Synthesis of Amido Esters and Amido Phosphonates through Carbonylation of Diazo Compounds Followed by Nucleophilic Addition Reaction

Article abstract of DOI:10.1002/ejoc.201700581

We report a method to produce amido esters and amido phosphonates. Octacarbonyldicobalt [Co₂(CO)₈] was found to be an efficient nongaseous CO source that could be used as a reagent for the carbonylation of diazo esters and diazo phosphonates under mild reaction conditions. A number of diazo esters and diazo phosphonates smoothly underwent the reaction with CO, which was generated from Co₂(CO)₈, to produce the corresponding ketenes. The subsequent reaction with an amine afforded the expected amido esters and phosphonates. By applying the developed protocol, we synthesized a number of amido esters and amido phosphonates. Characterization of these compounds was achieved by using standard spectroscopic and analytical techniques as well as crystal structure analysis for four of the products.

Full text of DOI:10.1002/ejoc.201700581

DOI: 10.1002/ejoc.201700581
Full Paper
Carbene Carbonylation
Synthesis of Amido Esters and Amido Phosphonates through
Carbonylation of Diazo Compounds Followed by Nucleophilic
Addition Reaction
Kankanala Ramakrishna[a] and Chinnappan Sivasankar*[a]
Abstract: We report a method to produce amido esters and produce the corresponding ketenes. The subsequent reaction
amido phosphonates. Octacarbonyldicobalt [Co2(CO)8] was with an amine afforded the expected amido esters and phos-
found to be an efficient nongaseous CO source that could be phonates. By applying the developed protocol, we synthesized
used as a reagent for the carbonylation of diazo esters and a number of amido esters and amido phosphonates. Characteri-
diazo phosphonates under mild reaction conditions. A number zation of these compounds was achieved by using standard
of diazo esters and diazo phosphonates smoothly underwent spectroscopic and analytical techniques as well as crystal struc-
the reaction with CO, which was generated from Co2(CO)8, to ture analysis for four of the products.
Introduction
thermal conditions.[21,26] The synthesis of ketenes by the carb-
onylation of carbenes using carbon monoxide offers several ad-
vantages when other known methods suffer from low yields
and harsh reaction conditions.[27]
Amides are an important functional group in organic chemistry
and biochemistry.[1–3] The amide functionality can serve as a
directing group in a synthetic method[4–6] and is related to
other groups such as esters and phosphonates, which are more
useful in total synthesis.[7–10] Because of its importance, several
synthetic methods have been developed to prepare different
types of amides, most of which start from carbonyl compounds
and amines.[11–13] Widely used methods include: (i) carbonyl-
ation followed by amidation and (ii) the hydroamidation of alk-
ynes and nitriles.[14–17] These known methods, however, are not
fully suitable to the synthesis of amido esters and amido phos-
phonates because of their low functional-group tolerance.[11,15]
Under certain reaction conditions, the Ritter reaction, the reac-
tion of isonitriles and compounds with active methylene
groups, and an amino carbonylation strategy can be employed
for the synthesis of amido esters.[18–20] Nonetheless, these
methods also suffer from harsh reaction conditions, low yields,
and narrow substrate scopes.[18,20]
In contrast, because of their diverse and reactive nature, ket-
enes are widely used as key intermediates in synthetic organic
chemistry.[21,22] Ketenes are known to participate in cycloaddi-
tions as well as nucleophilic and electrophilic addition reac-
tions, which result in the formation of ꢀ-lactones, ꢀ-lactams,
and many other synthetic and biologically important mol-
ecules.[23–25] Many methods are known for the preparation of
ketenes, including the use of chemical, photochemical, and
Similarly, the carbonylation of carbenes from diazo com-
pounds or tosyl hydrazones by using carbon monoxide cata-
lyzed by Pd or CoII catalysts offers both advantages and disad-
vantages.[28–30] These reactions (catalysts) are moderately suc-
cessful at higher temperature but result in low yields. Another
inevitable drawback includes the use of carbon monoxide gas,
which is highly flammable and poisonous. Because of the color-
less and odorless nature of CO, its handling can become ex-
tremely dangerous. The adequate equipment that is necessary
presents a challenge for a common synthetic laboratory and
also in chemical industry.[31–33] Although there are difficulties in
the handling of CO, few alternate methods have been devel-
oped for the carbonylation of alkyl or aryl halides by using non-
gaseous carbon monoxide sources.[34–36] Considering the im-
portance of amido esters and amido phosphonates, and in con-
tinuation of our research on carbenes,[37–40] we herein report
an efficient method for the synthesis of amido esters and amido
phosphonates that proceeds through the carbonylation of
carbenes by using a nongaseous CO source followed by a
nucleophilic addition reaction using different amines.
Results and Discussion
Among all of the nongaseous carbon monoxide sources,
carbonylmetal and typical organic carbonyl compounds have
gained much attention.[41,42] In general, organic carbonyl com-
pounds decompose and generate CO above room temperature
or in the presence of a strong base.[32,34,41] Carbene-related re-
actions, however, must be carried out at or below room temper-
ature to achieve maximum yields (and to minimize the carbene-
[a] Catalysis and Energy Laboratory, Department of Chemistry, Pondicherry
University (A Central University),
Puducherry 605014, India
E-mail: siva.che@pondiuni.edu.in
http://www.pondiuni.edu.in/profile/dr-c-sivasankar
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.201700581.
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dimerized products).[43–45] Thus, if we use an organic carbonyl
compound as a nongaseous CO source, we will need a separate
catalyst to activate the diazo compound and yield the carbene.
In the case of carbonylmetal compounds, the same complex
can simultaneously produce CO and activate diazo compounds
to produce the carbenes. Herein, we have chosen carbonyl-
metal compounds as a nongaseous carbon monoxide source.
Among the majority of these complexes, octacarbonyldicobalt
[Co2(CO)8] is one of the more interesting ones, as it is not only
a nongaseous CO source[46] but can also decompose diazo
compounds to produce ketenes under mild reaction condi-
tions.[47–49]
For the initial screening of different carbonylmetal com-
pounds, we chose commercially less expensive Co2(CO)8 and
Fe2(CO)9 as solid CO sources. First, we employed Co2(CO)8 with
methyl 2-diazo-2-phenylacetate and 4-chloroaniline as the
model substrates. The desired amido ester product was success-
fully produced after 6 h in 81 % yield (Table 1, Entry 1). Encour-
aged by this result, we then carried out similar reactions with
Fe2(CO)9 and Mn2(CO)10 as the CO sources. In case of Fe2(CO)9,
we obtained a moderate product yield (47 %) after 24 h
(Table 1, Entry 2). However, Mn2(CO)10 did not provide the ex-
pected product (Table 1, Entry 3).
Table 2. Optimization of solvent and carbonylmetal loading.[a]
Entry
Solvent
Co2(CO)8 [equiv.]
Time [h]
Yield [%][b]
1
2
DCM
THF
CH3OH
CH3CN
toluene
DCM
DCM
DCM
DCM
0.5
0.5
0.5
0.5
0.5
0.25
0.75
1
6
12
24
24
6
12
4
3
81
61 (13 % N-H IP)
3[c]
4[c]
5
trace
trace
79
6
7
43 (8 % N-H IP)
85
82
trace
8
9[d]
0.02
24
[a] Reagents and conditions: aniline (0.5 mmol) and diazo compound
(0.55 mmol) in solvent (5 mL). [b] Pure compound after column chromatogra-
phy. IP = insertion product. [c] Unreactive diazo compound and aniline were
recovered. [d] Reaction was carried out under 1 atm CO pressure (CO was
generated by dehydration of formic acid using sulfuric acid and was used
after purification).
