Synthesis of phosphorylated enaminoketones and their application in the preparation of trifluoromethyl-functionalized 2-phosphonopyrroles

Article abstract of DOI:10.1080/10426507.2011.590168

New trifluoromethyl-functionalized 2-phosphonopyrroles were obtained by 5-exotrig cyclization of trifluoromethyl and phosphonyl functionalized enaminoketones. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2011.590168

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Phosphorus, Sulfur, and Silicon and the
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Synthesis of Phosphorylated
Enaminoketones and Their Application
in the Preparation of Trifluoromethyl-
Functionalized 2-Phosphonopyrroles
Dariusz Cal a & Piotr Zagórski a
a Department of Organic and Applied Chemistry, University of Łódź,
Łódź, Poland
Published online: 31 Oct 2011.
To cite this article: Dariusz Cal & Piotr Zagrski (2011) Synthesis of Phosphorylated Enaminoketones
and Their Application in the Preparation of Trifluoromethyl-Functionalized 2-Phosphonopyrroles,
Phosphorus, Sulfur, and Silicon and the Related Elements, 186:12, 2295-2302, DOI:
10.1080/10426507.2011.590168
To link to this article: http://dx.doi.org/10.1080/10426507.2011.590168
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Phosphorus, Sulfur, and Silicon, 186:2295–2302, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.590168
SYNTHESIS OF PHOSPHORYLATED ENAMINOKETONES
AND THEIR APPLICATION IN THE PREPARATION
OF TRIFLUOROMETHYL-FUNCTIONALIZED
2-PHOSPHONOPYRROLES
Dariusz Cal and Piotr Zago´rski
Department of Organic and Applied Chemistry, University of Ło´dz´, Ło´dz´, Poland
GRAPHICAL ABSTRACT
Ph
O
H
N
Ph
P(OEt)2
H
O
P(OEt)2
R
Ph
R
N
O
O
N
R
F3C
Base
F3C
Cl
P(OEt)2
F3C
O
R = Ph, COOEt
Abstract New trifluoromethyl-functionalized 2-phosphonopyrroles were obtained by 5-exotrig
cyclization of trifluoromethyl and phosphonyl functionalized enaminoketones.
Keywords 2-Phosphonopyrroles; trifluoromethyl pyrroles; 5-exotrig cyclization trifluo-
romethyl enaminoketones; β-enaminoesters
INTRODUCTION
Heterocycles bearing a trifluoromethyl group have attracted much attention in phar-
maceutical sciences becausetheintroductionof fluorineintoanorganiccompound cancause
important changes in the physical, chemical, and biological properties such as enhanced
hydrophobic binding and increased stability.1 It has been also shown that the presence of
a phosphonyl group can influence the biological functions of heterocyclic systems.2 Some
synthetic approaches to 2-phosphonopyrroles have already been reported3: (1) 1,3-dipolar
cycloaddtion of nitrile ylides or carbanions derived from isocyanomethylphosphonate or
N-phosphonomethylimines to alkynes or alkenes containing a suitable leaving group,4 (2)
direct phosphonylation of pyrrole salts with chlorophosphates,2,5 (3) phosphonylation of
pyrrole with dimethyl phosphite and Mn(OAc)3 · 2 H2O as coupling agent,6 (4) thermol-
ysis of cyclic phosphonates in N-methylpyrrole,7 (5) aromatization of the corresponding
Received 8 April 2011; accepted 18 May 2011.
This research project was supported by the Faculty of Chemistry, University of Ło´dz´.
