 133.69, 129.02,
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for [C25H21NO6+Na]+
requires m/z 454.1267, found m/z 454.1263.
128.19, 126.40, 125.24, 124.79, 119.70, 82.72, 40.86. HRMS
(ESI-TOF) m/z: [M+Na]+ Calcd for [C16H13NO3+Na]+ requires
m/z 290.0793, found m/z 290.0790.
4.2.17 .2-benzoyloxy-1-oxo-N-phenyl-1,2,3,4-tetrahydronaphth-
alene-2-carboxylate (2q). Colorless oil, 26 mg, 68% yield; H
NMR (400 MHz, CDCl3) δ 8.49 (s, 1H), 8.11 (ddd, J = 24.9, 8.3,
1.5 Hz, 3H), 7.71 – 7.30 (m, 11H), 7.24 – 7.09 (m, 1H), 3.72 –
3.61 (m, 1H), 3.19 – 2.87 (m, 3H). 13C NMR (101 MHz, CDCl3)
4.3.2.
2-hydroxy-1-oxo-N-n-butyl-2,3-dihydro-1H-indene-2-
1
carboxamide (3h) Colorless wax; 22 mg,91% yield; 1H NMR
(400 MHz, CDCl3) δ 7.73 (d, J = 7.6 Hz, 1H), 7.63 (td, J = 7.5,
1.2 Hz, 1H), 7.44 (d, J = 7.7 Hz, 1H), 7.39 (d, J = 7.5 Hz, 1H),
6.90 (s, 1H), 3.69 (d, J = 16.7 Hz, 1H), 3.29 – 3.15 (m, 2H), 3.06
(d, J = 16.7 Hz, 1H), 1.55 – 1.38 (m, 2H), 1.38 – 1.28 (m, 2H),
0.90 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 203.34,
170.26, 153.03, 136.15, 133.90, 127.93, 126.37, 125.05, 82.08,
δ
192.17, 164.49, 164.08, 143.71, 137.06, 134.70, 133.85,
129.95, 129.08, 128.87, 128.68, 128.39, 127.03, 124.95, 120.07,
83.32, 29.91, 26.67. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
[C24H19NO4+Na]+ requires m/z 408.1212, found m/z 408.1216.
40.64, 39.24, 31.45, 19.94, 13.70.
HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for [C14H17NO3+Na]+ requires m/z 270.1106,
found m/z 270.1103.
4.2.18.
2-benzoyloxy
-1-oxo-N-phenyl-cyclohexanone-2-
1
carboxamide (2r). Colorless oil, 27 mg, 81% yield; H NMR
(400 MHz, CDCl3) δ 9.42 (s, 1H), 8.25 – 8.05 (m, 2H), 7.71 –
7.48 (m, 5H), 7.41 – 7.32 (m, 2H), 7.19 – 7.12 (m, 1H), 2.90 –
2.69 (m, 2H), 2.63 – 2.52 (m, 1H), 2.45 – 2.31 (m, 1H), 2.24 –
1.91 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 207.99, 165.59,
165.48, 137.24, 134.00, 130.09, 129.01, 128.70, 124.75, 120.30,
83.88, 40.08, 37.87, 27.97, 21.71. HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for [C20H19NO4+Na]+ requires m/z 360.1212,
found m/z 360.1208.
4.3.3. 2-hydroxy-5,6-dimethoxy-1-oxo-N-phenyl-2,3-dihydro-
1H-indene-2-carboxamide (3p). Yellow wax; 26 mg,78% yield;
1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 7.57 – 7.50 (m, 2H),
7.36 – 7.23 (m, 3H), 7.18 (s, 1H), 7.11 (d, J = 7.5 Hz, 1H), 3.99
(s, 3H), 3.89 (s, 3H), 3.76 (d, J = 16.4 Hz, 1H), 3.10 (d, J = 16.4
Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 201.06, 168.63, 157.09,
150.04, 149.22, 137.04, 128.96, 126.21, 124.66, 119.67, 107.31,
105.31, 83.04, 56.40, 56.14, 40.59. HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for [C18H18NO5+Na]+ requires m/z 350.1004,
found m/z 350.1010.
4.2.19.
2-benzoyloxy
-1-oxo-N-phenyl-cyclopentanone-2-
carboxamide (2s). Light yellow oil, 29 mg, 89% yield; 1H NMR
(400 MHz, CDCl3) δ 8.17 (s, 1H), 8.09 – 7.97 (m, 2H), 7.63 (d, J
= 7.5 Hz, 1H), 7.53 (dd, J = 16.6, 7.7 Hz, 4H), 7.35 (t, J = 7.7 Hz,
2H), 7.17 (d, J = 7.4 Hz, 1H), 3.04 (ddd, J = 13.4, 8.0, 3.4 Hz,
1H), 2.81 (dd, J = 18.9, 9.4 Hz, 1H), 2.62 – 2.40 (m, 2H), 2.38 –
2.14 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 210.92, 164.53,
164.38, 136.85, 134.12, 129.86, 129.12, 128.83, 128.51, 125.10,
120.20, 85.68, 36.15, 31.68, 18.92. HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for [C19H17NO4+Na]+ requires m/z 346.1055,
found m/z 346.1060.
4.3.4.