Experiments were also conducted to optimize the concentra-
tion of Co2(CO)8 for the above-mentioned reaction. The desired
product was produced in 81 % yield when the reaction was
carried out with 0.5 equiv. of Co2(CO)8, (Table 2, Entry 1). By
employing 0.75 equiv. of Co2(CO)8 over 4 h, we observed a
slight increase in the yield of the desired product to 85 %
(Table 2, Entry 7). Using 1 equiv. of Co2(CO)8 afforded the ex-
pected product in 82 % yield after 3 h (Table 2, Entry 8). When
the reaction was conducted with a catalytic amount of Co2(CO)8
under 1 atm of CO for 24 h, we obtained a trace amount of the
Table 1. Screening of various carbonylmetal compounds for the amido ester
synthesis.[a]
Entry
Carbonylmetal compound[b]
Time [h]
Yield [%][c]
1
2
3
Co2(CO)8
Fe2(CO)9
Mn2(CO)10
6
24
24
81
47
n.d.
[a] Reagents and conditions: aniline (0.5 mmol) and diazo compound
(0.55 mmol) in solvent (5 mL). [b] We used 0.25 mmol of the carbonylmetal
compound. [c] Pure compound after column chromatography (n.d. = not
detected).
From the results of screening different carbonylmetal com-
pounds, we found that Co2(CO)8 was the most suitable non-
gaseous CO source for the carbonylation of carbenes from diazo
compounds. Next, we screened other reaction conditions such
as solvent and catalyst loading. When the reaction was carried
out in tetrahydrofuran (THF), we observed a 61 % yield of the
amido ester along with 13 % of the N–H insertion product after
12 h (Table 2, Entry 2). When we conducted the reaction in
acetonitrile and methanol, only a trace amount of the expected
product was produced along with the recovery of the unre-
acted starting materials (Table 2, Entries 3 and 4). In the case
of toluene, we did observe the expected product (79 % yield;
Table 2, Entry 5), and the yield and reaction times were similar
to those that occurred when the transformation was carried out
in dichloromethane (DCM). For the sake of operational conve-
nience and to obtain maximum yields, we employed DCM for
our remaining investigations.
Scheme 1. Scope of diazo compounds for the amido ester synthesis.
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amido ester (Table 2, Entry 9). On the basis of the above results,
we decided to use 0.5 equiv. of Co2(CO)8 and DCM as a solvent
for further studies (Schemes 1, 2, 3, and 4).
Scheme 3. Scope of diazo phosphonates and anilines for the amido phos-
phonate synthesis.
Scheme 4. Carbazole as a heterocyclic amine source in the amido ester syn-
thesis.
Scheme 2. Scope of anilines for the amido ester synthesis.
92 %, respectively, after 6 h. Ethyl 2-diazopropanoate, however,
only afforded a moderate yield of 67 % after a reaction time of
4 h.
To explore the substrate scope of the reaction, we screened
various diazo acetates and treated them with 4-chloroaniline
Next, we screened a number of anilines under the optimized
(Scheme 1). Isopropyl 2-diazo-2-phenylacetate provided a de- reaction conditions to examine their scope in our developed
creased yield and afforded 76 % of the expected product 3b protocol (Scheme 2). Both anilines that have electron-donating
after 6 h. The diazo(phenyl)acetates that contain electron- (to give 4b–4e) as well as those that have electron-withdrawing
donating groups at the para position of the aromatic ring gave groups (to give 4f–4k) underwent the reaction and afforded
excellent yields. For example, methyl 2-diazo-2-(4-methoxy- good to very good yields. Aniline provided 4a in a very good
phenyl)acetate produced the expected product 3c in 93 % yield yield of 93 % after 6 h, and anilines that contain moderately
after 6 h of reaction time. In the case of ethyl 2-diazo-2-(3,4- electron-donating groups produced very good yields (i.e., 4b
dimethoxyphenyl)acetate, we observed a very good yield of and 4d). Anilines that have strong electron-donating groups,
91 % of 3e after 8 h. When we used ethyl 2-diazo-2-(2-methoxy- however, provided lower yields (i.e., 4c and 4e). From the above
phenyl)acetate, however, only a 52 % yield of 3d was obtained studies, we noted that among the anilines that contain elec-
after 12 h, which may be caused by the bulkiness of the 2-OMe tron-withdrawing groups, those halo-substituted anilines af-
group. We also screened various diazo(phenyl)acetates that forded good yields (i.e., 4f–4h). In addition, ortho-substituted
have electron-withdrawing groups, including ethyl 2-(3-chloro- anilines tended to give lower yields compared with meta- and
phenyl)-2-diazoacetate and ethyl 2-(4-chlorophenyl)-2-diazo- para-substituted anilines (e.g., 4i). Anilines that contain other
acetate, which gave 3g and 3h in very good yields of 93 and functional groups such as carbonyl or nitrile also produced
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Figure 1. Molecular structures of 3i, 4f, 6f, and 6i (hydrogen atoms are omitted for clarity). Thermal ellipsoids are set at 50 % probability.
good yields [i.e., 89 % (4j) and 85 % (4k)] after 8 h of reaction Conclusions
time. Additional reactions also provided good to very good
yields of 4l–4o.
We developed an efficient method for the synthesis of amido
esters and amido phosphonates from the reactions of diazo
compounds with anilines in the presence of Co2(CO)8 as a non-
gaseous carbon monoxide source. Various carbonylmetal com-
pounds and different organic solvents were screened to deter-
mine the optimal reaction conditions. By applying the devel-
oped protocol, we synthesized and characterized a number of
important amido esters and amido phosphonates. Further stud-
ies on the formation of ketenes from diazo compounds and CO
are in progress in our laboratory.
Taking into consideration the importance of amido phos-
phonates, we then applied our developed protocol for their
synthesis by using diazo phosphonates and anilines (Scheme 3).
In this regard, we screened various anilines and diazo phos-
phonates. The reaction of aniline with a diazo phosphonate af-
forded the expected product 6a in 71 % yield after 24 h. Stirring
of the reaction mixture for a longer period of time did not
improve the yield. We also screened different anilines that con-
tain electron-donating and electron-withdrawing groups (to
give 6b–6h) and observed good yields by employing anilines
that have moderately electron-donating groups (i.e., to give 6b
and 6c). A decrease in the yield was observed with anilines that
contain strong electron-donating groups (i.e., to give 6d). When
we used anilines that contain electron-withdrawing groups,
moderate to good yields resulted (i.e., to give 6e–6h). The reac-
tion of benzyl diazo phosphonate with 4-chloroaniline afforded
a good yield (78 %) of 6i after 24 h.
After successfully demonstrating the scope of the anilines
and diazo phosphonates, we examined the use of both aliphatic
(i.e., benzylamine) and heterocyclic (i.e., carbazole) amines in
the amido ester synthesis (Scheme 4). In the case of the hetero-
cyclic amine, we observed a moderate 63 % yield of 8a after
12 h, whereas the use of benzylamine afforded only a trace
amount of the product.
Experimental Section
General Methods: Unless otherwise mentioned, all reactions were
conducted under dry nitrogen with oven-dried glassware. All sol-
vents were distilled and stored under nitrogen prior to use accord-
ing to standard procedures. Methanol, dichloromethane, and aceto-
nitrile were dried with and distilled from CaH2. THF and toluene
were dried with and distilled from sodium/benzophenone. Unless
otherwise mentioned, commercially available chemicals were used
as received. All diazo compounds were prepared by applying the
standard reported procedures.[37–40] TLC analysis was performed on
precoated silica gel 60 F254 plates, and the developed plates were
visualized under UV light (254 nm). Column chromatography was
performed on silica gel (100–200 mesh). The 1H and 13C NMR spec-
troscopic data were recorded at 400 and 100 MHz, respectively.
