Cu(II)-Catalyzed Phosphonocarboxylative Cyclization Reaction of Propargylic Amines and Phosphine Oxide with CO2

Article abstract of DOI:10.1021/acs.joc.0c02172

Compounds bearing organophosphorus motifs and 2-oxazolidinone have found numerous applications in pharmaceutical chemistry, homogeneous catalysis, and organic materials. Here, we describe an efficient and selective protocol for straightforward access to a series of 5-((diarylphosphoryl)methyl)oxazolidin-2-ones via the copper-catalyzed difunctionalization of the CC bond of propargylic amines with CO2 and phosphine oxide. Notably, copper catalysis is a sustainable and benign catalytic mode. This reaction proceeds under mild reaction conditions, which is operationally simple and scalable with a broad scope, exclusive selectivity, and good functional group compatibility. Mechanistic studies suggest a one-pot tandem cyclization/radical addition sequence, along with the phosphorylation/cyclization scheme.

Full text of DOI:10.1021/acs.joc.0c02172

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Article
Cu(II)-Catalyzed Phosphonocarboxylative Cyclization Reaction of
Propargylic Amines and Phosphine Oxide with CO2
Wen-Bin Huang, Fang-Yu Ren, Ming-Wei Wang, Li-Qi Qiu, Kai-Hong Chen, and Liang-Nian He*
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ABSTRACT: Compounds bearing organophosphorus motifs and
2-oxazolidinone have found numerous applications in pharmaceut-
ical chemistry, homogeneous catalysis, and organic materials. Here,
we describe an efficient and selective protocol for straightforward
access to a series of 5-((diarylphosphoryl)methyl)oxazolidin-2-
ones via the copper-catalyzed difunctionalization of the CC
bond of propargylic amines with CO2 and phosphine oxide.
Notably, copper catalysis is a sustainable and benign catalytic
mode. This reaction proceeds under mild reaction conditions,
which is operationally simple and scalable with a broad scope,
exclusive selectivity, and good functional group compatibility. Mechanistic studies suggest a one-pot tandem cyclization/radical
addition sequence, along with the phosphorylation/cyclization scheme.
Scheme 1. Multicomponent Reactions (MCRs) Involving
Propargylic Amines with CO2
INTRODUCTION
■
In the past decades, we have witnessed dramatic advances in
the development of CO2 fixation from the viewpoint of the
environment and organic synthesis.1 CO2 can be used as a
ubiquitous nontoxic, nonflammable, and renewable one-carbon
(C1) synthon to achieve value-added chemicals, but due to the
thermodynamic stability and kinetic inertness, it is difficult to
realize its efficient utilization. Although challenging, numerous
strategies about the catalytic transformation of CO2 with
unsaturated substrates, small-ring compounds, amines, alco-
hols, hydrogen, and so on have been reported, resulting in the
construction of new C−C, C−N, and C−O bonds, involving
nucleophilic reactions,2 transition-metal catalysis,3 and photo-
catalysis.4 Among them, the catalytic difunctionalization of the
CC bond with CO2 to synthesize the carbonyl-containing
compounds with complex structural diversity is a compellingly
attractive transformation. Overall, the difunctionalization of the
CC bond with CO2 leads to the α,β-unsaturated carboxylic
acids and their derivatives,3a,5 which are important scaffolds in
bioactive molecules and useful organic synthetic intermedi-
ates.6
In this context, the difunctionalization of the CC bond
with CO2 is about the incorporation of CO2 into propargylic
alcohols or propargylic amines, thus providing the function-
alized methylene carbonates or 2-oxazolidinones. Although the
incorporation of CO2 into propargylic alcohols and propargylic
amines have been intensively studied in the past decade,7 the
multicomponent reactions involving propargylic amines, CO2
and another coupling partner are less investigated. Four kinds
of methods as depicted in Scheme 1a−d have been established
to synthesize arylated methylene 2-oxazolidinones,8 bromovi-
nyloxazolidinone,9 iodovinyloxazolidinone,2a,10 aminovinylox-
azolidinone,11 and selenyl 2-oxazolidinone12 via the incorpo-
ration of CO2 into propargylic amines. However, the types of
the functional groups are relatively limited. The mechanism of
these reactions usually involves vinyl-metal intermediates via
oxidative addition-reductive elimination, electrophilic, or
radical pathway. The final products are always functionalized
vinyloxazolidinones. To our knowledge, the synthesis of
functionalized-methyloxazolidin-2-ones through carboxylative
cyclization of propargylic amines with CO2 has not yet been
reported to date.
Received: September 8, 2020
https://dx.doi.org/10.1021/acs.joc.0c02172
© XXXX American Chemical Society
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A

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a
Organophosphorus compounds have attracted considerable
attention owing to wide applications as ligands in organic
synthesis,13 functional materials,14 and their important bio-
logical and pharmacological characteristics.15 In recent years,
transition metal-catalyzed phosphorous free-radical chemistry
has been intensively studied, especially reactions with alkenes
or alkynes leading to various C−P bond-containing com-
pounds.16 For example, organophosphorus compounds that
react with alkynes under the oxidative conditions could
produce a series of β-ketophosphonates.17 Meanwhile,
extraordinary advances have been made in the difunctionaliza-
tion of alkenes with organophosphorous compounds, such as
fluorphosphinoylation,18 oxyphosphinoylation,19 and carbo-
phosphinoylation,20 and so on. Notably, the phosphonyl
radical mechanism for this transformation can be induced by
copper catalysis.17a,19b
According to the previous studies, copper salts are able to
activate the CC bond efficiently, thus promoting the
carboxylative cyclization of propargylic amines.21 Inspired by
the difunctionalization of alkenes, if we could merge the
phosphorus chemistry with CO2 to perform oxyphosphor-
ylation of propargylic amines by copper catalysis, which is a
sustainable and benign catalytic mode, we hypothesized that
the propargylic amine could be used as a nucleophile to attack
CO2 assisted by a Cu catalyst to provide the 3-benzyl-5-
methyleneoxazolidin-2-one analogue, followed by the reaction
with the phosphine oxide via the phosphonyl radical
mechanism induced by single-electron transfer (SET). If
copper catalysis could promote both processes simultaneously,
the formation of the phosphorylated 2-oxazolidinone can be
attained.
Table 1. Optimization of Reaction Conditions
b
entry
catalyst
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
CuBr2
[Cu(MeCN)4]PF6
CuCl
AgOAc
base
solvent T (°C) yield (%)
1
2
3
4
5
6
7
8
t-BuOK
t-BuONa
Na2CO3
DBU
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
DMAc
NMP
DMF
DMF
DMF
DMF
DMF
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
60
50
60
60
60
39
47
60
n.d.
70
51
62
61
53
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
9
10
11
12
13
14
15
16
17
Ag2CO3
62
Co(OAc)2
Ni(acac)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
18%
trace
60
60
62
80
72
c
d
18
84 (75)
n.d.
n.d.
19
20
Cu(OAc)2
a
Reaction conditions unless otherwise specified: 1a (0.25 mmol, 1.0
equiv), 2a (0.75 mmol, 3.0 equiv), cat. (0.05 mmol), base (0.5 mmol,
2.0 equiv), solvent (2 mL), CO2 balloon, 24 h. Determined by H
NMR using 1,3,5-trimethoxybenzene as an internal standard. n.d. =
b
1
c
not detected. H2O (1.0 mmol, 4.0 equiv) was used as the additive.
d
Isolated yield is given in parentheses.
RESULTS AND DISCUSSION
■
Initially, the reaction of N-benzylprop-2-yn-1-amine (1a) with
diphenylphosphine oxide (2a) was performed under CO2
balloon condition in the presence of cupric acetate, 2.0 equiv
of potassium tert-butoxide (t-BuOK) in DMF at 80 °C for 24
h. Fortunately, under this redox neutral conditions,22 we were
delighted to identify the one-pot tandem cyclization/
phosphorylation product, delivering 5-((diphenylphosphoryl)-
methyl)oxazolidin-2-one 3aa in 39% NMR yield (entry 1,
Table 1). Subsequently, several kinds of bases were
investigated, and triethylenediamine (DABCO) showed higher
efficiency (entry 5 vs entries 1−4). Other bases such as
carbonates, alkali tert-butoxide, 1,8-diazabicyclo[5.4.0]undec-
7-ene (DBU), and Et3N could also promote the reaction but
with low yields (Table S1, Supporting Information). The base
effect in this study could presumably be ascribed to the
formation of the bulkier cation, i.e., DABCO-H+, which plays a
vital role in stabilizing the carbamic anion and increasing the
nucleophilicity of the carbamate intermediate.7b Then, screen-
ing of Cu compounds showed that either cupric salts or
cuprous salts could promote the reaction efficiently. Cupric
acetate was found to be the best efficient catalyst (entries 6−8
vs entry 5). As expected, silver compounds were also effective
but relatively less active than copper counterpart (entries 9 and
10 vs entry 5). However, some kinds of Pd, Fe, Co, Ni salts
could not promote the reaction (entries 11 and 12, Table S1).
As a consequence, the cheap and earth abundant Cu
compound, i.e., cupric acetate, was selected as the catalyst
for further investigation. We found that the reaction could
proceed well in polar solvents and DMF exhibits the best
(entries 13−15 vs 5). Afterward, lowering the reaction
temperature to 60 °C, the higher efficiency was observed
(entry 16 vs entry 5), while further decreasing the temperature
to 50 °C caused the 3aa yield to slightly decrease (entry 17 vs
entry 16). Finally, when 4.0 equiv of H2O was used as an
additive, the yield could be improved to 84% (entry 18),
implying that water may be used as a proton source to
protonate the intermediate with C−Cu bond in the final step
and is shown in Scheme 6. Control experiments demonstrated
that the reaction could not proceed in the absence of either
cupric acetate or DABCO (entries 19 and 20).
With the optimal conditions in hand, we examined the
generality and viability of this tandem reaction with various
propargylic amines. As a consequence, numerous propargylic
amines were converted into the desired products in moderate-
to-good yields and are shown in Scheme 2. Propargylic amines
with methyl substituted at the ortho, meta, or para position of
the benzene ring could proceed smoothly, giving the
diarylmethyloxazolidin-2-one products in good yields (3aa−
3da), which excluded the steric hindrance effect. Other
electron-sufficient groups like tert-butyl, methoxy at the para
position were well tolerated (3ea, 3fa). On the other hand,
amine substrates with electron-withdrawing substituents, such
as fluoro, chloro, bromo, cyano, and trifluoromethyl sub-
stituents at the para position were also successfully trans-
formed into the desired phosphorylation products with yields
ranging from 65 to 74% (3ga−3ka). The configuration of the
phosphorylated product 3ga was confirmed by the single-
crystal X-ray diffraction analysis (Table S2). Moreover, 3,4-di-
chloro substituted amine 1l can smoothly converted into the
phosphorylation product with 62% yield. However, bulky
B
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a b
,
Scheme 2. Substrate Scope Relative to Propargylic Amine
Scheme 3. Substrate Scope with Respect to Diarylphosphine
a b
,
Oxide
a
Reaction conditions: 1a (0.25 mmol, 1.0 equiv), diarylphosphine
oxide 2 (0.75 mmol, 3.0 equiv), Cu(OAc)2 (0.05 mmol), DABCO
(0.5 mmol, 2.0 equiv), H2O (1.0 mmol, 4.0 equiv), DMF (2 mL),
a
Unless noted otherwise, all the reactions were performed with
propargylic amine 1 (0.25 mmol, 1.0 equiv), diarylphosphine oxide 2
(0.75 mmol, 3.0 equiv), Cu(OAc)2 (0.05 mmol), DABCO (0.5 mmol,
2.0 equiv), H2O (1.0 mmol, 4.0 equiv), DMF (2 mL), CO2 balloon,
b
CO2 balloon, 60 °C, 24 h. Isolated yield. n.d. = not detected.
b
c
d
60 °C, 24 h. Isolated yield. n.d. = not detected. d.r. = 3:4. 2a (0.25
mmol, 1.0 equiv), 1r (0.375 mmol, 1.5 equiv). TBD (2.0 equiv) was
used as the base.
showed good reactivity (3ad), demonstrated the negligible
steric effect of the meta position. The configuration of the
phosphorylated product 3ad was confirmed by the single-
crystal X-ray diffraction analysis (Table S3). Moreover,
substrates bearing electron-donating and electron-withdrawing
functional groups on the para of the aryl rings proceeded well
with moderate yields ranging from 39 to 62% (3ae−3ai). In
addition, di(naphthalen-1-yl)phosphine oxide and di-
(naphthalen-2-yl)phosphine oxide delivered the target prod-
ucts in reasonable yields (3aj, 3ak).
To further investigate the potential application of this
protocol, a gram-scale experiment of the representative-titled
product of 5-((diphenylphosphoryl)methyl)oxazolidin-2-one,
i.e., 3aa, was carried out and are shown in Scheme 4.
Gratifyingly, a gram-scale synthesis of 3aa was implemented
successfully with a comparable yield. We also explored two
transformations of 3aa. First, the reaction of 3aa with t-BuOK
delivered a 80% yield of the privileged alkenyl phosphine oxide
4, whose molecules with such a skeleton possess potential
pharmacological properties.24 On the other hand, 3aa was
reduced by LiAlH4 producing amino-3-(diphenylphosphanyl)-
propan-2-ol 5 in 75% yield, analogous structures containing a
β-hydroxy alkylphosphine oxide motif usually act as important
organic intermediates;25 some of which even possess potential
applications in herbicides, moisture-resistant compounds, and
antioxidants.19a Accordingly, the synthetic utility of this
methodology was approved.
e
propargylic amines, i.e., 1m and 1n, made the reaction
efficiency sharply decreased presumably due to increasing in
steric hindrance (3ma, 3na). Furthermore, functional groups
such as n-butyl, cyclohexyl, phenethyl, and propargyl groups
substituted on the amine nitrogen, which reacted with diphenyl
phosphine oxide and CO2 with barely satisfactory-to-good
yields (3oa−3ra). Considering that the phenyl group may
reduce the nucleophilicity of amine 1s, which hampers the
reaction remarkably, only 10% yield of 3sa was isolated, along
with a small amount of 3sa′. It is worth mentioning that the
amine possessing gem-dimethyl at the propargylic position
could successfully afforded 82% yield 3ta probably owing to
the Thorpe−Ingold effect.23 Meanwhile, internal propargylic
amine 1u gave a messy result, forming only a 12% yield of 3ua
probably due to the steric effect. Unfortunately, the amine
substrates with acetyl (Ac-), tert-butoxycarbonyl (Boc-), or p-
toluenesulfonyl (Ts-) substituent on the nitrogen atom could
not deliver the desired product (3va) probably due to the poor
nucleophilicity.
On the other hand, several kinds of H-P(O) compounds 2
were examined under the standard reaction conditions
(Scheme 3). Diarylphosphine oxide with methyl substituent
on the para position of the benzene ring provided a higher
yield compared with the ortho-substituted analog (3ab vs 3ac),
being attributed to the steric hindrance. Notably, phosphine
oxide 2d with two tert-butyl groups on the meta position
To better understand the reaction mechanism, a series of
control experiments were conducted. Radical trapping experi-
ments demonstrated that the reaction could be extremely
C
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Then, treating 4 with CO2 under the standard conditions, the
cyclization product 3aa was obtained with 39% yield (eq5,
Scheme 5). These observations suggested that the reaction
could also undergo the radical addition/carboxylative cycliza-
tion process. Finally, H/D exchange experiments unraveled
that the deuteration occurred adjacent to oxygen and
phosphorus atoms, and the deuterium percentage increased
along with adding more D2O (eq6, Scheme 5), being supposed
that water could serve as the hydrogen source to promote this
process.
Scheme 4. Gram-Scale Experiment and Derivatization
To distinguish the charge distribution between 5-methylene-
oxazolidin-2-one 6 and the vinyl copper intermediate,
electronic static potential (ESP) analysis was conducted
(Figure 1, Figure S5 and Tables S4 and S5). ESP diagrams
inhibited by 2,2,6,6-tetramethyl-1-piperdinyloxy (TEMPO),
with the formation of 5-methyleneoxazolidin-2-one 6 and the
TEMPO adduct 7 concomitantly. (eq1, Scheme 5), suggesting
Scheme 5. Mechanistic Investigation
Figure 1. ESP diagrams of 6 and vinyl-copper intermediate.
revealed that the methylene of the vinyl copper intermediate is
more electron positive than vinyl oxazolidinone 6, which may
make it easier to proceed the phosphonyl radical addition to
the CC bond, being consistent with the result of eq4 in
scheme 5. In other words, 6 without a copper catalyst was
hardly run subsequent reaction to furnish the desired product.
To further confirm our hypothesis about the phosphonyl
radical mechanism, electron paramagnetic resonance (EPR)
spectroscopy was conducted (Figure 2). Delightfully, when
a
The isolated yield was relative to diphenylphosphine oxide 2a.
b
Ratio of E- and Z-isomers (>99%).
this reaction probably goes through a phosphonyl radical
pathway. Second, it showcased that the propargylic amine can
be transformed into 5-methylene-oxazolidin-2-one 6 in a 95%
yield under the standard conditions (eq2, Scheme 5). When
the reaction of 6 with H-P(O) compound 2a afforded a 10%
3aa yield (eq3, Scheme 5). These results supposed that the
first step of this three-component reaction would be
carboxylative cyclization of propargylic amine with CO2.
Furthermore, to verify the alternative pathway, i.e., phosphor-
ylation/cyclization sequence,26 the reaction of 1a and 2a was
performed in the absence of CO2, affording the alkenylphos-
phine oxide compound 4 in moderate yield (eq4, Scheme 5).
Figure 2. Electron paramagnetic resonance (EPR) spectra (X band,
9.4 GHz, room temperature). Reaction conditions: 1a (0.25 mmol,
1.0 equiv), 2a (0.75 mmol, 3.0 equiv), Cu(OAc)2 (0.05 mmol),
DABCO (0.5 mmol, 2.0 equiv), MNP (0.375 mmol, 1.5 equiv), DMF
(2 mL), CO2 balloon, 60 °C, 1 h. Curve a represents the experimental
signal (black) and the simulated signal (red). Curve b is the simulated
signal of radical A. Curve c is the simulated signal of radical B.
D
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free-radical spin-trapping agent 2-methyl-2-nitrosopropane
(MNP) was added to the model reaction, two EPR signals
emerged. The experimental EPR signal fits well with the
simulation curve. According to the previous report,22 EPR
spectral analysis suggested that both of the diphenyl phosphine
oxide radical and the alkyl radical II generated (scheme 6),
with CO2 and phosphine oxides using the sustainable copper
catalysis. This redox neutral multicomponent reaction of
propargylic amines, diarylphosphine oxides, and CO2 led to
the formation of three kinds of new carbon-hetero (N, O, P)
bonds efficiently. Mechanistic studies uncovered a one-pot
tandem cyclization/radical addition sequence, along with the
phosphorylation/cyclization scheme. This methodology exhib-
its broad substrate scope, excellent functional group tolerance,
and exclusive selectivity. Notably, this reaction is facilely
scalable, and the products are easily derived from important
organic intermediates and biologically active molecules.
Furthermore, the target products containing 2-oxazolidinone
and organophosphorus moieties may have latent bioactivities.
Scheme 6. Plausible Mechanism
EXPERIMENTAL SECTION
■
General Information. Unless otherwise noted, all solvents were
used directly without further purification. The products were isolated
by column chromatography on silica gel (100-200 mesh) using
petroleum ether and ethyl acetate. An oil bath was used as the heat
source for reactions that require heating. NMR spectra were obtained
1
on a Bruker 400 MHz spectrometer at 20 °C. The H NMR (400
MHz) chemical shifts were measured relative to CDCl3 as the internal
reference (CDCl3: δ = 7.260 ppm). The 13C NMR (101 MHz)
chemical shifts were given using CDCl3 as the internal standard
(CDCl3: δ = 77.16 ppm). The 31P NMR (162 MHz) data were
recorded with a Bruker 400 MHz spectrometer. EPR spectra were
recorded on a Bruker X-band A−200 spectrometer. The samples were
taken out by a capillary (ordinary glass, 0.5 mm × 100 mm) and then
recorded by an EPR spectrometer at indicated temperature and
parameters. FT-IR was recorded on a Bruker Tensor 27 FT-IR
spectrophotometer with KBr pellets. High-resolution mass spectra
(HR-MS) were obtained with a Waters-Q-TOF-Premier (ESI+ or
ESI−).
General Procedure for Oxyphosphorylation of Propargylic
Amines with Diarylphosphine Oxide and CO2. A 10 mL Schlenk
flask equipped with a magnetic stir bar was charged successively with
propargylic amine (0.25 mmol), diarylphosphine oxide (0.75 mmol),
copper acetate (9.1 mg, 20 mol % relative to propargylic amine),
DABCO (56.1 mg, 0.5 mmol), H2O (18 mL, 1 mmol), and DMF (2
mL). The reaction mixture is frozen with liquid nitrogen, then
degassed, exposed to a CO2 atmosphere (balloon), and warmed up to
room temperature. The flask was heated to 60 °C for 24 h. After the
reaction, DMF was distilled under reduced pressure. To identify the
structure of the oxyphosphorylated product, the reaction mixture was
concentrated and purified by silica gel column chromatography
(silica: 100−200 mesh, petroleum ether/ethyl acetate, from 1:1 to
1:3) to afford the corresponding 5-((diarylphosphoryl)methyl)-
oxazolidin-2-one products.
subsequently trapped by MNP to form the relatively stable
radical A (aN = 10.5 G, aP = 11.8 G) and B (aN = 15.5 G).
These results manifest phosphorus radical undergoes nucleo-
philic addition to the vinyl copper moiety, thus forming the
alkyl radical II.
Based on these results and the previous reports, two possible
reaction mechanisms are proposed using propargylic amine 1a
as a representative substrate and are depicted in Scheme 6. As
for pathway A, in the presence of DABCO, the reaction of 1a
with CO2 provides the carbamate stabilized by the bulkier
cation,7b i.e., DABCO-H+, which further goes through
intramolecular cyclization to furnish the vinyl copper
intermediate I via TS1a‑I, assisted by the Cu(II) compound
able to activate the CC bond of the amine.21 Meanwhile, a
single-electron transfer (SET) assisted by the oxidation of CuII
salt occurs between CuII and diphenylphosphine oxide to
generate the diphenyl phosphine oxide radical.17a,19b Then, the
nucleophilic attack of the phosphonyl radical on the vinyl
copper intermediate I delivers the phosphorus-containing alkyl
radical intermediate II. The intermediate II is further reduced
by CuI forming carbanion III. Finally, the carbanion III is
protonated by water or other hydrogen source to furnish the
phosphorylation target product 3aa and regenerate the Cu
catalytic species. The alternative pathway B involves the
addition of phosphonyl radical to the alkyne moiety of 1a, thus
forming alkenylphosphine oxide compound 4. Subsequently,
the direct introduction of CO2 into allylamine intermediate 4
results in the formation of 3aa.
3-Benzyl-5-((diphenylphosphoryl)methyl)oxazolidin-2-one
(3aa). White solid, mp: 142−143 °C, 73.4 mg, 75% yield, Rf = 0.30
1
(petroleum ether/ethyl acetate 1:3). H NMR (400 MHz, CDCl3) δ
7.69 (ddd, J = 26.9, 11.7, 7.4 Hz, 4H), 7.59−7.41 (m, 6H), 7.37−7.27
(m, 2H), 7.22 (d, J = 7.3 Hz, 2H), 4.70 (m, 1H), 4.44 (d, J = 14.8 Hz,
1H), 4.27 (d, J = 14.8 Hz, 1H), 3.57 (t, J = 8.8 Hz, 1H), 3.46−3.33
(m, 1H), 2.98−2.83 (m, 1H), 2.63 (td, J = 14.0, 10.7 Hz, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ 157.3, 135.6, 132.7 (d, J = 102.0
Hz), 132.4 (dd, J = 8.3, 2.3 Hz), 131.8, 130.8 (d, J = 9.4 Hz), 130.4
(d, J = 9.7 Hz), 129.1, 129.0, 128.9, 128.3, 128.0, 69.3, 50.1, 48.3, 35.7
(d, J = 68.0 Hz). 31P NMR (162 MHz, CDCl3) δ 27.34. IR (KBr):
3522, 3444, 3381, 3058, 2919, 1747, 1650, 1631, 1488, 1438, 1371,
1344, 1259, 1188, 1120, 1101, 1072, 747, 722, 698, 665, 546, 527
cm−1. HR-ESI-MS: calcd m/z [M + H]+ for [C23H23NO3P]+:
392.1415, found: 392.1411.
5-((Diphenylphosphoryl)methyl)-3-(2-methylbenzyl)oxazolidin-
2-one (3ba). Pale yellow oil, 76.0 mg, 75% yield, Rf = 0.30
1
In conclusion, we have developed a straightforward strategy
to access to 5-((diarylphosphoryl)methyl)oxazolidin-2-ones via
difunctionalization of the CC bond of propargylic amines
(petroleum ether/ethyl acetate 1:3). H NMR (400 MHz, CDCl3) δ
7.68 (ddd, J = 25.3, 11.7, 7.6 Hz, 4H), 7.55−7.37 (m, 6H), 7.20−7.05
(m, 4H), 4.71 (p, J = 10.3 Hz, 1H), 4.46 (d, J = 14.8 Hz, 1H), 4.24
E
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(d, J = 14.8 Hz, 1H), 3.46 (t, J = 8.8 Hz, 1H), 3.32−3.23 (m, 1H),
2.98−2.88 (m, 1H), 2.61 (td, J = 13.8, 10.3 Hz, 1H), 2.25 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ 156.9, 136.6, 133.2, 132.4 (d, J
= 103.02 Hz), 132.3 (dd, J = 8.1, 2.2 Hz), 131.7, 130.7 (d, J = 9.7
Hz), 130.3 (d, J = 9.7 Hz), 129.1, 128.9 (d, J = 22.2 Hz), 128.9
(overlapped), 128.1, 126.2, 69.1, 50.1, 46.2, 35.6 (d, J = 68.0 Hz),
19.0. 31P NMR (162 MHz, CDCl3) δ 27.53. IR (KBr): 3468, 3057,
2916, 1749, 1644, 1488, 1438, 1371, 1254, 1187, 1120, 746, 723, 696,
535, 516 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for
[C24H25NO3P]+: 406.1572, found: 406.1571.
1028, 847, 751, 721, 696, 514 cm−1. HR-ESI-MS: calcd m/z [M +
H]+ for [C24H25NO4P]+: 422.1521, found: 422.1522.
5-((Diphenylphosphoryl)methyl)-3-(4-fluorobenzyl)oxazolidin-2-
one (3ga). White solid, mp: 192−193 °C, 73.6 mg, 72% yield, Rf =
0.35 (petroleum ether/ethyl acetate 1:3). 1H NMR (400 MHz,
CDCl3) δ 7.68 (ddd, J = 26.1, 11.2, 8.0 Hz, 4H), 7.47 (ddt, J = 21.2,
14.0, 7.2 Hz, 6H), 7.21−7.14 (m, 2H), 6.97 (t, J = 8.4 Hz, 2H), 4.75−
4.64 (m, 1H), 4.36 (d, J = 14.8 Hz, 1H), 4.23 (d, J = 14.8 Hz, 1H),
3.54 (t, J = 8.7 Hz, 1H), 3.42−3.33 (m, 1H), 2.91 (t, J = 10.8 Hz,
1H), 2.61 (dd, J = 24.7, 13.8 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 163.7, 161.3, 157.2, 132.7 (d, J = 103.02 Hz), 132.4 (dd, J =
8.1, 2.2 Hz), 131.8, 131.4 (d, J = 3.0 Hz), 130.8 (d, J = 9.5 Hz), 130.3
(d, J = 9.7 Hz), 130.1 (d, J = 8.3 Hz), 129.0 (d, J = 23.2 Hz), 129.0
(overlapped), 115.7 (d, J = 21.6 Hz), 69.3, 50.0, 47.6, 35.6 (d, J = 67.9
Hz). 31P NMR (162 MHz, CDCl3) δ 27.17. IR (KBr): 3474, 3458,
3443, 3058, 2918, 1746, 1647, 1606, 1510, 1438, 1260, 1222, 1187,
1120, 1017, 809, 750, 722, 696, 662, 535, 514 cm−1. HR-ESI-MS:
calcd m/z [M + H]+ for [C23H22FNO3P]+: 410.1321, found:
410.1317.
3-(4-Chlorobenzyl)-5-((diphenylphosphoryl)methyl)oxazolidin-
2-one (3ha). White solid, mp: 136−137 °C, 69.1 mg, 65% yield, Rf =
0.30 (petroleum ether/ethyl acetate 1:3). 1H NMR (400 MHz,
CDCl3) δ 7.62 (ddd, J = 26.6, 11.6, 7.4 Hz, 4H), 7.51−7.31 (m, 6H),
7.20 (d, J = 8.3 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 4.72−4.59 (m,
1H), 4.29 (d, J = 14.9 Hz, 1H), 4.18 (d, J = 14.9 Hz, 1H), 3.48 (t, J =
8.8 Hz, 1H), 3.31 (dd, J = 9.1, 7.1 Hz, 1H), 2.92−2.80 (m, 1H), 2.56
(td, J = 13.9, 10.7 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ
157.2, 134.1, 133.9, 132.5 (d, J = 103.0 Hz), 132.4 (dd, J = 7.7, 1.8
Hz), 131.1 (d, J = 101.0 Hz), 130.7 (d, J = 9.4 Hz), 130.3 (d, J = 9.6
Hz), 129.6, 129.0 (d, J = 23.2 Hz), 129.0 (overlapped), 69.3, 50.0,
47.6, 35.5 (d, J = 67.9 Hz). 31P NMR (162 MHz, CDCl3) δ 27.42. IR
(KBr): 3545, 3503, 3425, 3386, 3360, 2956, 2923, 2852, 1748, 1649,
1490, 1438, 1376, 1264, 1186, 1092, 1015, 744, 696, 533, 512 cm−1.
HR-ESI-MS: calcd m/z [M + H]+ for [C23H22ClNO3P]+: 426.1026,
found: 426.1019.
3-(4-Bromobenzyl)-5-((diphenylphosphoryl)methyl)oxazolidin-
2-one (3ia). White solid, mp: 178−179 °C, 82.1 mg, 70% yield, Rf =
0.30 (petroleum ether/ethyl acetate 1:3). 1H NMR (400 MHz,
CDCl3) δ 7.67 (ddd, J = 26.5, 11.5, 8.0 Hz, 4H), 7.56−7.37 (m, 8H),
7.07 (d, J = 8.2 Hz, 2H), 4.76−4.64 (m, 1H), 4.32 (d, J = 14.9 Hz,
1H), 4.22 (d, J = 14.9 Hz, 1H), 3.53 (t, J = 8.8 Hz, 1H), 3.43−3.31
(m, 1H), 2.98−2.85 (m, 1H), 2.61 (dd, J = 24.5, 13.8 Hz, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ 157.2, 134.5, 132.5 (d, J = 98.0
Hz), 132.4 (dd, J = 7.8, 2.5 Hz), 131.9, 131.0 (d, J = 100.0 Hz), 130.7
(d, J = 9.6 Hz), 130.3 (d, J = 9.6 Hz), 130.0, 129.0 (d, J = 23.2 Hz),
129.0 (overlapped), 122.0, 69.3 (d, J = 1.4 Hz), 50.0 (d, J = 1.2 Hz),
47.6, 35.5 (d, J = 67.9 Hz). 31P NMR (162 MHz, CDCl3) δ 27.41. IR
(KBr): 3668, 3646, 3616, 3056, 2927, 1750, 1591, 1488, 1438, 1262,
1188, 1120, 745, 723, 696, 532, 515 cm−1. HR-ESI-MS: calcd m/z [M
+ H]+ for [C23H22BrNO3P]+: 470.0520, found: 470.0513.
5-((Diphenylphosphoryl)methyl)-3-(3-methylbenzyl)oxazolidin-
2-one (3ca). Pale blue oil, 77.0 mg, 76% yield, Rf = 0.30 (petroleum
1
ether/ethyl acetate 1:3). H NMR (400 MHz, CDCl3) δ 7.76−7.60
(m, 4H), 7.54−7.38 (m, 6H), 7.17 (t, J = 7.5 Hz, 1H), 7.07 (t, J = 6.6
Hz, 1H), 7.03−6.96 (m, 2H), 4.76−4.63 (m, 1H), 4.37 (d, J = 14.7
Hz, 1H), 4.20 (d, J = 14.7 Hz, 1H), 3.57−3.49 (m, 1H), 3.36 (dd, J =
9.5, 6.9 Hz, 1H), 2.91 (ddd, J = 14.5, 9.6, 3.6 Hz, 1H), 2.67−2.55 (m,
1H), 2.28 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.2, 138.5,
135.4, 132.5 (d, J = 103.0 Hz), 132.3 (dd, J = 8.7, 2.6 Hz), 131.1 (d, J
= 101.0 Hz), 130.7 (d, J = 9.7 Hz), 130.3 (d, J = 9.8 Hz), 129.0, 128.9
(d, J = 23.2 Hz), 128.9 (overlapped), 128.7 (d, J = 6.1 Hz), 125.3,
69.1, 50.0, 48.2, 35.5 (d, J = 68.1 Hz), 21.3. 31P NMR (162 MHz,
CDCl3) δ 27.43. IR (KBr): 3509, 3451, 3396, 1747, 1649, 1487, 1438,
1261, 1188, 1120, 1083, 745, 721, 697, 550, 531, 517 cm−1. HR-ESI-
MS: calcd m/z [M + H]+ for [C24H25NO3P]+: 406.1572, found:
406.1574.
5-((Diphenylphosphoryl)methyl)-3-(4-methylbenzyl)oxazolidin-
2-one (3da). Pale yellow solid, mp: 160−161 °C, 73.0 mg, 72% yield,
1
Rf = 0.30 (petroleum ether/ethyl acetate 1:3). H NMR (400 MHz,
CDCl3) δ 7.75−7.62 (m, 4H), 7.55−7.40 (m, 6H), 7.09 (s, 4H),
4.75−4.62 (m, 1H), 4.37 (d, J = 14.7 Hz, 1H), 4.22 (d, J = 14.7 Hz,
1H), 3.57−3.49 (m, 1H), 3.36 (dd, J = 9.5, 6.9 Hz, 1H), 2.91 (ddd, J
= 14.5, 9.5, 3.6 Hz, 1H), 2.61 (td, J = 14.1, 10.3 Hz, 1H), 2.30 (s,
3H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.2, 137.7, 132.6 (d, J =
102.0 Hz), 132.4, 132.3 (dd, J = 8.9, 2.6 Hz), 131.7, 130.8 (d, J = 9.7
Hz), 130.3 (d, J = 9.8 Hz), 129.5, 128.9 (d, J = 23.2 Hz), 128.9
(overlapped), 128.3, 69.2, 50.0, 48.0, 35.6 (d, J = 68.1 Hz), 21.1. 31P
NMR (162 MHz, CDCl3) δ 27.56. IR (KBr): 3554, 3504, 3460, 3055,
2921, 1750, 1515, 1486, 1438, 1372, 1258, 1188, 1120, 1022, 801,
748, 721, 697, 534, 515, 474 cm−1. HR-ESI-MS: calcd m/z [M + H]+
for [C24H25NO3P]+: 406.1572, found: 406.1572.
3-(4-(tert-Butyl)benzyl)-5((diphenylphosphoryl)methyl)-
oxazolidin-2-one (3ea). White solid, mp: 157−158 °C, 82.7 mg, 74%
1
yield, Rf = 0.35 (petroleum ether/ethyl acetate 1:3). H NMR (400
MHz, CDCl3) δ 7.78−7.62 (m, 4H), 7.50 (ddd, J = 22.2, 14.7, 7.3 Hz,
6H), 7.33 (d, J = 7.6 Hz, 2H), 7.15 (d, J = 7.7 Hz, 2H), 4.76−4.65
(m, 1H), 4.41 (d, J = 14.7 Hz, 1H), 4.23 (d, J = 14.7 Hz, 1H), 3.57 (t,
J = 8.8 Hz, 1H), 3.44−3.35 (m, 1H), 2.93 (t, J = 11.0 Hz, 1H), 2.64
(dd, J = 24.6, 13.8 Hz, 1H), 1.30 (s, 9H). 13C{1H} NMR (101 MHz,
CDCl3) δ 157.3, 151.0, 132.8 (d, J = 103.0 Hz), 132.5, 132.4 (dd, J =
8.7, 1.6 Hz), 131.8, 130.9 (d, J = 9.5 Hz), 130.4 (d, J = 9.7 Hz), 129.0
(d, J = 23.2 Hz), 129.0 (overlapped), 128.1, 125.8, 69.2, 50.2, 48.0,
35.7 (d, J = 68.1 Hz), 34.6, 31.4. 31P NMR (162 MHz, CDCl3) δ
27.37. IR (KBr): 3665, 3057, 2962, 2869, 1752, 1439, 1368, 1263,
1190, 1121, 1019, 745, 723, 696, 533, 515 cm−1. HR-ESI-MS: calcd
m/z [M + H]+ for [C27H31NO3P]+: 448.2041, found: 448.2042.
5-((Diphenylphosphoryl)methyl)-3-(4-methoxybenzyl)-
oxazolidin-2-one (3fa). White solid, mp: 165−166 °C, 73.7 mg, 70%
4-((5-((Diphenylphosphoryl)methyl)-2-oxooxazolidin-3-yl)-
methyl)benzonitrile (3ja). White solid, mp: 221−223 °C, 69.7 mg,
1
67% yield, Rf = 0.30 (petroleum ether/ethyl acetate 1:3). H NMR
(400 MHz, CDCl3) δ 7.76−7.63 (m, 4H), 7.61 (d, J = 8.2 Hz, 2H),
7.59−7.42 (m, 6H), 7.34 (d, J = 8.2 Hz, 2H), 4.79−4.68 (m, 1H),
4.48 (d, J = 15.3 Hz, 1H), 4.33 (d, J = 15.4 Hz, 1H), 3.60 (t, J = 8.8
Hz, 1H), 3.47 (dd, J = 9.1, 7.3 Hz, 1H), 2.95 (ddd, J = 14.0, 9.3, 3.3
Hz, 1H), 2.65 (td, J = 14.1, 10.6 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 157.3, 141.1, 132.8, 132.6 (dd, J = 7.5, 2.4 Hz), 132.5 (d, J
= 103.02 Hz), 131.0 (d, J = 100.0 Hz), 130.8 (d, J = 9.7 Hz), 130.4
(d, J = 9.6 Hz), 129.1 (d, J = 24.24 Hz), 129.1 (overlapped), 128.9,
118.5, 112.1, 69.6, 50.4, 48.0, 35.6 (d, J = 67.8 Hz). 31P NMR (162
MHz, CDCl3) δ 27.44. IR (KBr): 3686, 3664, 3645, 3268, 3057,
2923, 2229, 1751, 1487, 1439, 1372, 1264, 1188, 1121, 1019, 815,
748, 722, 697, 533, 514 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for
[C24H22N2O3P]+: 417.1368, found: 417.1365.
1
yield, Rf = 0.30 (petroleum ether/ethyl acetate 1:3). H NMR (400
MHz, CDCl3) δ 7.66 (ddd, J = 26.4, 11.7, 7.4 Hz, 4H), 7.55−7.36 (m,
6H), 7.11 (d, J = 8.5 Hz, 2H), 6.80 (d, J = 8.5 Hz, 2H), 4.74−4.60
(m, 1H), 4.31 (d, J = 14.6 Hz, 1H), 4.19 (d, J = 14.7 Hz, 1H), 3.73 (s,
3H), 3.51 (t, J = 8.8 Hz, 1H), 3.33 (dd, J = 9.2, 7.0 Hz, 1H), 2.94−
2.83 (m, 1H), 2.66−2.51 (m, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 159.3, 157.2, 132.6 (d, J = 103.0 Hz), 132.3 (dd, J = 8.3, 2.3
Hz), 131.2 (d, J = 101.0 Hz), 130.7 (d, J = 9.4 Hz), 130.3 (d, J = 9.6
Hz), 129.6, 128.9 (d, J = 22.2 Hz), 128.9 (overlapped), 127.5, 114.2,
69.1, 55.3, 49.9, 47.6, 35.6 (d, J = 68.1 Hz). 31P NMR (162 MHz,
CDCl3) δ 27.54. IR (KBr): 3702, 3685, 3648, 3590, 3310, 3274, 3256,
2957, 2921, 2850, 1745, 1587, 1513, 1438, 1374, 1247, 1179, 1120,
5-((Diphenylphosphoryl)methyl)-3-(4-(trifluoromethyl)benzyl)-
oxazolidin-2-one (3ka). White solid, mp: 159−160 °C, 84.9 mg, 74%
1
yield, Rf = 0.30 (petroleum ether/ethyl acetate 1:3). H NMR (400
MHz, CDCl3) δ 7.76−7.62 (m, 4H), 7.60−7.40 (m, 8H), 7.34 (d, J =
F
https://dx.doi.org/10.1021/acs.joc.0c02172
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
8.0 Hz, 2H), 4.80−4.66 (m, 1H), 4.47 (d, J = 15.1 Hz, 1H), 4.34 (d, J
= 15.1 Hz, 1H), 3.58 (t, J = 8.8 Hz, 1H), 3.43 (dd, J = 9.3, 7.1 Hz,
1H), 3.00−2.88 (m, 1H), 2.65 (td, J = 14.0, 10.6 Hz, 1H). 13C{1H}
NMR (101 MHz, CDCl3) δ 157.3, 139.7 (m), 132.6 (d, J = 102.0
Hz), 132.5 (dd, J = 8.1, 2.8 Hz), 131.1 (d, J = 101.0 Hz), 130.8 (d, J =
9.7 Hz), 130.4 (d, J = 33.3 Hz), 130.3 (d, J = 9.7 Hz), 129.1 (d, J =
25.3 Hz), 129.1 (overlapped), 128.6, 125.9 (q, J = 3.8 Hz), 125.4,
122.7, 69.5, 50.2 (d, J = 1.8 Hz), 47.9, 35.6 (d, J = 67.8 Hz). 31P NMR
(162 MHz, CDCl3) δ 27.25. IR (KBr): 3652, 3631, 3613, 3588, 2917,
2850, 1746, 1326, 1264, 1118, 1065, 749, 695, 532, 511 cm−1. HR-
ESI-MS: calcd m/z [M + H]+ for [C24H22F3NO3P]+: 460.1289,
found: 460.1289.
Hz), 35.7 (d, J = 68.3 Hz). 31P NMR (162 MHz, CDCl3) δ 27.16. IR
(KBr): 3524, 3482, 3470, 3437, 3057, 1748, 1649, 1494, 1437, 1420,
1367, 1249, 1189, 1120, 1074, 745, 699, 576, 533, 514 cm−1. HR-ESI-
MS: calcd m/z [M + H]+ for [C29H27NO3P]+: 468.1728, found:
468.1724.
3-Butyl-5-((diphenylphosphoryl)methyl)oxazolidin-2-one (3oa).
Pale yellow oil, 67.9 mg, 76% yield, Rf = 0.35 (petroleum ether/ethyl
1
acetate 1:3). H NMR (400 MHz, CDCl3) δ 7.79−7.66 (m, 4H),
7.58−7.43 (m, 6H), 4.77−4.64 (m, 1H), 3.67 (t, J = 8.8 Hz, 1H),
3.51 (dd, J = 9.2, 6.9 Hz, 1H), 3.28−3.07 (m, 2H), 3.00−2.87 (m,
1H), 2.66 (td, J = 14.1, 10.5 Hz, 1H), 1.51−1.36 (m, 2H), 1.27 (dt, J
= 14.9, 7.3 Hz, 2H), 0.87 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 157.2, 132.7 (d, J = 102.1 Hz), 132.4 (dd, J = 5.7, 2.2
Hz), 131.7, 130.8 (d, J = 9.5 Hz), 130.4 (d, J = 9.6 Hz), 129.0 (d, J =
21.4 Hz), 129.0 (d, J = 2.0 Hz), 69.0, 50.5, 43.8, 35.6 (d, J = 68.0 Hz),
29.3, 19.8, 13.6. 31P NMR (162 MHz, CDCl3) δ 27.39. IR (KBr):
3714, 3679, 3660, 3057, 2930, 2872, 1747, 1488, 1438, 1263, 1187,
1121, 749, 722, 697, 533, 514 cm−1. HR-ESI-MS: calcd m/z [M +
H]+ for [C20H25NO3P]+: 358.1572, found: 358.1570.
3-(3,4-Dichlorobenzyl)-5-((diphenylphosphoryl)methyl)-
oxazolidin-2-one (3la). White solid, mp: 177−178 °C, 71.2 mg, 62%
1
yield, Rf = 0.35 (petroleum ether/ethyl acetate 1:3). H NMR (400
MHz, CDCl3) δ 7.68 (ddd, J = 26.1, 11.6, 7.7 Hz, 4H), 7.56−7.39 (m,
6H), 7.36 (d, J = 8.2 Hz, 1H), 7.30 (s, 1H), 7.05 (d, J = 8.1 Hz, 1H),
4.79−4.67 (m, 1H), 4.33 (d, J = 15.0 Hz, 1H), 4.22 (d, J = 15.1 Hz,
1H), 3.55 (t, J = 8.7 Hz, 1H), 3.44−3.34 (m, 1H), 2.99−2.87 (m,
1H), 2.63 (dd, J = 24.6, 13.8 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 157.1, 135.9, 132.6 (d, J = 70.7 Hz), 132.5 (d, J = 103.0
Hz), 132.4 (dd, J = 7.8, 2.3 Hz), 131.7, 130.8, 130.7 (d, J = 9.5 Hz),
130.3 (d, J = 9.8 Hz), 130.1, 129.0 (d, J = 24.2 Hz), 129.0
(overlapped), 127.6, 69.4, 50.0, 47.2, 35.5 (d, J = 67.7 Hz). 31P NMR
(162 MHz, CDCl3) δ 27.13. IR (KBr): 3679, 3653, 3057, 2911, 1751,
1472, 1438, 1400, 1259, 1190, 1120, 1030, 810, 749, 723, 695, 531,
515 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for [C23H21Cl2NO3P]+:
460.0636, found: 460.0636.