2-hydroxy-1-oxo-N-phenyl-1,2,3,4-tetrahydronaphth-
alene-2-carboxylate (3q) Colorless wax; 22 mg,77% yield;1H
NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 8.07 (dd, J = 7.9, 1.4
Hz, 1H), 7.65 – 7.50 (m, 3H), 7.43 – 7.29 (m, 4H), 7.13 (t, J =
7.4 Hz, 1H), 4.88 (s, 1H), 3.74 – 3.49 (m, 1H), 3.04 (ddd, J =
17.4, 5.7, 2.0 Hz, 1H), 2.64 (ddd, J = 13.5, 5.4, 2.0 Hz, 1H), 2.36
(td, J = 13.2, 5.7 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 197.07,
167.81, 145.71, 136.94, 134.68, 130.66, 129.03, 128.01, 126.73,
124.68, 119.63, 78.26, 77.35, 77.24, 34.63, 26.34. HRMS (ESI-
TOF) m/z: [M+Na]+ Calcd for [C17H15NO3+Na]+ requires m/z
304.0950, found m/z 304.0953.
4.2.20. 2-benzoyloxy-4-phenyl-1-oxo-N-phenyl-cyclobut-anone-
1
2-carboxamide (2t). Colourless oil, 32 mg, 83% yield; H NMR
(400 MHz, CDCl3) δ 8.10 – 8.00 (m, 2H), 7.74 – 7.58 (m, 2H),
7.51 (t, J = 7.8 Hz, 2H), 7.45 – 7.40 (m, 2H), 7.34 – 7.26 (m,
4.3.5.
2-hydroxy-1-oxo-N-benzyl-1,2,3,4-tetrahydronaphth-
6H), 7.21 – 7.06 (m, 1H), 5.78 (s, 1H), 3.54 – 3.26 (m, 2H). 13
C
alene-2-carboxylate (3v) White soild; 22 mg,74% yield; mp:149-
152 °C. 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 7.8 Hz, 1H),
7.56 (t, J = 7.4 Hz, 1H), 7.43 – 7.24 (m, 8H), 4.67 (s, 1H), 4.40
(dd, J = 5.9, 3.8 Hz, 2H), 3.60 (ddd, J = 17.7, 12.8, 5.3 Hz, 1H),
3.00 (ddd, J = 17.3, 5.6, 2.3 Hz, 1H), 2.55 (ddd, J = 13.5, 5.3, 2.3
Hz, 1H), 2.28 (td, J = 13.1, 5.6 Hz, 1H). 13C NMR (101 MHz,
NMR (101 MHz, CDCl3) δ 167.10, 165.22, 136.62, 135.65,
133.82, 129.77, 129.71, 129.00, 128.74, 128.54, 127.12, 124.97,
120.44, 75.02, 37.77. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
[C24H19NO4+Na]+ requires m/z 408.1212, found m/z 408.1210.
4.3. General Proceduce for the α-hydroxylation of β-keto
amides.
The reaction was conducted with β-keto amides (0.1 mmol)
CDCl3)
δ 197.35, 169.86, 145.72, 137.79, 134.50, 130.69,
128.99, 128.77, 127.97, 127.71, 127.61, 126.64, 78.12, 43.03,
34.62, 26.37. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
[C18H17NO3+Na]+ requires m/z 318.1106, found m/z 318.1103.
in
the
presence
of
TBABr
(0.005
mmol)
and benzoyl peroxide (0.13 mmol) in a mixture containing
CH2Cl2/MeOH=4:1 (2mL) and 10% or 25% KOH (0.5 mL).
The reaction was stirred at this temperature for 6-12 h. After
the reaction was completed (confirmed by TLC analysis),
the mixture was diluted with EtOAc (30 mL), washed
with water (3 × 10 mL), dried over anhydrous Na2SO4,
filtered, and concentrated in vacuo. The residue was purified
by flash chromatography (silica gel; petroleum ether/ethyl
acetate = 10:1-2:1) to afford the α-hydroxylation products.
4.3.6. 2-hydroxy-6-methoxyl-1-oxo-N-phenyl-1,2,3,4-tetrahydr-
onaphthalene-2-carboxylate (3w) Light yellow oil; 20 mg,74%
yield; 1H NMR (400 MHz, CDCl3) δ 8.88 (s, 1H), 8.04 (d, J = 8.8
Hz, 1H), 7.65 – 7.48 (m, 2H), 7.38 – 7.28 (m, 3H), 7.13 (d, J =
7.5 Hz, 1H), 6.89 (dd, J = 8.8, 2.5 Hz, 1H), 6.77 (d, J = 2.4 Hz,
1H), 4.95 (s, 1H), 3.90 (s, 3H), 3.64 (td, J = 12.8, 6.5 Hz, 1H),
3.05 – 2.92 (m, 1H), 2.65 – 2.57 (m, 1H), 2.34 (td, J = 13.3, 5.7
Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 195.19, 168.10, 164.76,
148.45, 137.01, 130.58, 129.01, 124.61, 124.03, 119.60, 113.88,
112.67, 77.96, 55.58, 34.47, 26.67. HRMS (ESI-TOF) m/z:
[M+Na]+ Calcd for [C18H17NO4+Na]+ requires m/z 334.1055,
found m/z 334.1058.
4.3.1.
2-hydroxy-1-oxo-N-phenyl-2,3-dihydro-1H-indene-2-
carboxamide (3a) White solid; 23 mg, 85% yield; mp:149-152
1
°C. H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 7.82 (d, J = 7.7
Hz, 1H), 7.60 – 7.50 (m, 3H), 7.46 (d, J = 7.5 Hz, 1H), 7.32 (t, J
= 7.9 Hz, 2H), 7.15 (d, J = 7.3 Hz, 1H), 3.88 (d, J = 16.7 Hz,
1H), 3.22 (d, J = 16.7 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ
Acknowledgements

ACCEPTED MANUSCRIPT
8
Tetrahedron
We would like to thank the National Natural
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