Chemical shifts (δ) are reported in ppm. The residual solvent signal
was used as a reference for 1H NMR data, and the solvent signal
As a part of the characterization of these new products, crys-
tals of 3i, 4f, 6f, and 6i were analyzed by single-crystal XRD
studies to confirm their molecular structures (Figure 1).
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1
was used as a reference for the 13C NMR data. HRMS data were
recorded with a UHD Q-TOF mass spectrometer. CCDC 1529619 (for
127 °C. H NMR (400 MHz, CDCl3): δ = 9.04 (s, 1 H), 7.49–7.44 (m, 2
H), 7.27–7.21 (m, 2 H), 6.97 (dd, J = 11.0, 2.0 Hz, 2 H), 6.84 (d, J =
3i), 1521410 (for 4f), 1529617 (for 6f), and 1529618 (for 6i) contain 8.1 Hz, 1 H), 4.56 (s, 1 H), 4.30–4.20 (m, 2 H), 3.86 (s, 3 H), 3.85 (s, 3
the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre.
H), 1.28 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
171.1, 165.7, 149.4, 149.3, 136.1, 129.6, 129.0, 126.1, 121.3, 120.4,
111.5, 111.4, 62.3, 58.4, 55.98, 55.93, 14.0 ppm. IR (film): ν = 3292,
˜
2975, 2831, 1739, 1655, 1593, 1522, 1400, 1365, 1349, 1261, 1203,
1182, 1168, 1146, 1024, 818, 768, 760 cm–1. HRMS (ESI): calcd. for
C19H21ClNO5 [M + H]+ 378.1108; found 378.1111.
General Procedures for the Synthesis of the Amido Esters and
Amido Phosphonates: An oven-dried 20 mL Schlenk tube (not a
pressure tube) was charged with aniline (0.5 mmol) and Co2(CO)8
(0.25 mmol), and then the solvent (4 mL) was added through the
septum. The diazo compound (0.55 mmol) was dissolved in the
solvent (1 mL), and the solution was added to the reaction mixture
at 0 °C. The reaction mixture was warmed to room temperature
and stirred for the reported time. The progress of the reaction was
monitored by TLC analysis (hexane/ethyl acetate). Upon completion
of the reaction, the solvent was evaporated under reduced pressure,
and the crude residue was purified by column chromatography on
silica gel (hexane/ethyl acetate) to yield the desired product.
Ethyl 3-[(4-Chlorophenyl)amino]-3-oxo-2-(m-tolyl)propanoate
(3f): White solid (133 mg, 80 % yield); m.p. 121–123 °C. 1H NMR
(400 MHz, CDCl3): δ = 9.17 (s, 1 H), 7.48 (d, J = 8.8 Hz, 2 H), 7.25 (m,
5 H), 7.15 (d, J = 6.8 Hz, 1 H), 4.57 (s, 1 H), 4.33–4.18 (m, 2 H), 2.35
(s, 3 H), 1.28 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 171.5, 165.5, 139.2, 136.2, 133.8, 129.6, 129.5, 129.2, 129.1, 128.9,
125.0, 121.4, 62.4, 58.8, 21.6, 14.1 ppm. IR (film): ν = 3351, 2981,
˜
2834, 1724, 1693, 1599, 1536, 1488, 1393, 1366, 1250, 1192, 1167,
1093, 1029, 837, 816, 776, 748 cm–1. HRMS (ESI): calcd. for
C18H19ClNO3 [M + H]+ 332.1053; found 332.1052.
Methyl 3-[(4-Chlorophenyl)amino]-3-oxo-2-phenylpropanoate
(3a): White solid (124 mg, 81 % yield); m.p. 171–173 °C. 1H NMR
(400 MHz, CDCl3): δ = 9.11 (s, 1 H), 7.45 (dd, J = 11.8, 8.6 Hz, 4 H),
7.36 (q, J = 5.6 Hz, 3 H), 7.24 (d, J = 8.6 Hz, 2 H), 4.64 (s, 1 H), 3.78
Ethyl
2-(3-Chlorophenyl)-3-[(4-chlorophenyl)amino]-3-oxo-
propanoate (3g): White solid (165 mg, 93 % yield); m.p. 95–97 °C.
1H NMR (400 MHz, CDCl3): δ = 9.26 (s, 1 H), 7.48 (dd, J = 8.9, 2.8 Hz,
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.7, 165.3, 136.1, 2 H), 7.43 (d, J = 1.0 Hz, 1 H), 7.36–7.28 (m, 3 H), 7.27 (d, J = 2.5 Hz,
133.7, 129.7, 129.4, 129.1, 128.7, 128.2, 121.4, 58.7, 53.2 ppm. IR 1 H), 7.26 (d, J = 1.7 Hz, 1 H), 4.57 (s, 1 H), 4.34–4.16 (m, 2 H), 1.28
(film): ν = 3344, 3311, 3069, 2952, 2831, 1753, 1660, 1603, 1540, (td, J = 7.1, 1.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.9,
˜
1491, 1397, 1353, 1311, 1209, 1155, 1011, 973, 827, 775 cm–1. HRMS 164.6, 136.0, 135.7, 135.1, 130.5, 129.9, 129.1, 128.9, 128.4, 126.4,
(ESI): calcd. for C16H15ClNO3 [M + H]+ 304.0740; found 304.0746.
121.5, 62.7, 58.2, 14.1 ppm. IR (film): ν = 3295, 3132, 2831, 1748,
˜
1655, 1607, 1548, 1492, 1400, 1364, 1205, 1176, 1095, 1029, 825,
775 cm–1. HRMS (ESI): calcd. for C17H16Cl2NO3 [M + H]+ 353.0507;
found 352.0505.
Isopropyl 3-[(4-Chlorophenyl)amino]-3-oxo-2-phenylpropano-
1
ate (3b): Off-white solid (127 mg, 76 % yield); m.p. 107–109 °C. H
NMR (400 MHz, CDCl3): δ = 9.25 (s, 1 H), 7.51–7.47 (m, 2 H), 7.44
(dd, J = 8.0, 1.5 Hz, 2 H), 7.40–7.33 (m, 3 H), 7.28–7.24 (m, 2 H), 5.11
(dt, J = 12.5, 6.3 Hz, 1 H), 4.58 (s, 1 H), 1.31 (d, J = 6.3 Hz, 3 H), 1.19
(d, J = 6.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.1,
165.5, 136.2, 134.1, 129.6, 129.3, 129.1, 128.6, 128.0, 121.4, 70.4,
Ethyl
2-(4-Chlorophenyl)-3-[(4-chlorophenyl)amino]-3-oxo-
propanoate (3h): Off-white solid (162 mg, 92 % yield); m.p. 122–
1
124 °C. H NMR (400 MHz, CDCl3): δ = 9.22 (s, 1 H), 7.50–7.44 (m, 2
H), 7.39–7.31 (m, 4 H), 7.28–7.24 (m, 2 H), 4.57 (s, 1 H), 4.31–4.18
(m, 2 H), 1.27 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 171.1, 164.9, 136.0, 134.7, 132.4, 129.9, 129.6, 129.4, 129.1, 121.4,
59.0, 21.8, 21.5 ppm. IR (film): ν = 3298, 3195, 3131, 2831, 1740,
˜
1654, 1609, 1548, 1492, 1401, 1364, 1207, 1172, 1103, 833, 776,
735 cm–1. HRMS (ESI): calcd. for C18H19ClNO3 [M + H]+ 332.1053;
found 332.1058.