5-((Diphenylphosphoryl)methyl)-3-(1-phenylethyl)oxazolidin-2-
one (3ma-1). White solid, mp: 208−209 °C, 15.2 mg, 15% yield, Rf =
0.30 (petroleum ether/ethyl acetate 1:2). 1H NMR (400 MHz,
CDCl3) δ 7.78−7.68 (m, 4H), 7.52 (dd, J = 18.4, 6.3 Hz, 6H), 7.36−
7.24 (m, 5H), 5.16 (q, J = 7.1 Hz, 1H), 4.71−4.59 (m, 1H), 3.52 (dd,
J = 9.2, 6.7 Hz, 1H), 3.34 (t, J = 8.8 Hz, 1H), 2.94 (ddd, J = 12.8, 9.5,
3.2 Hz, 1H), 2.69 (td, J = 14.1, 10.7 Hz, 1H), 1.53 (d, J = 7.1 Hz,
3H). 13C{1H} NMR (101 MHz, CDCl3) δ 156.7, 139.4, 132.6 (d, J =
156.5 Hz), 132.4 (m), 130.9 (d, J = 9.4 Hz), 130.8, 130.4 (d, J = 9.8
Hz), 129.0 (d, J = 19.9 Hz), 129.0 (d, J = 3.9 Hz), 128.7, 127.9, 127.1,
69.3, 51.6, 46.3, 35.7 (d, J = 68.1 Hz), 16.4. 31P NMR (162 MHz,
CDCl3) δ 27.29. IR (KBr): 3491, 3454, 1744, 1649, 1489, 1436, 1365,
1255, 1186, 1121, 1076, 1024, 747, 722, 698, 559, 533, 515 cm−1.
HR-ESI-MS: calcd m/z [M + H]+ for [C24H25NO3P]+: 406.1572,
found: 406.1572.
3-Cyclohexyl-5-((diphenylphosphoryl)methyl)oxazolidin-2-one
(3pa). Pale yellow oil, 45.0 mg, 47% yield, Rf = 0.33 (petroleum
ether/ethyl acetate 1:3). 1H NMR (400 MHz, CDCl3) δ 7.72 (ddd, J
= 11.6, 11.1, 7.6 Hz, 4H), 7.58−7.43 (m, 6H), 4.76−4.57 (m, 1H),
3.70−3.54 (m, 2H), 3.49 (dd, J = 9.2, 6.9 Hz, 1H), 2.92 (ddd, J =
12.3, 9.1, 2.9 Hz, 1H), 2.65 (td, J = 14.0, 10.8 Hz, 1H), 1.83−1.65 (m,
4H), 1.60 (d, J = 12.2 Hz, 1H), 1.36−1.18 (m, 4H), 1.11−0.93 (m,
1H). 13C{1H} NMR (101 MHz, CDCl3) δ 156.5, 132.6 (d, J = 151.3
Hz), 132.4 (d, J = 6.6 Hz), 130.8 (d, J = 9.2 Hz), 130.3 (d, J = 9.5
Hz), 129.0 (d, J = 22.3 Hz), 129.0 (overlapped), 69.3, 52.5, 46.8, 35.5
(d, J = 68.0 Hz), 30.2 (d, J = 29.6 Hz), 25.3 (d, J = 4.6 Hz), 25.2. 31P
NMR (162 MHz, CDCl3) δ 27.66. IR (KBr): 3868, 3722, 3647, 3627,
3607, 3439, 3282, 2924, 2853, 1744, 1591, 1437, 1263, 1187, 1121,
996, 745, 723, 696, 535, 516 cm−1. HR-ESI-MS: calcd m/z [M + H]+
for [C22H27NO3P]+: 384.1728, found: 384.1729.
5-((Diphenylphosphoryl)methyl)-3-phenethyloxazolidin-2-one
(3qa). White solid, mp: 15−155 °C, 60.8 mg, 60% yield, Rf = 0.30
1
(petroleum ether/ethyl acetate 1:3). H NMR (400 MHz, CDCl3) δ
7.81−7.65 (m, 4H), 7.62−7.43 (m, 6H), 7.26 (dd, J = 9.2, 5.1 Hz,
2H), 7.19 (dd, J = 5.0, 2.6 Hz, 3H), 4.72−4.60 (m, 1H), 3.60 (t, J =
8.7 Hz, 1H), 3.48 (dd, J = 15.7, 8.4 Hz, 3H), 2.91−2.78 (m, 3H), 2.53
(td, J = 14.2, 10.5 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ
157.1, 138.1, 132.8 (d, J = 102.2 Hz), 132.4 (dd, J = 5.9, 2.6 Hz),
131.8, 130.8 (d, J = 9.5 Hz), 130.4 (d, J = 9.7 Hz), 129.1 (d, J = 22.4
Hz), 129.0, 128.7 (d, J = 7.8 Hz), 126.7, 69.1 (d, J = 1.5 Hz), 50.9 (d,
J = 1.4 Hz), 45.2, 35.5 (d, J = 68.0 Hz), 33.7. 31P NMR (162 MHz,
CDCl3) δ 27.14. IR (KBr): 3473, 3430, 3400, 3058, 3028, 2928, 2863,
1749, 1488, 1438, 1371, 1265, 1189, 1120, 1026, 998, 748, 722, 698,
522 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for [C24H25NO3P]+:
406.1572, found: 406.1569.
5-((Diphenylphosphoryl)methyl)-3-(prop-2-yn-1-yl)oxazolidin-2-
one (3ra). Yellow solid, mp: 145−146 °C, 39.8 mg, 47% yield, Rf =
0.40 (petroleum ether/ethyl acetate 1:3). 1H NMR (400 MHz,
CDCl3) δ 7.78−7.68 (m, 4H), 7.56−7.43 (m, 6H), 6.31 (dd, J = 9.4,
4.5 Hz, 1H), 4.80 (ddd, J = 18.0, 8.9, 6.1 Hz, 1H), 4.74 (dd, J = 5.5,
2.7 Hz, 1H), 4.47 (s, 2H), 4.33−4.28 (m, 1H), 3.23 (dd, J = 14.1, 8.6
Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 153.7, 148.5, 132.2 (d,
J = 2.3 Hz), 132.1 (d, J = 99.4 Hz), 130.9 (d, J = 9.4 Hz), 128.8 (d, J
= 11.8 Hz), 125.7 (d, J = 11.0 Hz), 104.1 (d, J = 9.3 Hz), 87.3, 48.9,
29.4 (d, J = 67.8 Hz). 31P NMR (162 MHz, CDCl3) δ 28.75. IR
(KBr): 3645, 3627, 3586, 1781, 1679, 1432, 1370, 1281, 1182, 1120,
1080, 997, 955, 857, 721, 697, 557, 509 cm−1. HR-ESI-MS: calcd m/z
[M + H]+ for [C19H19NO3P]+: 340.1103, found: 340.1102.
5-((Diphenylphosphoryl)methyl)-3-(1-phenylethyl)oxazolidin-2-
one (3ma-2). Yellow oil, 20.3 mg, 20% yield, Rf = 0.30 (petroleum
1
ether/ethyl acetate 1:3). H NMR (400 MHz, CDCl3) δ 7.78−7.70
(m, 2H), 7.57 (ddd, J = 26.3, 15.2, 7.3 Hz, 6H), 7.43 (dd, J = 10.3, 4.1
Hz, 2H), 7.32 (dt, J = 12.5, 6.1 Hz, 5H), 5.14 (q, J = 7.0 Hz, 1H),
4.82−4.71 (m, 1H), 3.65 (t, J = 8.6 Hz, 1H), 3.02 (t, J = 8.2 Hz, 1H),
2.88 (ddd, J = 13.4, 10.4, 2.7 Hz, 1H), 2.48 (dd, J = 24.2, 13.7 Hz,
1H), 1.52 (d, J = 7.1 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
156.7, 139.3, 132.5 (d, J = 101.9 Hz), 132.3 (dd, J = 13.5, 2.2 Hz),
131.8, 130.8 (d, J = 9.5 Hz), 130.3 (d, J = 9.6 Hz), 129.0 (d, J = 25.6
Hz), 128.9, 128.7, 127.9, 127.0, 69.4, 51.6, 46.5, 35.5 (d, J = 68.4 Hz),
16.7. 31P NMR (162 MHz, CDCl3) δ 27.63. IR (KBr): 3472, 3447,
3415, 1744, 1643, 1437, 1249, 1186, 1121, 749, 722, 698, 643, 533
cm−1. HR-ESI-MS: calcd m/z [M + H]+ for [C24H25NO3P]+:
406.1572, found: 406.1567.
3-Benzhydryl-5-((diphenylphosphoryl)methyl)oxazolidin-2-one
(3na). White solid, mp: 233−234 °C, 30.4 mg, 26% yield, Rf = 0.35
1
(petroleum ether/ethyl acetate 1:3). H NMR (400 MHz, CDCl3) δ
7.73 (dd, J = 11.6, 7.6 Hz, 2H), 7.65 (dd, J = 11.7, 7.6 Hz, 2H), 7.58−
7.40 (m, 6H), 7.31 (dd, J = 10.5, 5.2 Hz, 6H), 7.14 (d, J = 6.4 Hz,
4H), 6.29 (s, 1H), 4.92−4.77 (m, 1H), 3.53 (t, J = 8.8 Hz, 1H), 3.22
(t, J = 8.4 Hz, 1H), 2.97 (ddd, J = 13.8, 10.5, 3.3 Hz, 1H), 2.61 (dd, J
= 24.0, 13.6 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.2,
138.0 (d, J = 3.3 Hz), 132.7 (d, J = 101.7 Hz), 132.4 (dd, J = 11.6, 2.5
Hz), 131.4 (d, J = 100.6 Hz), 130.8 (d, J = 9.6 Hz), 130.5 (d, J = 9.7
Hz), 129.0 (d, J = 23.5 Hz), 129.0 (overlapped), 128.8 (d, J = 7.9
Hz), 128.6, 128.2, 127.9 (d, J = 11.4 Hz), 69.6, 60.8, 48.1 (d, J = 1.9
5-((Diphenylphosphoryl)methyl)-3-phenyloxazolidin-2-one
(3sa). Green solid, mp: 153−154 °C, 9.4 mg, 10% yield, Rf = 0.30
1
(petroleum ether/ethyl acetate 1:3). H NMR (400 MHz, CDCl3) δ
7.85−7.69 (m, 4H), 7.63−7.45 (m, 8H), 7.34 (dd, J = 10.8, 5.3 Hz,
2H), 7.11 (t, J = 7.4 Hz, 1H), 4.96−4.80 (m, 1H), 4.22−4.15 (m,
1H), 4.09 (dd, J = 9.6, 6.9 Hz, 1H), 3.02 (ddd, J = 14.5, 9.4, 3.4 Hz,
1H), 2.79 (td, J = 14.1, 10.5 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 154.1, 138.1, 132.7 (d, J = 102.5 Hz), 132.6 (dd, J = 6.7, 2.6
G
https://dx.doi.org/10.1021/acs.joc.0c02172
J. Org. Chem. XXXX, XXX, XXX−XXX

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Article
1
Hz), 131.2 (d, J = 100.4 Hz), 130.9 (d, J = 9.4 Hz), 130.5 (d, J = 9.8
Hz), 129.2 (d, J = 23.2 Hz), 129.1 (d, J = 5.2 Hz), 124.2, 118.4, 68.9
(d, J = 2.1 Hz), 51.3 (d, J = 1.2 Hz), 35.7 (d, J = 67.7 Hz). 31P NMR
(162 MHz, CDCl3) δ 27.26. IR (KBr): 3667, 3645, 3294, 3059, 2918,
1754, 1599, 1503, 1438, 1411, 1375, 1310, 1222, 1189, 1136, 999,
752, 694, 535, 510 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for
[C22H21NO3P]+: 378.1259, found: 378.1254.
(petroleum ether/ethyl acetate 1:3). H NMR (400 MHz, CDCl3) δ
7.57 (ddd, J = 26.9, 11.6, 8.0 Hz, 4H), 7.36−7.16 (m, 9H), 4.71 (p, J
= 10.5 Hz, 1H), 4.43 (d, J = 14.8 Hz, 1H), 4.28 (d, J = 14.8 Hz, 1H),
3.56 (t, J = 8.8 Hz, 1H), 3.39 (dd, J = 9.3, 7.0 Hz, 1H), 2.97−2.80 (m,
1H), 2.60 (td, J = 14.0, 10.6 Hz, 1H), 2.38 (d, J = 4.8 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 157.3, 142.8 (dd, J = 10.4, 2.5
Hz), 135.5, 130.8 (d, J = 9.9 Hz), 130.3 (d, J = 10.1 Hz), 129.6 (d, J =
25.3 Hz), 129.6 (overlapped), 129.5 (d, J = 104.8 Hz), 128.8, 128.2,
128.0 (d, J = 102.9 Hz), 127.9, 69.4 (d, J = 1.9 Hz), 50.1, 48.2, 35.8
(d, J = 68.1 Hz), 21.6. 31P NMR (162 MHz, CDCl3) δ 27.68. IR
(KBr): 3495, 3455, 1748, 1648, 1117, 1099, 807, 757, 703, 663, 525,
455 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for [C25H27NO3P]+:
420.1728, found: 420.1730.
5-(Diphenylphosphoryl)-5-methyl-3-phenyloxazolidin-2-one
(3sai). Pale yellow solid, mp: 194−195 °C, 7.5 mg, 8% yield, Rf = 0.40
1
(petroleum ether/ethyl acetate 1:3). H NMR (400 MHz, CDCl3) δ
8.29−8.16 (m, 2H), 8.01−7.90 (m, 2H), 7.69−7.53 (m, 3H), 7.51−
7.35 (m, 3H), 7.26 (ddd, J = 8.7, 6.7, 1.9 Hz, 2H), 7.16−7.04 (m,
3H), 4.43 (dd, J = 14.3, 10.0 Hz, 1H), 3.90 (dd, J = 15.3, 10.0 Hz,
1H), 1.79 (d, J = 12.0 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
153.3 (d, J = 1.7 Hz), 137.2, 132.9 (dd, J = 4.5, 2.9 Hz), 132.0 (d, J =
16.6 Hz), 131.9, 129.0 (d, J = 22.0 Hz), 129.0 (overlapped), 128.5 (d,
J = 41.7 Hz), 127.6 (d, J = 39.1 Hz), 124.8, 118.8, 53.0 (d, J = 4.1
Hz), 22.1 (d, J = 7.8 Hz). 31P NMR (162 MHz, CDCl3) δ 28.29. IR
(KBr): 3511, 3477, 3449, 3391, 1765, 1649, 1602, 1502, 1405, 1313,
1245, 1186, 1092, 749, 695, 586, 533, 515 cm−1. HR-ESI-MS: calcd
m/z [M + H]+ for [C22H21NO3P]+: 378.1259, found: 378.1255.
5-((Diphenylphosphoryl)methyl)-4,4-dimethyl-3-phenyloxazoli-
din-2-one (3ta). White solid, mp: 170−171 °C, 85.9 mg, 82% yield,
3-Benzyl-5-((bis(3,5-di-tert-butylphenyl)phosphoryl)methyl)-
oxazolidin-2-one (3ad). White solid, mp: 181−182 °C, 107.7 mg,
1
70% yield, Rf = 0.40 (petroleum ether/ethyl acetate 1:2). H NMR
(400 MHz, CDCl3) δ 7.62−7.49 (m, 6H), 7.30 (tdd, J = 6.6, 4.4, 2.1
Hz, 3H), 7.25−7.20 (m, 2H), 4.78−4.66 (m, 1H), 4.50 (d, J = 14.8
Hz, 1H), 4.24 (d, J = 14.8 Hz, 1H), 3.56−3.47 (m, 1H), 3.38 (dd, J =
9.4, 7.1 Hz, 1H), 2.94 (ddd, J = 13.5, 10.1, 3.2 Hz, 1H), 2.70−2.56
(m, 1H), 1.31 (d, J = 7.7 Hz, 36H). 13C{1H} NMR (101 MHz,
CDCl3) δ 157.4, 151.5 (d, J = 23.7 Hz), 151.5 (overlapped), 135.6,
131.8 (d, J = 101.2 Hz), 130.4 (d, J = 99.7 Hz), 128.8, 128.3, 128.0,
126.5 (dd, J = 10.3, 2.4 Hz), 124.9 (d, J = 10.2 Hz), 124.6 (d, J = 10.3
Hz), 69.7 (d, J = 2.3 Hz), 50.2, 48.3, 36.6 (d, J = 66.8 Hz), 35.1, 31.3
(d, J = 2.5 Hz). 31P NMR (162 MHz, CDCl3) δ 28.89. IR (KBr):
3496, 3450, 2962, 2905, 2870, 1752, 1648, 1425, 1364, 1250, 1186,
1148, 1095, 788, 736, 704, 663, 531, 497, 450 cm−1. HR-ESI-MS:
calcd m/z [M + H]+ for [C39H55NO3P]+: 616.3919, found: 616.3913.
3-Benzyl-5-((bis(4-(tert-butyl)phenyl)phosphoryl)methyl)-
oxazolidin-2-one (3ae). White solid, mp: 183−184 °C, 78.0 mg, 62%
1
Rf = 0.35 (petroleum ether/ethyl acetate 1:3). H NMR (400 MHz,
CDCl3) δ 7.88−7.70 (m, 4H), 7.56−7.43 (m, 6H), 7.32−7.19 (m,
5H), 4.52−4.40 (m, 2H), 4.20 (d, J = 15.7 Hz, 1H), 2.79 (dt, J = 15.0,
7.4 Hz, 1H), 2.54 (td, J = 15.7, 5.9 Hz, 1H), 1.17 (d, J = 15.1 Hz,
6H). 13C{1H} NMR (101 MHz, CDCl3) δ 156.9, 138.1, 133.2 (d, J =
102.3 Hz), 132.1 (dd, J = 9.0, 2.5 Hz), 131.1 (d, J = 100.7 Hz), 131.0
(d, J = 9.6 Hz), 130.4 (d, J = 9.4 Hz), 128.8 (d, J = 4.2 Hz), 128.7 (d,
J = 4.1 Hz), 128.5, 127.6, 127.4, 78.5, 61.9 (d, J = 6.7 Hz), 44.2, 30.8
(d, J = 70.0 Hz), 24.6, 20.2. 31P NMR (162 MHz, CDCl3) δ 27.95. IR
(KBr): 3580, 3515, 3445, 3379, 3058, 2972, 2914, 1743, 1651, 1631,
1437, 1403, 1371, 1183, 1119, 1092, 995, 748, 722, 697, 572, 539,
528 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for [C25H27NO3P]+:
420.1728, found: 420.1727.
1
yield, Rf = 0.40 (petroleum ether/ethyl acetate 1:3). H NMR (400
MHz, CDCl3) δ 7.61 (ddd, J = 26.0, 11.5, 8.4 Hz, 4H), 7.47 (ddd, J =
14.9, 8.4, 2.5 Hz, 4H), 7.34−7.26 (m, 3H), 7.24−7.18 (m, 2H),
4.76−4.62 (m, 1H), 4.44 (d, J = 14.8 Hz, 1H), 4.26 (d, J = 14.8 Hz,
1H), 3.55 (t, J = 8.9 Hz, 1H), 3.40 (dd, J = 9.5, 7.0 Hz, 1H), 2.89
(ddd, J = 14.4, 9.7, 3.2 Hz, 1H), 2.60 (td, J = 14.0, 10.9 Hz, 1H), 1.30
(dd, J = 5.1, 3.0 Hz, 18H). 13C{1H} NMR (101 MHz, CDCl3) δ
157.4, 155.9 (dd, J = 5.7, 2.7 Hz), 135.6, 130.7 (d, J = 9.8 Hz), 130.3
(d, J = 10.1 Hz), 129.6 (d, J = 104.6 Hz), 128.9, 128.4, 128.1, 128.0
(d, J = 102.5 Hz), 126.0 (d, J = 26.3 Hz), 126.0 (overlapped), 69.5 (d,
J = 2.4 Hz), 50.2, 48.4, 35.9 (d, J = 67.9 Hz), 35.1 (d, J = 2.3 Hz),
31.1. 31P NMR (162 MHz, CDCl3) δ 27.23. IR (KBr): 3645, 3615,
3579, 2961, 2927, 2869, 1752, 1599, 1495, 1443, 1394, 1265, 1188,
1093, 1016, 830, 755, 702, 664, 609, 566, 508 cm−1. HR-ESI-MS:
calcd m/z [M + H]+ for [C31H39NO3P]+: 504.2667, found: 504.2670.
3-Benzyl-5-((bis(4-methoxyphenyl)phosphoryl)methyl)-
oxazolidin-2-one (3af). Pale yellow oil, 47.4 mg, 42% yield, Rf = 0.30
3-Benzyl-5-(1-(diphenylphosphoryl)ethyl)oxazolidin-2-one
(3ua). White solid, mp: 164−165 °C, 12.2 mg, 12% yield, Rf = 0.3
1
(dichloromethane/methanol 40:1). H NMR (400 MHz, CDCl3) δ
7.78−7.69 (m, 4H), 7.57−7.41 (m, 6H), 7.37−7.26 (m, 3H), 7.16
(dd, J = 7.2, 2.0 Hz, 2H), 4.69 (p, J = 7.9 Hz, 1H), 4.29 (q, J = 14.7
Hz, 2H), 3.34 (t, J = 8.9 Hz, 1H), 3.21 (dd, J = 9.2, 8.0 Hz, 1H), 2.75
(dp, J = 11.2, 7.2 Hz, 1H), 1.21 (dd, J = 16.5, 7.2 Hz, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ 157.3, 135.6, 132.4−132.3 (m), 131.6 (d,
J = 8.8 Hz), 131.4, 131.0 (d, J = 9.0 Hz), 130.4 (d, J = 97.9 Hz), 128.9
(d, J = 23.9 Hz), 128.9 (overlapped), 128.4, 128.1, 73.7 (d, J = 2.2
Hz), 48.9 (d, J = 3.3 Hz), 48.3, 38.7 (d, J = 68.5 Hz), 11.2 (d, J = 1.6
Hz). 31P NMR (162 MHz, CDCl3) δ 33.08. IR (KBr): 3548, 3502,
3401, 3338, 2957, 2933, 2890, 2856, 1745, 1613, 1545, 1437, 1265,
1200, 1120, 1022, 800, 744, 527. HR-ESI-MS: calcd m/z [M + Na]+
for [C24H24NO3PNa]+: 428.1392, found: 428.1390.