Address correspondence to Dariusz Cal, Department of Organic and Applied Chemistry, University of Ło´dz´,
Tamka 12, PL 91-403 Ło´dz´, Poland. E-mail: darekcal@uni.lodz.pl
2295

´
D. CAL AND P. ZAGORSKI
2296
2-phosphonate NH-pyrrolidines using air,8 and (6) an excellent procedure, in which the key
step involves a ring-closing metathesis/oxidation sequence of dienes or enynes bearing an
amino and a phosphonyl function.9
RESULTS AND DISCUSSION
3-Chloro-4,4,4-trifluoro-2-phenylbutenal (1a), easily available (as a 40:60 E/Z mix-
ture) from the Vilsmeier reaction of 1,1,1-trifluoro-3-phenylacetone,10 is known to be
a versatile building block for the synthesis of both acyclic and cyclic trifluoromethyl-
functionalized compounds.11 This acroleine can be converted into enaminoketone by re-
action with N-benzylglycine ethyl ester. The resulting enaminoketone was cyclized to the
corresponding pyrrole containing trifluoromethyl and carboxylic group.12 In our present
work, we first make use of this acrolein and the phosphorus analogue of N-benzylglycinate
to prepare the enaminoketone 2a. Similarly enaminoketones 2b,c were prepared (Scheme 1,
Table 1).
O
Ph
P(OEt)2
O
N
R2
R1
Ph
R2
R1
H N
+
P(OEt)2
O
Cl
O
1
2
2a--c
1a
b
c
: R = CF3; R = Ph
1
2
: R = CF3; R = CO2Et
1
2
: R = CH3; R = Ph
Scheme 1
The enaminoketone 2a exists in the form of one diastereomer (only one signal
observed in both 31P and 19F NMR spectrum); its configuration (E or Z) was not determined,
however.
The enaminoketone 2b was isolated as 6:4 mixture of diastereomers (based on 19F
NMR and confirmed by 31P NMR spectroscopy). The enaminoketone 2c was obtained as
only one diastereomer (one signal in the 31P NMR spectrum), and its E configuration was
confirmed by the nuclear Overhauser effect spectroscopy (NOESY) correlation between the
vinylic and the methyl protons of the acetyl group. We tried to cyclize the enaminoketone
Table 1 Synthesis of enaminoketones 2a–c
2
R1
R2
Conditions
Yield (%)
a
b
c
CF3
CF3
CH3
Ph
COOEt
Ph
NEt3/Et2O, r.t., 96 h
THF, r.t., 48 h
NEt3/Et2O, r.t., 240 h
59
68
63
Note: r.t., room temperature.

SYNTHESIS OF PHOSPHORYLATED ENAMINOKETONES AND THEIR APPLICATION 2297
2a with NEt3 (3 eq.) in MeCN as a solvent by refluxing for 72 h but only the start-
ing enaminoketone was recovered. However, when we used hard basic conditions—NaH
(2 eq.), C6H6/dimethyl sulfoxide (DMSO)—which were also used for the cyclization of
nonphosphorylated enaminoketones,12 we obtained 2-phosphonopyrrole 3 and the dephos-
phorylated5a pyrrole 4 (Scheme 2).
Scheme 2
The structure of 3 was confirmed by a NOESY experiment, in which a correlation
between the H-5 of the pyrrole ring and the benzylic protons was observed. The structure
of 4 was confirmed by the heteronuclear multiple bond correlation (HMBC) experiment in
which the signal of the benzyl carbon atom correlates with the signals of the pyrrole protons
H-1 and H-5. In addition, the NOESY spectrum displays a correlation between the benzylic
protons and the protons H-1 and H-5 of the pyrrole ring, while no correlation between H-1
and H-5 of the pyrrole ring is observed. Thus only the products of 5-exotrig cyclization
have been obtained, and in contrast to nonphosphorylated enaminoketones,12 no 3-exotrig
cyclization products were found. From the reaction of enaminoketone 2b under the same
experimental conditions, only the dephosphorylated products of a 5-exotrig cyclization 5
and 6 were isolated (Scheme 3).
