Флуоровані NH-імінофосфонати в синтезі біологічно важливих похідних α-амінофосфонових кислот
Reactions of (poly)fluoroalkylated NH-iminophosphonates with nitromethane, trimethylsilylcyanide, and diphenylphosphine oxide lead to respective fluorinated β-nitro-α-aminophosphonates, α-cyano-α-aminophosphonates, and heminal bisphosphonates.  Reaction with 3-aminocrotonitrile 5 proced...
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V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
2022
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Ukrainica Bioorganica Acta| _version_ | 1871193546901422080 |
|---|---|
| author | Rassukana, Yulia V. Yelenich, Ivanna P. Onysʹko, Petro P. |
| author_facet | Rassukana, Yulia V. Yelenich, Ivanna P. Onysʹko, Petro P. |
| author_institution_txt_mv | [
{
"author": "Yulia V. Rassukana",
"institution": "Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, 5 Murmanska St., Kyiv, 02094, Ukraine"
},
{
"author": "Ivanna P. Yelenich",
"institution": "Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, 5 Murmanska St., Kyiv, 02094, Ukraine"
},
{
"author": "Petro P. Onysʹko",
"institution": "Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, 5 Murmanska St., Kyiv, 02094, Ukraine"
}
] |
| author_sort | Rassukana, Yulia V. |
| baseUrl_str | https://bioorganica.com.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-19T14:56:53Z |
| description | Reactions of (poly)fluoroalkylated NH-iminophosphonates with nitromethane, trimethylsilylcyanide, and diphenylphosphine oxide lead to respective fluorinated β-nitro-α-aminophosphonates, α-cyano-α-aminophosphonates, and heminal bisphosphonates.  Reaction with 3-aminocrotonitrile 5 proceds at the β-position of enamine. In the case of α-imino chlorodifluoroethylphosphonate 1c the reaction is accompanied by an unusual nucleophilic substitution of the chlorine atom in CF2Cl group with the formation of pyrroline bearing a difluoromethylated aminophosphonate moiety |
| doi_str_mv | 10.15407/bioorganica2022.01.101 |
| first_indexed | 2025-07-17T12:19:26Z |
| format | Article |
| fulltext |
ISSN 1814-9758. Ukr. Bioorg. Acta, 2022, Vol. 17, N 1
UDC 547.466+ 547.742
DOI: https://doi.org/10.15407/bioorganica2022.01.101
101
SHORT COMMUNICATION
Fluorinated NH-iminophosphonates in synthesis of biorelevant
α-aminophosphonic acids derivatives
Yulia V. Rassukana1,2, Ivanna P. Yelenich1, Petro P. Onys’ko1*
1 Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, 5 Murmanska St., Kyiv, 02094, Ukraine
2 National Technical University of Ukraine “Kyiv Polytechnic Institute”, 37 Peremoga Ave., Kyiv, 03056, Ukraine
Abstract: Reactions of (poly)fluoroalkylated NH-iminophosphonates with nitromethane, trimethylsilylcyanide, and diphenylphosphine
oxide lead to respective fluorinated β-nitro-α-aminophosphonates, α-cyano-α-aminophosphonates, and heminal bisphosphonates. Reaction
with 3-aminocrotonitrile 5 proceds at the β-position of enamine. In the case of α-imino chlorodifluoroethylphosphonate 1c the reaction is
accompanied by an unusual nucleophilic substitution of the chlorine atom in CF2Cl group with the formation of pyrroline bearing a
difluoromethylated aminophosphonate moiety.
Keywords: iminophosphonates; aza-Henry reaction; cyanation; enamines; fluoroalkyl.
Introduction
α-Aminophosphonic acids are phosphorus analogs of
α-amino acids in which the planar carboxylic group is
replaced with a tetrahedral phosphonate moiety and because
of this they can serve as surrogates of α-amino acids in
peptides, modifying their properties [1]. They reveal a wide
spectrum of biological activity and have numerous
applications in medicinal and pharmaceutical sciences as
haptens of catalytic antibodies, enzyme inhibitors,
antibacterial agents as well as agrochemicals [1-6]. Of
particular importance are fluorinated aminophosphonic acid
derivatives. They are expected to be resistant to metabolic
degradation. In addition, the presence of fluorine could
improve the lipophilicity and pharmacokinetic profile [7].
Incorporation of the fluorinated group in organic molecules
became almost a standard tool in the design and lead
optimization of drug candidates in medicinal chemistry.