62.7, 58.0, 14.0 ppm. IR (Film): ν = 3330, 2988, 2832, 2717, 1749,
˜
1661, 1600, 1538, 1492, 1397, 1365, 1335, 1303, 1213, 1165, 1088,
1017, 827, 775 cm–1. HRMS (ESI): calcd. for C17H16Cl2NO3 [M + H]+
352.0507; found 352.0511.
Methyl 3-[(4-Chlorophenyl)amino]-2-(4-methoxyphenyl)-3-oxo-
propanoate (3c): Light brown semisolid (155 mg, 93 % yield). 1H
NMR (400 MHz, CDCl3): δ = 9.04 (s, 1 H), 7.47–7.40 (m, 2 H), 7.37–
7.30 (m, 2 H), 7.23 (d, J = 8.7 Hz, 2 H), 6.90–6.85 (m, 2 H), 4.58 (s, 1
H), 3.77 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.6, 165.8,
159.8, 136.1, 129.6, 129.5, 129.0, 125.6, 121.4, 114.6, 58.0, 55.3,
Ethyl
3-[(4-Chlorophenyl)amino]-2-methyl-3-oxopropanoate
(3i): White solid (86 mg, 67 % yield); m.p. 89–91 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.80 (s, 1 H), 7.50 (d, J = 8.7 Hz, 2 H), 7.31–
7.25 (m, 2 H), 4.24 (q, J = 7.1 Hz, 2 H), 3.43 (q, J = 7.3 Hz, 1 H), 1.54
(d, J = 7.3 Hz, 3 H), 1.31 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 172.9, 167.3, 136.3, 129.5, 129.1, 121.3, 62.1, 47.4, 15.6,
53.0 ppm. IR (film): ν = 3319, 3124, 3001, 2953, 2833, 1738, 1667,
˜
1630, 1600, 1539, 1512, 1492, 1399, 1364, 1250, 1178, 1154, 1092,
1031, 1012, 828, 775 cm–1. HRMS (ESI): calcd. for C17H17ClNO4 [M +
H]+ 334.0846; found 334.0844.
14.1 ppm. IR (film): ν = 3301, 3190, 3123, 2983, 2831, 1745, 1677,
˜
1651, 1600, 1543, 1490, 1455, 1396, 1362, 1326, 1293, 1243, 1209,
1176, 1092, 1037, 1010, 934, 838, 818, 775, 721 cm–1. HRMS (ESI):
calcd. for C12H15ClNO3 [M + H]+ 256.0740; found 256.0731.
Ethyl 3-[(4-Chlorophenyl)amino]-2-(2-methoxyphenyl)-3-oxo-
propanoate (3d): White solid (91 mg, 52 % yield); m.p. 114–116 °C.
1H NMR (400 MHz, CDCl3): δ = 8.78 (s, 1 H), 7.51–7.43 (m, 2 H), 7.41 Methyl 3-Oxo-2-phenyl-3-(phenylamino)propanoate (4a): Off-
(dd, J = 7.6, 1.6 Hz, 1 H), 7.33 (td, J = 8.2, 1.7 Hz, 1 H), 7.25 (dd, J = white solid (126 mg, 93 % yield); m.p. 102–104 °C. 1H NMR
7.4, 1.4 Hz, 2 H), 7.00 (td, J = 7.5, 1.0 Hz, 1 H), 6.94 (d, J = 8.2 Hz, 1
H), 4.89 (s, 1 H), 4.24 (q, J = 7.1 Hz, 2 H), 3.86 (s, 3 H), 1.25 (t, J = J = 6.6 Hz, 2 H), 7.40–7.32 (m, 3 H), 7.29 (t, J = 7.9 Hz, 2 H), 7.10 (d,
7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.8, 165.9, 156.8, J = 7.4 Hz, 1 H), 4.66 (d, J = 1.3 Hz, 1 H), 3.78 (s, 3 H) ppm. 13C NMR
136.5, 130.2, 129.9, 129.4, 129.0, 122.9, 121.5, 121.2, 111.4, 62.0, 55.9, (100 MHz, CDCl3): δ = 171.7, 165.2, 137.5, 133.9, 129.3, 129.1, 128.6,
(400 MHz, CDCl3): δ = 9.00 (s, 1 H), 7.51 (d, J = 7.9 Hz, 2 H), 7.45 (d,
54.0, 14.2 ppm. IR (film): ν = 3308, 3125, 2940, 2831, 2710, 1735,
128.3, 124.8, 120.1, 58.9, 53.1 ppm. IR (film): ν = 3288, 3064, 2951,
˜
˜
1665, 1603, 1543, 1493, 1462, 1399, 1365, 1248, 1213, 1228, 1158,
1093, 1031, 839, 826, 775, 754 cm–1. HRMS (ESI): calcd. for
C18H19ClNO4 [M + H]+ 348.1003; found 348.1000.
2831, 1750, 1652, 1598, 1535, 1496, 1444, 1362, 1310, 1274, 1243,
1207, 1159, 1075, 1009, 986, 774, 737 cm–1. HRMS (ESI): calcd. for
C16H16NO3 [M + H]+ 270.1130; found 270.1136.
Ethyl
3-[(4-Chlorophenyl)amino]-2-(3,4-dimethoxyphenyl)-3- Methyl 3-Oxo-2-phenyl-3-(p-tolylamino)propanoate (4b): White
oxopropanoate (3e): White solid (172 mg, 91 % yield); m.p. 125–
solid (135 mg, 95 % yield); m.p. 148–150 °C. 1H NMR (400 MHz,
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Full Paper
CDCl3): δ = 8.91 (s, 1 H), 7.46 (dd, J = 7.9, 1.5 Hz, 2 H), 7.42–7.32 (m,
5 H), 7.10 (d, J = 8.3 Hz, 2 H), 4.66 (s, 1 H), 3.79 (s, 3 H), 2.30 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 171.6, 165.1, 135.0, 134.4,
134.0, 129.5, 129.3, 128.6, 128.3, 120.2, 58.9, 53.1, 21.0 ppm. IR (film):
(d, JC,F = 22.1 Hz), 58.55, 53.22 ppm. IR (film): ν = 3425, 3309, 2830,
˜
2716, 1741, 1675, 1605, 1498, 1355, 1301, 1221, 1199, 1154, 1024,
877, 825, 773, 728 cm–1. HRMS (ESI): calcd. for C16H14ClFNO3 [M +
H]+ 322.0646; found 322.0643.
ν = 3342, 2954, 2716, 1753, 1656, 1539, 1363, 1270, 1208, 1156,
˜
Methyl 3-Oxo-2-phenyl-3-{[2-(trifluoromethyl)phenyl]amino}-
propanoate (4i): White solid (117 mg, 69 % yield); m.p. 105–107 °C.
1H NMR (400 MHz, CDCl3): δ = 9.20 (s, 1 H), 8.21 (d, J = 8.3 Hz, 1 H),
7.59 (d, J = 7.9 Hz, 1 H), 7.54–7.46 (m, 3 H), 7.43–7.35 (m, 3 H), 7.20
(t, J = 7.7 Hz, 1 H), 4.71 (s, 1 H), 3.81 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 171.1, 165.7, 135.0, 133.13 (d, JC,F = 47.2 Hz), 129.5,
1012, 816, 774, 708 cm–1. HRMS (ESI): calcd. for C17H18NO3 [M + H]+
284.1287; found 284.1293.