Scheme 3
The structure of these products was established by NOESY experiments, which
show a correlation between the benzylic protons and the two pyrrole protons and no
correlation between the two pyrrole protons. Since the presence of an electron-withdrawing
group (COOEt) may favor carbon–phosphorus bond cleavage under basic conditions,5a we

´
D. CAL AND P. ZAGORSKI
2298
examined the reaction of 2b under mild basic conditions using NEt3 (3 eq.) in MeCN
as solvent on refluxing for 20 h. Thus, the 2-phosphonopyrrole 7 was formed together
with enaminoester 8. The structure of pyrrole 7 was confirmed by the NOESY correlation
between H-2 of the pyrrole ring and the benzylic protons. The structure of enaminoester
8 was confirmed by the 1H NMR spectra. The characteristic coupling constant of the two
protons at the double bond is about 13 Hz that indicates the presence of the E-isomer
instead of the Z-isomer. This indication was confirmed by a NOESY experiment, in which
a correlation between the protons of two methylene groups attached to nitrogen and the
vinylic proton H-2 is observed. When we tried to cyclize enaminoketone 2c, which contains
a methyl group instead of a trifluoromethyl group, and mild basic conditions (NEt3 3 eq.,
MeCN, refluxing for 7 days) were applied, the unreacted substrate was almost quantitatively
recovered. However, when hard basic conditions were applied (NaH, 2 eq., C6H6/DMSO),
only the hydrolysis products 9, the known 2-acetylphenylacetaldehyde 10,13 and 43% of
unreacted substrate were obtained (Scheme 4).
Scheme 4
Thus in contrast to fluorinated or not phosphorylated12 enaminoketones in this case,
no pyrroles were formed.
CONCLUSION
In summary, we have presented a first synthetic approach to 2-phosphono-pyrroles
containing a trifluoromethyl group. The preparation requires enaminoketones which have
never been used previously as starting materials for the synthesis of 2-phosphonopyrroles.
Although the yields are low and the method failed for nonfluorinated enaminoketone 2c,
in case of 2b, it enabled the synthesis of trifluoromethyl and phosphonyl functionalized
enaminoester 8. As far as we know, the synthesis of this kind of compounds is still of great
interest for their synthetic and biological applications.14
EXPERIMENTAL
Melting points (mp) are uncorrected. NMR spectra were obtained with a Bruker
DPX 250, a Bruker Avance III 600, a Bruker Avance II Plus 700, a Varian Gemini 200,
and a Tesla BS 687 spectrometer operating at 600, 700, and 80 MHz for 1H (TMS); 151,
63, and 50 MHz for 13C; 235 and 565 MHz for 19F (CFCl3); and 101 and 80 MHz for
31P (H3PO4). Electrospray ionization-mass spectrometry (ESI-MS) spectra were recorded
with a Bruker Esquire-LC instrument. High-resolution mass spectra [HRMS; electron-
impact (EI), 70 eV] were recorded with a Finnigan MAT 95 instrument. The elemental
analysis was performed by the Laboratory of Microanalysis of the Centre of Molecular and

SYNTHESIS OF PHOSPHORYLATED ENAMINOKETONES AND THEIR APPLICATION 2299
Macromolecular Studies, Polish Academy of Science, Ło´dz´. Starting acroleines 1a–c were
obtained according to a literature method.10,15
Synthesis of Enaminoketones 2a–c: General Procedure
To a solution of (benzylaminomethyl)phosphonic acid diethyl ester (2.57 g, 10.0
mmol, for 2a,c; 5.14 g, 20.0 mmol, for 2b) in Et2O (30.0 mL, for 2a,c) or tetrahydrofuran
(THF; 20.0 mL, for 2b), NEt3 (1.36 g, 13.4 mmol, for 2a,c) and the chloroacroleine 1a–c
(9.0 mmol) was added under argon atmosphere. The mixture was stirred at room temperature
(time given in Table 1). In the case of 3c, an additional portion of chloroacroleine 1c (0.77
g, 3.0 mmol) was added after a period of 120 h and stirring was continued for additional 120
h. The precipitate, if present, was filtered off, and the filtrate was evaporated. The residue
was purified by column chromatography (silica gel, hexane/Et2O, 6:4–2:8) to afford 2a–c
as yellow oils.