Received:
Revised:
Accepted:
Published online:
04.04.2022
26.04.2022
12.05.2022
30.06.2022
Corresponding author. Tel.: +380-44-573-2643;
e-mail: onysko_@ukr.net (P. Onys’ko)
ORCID: 0000-0002-6137-2778
However, synthetic approaches to fluorinated
aminophosphonic derivatives are few in number and of
limited applicability. Most of the reported methods for
preparation of aminophosphonates are based on the addition
of phosphites to non-phosphorylated imines as the key step
(Pudovik reaction or Kabachnik-Fields reaction). Despite
seeming simplicity, these methods have some drawbacks
such as purification of final compounds, and low reactivity,
and are of limited utility for the preparation of fluoroalkyl
substituted aminophosphonates. We have developed an
alternative general approach based on the use
iminophosphonates as starting compounds for construction
of various functionalized aminophosponates [8, 9]. The
fluorinated imidoylphosphonates with a free N-H group
seem especially promising for this purpose due to enhanced
reactivity and the possibility to prepare directly
aminophosphonate with the unprotected amino group.
Recently we have developed convenient synthetic methods
for the fluorinated NH-iminophosphoante and demonstrated
their potential as novel promising building blocks for the
construction of acyclic and heterocyclic fluoroalkylated
aminophosphonic acid derivatives [10, 11]. Of particular
interest is the possibility to prepare in this way quaternary
aminophosphonates as they are promising compounds for
the construction of novel peptide sequences with tailor-
made improved properties [6]. In the present work, we
describe the synthesis of fluoroalkylated quaternary
aminophosphonates based on reactions of fluoroalkylated
iminophosphonates with some C-centered nucleophiles.
© Rassukana Y. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Ukrainica Bioorganica Acta
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ISSN 1814-9758. Ukr. Bioorg. Acta, 2022, Vol. 17, N 1
102
Results and Discussion
Reactions of imines with nitromethane is a powerful tool
for the preparation of β-nitroamines and respective
diamines. Recently, the Palacios group reported the
enantioselective nucleophilic addition of nitromethane to
C-arylated tosyliminophosphonates, catalyzed by cinchona
alkaloids derived thioureas, affording non-racemic β-nitro-
α-aminophosphonates [12]. Fluoroalkylated iminophospho-
nates were never utilized in the aza-Henry reaction. It is
worth noting here that according to the publication [13]
fluorinated aldimines exhibit a specific behavior in the aza-
Henry reaction: in contrast to their non-fluorinated analogs,
they do not react with nitromethane in the presence of
organic or inorganic bases. It was concluded that the
addition of nitroalkanes to the C=N bond of trifluoro-
methylaldimines occurs only upon catalysis by Lewis acids
[14]. We have found that trifluoromethylated NH-
iminophosphonate 1a in the presence of triethylamine reacts
with nitromethane at room temperature to afford β-nitro-α-
aminotrifluoroethylphosphonate 2 in almost quantitative
yield (Scheme 1).
Scheme 1. Synthesis of β-nitro-α-aminophosphonate.
Next, we studied cyanation of polyfluoroalkylated NH-
iminophosphonates 1a,b with TMSCN. Addition of
cyanides to C=N bond is widely used for the synthesis of α-
aminonitriles, precursors of α-amino acids. We have found
that iminophosphonates 1a,b react with the commercially
accessible trimethylsilyl cyanide in the presence of 10
mol.% triethylamine with the formation of α-amino-α-
cyanopolyfluoroalkylphosphonates 3a,b in high yields
(Scheme 2).
Scheme 2. Addition of TMSCN and hydrophosphoryl compounds
to the C=N bond of iminophosphonates.
It is worth noting that C-arylated tosyliminophospho-
nates do not react with TMSCN in the presence of
triethylamine and other various basic catalysts [15].
Effective enantioselective cyanation of C-arylated
tosyiminophosphonates has only been achieved using
MeCOCN, as cyanatimg agent, and Cinchona alkaloids, as
chiral catalysts [15]. Thus, enhanced reactivity of
fluorinated NH-iminophosphonates clearly reveals itself in
cyanation reaction with TMSCN. Even without bases, NH-
iminophosphonates 1a,b at room temperature react with
hydrophosphoryl compounds to afford fluorinated heminal
diphosphorylated derivatives 4. Compounds of such type
are known to reveal a wide spectrum of biological activity.