Methyl 3-(Mesitylamino)-3-oxo-2-phenylpropanoate (4c): White
solid (126 mg, 81 % yield); m.p. 151–153 °C. 1H NMR (400 MHz,
CDCl3): δ = 8.03 (s, 1 H), 7.50 (d, J = 6.9 Hz, 2 H), 7.42–7.32 (m, 3
H), 6.82 (s, 2 H), 4.72 (s, 1 H), 3.79 (s, 3 H), 2.22 (s, 3 H), 2.03 (s, 6 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 171.3, 165.7, 137.0, 135.0,
134.1, 130.7, 129.2, 128.9, 128.5, 128.3, 58.9, 52.9, 21.0, 18.2 ppm. IR
128.9, 128.3, 126.43–125.88 (m), 124.8, 124.2, 122.5, 120.56 (d, JC,F
=
29.9 Hz), 59.2, 53.2 ppm. IR (film): ν = 3426, 3270, 2956, 2831, 2716,
˜
1749, 1659, 1600, 1531, 1455, 1363, 1321, 1277, 1215, 1163, 1117,
(film): ν = 3347, 3261, 2956, 2831, 2717, 1750, 1730, 1643, 1596, 1060, 1036, 989, 772, 710 cm–1. HRMS (ESI): calcd. for C17H15F3NO3
˜
1437, 1363, 1249, 1255, 1171, 1015, 842, 775, 731, 703 cm–1. HRMS [M + H]+ 338.1004; found 338.1007.
(ESI): calcd. for C19H22NO3 [M + H]+ 312.1600; found 312.1605.
Methyl 3-[(4-Acetylphenyl)amino]-3-oxo-2-phenylpropanoate
Methyl 3-[(4-Methoxyphenyl)amino]-3-oxo-2-phenylpropano-
(4j): White solid (139 mg, 89 % yield); m.p. 113–115 °C. 1H NMR
(400 MHz, CDCl3): δ = 9.41 (s, 1 H), 7.90 (d, J = 8.7 Hz, 2 H), 7.63 (d,
ate (4d): Light brown solid (135 mg, 90 % yield); m.p. 132–133 °C.
1H NMR (400 MHz, CDCl3): δ = 8.90 (s, 1 H), 7.45–7.27 (m, 7 H), 6.80 J = 8.7 Hz, 2 H), 7.47–7.42 (m, 2 H), 7.39–7.32 (m, 3 H), 4.70 (s, 1 H),
(d, J = 9.0 Hz, 2 H), 4.64 (s, 1 H), 3.76 (s, 3 H), 3.74 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 171.5, 165.1, 156.6, 133.9, 130.6, 129.2,
3.79 (s, 3 H), 2.55 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 197.1,
171.3, 165.6, 141.9, 133.5, 133.2, 129.7, 129.3, 128.7, 128.3, 119.4,
128.5, 128.4, 121.9, 114.1, 58.7, 55.5, 53.0 ppm. IR (film): ν = 3343, 58.8, 53.2, 26.5 ppm. IR (film): ν = 3323, 2955, 2834, 1748, 1680,
˜
˜
3078, 2953, 2834, 1752, 1657, 1608, 1545, 1511, 1438, 1409, 1665, 1598, 1522, 1500, 1435, 1403, 1362, 1271, 1245, 1208, 1155,
1361, 1320, 1299, 1272, 1249, 1208, 1154, 1034, 971, 831, 757,
1014, 976, 848, 819, 775, 741, 700 cm–1. HRMS (ESI): calcd. for
711 cm–1. HRMS (ESI): calcd. for C17H17NNaO4 [M + H]+ 322.1055; C18H18NO4 [M + H]+ 312.1236; found 312.1240.
found 322.1062.
Methyl 3-[(4-Cyanophenyl)amino]-3-oxo-2-phenylpropanoate
Methyl 3-[(3,4-Dimethoxyphenyl)amino]-3-oxo-2-phenylprop-
anoate (4e): Off-white solid (129 mg, 78 % yield); m.p. 125–127 °C.
1H NMR (400 MHz, CDCl3): δ = 8.94 (s, 1 H), 7.45 (d, J = 6.6 Hz, 2 H),
7.42–7.29 (m, 4 H), 6.89 (dd, J = 8.6, 2.3 Hz, 1 H), 6.77 (d, J = 8.6 Hz,
(4k): White solid (126 mg, 85 % yield); m.p. 144–146 °C. 1H NMR
(400 MHz, CDCl3): δ = 9.44 (s, 1 H), 7.67 (d, J = 8.6 Hz, 2 H), 7.58 (d,
J = 8.6 Hz, 2 H), 7.46–7.34 (m, 5 H), 4.67 (s, 1 H), 3.81 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 171.6, 165.6, 141.5, 133.4, 133.3,
1 H), 4.64 (s, 1 H), 3.83 (s, 3 H), 3.83 (s, 3 H), 3.79 (s, 3 H) ppm. 13C 129.5, 128.9, 128.1, 120.0, 118.9, 107.6, 58.7, 53.3 ppm. IR (film): ν =
˜
NMR (100 MHz, CDCl3): δ = 171.7, 165.2, 149.0, 146.1, 133.9, 131.2,
3426, 3318, 3198, 3120, 2954, 2223, 1737, 1681, 1596, 1536, 1503,
129.3, 128.6, 128.3, 111.9, 111.2, 104.8, 58.8, 56.1, 55.9, 53.1 ppm. IR
1405, 1360, 1324, 1296, 1251, 1153, 1025, 851, 774, 700 cm–1. HRMS
(film): ν = 3431, 3286, 2954, 2832, 1747, 1650, 1602, 1518, 1459, (ESI): calcd. for C17H15N2O3 [M + H]+ 295.1083; found 295.1072.
˜
1363, 1266, 1229, 1199, 1168, 1133, 1024, 773, 702 cm–1. HRMS
Isopropyl 3-[(3-Chloro-4-fluorophenyl)amino]-3-oxo-2-phenyl-
propanoate (4l): White solid (146 mg, 83 % yield); m.p. 105–107 °C.
(ESI): calcd. for C18H20NO5 [M + H]+ 330.1341; found 330.1346.
Methyl 3-[(4-Bromophenyl)amino]-3-oxo-2-phenylpropanoate 1H NMR (400 MHz, CDCl3): δ = 9.32 (s, 1 H), 7.71 (dd, J = 6.6, 2.6 Hz,
(4f): White solid (138 mg, 79 % yield); m.p. 51–53 °C. 1H NMR
(400 MHz, CDCl3): δ = 9.09 (s, 1 H), 7.51–7.31 (m, 9 H), 4.64 (s, 1 H),
3.80 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.9, 165.2, 136.6,
1 H), 7.44–7.30 (m, 6 H), 7.04 (t, J = 8.8 Hz, 1 H), 5.17–5.06 (m, 1 H),
4.57 (s, 1 H), 1.31 (d, J = 6.3 Hz, 3 H), 1.19 (d, J = 6.3 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.9, 165.6, 156.2, 153.7, 134.23 (d,
133.7, 132.1, 129.4, 128.8, 128.2, 121.7, 117.4, 58.8, 53.3 ppm. IR JC,F = 3.4 Hz), 133.9, 128.64 (d, JC,F = 133.8 Hz), 128.6, 122.3, 121.16
(film): ν = 3443, 3345, 2952, 2831, 2716, 1753, 1662, 1602, 1537, (d, JC,F = 18.6 Hz), 119.80 (d, JC,F = 6.9 Hz), 116.62 (d, JC,F = 22.1 Hz),
˜
1486, 1391, 1362, 1311, 1209, 1157, 1070, 1009, 972, 823, 775,
70.4, 58.8, 21.7, 21.4 ppm. IR (film): ν = 3266, 3096, 2990, 2813,
˜
725 cm–1. HRMS (ESI): calcd. for C16H15BrNO3 [M + H]+ 348.0235; 1726, 1673, 1599, 1501, 1383, 1350, 1304, 1258, 1211, 1169, 1105,
found 348.0232.
