Mn(OAc)3-Promoted Oxidative Csp3-P Bond Formation through Csp2-Csp2 and P-H Bond Cleavage: Access to β-Ketophosphonates

Article abstract of DOI:10.1021/acs.joc.7b02391

The Mn(OAc)₃-promoted oxidative phosphonylation of N,N-dimethylenaminones with H-phosphonates, involving a chemo- and regioselective C_sp²-C_sp² bond cleavage and C_sp³-P bond formation in one step, provided successfully functionalized β-ketophosphonates under mild reaction conditions. Oxidative C_sp³-H/P-H cross-coupling reactions via C_sp³-C(C=O) bond cleavage and mechanistic studies are conducted preliminarily, and a possible mechanism is proposed. This novel method proceeds in good to excellent yields, shows operational simplicity, broad substrate scope, and large-scale preparation.

Full text of DOI:10.1021/acs.joc.7b02391

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Article
Mn(OAc)3-Promoted Oxidative Csp3-P Bond Formation through
Csp2-Csp2 and P-H Bond Cleavage: Access to #-Ketophosphonates
Pan Zhou, Biao Hu, Lingdan Li, Kairui Rao, Jiao Yang, and Fuchao Yu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02391 • Publication Date (Web): 14 Nov 2017
Downloaded from http://pubs.acs.org on November 14, 2017
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Mn(OAc)3-Promoted Oxidative Csp3-P Bond Formation through Csp2-Csp2 and P-H
Bond Cleavage: Access to β-Ketophosphonates.
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Pan Zhou, Biao Hu, Lingdan Li, Kairui Rao, Jiao Yang, and Fuchao Yu*
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Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, P. R.
China.
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ABSTRACT: The Mn(OAc)3ꢀpromoted oxidative phosphonylation of N,Nꢀdimethylenaminones with
Hꢀphosphonates, involving a chemoꢀ and regioselective Csp2–Csp2 bond cleavage and Csp3–P bond formation in one
step, provid successfully functionalized βꢀketophosphonates under mild reaction conditions. Oxidative Csp3–H/P–H
crossꢀcoupling reactions via Csp3–C(C=O) bond cleavage and mechanistic studies are conducted preliminarily, and
a possible mechanism is proposed. This novel method proceeds in good to excellent yields, shows operational
simplicity, broad substrate scope and largeꢀscale preparation.
■ INTRODUCTION
Organophosphorus compounds play a crucial role in organic chemistry,1 medicinal chemistry2 and material
chemistry.3 Thus, great progress has been achieved in the development of new methods for the construction of the
carbon–phosphorus bond.4 Among them, the Mn(III)ꢀpromoted radical phosphonylations of Csp2–Csp2 compounds
(alkenes,5 heteroarenes,6 arenes,7 fullerene dimers,8 etc.) have been developed as a powerful strategy for the
formation of Csp2−P bonds. However, these Csp2ꢀH phosphonylations have been limited to construct Csp2−P bonds
through phosphonyl radical addition and elimination process. To the best of our knowledge, no example of
Mn(III)ꢀpromoted new Csp3−P bond formation through selective cleavage of Csp2–Csp2 bonds has been described
(Scheme 1). Therefore, the development of a Mn(III)ꢀpromoted radical phosphonylation protocol for the formation
of Csp3−P bond through cleavage of Csp2–Csp2 bond remains an unsolved challenge.
Scheme 1 Comparison of previous works with this work by Mn(III)ꢀpromoted phosphonylation.
βꢀKetophosphonates, on the other hand, are a highly useful class of organophosphorus compounds, owing to
their remarkable biological activities, eminent metalꢀcomplexing abilities and synthetic versatile applications in
organic synthesis.9 Thus, many efforts have been put into the development of efficient synthetic approaches for the
Csp3−P bond construction to construct these scaffolds.10 Traditionally, βꢀketophosphonates are prepared by the
Arbuzov reaction (reaction with αꢀhaloketones and trialkylphosphites) (Scheme 2a),11 or the acylation of
alkylphosphonates by using esters as the acylation reagent under strongꢀbase conditions (Scheme 2b).12 Recently,
three methodologies were described in the hydration of alkynylphosphonates based on the use of Pd(II) or Au(I) or
Ag(I) catalysts (Scheme 2c).13 Very recently, various research groups (Song,14 Zhao,15 He,16 Ji17 and others18)
independently reported elegant studies on the aerobic oxyphosphorylation of alkenes or alkynes, and the
decarboxylationꢀ or deesterificationꢀ or deamidation–oxyphosphorylation of cinnamyl/alkynyl carboxylic
acids/carboxylates/amides under different bimetallic synergistically catalyzed (Cu/Fe, Cu/Ag, etc), which involved
sequential Csp/sp2–H/Csp/sp2–C(C=O) bondꢀbreaking followed by C=O and Csp3−P bondꢀreconstruction (Scheme 2d
and 2e). In addition, the Lei group developed a direct radical/radical Csp3–H/P–H crossꢀcoupling reaction of aryl
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ketone oꢀacetyloximes leading to the construction of Csp3−P bond with the assistance of CuCl and PCy3 (Scheme
2f);19 and Peng and coꢀworkers disclosed a novel Ag(I)ꢀcatalyzed direct oxidative Csp3–H/P–H crossꢀcoupling
reaction of 1,3ꢀdicarbonyl compounds, which involved oxidative Csp3−P bond formation and selective Csp3–C(C=O)
bond cleavage (Scheme 2g).20 However, to the best of our knowledge, just one example of the reconstruction of
Csp3−P bond via the selective cleavage of the Csp2–Csp2 bond was reported by the Song group, which involved the
phosphorylation reaction of α,βꢀunsaturated carbonyl compounds (Scheme 2h).21 This approach would be valuable
for direct the Csp3−P bond formation, but the choice of transitionꢀmetal catalyst of this aerobic phosphorylation is
limited to Cu/Fe cocatalyzed system. Therefore, the development of an efficient catalytic phosphorylation system
leading to the formation of Csp3−P bond through Csp2–Csp2 bond cleavage would be highly desirable. Enaminones
versatile building blocks in heterocyclic synthesis,22 which have attracted more and more attention during the past
few decades owing to their excellent reactivity in various organic transformations.23 As our ongoing interest in
enaminone chemistry24 and Mn(III)ꢀpromoted radical phosphonylation,25 we report herein an unprecendent
Mn(OAc)3ꢀpromoted strategy to construct βꢀketophosphonates from readily available N,Nꢀdimethylenaminones and
Hꢀphosphonates in good yields, through selective oxidative Csp2–Csp2 bond cleavage and Csp3−P bond formation
(Scheme 2i).
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Scheme 2 Strategies for the formation of βꢀketophosphonates.