α-Methyl-substituted push-pull enamines are other types
of polyfunctional nucleophilic agents that are known to
react with the involvement of nitrogen atom, β- or
β′-position of enamine [16-18]. In particular, reactions with
imines can lead to completely different products depending
on the substituents at the C=N bond. Thus, the regio-
selectivity of the reactions of such enamines with NH-
iminophopshonates remained unclear. We have found that
NH-iminophosphonate 1a reacts with enamine 5 with the
involvement of only β-position of enamine to afford highly
functionalized aminophosphonate 6 bearing an enamine
moiety capable of further functionalization (Scheme 3). It
should be noted that analogs of enamine 5 containing an
alkoxycarbonyl substituent instead of a nitrile group react
with iminopyruvates by a completely different scheme,
involving the α-methyl group of enamine [17].
Scheme 3. Synthesis of enamine-derived aminophosphonate.
Reaction of enamine 5 with chlorodifluoromethylated
analog 1c does not stop at the formation of enamine A. The
latter undergoes intramolecular condensation affording
highly functionalized pyrroline 7 (Scheme 4). Rather
unusual nucleophilic substitution of chlorine atom in CF2Cl
group is associated with the advantage of five-member ring
formation and is promising for the construction of
compounds combining in their structure biorelevant
aminophosphonic fragment, difluoromethyl group, and
pyrroline moiety in a single molecular platform.
Scheme 4. Synthesis of pyrroline-derived aminophosphonate.
Conclusions
(Poly)fluoroalkylated NH-iminophosphonates are
convenient low-molecular starting compounds for the
creation of substances incorporating biorelevant fluorinated
aminophosphonic moiety. High reactivity of the compounds
ensures C-C bond formation in reactions with nitromethane,
trimethylsilylcyanide, and push-pull enamines providing
easy access to highly functionalized tetrasubstituted
aminophosphonates. The presence of an unprotected imine
nitrogen atom in the iminophosphontes 1a-c allows the
direct synthesis of N-unprotected aminophosphonates.
Rassukana Y. et al.
103
Experimental section
NMR spectra were recorded with a Bruker Avance DRX
500 spectrometer with operating frequency 500 (1H), 202
(31P), 126 MHz (13C), a Varian Unity Plus 400 instrument
with operating frequency 400.4 MHz (1H), and a Gemini
200 Varian spectrometer with operating frequency 80.95
MHz (31P). Chemical shifts are reported relative to internal
TMS (1H, 13C) and external 85%-H3PO4 (31P) standards.
The solvents were dried according to the standard
procedures.
(O,O)-Diethyl-1-amino-2,2,2-trifuoroethyl-1-(nitromethyl)-
ethylphosphonate (2).
A solution of triethylamine (130 mg, 0.18 mL, 1.29 mmol)
and imine 1а in nitromethane (1 mL) was left at room
temperature overnight. The mixture was evaporated,
washed with hexane and dried. Yellow oil. Yield: 370 mg,
97%; 1Н NMR (500 MHz, CDCl3) δ: 4.90 (dd, 2JH-Н 12.6,
3JH-Р 8.1 Hz, 1H, CH2NO2), 4.78 (dd, 2JH-Н 12.6, 3JH-Р 6.6
Hz, 1H, CH2NO2), 4.23-4.33 (m, 4H, 2×СН2О), 2.52 (br d,
3JH-Р 15.6 Hz, 2Н, NH2), 1.38 (t, 3JH-Н 7.1 Hz, 6H, 2×СН3),
ppm; 13C NMR (125 MHz, CDCl3) δ: 123.6 (qd, 1JC-F 285.9,
2JC-P 4.9 Hz, CF3), 75.1 (s, CH2), 64.9 (d, 2JC-P 7.1 Hz,
CH2O), 64.2 (d, 2JC-P 7.1 Hz, CH2O), 59.8 (dq, 1JC-P 153.7,
2JC-F 28.9 Hz, CP), 15.61 (d, 3JC-Р 5.9 Hz, CH3), 15.55 (d,
3JC-Р 5.9 Hz, CH3), ppm; 19F NMR (188 MHz, CDCl3) δ:
-73.0 ppm; 31Р NMR (81 MHz, CDCl3) δ: 13.6 ppm;
IR (neat) νmax: 3430 (NH2), 3340, 1575 (NO2), 1270 (P=O),
1060 (POC), cm-1; Сalcd. For C7H14F3N2O5P (294.2):
C 28.58; H 4.80; N 9.52; P 10.53. Found: C 28.54; H 4.80;
N 9.50; P 10.50.
General procedure for compounds 3a,b.
A mixture of imine 1а or 1b (0.64 mmol), trimethyl-
sylilcyanide (190 mg, 0.24 mL, 1.92 mmol) and
triethylamine (6.5 mg, 0.0089 mL, 0.064 mmol) in CH3CN
(1 mL) was refluxed for 3 hrs. After then 1 drop of
methanol was added, the mixture was evaporated, washed
with hexane and dried.
(O,O)-Diethyl-1-amino-1-cyano-2,2,2-trifuoroethyl-
phosphonate (3a).
Brown oil. Yield: 160 mg, 96%; 1Н NMR (500 MHz,
CDCl3) δ: 4.31-4.47 (m, 4H, 2×CH2O), 2.44 (br s, 2Н,
NH2), 1.44 (t, 3JH-H 7.2 Hz, 3Н, СН3), 1.42 (t, 3JH-H 7.2 Hz,
3Н, СН3), ppm; 13C NMR (125 MHz, CDCl3) δ: 121.6 (q,
1JC-F 285.0 Hz, CF3), 113.5 (d, 2JC-P 7.2 Hz, CN), 66.2 (d,
2JC-P 7.4 Hz, CH2O), 65.9 (d, 2JC-P 7.4 Hz, CH2O), 56.1 (dq,
1JC-P 151.5, 2JC-F 33.3 Hz, CP), 15.8 (d, 3JC-P 5.9 Hz, CH3),
15.7 (d, 3JC-P 5.9 Hz, CH3), ppm; 19F NMR (188 MHz,
CDCl3) δ: -73.9 ppm; 31Р NMR (81 MHz, CDCl3) δ:
7.6 ppm; Сalcd. For C7H12F3N2O3P (260.2): C 32.32;
H 4.65; N 10.77; P 11.91. Found: C 32.29; H 4.64; N 10.74;
P 11.92.
(O,O)-Diethyl-1-amino-1-cyano-2,2,3,3,4,4,4-hepta-
fluorobutylphosphonate (3b).
Brown oil. Yield: 220 mg, 96%; 1Н NMR (500 MHz,
CDCl3) δ: 4.30-4.47 (m, 4H, 2×CH2O), 2.40 (br s, 2Н,
NH2), 1.42 (t, 3JH-H 7.2 Hz, 3Н, СН3), 1.37 (t, 3JH-H 7.2 Hz,
3Н, СН3), ppm; 19F NMR (188 MHz, CDCl3) δ: -124.3 (m,
J 290.1, 15.4 Hz, 1F, CF2), -121.2 (m, J 290.1, 15.4 Hz, 1F,
CF2), -116.6 (m, 2J 279.4 Hz, 1F, CF2), -111.3 (m, 2J 279.4
Hz, 1F, CF2), -81.2 (m, 3F, CF3), ppm; 31Р NMR (81 MHz,
CDCl3) δ: 8.3 ppm; IR (neat) νmax: 1060 (POC), 1250
(P=O), 2200 (C≡N), 3220, 3340 (NH2) cm-1; Сalcd. For
C9H12F7N2O3P (360.2): 30.01; H 3.36; N 7.78; P 8.60.
Found: C 29.95; H 3.33; N 7.80; P 8.60.
(O,O)-Diethyl-1-amino-1-(diphenylphosphinoyl)-
2,2,3,3,4,4,4-heptafluorobutylphosphonate (4b).