[Benzyl-(4,4,4-trifluoro-3-oxo-2-phenylbut-1-enyl)amino]methylphospho
1
nic Acid Diethyl Ester (2a). Yield: 59%. H NMR (CDCl3, 80 MHz): δ = 1.32 (t,
2
3JHH = 7.1 Hz, 6H, CH3), 3.30 (d, JPH = 11.2 Hz, 2H, CH2), 3.92–4.33 (m, 6H, CH2),
7.13–7.37 (m, 5H, arom-H), 7.85 (s, 1H, CH). 13C NMR (CDCl3, 50 MHz): δ = 16.4 (d,
3JPC = 5.6 Hz, CH3), 51.4 (d, 1JPC = 184.6 Hz, CH2P), 62.1 (CH2N), 62.8 (d, 2JPC = 7.1
Hz, CH2O), 118.1 (q, 1JFC = 291.1 Hz, C-4), 127.7 (Carom), 128.1 (Carom), 128.4 (Carom),
129.0 (Carom), 132.1 (Carom), 133.3 (Carom or C-2), 134.7 (Carom or C-2), 153.5 (C-1), 178.2
(q, 2JFC = 32.0 Hz, C-3). 31P NMR (CDCl3, 80 MHz): δ = 19.1. 19F NMR (CDCl3, 235
MHz): δ = −75.7. HRMS (EI) Calcd. for C22H25F3NO4P: 455.1473. Found: 455.1475.
[Benzyl(diethoxyphosphorylmethyl)amino]methylene-4,4,4-trifluoro-3-
1
oxo-butyric Acid Ethyl Ester (2b). Yield: 68%. H NMR (CDCl3, 80 MHz): δ =
1.17–1.41 (m, 9H, CH3), 3.55–4.33 (m, 8H, CH2O + CH2P), 4.75 (br s, 2H, CH2N),
7.19–7.44 (m, 5H, arom-H), 7.77 (s, 1H, CHN). 13C NMR (CDCl3, 50 MHz): δ = 13.3
(CH3, Z or E), 13.4 (CH3, Z or E), 15.9 (CH3, Z or E), 16.0 (CH2 Z or E), 44.7 (d, 1JPC
=
154.1 Hz, CH2, Z or E), 51.9 (d, 1JPC = 154.7 Hz, CH2, Z or E), 55.7 (CH2N, Z or E), 61.0
1
(CH2O), 62.7 (CH2O), 64.6 (CH2O), 100.0 (br s, C-2), 116.8 (q, JFC = 289.3 Hz, C-4),
127.8 (Carom), 128.3 (Carom), 128.7 (Carom), 128.8 (Carom), 129.0 (Carom), 133.0 (Carom),
133.4 (Carom), 156.0 (CHN, Z or E), 156.6 (CHN, Z or E), 165.8 (C-1), 165.9 (br s, C-3).
31P NMR (CDCl3, 80 MHz): δ = 19.3 (br s), 17.7 (br s), 63:37. 19F NMR (CDCl3, 235
MHz): δ = −71.9 (br s), −75.8 (br s), 59:41. Anal. Calcd. for C19H25F3NO6P: C, 50.56;
H, 5.58%. Found: C, 49.94; H, 5.74%.
[Benzyl-((E)-3-oxo-2-phenylbut-1-enyl)amino]methylphosphonic Acid
(2c). Yield: 63%. 1H NMR (CDCl3, 80 MHz): δ = 1.31 (t, 3JHH = 7.1 Hz, 6H, CH3), 1.96
(s, 3H, CH3), 3.28 (d, 2JPH = 10.3 Hz, 2H, CH2P), 3.91–4.23 (m, 4H, CH2O), 4.27 (s, 2H,
CH2N), 7.01–7.43 (m, 10H, C6H5), 7.71 (s, 1H, CHN). 13C NMR (CDCl3, 50 MHz): δ =
15.8 (d, 3JPC = 5.6 Hz, CH3), 27.0 (C-4), 46.7 (d, 1JCP = 156.7 Hz, CH2P), 55.2 (CH2N),
2
61.7 (d, JPC = 7.0 Hz, CH2O), 112.6 (C-2), 126.5 (CHarom), 126.8 (CHarom), 127.1
(CHarom), 127.7 (CHarom), 128.0 (CHarom), 131.0 (CHarom), 135.2 (Carom), 136.7 (Carom),
147.4 (C-1), 196.0 (C-3). 31P NMR (CDCl3, 80 MHz): δ = 20.4. HRMS (EI) Calcd. for
C22H28NO4P: 401.1756. Found: 401.1745.