■ RESULTS AND DISCUSSION
At the outset, the coupling of N,Nꢀdimethylenaminone 1a with readily available diethyl phosphite 2a was studied
with Mn(OAc)3 (3.0 equiv) as a catalyst in air. As shown in Table 1, the reaction in toluene at 80 °C for 12 h did
not afford any phosphorylation product (entry 1). To our delight, the desired product 3a was isolated in lower yield
when the reaction was performed in acetic acid (AcOH) (entry 2). Gratifyingly, the yield was remarkably improved
to 62% in toluene when AcOH was selected as a coꢀcatalyst (entry 3). Comparable results were observed for
reactions in tetrahydrofuran (THF), CH3CN, and dichloroethane (DCE) (entries 4–6), and the results were
significantly improved for reactions in 1,4ꢀdioxane, as 3a was obtained in 82% yield (entry 7). However,
Subsequent catalyst and coꢀcatalyst screening indicated that generally Mn(OAc)3/AcOH was more efficient
catalytic system than other catalysts and coꢀcatalysts, including Mn(OAc)3, FeCl3, CuCl2, Fe(NO3)3, CuSO4,
tolueneꢀpꢀsulfonic acid (pꢀTSA) and benzoic acid (BA) (entry 7 vs entries 8–14). After further investigation of the
catalyst and coꢀcatalyst amounts, reaction temperature and times, we found that these variables were not provided
the best result (entry 7 vs entries 15–22). The role of AcOH and O2 have also been tested. The reaction with 3.0
equiv Mn(OAc)3 in 1,4ꢀdioxane under air at 80 °C for 12 h in absence of AcOH did not obtained the desired
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product 3a (entry 23), and the reaction without O2 had little impact on the results (entry 24). Therefore, the best
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results were obtained using 3.0 equiv Mn(OAc)3 and 2.0 mL AcOH in 4.0 mL of 1,4ꢀdioxane under air at 80 °C for
12 h.
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Table 1 Optimization of the reaction conditions.a
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Entry
1
Oxidant [equiv]
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)2 (3.0)
FeCl3 (3.0)
Acid [mL]
ꢀ
Solvent
toluene
Temp [oC]
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
80 oC
60 oC
100 oC
80oC
80 oC
80 oC
80 oC
Time [h]
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12
12
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12
12
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12
12
12
12
10
14
12
12
Yield [%]b
n.d. c
28
2
ꢀ
AcOH
3
AcOH (2.0)
AcOH (2.0)
AcOH (2.0)
AcOH (2.0)
AcOH (2.0)
AcOH (2.0)
AcOH (2.0)
AcOH (2.0)
AcOH (2.0)
AcOH (2.0)
pꢀTSA (2 mmol)
BA (2 mmol)
AcOH (2.0)
AcOH (2.0)
AcOH (1.0)
AcOH (3.0)
AcOH (2.0)
AcOH (2.0)
AcOH (2.0)
AcOH (2.0)
ꢀ
toluene
62
4
THF
51
5
CH3CN
63
6
DCE
57
7
1,4-dioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
1,4ꢀdioxane
82
8
n.d. c
n.d. c
n.d. c
n.d. c
n.d. c
38
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24
CuCl2 (3.0)
Fe(NO3)3 (3.0)
CuSO4 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (4.0)
Mn(OAc)3 (2.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
Mn(OAc)3 (3.0)
33
73
53
69
80
71
77
76
80
n.d. c
83 d
AcOH (2.0)
a Reaction conditions: N,NꢀDimethylenaminone 1a (1.0 mmol, 1.0 equiv), diethyl phosphite 2a (2.0 mmol, 2.0 equiv),
oxidant and acid in air; b Isolated yield based on N,Nꢀdimethylenaminone 1a; c No detected; d N2 atmosphere.
Under the optimized reaction conditions, we next examined the scope of N,Nꢀdimethylenaminones.
Representative products are summarized in Table 2. Electronꢀrich (4ꢀOMe), electronꢀneutral (4ꢀH, 4ꢀMe) and
halogenated (4ꢀF, 4ꢀCl, 2ꢀF) on the aromatic ring were smoothly converted to the corresponding products 3a–3f in
good to excellent yields (64–83%). When the substituent of aromatic ring was changed to strong
electronꢀwithdrawing groups (4ꢀCF3, 4ꢀCN and 4ꢀNO2), low to moderate yields were obtained in certain cases
(3g–3i, 41–54%). Gratifyingly, substrates bearing polycyclic aromatic (1,1'ꢀbiphenyl and naphthalene) and
heterocyclic substituents (furyl and thienyl) at the αꢀposition of the carbonyl group successfully participated in the
reaction, providing access to the desired products 3j–3n (57–80%), though the reactions failed for substrates
containing pyridyl or pyrazinyl group, presumably due to their highly electron deficient natures (3o–3p).
Interestingly, substrates containing a phenemyl moiety at the αꢀposition of the carbonyl group proceeded smoothly
and afforded the βꢀketophosphonate 3q in 63% yield, but styrylphosphonate 3r was obtained in 76% yield when the
substituent at αꢀposition of the enaminone moiety was changed to a styryl group, which involved the selective
cleavage of the Csp2–Csp2 bond of styryl group instead of the cleavage of Csp2–Csp2 bond of enaminone structure to
the corresponding βꢀketophosphonate. Moreover, aliphatic N,Nꢀdimethylenaminone 1s was also employed
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successfully and the desired phosphonylation product 3s was generated in excellent yield (81%). Furthermore,
reaction of 2ꢀhydroxyphenyl moiety N,Nꢀdimethylenaminone 1t with diethyl phosphite 2a afforded phosphinative
cyclization product 4a (20%) and chromone 5 (52%), and could not to cleave the Csp2–Csp2 bond of enaminone
structure to βꢀketophosphonate products (Scheme 3a). Consequently, in order to identify the first process of the
phosphinative cyclization concerning phosphorylation and cyclization, chromone 5 was treated with diethyl
phosphite 2a under the optimal reaction conditions and failed to give phosphinative cyclization product 4a (Scheme
3b). The result indirectly indicated that the phosphinative cyclization could occur firstly phosphorylation and
intermediate 6 was formed, follow by cyclization to 4a in oneꢀstep process.
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Table 2 Scope of various N,Nꢀdimethylenaminones by changing the substituents on the aromatic ringa,b
Entry N,NꢀDimethylenaminones 1
yiledb
1
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7
O
O
P
OEt
OEt
8
3h
, 41%
NC
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a Reaction conditions: N,NꢀDimethylenaminones 1 (1.0 mmol, 1.0
equiv) and diethyl phosphite 2a (2.0 mmol, 2.0 equiv) and
b
Mn(OAc)3 (3.0 mmol, 3.0 equiv) and AcOH (2.0 mL) in air;
Isolated yield based on N,Nꢀdimethylenaminones 1; c No reaction.
O
O
O
O
P
O
OEt
OEt
H
P(OEt)2 2a
(a)
(b)
Me
standard
conditions
O
OH
N
O
4a, 20%
5, 52%
1t
Me
O
O
P
standard
conditions
OEt
OEt
2a
OH
Me
N
Me
6
Scheme 3 Mn(OAc)3ꢀpromoted phosphonation of 2ꢀhydroxyphenyl moiety N,Nꢀdimethylenaminone 1s.
To elaborate further the scope of this reaction, we tested the behavior of a linker of enaminones (Table 3).
Surprisingly, the unusual N,Nꢀdisubstituent was also viable, including N,Nꢀdiethyl, N,Nꢀdiisopropyl, N,Nꢀdibenzyl
and Nꢀtetrahydropyrrolyl. Reaction of these enaminones (1a, 1uꢀ1x) formed 3a under the standard conditions,
respectively. Notably, when the αꢀ or βꢀposition of enaminone had an acetyl or formyl or methyl group (1y, 1z and
1a’), the radical phosphonylation also could be achieved and βꢀketophosphonate 3a was obtained in moderate to
good yields (51%, 53% and 75%), involving the chemoselective cleavage of the Csp2–Csp2 bond and Csp2–C(C=O)
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bond access to Csp3−P bondꢀreconstruction.
Table 3 Scope of various N,Nꢀdimethylenaminones by changing the N,Nꢀsubstituentsa,b
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Entry
1
N,NꢀDimethylenaminone 1
yiledb
85%
2
3
4
5
73%
71%
65%
68%
6
7
8
51%
53%
75%
a Reaction conditions: N,NꢀDimethylenaminones 1 (1.0 mmol, 1.0
equiv) and diethyl phosphite 2a (2.0 mmol, 2.0 equiv) and
Mn(OAc)3 (3.0 mmol, 3.0 equiv) and AcOH (2.0 mL) in air;
Isolated yield based on N,Nꢀdimethylenaminones 1.
b
We subsequently investigated the scope of Hꢀphosphonates 2 to test the compatibility of this transformation,
as shown in Table 4. A wide range of Hꢀphosphonates with ether groups (such as MeO, EtO, iꢀPrO, PhO and BnO)
underwent the desired reactions with N,Nꢀdimethylenaminones 1a to afford phosphonylation products in moderate
to high yields (3a and 3t–3w, 61–85%). However, no desired product 3x was obtained from diphenylphosphine
oxide 2f, which might demonstrate that phosphonates were desirable donors and phosphine oxide could not
suitable for this transformation.
Table 4 HꢀPhosphonates scopea,b
Entry
Phosphite ester 2
yiledb
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a Reaction conditions: N,NꢀDimethylenaminone 1a (1.0 mmol, 1.0
equiv) and Hꢀdiethyl phosphonate 2 (2.0 mmol, 2.0 equiv) and
Mn(OAc)3 (3.0 mmol, 3.0 equiv) and AcOH (2.0 mL) in air;
Isolated yield based on N,Nꢀdimethylenaminone 1a.
b
Additionally, inspired by the very recent development of synthetic routes towards βꢀketophosphonate via
Ag(I)ꢀcatalyzed direct oxidative Csp3–H/P–H crossꢀcoupling reaction with 1,3ꢀdicarbonyl compounds,20 we pursued
this Mn(III)ꢀpromoted radical phosphonylation that could be used to produce these compounds from the same
substrate through Csp3–H/P–H crossꢀcoupling reaction, involving the direct selective oxidative Csp3–C(C=O) bond
cleavage and Csp3−P bond formation. Remarkably, the treatment of diethyl phosphite 2a with 1,3ꢀdicarbonyl
compounds 7a and 7b under the standard conditions afforded βꢀketophosphonate 3a in 9% and 48%, respectively
(Scheme 4). Meanwhile, we further demonstrated the utility of this transformation in the possibility of
industrialized synthesis. The present Mn(OAc)3ꢀpromoted tandem transformationꢀtype reaction could be conducted
on gram scale; 3a was obtained in 79% yield (1.2 g, 6 mmol scale, Scheme 5). These extension and scalability
significantly broaden the applicability of Mn(III)ꢀpromoted radical phosphonylation reaction.
Scheme 4 Mn(OAc)3ꢀpromoted phosphonation of 1,3ꢀdicarbonyl compounds.
Scheme 5 Largeꢀscale synthesis of 3a.
To gain preliminary mechanistic insight into this transformation, a series of control experiments were
performed (Scheme 6). Frist, the reaction of N,Nꢀdimethylenaminones 1a and diethyl phosphite 2a with the
addition of 3.0 eqivalents radicalꢀtrapping reagent under the standard conditions was performed, such as
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2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy (TEMPO), butylated hydroxytoluene (BHT) and 1,1ꢀdiphenylethylene (DPE)
(Scheme 6a, 6b and 6c). The formation of desired product 3a was suppressed, and only the BHT adduct 8 was
detected by ESI (Fig. S1) and diethyl (2,2ꢀdiphenylvinyl)phosphonate 9 was isolated in 31% yield, indicating that a
phosphonate radical is involved in this transformation. These experiments demonstrate that the phosphonylation
transformation may proceed by a radical mechanism. Subsequently, the reaction was conducted in the presence of
D2O under the standard conditions, and deuteriumꢀincorporated βꢀketophosphonate product [d1]-3a was isolated in
16% yield, whereas the deuteriumꢀincorporated product [d1]-3a was observed in tetradeuteroacetic acid, indicating
that the hydrogen in the methene group came from D2O (Scheme 6d and Fig. S2). Remarkably, 2ꢀdiethyl phosphate
N,Nꢀdimethylenaminone 10a was synthetized by the condensation of βꢀketophosphonate 3a with DMFꢀDMA in
73% yield (Scheme 6e), and the pure 10a, which is unstable and only be stored for two days, was also easily
converted into 3a at room temperature. Meanwhile, 10a can be transformed quickly into 3a under the standard
conditions, and under an atmosphere of N2 had little impact on the results (Scheme 6f). These results illustrated that
10a could be formed during the crossꢀcoupling transformation, and O2 was not essential for the reaction to proceed
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which was different from the previous reports on aerobic phosphorylation 14ꢀ16,21
.
Scheme 6 Control experiments.
Based on the preliminary mechanistic studies and previous reports,14ꢀ16,21 a tentative reaction mechanism for
the tandem radical phosphonylation is proposed in Scheme 7. HꢀPhosphonates 2 was oxidized by the Mn(III) to
generate the corresponding Pꢀcentered radical 11 and Mn(II). The radical addition of intermediate 11 to the
αꢀposition of N,Nꢀdimethylenaminones 1 gave carbon radical 12, which was reoxidized to carbocation intermediate
13 by the Mn(III), followed by the nucleophilic attack of H2O to give intermediate 14. Then, there were two
groupꢀleaving pathways for subsequent elimination of intermediate 13: path A generated the desired products 3 by
loss of a molecule of N,Nꢀdimethylformamide (DMF); path B formed products 10 through losing a molecule of
H2O, which also retransformed to 14 via the nucleophilic attack of H2O and explained the results in Scheme 6f.
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Scheme 7. Proposed mechanisms for the formation of βꢀketophosphonates 3.