908, 873, 823, 774, 733 cm–1. HRMS (ESI): calcd. for C18H18ClFNO3
[M + H]+ 350.0959; found 350.0964.
Methyl 3-Oxo-2-phenyl-3-[(2,4,5-trichlorophenyl)amino]prop-
anoate (4g): White solid (153 mg, 82 % yield); m.p. 100–102 °C. H
1
Ethyl 3-[(4-Methoxyphenyl)amino]-3-oxo-2-(m-tolyl)propanoate
1
NMR (400 MHz, CDCl3): δ = 9.64 (s, 1 H), 8.59 (d, J = 4.7 Hz, 1 H),
(4m): Off-white solid (117 mg, 71 % yield); m.p. 51–53 °C. H NMR
7.48–7.37 (m, 6 H), 4.69 (s, 1 H), 3.82 (s, 3 H) ppm. 13C NMR (400 MHz, CDCl3): δ = 8.91 (s, 1 H), 7.47–7.39 (m, 2 H), 7.25 (d, J =
(100 MHz, CDCl3): δ = 171.4, 165.5, 133.9, 133.3, 131.9, 129.9, 129.6,
4.7 Hz, 3 H), 7.14 (dd, J = 6.6, 2.9 Hz, 1 H), 6.87–6.76 (m, 2 H), 4.58
129.0, 128.2, 127.8, 122.5, 121.9, 59.0, 53.4 ppm. IR (film): ν = 3430, (s, 1 H), 4.32–4.16 (m, 2 H), 3.77 (s, 3 H), 2.35 (s, 3 H), 1.27 (t, J =
˜
3208, 3091, 2995, 2831, 1739, 1662, 1601, 1517, 1457, 1361, 1316,
1296, 1272, 1211, 1152, 1080, 1013, 895, 774, 714 cm–1. HRMS (ESI):
calcd. for C16H13Cl3NO3 [M + H]+ 371.9961; found 371.9960.
7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.47, 165.19,
156.65, 139.08, 134.05, 130.78, 129.29, 129.12, 128.96, 125.11,
121.81, 114.17, 62.21, 58.92, 55.57, 21.55, 14.08 ppm. IR (film): ν =
˜
3293, 2981, 2832, 1740, 1650, 1602, 1531, 1364, 1314, 1254, 1189,
1167, 1031, 823, 774 cm–1. HRMS (ESI): calcd. for C19H22NO4 [M +
H]+ 328.1549; found 328.1543.
Methyl
3-[(3-Chloro-4-fluorophenyl)amino]-3-oxo-2-phenyl-
propanoate (4h): White solid (147 mg, 91 % yield); m.p. 141–
143 °C. 1H NMR (400 MHz, CDCl3): δ = 9.17 (s, 1 H), 7.68 (dd, J =
6.5, 2.5 Hz, 1 H), 7.48–7.23 (m, 6 H), 7.03 (t, J = 8.8 Hz, 1 H), 4.63 (s,
1 H), 3.79 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.6, 165.5,
155.0 (d, JC,F = 246.5 Hz), 134.1 (d, JC,F = 3.3 Hz), 133.5, 129.4, 128.7,
128.2, 122.4, 121.2 (d, JC,F = 18.6 Hz), 119.9 (d, JC,F = 6.9 Hz), 116.6
Ethyl
3-[(4-Cyanophenyl)amino]-2-(3,4-dimethoxyphenyl)-3-
oxopropanoate (4n): White solid (155 mg, 84 % yield); m.p. 51–
53 °C. 1H NMR (400 MHz, CDCl3): δ = 9.35 (s, 1 H), 7.67 (d, J = 8.7 Hz,
2 H), 7.59 (d, J = 8.7 Hz, 2 H), 6.97 (d, J = 6.6 Hz, 2 H), 6.86 (d, J =
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© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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1
8.9 Hz, 1 H), 4.58 (s, 1 H), 4.27 (dddd, J = 17.9, 10.8, 7.2, 3.7 Hz, 2
51–53 °C. H NMR (400 MHz, CDCl3): δ = 9.37 (s, 1 H), 7.59–7.46 (m,
H), 3.88 (s, 3 H), 3.87 (s, 3 H), 1.29 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR 2 H), 7.32 (m, 4 H), 6.99 (dd, J = 8.6, 2.4 Hz, 1 H), 6.78–6.71 (m, 1
(100 MHz, CDCl3): δ = 171.18, 166.07, 149.51, 149.46, 141.58, 133.30,
H), 4.33 (d, JH,P = 23.4 Hz, 1 H), 4.19–4.02 (m, 3 H), 4.01–3.89 (m, 1
H), 3.84 (s, 3 H), 3.82 (s, 3 H), 1.27 (t, J = 6.9 Hz, 3 H), 1.19 (t, J =
125.76, 120.22, 119.95, 118.84, 111.59, 111.37, 107.52, 62.53, 58.41,
56.07, 56.00, 14.05 ppm. IR (film): ν = 3300, 2997, 2940, 2833, 2234, 6.9 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 164.12, 148.97 (d,
˜
1734, 1666, 1593, 1515, 1467, 1409, 1364, 1304, 1257, 1207, 1181,
1146, 1024, 877, 829, 776 cm–1. HRMS (ESI): calcd. for C20H21N2O5
[M + H]+ 369.1450; found 369.1438.
JC,P = 7.4 Hz), 145.86 (d, JC,P = 8.9 Hz), 133.21–130.76 (m), 129.63 (d,
JC,P = 6.9 Hz), 128.91 (d, JC,P = 3.0 Hz), 128.2, 111.7, 111.23 (d, JC,P
=
3.7 Hz), 104.5, 64.27 (d, JC,P = 7.1 Hz), 63.26 (d, JC,P = 7.1 Hz), 56.1,
55.9, 54.00 (d, JC,P = 131.2 Hz), 19.40–12.79 (m) ppm. IR (film): ν =
˜
Ethyl 3-[(4-Acetylphenyl)amino]-2-(4-chlorophenyl)-3-oxoprop-
anoate (4o): Off-white solid (166 mg, 92 % yield); m.p. 51–53 °C.
1H NMR (400 MHz, CDCl3): δ = 9.53 (s, 1 H), 7.90 (d, J = 8.4 Hz, 2 H),
7.63 (d, J = 8.1 Hz, 2 H), 7.35 (dd, J = 22.8, 8.0 Hz, 4 H), 4.64 (s, 1
H), 4.34–4.19 (m, 2 H), 2.56 (s, 3 H), 1.27 (t, J = 6.9 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 197.2, 170.6, 165.3, 141.8, 134.7,
133.3, 132.1, 129.7, 129.7, 129.3, 119.4, 62.6, 58.1, 26.5, 14.0 ppm. IR
3427, 3264, 2962, 2831, 1674, 1604, 1514, 1450, 1363, 1233, 1140,
1024, 979, 774 cm–1. HRMS (ESI): calcd. for C20H27NO6P [M + H]+
408.1576; found 408.1574.
Diethyl
{2-[(4-Chlorophenyl)amino]-2-oxo-1-phenylethyl}-
1
phosphonate (6e): Light brown semisolid (147 mg, 77 % yield). H
NMR (400 MHz, CDCl3): δ = 9.53 (s, 1 H), 7.52 (dd, J = 6.2, 1.5 Hz, 2
H), 7.49–7.41 (m, 2 H), 7.38–7.29 (m, 3 H), 7.24–7.11 (m, 2 H), 4.35
(d, JH,P = 23.4 Hz, 1 H), 4.17–4.02 (m, 3 H), 4.01–3.93 (m, 1 H), 1.27
(t, J = 7.0 Hz, 3 H), 1.19 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 164.5, 136.6, 131.7, 131.6, 129.61 (d, JC,P = 6.8 Hz), 129.3,
128.9, 128.28 (d, JC,P = 2.6 Hz), 121.1, 63.90 (dd, JC,P = 110.3, 7.1 Hz),
(film): ν = 3337, 2987, 2831, 2713, 1725, 1669, 1594, 1526, 1489,
˜
1407, 1363, 1274, 1210, 1176, 1145, 1094, 1019, 836, 775 cm–1
.