Reactions of Enaminoketones in the Presence of Sodium Hydride
Under argon atmosphere, sodium hydride (0.16 g, 6.5 mmol) was added to a solu-
tion of DMSO (4.0 mL) in benzene (10.5 mL), and the suspension was stirred at room

´
D. CAL AND P. ZAGORSKI
2300
temperature for 30 min. A solution of the respective enaminoketone 2a–c (3.2 mmol) in
benzene (3.5 mL) was added for a period of 5 min, and stirring was continued for 72
h. Subsequently diethyl ether (30 mL) was added. The mixture was extracted with water
(3 × 10.0 mL for 2a,c; 1 × 10 mL for 2b). The organic phase was dried over MgSO4. After
removal of the solvent, the residue was separated by column chromatography (silica gel,
petroleum ether/Et2O 4:6–2:8) to give pyrroles 3–5 or unreacted 2c was recovered. The
combined water phase was acidified to pH ≈ 2 with HCl (aqueous solution, 3 mol/L) and
extracted with Et2O (3 × 30 mL). The organic phases were combined, the precipitate of 9
(in the case of 2c) was filtered, and the filtrate was dried over MgSO4. After evaporation
of the solvent, the products 6 and 1013 were obtained. The pyrrole 6 required additional
purification by column chromatography (silica gel, petroleum ether/Et2O 2:8).
(1-Benzyl-4-phenyl-3-trifluoromethyl-1H-pyrrol-2-yl)phosphonic
Acid
1
Di-ethyl Ester (3). Yield: 18%. Colorless crystals, mp 76–78◦C. H NMR (CDCl3, 80
MHz): δ = 1.25 (t, 3JHH = 7.1 Hz, 6H, CH3), 4.01 (m, 4H, CH2O), 5.69 (s, 2H, CH2N),
6.87 (d, 5JPH = 5.3 Hz, 1H, CHN), 7.15–7.42 (m, 10H, arom-H). 13C NMR (CDCl3, 151
3
2
MHz): δ = 16.0 (d, JPC = 6.6 Hz, CH3), 53.1 (CH2N), 62.5 (d, JPC = 5.4 Hz, CH2O),
119.3 (dq, 1JPC = 220.9 Hz, 3JFC = 3.1 Hz, C-2), 120.5 (dq, 2JPC = 14.3 Hz, 2JFC = 35.3
1
3
3
Hz, C-3), 123.0 (q, JCF = 269.6 Hz, CF3), 125.9 (dq, JPC = 11.0 Hz, JFC = 2.5 Hz,
C-4), 127.2 (CHN), 127.4 (CHarom). 127.76 (CHarom), 127.8 (CHarom), 128.0 (CHarom),
128.7 (CHarom), 129.3 (CHarom), 133.6 (Carom), 137.5 (Carom). 31P NMR (CDCl3, 80 MHz):
δ = 5.7 (q, 4JFP = 2.4 Hz). 19F NMR (CDCl3, 235 MHz): δ = −51.4 (d, 4JPF = 2.6 Hz).
Anal. Calcd. for C22H23F3NO3P: C, 60.41; H, 5.30%. Found: C, 60.49; H, 5.20%.
1-Benzyl-3-phenyl-4-trifluoromethyl-1H-pyrrole (4). Yield: 24%. Yellow oil.
1H NMR (CDCl3, 600 MHz): δ = 5.10 (s, 2H, CH2), 6.79 (d, 4JHH = 2.0 Hz, 1H, CHN),
7.09 (m, CHN), 7.24–7.28 (m, 10H, arom-H). 13C NMR (CDCl3, 151 MHz): δ = 53.6
2
3
(CH2N), 112.3 (q, JFC = 35.4 Hz, C-4), 121.3 (C-2), 122.4 (q, JFC = 5.8 Hz, C-5),
3
1
123.8 (q, JFC = 2.0 Hz, C-3), 124.1 (q, JFC = 266.7 Hz, CF3), 126.6 (CHarom), 127.3
(CHarom), 128.1 (CHarom), 128.2 (CHarom), 128.3 (CHarom), 128.9 (CHarom), 133.9 (Carom),
136.3 (Carom). 19F NMR (CDCl3, 565 MHz): δ = −54.5. HRMS (EI) Calcd. for C18H14F3N:
301.1078. Found: 301.1074.
1-Benzyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic Acid Ethyl Ester (5).
Yield: 9%. Yellow oil. 1H NMR (CDCl3, 700 MHz): δ = 1.35 (t, 3JHH = 7.0 Hz, 3H, CH3),
4.30 (q, 3JHH = 7.0 Hz, 2H, CH2), 5.07 (s, 2H, CH2), 7.02 (d, 4JHH = 2.1 Hz, CHN), 7.19
(d, JHH = 7.0 Hz, 2H, arom-H), 7.38–7.42 (m, 4H, CHN + arom-H). 13C NMR (CDCl3,
2
63 MHz): δ = 14.1 (CH3), 54.1 (CH2N), 60.2 (CH2O), 114.0 (C-3), 114.9 (q, JFC
=
1
3
37.8 Hz, C-4), 122.7 (q, JCF = 266.8 Hz, CF3), 123.4 (q, JCF = 6.1 Hz, CHN), 127.5
(CHarom), 128.6 (CHarom), 128.9 (CHarom), 129.1 (CHN), 135.0 (Carom), 162.6 (COO). 19
F
NMR (CDCl3, 235 MHz): δ = −57.7. HRMS (EI) Calcd. for C15H14F3NO2: 297.0977.
Found: 297.0968.
1-Benzyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic Acid (6). Yield: 10%.
1H NMR (CDCl3, 600 MHz): δ = 5.06 (s, 2H, CH2N), 7.02 (d, 4JHH = 2.4 Hz, 1H, CHN),
4
7.17–7.19 (m, 2H, arom-H), 7.35–7.41 (m, 3H, arom-H), 7.45 (d, JHH = 2.4 Hz, 1H,
CHN). 13C NMR (CDCl3, 50 MHz): δ = 54.2 (CH2N), 115.3 (q, 2JFC = 37.4 Hz, Carom),
122.4 (q, 1JFC = 265.2 Hz, CF3), 123.8 (q, 3JFC = 6.1 Hz, Carom), 127.6 (CHarom), 128.7
(CHarom), 129.1 (CHarom), 130.3 (CHarom), 133.6 (Carom), 135.0 (COOH). 19F NMR (CDCl3,
235 MHz): δ = −57.9. HRMS (EI) Calcd. for C13H10F3NO2: 269.0664. Found: 269.0661.
Benzylaminomethylphosphonic Acid Ethyl Ester (9). Yield: 16%. Colorless
1
3
crystals, mp 198–200◦C. H NMR (CDCl3, 600 MHz): δ = 1.26 (t, JHH = 7.2 Hz, 3H,

SYNTHESIS OF PHOSPHORYLATED ENAMINOKETONES AND THEIR APPLICATION 2301
CH3), 2.77 (d, 2JPH = 12.6 Hz, 2H, CH2P), 3.92 (m, 2H, CH2), 7.23–7.32 (m, 3H, arom-
H), 7.54 (d, JHH = 7.2 Hz, arom-H), 10.35 (br s, 1H, NH). 13C NMR (CDCl3, 151 MHz):
3
1
3
δ = 16.9 (d, JPC = 7.6 Hz, CH3), 42.5 (d, JPC = 138.9 Hz, CH2P), 52.8 (d, JPC
=
2
12.1 Hz, CH2N), 60.7 (d, JPC = 4.5 Hz, CH2O), 128.7 (CHarom), 128.9 (CHarom), 130.9
(CHarom), 131.1 (Carom). 31P NMR (CDCl3, 80 MHz): δ = 8.28. m/z (ESI/MeOH): 252
(100%, M+Na]+). Anal. Calcd. for C10H16NO3P: C, 52.40; H, 7.04%. Found: C, 52.63;
H, 7.17%.
Reaction of Enaminoketone 2b in the Presence of Triethylamine
Under argon atmosphere, a solution of enaminoketone 2b (1.65 g, 3.6 mmol) and
NEt3 (1.12 g, 11.0 mmol) in MeCN (14.0 mL) was refluxed for 20 h. Then the solvent
was evaporated and the residue was separated by column chromatography (silica gel,
hexanes/Et2O, 1:1) to afford 2-phosphonopyrrole 7 and β-enaminoester 8 as yellow oils.
1-Benzyl-5-(diethoxyphosphoryl)-4-trifluoromethyl-1H-pyrrole-3-carboxy-
1
lic Acid Ethyl Ester (7). Yield: 5%. H NMR (CDCl3, 80 MHz): δ = 1.13–1.43 (m,
3
9H, CH3), 3.75–4.14 (m, 4H, CH2O), 4.30 (q, JHH = 7.1 Hz, 2H, CH2O), 5.70 (s, 2H,
CH2N), 7.08–7.37 (m, 5H, C6H5), 7.50 (d, 4JPH = 5.1 Hz, 1H, CHN). 13C NMR (CDCl3,
3
151 MHz): δ = 14.1 (CH3), 16.0 (d, JPC = 6.6 Hz, CH3), 53.8 (CH2N), 60.8 (CH2O),
62.8 (d, 2JPC = 5.5 Hz, CH2O), 115.9 (dq, 3JPC = 10.8 Hz, 3JFC = 3.3 Hz, C-5) 121.8 (q,
1JFC = 269.7 Hz, CF3), 122.6 (dq, 2JPC = 14.7 Hz, 2JFC = 37.8 Hz, C-4), 127.3 (CHarom),
3
128.1 (CHarom), 128.8 (CHarom), 133.6 (d, JPC = 11.2 Hz, CHN), 136.9 (Carom), 162.2
4
(COO). 31P NMR (CDCl3, 80 MHz): δ = 4.5 (q, JPF = 2.5 Hz). 19F NMR (CDCl3, 235
4
MHz): δ = −53.7 (d, JPF = 2.6 Hz). HRMS (EI) Calcd. for C19H23F3NO5P: 433.1266.
Found: 433.1263.
(E)-3-Benzyl(diethoxyphosphorylmethyl)amino]acrylic Acid Ethyl Ester
(8). Yield: 93%. 1H NMR (CDCl3, 80 MHz): δ = 1.28 (q, 3JHH = 6.8 Hz, 9H, CH3), 3.42
(d, 2JPH = 9.5 Hz, 2H, CH2P), 3.96–4.33 (m, 6H, CH2O), 4.51 (s, 2H, CH2N), 4.82 (dd,
4
4
3JHH = 13.2 Hz, JHP = 1.6 Hz, 1H, CHN), 7.16–7.36 (m, 5H, C6H5), 7.59 (d, JHH
=
13.1 Hz, 1H, CH). 13C NMR (CDCl3, 50 MHz): δ = 14.2 (CH3), 16.1 (d, 3JPC = 5.6 Hz,
1
2CH3), 45.5 (br d, JCP = 146.9 Hz, CH2P), 56.3 (br s, CH2N), 58.7 (CH2O), 62.1 (d,
2JPC = 7.0 Hz, CH2O), 87.0 (C-2), 127.2 (CHarom), 127.6 (CHarom), 128.5 (CHarom), 135.1
(Carom), 151.5 (C-3), 168.9 (C-1). 31P NMR (CDCl3, 80 MHz): δ = 20.4. m/z (ESI, MeOH)
356.0 (18.7%, M+H]+), 378.1 (100%, M+Na]+). HRMS (EI) Calcd. for C17H26NO5P:
355.1548. Found: 355.1542.
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