■ CONCLUSION
In conclusion, we have reported a simple and highly efficient Mn(OAc)3ꢀpromoted radical phosphonylation of
readily available N,Nꢀdimethylenaminones with Hꢀphosphonates to afford functionalized βꢀketophosphonates in
good to excellent yields. Importantly, this transformation offered the first Mn(III)ꢀpromoted protocol for Csp3–P
bond formation by oxidative Csp2–Csp2 bond cleavage in one step. Notably, this powerful strategy also preliminarily
promoted to other oxidative Csp3–H/P–H crossꢀcoupling reactions of simple 1,3ꢀdicarbonyl compounds, involving
the selective oxidative Csp3–C(C=O) bond cleavage and Csp3−P bond formation. A putative mechanism was
proposed on the basis of mechanistic studies and isotopeꢀlabeling studies. This method proceeds under mild
reaction conditions, shows good functionalgroup compatibility and can be effectively scaled up. Further
mechanistic details and synthetic applications are underway in our laboratory.
■ EXPERIMENTAL SECTION
General Information. All compounds were fully characterized by spectroscopic data. The NMR spectra were
recorded on a Bruker Avance 400 (1H: 400 MHz, 13C: 100 MHz), Bruker DRX500 (1H: 500 MHz, 13C: 125 MHz)
and Bruker DRX500 (1H: 600 MHz, 13C: 150 MHz), chemical shifts (δ) are expressed in ppm, and J values are
given in Hz, and deuterated CDCl3, Acetoneꢀd6 and DMSOꢀd6 were used as solvent. IR spectra were recorded on a
FTꢀIR Thermo Nicolet Avatar 360 using KBr pellet. The reactions were monitored by thin layer chromatography
(TLC) using silica gel GF254. The melting points were determined on XTꢀ4A melting point apparatus and are
uncorrected. HRMs were performed on an Agilent LC/MS TOF instrument.
All chemicals and solvents were used as received without further purification unless otherwise stated. Column
chromatography was performed on silica gel (200–300 mesh).
Compounds 1 were prepared according to the literature26. The materials 2a–e were purchased from
Adamasꢀbeta® and Aldrich Corporation Limited.
General Procedure for the Synthesis of β-ketophosphonates 3. N,NꢀDimethylenaminones 1 (1 mmol, 1.0
equiv), Hꢀphosphonates 2 (2.0 mmol, 2.0 equiv) , Mn(OAc)3 (3 mmol, 3.0 equiv), AcOH (2 mL) 1,4ꢀdioxane (4 mL)
were charged into a 15 mL ace glass pressure tub, and the mixture was stirred at 80 oC for 12 h until
N,Nꢀdimethylenaminones 1 were completely consumed. The mixture was cooled to room temperature, neutralized
with a saturated solution of NaHCO3 to pH 8–9, and then EtOAc (30 mL × 2) were added. The organic phase was
washed with water (20 mL), dried over Na2SO4, concentrated and purified by flash column chromatography to
afford βꢀketophosphonates 3.
The products were further identified by FTꢀIR, NMR and HRMS, being in good agreement with the assigned
structures. (see ESI†).
Diethyl (2ꢀoxoꢀ2ꢀphenylethyl)phosphonate (3a). Yield: 85% (217 mg); Yellow liquid; IR (KBr): 1681, 1598,
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1449, 1394, 1252, 1163, 1026, 786, 690, 585, 509 cmꢀ1; H NMR (600 MHz, CDCl3): δ = 1.27–1.29 (m, 6H,
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C–CH3), 3.65 (d, J = 22.7 Hz, 2H, P–CH2–C), 4.13–4.17 (m, 4H, P–CH2–C), 7.47–7.50 (m, 2H, ArH), 7.59 (m, 1H,
ArH), 8.02 (d, J =7.4Hz, 2H, ArH); 13C NMR (150 MHz, CDCl3): δ = 16.2, 16.3, 38.5 (d, J = 129 Hz, P–CH2–C),
62.6, 62.7, 128.6, 128.6, 129.0, 129.0, 133.7, 136.5, 191.5 (d, J = 6.5 Hz); HRMS (TOF ES+): m/z calcd for
C12H18O4P+ [(M+H)+], 257.0937; found, 257.0936.
Diethyl (2ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀoxoethyl)phosphonate (3b). Yield: 82% (235 mg); Yellow liquid; IR (KBr): 1670,
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1
1601, 1513, 1422, 1259, 1176, 1026, 824, 578, 522 cmꢀ1; H NMR (600 MHz, CDCl3): δ = 1.28–1.30 (m, 6H,
C–CH3), 3.59 (d, J = 22.7 Hz, 2H, P–CH2–C), 3.88 (s, 3H, ArOCH3), 4.13–4.15 (m, 4H, O–CH2–C), 6.95 (d, J =
8.9 Hz, 2H, ArH), 8.01 (m, 2H, ArH); 13C NMR (150 MHz, CDCl3): δ = 16.2, 16.3, 38.3 (d, J = 129 Hz, P–CH2–C),
55.5, 62.6, 62.6, 113.8, 113.8, 129.6, 131.5, 131.5, 164.0, 190.3 (d, J = 6.0 Hz); HRMS (TOF ES+): m/z calcd for
C13H20O5P+ [(M+H)+], 287.1043; found, 287.1043.
Diethyl (2ꢀoxoꢀ2ꢀ(pꢀtolyl)ethyl)phosphonate (3c). Yield: 83% (224 mg); Yellow liquid; IR (KBr): IR (KBr): 1681,
1603, 1449, 1394, 1254, 1025, 970, 786, 690, 585, 511 cmꢀ1; cmꢀ1; 1H NMR (500 MHz, CDCl3): δ = 1.26–1.30 (m,
6H, C–CH3), 2.42 (s, 3H, ArCH3), 3.59–3.64 (d, J = 22.5 Hz, 2H, P–CH2–C), 4.11–4.17 (m, 4H, O–CH2–C), 7.27
(d, J = 8.0 Hz, 2H, ArH), 7.91 (d, J = 8.0 Hz, 2H, ArH); 13C NMR (125 MHz, CDCl3): δ = 16.2, 16.3, 21.7, 38.3 (d,
J = 130 Hz, P–CH2–C), 62.6, 62.7, 129.2, 129.2, 129.3, 129.3, 134.1, 144.7, 191.5 (d, J = 6.25 Hz); HRMS (TOF
ES+): m/z calcd for C13H20O4P+ [(M+H)+], 271.1094; found, 271.1094.
Diethyl (2ꢀ(4ꢀchlorophenyl)ꢀ2ꢀoxoethyl)phosphonate (3d). Yield: 79% (229 mg); Yellow liquid; IR (KBr): 1681,
1
1589, 1489, 1399, 1252, 1026, 815, 605, 523 cmꢀ1; H NMR (600 MHz, CDCl3): δ = 1.20–1.22 (m, 6H, C–CH3),
3.54 (d, J = 22.8 Hz, 2H, P–CH2–C), 4.04–4.09 (m, 4H, O–CH2–C), 7.38 (d, J = 8.5 Hz, 2H, ArH), 7.89 (d, J = 8.5
Hz, 2H, ArH); 13C NMR (150 MHz, CDCl3): δ = 16.2, 16.3, 38.2 (d, J = 128 Hz, P–CH2–C), 62.7, 62.8, 128.9,
128.9, 130.5, 130.5, 134.8, 140.2, 190.7 (d, J = 6 Hz); HRMS (TOF ES+): m/z calcd for C12H17ClO4P+ [(M+H)+],
291.0547; found, 291.0547.
Diethyl (2ꢀ(4ꢀfluorophenyl)ꢀ2ꢀoxoethyl)phosphonate (3e). Yield: 70% (192 mg); Yellow liquid; IR (KBr): 1680,
1
1599, 1509, 1413, 1242, 1160, 970, 823, 570 cmꢀ1; H NMR (600 MHz, CDCl3): δ = 1.19–1.22 (m, 6H, C–CH3),
3.54 (d, J = 22.9 Hz, 2H, P–CH2–C), 4.04–4.09 (m, 4H, O–CH2–C), 7.05–7.08 (m, 2H, ArH), 7.97–7.99 (m, 2H,
ArH); 13C NMR (150 MHz, CDCl3): δ = 16.2, 16.2, 38.5 (d, J = 129 Hz, P–CH2–C), 62.6, 62.7, 115.7 (d, J = 22.5
Hz), 115.7 (d, J = 22.5 Hz), 131.8 (d, J = 9.0 Hz), 131.8 (d, J = 9.0 Hz), 132.9, 166.0 (d, J = 255 Hz), 190.3 (d, J =
7.5 Hz); HRMS (TOF ES+): m/z calcd for C12H17FO4P+ [(M+H)+], 275.0843; found, 275.0843.
Diethyl (2ꢀ(2ꢀfluorophenyl)ꢀ2ꢀoxoethyl)phosphonate (3f). Yield: 64% (175 mg); Yellow liquid; IR (KBr): 1685,
1
1610, 1482, 1453, 1395, 1256, 1026, 970, 876, 830, 773, 590, 500 cmꢀ1; H NMR (500 MHz, CDCl3): δ =
1.18–1.20 (m, 6H, C–CH3), 3.64 (d, J = 22.0 Hz, 2H, P–CH2–C), 4.03–4.09 (m, 4H, O–CH2–C), 7.05–7.09 (m, 1H,
ArH), 7.15–7.18 (m, 1H, ArH), 7.47–7.48 (m, 1H, ArH), 7.77–7.81 (m, 1H, ArH); 13C NMR (125 MHz, CDCl3): δ
= 16.2, 16.2, 42.4 (d, J = 129 Hz, P–CH2–C), 62.5, 62.5, 116.6 (d, J = 23.8 Hz) , 124.5 (d, J = 3.8 Hz), 125.5 (d, J =
12.5 Hz), 131.1 (d, J = 2.5 Hz), 135.2 (d, J = 10.0 Hz), 161.8 (d, J = 252.5 Hz), 190.0; HRMS (TOF ES+): m/z
calcd for C12H17FO4P+ [(M+H)+], 275.0843; found, 275.0843.
Diethyl (2ꢀoxoꢀ2ꢀ(4ꢀ(trifluoromethyl)phenyl)ethyl)phosphonate (3g). Yield: 46% (149 mg); Yellow liquid; IR
(KBr): 1679, 1424, 1365, 1269, 1143, 1078, 970, 814, 730, 598 cmꢀ1; 1H NMR (600 MHz, CDCl3): δ = 1.20–1.23
(m, 6H, C–CH3), 3.59 (d, J = 22.9 Hz, 2H, P–CH2–C), 4.06–4.09 (m, 4H, O–CH2–C), 7.67 (d, J = 8.3 Hz, 2H, ArH),
8.07 (d, J = 8.2 Hz, 2H, ArH); 13C NMR (150 MHz, CDCl3): δ = 16.2, 16.2, 38.9 (d, J = 129 Hz, P–CH2–C), 62.8,
62.8, 123.5 (d, J = 271.5 Hz), 125.5, 125.5, 129.4, 129.4, 134.7 (dd, J = 69 Hz), 139.1, 191.1 (d, J = 6.0 Hz);
HRMS (TOF ES+): m/z calcd for C13H17F3O4P+ [(M+H)+], 325.0811; found, 325.0814.
Diethyl (2ꢀ(4ꢀcyanophenyl)ꢀ2ꢀoxoethyl)phosphonate (3h). Yield: 41% (115 mg); Yellow liquid; IR (KBr): 2072,
1
1743, 1638, 1402, 1268, 1244, 1024, 823, 618, 570 cmꢀ1; H NMR (600 MHz, CDCl3): δ = 1.21–1.23 (m, 6H,
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C–CH3), 3.58 (d, J = 22.9 Hz, 2H, P–CH2–C), 4.05–4.10 (m, 4H, O–CH2–C), 7.72 (d, J = 9.4 Hz, 2H, ArH), 8.06 (d,
J = 8.3 Hz, 2H, ArH); 13C NMR (150 MHz, CDCl3): δ = 16.2, 16.3, 39.0 (d, J = 129 Hz, P–CH2–C), 62.9, 63.0,
116.9, 117.8, 129.5, 129.5, 132.5, 132.5, 139.3, 190.8 (d, J = 7.5 Hz); HRMS (TOF ES+): m/z calcd for
C13H17NO4P+ [(M+H)+], 282.0890; found, 282.0889.
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Diethyl (2ꢀ(4ꢀnitrophenyl)ꢀ2ꢀoxoethyl)phosphonate (3i). Yield: 54% (162 mg); Yellow liquid; IR (KBr): 1673,
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C–CH3), 3.68 (d, J = 23.0 Hz, 2H, P–CH2–C), 4.14–4.18 (m, 4H, O–CH2–C), 8.21 (d, J = 8.8 Hz, 2H, ArH), 8.33 (d,
J = 8.8 Hz, 2H, ArH); 13C NMR (150 MHz, CDCl3): δ = 16.2, 16.3, 39.3 (d, J = 128 Hz, P–CH2–C), 62.9, 63.0,
123.8, 123.8, 130.2, 130.2, 140.8, 150.6, 190.6 (d, J = 7.5 Hz); HRMS (TOF ES+): m/z calcd for C12H17NO6P+
[(M+H)+], 302.0788; found, 302.0789.
Diethyl (2ꢀ([1,1'ꢀbiphenyl]ꢀ4ꢀyl)ꢀ2ꢀoxoethyl)phosphonate (3j). Yield: 77% (256 mg); Yellow liquid; IR (KBr):
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1674, 1470, 1392, 1252, 1025, 970, 819, 478 cmꢀ1; H NMR (600 MHz, CDCl3): δ = 1.19–1.21 (m, 6H, C–CH3),
3.57 (d, J = 22.7 Hz, 2H, P–CH2–C), 4.04–4.09 (m, 4H, O–CH2–C), 7.31 (d, J = 7.4 Hz, 1H, ArH), 7.35–7.38 (m,
2H, ArH), 7.53 (d, J = 7.3 Hz, 2H, ArH), 7.60 (d, J = 8.3 Hz, 2H, ArH), 7.99 (d, J = 8.4 Hz, 2H, ArH); 13C NMR
(150 MHz, CDCl3): δ = 16.3, 16.3, 38.5 (d, J = 129 Hz, P–CH2–C), 62.7, 62.7, 127.7, 127.2, 127.3, 127.3, 128.4,
129.0, 129.0, 129.7, 129.7, 135.2, 139.6, 146.3, 191.5 (d, J = 6.0 Hz); HRMS (TOF ES+): m/z calcd for C18H22O4P+
[(M+H)+], 333.1250; found, 333.1259.
Diethyl (2ꢀ(naphthalenꢀ2ꢀyl)ꢀ2ꢀoxoethyl)phosphonate (3k). Yield: 80% (245 mg); Yellow liquid; IR (KBr): 1677,
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1604, 1560, 1486, 1448, 1409, 1253, 1025, 823, 767, 698, 658, 589, 510 cmꢀ1; H NMR (600 MHz, CDCl3): δ =
1.18–1.21 (m, 6H, C–CH3), 3.69 (d, J = 22.7 Hz, 2H, P–CH2–C), 4.06–4.10 (m, 4H, O–CH2–C), 7.48 (d, J = 7.5 Hz,
1H, ArH), 7.52–7.54 (m, 1H, ArH), 7.78–7.82 (m, 2H, ArH), 7.90 (d, J = 8.1 Hz, 1H, ArH), 7.97–7.98 (m, 1H,
ArH), 8.47 (s, 1H, ArH); 13C NMR (150 MHz, CDCl3): δ = 16.3, 16.3, 38.6 (d, J = 129 Hz, P–CH2–C), 62.7, 62.7,
124.2, 126.9, 127.8, 128.5, 128.9, 129.8, 131.5, 132.4, 133.9, 135.8, 191.8 (d, J = 6.0 Hz); HRMS (TOF ES+): m/z
calcd for C16H20O4P+ [(M+H)+], 307.1094; found, 307.1097.
Diethyl (2ꢀ(naphthalenꢀ1ꢀyl)ꢀ2ꢀoxoethyl)phosphonate (3l). Yield: 74% (226 mg); Yellow liquid; IR (KBr): 1680,
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1508, 1442, 1393, 1247, 1025, 972, 804, 589, 484 cmꢀ1; H NMR (600 MHz, CDCl3): δ = 1.13–1.16 (m, 6H,
C–CH3), 3.68 (d, J = 22.6 Hz, 2H, P–CH2–C), 4.01–4.06 (m, 4H, O–CH2–C), 7.43–7.47 (m, 2H, ArH), 7.51–7.53
(m, 1H, ArH), 7.79 (d, J = 8.0 Hz, 1H, ArH), 7.92–7.96 (m, 2H, ArH), 8.59 (d, J = 8.6 Hz, 1H, ArH); 13C NMR
(150 MHz, CDCl3): δ = 16.2, 16.3, 41.8 (d, J = 128 Hz, P–CH2–C), 62.6, 62.7, 124.3, 125.8, 126.6, 128.3, 128.4,
129.3 130.3, 133.6, 133.9, 135.1, 195.1 (d, J = 7.5 Hz); HRMS (TOF ES+): m/z calcd for C16H20O4P+ [(M+H)+],
307.1094; found, 307.1093.
Diethyl (2ꢀ(furanꢀ2ꢀyl)ꢀ2ꢀoxoethyl)phosphonate (3m). Yield: 57% (140 mg); Yellow liquid; IR (KBr): 1672, 1568,
1467, 1392, 1305, 1253, 1164, 1026, 972, 884, 777, 594, 510 cmꢀ1; 1H NMR (500 MHz, CDCl3): δ = 1.18–1.24 (m,
6H, C–CH3), 3.44 (d, J = 22.5 Hz, 2H, P–CH2–C), 4.07–4.09 (s, 4H, O–CH2–C), 6.51 (s, 1H, ArH), 7.25 (s, 1H,
ArH), 7.57 (s, 1H, ArH); 13C NMR (125 MHz, CDCl3): δ = 16.2, 16.3, 38.2 (d, J = 129.0 Hz, P–CH2–C), 62.7, 62.7,
112.8, 119.0, 147.2, 152.3, 180.0 (d, J = 7.5 Hz); HRMS (TOF ES+): m/z calcd for C10H16O5P+ [(M+H)+],
247.0730; found, 247.0726.
Diethyl (2ꢀoxoꢀ2ꢀ(thiophenꢀ2ꢀyl)ethyl)phosphonate (3n). Yield: 65% (170 mg); Yellow liquid; IR (KBr): 1657,
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1520, 1416, 1356, 1251, 1244, 1025, 973, 860, 827, 735, 589, 509 cmꢀ1; H NMR (600 MHz, CDCl3): δ =
1.29–1.31 (m, 6H, C–CH3), 3.56 (d, J = 22.6 Hz, 2H, P–CH2–C), 4.13–4.18 (m, 4H, O–CH2–C), 7.15–7.17 (m, 1H,
ArH), 7.71 (d, J = 4.9 Hz, 1H, ArH), 7.71 (d, J = 3.6 Hz, 1H, ArH) ; 13C NMR (150 MHz, CDCl3): δ = 16.2, 16.3,
39.4 (d, J = 129 Hz, P–CH2–C), 62.8, 62.8, 128.3, 134.2, 135.1, 143.9, 184.2 (d, J = 6.0 Hz); HRMS (TOF ES+):
m/z calcd for C10H16O4PS+ [(M+H)+], 263.0501; found, 263.0500.
Diethyl (2ꢀoxoꢀ4ꢀphenylbutyl)phosphonate (3q). Yield: 63% (179 mg); Yellow liquid; IR (KBr): 1715, 1604,
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1497, 1454, 1395, 1253, 1025, 970, 809, 750, 701, 538, 494 cmꢀ1; 1H NMR (600 MHz, CDCl3): δ = 1.21–1.24 (m,
6H, C–CH3), 2.80–2.83 (m, 2H, CH2), 2.86–2.89 (m, 2H, CH2) 3.00 (d, J = 22.8 Hz, 2H, P–CH2–C), 4.00–4.05 (m,
4H, O–CH2–C), 7.10 (m, 3H, ArH), 7.17–7.19 (m, 2H, ArH); 13C NMR (150 MHz, CDCl3): δ = 16.3, 16.3, 29.4,
42.4 (d, J = 126 Hz, P–CH2–C), 45.4, 62.6, 62.6, 126.1, 128.4, 128.4, 128.4, 128.4, 140.6, 201.1 (d, J = 6.0 Hz);
HRMS (TOF ES+): m/z calcd for C14H22O4P+ [(M+H)+], 285.1250; found, 285.1253.
Diethylꢀstyrylphosphonate (3r). Yield: 76% (182 mg); Yellow liquid; IR (KBr): 1617, 1449, 1394, 1247, 1026,
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967, 858, 745, 692, 521 cmꢀ1; H NMR (500 MHz, CDCl3): δ = 1.27–1.30 (m, 6H, C–CH3), 4.03–4.10 (m, 4H,
O–CH2–C), 6.15–6.22 (m, 1H, C=CH), 7.31–7.33 (m, 3H, ArH), 7.40–7.48 (m, 3H, C=CH+ArH), 13C NMR (125
MHz, CDCl3): δ = 16.4, 16.4, 61.9, 61.9, 114.0 (d, J = 190.0 Hz), 127.7, 127.7, 128.9, 128.9, 130.2, 134.9 (d, J =
22.5 Hz), 148.8 (d, J = 6.3 Hz); HRMS (TOF ES+): m/z calcd for C12H18O3P+ [(M+H)+], 241.0988; found,
241.0989.
Diethyl (2ꢀoxooctyl)phosphonate (3s). Yield: 81% (232 mg); Yellow liquid; IR (KBr): 1714, 1633, 1454, 1396,
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1252, 1163, 1028, 967, 799, 622, 547 cmꢀ1; H NMR (500 MHz, CDCl3): δ = 0.79–0.82 (m, 3H, CH3), 1.21–1.22
(m, 6H, CꢀCH3), 1.23–1.28 (m, 6H, CH2), 1.49–1.52 (m, 2H, CH2), 2.53–2.56 (m, 2H, CH2), 3.01 (d, J = 25.0 Hz,
2H, CH2), 4.04–4.11 (m, 4H, O–CH2–C); 13C NMR (125 MHz, CDCl3): δ = 13.9, 16.2, 16.2, 22.4, 23.3, 28.6, 31.5,
42.3 (d, J = 126.3 Hz, P–CH2–C), 44.0, 62.5, 62.5, 203.1; HRMS (TOF ES+): m/z calcd for C12H25NaO4P+
[(M+Na)+], 287.1383; found, 287.1387.
Dimethyl (2ꢀoxoꢀ2ꢀphenylethyl)phosphonate (3t). Yield: 83% (189 mg); Yellow liquid; IR (KBr): 1680, 1598,
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1449, 1254, 1032, 877, 812, 690, 585, 505 cmꢀ1; H NMR (500 MHz, CDCl3): δ = 3.58 (d, J = 22.5 Hz, 2H,
P–CH2–C), 3.70 (s, 3H, O–CH3), 3.72 (s, 3H, O–CH3), 7.40–7.43 (m, 2H, ArH), 7.52 (d, J = 7.0 Hz, 1H, ArH),
7.92–7.94 (m, 2H, ArH); 13C NMR (125 MHz, CDCl3): δ = 37.5 (d, J = 131.3 Hz, P–CH2–C), 53.1, 53.2, 128.7,
128.7, 129.0, 129.0, 133.8, 136.4, 191.8 (d, J = 7.5 Hz); HRMS (TOF ES+): m/z calcd for C10H14O4P+ [(M+H)+],
229.0624; found, 229.0622.
Diisopropyl (2ꢀoxoꢀ2ꢀphenylethyl)phosphonate (3u). Yield: 78% (221 mg); Yellow liquid; IR (KBr): 1681, 1599,
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1449, 1386, 1251, 1106, 992, 889, 777, 690, 585, 525 cmꢀ1; H NMR (500 MHz, CDCl3): δ = 1.19–1.21 (m, 12H,
C–CH3), 3.52 (d, J = 23.0 Hz, 2H, P–CH2–C), 4.63–4.67 (m, 2H, O–CH–C), 7.38–7.41 (m, 2H, ArH), 7.49 (d, J =
7.0 Hz, 1H, ArH), 7.93–7.95 (m, 2H, ArH); 13C NMR (125 MHz, CDCl3): δ = 23.7, 23.7, 23.9, 23.9, 39.7 (d, J =
130.0 Hz, P–CH2–C), 71.4, 71.5, 128.5, 128.5, 129.5, 129.5, 133.5, 136.7, 192.1 (d, J = 7.5 Hz); HRMS (TOF ES+):
m/z calcd for C14H22O4P+ [(M+H)+], 285.1250; found, 285.1247.
Diphenyl (2ꢀoxoꢀ2ꢀphenylethyl)phosphonate (3v). Yield: 78% (274 mg); Yellow liquid; IR (KBr): 1682, 1594,
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1490, 1449, 1401, 1277, 1187, 1008, 939, 765, 689, 589, 496 cmꢀ1; H NMR (500 MHz, CDCl3): δ = 3.84 (d, J =
23.0 Hz, 2H, P–CH2–C), 7.04–7.07 (m, 6H, ArH), 7.16–7.21 (m, 4H, ArH), 7.36–7.39 (m, 2H, ArH), 7.48–7.51 (d,
J = 7.0 Hz, 1H, ArH), 7.93–7.93 (m, 2H, ArH); 13C NMR (125 MHz, CDCl3): δ = 37.8 (d, J = 133 Hz, P–CH2–C),
120.6, 120.6, 120.7, 120.7, 125.5, 125.5, 128.8, 128.8, 129.1, 129.1, 129.9, 129.9, 129.9, 129.9, 134.0, 136.4, 150.0,
150.1, 190.8 (d, J = 7.5 Hz); HRMS (TOF ES+): m/z calcd for C20H18O4P+ [(M+H)+], 353.0937; found, 353.0940.
Dibenzyl (2ꢀoxoꢀ2ꢀphenylethyl)phosphonate (3w). Yield: 61% (232 mg); Yellow liquid; IR (KBr): 1681, 1598,
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1498, 1450, 1380, 1256, 1130, 995, 886, 734, 696, 591, 462 cmꢀ1; H NMR (500 MHz, CDCl3): δ = 3.57 (d, J =
22.5 Hz, 2H, P–CH2–C), 4.91–5.01 (m, 4H, O–CH2–C), 7.17–7.25 (m, 10H, ArH), 7.32–7.35 (m, 2H, ArH),
7.46–7.49 (m, 1H, ArH), 7.85–7.87 (m, 2H, ArH); 13C NMR (125 MHz, CDCl3): δ = 38.7 (d, J = 131 Hz,
P–CH2–C), 68.0, 68.1, 128.1, 128.1, 128.1, 128.1, 128.5, 128.5, 128.6, 128.6, 128.6, 128.6, 128.7, 128.7, 129.0,
129.0, 133.7, 135.9, 135.9, 136.5, 191.7 (d, J = 7.5 Hz); HRMS (TOF ES+): m/z calcd for C22H22O4P+ [(M+H)+],
381.1250; found, 381.1251.
Diethyl (4ꢀoxoꢀ4Hꢀchromenꢀ3ꢀyl)phosphonate (4a). Yield: 20% (56 mg); Yellow liquid; IR (KBr): 1655, 1611,
1556, 1460, 1381, 1343, 1307, 1258, 1056, 1026, 969, 806, 752, 692, 591, 535; 1H NMR (600 MHz, CDCl3): δ =
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1.29–1.31 (m, 6H, C–CH3), 4.15–4.23 (m, 4H, O–CH2–C), 7.38–7.40 (m, 1H, ArH), 7.43 (d, J = 8.3 Hz, 1H, ArH),
7.64–7.66 (m, 1H, ArH), 8.14–8.16 (m, 1H, ArH), 8.45 (d, J = 9.5 Hz, 1H, C=CH); 13C NMR (150 MHz, CDCl3): δ
= 16.3, 16.4, 63.0, 63.1, 114.0 (d, J = 157.5 Hz, P–C–C), 118.3, 124.4 (d, J = 7.5 Hz), 126.2, 126.2, 134.5, 156.2,
163.4 (d, J = 19.5 Hz), 175.3; HRMS (TOF ES+): m/z calcd for C13H16O5P+ [(M+H)+], 283.0730; found, 283.0729.
4HꢀChromenꢀ4ꢀone (5). Yield: 52% (76 mg); Yellow liquid; IR (KBr): 1653, 1462, 1401, 1338, 1243, 1185, 1123,
1006, 962, 836, 756, 678, 527, 465 cmꢀ1; 1H NMR (500 MHz, CDCl3): δ = 6.25 (d, J = 6.0 Hz, 1H, C=CH),
7.30–7.33 (m, 1H, ArH), 7.36 (d, J = 8.5 Hz, 1H, ArH), 7.56–7.60 (m, 1H, ArH), 7.77 (d, J = 10.0 Hz, 1H, C=CH),
8.11 (d, J = 9.5 Hz, 1H, ArH); 13C NMR (125 MHz, CDCl3): δ = 113.0, 118.2, 124.9, 125.2, 125.8, 133.8, 155.3,
156.5, 177.6; HRMS (TOF ES+): m/z calcd for C9H7O2+ [(M+H)+], 147.0441; found, 147.0443.
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Diethyl (2,2ꢀdiphenylvinyl)phosphonate (9). Yield: 31% (98 mg); Yellow liquid; IR (KBr): 1600, 1487, 1445,
1394, 1242, 1161, 1038, 962, 840, 767, 701, 526 cmꢀ1; 1H NMR (500 MHz, CDCl3): δ = 1.04–1.07 (m, 6H, C–CH3),
3.72–3.77 (m, 2H, O–CH2–C), 3.82–3.87 (m, 2H, O–CH2–C), 6.11 (d, J = 15.5 Hz, 1H, C–CH–P), 7.19–7.27 (m,
5H, ArH), 7.29–7.31 (m, 5H, ArH); 13C NMR (125 MHz, CDCl3): δ = 15.1, 15.1, 60.5, 60.6, 113.7 (d, J = 192.5 Hz,
P–CH–C), 126.8, 127.2, 127.2, 127.3, 127.3, 127.6, 127.6, 128.4, 128.7, 137.9 (d, J = 7.5 Hz), ,140.5 (d, J = 22.5
Hz), 159.1 (d, J = 5 Hz); HRMS (TOF ES+): m/z calcd for C18H22O3P+ [(M+H)+], 317.1301; found, 317.1305.
General Procedure for the Large-scale synthesis of β-ketophosphonate 3a. N,NꢀDimethylenaminone 1a (6
mmol, 1.0 equiv), diethyl phosphite 2a (12.0 mmol, 2.0 equiv) , Mn(OAc)3 (18 mmol, 3.0 equiv), AcOH (12 mL)
1,4ꢀdioxane (24 mL) were charged into a 100 mL roundꢀbottom flask, and the mixture was stirred at 80 oC for 12 h
until N,Nꢀdimethylenaminone 1a were completely consumed. The mixture was cooled to room temperature,
neutralized with a saturated solution of NaHCO3 to pH 8–9, and then EtOAc (30 mL × 2) were added. The organic
phase was washed with water (120 mL), dried over Na2SO4, concentrated and purified by flash column
chromatography to afford βꢀketophosphonate 3a (79%, 1.2g).
General Procedure for the Synthesis of intermediate bis-enaminones 10a. To
a solution of
βꢀketophosphonates 3a (1.00 mmol, 1.0 equiv) in DMFꢀDMA (1.0 mL) at 80 °C (oil bath) was added Lꢀproline
(0.10 mmol, 0.1 equiv), and the mixture was stirred for 2 h, the full conversion of βꢀketophosphonates 3a
monitored by TLC. To the resulting mixture was added 25 mL of brine and extracted with ethyl acetate (10 mL × 3).
The combined organic layers were washed with brine and dried over anhydrous Na2SO4, filtered and concentrated
under reduced pressure. Purification by flash chromatography on silica gel afforded the intermediate compound
10a.
Diethyl (E)ꢀ(1ꢀ(dimethylamino)ꢀ3ꢀoxoꢀ3ꢀphenylpropꢀ1ꢀenꢀ2ꢀyl)phosphonate (10a). Yield: 73% (227 mg); Yellow
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liquid; IR (KBr): 1627, 1603, 1383, 1257, 1027, 963, 794, 614 cmꢀ1; H NMR (500 MHz, CDCl3): δ = 1.10–1.18
(m, 6H, C–CH3), 2.77–2.80 (m, 6H, N–CH3), 3.88–3.95 (m, 4H, O–CH2–C), 7.31–7.34 (m, 2H, ArH), 7.40–7.43
(m, 1H, ArH), 7.59 (d, J = 16.0 Hz, 1H, C=CH), 7.73 (d, J = 8.0 Hz, 2H, ArH); 13C NMR (125 MHz, CDCl3): δ =
16.0, 16.1, 44.7, 44.7, 61.7, 61.8, 128.1, 128.1, 128.9, 128.9, 132.0, 140.8, 158.4, 173.7, 193.3; HRMS (TOF ES+):
m/z calcd for C15H23NO4P+ [(M+H)+], 312.1359; found, 312.1366.
■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
xx.xxxx/acs.joc.xxxxxxx.
Copies of 1H NMR and 13C NMR spectra for compounds 3a−3w, 4a, 5, 8 and 9a (PDF)
■ AUTHOR INFORMATION
Corresponding Author
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*Eꢀmail: yufuchao05@126.com
ORCID
Fuchao Yu: 0000ꢀ0001ꢀ5557ꢀ3824
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■ ACKNOWLEDGMENTS
We are grateful for the financial support from the National Natural Science Foundation of China
(21402070), the Analytical & Testing Foundation of Kunming University of Science and Technology
(2017T20130137, 2017M20152118097 and 2017M20162218006).
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