A mixture of imine 1b (100 mg, 0.31 mmol) and
diphenylphosphine oxide (60 mg, 0.31 mmol) in Et2O
(2 mL) was left at room temperature overnight. The mixture
was evaporated, the residue was triturated with hexane and
dried. White crystals. Yield: 130 mg, 81%; mp 119-121 °С;
1Н NMR (500 MHz, CDCl3) δ: 8.35 (dd, 3JH-Н 8.1, 3JH-P
10.5 Hz, 2Н, НPh), 8.03 (dd, 3JH-Н 8.1, 3JH-P 10.5 Hz, 2Н,
НPh), 7.46-7.54 (m, 6Н, НPh), 4.17-4.29 (m, 1H, CH2O),
3.95-4.09 (m, 1H, CH2O), 3.77-3.90 (m, 1H, CH2O), 3.55-
3.69 (m, 1H, CH2O), 2.72 (br s, 2Н, NH2), 1.26 (t, 3JH-Н 7.1
Hz, 3Н, СН3), 1.04 (t, 3JH-Н 7.1 Hz, 3Н, СН3), ppm;
19F NMR (188 MHz, CDCl3) δ: -123.2 (m, 2JF-F 284.5 Hz,
1F, CF2), -120.5 (m, 2JF-F 284.5 Hz, 1F, CF2), -104.0 (m,
2JF-F 296.0 Hz, 1F, CF2), -102.2 (m, 2JF-F 296.0 Hz, 1F,
CF2), -81.0 (m, 3F, CF3), ppm; 31Р NMR (81 MHz, CDCl3)
δ: 30.6 (m, 1P, PPh), 13.9 (m, 1P, POEt), ppm; IR (KBr)
νmax: 3420 (NH2), 1270 (P=O), 1220, 1065 (POC), cm-1;
Сalcd. For C20H22F7NO4P2 (535.3): C 44.87; H 4.14;
N 2.62; P 11.57. Found: C 44.78; H 4.13; N 2.63; P 11.55.
(O,O)-Diethyl-3-diamino-2-cyano-1-(trifluoromethyl)-
but-2-en-1-yl]phosphonate (6).
A mixture of imine 1а (0.51 g, 2.2 mmol) and enamine 5
(0.18 g, 2.2 mmol) was heated at 50 ºС for 5 hrs. The
product was purified by preparative TLC (EtOAc/MeOH
20:1) Rf 0.6. White crystals. Yield: 0.52 g, 76%; mp 104-
106 °С; 1Н NMR (500 MHz, CDCl3) δ: 4.18-4.33 (m, 4H,
2×CH2O), 2.22 (s, 3H, =CCH3), 2.12 (br, 2Н, NH2), 2.10
(br d, 3JH-P 15.3 Hz, 2Н, NH2), 1.39 (t, 3JH-H 6.9 Hz, 3H,
СН3), 1.37 (t, 3JH-H 6.9 Hz, 3H, СН3), ppm; 13C NMR (125
MHz, CDCl3) δ: 161.2 (d, 3JC-P 5.2 Hz, =CNH2), 124.8 (qd,
1JC-F 286.1, 2JC-P 13.1 Hz, CF3), 120.4 (d, 3JC-P 4.9 Hz, CN),
67.6 (m, =CCN), 64.2 (d, 2JC-P 7.2 Hz, CH2O), 64.0 (d, 2JC-P
7.2 Hz, CH2O), 60.3 (dq, 1JC-P 156.8, 2JC-F 29.1 Hz, CP),
23.1 (d, 4JC-P 1.0 Hz, =CCH3), 16.0 (d, 3JC-P 5.2 Hz, CH3),
15.9 (d, 3JC-P 5.2 Hz, CH3), ppm; 19F NMR (188 MHz,
CDCl3) δ: -73.9 ppm; 31Р NMR (81 MHz, CDCl3) δ: 16.3
ppm; IR (KBr) νmax: 3440 (NH2), 3340, 2210 (C≡N), 1650
(С=С), 1260 (P=O), 1065 (POC), cm-1. Сalcd. For
C10H17F3N3O3P (315.2): C 38.10; H 5.44; N 13.33; P 9.83.
Found: C 37.98; H 5.42; N 13.36; P 9.81.
ISSN 1814-9758. Ukr. Bioorg. Acta, 2022, Vol. 17, N 1
104
(O, O)-Diethyl- (3-amino-4-cyano-2,2-difluoro-5-methyl-
2,3-dyhydro-1Н-pyrrol-3-yl)phosphonate (7).
