Substituent-Controlled Chemoselective Cleavage of C = C or Csp2 - C(CO) Bond in α,β-Unsaturated Carbonyl Compounds with H-Phosphonates Leading to β-Ketophosphonates

Article abstract of DOI:10.1021/acs.joc.5b02887

An unprecedented substituent-controlled chemoselective cleavage of C = C double bond or C(sp²)-C(CO) bond along with aerobic phosphorylation of α,β-unsaturated carbonyl compounds with H-phosphonates through a radical process has been disclosed. The current strategy provides an access to β-ketophosphonates under mild conditions with a wide substrate scope.

Full text of DOI:10.1021/acs.joc.5b02887

Article
pubs.acs.org/joc
2
Substituent-Controlled Chemoselective Cleavage of CC or Csp −
C(CO) Bond in α,β-Unsaturated Carbonyl Compounds with
H‑Phosphonates Leading to β‑Ketophosphonates
Yao Zhou, Changqing Rao, Shaoyu Mai, and Qiuling Song*
Institute of Next Generation Matter Transformation, College of Chemical Engineering, College of Materials Science & Engineering,
Huaqiao University, 668 Jimei Blvd, Xiamen, Fujian 361021, P. R. China
S
* Supporting Information
ABSTRACT: An unprecedented substituent-controlled che-
moselective cleavage of CC double bond or C(sp2)−
C(CO) bond along with aerobic phosphorylation of α,β-
unsaturated carbonyl compounds with H-phosphonates
through a radical process has been disclosed. The current
strategy provides an access to β-ketophosphonates under mild
conditions with a wide substrate scope.
Scheme 1. Transition-Metal-Catalyzed Carbon−Carbon
Bond Cleavage Leading to β-Ketophosphonates
INTRODUCTION
■
Transition-metal-catalyzed selective cleavage of carbon−carbon
bond is a formidable challenging subject in the art of organic
synthesis owing to the ubiquity of carbon−carbon bonds in
organic molecules, and it has attracted great attentions in recent
years.1 Many noble transition metals have been employed in
carbon−carbon cleavage reactions.2 In recent times, great effort
has been devoted to the development of new catalytic systems
based on less expensive, nontoxic, earth-abundant, environ-
mentally benign, and user-friendly metals, such as Cu and Fe.
Therefore, many methods have been developed with Cu/Fe
cocatalytic systems in the past decade due to their superior
combined bimetallic catalytic reactivities.3 Among carbon−
carbon cleavage reactions, chemoselective cleavage of one
carbon−carbon bond over the others is one of the most
appealing yet highly challenging themes in target-oriented
reconstruction of organic molecules.4 In most of cases, the
chemoselective cleavage of C−C bonds was realized by utilizing
different ligands5 or even by changing transition-metal species.2
α,β-Unsaturated compounds are very important building blocks
in organic synthesis. There are two types of functional moieties
existing in them: carbon−carbon unsaturated bonds (CC or
CC bonds) and carbonyl groups. As a special C−C cleavage
reaction, decarboxylations (cleavage of C(sp2)−C(CO) bond)
of α,β-unsaturated acids have been widely explored.6 Very
recently, several elegant methods converting cinnamic or
acetylenic acids into β-ketophosphonates or β-ketophosphine
oxides via carbon−carbon bond cleavage (decarboxylation)
have been reported (Scheme 1a).6a−d In 2014, Liu and his co-
workers reported copper-catalyzed oxidative cyclization of 1,5-
enynes through C(sp2)−C(CO) bond cleavage.7 To our
knowledge, cleavage of carbon−carbon unsaturated bonds
instead of C−C(CO) single bonds in α,β-unsaturated
compounds has yet to be reported, especially the chemo-
selective cleavage of carbon−carbon unsaturated bonds or
C(sp2)−C(CO) single bonds of α,β-unsaturated compounds
could be realized by changing substituents, which is in sharp
contrast to conventional strategies by utilizing different ligands
or by changing transition metals catalysts. As our ongoing
interest in carbon−carbon activation chemistry,8 we report
herein an unprecendent Cu/Fe cocatalyzed substituent-
controlled chemoselective cleavage of carbon−carbon unsatu-
rated bond or C(sp2)−C(CO) single bond of α,β-unsaturated
carbonyl compounds with H-phosphonate under mild con-
dition (Scheme 1b,c) .