3-Benzyl-5-((di-o-tolylphosphoryl)methyl)oxazolidin-2-one
(3ab). Pale yellow oil, 43.0 mg, 41% yield, Rf = 0.30 (petroleum
ether/ethyl acetate 1:3). 1H NMR (400 MHz, CDCl3) δ 7.77 (dd, J =
12.7, 7.5 Hz, 1H), 7.59 (dd, J = 13.0, 7.6 Hz, 1H), 7.42 (dt, J = 8.8,
7.6 Hz, 2H), 7.35−7.26 (m, 5H), 7.25−7.15 (m, 4H), 4.82−4.69 (m,
1H), 4.41 (d, J = 14.7 Hz, 1H), 4.31 (d, J = 14.7 Hz, 1H), 3.62−3.54
(m, 1H), 3.40 (dd, J = 9.6, 6.8 Hz, 1H), 3.02 (ddd, J = 14.2, 9.5, 2.9
Hz, 1H), 2.73 (td, J = 13.9, 10.9 Hz, 1H), 2.23 (d, J = 4.9 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 157.4, 141.5 (dd, J = 15.7, 9.0
1
(petroleum ether/ethyl acetate 1:4). H NMR (400 MHz, CDCl3) δ
7.58 (dt, J = 25.6, 8.8 Hz, 4H), 7.38−7.27 (m, 3H), 7.25−7.18 (m,
2H), 6.96 (dd, J = 17.7, 8.1 Hz, 4H), 4.79−4.64 (m, 1H), 4.43 (d, J =
14.8 Hz, 1H), 4.28 (d, J = 14.8 Hz, 1H), 3.83 (d, J = 3.4 Hz, 6H),
3.55 (t, J = 8.1 Hz, 1H), 3.45−3.30 (m, 1H), 2.84 (dd, J = 10.9, 7.6
Hz, 1H), 2.57 (dd, J = 23.0, 12.7 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 162.8 (dd, J = 9.7, 1.7 Hz), 157.4, 135.6, 132.8 (d, J = 10.9
Hz), 132.3 (d, J = 11.0 Hz), 128.9, 128.4, 128.1, 124.0 (d, J = 109.0
Hz), 122.4 (d, J = 106.8 Hz), 114.6 (d, J = 27.3 Hz), 114.6
(overlapped), 69.5, 55.5, 50.3, 48.4, 36.2 (d, J = 69.0 Hz). 31P NMR
(162 MHz, CDCl3) δ 27.86. IR (KBr): 3720, 3686, 3645, 3280, 3150,
3088, 2962, 2937, 1746, 1597, 1503, 1258, 1180, 1121, 1024, 830,
703, 547, 469 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for
[C25H27NO5P]+: 452.1627, found: 452.1621.
Hz), 135.7, 132.5 (dd, J = 7.4, 2.5 Hz), 132.4, 132.2 (d, J = 10.7 Hz),
131.3 (d, J = 10.9 Hz), 131.2 (d, J = 99.7 Hz), 129.9 (d, J = 97.1 Hz),
128.9, 128.4, 128.1, 126.2 (d, J = 11.9 Hz), 126.0 (d, J = 12.2 Hz),
69.7 (d, J = 2.5 Hz), 50.5, 48.4, 34.8 (d, J = 68.6 Hz), 21.2 (dd, J =
24.0, 4.4 Hz). 31P NMR (162 MHz, CDCl3) δ 29.26. IR (KBr): 3550,
3505, 3459, 3444, 3059, 2924, 1752, 1647, 1445, 1263, 1183, 1138,
1086, 805, 752, 701, 526, 474 cm−1. HR-ESI-MS: calcd m/z [M +
H]+ for [C25H27NO3P]+: 420.1728, found: 420.1730.
3-Bbenzyl-5-((di([1,1′-biphenyl]-4-yl)phosphoryl)methyl)-
oxazolidin-2-one (3ag). White solid, mp: 132−133 °C, 81.5 mg, 60%
1
yield, Rf = 0.35 (petroleum ether/ethyl acetate 1:3). H NMR (400
MHz, CDCl3) δ 7.89−7.66 (m, 8H), 7.62−7.54 (m, 4H), 7.42 (dt, J =
26.4, 7.3 Hz, 6H), 7.28 (dt, J = 17.0, 6.7 Hz, 5H), 4.89−4.70 (m, 1H),
4.45 (d, J = 14.7 Hz, 1H), 4.30 (d, J = 14.8 Hz, 1H), 3.61 (t, J = 8.5
Hz, 1H), 3.44 (t, J = 7.7 Hz, 1H), 3.07−2.92 (m, 1H), 2.70 (dd, J =
24.3, 13.4 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.4, 145.3
3-Benzyl-5-((di-p-tolylphosphoryl)methyl)oxazolidin-2-one
(3ac). White solid, mp: 178−180 °C, 60.8 mg, 58% yield, Rf = 0.33
H
https://dx.doi.org/10.1021/acs.joc.0c02172
J. Org. Chem. XXXX, XXX, XXX−XXX

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Article
(dd, J = 11.8, 2.6 Hz), 139.6, 135.6, 131.4 (d, J = 9.9 Hz), 131.2 (d, J
= 103.6 Hz), 131.0 (d, J = 10.1 Hz), 130.2, 129.1, 128.9, 128.4, 128.1,
127.8 (d, J = 12.5 Hz), 127.7 (d, J = 12.5 Hz), 127.3 (d, J = 3.1 Hz),
69.3 (d, J = 1.8 Hz), 50.2 (d, J = 1.7 Hz), 48.4, 35.9 (d, J = 68.3 Hz).
31P NMR (162 MHz, CDCl3) δ 27.47. IR (KBr): 3898, 3850, 3815,
3765, 3731, 3686, 3645, 3608, 3563, 2959, 2923, 2354, 1748, 1597,
1482, 1391, 1264, 1156, 1126, 1005, 885, 826, 759, 697, 632, 583,
536, 505, 475, 445, 428 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for
[C35H31NO3P]+: 544.2041, found: 544.2042.
5.6 Hz), 128.5 (d, J = 102.2 Hz), 128.3, 128.0 (d, J = 2.7 Hz), 127.8,
127.3 (d, J = 4.3 Hz), 125.2 (d, J = 10.9 Hz), 125.0 (d, J = 10.8 Hz),
69.4 (d, J = 1.6 Hz), 50.2 (d, J = 1.2 Hz), 48.3, 35.6 (d, J = 68.1 Hz).
31P NMR (162 MHz, CDCl3) δ 27.52. IR (KBr, cm−1): 3666, 3645,
3626, 3311, 3056, 2914, 1751, 1496, 1441, 1343, 1265, 1186, 1091,
1018, 861, 819, 749, 702, 662, 525, 478 cm−1. HR-ESI-MS: calcd m/z
[M + H]+ for [C31H27NO3P]+: 492.1728, found: 492.1724.
Gram-Scale Synthesis of 3aa. An oven-dried Schlenk flask (100
mL) equipped with a magnetic stir bar was charged successively with
copper acetate (218.4 mg, 20 mol % relative to 1a), propargylic amine
1a (940 μL, 6 mmol), diarylphosphine oxide (15 mmol, 3.03 g),
DABCO (12 mmol, 1.35 g) and DMF (36 mL). The reaction mixture
is frozen with liquid nitrogen, then degassed, exposed to a CO2
atmosphere (balloon), and warmed up to room temperature. The
flask was heated to 60 °C for 24 h. After the reaction, DMF was
distilled under reduced pressure. Then, 20 mL of dichloromethane
was added to the flask, and the mixture was filtered through a Celite
pale to remove the precipitates. The reaction mixture was
concentrated and purified by silica gel column chromatography
(petroleum ether/ethyl acetate 1:3) to afford the desired product 3aa
as a white solid (1.35 g, 58% yield).
3-Benzyl-5-((bis(4-fluorophenyl)phosphoryl)methyl)oxazolidin-
2-one (3ah). Colorless oil, 48.1 mg, 45% yield, Rf = 0.30 (petroleum
ether/ethyl acetate 1:4). 1H NMR (400 MHz, CDCl3) δ 7.69 (dd, J =
15.8, 12.3 Hz, 4H), 7.34−7.27 (m, 3H), 7.25−7.08 (m, 6H), 4.72 (s,
1H), 4.41 (d, J = 14.6 Hz, 1H), 4.29 (d, J = 14.7 Hz, 1H), 3.56 (s,
1H), 3.35 (s, 1H), 2.89 (s, 1H), 2.75−2.46 (m, 1H). 13C{1H} NMR
(101 MHz, CDCl3) δ 166.6 (dd, J = 10.4, 2.2 Hz), 164.1 (dd, J =
10.2, 2.2 Hz), 157.2, 135.5, 133.4 (d, J = 19.2 Hz), 133.4
(overlapped), 133.0 (dd, J = 10.5, 9.3 Hz), 128.9, 128.6 (dd, J =
105.1, 3.1 Hz), 128.3, 128.1, 127.1 (dd, J = 103.5, 2.3 Hz), 116.7 (d, J
= 21.2 Hz), 116.7 (overlapped), 116.5, 116.4 (d, J = 21.2 Hz), 69.0,
50.2, 48.4, 36.0 (d, J = 69.2 Hz). 31P NMR (162 MHz, CDCl3) δ
26.37. IR (KBr): 3493, 3470, 3450, 3066, 2918, 1748, 1592, 1500,
1443, 1398, 1235, 1188, 1163, 1118, 1096, 1014, 831, 759, 702, 665,
532, 460 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for
[C23H21F2NO3P]+: 428.1227, found: 428.1213.
3-Benzyl-5-((bis(4-bromophenyl)phosphoryl)methyl)oxazolidin-
2-one (3ai). White solid, mp: 189−190 °C, 53.4 mg, 39% yield, Rf =
0.30 (petroleum ether/ethyl acetate 1:4). 1H NMR (400 MHz,
CDCl3) δ 7.68−7.44 (m, 8H), 7.38−7.26 (m, 3H), 7.23 (t, J = 8.2
Hz, 2H), 4.81−4.63 (m, 1H), 4.41 (d, J = 14.8 Hz, 1H), 4.30 (d, J =
14.8 Hz, 1H), 3.55 (t, J = 8.8 Hz, 1H), 3.41−3.25 (m, 1H), 2.93−2.81
(m, 1H), 2.59 (m, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.1,
135.5, 132.6 (d, J = 11.6 Hz), 132.3 (d, J = 10.5 Hz), 131.9 (d, J =
10.5 Hz), 130.8, 130.0 (d, J = 101.4 Hz), 129.0, 128.4, 128.2, 128.0
(dd, J = 14.9, 3.3 Hz), 68.9, 50.1 (d, J = 3.0 Hz), 48.4, 35.6 (d, J =
69.1 Hz). 31P NMR (162 MHz, CDCl3) δ 26.66. IR (KBr): 3561,
3541, 3523, 3495, 3449, 3419, 3083, 3062, 3029, 2923, 2856, 1749,
1576, 1480, 1441, 1385, 1259, 1189, 1086, 1068, 1009, 816, 741, 702,
560, 524 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for
[C23H21Br2NO3P]+: 547.9626, found: 547.9609.
3-Benzyl-5-((di(naphthalen-1-yl)phosphoryl)methyl)oxazolidin-
2-one (3aj). White solid, mp: 210−211 °C, 56.5 mg, 46% yield, Rf =
0.30 (petroleum ether/ethyl acetate 1:4). 1H NMR (400 MHz,
CDCl3) δ 8.52 (dd, J = 18.2, 8.5 Hz, 2H), 8.09−7.97 (m, 3H), 7.93−
7.86 (m, 2H), 7.82 (dd, J = 15.5, 6.9 Hz, 1H), 7.59−7.39 (m, 6H),
7.35−7.27 (m, 3H), 7.24−7.17 (m, 2H), 4.93−4.79 (m, 1H), 4.41 (d,
J = 14.8 Hz, 1H), 4.29 (d, J = 14.8 Hz, 1H), 3.59 (t, J = 8.9 Hz, 1H),
3.45 (dd, J = 9.4, 6.9 Hz, 1H), 3.27 (ddd, J = 13.2, 9.9, 3.0 Hz, 1H),
3.10−2.95 (m, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.3,
135.6, 134.1 (d, J = 9.8 Hz), 133.9 (dd, J = 13.0, 2.1 Hz), 133.3 (d, J =
8.7 Hz), 133.0 (d, J = 8.7 Hz), 132.4 (d, J = 10.0 Hz), 131.8 (d, J =
10.7 Hz), 129.4 (d, J = 6.2 Hz), 129.2 (d, J = 99.4 Hz), 128.9, 128.3,
128.1, 127.8, 127.4, 126.8 (d, J = 1.5 Hz), 126.1 (d, J = 13.1 Hz),
126.0 (d, J = 1.3 Hz), 124.8 (d, J = 25.3 Hz), 124.7 (d, J = 1.5 Hz),
69.9 (d, J = 2.0 Hz), 50.5, 48.4, 36.3 (d, J = 69.4 Hz). 31P NMR (162
MHz, CDCl3) δ 31.98. IR (KBr, cm−1): 3645, 3604, 3554, 3486,
3455, 3058, 2919, 1753, 1505, 1432, 1261, 1182, 1026, 988, 803, 776,
702, 555, 484 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for
[C31H27NO3P]+: 492.1728, found: 492.1718.
3-Benzyl-5-((di(naphthalen-2-yl)phosphoryl)methyl)oxazolidin-
2-one (3ak). White solid, mp: 188−189 °C, 49.1 mg, 40% yield, Rf =
0.30 (petroleum ether/ethyl acetate 1:4). 1H NMR (400 MHz,
CDCl3) δ 8.44 (d, J = 13.7 Hz, 1H), 8.33 (d, J = 13.8 Hz, 1H), 7.89
(ddd, J = 21.9, 10.8, 5.5 Hz, 6H), 7.72−7.51 (m, 6H), 7.31−7.24 (m,
3H), 7.23−7.12 (m, 2H), 4.87−4.74 (m, 1H), 4.42 (d, J = 14.8 Hz,
1H), 4.28 (d, J = 14.8 Hz, 1H), 3.60 (t, J = 8.8 Hz, 1H), 3.45 (dd, J =
9.4, 7.0 Hz, 1H), 3.21−3.08 (m, 1H), 2.81 (td, J = 14.1, 10.6 Hz, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ 157.3, 135.5, 134.9 (dd, J = 6.8,
Synthesis of (E)-(3-(Benzylamino)prop-1-en-1-yl)-
diphenylphosphine Oxide. A 25 mL Schlenk tube equipped
with a magnetic stir bar was charged with 3aa (156.6 mg, 0.4 mmol),
potassium tert-butoxide (0.44 mmol, 1.1 equiv), and THF (4 mL)
under an Ar atmosphere. Afterward, the solution was stirred at room
temperature for 12 h. Then, 4 mL of water was added into the
solution and the mixture was extracted with ethyl acetate (3 × 10
mL). The combined organic extracts were concentrated in vacuo, and
the residue was purified by column chromatography on silica gel
(dichloromethane/methanol 30:1) to give compound 4 as a pale
1
yellow solid (111.0 mg, 80% yield). mp: 82−83 °C. H NMR (400
MHz, CDCl3) δ 7.74−7.66 (m, 4H), 7.55−7.49 (m, 2H), 7.48−7.42
(m, 4H), 7.35−7.28 (m, 4H), 7.27−7.22 (m, 1H), 6.80 (ddt, J = 19.6,
17.1, 4.7 Hz, 1H), 6.52 (ddt, J = 23.9, 17.0, 1.8 Hz, 1H), 3.81 (s, 2H),
3.54−3.46 (m, 2H), 1.77 (s, 1H). 13C{1H} NMR (101 MHz, CDCl3)
δ 150.15 (d, J = 2.6 Hz), 139.75, 133.03 (d, J = 105.0 Hz), 131.87 (d,
J = 2.6 Hz), 131.46, 131.36, 128.70, 128.59, 128.25, 127.28, 122.26
(d, J = 103.0 Hz), 53.46, 51.29 (d, J = 17.1 Hz). 31P NMR (162 MHz,
CDCl3) δ 23.72. IR (KBr, cm−1): 3707, 3687, 3669, 3056, 3027,
2924, 1590, 1490, 1437, 1184, 1120, 1071, 998, 813, 744, 720, 697,
529 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for [C22H23NOP]+:
348.1517, found: 348.1516.
S y n t h e s i s o f 1 - ( B e n z y l ( m e t h y l ) a m i n o ) - 3 -
(diphenylphosphanyl)propan-2-ol. To a 25 mL Schlenk tube
charged with 3aa (156.6 mg, 0.4 mmol) was added 1.6 mL of LiAlH4
(1.6 mmol, 4.0 equiv, 1 M in THF) under an Ar atmosphere.
Following, 2.4 mL of anhydrous THF was added into the Schlenk
tube. After the Schlenk tube was sealed, the resulting mixture was
refluxed for 2 h. The reaction was quenched by aqueous solution of
NaOH (2 M, 4 mL), and the mixture was filtered through a Celite
pale. The combined organic phase was dried over anhydrous Na2SO4
and concentrated in vacuo, and the residue was purified by column
chromatography on silica gel (petroleum ether/ethyl acetate 4:1) to
give compound 5 as a colorless oil (109.2 mg, 75% yield). Colorless
1
oil. H NMR (400 MHz, CDCl3) δ 7.47 (dd, J = 29.3, 6.7 Hz, 4H),
7.35−7.19 (m, 11H), 3.86−3.75 (m, 1H), 3.61 (d, J = 13.1 Hz, 1H),
3.43 (d, J = 13.1 Hz, 1H), 2.54−2.43 (m, 2H), 2.37 (dd, J = 13.7, 6.6
Hz, 1H), 2.22−2.10 (m, 4H). 13C{1H} NMR (101 MHz, CDCl3) δ
138.76 (dd, J = 12.2, 4.5 Hz), 138.20, 132.88 (d, J = 35.4 Hz), 132.87
(d, J = 2.2 Hz), 128.79 (d, J = 69.7 Hz), 128.72 (d, J = 9.1 Hz),
128.58 (d, J = 3.3 Hz), 128.51 (d, J = 3.2 Hz), 127.36, 65.36 (d, J =
16.9 Hz), 64.17 (d, J = 9.7 Hz), 62.45, 42.11, 34.51 (d, J = 13.7 Hz).
31P NMR (162 MHz, CDCl3) δ −23.46. IR (KBr, cm−1): 3700, 3685,
2955, 2924, 2852, 1582, 1491, 1461, 1437, 1377, 1083, 1023, 740,
697 cm−1. HR-ESI-MS: calcd m/z [M + H]+ for [C23H27NOP]+:
364.1830, found: 364.1831.
Radical Trapping Experiment. A 10 mL Schlenk flask equipped
with a magnetic stir bar was charged successively with propargylic
amine 1a (39 μL, 0.25 mmol), diphenylphosphine oxide (151.7 mg,
2.2 Hz), 133.2 (d, J = 8.5 Hz), 132.7 (d, J = 10.2 Hz), 132.6, 132.5 (d,
J = 8.9 Hz), 129.8 (d, J = 102.6 Hz), 129.2, 129.0, 128.9, 128.6 (d, J =
I
https://dx.doi.org/10.1021/acs.joc.0c02172
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
0.75 mmol), copper acetate (9.1 mg, 0.05 mol), DABCO (56.1 mg,
0.5 mmol), TEMPO (3 or 5 equiv), and DMF (2 mL). The reaction
mixture is frozen with liquid nitrogen, then degassed, exposed to a
CO2 atmosphere (balloon), and warmed up to room temperature.
The flask was heated to 60 °C for 24 h. After the reaction, DMF was
distilled under reduced pressure, 5 mL of dichloromethane was added
into the flask, and the reaction mixture was concentrated and purified
by silica gel column chromatography (petroleum ether/ethyl acetate
10:1 for 6, petroleum ether/ethyl acetate 2:1 for 7, then petroleum
ether/ethyl acetate 1:3 for 3aa).
Accession Codes
CCDC 2014014 and 2017083 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
3-Benzyl-5-methyleneoxazolidin-2-one (6). White solid, mp: 42−
Corresponding Author
43 °C, 26.9 mg, 57% yield (3 equiv of TEMPO was used); 29.8 mg,
1
Liang-Nian He − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China; orcid.org/0000-0002-
6067-5937; Email: heln@nankai.edu.cn
63% yield (5 equiv of TEMPO was used). H NMR (400 MHz,
CDCl3) δ 7.40−7.31 (m, 3H), 7.31−7.23 (m, 2H), 4.73 (dd, J = 5.5,
2.7 Hz, 1H), 4.46 (s, 2H), 4.23 (dd, J = 5.0, 2.3 Hz, 1H), 4.02 (t, J =
2.3 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 155.7, 149.1,
135.1, 129.0, 128.3, 128.2, 86.8, 47.9, 47.3. HR-ESI-MS: calcd m/z
[M+Na]+ for [C11H11NO2Na]+: 212.0688, found: 212.0685.
Diphenyl(2,2,6,6-tetramethylpiperidin-1-yl)phosphine oxide (7)
Pale yellow solid, mp: 85−86 °C, 75.1 mg, 29% yield (yield was
relative to diphenylphosphine oxide, 3 equiv of TEMPO was used);
Authors
Wen-Bin Huang − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
Fang-Yu Ren − State Key Laboratory and Institute of Elemento-
Organic Chemistry, College of Chemistry, Nankai University,
Tianjin 300071, China
Ming-Wei Wang − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
Li-Qi Qiu − State Key Laboratory and Institute of Elemento-
Organic Chemistry, College of Chemistry, Nankai University,
Tianjin 300071, China
1
81.9 mg, 32% yield (5 equiv of TEMPO was used). H NMR (400
MHz, CDCl3) δ 7.76−7.66 (m, 4H), 7.49−7.36 (m, 6H), 1.73−1.66
(m, 2H), 1.65−1.57 (m, 4H), 1.35 (s, 12H). 13C{1H} NMR (101
MHz, CDCl3) δ 139.5, 138.2, 133.1 (d, J = 10.0 Hz), 131.9 (d, J = 9.3
Hz), 131.0 (d, J = 2.8 Hz), 128.5 (d, J = 12.6 Hz), 127.8 (d, J = 12.8
Hz), 56.7 (d, J = 1.0 Hz), 43.8 (d, J = 6.3 Hz), 32.6, 17.3. 31P NMR
(162 MHz, CDCl3) δ 32.56. HR-ESI-MS: calcd m/z [M + H]+ for
[C21H29NOP]+: 342.1987, found: 342.1985.
Deuterium Experiments. A 10 mL Schlenk flask equipped with a
magnetic stir bar was charged successively with propargylic amine 1a
(39 μL, 0.25 mmol), diphenylphosphine oxide (151.7 mg, 0.75
mmol), copper acetate (9.1 mg, 0.05 mol), DABCO (56.1 mg, 0.5
mmol), D2O (4 or 12 equiv), and DMF (2 mL). The reaction mixture
is frozen with liquid nitrogen, then degassed, exposed to a CO2
atmosphere (balloon), and warmed up to room temperature. The
flask was heated to 60 °C for 24 h. After the reaction, DMF was
distilled under reduced pressure, 5 mL of DCM was added into the
flask, and the reaction mixture was concentrated and purified by silica
Kai-Hong Chen − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02172
1
Notes
gel column chromatography (petroleum ether/ethyl acetate 1:3). H
NMR spectra were used for deuterium analysis.
The authors declare no competing financial interest.
General Procedure for the Electron Paramagnetic Reso-
nance (EPR) Experiment. A mixture of 1a (39 μL, 0.25 mmol), 2a
(151.7 mg, 0.75 mmol), Cu(OAc)2 (9.1 mg, 0.05 mmol), DABCO
(56.1 mg, 0.5 mmol), and MNP (65.4 mg, 0.375 mmol) in DMF (2
mL) was stirred under a CO2 atmosphere at 60 °C for 1 h. Then, this
reaction solution was taken out by capillary (ordinary glass, 0.5 × 100
mm) and was analyzed by EPR at room temperature.
X-ray Crystallography. Recrystallization of the product 3ga and
3ad from CDCl3 afforded crystals suitable for X-ray diffraction
analysis. The intensities were collected on a Bruker SMART APEX
CCD diffractometer equipped with a graphite monochromated Mo
Kα (λ = 0.71073) radiation source. The data were obtained using
SAINT and SMART programs. The structures were identified by
direct methods and refined on F2 by full matrix least-squares methods
using the SHELXTL version 5.1 software.
ACKNOWLEDGMENTS
■
We are grateful to National Natural Science Foundation of
China (21975135), China Postdoctoral Science Foundation
(2018M641624) for financial support. We are grateful to Dr.
Yin Yang for EPR analysis.
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