HRMS (ESI): calcd. for C19H19ClNO4 [M + H]+ 360.1003; found
360.1003.
Diethyl
[2-Oxo-1-phenyl-2-(phenylamino)ethyl]phosphonate
(6a): White solid (124 mg, 71 % yield); m.p. 119–121 °C. 1H NMR
(400 MHz, CDCl3): δ = 9.37 (s, 1 H), 7.54 (d, J = 7.9 Hz, 4 H), 7.40–
7.30 (m, 3 H), 7.27 (dd, J = 9.8, 6.2 Hz, 2 H), 7.07 (t, J = 7.2 Hz, 1 H),
4.31 (dd, JH,P = 23.3 Hz, JH,H = 2.5 Hz, 1 H), 4.17–4.01 (m, 3 H), 3.89
(m, 1 H), 1.27 (t, J = 7.1 Hz, 3 H), 1.16 (t, J = 7.0 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 164.4, 138.0, 131.82 (d, JC,P = 7.4 Hz),
129.62 (d, JC,P = 6.9 Hz), 129.0, 128.9, 128.2, 124.5, 120.0, 64.22 (d,
54.01 (d, JC,P = 131.3 Hz), 16.38 (t, JC,P = 5.5 Hz) ppm. IR (film): ν =
˜
3458, 3240, 2984, 2931, 2831, 1673, 1601, 1545, 1493, 1400, 1365,
1232, 1206, 1051, 1025, 973, 960, 832, 775, 701 cm–1. HRMS (ESI):
calcd. for C18H22ClNO4P [M + H]+ 382.0975; found 382.0973.
Diethyl
{2-[(4-Bromophenyl)amino]-2-oxo-1-phenylethyl}-
phosphonate (6f): White solid (148 mg, 69 % yield); m.p. 176–
1
178 °C. H NMR (400 MHz, CDCl3): δ = 9.50 (s, 1 H), 7.55–7.49 (m, 2
JC,P = 6.9 Hz), 63.29 (d, JC,P = 7.2 Hz), 54.11 (d, JC,P = 130.9 Hz), 16.40
H), 7.45–7.40 (m, 2 H), 7.39–7.30 (m, 5 H), 4.32 (d, JH,P = 23.4 Hz, 1
H), 4.18–4.03 (m, 3 H), 4.00–3.91 (m, 1 H), 1.28 (t, J = 7.1 Hz, 3 H),
1.19 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 137.1,
131.9, 131.64 (d, JC,P = 7.5 Hz), 129.62 (d, JC,P = 6.9 Hz), 128.96 (d,
JC,P = 2.0 Hz), 128.3, 121.5, 117.0, 64.45 (d, JC,P = 7.0 Hz), 63.35 (d,
JC,P = 7.3 Hz), 54.08 (d, JC,P = 130.9 Hz), 20.85–14.85 (m) ppm. IR
(d, JC,P = 6.0 Hz), 16.31 (d, JC,P = 5.8 Hz) ppm. IR (film): ν = 3359,
˜
2980, 2934, 2831, 1680, 1598, 1521, 1495, 1439, 1361, 1325, 1294,
1236, 1163, 1098, 1034, 970, 944, 806, 757, 732 cm–1. HRMS (ESI):
calcd. for C18H23NO4P [M + H]+ 348.1365; found 348.1369.
Diethyl
[2-Oxo-1-phenyl-2-(p-tolylamino)ethyl]phosphonate
(6b): White solid (143 mg, 79 % yield); m.p. 122–124 °C. 1H NMR
(400 MHz, CDCl3): δ = 9.20 (s, 1 H), 7.56–7.49 (m, 2 H), 7.43 (d, J =
8.4 Hz, 2 H), 7.39–7.29 (m, 3 H), 7.09 (d, J = 8.3 Hz, 2 H), 4.24 (d,
JH,P = 23.4 Hz, 1 H), 4.18–4.07 (m, 2 H), 4.06–3.98 (m, 1 H), 3.86 (m,
1 H), 2.29 (s, 3 H), 1.28 (t, J = 7.1 Hz, 3 H), 1.15 (d, J = 7.1 Hz, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 164.1, 135.4, 134.2, 131.89 (d,
(film): ν = 3426, 3243, 3182, 3112, 3058, 2984, 2831, 2713,
˜
1674, 1602, 1542, 1498, 1392, 1362, 1323, 1233, 1050, 1025, 973,
775 cm–1. HRMS (ESI): calcd. for C18H22BrNO4P [M + H]+ 426.0470;
found 426.0461.
Diethyl
{2-[(3-Chloro-4-fluorophenyl)amino]-2-oxo-1-phenyl-
ethyl}phosphonate (6g): White solid (142 mg, 71 % yield); m.p.
1
J
C,P = 7.2 Hz), 129.63 (d, JC,P = 6.9 Hz), 129.5, 128.93 (d, JC,P = 1.9 Hz),
128.18 (d, JC,P = 2.6 Hz), 120.1, 64.17 (d, JC,P = 7.0 Hz), 63.28 (d,
C,P = 7.1 Hz), 54.12 (d, JC,P = 130.4 Hz), 21.0, 16.43 (d, JC,P = 6.0 Hz),
180–182 °C. H NMR (400 MHz, CDCl3): δ = 9.84 (d, JH,P = 15.1 Hz,
1 H), 7.69 (d, J = 6.5 Hz, 1 H), 7.55 (d, J = 6.2 Hz, 2 H), 7.40–7.27 (m,
J
4 H), 6.94 (td, J = 8.8, 4.6 Hz, 1 H), 4.46 (dd, JH,P = 23.4 Hz, JH,H
=
16.30 (d, JC,P = 5.8 Hz) ppm. IR (film): ν = 3426, 3256, 3122, 2982,
˜
8.5 Hz, 1 H), 4.25–4.01 (m, 4 H), 1.29 (dt, J = 10.0, 7.0 Hz, 6 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 164.7, 155.9, 153.4, 134.9, 131.65 (d,
J = 8.3 Hz), 129.59 (d, J = 6.8 Hz), 128.9, 128.3, 121.8, 120.88 (d,
JC,F = 17.4 Hz), 119.25 (d, JC,P = 7.1 Hz), 116.33 (d, JC,F = 22.2 Hz),
2832, 1677, 1605, 1515, 1362, 1236, 1161, 1054, 1031, 964, 819,
776 cm–1. HRMS (ESI): calcd. for C19H25NO4P [M + H]+ 362.1521;
found 362.1521.