RESULTS AND DISCUSSION
■
We commenced our study with chalcone (1a) and H-diethyl
phosphonate (2a) as model substrates, using 5 mol %
Cu(acac)2 together with 10 mol % FeCl3 at 90 °C under O2
atmosphere. To our delight, the desired product β-ketophosph-
onate was formed in 49% yield in the presence of Et3N in
DMSO within 24 h (Table 1, entries 1). Subsequently, when
we replaced the catalyst with other copper salts, Cu(OTf)2 or
Cu(OAc)2 gave lower yields of 41% or 48%, respectively (Table
Received: December 24, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b02887
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a
Table 1. Optimization of the Reaction Parameters
b
entry
Fe (10 mol %)
Cu (5 mol %)
base (1 equiv)
temp (°C)
solvent
yield (%)
1
FeCl3
Cu(acac)2
Cu(OTf)2
Cu(OAc)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
−
Et3N
90
90
90
90
90
90
90
90
90
90
90
80
100
90
90
90
90
90
90
90
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
49
41
2
FeCl3
Et3N
3
FeCl3
Et3N
48
4
FeSO4·7H2O
FeCl2
Et3N
N.D.
40
5
Et3N
6
Fe(acac)2
Fe2(SO4)3
FeCl3
Et3N
trace
N.D.
55
7
Et3N
8
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
−
9
FeCl3
48
10
11
12
13
FeCl3
CH3CN
DCE
66
g
FeCl3
FeCl3
(70)
g
DCE
63
FeCl3
DCE
60
c
14
FeCl3
DCE
53
d
15
FeCl3
DCE
55
e
16
FeCl3
DCE
52
f
17
FeCl3
DCE
N.D
N.D.
N.D.
N.D.
18
19
20
−
FeCl3
DCE
DCE
FeCl3
Cu(acac)2
DCE
a
Reaction conditions: chalcone (1) (0.5 mmol), H-diethyl phosphonate (2) (2.5 equiv), Cu salt (5 mol %), and Fe salt (10 mol %) in solvent (0.5
b
c
d
e
f
g
M), base (1 equiv), O2 atmosphere, 24 h. GC yield. With 5 mol % FeCl3 With 2 equiv of 2a. Under air. Under N2. Isolated yield in parentheses.
Table 2. Substrate Scopes of Various Chalcones by Changing the Substituents on the Aromatic Ring Adjacent to CC Double
a
Bond
a
Reaction conditions: 1 (0.5 mmol), H-diethyl phosphonate 2a (2.5 equiv), Cu(acac)2 (5 mol %), FeCl3 (10 mol %) and DIPEA (0.5 mmol) in
b
DCE (1 mL), O2 atmosphere, 90 °C, 24 h. With 28 h.
1, entries 2−3). Among various iron salts tested, FeCl3 showed
the optimal efficiency (entries 4−7). When the base was
changed from Et3N to DIPEA, the yield of product was
increased to 55%. Solvent was also important for this
transformation (entries 8−11): When the reaction was
performed in DCE, the yield was increased to 70%. The
model reaction failed to give better results even with increasing
or decreasing the temperature (entries 12−13). Moreover,
B
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reducing the amount of FeCl3 or H-diethyl phosphonate (2a),
the yield of product was significantly decreased correspond-
ingly. Ultimately, the use of 5 mol % Cu(acac)2 together with
10 mol % FeCl3 and 2.5 equiv of H-phosphonate in DCE at 90
°C was identified as the optimal reaction protocol (Table 1,
entry 11). Control experiments suggested that molecular
dioxygen, base, Cu(acac)2, and FeCl3 were all indispensable
to this reaction (Table 1, entries 16−20).
Table 3. Substrate Scopes of Various Chalcones Changing
the Aromatic Ring Adjacent to Carbonyl Groups
a
Since there are two possibilities to lead to the desired
products by either cleavage of C(CO)−C(sp2) bond or scission
of CC bond in chalcones, several reactions were conducted
under the optimized conditions in order to figure out which
way was involved in the transformation. As shown in Table 2,
when the substituents on the aromatic ring adjacent to CC
bond on chalcones changed, the same product 3aa was
obtained, which clearly demonstrated that CC double bonds
were scissored in chalcones in this process with the carbonyl
part incorporated into the final products, which was in sharp
contrast to our previous report6b,c and Liu’s work7 where
C(CO)−C(sp2) single bonds were cleaved in α,β-unsaturated
compounds. To our delight, both electron-donating (1b-1d)
and electron-withdrawing (1e) substituented chalcones were
both well tolerated in this transformation, affording the desired
product 3aa in moderate to good yields. (E)-3-(2-nitrophenyl)-
1-phenylprop-2-en-1-one (1e) decreased the yield of 3aa,
presumably due to steric hindrance of ortho-substitution. Halo-
substituted, such as fluoro (1g), chloro (1h), and bromo (1f)
chalcones were also compatible substrates, and the product 3aa
was obtained in 77%, 68%, and 67%, respectively. Poly-
phenylene chalcone, for instance, (E)-3-(naphthalen-2-yl)-1-
phenylprop-2-en-1-one (1i), was also a good candidate for this
transformation and gave β-ketophosphonate 3aa in 65% yield.
Subsequently, the substrate scopes of chalcones by changing
the aromatic ring adjacent to carbonyl were also studied to
obtain diversified β-ketophosphonates, as summarized in Table
3. To our satisfaction, versatile β-ketophosphonates were
obtained in moderate to excellent yields. Once again, the
results suggested that cleavage of CC bond in chalcones
occurred in this transformation since the substituent groups of
the products were in accordance with the kinds on the aromatic
ring adjacent to carbonyl groups of chalcones and correspond-
ing benzaldehydes were detected by GC-MS as well. Although
benzaldehydes could generate in this transformation, no
phosphoaldol product was detected in this reaction.
To evaluate the generality of this aerobic oxyphosphorylation
reaction, other varieties of α,β-unsaturated carbonyl systems
were further employed under the standard conditions as well
(Table 4). In addition to chalcones, alkynones (5a−5c) were
also good substrates for this transformation. In this case,
carbonyl parts were once again incorporated into the desired
product by cleavage of CC bond in the above cases.
Compound 5d was to some extent inert in this transformation
partially due to the inferior free radical stabilization capacity of
ester to aryl groups. Gratifyingly, multiconjugated α,β-
unsaturated carbonyl compounds such as 5e, 5f and 5g were
compatible for this transformation and lead to the desired
product 3ae in moderate to excellent yields. Yet in 5g, the
cleavage of C(sp2)−C(CO) bond occurred instead of a CC
bond as previous cases demonstrated. Intriguingly while
surprisingly, α,β-unsaturated ketones (5h and 5i) and
cinnamaldehyde (5j) demonstrated to be suitable candidates
in this reaction as well to render product 3aa. Obviously, in
these cases (5h−5j) the CC or CC bond part was
a
Reaction conditions: 1 (0.5 mmol), 2 (1.25 mmol), Cu(acac)2 (5 mol
%), FeCl3 (10 mol %), DIPEA (0.5 mmol), DCE (1 mL) in a sealed
tube under O2 atmosphere at 90 °C for 24 h.
incorporated into the final product by cleavage of C(sp2)−
C(CO) bond, which once again in sharp constrast to chalcone
cases. Additionally, phenylallylic alcohol (5k) was also suitable
for this reaction albeit with a low yield of 3ae (35% yield), most
likely the alcohol was oxidized into either aldehyde or
carboxylic acid first, thus making the further transformation
feasible. Therefore, this reaction reveals a clear substituent-
controlled C−C bond cleavage protocol: If the α,β-unsaturated
systems are chalcones, the CC bonds are cleaved with the
carbonyl part incorporated into the final products; if the α,β-
unsaturated systems are aromatic conjugated ketones or
aldehydes, the C(sp2)−C(CO) bonds are cleaved with the
CC part or CC incorporated into the desired products.
In regard to the H-phosphonates, various H-phosphonates
were also investigated to test the compatibility of this
transformation. As shown in Table 5, the reaction was
amenable to different H-phosphonates. Phosphonates 2b, 2c,
2f, and 2g were all suitable donors in this oxidative
transformation in addition to diethyl phosphonate (2a),
generating corresponding β-ketophosphonates 3ab, 3ac, 3af,
and 3ag in moderate to good yields. However, diphenylphos-
phine oxide (2d) and ethyl phenylphosphinate (2e) produced
the desired product 3ad and 3ae in only 36% and 57%,
respectively, which might demonstrate that phosphonates were
more suitable donors than phosphine oxide or phosphinate in
this transformation.
Since 1 equiv of aldehydes was eliminated as byproduct, we
wondered whether the byproducts could be converted into
useful compounds by addition of other nucleophiles. To verify
our hypothesis, alcohols were selected as the nucleophiles. To
our delight, alcohols did capture the abandoned moiety of
chalcones and various benzoates were obtained as one of
products as shown in Table 6, albeit the yields of benzoates
were relatively low. Interestingly, the yields of β-ketophosph-
C
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a
Table 4. α,β-Unsaturated Compound Scope
a
Reaction conditions: 5 (0.5 mmol), 2e (1.3 mmol), Cu(acac)2 (5 mol %), FeCl3 (10 mol %), DIPEA (0.5 mmol), DCE (1 mL) in a sealed tube
b
c
under O2 atmosphere at 90 °C for 24 h. 2e (1.5 mmol) Reaction was performed in 0.3 mmol of 5 with 3 equiv of 2.
a
a
Table 5. H-Phosphonates Scope
Table 6. Utilization Two Moieties of Chalcones
a
Reaction conditions: ROH (2 equiv), 1a (0.5 mmol), 2a (2.5 equiv),
Cu(acac)2 (5 mol %), FeCl3 (10 mol %), DIPEA (0.5 mmol), DCE (1
mL) in a sealed tube under O2 at 90 °C for 24 h.
Not surprisingly, two kinds of benzyl benzoates were
obtained when adscititious alcohols reacted with the unsym-
metric chalcones under standard conditions with 2a (eq 1).
The result along with all above results appealed us to
understand the possible mechanism of this chemoselective
cleavage reaction. First, chalcone 1a was performed under the
standard conditions in absence of diethyl phosphonate (2a) (eq
2), and it still stayed intact, indicating that chalcones were inert
in this copper/iron cocatalyzed system. Subsequently, 2,6-
ditert-butyl-4-methylphenol (BHT) and 2,2,6,6-tetramethyl-1-
piperidinyloxy (TEMPO) were employed as radical probe to
a
Reaction conditions: 1 (0.5 mmol), 2 (2.5 equiv), Cu(acac)2 (5 mol
%), FeCl3 (10 mol %) and DIPEA (0.5 mmol) in DCE (0.5 M), O2
atmosphere, 90 °C, 24 h. 3 equiv of 2, 28 h.
b
onates were significantly increased by the addition of alcohols,
suggesting that extra nucleophiles could markedly promote the
chemoselective cleavage of chalcones in this aerobic phosphor-
ylation reaction.
D
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phosphonate cation radical I was grabbed to release the P-
radical II. Subsequently, the Cu(III)-(•O-OH) hydroperoxide
species was formed in the presence of base under O2
atmosphere. Since the α-position of chalcone has a higher
electron density than the β-position, it induces this P-radical II
attacking at the α-position of chalcone 1 to generate a more
stable benzyl radical,11 which further reacted with Cu(III)-(•O-
OH) species under dioxygen atmosphere to form hydro-
peroxide species III. The oxygen−oxygen bond of hydro-
peroxide species III is weak and broken by H-phosphonate
along with a retro-aldol process12 leaving of an aldehyde 4 and
intermediate IV, which further generated the desired product 3.
The hydroperoxide species III was converted to 1,3-dicarbonyl
compound V as a byproduct as well with the help of base and
H-phosphonate. If an external nucleophile existed, then there
were two retro-claisen pathways13 for subsequent nucleophilic
addition of compound V in which path a gave the desired
product 3 and path b generated product 3′, which explained the
results in eq 1. When Ar2 is equal to Ar1, the two pathways will
give the same results.
react with chalcones and H-phosphonate under the standard
conditions (eq 3), which turned out the reactions were totally
inhibited by TEMPO and BHT, suggesting that a radical
process might be involved in the transformation.
CONCLUSIONS
■
In summary, a substituents-controlled aerobic oxidative chemo-
selective C−C bond cleavage of α,β-unsaturated carbonyl
compounds with H-phosphonates under a dual metal catalysts
has been disclosed, and various α,β-unsaturated carbonyl
compounds can be transformed to valuable β-ketophosphonat-
ess in moderate to good yields via a retro-HWE process.
Isotope-labeling experiments suggested that the oxygen in the
carbonyl of β-ketophosphonates should originate from
chalcones rather than molecular oxygen. Further mechanism
studies revealed that a retro-aldo process released the products
and aldehydes, and if alcohols existed as an external
nucleophile, the abandoned moiety of chalcones could be
captured by alcohols to give various benzoates via the retro-
Claisen process. Research along the future application is
ongoing in our laboratory.
To elucidate the origination of the carbonyl oxygen atom of
β-ketophosphonates, an isotope-labeling experiment was
investigated. Substrates 1h and 2a were performed with 18O2
under the standard conditions, only 4% of 18O-labeled product
3aa was detected (eq 4). Meanwhile, 47% of 18O-labeled 4-
EXPERIMENTAL SECTION
■
General Information. All reagents and solvents were purchased
from commercial suppliers and used without further purification.
Unless otherwise stated, all experiments were conducted in a sealed
tube under O2 atmosphere. Reactions were monitored by thin-layer
chromatography (TLC) or GC-MS analysis. The products were
purified by column chromatography on silica gel using petroleum ether
1
and ethyl acetate as the eluent. H NMR and 13C NMR spectra were
recorded in CDCl3 on a 500 M spectrometer (500 MHz 1H, 125 MHz
13C) at room temperature. Chemical shifts were reported in ppm on
the scale relative to CDCl3 (δ = 7.26 for H NMR, δ = 77.00 for 13C
1
NMR) as an internal reference. 31P NMR spectra were recorded at 200
MHz, and chemical shifts were reported in ppm relative to external
85% phosphoric acid (d = 0.0 ppm).
methoxybenzaldehyde (4h) was detected by GC-MS as well.
The 18O-labeled experiment indicated that the oxygen in the
carbonyl group of β-ketophosphonates should be originated
from chalcone rather than the molecular dioxygen. The low
level of 18O in 4-methoxybenzaldehyde in eq 4 was probably
due to the water scrambling.9
General Procedure for Starting Materials. To a solution of the
acetophenone derivative (5 mmol) and the corresponding benzalde-
hyde (5 mmol) in EtOH (25 mL), NaOH (400 mg, 10 mmol) was
added when corresponding acetophenone and benzaldehyde were
absolutely dissolved, then 1 mL water was added to the mixture. The
resulting mixture was stirred overnight at room temperature. The
resulting solution was extracted with EtOAc (3 × 30 mL), the
combined organic layers were dried over Na2SO4, and the solvents
were removed in vacuo. The corresponding chalcone was obtained
after crystallization from 75% EtOH or by column chromatography
(petroleum ether:AcOEt (30:1, v/v)). Alkynones were synthesized
following the method of the previous procedure.14 Other α,β-
Based on results described above and previous reports,6b,c,10
a tentative mechanism for this tandem oxyphosphorylation is
illustrated in Scheme 2: In the presence of iron(III), a single
electron transfers from an iron(III) species to HP(O) (OR)2
with molecular oxygen, leading to dialkyl phosphonate cation
radical I. With the help of a base, the H+ from the dialkyl
E
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Article
Scheme 2. Plausible Reaction Mechanism for Oxyphosphorylation of Chalcone
unsaturated carbonyl compounds were purchased from commercial
companies.
CDCl3, ppm) δ = 7.98 (d, J = 8.9 Hz, 2H), 6.93 (d, J = 8.9 Hz, 2H),
4.17−4.06 (m, 2H), 3.86 (s, 3H), 3.56 (d, JP−H = 22.7 Hz, 2H), 1.27
(t, J = 7.1 Hz, 6H). 13C{1H}NMR (125 MHz, CDCl3) δ = 190.3 (d,
JP−C = 6.3 Hz), 164.0, 131.5, 129.6, 113.7, 62.6 (d, JP−C = 7.5 Hz),
55.5, 38.7 (d, JP−C = 128.8 Hz), 16.3 (d, JP−C = 6.3 Hz). 31P NMR
(200 MHz, CDCl3) δ = 20.4.
General Procedure for the Synthesis of β-Ketophospho-
nates. To a solution of Cu(acac)2 (6.5 mg, 0.025 mmol, 5 mol %),
anhydrous FeCl3 (8.1 mg, 0.05 mmol, 10 mol %), chalcone 1 (0.5
mmol, 1 equiv), and H-phosphonates 2 (1.25 mmol, 2.5 equiv) in
DCE (1 mL), DIPEA (64.6 mg, 0.5 mmol, 0.083 mL, 1 equiv) was
added at room temperature. Then the mixture was stirred at 90 °C for
24 h. Upon completion of the reaction, the solvent was removed under
reduced pressure. The crude product was purified by column
chromatography using petroleum ether:AcOEt (2:1, v/v) as the
eluent to afford compound 3.
(2-(4-Fluorophenyl)-2-oxoethyl) Phosphonate (3ca).6b−d,10b,15,16
1
Yellow oil (92 mg, 67%). H NMR (500 MHz, CDCl3, ppm) δ =
8.06−8.03 (m, 2H), 7.14 (t, J = 8.6 Hz, 2H), 4.17−4.09 (m, 4H), 3.59
(d, JP−H = 22.8 Hz, 2H), 1.28 (t, J = 7.1 Hz, 6H). 13C{1H}NMR (125
MHz, CDCl3) δ = 190.3 (d, JP−C = 6.6 Hz), 167.1 (d, JF−C = 254.5
Hz), 132.9, 131.8 (d, JF−C = 8.8 Hz), 115.8 (d, JF−C = 22.5 Hz), 62.7
(d, JP−C = 6.3 Hz), 39.1 (d, JP−C = 128.8 Hz), 16.2 (d, JP−C = 6.3 Hz).
31P NMR (200 MHz, CDCl3) δ = 19.6.
Diethyl (2-(4-Chlorophenyl)-2-oxoethyl) Phosphonate
(3da).6b−d,10b,16 Yellow oil (89 mg, 61%). 1H NMR (500 MHz,
CDCl3, ppm) δ = 7.95 (d, J = 8.7 Hz, 2H), 7.44 (d, J = 8.7 Hz, 2H),
4.17−4.08 (m, 4H), 3.59 (d, JP−H = 22.8 Hz, 2H), 1.28 (t, J = 7.1, 6H).
13C{1H}NMR (125 MHz, CDCl3) δ = 190.7 (d, JP−C = 6.3 Hz), 140.3,
General Procedure for the Utilization of Two Sections of
Chalcones. To a solution of Cu(acac)2 (6.5 mg, 0.025 mmol, 5 mol
%), anhydrous FeCl3 (8.1 mg, 0.05 mmol, 10 mol %), chalcone 1 (0.5
mmol, 1 equiv), H-phosphonates 2 (1.25 mmol, 2.5 equiv), and
alcohol 5 (1 mmol, 2 equiv) in DCE (1 mL), DIPEA (64.6 mg, 0.5
mmol, 0.083 mL, 1 equiv) was added at room temperature. Then the
mixture was stirred at 90 °C for 24 h. Upon completion of the
reaction, ethyl acetate (20 mL) was added to the resulting solution and
then washed with saturated NaHSO3 aqueous solution and saturated
brine three times. The combined water layers were extracted with ethyl
acetate (15 mL × 2). The combined organic layers were dried over
anhydrous Na2SO4. Then the solvent was removed under reduced
pressure. The crude product was purified by column chromatography
using petroleum ether:AcOEt (150:1, v/v) as the eluent to afford
benzoates and using petroleum ether:AcOEt (2:1, v/v) as the eluent to
afford β-Ketophosphonates.
134.8, 130.5, 128.9, 62.7 (d, JP−C = 6.5 Hz), 38.6 (d, JP−C = 128.8 Hz),
16.2 (d, JP−C = 6.3 Hz).31P NMR (200 MHz, CDCl3) δ = 19.5.
Diethyl (2-Oxo-2-(m-tolyl)ethyl) Phosphonate (3ea).6b−d,10b,15,16
Yellow oil (95 mg, 70%). 1H NMR (500 MHz, CDCl3, ppm) δ = 7.90
(d, J = 8.3 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H) 4.15−4.09 (m, 4H), 3.60
(d, JP−H = 22.7 Hz, 2H), 2.40 (s, 3H), 1.28 (t, J = 7.1 Hz, 6H).
13C{1H}NMR (125 MHz, CDCl3) δ = 191.4, 144.6, 134.1, 129.3,
129.2, 62.6 (d, JP−C = 6.3 Hz), 38.9 (d, JP−C = 130.0 Hz), 21.6, 16.2 (d,
JP−C = 6.3 Hz). 31P NMR (200 MHz, CDCl3) δ = 20.2.
Diethyl (2-Oxo-2-phenylethyl)phosphonate (3aa).6a−d,10,15,16
1
Yellow oil (90 mg, 70%). H NMR (500 MHz, CDCl3, ppm) δ =
Diethyl (2-Oxo-2-(thiophen-2-yl)ethyl) Phosphonate (3fa).6b,c,10b
Yellowish-brown oil (78 mg, 60%). 1H NMR (500 MHz, CDCl3,
ppm) δ = 7.80 (d, J = 3.8 Hz, 1H), 7.68 (d, J = 4.9 Hz, 1H), 7.12−7.13
(m, 1H), 4.15−4.09 (m, 4H), 3.53 (d, JP−H = 22.5 Hz, 2H), 1.27 (t, J =
8.01(d, J = 7.3 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.8 Hz,
2H), 4.16−4.10 (m, 2H), 3.63 (d, JP−H = 22.7 Hz, 2H), 1.27 (t, J = 7.1
Hz, 6H). 13C{1H}NMR (125 MHz, CDCl3) δ = 191.9 (d, JP−C = 6.5
Hz), 136.5, 133.6, 129.0, 128.6, 62.6 (d, JP−C = 6.3 Hz), 38.5 (d, JP−C
=
7.1 Hz, 6H). 13C{1H}NMR (125 MHz, CDCl3) δ = 184.1 (d, JP−C
=
128.8 Hz), 16.2 (d, JP−C = 6.3 Hz). 31P NMR (200 MHz, CDCl3) δ =
19.9.
6.3 Hz), 143.8, 135.0, 134.1, 128.3, 62.7 (d, JP−C = 6.3 Hz), 39.3 (d,
JP−C = 130.0 Hz), 16.2 (d, JP−C = 6.3 Hz). 31P NMR (200 MHz,
CDCl3) δ = 19.4.
Diethyl (2-(4-Methoxyphenyl)-2-oxoethyl) Phosphonate
(3ba).6b−d,10b,16 Yellow oil (91 mg, 63%). 1H NMR (500 MHz,
F
DOI: 10.1021/acs.joc.5b02887
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The Journal of Organic Chemistry
Article
Diethyl (2-(Naphthalen-2-yl)-2-oxoethyl) Phosphonate
Hz, 2H), 3.11 (t, J = 7.0 Hz, 2H). 13C{1H}NMR (125 MHz, CDCl3) δ
= 166.5, 137.9, 132.9, 130.3, 129.5, 128.9, 128.5, 128.3, 126.6, 65.5,
35.2.
(3ga).6c,10b Yellow oil (86 mg, 56%). H NMR (500 MHz, CDCl3)
1
δ = 8.56 (s, 1H), 8.05 (dd, J = 8.6, 1.7 Hz, 1H), 7.98 (d, J = 8.1 Hz,
1H), 7.88 (t, J = 8.5 Hz 2H), 7.62 (t, 3.9 Hz, 1H), 7.56 (t, J = 7.4 Hz,
1H), 4.19−4.11 (m, 4H), 3.76 (d, JP−H = 22.7 Hz, 2H), 1.27 (t, J = 7.1
Hz, 6H). 13C{1H}NMR (125 MHz, CDCl3) δ = 191.8 (d, J = 6.5 Hz),
135.8, 133.8, 132.4, 131.4, 129.8, 128.9, 128.5, 127.7, 126.9, 124.1, 62.7
(d, J = 6.3 Hz), 39.1 (d, J = 128.8 Hz), 16.2 (d, J = 6.3 Hz). 31P NMR
(200 MHz, CDCl3) δ = 20.1.
Thiophen-2-ylmethyl Benzoate (6d). Colorless oil.20 1H NMR
(500 MHz, CDCl3) δ = 8.07 (d, J = 7.5 Hz, 2H), 7.56 (t, J = 7.4 Hz,
1H), 7.44 (t, J = 7.7 Hz, 2H), 7.34 (d, J = 5.0 Hz, 1H), 7.18 (d, J = 3.4
Hz, 1H), 7.02 (d, J = 5.0 Hz, 1H), 5.52 (s, 2H). 13C{1H}NMR (125
MHz, CDCl3) δ = 166.2, 138.0, 133.1, 129.9, 129.7, 128.3, 128.1,
126.8, 61.0.
Diisopropyl (2-Oxo-2-phenylethyl) Phosphonate (3ab).6b,c,10,15
Light-yellow oil (91 mg, 68%). 1H NMR (500 MHz, CDCl3, ppm) δ =
8.01 (d, J = 7.5 Hz, 2H), 7.56 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz,
2H), 4.75−4.67 (m, 2H), 3.58 (d, JP−H = 22.9 Hz, 2H), 1.27 (dd, J =
4.0 Hz, 4.0 Hz, 12H). 13C{1H}NMR (125 MHz, CDCl3) δ = 192.1 (d,
JP−C = 6.8 Hz), 136.7, 133.5, 129.1, 128.5, 71.5 (d, JP−C = 6.3 Hz), 39.7
(d, JP−C = 130.0 Hz), 23.8 (dd, JP−C = 3.8 Hz, 5.0 Hz). 31P NMR (200
MHz, CDCl3) δ = 17.7.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b02887.
■
S
1H NMR, 13C{1H} NMR and 31P NMR spectra for all
compounds (PDF)
Dimethyl (2-Oxo-2-phenylethyl)phosphonate (3ac).6b,c,10b Color-
less oil (82 mg, 72%). 1H NMR (500 MHz, CDCl3, ppm) δ = 8.01 (d,
J = 7.2 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 3.80
(d, J = 11.2 Hz, 6H), 3.67 (d, JP−H = 23.0 Hz, 2H). 13C{1H}NMR
(125 MHz, CDCl3) δ = 191.7 (d, JP−C = 6.5 Hz), 136.3, 133.8, 128.9,
128.7, 53.2 (d, JP−C = 6.3 Hz), 37.9 (d, JP−C = 131.3 Hz). 31P NMR
(200 MHz, CDCl3) δ = 22.8.
AUTHOR INFORMATION
Corresponding Author
*E-mail: qsong@hqu.edu.cn. Fax: 86-592-6162990.
■
Notes
2-(Diphenylphosphoryl)-1-phenylethanone (3ad).6a−d,10b,15 Yel-
The authors declare no competing financial interest.
1
low oil (58 mg, 36%). H NMR (500 MHz, CDCl3, ppm) δ = 7.98
(dd, J = 8.4, 1.2 Hz, 2H), 7.82−7.78 (m, 4H), 7.55−7.49 (m, 3H),
7.54−7.39 (m, 6H), 4.14 (d, JP−H = 15.4 Hz, 2H). 13C{1H}NMR (125
MHz, CDCl3) δ = 192.8 (d, JP−C = 5.7 Hz), 136.9, 133.6, 132.3, 132.1
ACKNOWLEDGMENTS
■
Financial support from the National Science Foundation of
China (21202049), the Recruitment Program of Global Experts
(1000 Talents Plan), Fujian Hundred Talents Plan, the
Program of Innovative Research Team of Huaqiao University
(Z14X0047), and Graduate innovation fund (for Y.Z.) of
Huaqiao University are gratefully acknowledged. We also thank
the Instrumental Analysis Center of Huaqiao University for
analysis support.
(d, JP−C = 2.5 Hz), 131.1 (d, JP−C = 9.8 Hz), 129.2, 128.6 (d, JP−C
=
11.2 Hz), 128.5, 43.3 (d, JP−C = 57.5 Hz). 31P NMR (200 MHz,
CDCl3) δ = 27.0.
Ethyl (2-Oxo-2-phenylethyl) (Phenyl) Phosphinate (3ae).6a−c,10,15
Yellow oil (94 mg, 54%). 1H NMR (500 MHz, CDCl3, ppm) δ = 7.94
(d, J = 7.2 Hz, 2H), 7.80−7.75 (m, 2H), 7.55−7.51 (m, 2H), 7.46−
7.40 (m, 4H), 4.15−4.07 (m, 1H), 3.97−3.89 (m, 1H), 3.80 (dd, JP−H
= 18.7, 5.6 Hz, 2H), 1.24 (t, J = 7.0 Hz, 3H). 13C{1H}NMR (125
MHz, CDCl3) δ = 192.1 (d, JP−C = 5.5 Hz), 136.7, 133.5, 132.7 (d,
REFERENCES
■
JP−C = 2.9 Hz), 131.8 (d, JP−C = 10.3 Hz), 130.5 129.5, 128.6 (d, JP−C
=
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13.3 Hz), 128.5, 61.4 (d, JP−C = 6.3 Hz), 43.0 (d, JP−C = 85.8 Hz), 16.2
(d, JP−C = 6.5 Hz). 31P NMR (200 MHz, CDCl3) δ = 34.4.
Dibutyl (2-Oxo-2-phenylethyl) Phosphonate (3af).6b,c,10 Yellow
oil (104 mg, 74%). 1H NMR (500 MHz, CDCl3, ppm) δ = 7.99 (d, J =
7.2 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 4.08−
4.01 (m, 4H), 3.62 (d, JP−H = 22.8 Hz, 1H), 1.58 (dt, J = 14.5, 6.6 Hz,
4H), 1.31 (dt, J = 15.1, 7.5 Hz, 4H), 0.87 (t, J = 7.4 Hz, 6H).
13C{1H}NMR (125 MHz, CDCl3) δ = 191.9 (d, JP−C = 6.5 Hz), 136.5,
133.6, 129.0, 128.5, 66.3 (d, JP−C = 6.5 Hz), 38.3 (d, JP−C = 130.0 Hz),
32.3 (d, JP−C = 6.3 Hz), 18.6, 13.5. 31P NMR (200 MHz, CDCl3) δ =
19.9.
Dibenzyl (2-Oxo-2-phenylethyl) Phosphonate (3ag).6b,c,10 Yellow
oil (78 mg, 57%). 1H NMR (500 MHz, CDCl3, ppm) δ = 7.95 (d, J =
7.9 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.7 Hz, 2H), 7.32−
7.26 (m, 10H), 5.04 (ddd, JP−H = 19.9, 11.7, 8.6 Hz, 4H), 3.68 (d, J =
22.6 Hz, 2H). 13C{1H}NMR (125 MHz, CDCl3) δ = 191.6 (d, JP−C
=
6.7 Hz), 136.4 (d, J = 2.5 Hz), 135.8 (d, J = 6.3 Hz), 133.6, 129.0,
128.6, 128.5, 128.4, 128.0, 68.0 (d, JP−C = 6.3 Hz), 39.2 (d, JP−C
=
131.3 Hz). 31P NMR (200 MHz, CDCl3) δ = 21.2.
Naphthalen-1-ylmethyl Benzoate (6a).17 Colorless oil. H NMR
(500 MHz, CDCl3) δ 8.13 (d, J = 7.4 Hz, 2H), 7.61 (m, 7H), 7.47 (d,
J = 7.7 Hz, 2H), 7.39 (t, J = 7.3 Hz, 1H), 5.44 (s, 2H).13C{1H}NMR
(125 MHz, CDCl3) δ 134.0, 133.0, 131.1, 129.8, 128.9, 127.7, 126.7,
126.1, 125.3, 123.6, 44.5.
1
Benzyl Benzoate (6b). Colorless oil.18 1H NMR (500 MHz,
CDCl3) δ= 8.10 (d, J = 7.6 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.34−
7.47 (m, 7H), 5.38 (s, 2H). 13C{1H}NMR (125 MHz, CDCl3) δ =
166.4, 136.1, 133.0, 130.1, 129.7, 128.6, 128.3, 128.2, 128.1, 66.7.
Phenethyl Benzoate (6c). Colorless oil.19 1H NMR (500 MHz,
CDCl3) δ = 8.05 (d, J = 7.1 Hz, 2H), 7.60−7.56 (m, 1H), 7.46 (t, J =
7.7 Hz, 2H), 7.37−7.31 (m, 4H), 7.29−7.27 (m, 1H), 4.57 (t, J = 7.0
G
DOI: 10.1021/acs.joc.5b02887
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J. Org. Chem. XXXX, XXX, XXX−XXX