Highly Selective Synthesis of 2- tert-Butoxy-1-Arylethanones via Copper(I)-Catalyzed Oxidation/ tert-Butoxylation of Aryl Olefins with TBHP

Article abstract of DOI:10.1021/acs.joc.9b03156

A practical and environmentally friendly protocol for the selective oxidation of aryl olefins to arylethanone derivatives by using a Cu(I) catalyst and tert-butyl hydroperoxide (TBHP) has been developed. A series of 2-tert-butoxy-1-arylethanones were obtained in moderate to good yields under mild conditions with high selectivity. In this method, TBHP acts not only as an oxidant but also as the tert-butoxy and carbonyl oxygen sources. This enables one-step oxidation/tert-butoxylation. Various allyl peroxides were also synthesized from allyl substrates.

Full text of DOI:10.1021/acs.joc.9b03156

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Note
Highly Selective Synthesis of 2-tert-Butoxy-1-Arylethanones via
Copper(I)-Catalyzed Oxidation/tert-Butoxylation of Aryl Olefins with TBHP
Jiantao Zhang, Duoduo Xiao, Hua Tan, and Weibing Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b03156 • Publication Date (Web): 13 Feb 2020
Downloaded from pubs.acs.org on February 16, 2020
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Highly Selective Synthesis of 2-tert-Butoxy-1-Arylethanones via
Copper(I)-Catalyzed Oxidation/tert-Butoxylation of Aryl Olefins with
TBHP
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Jiantao Zhang, Duoduo Xiao*, Hua Tan, Weibing Liu*
*College of Chemistry, Guangdong University of Petrochemical Technology, Guandu Road, Maoming 525000, P.
R. China; Email address: lwb409@gdupt.edu.cn; dd.xiao@gdupt.edu.cn
O
CuCl (10mol%)
tBuOOH
OtBu
Ar
Ar
DCE (2.0 mL), RT, 24 h
2.0 (equiv.)
Abstract: A practical and environmentally friendly protocol for the selective oxidation of aryl
olefins to arylethanone derivatives by using a Cu(I) catalyst and tert-butyl hydroperoxide (TBHP)
has been developed. A series of 2-tert-butoxy-1-arylethanones were obtained in moderate to good
yields under mild conditions with high selectivity. In this method, TBHP acts not only as an
oxidant but also as the tert-butoxy and carbonyl oxygen sources. This enables one-step
oxidation/tert-butoxylation. Various allyl peroxides were also synthesized from allyl substrates.
Alkenes are abundant organic molecules and represent a useful chemical feedstock. They are
extensively used in organic synthesis because of their simplicity, low cost, ready availability, and
unique reactivity profiles. Methods for their direct, selective functionalization are attractive as an
important approach to assembling more complex molecular structures.1 With the renaissance of radical
chemistry, the radical three-component difunctionalization of alkenes is attracting increasing attention
and has been intensively studied in recent years.2-3
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Scheme 1. Difuctionlization of Alkenes with TBHP.
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Previous work
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O
Ar1NH2
tBuOOH
Ar
N Ar1
(a)
(b)
Ar
dioxane, 70 oC
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Cl
Ar
CHCl3
tBuOOH
tBuOOH
Ar
t
Cl
O2 Bu
Et3N, R.T.
CHCl3
Cl
(c)
Ar
Ar
Et3N, 70 oC
H
Cl
This work
O
CuCl
OtBu
tBuOOH
(d)
Ar
Ar
DCE, R. T.
Tert-butyl hydroperoxide (TBHP) is a commercially available, inexpensive, and versatile reagent,
with roles such as an oxidant,4 radical initiator,5 and precursor of the tert-butoxy6 and tert-butyl
peroxide7 radicals. For example, in 2012, Wang’s group reported a novel and efficient
TBHP/I2-promoted oxidative coupling reaction of acetophenones with amines for the synthesis of
α-ketoamides.4f Recently, Bao et al. developed the Cu-catalyzed radical acyl-cyanation of alkenes with
aldehydes, by using TBHP as an initiator, to access various unsymmetrical β-cyano ketones with
various functional groups.5a In 2019, Yang and co-workers reported a convenient Fe-catalyzed
decarbonylative alkylation–peroxidation of alkenes with aliphatic aldehydes and TBHP to provide
chain-elongated peroxides.7c Syntheses of aldehydes,8 styrene epoxides,9 and acidic compounds10
through the selective oxidation of styrenes by peroxides in the presence of transition-metal catalysts
have been well documented. However, to the best of our knowledge, relatively few studies have
focused on the oxidation/tert-butoxylation of styrenes. Here, as a continuation of our work on
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TBHP-mediated oxidative coupling reactions (Scheme 1a–c),11 we report a highly efficient and general
strategy for the preparation of various 2-tert-butoxy-1-arylethanones via Cu(I)-catalyzed
oxidation/tert-butoxylation of alkenes with TBHP under mild conditions (Scheme 1d). Notably, the
oxygen atom in the newly formed carbonyl moiety is derived from TBHP.
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Table 1. Optimization Studies a
O
OtBu
Catalyst (10 mol%), TBHP
Solvent, R.T.
1a
2a
Entry
1
Catalyst
CuCl
CuCl
CuI
Solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Hexane
Dioxane
DMF
Time /h
12
Yieldb /%
26
2
24
45
3
24
32
4
CuBr
Cu2O
CuBr2
CuCl2
CuO
24
20
5
24
28
6
24
trace
trace
trace
trace
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7
24
8
24
9
Cu(OAc)2
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
-
24
10
11
12
13
14c
15d
16e
17
18f
19g
24
24
68
24
trace
77
DCE
24
DCE
24
36
DCE
24
77
DCE
24
77
DCE
36
trace
77
CuCl
CuCl
DCE
24
DCE
24
77
b
a Reaction conditions: 1a (0.5 mmol), TBHP (2.0 equiv.), solvent (2.0 mL), catalyst (10 mol%). GC
yield. c TBHP: 1.0 equiv. d TBHP: 3.0 equiv. e CuCl: 50 mol%. f O2 (balloon). g N2 (balloon).
Initially, we selected styrene 1a as a model substrate for optimization of the reaction conditions
(Table 1). First, the reaction was performed in the presence of CuCl (10 mol%) in combination with
TBHP (2.0 equiv) in DMSO at room temperature for 12 h. The desired product 2a was obtained in 26%
yield; most of the starting material was recovered (entry 1). Prolonging the reaction time to 24 h
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increased the yield of 2a to 45% (entry 2). We next explored the use of various Cu salts for this
transformation (entries 3–9). The results indicate that the type of metal catalyst significantly affects the
reaction yield and CuCl is a better choice than other Cu salts. In the next optimization step, we
examined the effects of the solvent by screening various reaction media, namely hexane, dioxane, DMF,
and DCE. The results show that the conversion is sensitive to the solvent; DCE is the best solvent
because the other solvents gave smaller yields of the expected product 2a (entries 10–13). A lower
yield was obtained when the TBHP loading was decreased to 1.0 equiv (entry 14). However, increasing
the amount of TBHP or CuCl had no obvious effect on the outcome (entries 15 and 16). It is worth
noting that in the absence of the CuCl catalyst only a trace amount of 2-tert-1-butoxyphenylethanone
(2a) was formed and the starting material remained almost intact (entry 17). The yields of the desired
product 2a were the same under an O2 or N2 atmosphere (entries 18 and 19).
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With the optimum conditions in hand (Table 1, entry 13), we then systematically studied the
generality and limitations of this oxidation/tert-butoxylation reaction; the results are summarized in
Table 2. Groups with different electronic properties at the para position of the aromatic ring were
examined. All the reactions proceeded smoothly to give the desired products in moderate to good
yields (2b–k). The reactivities of phenyl rings with strongly electron-withdrawing substituents (–CF3,
–NO2) were higher than those of phenyl rings with electron-donating substituents. This suggests that
electron-withdrawing groups enhance the reaction efficiency (2j and 2k). Substrates with substituents
at the ortho or meta positions were also compatible with this mild Cu-catalyzed protocol. The
corresponding products were obtained in 60%–73% yields (2l–p).
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Table 2. Scope of the Substratesa
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O
CuCl (10 mol%), TBHP (2.0 equiv.)
DCE (2 mL), R.T., 24 h
OtBu
Ar
Ar
1
2
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O
O
O
OtBu
OtBu
OtBu
OtBu
OtBu
OtBu
OtBu
OtBu
OtBu
OtBu
tBuO
tBu
F
AcO
Ph
2a
2b
2c
, 72%
O
, 62%
O
, 63%
O
2d
2g
2e
2h
2f
, 69%
O
, 67%
, 64%
O
O
OtBu
Cl
Cl
2i
, 65%
O
, 73%
O
, 72%
O
F
OtBu
OtBu
F3C
O2N
2j
2k
2n
2l
, 85%
O
, 82%
, 70%
O
O
H3CO
OtBu
F
OtBu
2m
2o
, 60%
O
, 70%
, 73%
O
O
Cl
OtBu
OtBu
OtBu
R
c
2p
2q
2r
, R = CH3, n.d.
, 69%
O
, 63%
O
c
2s
, R = n-Pr, n.d.
OtBu
OtBu
Ph
S
c
2u
, 89%
2t
, n.d.
a Unless otherwise specified, all reactions were carried out on 1.0 mmol scale for 24 h. b Isolated yield.
c A complex system was obtained, and no desired product was detected.
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Notably, the position of the substituent did not affect the reaction productivities and yields (2h, 2l,
and 2o). 2-Naphthyl-substituted 1q was also tolerated in the present system, and the
oxidation/tert-butoxylation product 2q was obtained in reasonable yield. Disubstituted alkenes are not
good candidates for this Cu-catalyzed reaction. 1r–1t cound not provided the desired products under
the optimum conditions, and complex reaction systems were formed. The phenyl ring in 1a can be
replaced by a heterocycle (thienyl, 1u) to yield 2u.
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Scheme 2. Explore the Substrate Scope.
OtBu
CuCl, TBHP (2.0 equiv.)
DCE (2.0 mL), R.T., 24 h
(a)
(b)
O
3a
3a
4a
, n.d.
t
TBHP (2.0 equiv.)
DCE (2.0 mL), 70 oC, 24 h
O2 Bu
5a
5b
5c
, 77%
, 84%
, 69%
t
TBHP (2.0 equiv.)
DCE (2.0 mL), 70 oC, 24 h
O2 Bu
(c)
(d)
(e)
F
F
3b
3c
3d
t
O2 Bu
TBHP (2.0 equiv.)
DCE (2.0 mL), 70 oC, 24 h
F3C
F3C
t
TBHP (2.0 equiv.)
DCE (2.0 mL), 70 oC, 24 h
O2 Bu
OCH3
5d
OCH3
, 73%
Failed subdtrates
3e
3f
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To further expand the substrate scope, we investigated the use of alkenes with a terminal alkyl
group, i.e., 3a–d, as substrates for this oxidation/tert-butoxylation reaction under the standard
conditions. These alkenes proved to be poor substrates for this transformation. When the reactions were
performed at 70 °C, these substrates failed to provide the desired products, and the allyl peroxide
products 5a–d were obtained as the main products (Scheme 2b–e). Organic peroxides not only serve as
key reactive intermediates in diverse organic synthetic reactions such as Kornblum–DeLaMare
reactions12 and epoxidations,13-14 but also have important roles in cell damage, food safety, and as
therapeutic drugs in medicinal chemistry. We investigated the need to use CuCl and found that its
presence was unnecessary (Scheme 2). The reactions of other internal or terminal alkenes, i.e.,
(E)-non-4-ene (3e) and oct-1-ene (3f), were also examined under these conditions, but the reactions
were sluggish and no major products were formed.
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Scheme 3. Control Experiments.
O
TEMPO (4.0 eq.)
OtBu
CuCl, DCE, R. T.
tBuOOH
(a)
Ph
Ph
2a
: n.d.
O
O
CuCl
OtBu
tBuOOH
(b)
Ph
2a
Ph
DCE, R. T.
: n.d.
Several control experiments were conducted to clarify the reaction mechanism (Scheme 3). The
reaction was completely inhibited by TEMPO (4.0 equiv), which suggests that a radical pathway is
probably involved (Scheme 3a). When acetophenone was treated with TBHP under the standard
conditions, 2a was not detected (Scheme 3b).
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Scheme 4. Possible Mechanism for Cu(I)-Catalyzed Oxidation/tert-Butoxylation Transformation.
path A:
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Cu(I)
tBuO
tBuOOH
Cu(II) OH
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9
A
tBuO
Cu(I)
Cu(II) OH
OtBu
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OtBu
Ph
Ph
Ph
C
B
1a
Cu(I)
O
OH
H2O
OtBu
TBHP
OtBu
Ph
Ph
D
2a
path B:
Cu(I)
tBuO
tBuOOH
Cu(II) OH
A
Cu(II) OH
tBuO
tBuOOH
tBuOO
H2O
Cu(I)
E
OOtBu
OtBu
VI
OtBu
Ph
Ph
Ph
B
F
1a
Kornbium-DeLaMare
rearrangement
O
OtBu
Ph
2a
Based on the these results and literature reports,4-7,11 a possible mechanism for this Cu(I)-catalyzed
oxidation/tert-butoxylation transformation, with 1a as an example, is shown in Scheme 4. Initially,
TBHP is reduced by low-valent Cu(I) to generate a tert-butoxy radical A and a Cu(II) complex.14-15
Radical addition to styrene then produces benzyl radical B, which undergoes direct oxidation to C by
Cu(II),16 along with regeneration of Cu(I) for the next catalytic cycle. Next, species C is trapped by
H2O17 to form species D, which is further oxidized by TBHP to give the final product 2a (path a).18
Another possible mechanism, namely path b, cannot be excluded. First, alkyloxy radical A and
alkylperoxy radical E are generated via a series of steps. Benzyl radical B is then obtained via a radical
addition process and is selectively trapped by the BuOO. radical to afford the tert-butyl peroxide
t
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intermediate F.19 In the final step, F undergoes a Kornblum–DeLaMare rearrangement12 to give the
desired product 2a.
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In conclusion, we have developed an efficient and general method for the highly selective
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construction
of
2-tert-1-butoxyarylethanone
frameworks
via
a
Cu(I)-catalyzed
oxidation/tert-butoxylation reaction. This synthetic method has many advantages such as simple
starting materials, green reaction conditions, and high selectivity, and is expected to provide a valuable
alternative protocol in appropriate areas. In this method, TBHP acts not only as the oxidant but also as
the tert-butoxy and carbonyl oxygen sources for this oxidation/tert-butoxylation transformation.
Various allyl peroxides were also synthesized from allyl substrates. Further investigations into the
difunctionalization of alkenes with TBHP are currently underway in our laboratory.
EXPERIMENTAL SECTION
General Information. All the reactions were carried out at room temperature for 24 h in a
round-bottom flask equipped with a magnetic stir bar. Unless otherwise stated, all reagents and
1
solvents were purchased from commercial suppliers and used without further purification. H
NMR and 13C NMR spectra were recorded on a 400 MHz spectrometer in solutions of CDCl3
using tetramethylsilane as the internal standard; δ values are given in ppm, and coupling constants
(J) in Hz. Mass spectra were obtained from high resolution ESI mass spectrometer. HR-MS were
obtained on a Q-TOF micro spectrometer.
Typical procedure for the synthesis of 2a: 2-tert-butoxy-1-phenylethanone (2a). A mixture of
styrene (1a) (104 mg, 1.0 mmol), CuCl (9.8 mg, 0.1 mmol), TBHP (258 mg, 2.0 mmol, 70% in
water), and 1,2-dichloroethane (DCE) (2.0 mL) was added successively in a round-bottom flask,
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and the resulting solution was stirred for 24 h at room temperature. The mixture was purified by
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column chromatography on silica gel to afford product 2a with PE/EA = 30:1 as the eluent.
2-tert-butoxy-1-phenylethanone (2a) 20
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O
OtBu
1
Yield: 72% (138 mg); a pale yellow oil liquids; H NMR (CDCl3, 400 Hz) δ 7.97 (d, J = 8.4 Hz,
2H), 7.57 (t, J = 7.6 Hz, 1H), 7.46 (t, J = 7.2 Hz, 2H), 4.66 (s, 2H), 1.29 (s, 9H); 13C NMR {1H}
(CDCl3, 100 Hz) δ 197.2, 135.4, 133.1, 128.5, 128.1, 74.6, 66.3, 27.4.
2-tert-butoxy-1-(4-tert-butoxyphenyl)ethanone (2b)
O
OtBu
tBuO
Yield: 62% (163 mg); a pale yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 7.93 (d, J = 7.6 Hz,
2H), 7.03 (d, J = 7.6 Hz, 2H), 4.61 (s, 2H), 1.42 (s, 9H), 1.28 (s, 9H); 13C NMR {1H} (CDCl3, 100
Hz) δ 196.4, 160.4, 129.9, 129.7, 122.2, 74.5, 66.2, 28.9, 27.4; HRMS (ESI): calcd for
C16H24NaO3: [M+Na+] 287.1612, found 287.1619.
4-(2-tert-butoxyacetyl)phenyl acetate (2c)
O
OtBu
AcO
1
Yield: 63% (157 mg); a pale yellow oil liquids; H NMR (CDCl3, 400 Hz) δ 8.03 (d, J = 7.6 Hz,
2H), 7.20 (d, J = 7.6 Hz, 2H), 4.62 (s, 2H), 2.33 (s, 9H), 1.28 (s, 9H); 13C NMR {1H} (CDCl3, 100
Hz) δ 196.0, 168.8, 154.8, 133.0, 129.9, 121.7, 74.7, 66.4, 27.4, 21.1; HRMS (ESI): calcd for
C14H18NaO4: [M+Na+] 273.1097, found 273.1099.
2-tert-butoxy-1-p-tolylethanone (2d)
O
OtBu
1
Yield: 69% (142 mg); a pale yellow oil liquids; H NMR (CDCl3, 400 Hz) δ 7.88 (d, J = 8.4 Hz,
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2H), 7.26 (d, J = 8.0 Hz, 2H), 4.66 (s, 2H), 2.42 (s, 3H), 1.29 (s, 9H); 13C NMR {1H} (CDCl3, 100
Hz) δ 196.8, 144.0, 132.9, 129.2, 128.2, 74.5, 66.2, 27.4; HRMS (ESI): calcd for C13H18NaO2:
[M+Na+] 229.1199, found 229.1195.
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2-tert-butoxy-1-(4-tert-butylphenyl)ethanone (2e)
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O
OtBu
tBu
1
Yield: 67% (166 mg); a pale yellow oil liquids; H NMR (CDCl3, 400 Hz) δ 7.92 (d, J = 8.8 Hz,
2H), 7.47 (d, J = 8.8 Hz, 2H), 4.65 (s, 2H), 1.35 (s, 9H), 1.29 (s, 9H); 13C NMR {1H} (CDCl3, 100
Hz) δ 196.7, 156.9, 132.8, 128.0, 125.4, 74.5, 66.2, 35.1, 31.0, 27.4; HRMS (ESI): calcd for
C16H24NaO2: [M+Na+] 271.1668, found 271.1677.
2-tert-butoxy-1-(4-phenylphenyl)ethanone (2f)
O
OtBu
1
Yield: 64% (171 mg); a pale yellow oil liquids; H NMR (CDCl3, 400 Hz) δ 8.06 (d, J = 8.4 Hz,
2H), 7.69 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.40 (t, J = 8.4 Hz,
1H), 4.68 (s, 2H), 1.31 (s, 9H); 13C NMR {1H} (CDCl3, 100 Hz) δ 196.5, 154.1, 139.6, 134.3,
128.9, 128.8, 128.2, 127.2, 127.1, 74.9, 65.6, 27.5; HRMS (ESI): calcd for C18H20NaO2: [M+Na+]
291.1355, found 291.1368.
2-tert-butoxy-1-(4-(chloromethyl)phenyl)ethanone (2g)
O
OtBu
Cl
1
Yield: 65% (156 mg); a pale yellow oil liquids; H NMR (CDCl3, 400 Hz) δ 7.98 (d, J = 8.4 Hz,
2H), 7.49 (d, J = 8.0 Hz, 2H), 4.63 (s, 2H), 4.62 (s, 2H), 1.29 (s, 9H); 13C NMR {1H} (CDCl3, 100
Hz) δ 196.8, 144.0, 132.9, 129.2, 128.2, 74.5, 66.2, 27.4; HRMS (ESI): calcd for C13H17ClNaO2:
[M+Na+] 263.0809, found 263.0814.
2-tert-butoxy-1-(4-fluorophenyl)ethanone (2h)
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O
OtBu
5
6
7
8
F
Yield: 73% (153 mg); a yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 8.04 (m, 2H), 7.13 (t, J =
8.4 Hz, 2H), 4.60 (s, 2H), 1.28 (s, 9H); 13C NMR {1H} (CDCl3, 100 Hz) δ 195.9, 165.8 (d, 1JC-F
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=
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2
246.4 Hz), 131.8 (d, JC-F = 3.1 Hz), 131.0 (d, JC-F = 9.2 Hz), 115.6 (d, JC-F = 21.7 Hz), 74.7, 66.5,
27.4; HRMS (ESI): calcd for C12H15FNaO2: [M+Na+] 233.0948, found 233.0952.
2-tert-butoxy-1-(4-chlorophenyl)ethanone (2i) 21
O
OtBu
Cl
1
Yield: 72% (162 mg); a pale yellow oil liquids; H NMR (CDCl3, 400 Hz) δ 7.94 (d, J = 8.8 Hz,
2H), 7.44 (d, J = 8.8 Hz, 2H), 4.59 (s, 2H), 1.28 (s, 9H); 13C NMR {1H} (CDCl3, 100 Hz) δ 196.3,
139.3, 133.3, 129.8, 128.8, 74.7, 66.5, 27.4.
2-tert-butoxy-1-(4-(trifluoromethyl)phenyl)ethanone (2j)
O
OtBu
F3C
Yield: 85% (221 mg); a pale yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 8.10 (d, J = 7.6 Hz,
2H), 7.73 (d, J = 7.6 Hz, 2H), 4.63 (s, 2H), 1.28 (s, 9H); 13C NMR {1H} (CDCl3, 100 Hz) δ 196.7,
1
138.1, 128.7, 125.7, 125.5 (q, JC-F = 269.5 Hz), 124.8, 74.9, 66.7, 27.4; HRMS (ESI): calcd for
C13H15F3NaO2: [M+Na+] 283.0916, found 283.0924.
2-tert-butoxy-1-(4-nitrophenyl)ethanone (2k)
O
OtBu
O2N
Yield: 82% (194 mg); an orange oil liquids; 1H NMR (CDCl3, 400 Hz) δ 8.31 (d, J = 7.6 Hz, 2H),
8.16 (d, J = 7.6 Hz, 2H), 4.62 (s, 2H), 1.28 (s, 9H); 13C NMR {1H} (CDCl3, 100 Hz) δ 196.3,
150.2, 140.0, 129.6, 123.6, 75.2, 67.0, 27.4; HRMS (ESI): calcd for C12H15NNaO4: [M+Na+]
260.0893, found 260.0888.
2-tert-butoxy-1-(2-fluorophenyl)ethanone (2l)
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F
O
OtBu
5
6
7
8
9
1
Yield: 70% (147 mg); a yellow oil liquids; H NMR (CDCl3, 400 Hz) δ 7.94 (m, 1H), 7.52 (m,
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1H), 7.26 (m, 1H), 7.14 (m, 1H), 4.62 (s, 2H), 1.28 (s, 9H); 13C NMR {1H} (CDCl3, 100 Hz) δ
195.7, 162.8 (d, 1JC-F = 256.0 Hz), 134.5 (d, 3JC-F = 8.8 Hz), 130.7 (d, 4JC-F = 3.5 Hz), 124.5 (d, 3JC-F
=
3.1 Hz), 123.8 (d, 2JC-F = 21.8 Hz), 116.3 (d, 2JC-F = 23.6 Hz), 74.3, 69.2, 27.4; HRMS (ESI): calcd for
C12H15FNaO2: [M+Na+] 233.0948, found 233.0955.
2-tert-butoxy-1-(3-methoxyphenyl)ethanone(2m)
O
H3CO
OtBu
Yield: 60% (133 mg); a pale yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 7.54 (m, 2H), 7.37 (d,
J = 7.6 Hz, 1H), 7.54 (m, 1H), 4.65 (s, 2H), 3.86 (s, 3H), 1.29 (s, 9H), 1.28 (s, 9H); 13C NMR {1H}
(CDCl3, 100 Hz) δ 197.0, 159.6, 136.6, 129.5, 120.5, 119.6, 112.5, 74.6, 66.3, 55.4, 27.4; HRMS
(ESI): calcd for C13H18NaO3: [M+Na+] 245.1148, found 245.1155.
2-tert-butoxy-1-m-tolylethanone (2n)
O
OtBu
Yield: 70% (144 mg); a pale yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 7.79 (s, 1H), 7.77 (d,
J = 8.4 Hz, 1H), 7.37 (m, 2H), 4.67 (s, 2H), 2.43 (s, 3H), 1.31 (s, 9H); 13C NMR {1H} (CDCl3,
100 Hz) δ 196.8, 138.3, 134.9, 133.9, 128.5, 128.4, 125.2, 74.5, 66.2, 27.4, 21.3; HRMS (ESI):
calcd for C13H18NaO2: [M+Na+] 229.1199, found 229.1208.
2-tert-butoxy-1-(3-fluorophenyl)ethanone (2o)
O
F
OtBu
Yield: 73% (153 mg); a yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 7.77 (t, J = 8.0 Hz, 1H),
7.69 (m, 1H), 7.44 (m, 1H), 7.26 (m, 1H), 4.61 (s, 2H), 1.29 (s, 9H); 13C NMR {1H} (CDCl3, 100
Hz) δ 196.1, 162.6 (d, 1JC-F = 256.0 Hz), 137.3 (d, 3JC-F = 8.1 Hz), 130.1 (d, 3JC-F = 8.2 Hz), 123.9 (d,
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4JC-F = 3.0 Hz), 120.1 (d, JC-F = 21.4 Hz), 115.1 (d, JC-F = 22.3 Hz), 74.7, 66.5, 27.4; HRMS (ESI):
5
6
calcd for C12H15FNaO2: [M+Na+] 233.0948, found 233.0944.
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2-tert-butoxy-1-(3-chlorophenyl)ethanone (2p)
9
O
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Cl
OtBu
Yield: 69% (155 mg); a pale yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 7.96 (s, 1H), 7.87 (d,
J = 8.4 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.41 (t, J = 8.4 Hz, 1H), 4.61 (s, 2H), 1.29 (s, 9H); 13
C
NMR {1H} (CDCl3, 100 Hz) δ 196.2, 136.9, 133.1, 129.8, 129.6, 128.4, 126.4, 74.5, 66.5, 27.4;
HRMS (ESI): calcd for C12H15ClNaO2: [M+Na+] 249.0653, found 249.0655.
2-tert-butoxy-1-(naphthalen-3-yl)ethanone (2q)
O
OtBu
Yield: 63% (152 mg); an orange oil liquids; 1H NMR (CDCl3, 400 Hz) δ 8.53 (s, 1H), 8.02 (d, J =
8.4 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.89 (t, J = 8.4 Hz, 2H), 7.58 (m, 2H), 4.78 (s, 2H), 1.33 (s,
9H); 13C NMR {1H} (CDCl3, 100 Hz) δ 197.1, 135.6, 132.7, 132.4, 129.8, 129.5, 128.4, 128.3,
127.8, 126.7, 123.9, 74.7, 66.5, 27.5; HRMS (ESI): calcd for C16H18NaO2: [M+Na+] 265.1199,
found 265.1191.
2-tert-butoxy-1-(thiophen-2-yl)ethanone (2u)
O
OtBu
S
Yield: 89% (176 mg); a pale yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 7.31 (dd, J = 1.2 Hz,
J = 4.0 Hz, 1H), 7.65 (dd, J = 1.2 Hz, J = 4.0 Hz, 1H), 7.14 (dd, J = 4.0 Hz, J = 5.2 Hz, 1H), 4.45
(s, 2H), 1.30 (s, 9H); 13C NMR {1H} (CDCl3, 100 Hz) δ 191.1, 141.1, 133.9, 133.2, 127.7, 74.9,
67.4, 27.3; HRMS (ESI): calcd for C10H14NaO2S: [M+Na+] 221.0606, found 221.0612.
1-((E)-3-(tert-butylperoxy)prop-1-enyl)benzene (5a)
t
O2 Bu
Yield: 77% (158 mg); a pale yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 7.31 (m, 5H), 6.07 (m,
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1H), 5.29 (m, 3H), 1.26 (s, 9H); 13C NMR {1H} (CDCl3, 100 Hz) δ 139.3, 136.8, 128.3, 127.9,
127.4, 86.8, 80.4, 26.5; HRMS (ESI): calcd for C13H18NaO2: [M+Na+] 229.1199, found 229.1192.
1-((E)-3-(tert-butylperoxy)prop-1-enyl)-4-fluorobenzene (5b)
9
t
O2 Bu
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F
Yield: 84% (188 mg); a pale yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 7.37 (m, 2H), 6.99 (m,
2H), 6.58 (d,J = 16 Hz,1H), 6.23 (m, 1H), 4.57 (dd, J = 6.8 Hz, J = 1.2 Hz, 1H), 1.28 (s, 9H); 13
C
1
4
NMR {1H} (CDCl3, 100 Hz) δ 141.6 (d, JC-F = 247.0 Hz), 133.1, 132.7 (d, JC-F = 3.2 Hz),
3
2
128.1(d, JC-F = 8.1 Hz), 123.6, 115.5 (d, JC-F = 21.5 Hz), 80.4, 75.7, 26.3; HRMS (ESI): calcd
for C13H17FNaO2: [M+Na+] 247.1105, found 247.1117.
1-((E)-3-(tert-butylperoxy)prop-1-enyl)-4-(trifluoromethyl)benzene (5c)
t
O2 Bu
F3C
1
Yield: 69% (189 mg); a pale yellow oil liquids; H NMR (CDCl3, 400 Hz) δ 7.57 (d,J = 8.0 Hz,
2H), 7.49 (d,J = 8.0 Hz, 2H),6.66 (d,J = 16 Hz, 1H), 6.44 (m, 1H), 4.61 (dd,J = 1.2 Hz, J = 6.4 Hz,
13
1
2H), 1.28 (s, 9H); C NMR {1H} (CDCl3, 100 Hz) δ 140.0, 132.4, 126.9, 126.7 (q, JC-F = 245.8
Hz), 125.5, 125.4, 125.3, 80.5, 75.3, 26.3; HRMS (ESI): calcd for C14H17F3NaO2: [M+Na+]
297.1073, found 297.1061.
1-((E)-3-(tert-butylperoxy)prop-1-enyl)-2-methoxybenzene (5d)
t
O2 Bu
O
Yield: 73% (172 mg); a pale yellow oil liquids; 1H NMR (CDCl3, 400 Hz) δ 7.47 (dd,J = 2.4 Hz, J
= 7.6 Hz, 1H), 7.25 (m,1H), 6.94 (m,3H), 6.34 (m, 1H), 4.61 (dd,J = 1.2 Hz, J = 6.4 Hz, 2H), 3.81
( s, 3H), 1.29 (s, 9H); 13C NMR {1H} (CDCl3, 100 Hz) δ 156.8, 129.4, 128.9, 127.1, 125.4, 124.2,
120.6, 110.8, 80.3, 76.3, 55.4, 26.4; HRMS (ESI): calcd for C14H20NaO3: [M+Na+] 259.1305,
found 259.1310.
Supporting Information Available: Copies of 1H and 13C NMR {1H} of all the new compounds. This
material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Authors
7
*E-mail: lwb409@gdupt.edu.cn; dd.xiao@gdupt.edu.cn
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9
Acknowledgements
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This work was supported by the National Natural Science Foundation of China (21602035), the
Foundation of Department of Science and Technology of Guangdong Provincial (No.
2016A020221038) and Guangdong Natural Science Foundation (No. 2017A030307006). Besides, we
thank Peng Zhou, Cui Chen, Yupeng Pan and Linhai Duan for their contributions to this work.
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