64.73 (d, JC,P = 6.6 Hz), 63.35 (d, JC,P = 7.4 Hz), 53.91 (d, JC,P
=
Diethyl
{2-[(4-Methoxyphenyl)amino]-2-oxo-1-phenylethyl}-
131.9 Hz), 16.48–16.38 (m) ppm. IR (film): ν = 3254, 3063, 2831,
phosphonate (6c): White solid (157 mg, 83 % yield); m.p. 129–
131 °C. 1H NMR (400 MHz, CDCl3): δ = 9.20 (s, 1 H), 7.53 (dd, J =
6.3, 1.3 Hz, 2 H), 7.45 (d, J = 8.5 Hz, 2 H), 7.38–7.29 (m, 3 H), 6.84–
6.78 (m, 2 H), 4.26 (d, JH,P = 23.3 Hz, 1 H), 4.17–3.97 (m, 3 H), 3.89
(m, 1 H), 3.76 (s, 3 H), 1.28 (t, J = 7.1 Hz, 3 H), 1.15 (t, J = 7.1 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 164.1, 156.5, 131.95 (d,
JC,P = 7.3 Hz), 131.1, 129.61 (d, JC,P = 6.9 Hz), 128.9, 128.2, 121.7,
114.1, 64.18 (d, JC,P = 7.0 Hz), 63.25 (d, JC,P = 7.2 Hz), 55.5, 53.97 (d,
˜
2710, 1686, 1606, 1556, 1498, 1395, 1363, 1236, 1215, 1034, 978,
774 cm–1. HRMS (ESI): calcd. for C18H21ClFNO4P [M + H]+ 400.0881;
found 400.0874.
Diethyl {2-[(4-Acetylphenyl)amino]-2-oxo-1-phenylethyl}phos-
phonate (6h): White solid (127 mg, 65 % yield); m.p. 180–182 °C.
1H NMR (400 MHz, CDCl3): δ = 9.98 (d, J = 8.3 Hz, 1 H), 7.77 (dd, J =
8.7, 3.5 Hz, 2 H), 7.58 (dd, J = 10.8, 3.7 Hz, 4 H), 7.41–7.31 (m, 3 H),
4.54 (dd, JH,P = 23.5 Hz, JH,H = 6.3 Hz, 1 H), 4.24–4.02 (m, 4 H), 2.51
(d, J = 1.5 Hz, 3 H), 1.32–1.22 (m, 6 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 197.1, 165.1, 142.6, 132.7, 131.6, 129.63 (d, JC,P = 6.8 Hz),
129.5, 128.84 (d, JC,P = 6.3 Hz), 128.3, 119.0, 64.63 (d, JC,P = 6.7 Hz),
63.39 (d, JC,P = 7.3 Hz), 54.06 (d, JC,P = 133.6 Hz), 26.4, 16.4,
JC,P = 130.5 Hz), 16.42 (d, JC,P = 6.1 Hz), 16.31 (d, JC,P = 5.9 Hz) ppm.
IR (film): ν = 3426, 3262, 3208, 3134, 3076, 2981, 2926, 2832, 1679,
˜
1605, 1553, 1510, 1412, 1298, 1246, 1213, 1179, 1159, 1045, 974,
830, 759 cm–1. HRMS (ESI): calcd. for C19H25NO5P [M + H]+ 378.1470;
found 378.1471.
Diethyl {2-[(3,4-Dimethoxyphenyl)amino]-2-oxo-1-phenylethyl}-
phosphonate (6d): Light brown solid (139 mg, 68 % yield); m.p.
16.3 ppm. IR (film): ν = 3432, 3254, 3188, 3107, 3059, 2979,
2831, 1679, 1600, 1541, 1362, 1270, 1240, 1211, 1024, 975, 840,
˜
Eur. J. Org. Chem. 2017, 4035–4043
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© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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774 cm–1. HRMS (ESI): calcd. for C20H25NO5P [M + H]+ 390.1470;
found 390.1465.
[5]
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Diethyl {1-(4-Chlorophenyl)-2-[(4-chlorophenyl)amino]-2-oxo-
ethyl}phosphonate (6i): White solid (163 mg, 78 % yield); m.p. 51–
1
53 °C. H NMR (400 MHz, CDCl3): δ = 9.63 (s, 1 H), 7.47 (dd, J = 8.6,
2.1 Hz, 2 H), 7.45–7.40 (m, 2 H), 7.33 (d, J = 8.4 Hz, 2 H), 7.20–7.12
(m, 2 H), 4.41 (d, JH,P = 23.7 Hz, 1 H), 4.22–4.04 (m, 4 H), 1.28 (m, 6
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 164.2, 136.6, 134.30 (d,
JC,P = 3.4 Hz), 131.00 (d, JC,P = 6.8 Hz), 130.27 (d, JC,P = 8.2 Hz),
129.4, 128.97 (d, JC,P = 2.1 Hz), 128.9, 121.0, 64.63 (d, JC,P = 6.9 Hz),
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[10]
63.46 (d, JC,P = 7.3 Hz), 53.15 (d, JC,P = 131.9 Hz), 16.46 (d, JC,P
=
4.1 Hz), 16.41 (d, JC,P = 4.3 Hz) ppm. IR (film): ν = 3425, 3243, 3185,
˜
3117, 3060, 2985, 2831, 2713, 1676, 1601, 1545, 1490, 1396, 1363,
1234, 1207, 1094, 1049, 1025, 974, 832, 776 cm–1. HRMS (ESI): calcd.
for C18H21Cl2NO4P [M + H]+ 416.0585; found 416.0579.
[11]
[12]
Diethyl {1-[(4-Chlorophenyl)amino]-1-oxo-3-phenylpropan-2-
yl}phosphonate (6j): White solid (147 mg, 74 % yield); m.p. 147–
149 °C. 1H NMR (400 MHz, CDCl3): δ = 9.55 (s, 1 H), 7.30 (d, J =
8.8 Hz, 2 H), 7.26–7.15 (m, 5 H), 7.01 (d, J = 8.8 Hz, 2 H), 4.30–4.01
(m, 4 H), 3.48–3.35 (m, 2 H), 3.14–3.01 (m, 1 H), 1.38 (t, J = 7.1 Hz,
3 H), 1.30 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
165.4, 139.04 (d, JC,P = 14.1 Hz), 136.9, 128.8, 128.7, 128.6, 128.5,
126.7, 120.8, 64.06 (d, JC,P = 6.3 Hz), 62.37 (d, JC,P = 7.0 Hz), 48.97
(d, JC,P = 127.9 Hz), 32.86 (d, JC,P = 4.9 Hz), 16.55 (d, JC,P = 5.9 Hz),
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16.44 (d, JC,P = 6.2 Hz) ppm. IR (film): ν = 3262, 3121, 3068, 2983,
˜
1690, 1605, 1547, 1492, 1398, 1359, 1250, 1222, 1088, 1050, 1026,
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[20]
Methyl 3-(9H-Carbazol-9-yl)-3-oxo-2-phenylpropanoate (8a):
White solid (109 mg, 63 % yield); m.p. 121–123 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.19 (d, J = 8.2 Hz, 2 H), 7.99 (d, J = 7.7 Hz,
2 H), 7.52–7.36 (m, 9 H), 5.80 (s, 1 H), 3.81 (s, 3 H) ppm. 13C NMR
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˜
[25]
[26]
[27]
[28]
2831, 2716, 1725, 1667, 1595, 1494, 1445, 1368, 1334, 1255, 1236,
1199, 1161, 1018, 982, 865, 826, 775, 753 cm–1. HRMS (ESI): calcd.
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Acknowledgments
C. S. gratefully acknowledges the University Grants Commission,
New Delhi, India for financial support [MRP-M (SC)]. K. R. grate-
fully acknowledges the University Grants Commission (UGC) for
a Senior Research Fellowship. We thank the Central Instrumen-
tation Facility, Pondicherry University, for the NMR spectra and
the Department of Science and Technology-Fund for Improve-
ment of Science and Technology (DST-FIST) for the ESI-MS and
single-crystal X-ray diffraction facility.
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Keywords: Carbenes · Carbonylation · Diazo compounds ·
Amides · Nucleophilic addition
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Received: April 26, 2017
Eur. J. Org. Chem. 2017, 4035–4043
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© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim