PIFA-Mediated Dearomatizative Spirocyclization of Phenolic Biarylic Ketones via Oxidation and C-C Bond Cleavage

Article abstract of DOI:10.1021/acs.joc.0c00971

The dearomatizing spirocyclization of phenolic biarylic ketones using PhI(OCOCF3)2 as oxidant is presented. The reaction affords various cyclohexadienones through C-C bond cleavage under mild conditions. Mechanistic investigations reveal that an exocyclic

Full text of DOI:10.1021/acs.joc.0c00971

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Note
PIFA-mediated dearomatizative spirocyclization of phenolic
biarylic ketones via oxidation and C-C bond cleavage
Guihua Zhao, Biqing Li, Shuangshuang Wang, Man Liu, Yuan Chen, and Bin Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00971 • Publication Date (Web): 24 Jun 2020
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The Journal of Organic Chemistry
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PIFA-mediated dearomatizative spirocyclization of phenolic biarylic
ketones via oxidation and C-C bond cleavage
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Gui-Hua Zhao, Bi-Qing Li, Shuang-Shuang Wang, Man Liu, Yuan Chen and Bin Wang*
College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education
Park, 38 Tongyan Road, Tianjin 300353, P. R. China.
Supporting Information Placeholder
ABSTRACT: The dearomatizing spirocyclization of phenolic biarylic ketones using PhI(OCOCF3)2 as oxidant is presented.
The reaction affords various cyclohexadienones through C-C bond cleavage under mild conditions. Mechanistic
investigations reveal that an exocyclic enol ether acts as the key intermediate in the transformation.
Many elegant synthetic methodologies and strategies have
been achieved by the use of hypervalent iodine （ III ）
reagents during the last decades. These environmentally
friendly reagents are versatile and play important roles in
organic synthesis.1 One of the most well-known
applications of the hypervalent iodine is the use in the
dearomatization of phenols to form cyclohexadienones,2
which were considered valuable intermediates in natural
product synthesis.3 The currently accepted mechanism was
cyclopentanone (C-spirocycle) could not be constructed by
this hypervalent iodine-mediated method. We found that
an exocyclic enol ether (O-spirocycle) was formed during
the reaction. It further underwent oxidation and C-C bond
cleavage to afford spirolactone (Scheme 1B). Herein, we
report this novel dearomatizative spirocyclization reaction
of phenolic biarylic ketones. To our knowledge, this
spirocyclization
Scheme
1.
Hypervalent
iodine-mediated
that the para-substituted phenol initially forms
a
dearomatizative spirocyclization
phenoxyiodine (III) intermediate, which is then converted
to a phenoxenium ion through the departure of high-
valent iodine atom. The phenoxenium ion is further
trapped by an internal nucleophile to offer the final
spirodienone (Scheme 1A).4 This also applies to the
dearomatizative cyclization of ortho-substituted phenols.
The oxygen and nitrogen nucleophiles such as carboxylic
acid, alcohol, amine, amide and guanidine, are suitable
groups for the spirocyclization.5 To date, the use of ketones
as substrates has been unexplored for this dearomatizing
spirocyclization. There are two possible sites of
spirocyclization, oxygen or α-carbon of ketone. We
envisioned the use of phenolic biarylic ketones as
substrates, with the anticipation that such substrates
might enable the formation of a five-membered C-
spirocycle or (and) an O-spirocycle with an exocyclic
double bond, under basic conditions (Scheme 1B).
Interestingly, our subsequent studies indicated that the
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A. mechanism of spirocyclization
NaOH (entries 1 and 2). When the reaction was carried out
1
2
3
4
5
6
7
8
in the absence of base, product 2a was isolated in higher
yield (entry 3). Among various solvents examined, the
reaction conducted in THF provided the best results
(entries 3-6). Increasing the amount of PIFA from 2.5
equivalents to 4.0-6.0 equivalents dramatically improved
the yield of 2a (entries 7-9). The high-yielding
spirocyclization could be achieved by use of 6.0 equiv of
PIFA, while further increasing the amount of PIFA to 7.0
equiv led to decreased yield of 2a due to side reactions
(entry 10). Other hypervalent iodine reagents such as
phenyl iodine (III) diacetate (PIDA), PhIO, and
OCOR
O
OH
O
I
O
Ph
R
R
PhI(OCOR)2
R
R
PhI
-OCOR
NuH
Nu
NuH
NuH
phenoxyiodine
NR1
phenoxenium ion
NuH = CO2H, OH, NHR, CONHR,
NHR2
B. this design: using ketones as nucleophilies
OH
N
H
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ketone
O
O
O
pentafluorophenyliodine
(III)
bis(trifluoroacetate)
PIFA
✅
C-C bond
cleavage
PIFA
R
(FPIFA), were also investigated for this dearomatizative
spirocyclization (entries 11-13). However, they were
completely ineffective because some unknown complex
products were formed. As PIFA was used in excess in the
present reaction, we attempted to realize a catalytic
transformation by use of the combination of PhI/Oxone or
PhI/mCPBA, but they proved to be unsuccessful (entry 14).
�
R
O
O
O
R
O
O
C-spirocycle
O-spirocycle
spirolactone
O-Nu vs C-Nu
through the oxidation of ketones and C-C bond breaking is
unknown in the hypervalent iodine chemistry.
Table 1. Screening of the reaction conditionsa
Having developed the effective conditions for the
spiroannulation, the scope of the substrates was further
investigated. First, the reactivity of phenyl methyl ketone
moiety with different substitutes on the phenyl ring was
tested (Table 2, 1b-h). These substrates with chloro, fluoro,
methoxyl and nitro groups underwent the spirocyclization
smoothly, furnishing the desired products 2b-h in
moderate to good yields. The structure of 2b was
confirmed unambiguously by single crystal X-ray
diffraction.6 Among the fluoro-substituted substrates 1c-e,
the para-fluoro-biphenylic ketone 1d was found to give the
highest yield. In the cases of methoxyl-substituted 1f and
1g, the position of methoxyl group on the phenyl ring had
no influence on the yield. Variations in the substituents of
phenol moiety were further evaluated (Table 2, 1i-r).
Substrate 1i with a naphthol moiety was compatible with
the reaction, producing 2i in 64% yield. Furthermore,
phenols
entry
iodine
solvent
THF
base
yield %
1
2
PIFA (2.5)
PIFA (2.5)
PIFA (2.5)
PIFA (2.5)
PIFA (2.5)
PIFA (2.5)
PIFA (4.0)
PIFA (5.0)
PIFA (6.0)
PIFA (7.0)
PIDA (6.0)
PhIO (6.0)
EtONa
15
0
THF
NaOH
3
THF
-
-
-
-
-
-
-
-
-
-
35
25
0
4
5
DCM
DME
CH3CN
THF
6
7
0
59
72
82
50
0
Table 2. Scope of the phenolic biarylic ketonesa
8
9
10
11
12
THF
THF
THF
THF
THF
0
FPIFA
(6.0)
13
THF
THF
-
-
0
0
14b
PhI (1.0)
aReaction conditions: 1a (0.3 mmol), solvent (2 mL), rt,
under air, 20 h, isolated yield. PIFA, phenyliodine (III)
bis(trifluoroacetate); PIDA, phenyliodine (III) diacetate;
FPIFA, pentafluorophenyliodine (III) bis(trifluoroacetate).
bOxone or mCPBA (2.5 eq).
We began by testing the combination of phenyliodine (III)
bis(trifluoroacetate) (PIFA) and base to effect the
spirocyclization of 4-(2-acetylphenyl) phenol 1a in THF
(Table 1). The spirolactone 2a was obtained in 15% yield
with EtONa, while no conversion was observed by use of
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aReaction conditions: 1s-x (0.3 mmol), PIFA (1.8 mmol),
THF (2 mL), rt, under air, 7-24 h, determined by TLC, isolated
yield.
We then investigated other potential substrates in this
transformation (Table 3). When the ketones with long
alkyl chains, including ethyl, phenylpropyl and (4-
methoxyphenyl) ethyl groups, were subjected to the
spirocyclization conditions, the spirocyclization occurred
to afford product 2a in moderate yields (Table 3, 1s-u).
Surprisingly, the phenolic biaryl substrates containing β-
ketoester and aldehyde functional groups could also
undergo the dearomatizing spirocyclization to give the
corresponding products 2a and 2w, albeit in low yields. In
addition, the reaction constructed a γ-crotolactone on the
para-position of phenol by use of 4-(4-hydroxyphenyl)-2-
aReaction conditions: 1a-r (0.3 mmol), PIFA (1.8 mmol),
THF (2 mL), rt, under air, 2-24 h ， determined by TLC,
isolated yield.
with dimethyl, methyl/chloro, dichloro, methoxyl/fluoro
groups on their ortho- or meta-positions reacted smoothly,
affording products 2k-m, 2o and 2q in 40-78% yields.
Surprisingly, meta-methoxyl substituted substrate 1r gave
the desired product 2r in 86% yield, which was much
higher than that of ortho-methoxyl substituted substrate
1p (49%). It indicated that the efficiency of annulation was
not influenced by the steric hindrance of methoxyl group.
Instead, the presence of a methoxyl group adjacent to the
reaction site improved the spirocyclization. A similar
promotion from meta-methyl groups was also observed in
the reaction of 1o (65%), which gave higher yield than 1k
(42%).
butanone 1x.
A dehydrogenation of five-membered
spirocycle was achieved by this strategy (2x). This kind of
product could not be obtained by the existing hypervalent-
iodine (III)-mediated spirocyclization of carboxylic acid.5b
Scheme 2. Control experiments
Table 3. Scope of the phenolic biarylic ketones with
long alkyl side chaina
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through addition/elimination, resulting in the formation
of intermediate E (pathway b).8a The hydrolysis of F gave
glycol intermediate G, which afforded the final product 2a
and aldehyde through the well-established hypervalent
iodine (III)-mediated oxidation and C-C bond cleavage of
glycols.7, 10
1
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7
Scheme 3. proposed mechanism
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After the investigation of substrate scope, we performed
control experiments to explore the reaction mechanism
(Scheme 2). When 2-acetylnaphthalene
3 and 2'-
phenylacetophenone 4 were respectively subjected to the
standard reaction conditions, the acetyl group remained
intact and no reaction was observed (eqs 1 and 2). The
results excluded the possibility that the corresponding
carboxylic acids were the intermediates of the
spirocyclization. We then carried out the experiments of 1t
by reducing the amount of PIFA from 0.8 to 0.4 equiv (eq
3). The reaction produced the desired product 2a and
simultaneously afforded an exocyclic enol ether B after 3
hours. The transformation of B leading to 2a was further
achieved by the addition of PIFA and prolonging reaction
time. Compound B was isolated and its structure was
confirmed by NMR and HR MS. It was further subjected to
the present spirocyclization conditions. Product 2a was
formed in almost quantitative yield (eq 4). These results
suggest that enol ether B is most likely an intermediate of
the present spirocyclization. Unfortunately, attempts to
capture the fragment from phenylpropyl group of 1t failed.
We propose that this alkyl moiety is further oxidized by
PIFA to the undetectable small molecules.7
In conclusion, we have developed a spirocyclization
reaction using phenolic biarylic ketones as starting
materials
under
mild
conditions.
This
novel
transformation involves dearomatization/oxidation/C-C
bond cleavage processes. The proposed mechanism is
supported by the isolation and identification of an
exocyclic enol ether intermediate.
EXPERIMENTAL SECTION
General Remarks
13
1H NMR and C NMR spectra were recorded on a Bruker
AVANCE AV400 (400 MHz for H and 101 MHz for C).
Signal positions were recorded in ppm with the
abbreviations s, d, t, q, and m denoting singlet, doublet,
triplet, quartet, and multiplet respectively. All NMR
chemical shifts were referenced to residual solvent peaks
or to Si(CH3)4 as an internal standard. NMR Spectra
recorded in CDCl3 were referenced to residual CHCl3 at
7.26 ppm for 1H or 77.0 ppm for 13C. NMR spectra recorded
in DMSO-d6 were referenced to residual DMSO at 2.49
ppm and 3.33 ppm for 1H or 39.6 ppm for 13C. All coupling
constants J were quoted in Hz. Data were reported as
follows: chemical shift, multiplicity, coupling constant and
integration. HRMS were measured using Q-TOF LC−MS
and the ESI-FTICR technique. Reactions were monitored
by thin-layer chromatography (TLC) on 0.25mm silica gel
glass plates coated with 60 F254. Column chromatography
Based on our results and previous reports,7-8 a mechanism
for the spirocyclization was proposed (Scheme 3). First, the
phenolic oxygen of substrate 1 attacks PIFA to give
intermediate A, which further underwent intramolecular
spirocyclization to afford enol ether B. The excess PIFA
then reacted with alkene moiety of B to form intermediate
8a
C,1e,
which was converted to cyclic intermediate F8a,9
through two possible pathways. In pathway a, an
intramolecular rearrangement of C occurred to yield
intermediate D. Intermediate C could also react with TFA
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was performed on silica gel (200-300 mesh) using a mixture
80.1. HRMS (ESI) m/z: [M+H]+ calcd for C13H8FO3 231.0457;
found, 231.0483.
1
2
3
4
5
6
7
8
of petroleum ether (60-90°C) and ethyl acetate as eluant.
All reagents were weighed and handled in air at room
temperature and all reactions were performed under an air
atmosphere. Commercially available reagents were used as
received without further purification. Reactants 1x were
purchased from commercial sources, and reactants 1a-h,
1s-u, 1v, 1i-1r were prepared by the known method11and
analytical data matched literature values.
5'-fluoro-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
diene-3',4-dione (2d). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
yellow oil (51.8mg, 75%) 1H NMR (400 MHz, CDCl3) δ 7.64
(dd, J = 6.9, 2.4 Hz, 1H), 7.46 (td, J = 8.5, 2.4 Hz, 1H), 7.32
(dd, J = 8.4, 4.2 Hz, 1H), 6.73 – 6.59 (m, 2H), 6.51 – 6.36 (m,
13
2H). C{1H} NMR (101 MHz, CDCl3) δ 184.0, 167.7, 165.2 ,
9
162.7, 143.9, 142.1, 130.1, 123.4, 123.2, 113.1, 80.3. HRMS (ESI)
General Procedure for the Preparation of Products
2a-r, 2w, 2x
m/z: [M+H]+ calcd for C13H8FO3 231.0457; found, 231.0456.
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4'-fluoro-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
diene-3',4-dione (2e). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
colorless oil (42.6 mg, 61%) 1H NMR (400 MHz, DMSO-d6)
δ 7.85 (td, J = 8.0, 4.7 Hz, 1H), 7.50 (t, J = 8.9 Hz, 1H), 7.32
(d, J = 7.7 Hz, 1H), 7.06 (d, J = 9.7 Hz, 2H), 6.44 (d, J = 9.8
Hz, 2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 184.6, 165.5,
165.5, 160.6, 157.9, 149.3, 138.7, 138.6, 130.1, 119.6, 119.6, 117.9,
117.7, 114.0, 113.9, 80.4. HRMS (ESI) m/z: [M+H]+ calcd for
C13H8FO3 231.0457; found, 231.0450.
Substrate 1 (0.3 mmol, 1 equiv) was added to PIFA (1.8
mmol, 774.07 mg, 6.0 equiv) under air, and THF (2 mL)
were added. After the mixture was stirred at room
temperature for 2-24 h, the residue was mixed with silica
gel and concentrated. The resulting mixture was purified
by silica gel column chromatography on silica gel with
petroleum ether and EtOAc as eluent to give the desired
product 2.
Large Scale for the Synthesis of Product 2a.
6'-methoxy-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
diene-3',4-dione (2f). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
yellow solid (44.8 mg, 62%). Mp: 218-228 °C. 1H NMR (400
MHz, DMSO-d6) δ 7.87 (d, J = 8.5 Hz, 1H), 7.21 (dd, J = 8.6,
2.2 Hz, 1H), 7.04 (d, J = 2.1 Hz, 1H), 6.96 (d, J = 9.7 Hz, 2H),
6.41 (d, J = 9.9 Hz, 2H), 3.85 (s, 3H). 13C{1H} NMR (101 MHz,
DMSO-d6) δ 184.7, 168.8, 165.6, 150.1, 145.3, 130.1, 128.1, 118.9,
117.9, 106.9, 80.0, 56.8. HRMS (ESI) m/z: [M+H]+ calcd for
C14H11O4 243.0657; found, 243.0648.
Substrate 1-(4'-hydroxy-[1,1'-biphenyl]-2-yl)ethan-1-one 1a
(1 mmol, 1.0 equiv) was added to PIFA (6.0 mmol, 2580 mg,
6.0 equiv) under air, and THF (7mL) were added. After the
mixture was stirred at room temperature for 20 h, the
residue was mixed with silica gel and concentrated. The
resulting mixture was purified by silica gel column
chromatography on silica gel with petroleum ether: EtOAc
(10:1) as eluent to give the desired product 2a (141 mg, 66%).
3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-diene-3',4-
dione (2a).12 Following general procedure 1a in 0.3 mmol
scale. Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1:10), colorless solid (52.1 mg,
82%). 1H NMR (400 MHz, CDCl3) δ 8.00 (t, J = 5.2 Hz, 1H),
7.78 – 7.61 (m, 2H), 7.32 (dd, J = 7.9, 2.9 Hz, 1H), 6.67 (dd, J
= 9.8, 3.1 Hz, 2H), 6.43 (dd, J = 9.9, 3.1 Hz, 2H). 13C{1H} NMR
(101 MHz, CDCl3) δ 184.3, 169.0, 146.6, 144.3, 135.23, 130.7,
129.9, 126.8, 125.6, 122.5, 80.4. HRMS (ESI) m/z: [M + Na]+
calcd for C13H8O3Na 235.0366; found, 235.0369.
5'-methoxy-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
diene-3',4-dione (2g). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
yellow oil (44.3 mg, 61%). 1H NMR (400 MHz, DMSO-d6) δ
7.44 (d, J = 2.2 Hz, 1H), 7.41 – 7.33 (m, 2H), 7.00 – 6.93 (m,
2H), 6.42 – 6.36 (m, 2H), 3.88 (s, 3H).13C{1H} NMR (101
MHz, DMSO-d6) δ 184.7, 169.1, 161.8, 145.8, 138.7, 129.7,
127.5, 124.3, 123.9, 109.2, 80.5, 56.6. HRMS (ESI) m/z:
[M+Na]+ calcd for C14H11O4Na 265.0471; found, 265.0475.
6'-chloro-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
5'-nitro-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
diene-3',4-dione (2h). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
13
diene-3',4-dione (2b). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
white solid (51.3 mg, 70%). 1H NMR (400 MHz, CDCl3) δ
7.92 (d, J = 8.2 Hz, 1H), 7.61 (dd, J = 8.1, 1.7 Hz, 1H), 7.29 (d,
J = 1.7 Hz, 1H), 6.70 – 6.59 (m, 2H), 6.50 – 6.38 (m, 2H).
13C{1H} NMR (101 MHz, CDCl3) δ 183.9, 167.8, 148.4, 143.5,
142.1, 131.5, 130.3, 127.9, 124.1, 122.9, 79.8. HRMS (ESI) m/z:
[M+H]+ calcd for C13H8ClO3 247.0162; found, 247.0161.
1
yellow solid (30.8 mg, 40%). H NMR (400 MHz, DMSO-
d6) δ 8.64 (d, J = 2.1 Hz, 1H), 8.58 (dd, J = 8.4, 2.2 Hz, 1H),
7.84 (d, J = 8.4 Hz, 1H), 7.07 (d, J = 9.9 Hz, 2H), 6.49 (d, J =
9.9 Hz, 2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 184.4,
167.5, 152.1, 150.0, 144.0, 130.7, 130.4, 128.0, 125.2, 121.5, 81.0.
3H,4'H-spiro[isobenzofuran-1,1'-naphthalene]-3,4'-dione
14
(2i). Purification by flash column chromatography (ethyl
6'-fluoro-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
diene-3',4-dione (2c). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
colorless solid (35.3 mg, 46%). Mp: 172-178 °C. 1H NMR (400
MHz, DMSO-d6) δ 8.05 (dd, J = 9.1, 4.7 Hz, 1H), 7.55 (ddt, J
= 7.0, 4.3, 2.1 Hz, 2H), 7.05 – 6.93 (m, 2H), 6.52 – 6.36 (m,
2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 184.5, 168.2, 168.1,
165.5, 150.2, 150.1, 130.5, 129.3, 122.4, 119.3, 119.1, 111.0, 110.8,
acetate/petroleum ether, v/v, 1:10), russet solid (48.2 mg,
64%). 1H NMR (400 MHz, CDCl3) δ 8.26 – 8.18 (m, 1H), 8.08
– 8.00 (m, 1H), 7.66 – 7.56 (m, 2H), 7.55 – 7.48 (m, 2H), 7.13
– 7.05 (m, 1H), 7.04 – 6.97 (m, 1H), 6.78 (d, J = 10.1 Hz, 1H),
13
6.61 (d, J = 10.1 Hz, 1H). C{1H} NMR (101 MHz, CDCl3) δ
183.53, 169.7,150.2, 144.7, 139.0, 135.3, 133.6, 130.2, 130.0, 129.5,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 10
127.2, 126.5, 126.5, 125.1, 122.6, 81.6. HRMS (ESI) m/z:
brown oil (47.1 mg, 65%). 1H NMR (400 MHz, CDCl3) δ 8.00
[M+H]+ calcd for C17H11O3 263.0703; found, 263.0700.
(d, J = 7.7 Hz, 1H), 7.69 (dtd, J = 32.5, 7.4, 1.0 Hz, 2H), 7.21
1
2
3
4
5
6
7
8
13
(d, J = 7.6 Hz, 1H), 6.27 (s, 2H), 1.65 (s, 6H). C{1H} NMR
3-methyl-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
diene-3',4-dione (2j). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
brown solid (39.5 mg, 59%). Mp: 152-158 °C. 1H NMR (400
MHz, CDCl3) δ 7.98 (dd, J = 7.5, 2.7 Hz, 1H), 7.66 (dtd, J =
36.9, 7.3, 3.0 Hz, 2H), 7.34 – 7.22 (m, 1H), 6.62 (dt, J = 9.8,
3.1 Hz, 1H), 6.41 (dd, J = 9.7, 2.9 Hz, 2H), 1.97 (s, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ 185.1, 144.0, 139.4, 137.1, 130.5,
129.9, 126.7, 122.4, 15.7. HRMS (ESI) m/z: [M+H]+ calcd for
C14H12O3 227.0708; found, 227.0706.
(101 MHz, CDCl3) δ 184.9, 169.9, 154.6, 148.1, 135.4, 130.6,
126.4, 126.1, 121.4, 17.1. HRMS (ESI) m/z: [M+H]+ calcd for
C15H13O3 241.0865; found, 241.0866.
3-methoxy-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
diene-3',4-dione (2p). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
pale yellow solid (35.5 mg, 49%). Mp: 176-182 °C.1H NMR
(400 MHz, CDCl3) δ 7.99 (dt, J = 7.6, 1.0 Hz, 1H), 7.69 (dtd,
J = 38.7, 7.5, 1.1 Hz, 2H), 7.33 (dt, J = 7.7, 0.9 Hz, 1H), 6.65
(dd, J = 9.9, 2.7 Hz, 1H), 6.42 (d, J = 10.0 Hz, 1H), 5.57 (d, J =
2.8 Hz, 1H), 3.69 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
179.8, 169.0, 151.5, 147.8, 144.9, 135.2, 130.5, 129.1, 126.7, 125.6,
122.4, 111.3, 82.6, 55.4. HRMS (ESI) m/z: [M+H]+ calcd for
C14H11O4 243.0657; found, 243.0658.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3,5-dimethyl-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-
2,5-diene-3',4-dione (2k). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
1
gray solid (30.3 mg, 42%). Mp: 148-150 °C. H NMR (400
MHz, CDCl3) δ 7.96 (dt, J = 7.6, 1.0 Hz, 1H), 7.69 (td, J = 7.5,
1.2 Hz, 1H), 7.60 (td, J = 7.5, 1.0 Hz, 1H), 7.28 – 7.25 (m, 1H),
6.40 (d, J = 1.2 Hz, 2H), 1.98 (s, 6H). 13C{1H} NMR (101 MHz,
CDCl3) δ 185.9, 169.3, 147.8, 139.1, 136.9, 134.9, 130.2, 126.6,
125.8, 122.4, 81.3, 15.9. HRMS (ESI) m/z: [M+H]+ calcd for
C15H13O3 241.0865; found, 241.0867, 242.0880.
2-fluoro-5-methoxy-3'H-spiro[cyclohexane-1,1'-
isobenzofuran]-2,5-diene-3',4-dione (2q). Purification by
flash column chromatography (ethyl acetate/petroleum
ether, v/v, 1:10), white solid (61.2 mg, 78%). Mp: 193-196 °C.
1H NMR (400 MHz, CDCl3) δ 8.02 (dt, J = 7.6, 1.0 Hz, 1H),
7.77 (td, J = 7.5, 1.2 Hz, 1H), 7.69 (td, J = 7.5, 1.0 Hz, 1H), 7.39
(dt, J = 7.8, 1.0 Hz, 1H), 6.15 (d, J = 10.9 Hz, 1H), 5.42 (d, J =
3-chloro-5-methyl-3'H-spiro[cyclohexane-1,1'-
isobenzofuran]-2,5-diene-3',4-dione (2l). Purification by
flash column chromatography (ethyl acetate/petroleum
ether, v/v, 1:10), yellow solid (49.8 mg, 65%). Mp: 129-135°C.
1H NMR (400 MHz, CDCl3) δ 8.03 – 7.96 (m, 1H), 7.75 (t, J
= 7.5 Hz, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.34 (d, J = 7.7 Hz, 1H),
6.81 (d, J = 3.0 Hz, 1H), 6.46 (dd, J = 3.3, 1.7 Hz, 1H), 2.04 (s,
3H). 13C{1H} NMR (101 MHz, CDCl3) δ 178.5, 168.6, 146.2,
139.6, 136.6, 135.3, 134.4, 130.8, 126.9, 125.6, 122.5, 81.33, 16.2.
HRMS (ESI) m/z: [M+H]+ calcd for C14H10ClO3 261.0318;
found:261.0316.
13
9.1 Hz, 1H), 3.72 (s, 3H). C{1H} NMR (101 MHz, CDCl3) δ
180.7, 171.1, 168.2, 151.4, 145.3, 135.4, 131.2, 126.7, 126.1, 122.2,
110.1, 107.2, 80.9, 556.0. HRMS (ESI) m/z: [M+H]+ calcd for
C14H10FO4 261.0563; found, 261.0559.
2-methoxy-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
diene-3',4-dione (2r). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
yellow solid (62.7 mg, 86%). Mp: 142-146 °C. 1H NMR (400
MHz, CDCl3) δ 7.99 (dt, J = 7.6, 1.1 Hz, 1H), 7.68 (dtd, J =
30.8, 7.5, 1.1 Hz, 2H), 7.28 (dt, J = 7.7, 0.9 Hz, 1H), 6.51 – 6.34
(m, 2H), 5.72 (d, J = 1.5 Hz, 1H), 3.64 (s, 3H).13C{1H} NMR
(101 MHz, CDCl3) δ 186.2, 169.0, 146.8, 140.1, 135.0, 130.6,
129.7, 126.5, 126.1, 121.7, 103.0, 80.3, 56.4. HRMS (ESI) m/z:
[M+H]+ calcd for C14H11O4 243.0657; found, 243.0658.
3,5-dichloro-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-
2,5-diene-3',4-dione (2m). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
pale yellow solid (39.6 mg, 40%). Mp: 197-199 °C. 1H NMR
(400 MHz, CDCl3) δ 8.03 (dt, J = 7.5, 0.9 Hz, 1H), 7.75 (dtd,
J = 37.8, 7.5, 1.1 Hz, 2H), 7.41 (dt, J = 7.8, 0.9 Hz, 1H), 6.86 (s,
2H).13C{1H} NMR (101 MHz, CDCl3) δ 171.9, 167.8, 144.8,
140.3, 135.6, 133.5, 131.4, 127.3, 125.4, 122.6, 81.2. HRMS (ESI)
m/z: [M+H]+ calcd for C13H7Cl2O3 280.9772; found,
280.9765.
3'H-spiro[cyclohexane-1,1'-naphtho[1,2-c]furan]-2,5-diene-
3',4-dione (2w). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
yellow oil (19.6 mg, 23%). 1H NMR (400 MHz, CDCl3) δ 8.08
(dd, J = 20.5, 8.3 Hz, 2H), 7.95 (d, J = 8.4 Hz, 1H), 7.81 – 7.68
(m, 2H), 7.67 – 7.57 (m, 1H), 6.81 – 6.69 (m, 2H), 6.67 – 6.54
(m, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 184.4, 144.9, 144.3,
136.7, 132.5, 131.1, 129.6, 128.6, 126.5, 124.2, 122.8, 120.9, 79.5.
HRMS (ESI) m/z: [M + Na]+ calcd for C17H10O3Na 285.0528;
found, 285.0528.
2-methyl-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-2,5-
diene-3',4-dione (2n). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
1
white solid (39.6 mg, 59%). Mp: 86-95 °C. H NMR (400
MHz, CDCl3) δ 8.01 (d, J = 7.6 Hz, 1H), 7.69 (dt, J = 34.6, 7.5
Hz, 2H), 7.24 (d, J = 7.7 Hz, 1H), 6.63 (dd, J = 9.9, 1.4 Hz,
1H), 6.46 – 6.23 (m, 2H), 1.66 (s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 185.0, 169.4, 154.2, 147.3, 144.7, 135.3, 129.4,
128.5, 126.6, 125.9, 122.0, 82.6, 17.2. HRMS (ESI) m/z: [M+H]+
calcd for C14H11O3 227.0708; found, 227.0709.
15
1-oxaspiro[4.5]deca-3,6,9-triene-2,8-dione
(2x).
Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/5), colorless solid (10 mg,
20%). 1H NMR (400 MHz, CDCl3) δ 7.18 (d, J = 5.5 Hz, 1H),
6.61 – 6.51 (m, 2H), 6.46 – 6.39 (m, 2H), 6.36 (d, J = 5.4 Hz,
1H). 13C{1H} NMR (101 MHz, CDCl3) δ 183.6, 171.3, 154.4, 131.3,
123.6, 81.9. HRMS (ESI) m/z: [M+H]+ calcd for C9H7O3
163.0395; found, 163.0391.
2,6-dimethyl-3'H-spiro[cyclohexane-1,1'-isobenzofuran]-
2,5-diene-3',4-dione (2o). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1:10),
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The Journal of Organic Chemistry
1-(4'-hydroxy-[1,1'-biphenyl]-2-yl)ethan-1-one
Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), white solid (78%). H
NMR (400 MHz, CDCl3) δ 7.55 – 7.46 (m, 2H), 7.38 (d, J =
7.4 Hz, 2H), 7.19 (dd, J = 8.5, 2.3 Hz, 2H), 6.89 (dd, J = 8.5,
2.3 Hz, 2H), 6.50 (s, 1H), 2.06 (s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 206.9, 156.2, 140.6, 132.7, 131.0, 130.3, 127.8,
127.1, 30.5. HRMS (ESI) m/z: [M+H]+ calcd for C14H13O2
213.0916; found, 213.0912.
(1a).
1-(4'-hydroxy-4-methoxy-[1,1'-biphenyl]-2-yl)ethan-1-one
1
2
3
4
5
6
7
8
16
(1g). Purification by flash column chromatography (ethyl
1
acetate/petroleum ether, v/v, 1/15), pale yellow oil (78%).
1H NMR (400 MHz, DMSO-d6) δ 9.56 (s, 1H), 7.29 (d, J = 8.5
Hz, 1H), 7.13 – 7.03 (m, 3H), 7.01 (d, J = 2.7 Hz, 1H), 6.85 –
6.78 (m, 2H), 3.81 (s, 3H), 2.04 (s, 3H). 13C{1H} NMR (101
MHz, DMSO-d6) δ 204.2, 158.4, 157.4, 141.8, 132.8, 131.8,
131.0, 130.2, 116.9, 116.0, 112.8, 55.9, 30.7. HRMS (ESI) m/z:
[M+H]+ calcd for C15H15O3 243.1016; found, 243.1019.
9
1-(5-chloro-4'-hydroxy-[1,1'-biphenyl]-2-yl)ethan-1-one
(1b). Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), white solid (75%). H
NMR (400 MHz, CDCl3) δ 7.49 (d, J = 8.1 Hz, 1H), 7.40 –
7.33 (m, 2H), 7.20 – 7.08 (m, 3H), 6.93 – 6.87 (m, 2H), 2.06
(s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 206.0, 156.7, 142.4,
138.6, 137.1, 130.3, 130.1, 129.5, 127.2, 116.0, 30.4. HRMS (ESI)
m/z: [M+H]+ calcd for C14H12ClO2 247.0526; found,
247.0519.
1-(4'-hydroxy-4-nitro-[1,1'-biphenyl]-2-yl)ethan-1-one (1h).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
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50
51
52
53
54
55
56
57
58
59
60
Purification by flash column chromatography (ethyl
1
1
acetate/petroleum ether, v/v, 1/15), yellow solid. H NMR
(400 MHz, DMSO-d6) δ 9.91 (s, 1H), 8.35 (dd, J = 8.5, 2.5 Hz,
1H), 8.29 (d, J = 2.5 Hz, 1H), 7.69 (d, J = 8.5 Hz, 1H), 7.21 (d,
J = 8.2 Hz, 2H), 6.90 (d, J = 8.3 Hz, 2H), 2.15 (s, 3H). 13C{1H}
NMR (101 MHz, DMSO-d6) δ 202.7, 159.0, 146.5, 146.4, 141.4,
132.0, 130.6, 129.0, 125.5, 123.1, 30.5.
1-(2-(4-hydroxynaphthalen-1-yl)phenyl)ethan-1-one (1i).
1-(5-fluoro-4'-hydroxy-[1,1'-biphenyl]-2-yl)ethan-1-one (1c).
Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), yellow solid (85%). H
NMR (400 MHz, CDCl3) δ 7.57 (dd, J = 9.4, 5.7 Hz, 1H), 7.23
– 7.15 (m, 2H), 7.07 (ddt, J = 8.2, 3.8, 2.0 Hz, 2H), 6.94 – 6.85
(m, 2H), 2.05 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 205.1,
165.1, 162.6, 156.6, 143.5, 136.7, 131.7, 130.6, 130.5, 130.0, 117.2,
116.9, 115.9, 114.2, 114.0, 30.4. HRMS (ESI) m/z: [M+H]+ calcd
for C14H12FO2 231.0816; found, 231.0812.
Purification by flash column chromatography (ethyl
1
acetate/petroleum ether, v/v, 1/15), yellow solid (60%). H
1
NMR (400 MHz, CDCl3) δ 8.33 – 8.25 (m, 1H), 7.73 (dd, J =
7.7, 1.5 Hz, 1H), 7.68 – 7.60 (m, 1H), 7.60 – 7.40 (m, 5H), 7.10
(d, J = 7.6 Hz, 1H), 6.89 (d, J = 8.4 Hz, 1H), 6.75 (d, J = 7.7
Hz, 1H), 1.83 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 205.6,
152.3, 141.6, 139.3, 132.9, 132.1, 130.9, 130.5, 128.2, 127.9, 127.5,
127.1, 125.5, 125.3, 124.7, 122.4, 108.1, 29.8. HRMS (ESI) m/z:
[M+H]+ calcd for C18H15O2 263.1067; found, 263.1067.
1-(4-fluoro-4'-hydroxy-[1,1'-biphenyl]-2-yl)ethan-1-one
(1d). Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), yellow solid (85%). Mp:
130-136 °C. 1H NMR (400 MHz, CDCl3) δ 7.39 – 7.24 (m, 5H),
5.42 (dd, J = 7.6, 5.7 Hz, 1H), 3.23 (dd, J = 15.7, 7.7 Hz, 1H),
2.81 (dd, J = 15.7, 5.6 Hz, 1H), 1.94 (ddd, J = 12.4, 7.9, 4.6 Hz,
1H), 1.21 (s, 9H), 1.06 – 0.94 (m, 2H), 0.89 – 0.79 (m, 2H).
13C{1H} NMR (101 MHz, CDCl3) δ 207.8, 140.1, 128.3, 128.0,
127.0, 82.0, 80.6, 48.6, 26.4, 21.3, 11.1, 11.0. HRMS (ESI) m/z:
[M+H]+ calcd for C14H12FO2 231.0816; found, 231.0811.
1-(4'-hydroxy-3'-methyl-[1,1'-biphenyl]-2-yl)ethan-1-one
(1j). Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), yellow solid (85%). Mp:
77-80 °C. 1H NMR (400 MHz, CDCl3) δ 7.56 – 7.45 (m, 2H),
7.40 – 7.34 (m, 2H), 7.12 (d, J = 2.3 Hz, 1H), 6.99 (dd, J = 8.1,
2.3 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 2.28 (s, 3H), 2.05 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ 206.8, 154.4, 140.7, 132.7,
131.3, 130.9, 130.2, 127.8, 127.7, 126.9, 124.7, 115.2, 30.5. HRMS
(ESI) m/z: [M+H]+ calcd for C15H15O2 227.1067; found,
227.1069.
1-(3-fluoro-4'-hydroxy-[1,1'-biphenyl]-2-yl)ethan-1-one
(1e). Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), white solid (78%) H
NMR (400 MHz, CDCl3) δ 7.40 (td, J = 8.0, 5.7 Hz, 1H), 7.16
(dd, J = 7.9, 5.2 Hz, 3H), 7.08 (t, J = 8.9 Hz, 1H), 6.87 – 6.78
(m, 2H), 2.26 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
203.2, 160.0, 157.5, 156.2, 141.3, 131.0, 130.9, 130.1, 125.8, 115.8,
114.2, 32.4. HRMS (ESI) m/z: [M+H]+ calcd for C14H12FO2
231.0816; found, 231.0819.
1-(4'-hydroxy-3',5'-dimethyl-[1,1'-biphenyl]-2-yl)ethan-1-
one (1k). Purification by flash column chromatography
(ethyl acetate/petroleum ether, v/v, 1/15), brown solid
(80%). Mp: 120-122 °C. 1H NMR (400 MHz, CDCl3) δ 7.52 –
7.43 (m, 2H), 7.34 (ddd, J = 8.9, 7.2, 1.3 Hz, 2H), 6.94 (s, 2H),
2.27 (s, 6H), 2.03 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
206.3, 152.7, 140.7, 132.5, 130.8, 130.2, 129.1, 127.8, 126.8, 123.9,
30.5, 16.1. HRMS (ESI) m/z: [M+H]+ calcd for C16H17O2
241.1223; found, 241.1227.
1
1-(4'-hydroxy-5-methoxy-[1,1'-biphenyl]-2-yl)ethan-1-one
(1f). Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), yellow solid (68%). Mp:
1-(3'-chloro-4'-hydroxy-5'-methyl-[1,1'-biphenyl]-2-
yl)ethan-1-one (1l). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1/15),
1
134-136 °C. H NMR (400 MHz, DMSO-d6) δ 9.63 (s, 1H),
1
brown solid (75%). Mp: 88-91 °C. H NMR (400 MHz,
7.53 (d, J = 8.6 Hz, 1H), 7.16 – 7.09 (m, 2H), 6.96 (dd, J = 8.6,
2.6 Hz, 1H), 6.88 – 6.80 (m, 3H), 3.84 (s, 3H), 1.99 (s, 3H).
CDCl3) δ 7.54 (dd, J = 7.6, 1.5 Hz, 1H), 7.49 (td, J = 7.5, 1.5
Hz, 1H), 7.40 (td, J = 7.5, 1.3 Hz, 1H), 7.33 (dd, J = 7.6, 1.3 Hz,
1H), 7.17 (d, J = 2.2 Hz, 1H), 7.01 (dd, J = 2.0, 1.0 Hz, 1H), 5.74
(s, 1H), 2.32 (s, 3H), 2.09 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 204.7, 149.5, 140.6, 139.1, 133.4, 130.8, 130.2, 127.5,
126.4, 126.3, 119.8, 30.5, 16.4. HRMS (ESI) m/z: [M+H]+ calcd
for C15H14ClO2 261.0677; found, 261.0678.
13C{1H}
NMR (101 MHz, DMSO-d6) δ 202.3, 161.4, 157.9, 143.3,
133.2, 131.6, 130.7, 130.3, 115.9, 115.6, 112.8, 55.9, 30.5. HRMS
(ESI) m/z: [M+H]+ calcd for C15H15O3 243.1016; found,
243.1018.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
3-(tert-butylperoxy)-3-(naphthalen-2-yl)-1-phenylpropan- 1-(4'-hydroxy-[1,1'-biphenyl]-2-yl)propan-1-one
Page 8 of 10
(1s).
1
2
3
4
5
6
7
8
1-one (1m). Purification by flash column chromatography
(ethyl acetate/petroleum ether, v/v, 1/15), pale yellow solid
(52%). Mp: 126-128 °C. 1H NMR (400 MHz, CDCl3) δ 7.62 –
7.56 (m, 1H), 7.51 (td, J = 7.5, 1.5 Hz, 1H), 7.44 (td, J = 7.5, 1.3
Hz, 1H), 7.34 – 7.29 (m, 1H), 7.26 (d, J = 5.0 Hz, 2H), 2.20 (s,
3H). 13C{1H} NMR (101 MHz, CDCl3) δ 203.5, 140.2, 137.8,
134.4, 131.1, 130.4, 128.5, 128.3, 128.1, 121.3, 30.4. HRMS (ESI)
m/z: [M+H]+ calcd for C14H11Cl2O2 281.0131; found, 281.0128.
Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), brown solid (75%). Mp:
100-101 °C. 1H NMR (400 MHz, CDCl3) δ 7.52 – 7.41 (m, 2H),
7.38 (d, J = 7.5 Hz, 2H), 7.18 (dt, J = 8.5, 2.0 Hz, 2H), 6.88
(dt, J = 8.5, 2.0 Hz, 2H), 6.43 (d, J = 3.5 Hz, 1H), 2.34 (q, J =
13
6.4, 5.8 Hz, 2H), 0.94 (t, J = 7.1 Hz, 3H). C{1H} NMR (101
MHz, CDCl3) δ 210.7, 156.0, 140.7, 139.8, 130.6, 130.1, 130.1,
127.5, 127.0, 115.8, 36.3, 8.7. HRMS (ESI) m/z: [M+H]+ calcd
for C15H15O2 227.1067; found, 227.1067.
9
1-(4'-hydroxy-2'-methyl-[1,1'-biphenyl]-2-yl)ethan-1-one
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(1n). Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), brown oil (42%). H
1-(4'-hydroxy-[1,1'-biphenyl]-2-yl)-4-phenylbutan-1-one
(1t). Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), brown oil (65%). H
1
1
NMR (400 MHz, CDCl3) δ 7.70 – 7.58 (m, 1H), 7.53 – 7.32
(m, 2H), 7.24 (dd, J = 7.6, 1.5 Hz, 1H), 6.98 – 6.60 (m, 4H),
2.07 (d, J = 6.5 Hz, 3H), 2.02 – 1.95 (m, 3H).13C{1H} NMR (101
MHz, CDCl3) δ 205.4, 156.0, 140.5, 137.1, 132.6, 131.2, 131.1,
130.8, 128.1, 127.2, 117.2, 29.9, 20.3. HRMS (ESI) m/z: [M+H]+
calcd for C15H15O2 227.1067; found, 227.1069.
NMR (400 MHz, CDCl3) δ 7.49 – 7.40 (m, 2H), 7.34 (q, J =
5.2, 2.8 Hz, 2H), 7.18 (dd, J = 18.7, 11.3 Hz, 5H), 6.98 (d, J =
7.2 Hz, 2H), 6.85 (d, J = 7.6 Hz, 2H), 6.54 (s, 1H), 2.40 (t, J =
6.8 Hz, 2H), 2.32 (t, J = 6.5 Hz, 2H), 1.76 (p, J = 7.7 Hz, 2H).
13C{1H} NMR (101 MHz, CDCl3) δ 210.0, 156.1, 141.4, 140.7,
140.0, 132.6, 130.7, 130.2, 130.1, 128.4, 128.4, 127.6, 127.1, 125.9,
115.8, 42.4, 35.0, 26.3. HRMS (ESI) m/z: [M+H]+ calcd for
C22H21O2 317.1536, found, 317.1538.
1-(4'-hydroxy-2',6'-dimethyl-[1,1'-biphenyl]-2-yl)ethan-1-
one (1o). Purification by flash column chromatography
(ethyl acetate/petroleum ether, v/v, 1/15), brown solid
(60%). Mp: 52-55 °C. 1H NMR (400 MHz, CDCl3) δ 7.74 (d,
J = 7.8 Hz, 1H), 7.47 (dt, J = 44.4, 7.5 Hz, 3H), 7.13 (d, J = 7.6
Hz, 1H), 6.60 (s, 2H), 2.00 (s, 3H), 1.92 (s, 6H). 13C{1H} NMR
(101 MHz, CDCl3) δ 155.2, 140.1, 139.6, 137.4, 132.7, 131.7, 131.2,
128.6, 127.3, 29.3, 20.8. HRMS (ESI) m/z: [M+H]+ calcd for
C16H17O2 ( M+H)+: 241.1223; found, 241.1228.
1-(4'-hydroxy-[1,1'-biphenyl]-2-yl)-3-(4-
methoxyphenyl)propan-1-one (1u). Purification by flash
column chromatography (ethyl acetate/petroleum ether,
v/v, 1/15), brown solid (50%). Mp: 87-90 °C.1H NMR (400
MHz, CDCl3) δ 7.39 (d, J = 7.7 Hz, 1H), 7.34 – 7.24 (m, 3H),
7.07 (t, J = 5.5 Hz, 2H), 6.76 (dt, J = 9.4, 5.0 Hz, 4H), 6.65
(dd, J = 8.6, 3.2 Hz, 2H), 5.98 – 5.61 (m, 1H), 3.67 (s, 3H),
2.63 (t, J = 7.5 Hz, 2H), 2.50 (t, J = 7.5 Hz, 2H). 13C{1H} NMR
(101 MHz, CDCl3) δ 208.4, 157.8, 155.9, 140.7, 139.8, 132.9,
132.8, 130.6, 130.1, 130.1, 129.3, 127.6, 127.1, 115.8, 113.8, 55.3,
45.0, 29.8. HRMS (ESI) m/z: [M+H]+ calcd for C22H21O3
333.1485; found, 333.1482.
3-(tert-butylperoxy)-1-phenyl-3-(thiophen-2-yl)propan-1-
one (1p). Purification by flash column chromatography
(ethyl acetate/petroleum ether, v/v, 1/15), brown oil (74%).
1H NMR (400 MHz, CDCl3) δ 7.54 – 7.46 (m, 2H), 7.39 (ddd,
J = 7.4, 4.3, 2.7 Hz, 2H), 6.98 (d, J = 8.0 Hz, 1H), 6.89 – 6.81
(m, 2H), 3.89 (s, 3H), 2.02 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 205.6, 146.7, 145.7, 141.1, 140.3, 132.8, 130.6, 130.1,
127.7, 127.2, 122.0, 114.8, 111.5, 56.1. HRMS (ESI) m/z: [M+H]+
calcd for C15H15O3 243.1016; found, 243.1019.
ethyl 3-(4'-hydroxy-[1,1'-biphenyl]-2-yl)-3-oxopropanoate
(1v). Purification by flash column chromatography (ethyl
acetate/petroleum ether, v/v, 1/15), brown oil (50%) H
NMR (400 MHz, CDCl3) δ 7.58 (dd, J = 7.7, 1.4 Hz, 1H), 7.52
(td, J = 7.5, 1.4 Hz, 1H), 7.42 – 7.36 (m, 2H), 7.19 (d, J = 6.6
Hz, 2H), 6.93 – 6.87 (m, 2H), 4.08 (q, J = 7.1 Hz, 2H), 3.36
(s, 2H), 1.17 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3)
δ 199.9, 167.6, 156.6, 140.6, 139.1, 131.9, 131.5, 130.4, 130.3,
128.6, 127.1, 116.0, 61.5, 48.7, 13.9.
1
1-(2'-fluoro-4'-hydroxy-5'-methoxy-[1,1'-biphenyl]-2-
yl)ethan-1-one (1q). Purification by flash column
chromatography (ethyl acetate/petroleum ether, v/v, 1/15),
1
white solid (85%). Mp: 155-157 °C. H NMR (400 MHz,
CDCl3) δ 7.63 (dd, J = 7.7, 1.4 Hz, 1H), 7.52 (td, J = 7.5, 1.4
Hz, 1H), 7.46 – 7.33 (m, 2H), 6.78 – 6.69 (m, 2H), 5.88 (d, J
= 1.5 Hz, 1H), 3.87 (s, 3H), 2.27 (s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 203.1, 154.7, 146.4, 143.2, 140.7, 134.2, 131.4,
130.9, 127.8, 127.7, 118.9, 112.4, 103.2, 102.9, 56.5, 29.3. HRMS
(ESI) m/z: [M+H]+ calcd for C15H14FO3 261.0921; found,
261.0927.
1-(4-hydroxyphenyl)-2-naphthaldehyde (1w). Purification
by flash column chromatography (ethyl acetate/petroleum
ether, v/v, 1/15), yellow solid (50%). Mp: 226-231 °C. 1H NMR
(400 MHz, DMSO-d6) δ 9.83 (d, J = 5.7 Hz, 2H), 8.06 (dd, J
= 8.5, 4.9 Hz, 2H), 7.92 (d, J = 8.6 Hz, 1H), 7.70 (t, J = 7.9
Hz, 2H), 7.57 (ddd, J = 8.2, 6.7, 1.3 Hz, 1H), 7.26 (d, J = 8.1
1-(4'-hydroxy-2'-methoxy-[1,1'-biphenyl]-2-yl)ethan-1-one
13
Hz, 2H), 6.99 (d, J = 7.9 Hz, 2H). C{1H} NMR (101 MHz,
(1r). Purification by flash column chromatography (ethyl
1
DMSO-d6) δ 192.6, 158.1, 146.8, 132.7, 131.3, 129.4, 128.8, 128.5,
127.7, 127.6, 1245.0, 122.2, 115.6. HRMS (ESI) m/z: [M+H]+
calcd for C17H13O2 249.0910, found, 249.0910.
acetate/petroleum ether, v/v, 1/15), yellow solid (85%). H
NMR (400 MHz, CDCl3) δ 7.58 (dd, J = 7.6, 1.4 Hz, 1H), 7.50
(td, J = 7.5, 1.5 Hz, 1H), 7.40 – 7.29 (m, 2H), 7.06 (d, J = 8.2
Hz, 1H), 6.89 (s, 1H), 6.46 – 6.35 (m, 2H), 3.64 (s, 3H), 2.29
(s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 204.9, 157.7, 156.6,
140.4, 136.8, 131.5, 131.3, 131.2, 127.2, 126.8, 121.5, 107.9, 99.2,
28.9. HRMS (ESI) m/z: [M+H]+ calcd for C15H15O3 243.1016;
found, 243.1019.
(Z)-3'-(3-phenylpropylidene)-3'H-spiro[cyclohexane-1,1'-
isobenzofuran]-2,5-dien-4-one (B). Purification by flash
column chromatography (ethyl acetate/petroleum ether,
v/v, 1/15), yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J
= 7.7 Hz, 1H), 7.35 (t, J = 7.5 Hz, 1H), 7.26 (p, J = 7.3 Hz, 5H),
7.18 (t, J = 7.1 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 6.68 (d, J =
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(a) Uyanik, M.; Sasakura, N.; Mizuno, M.; Ishihara, K.
9.7 Hz, 2H), 6.24 (d, J = 9.6 Hz, 2H), 5.09 (t, J = 7.5 Hz, 1H),
2.80 (t, J = 7.5 Hz, 2H), 2.63 (q, J = 7.5 Hz, 2H). 13C{1H} NMR
(101 MHz, CDCl3) δ 185.3, 153.2, 147.0, 141.9, 138.5, 129.4,
128.9, 128.6, 128.2, 127.6, 125.8, 122.0, 120.4, 97.4, 83.3, 35.9,
26.6. HRMS (ESI) m/z: [M+H]+ calcd for C17H13O2 315.1380,
found, 315.1378.
Enantioselective Synthesis of Masked Benzoquinones Using
Designer Chiral Hypervalent Organoiodine(III) Catalysis. ACS
Cat. 2017, 7, 872-876; (b) Odagi, M.; Okuda, K.; Ishizuka, H.;
Adachi, K.; Nagasawa, K. Synthesis of Spiroguanidine Derivatives
by Dearomative Oxidative Cyclization using Hypervalent Iodine
Reagent. Asian J. Org. Chem. 2020, 9, 218-221; and references cited
therein.
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ASSOCIATED CONTENT
Supporting Information
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CCDC Deposition Number 1972295.
Podolesov, B. Oxidation of β-diketones with
(diacetoxyiodo)benzene. J. Org. Chem. 1984, 49, 2644-6.
8. (a) Kang, Y.-B.; Gade, L. H. The Nature of the
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The Supporting Information is available free of charge on the
ACS Publications website.
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Catalytically Active Species in Olefin Dioxygenation with
PhI(OAc)2: Metal or Proton? J. Am. Chem. Soc. 2011, 133, 3658-
3667; (b) Xu, J.-H.; Jiang, Q.; Guo, C.-C. Phenyliodonium
Diacetate Mediated Direct Synthesis of Benzonitriles from
Styrenes through Oxidative Cleavage of C═C Bonds. J. Org. Chem.
2013, 78, 11881-11886.
9.
Dioxygenation. J. Am. Chem. Soc. 2008, 130, 2962-2964.
10. (a) Nicolaou, K. C.; Adsool, V. A.; Hale, C. R. H. An
Expedient Procedure for the Oxidative Cleavage of Olefinic Bonds
with PhI(OAc)2, NMO, and Catalytic OsO4. Org. Lett. 2010, 12,
1552-1555; (b) Hong, Z.; Liu, L.; Sugiyama, M.; Fu, Y.; Wong, C.-H.
Concise Synthesis of Iminocyclitols via Petasis-Type
Aminocyclization. J. Am. Chem. Soc. 2009, 131, 8352-8353; (c)
Ohno, M.; Oguri, I.; Eguchi, S. PhI(OAc)2-Promoted
Rearrangement of the Hydroxyl Group:ꢀ Ring Expansion of 4-
Hydroxy-2-cyclobutenone to 2(5H)-Furanone in Comparison
with Ring Cleavage of the α-Hydroxycycloalkanone to the ω-
Formyl Ester. J. Org. Chem. 1999, 64, 8995-9000; (d) Moorthy, J.
N.; Parida, K. N. Oxidative Cleavage of Olefins by In Situ-
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H, C NMR and HRMS spectra for all compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: wangbin@nankai.edu.cn (B. W.).
Li, Y.; Song, D.; Dong, V. M. Palladium-Catalyzed Olefin
ROCID
Bin Wang: 0000-0002-3674-8980
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Financial support by the National Science Foundation of
China (no. 21172120 and 21472093), Tianjin Municipal Science
and Technology Commission (No. 19JCTPJC48400) ，
National
University
Student
Innovation
Program
(201910055456) and the Fundamental Research Funds for the
Central Universities，Nankai University (63201023).
Generated
Catalytic
3,4,5,6-Tetramethyl-2-iodoxybenzoic
Acid/Oxone. J. Org. Chem. 2014, 79, 11431-11439; (e) Miyamoto, K.;
Yamashita, J.; Narita, S.; Sakai, Y.; Hirano, K.; Saito, T.; Wang, C.;
Ochiai, M.; Uchiyama, M. Iodoarene-catalyzed oxidative
transformations using molecular oxygen. Chem. Commun. 2017,
53, 9781-9784.
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