A mixture of imine 1c (250 mg, 1 mmol) and enamine 5
(70 mg, 0.9 mmol) was heated at 100 ºС for 3 hrs. The
mixture was triturated with Et2O. Brown powder. Yield:
160 mg, 54%; mp 109-112 °С; 1Н NMR (500 MHz, CDCl3)
δ: 4.18-4.34 (m, 4H, 2×CH2O), 2.25 (s, 3H, CH3), 2.20 (br
d, 3JH-P 17.7 Hz, 2H, NН2), 1.39 (t, 3JH-H 7.2 Hz, 3H, СН3),
1.36 (t, 3JH-H 7.2 Hz, 3H, СН3), ppm; 19F NMR (188 MHz,
CDCl3) δ: -56.9 (m, 2JF-F 159.9, 1F), -55.8 (m, 2JF-F 159.9
Hz, 1F), ppm; 31Р NMR (81 MHz, CDCl3) δ: 16.6 ppm; IR
(KBr) νmax: 3450 (NH2), 3310 (NH), 2210 (C≡N), 1650
(С=С), 1260 (P=O), 1065 (POC), cm-1; Сalcd. For
C10H16F2N3O3P (295.2): C 40.68; H 5.46; N 14.23; P 10.49.
Found: C 40.60; H 5.44; N 14.25; P 10.47.
Notes
The authors declare no conflict of interest.
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Флуоровані NH-імінофосфонати в синтезі біологічно важливих похідних
α-амінофосфонових кислот
Ю. В. Рассукана1,2, І. П. Єленіч1, П. П. Онисько1*
1 Інститут органічної хімії НАН України, вул. Мурманська, 5, Київ, 02094, Україна
2 Національний технічний університет України «Київський політехнічний інститут ім. Ігоря Сікорського», пр. Перемоги, 37, Київ, 03056,
Україна
Резюме: Реакції (полі)флуороалкільованих NH-імінофосфонатів із нітрометаном, триметилсилілціанідом, та дифенілфосфіноксидом призводять
до відповідних флуорованих β-нітро-α-амінофосфонатів, α-ціано-α-амінофосфонатів, та гемінальних бісфосфонатів. Взаємодія із 3-аміно-
кротононітрилом здійснюється по β-положенню єнаміну. У випадку α-іміно хлородифлуороетилфосфонату 1c реакція супроводжується
незвичним нуклеофільним заміщенням атома хлору CF2Cl групи з утворенням піроліну, що містить дифлуорометильований амінофосфонатний
залишок.
Ключові слова: імінофосфонати; реакція аза-Генрі; ціанування; енаміни; флуороалкіл.
https://pubs.rsc.org/en/results?searchtext=Author%3ALucio%20Pellacani
https://pubs.rsc.org/en/results?searchtext=Author%3AMaria%20Cecilia%20Vergari
https://pubs.rsc.org/en/results?searchtext=Author%3ALucio%20Pellacani
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| id | oai:ojs2.bioorganica.com.ua:article-17 |
| institution | Ukrainica Bioorganica Acta |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-20T01:00:26Z |
| publishDate | 2022 |
| publisher | V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine |
| record_format | ojs |
| resource_txt_mv | bioorganicacomua/c7/4a0b1f5ed6bd0ccda093c0048ccabbc7.pdf |
| spelling | oai:ojs2.bioorganica.com.ua:article-172026-07-19T14:56:53Z Fluorinated NH-iminophosphonates in synthesis of biorelevant α-aminophosphonic acids derivatives Флуоровані NH-імінофосфонати в синтезі біологічно важливих похідних α-амінофосфонових кислот Rassukana, Yulia V. Yelenich, Ivanna P. Onysʹko, Petro P. iminophosphonates aza-Henry reaction cyanation enamines fluoroalkyl імінофосфонати реакція аза-Генрі ціанування енаміни флуороалкіл Reactions of (poly)fluoroalkylated NH-iminophosphonates with nitromethane, trimethylsilylcyanide, and diphenylphosphine oxide lead to respective fluorinated β-nitro-α-aminophosphonates, α-cyano-α-aminophosphonates, and heminal bisphosphonates.  Reaction with 3-aminocrotonitrile 5 proceds at the β-position of enamine. In the case of α-imino chlorodifluoroethylphosphonate 1c the reaction is accompanied by an unusual nucleophilic substitution of the chlorine atom in CF2Cl group with the formation of pyrroline bearing a difluoromethylated aminophosphonate moiety Реакції (полі)флуороалкільованих NH-імінофосфонатів із нітрометаном, триметилсилілціанідом, та дифенілфосфіноксидом призводять до відповідних флуорованих β-нітро-α-амінофосфонатів, α-ціано-α-амінофосфонатів, та гемінальних бісфосфонатів. Взаємодія із 3-аміно-кротононітрилом здійснюється по β-положенню єнаміну. У випадку α-іміно хлородифлуороетилфосфонату 1c реакція супроводжується незвичним нуклеофільним заміщенням атома хлору CF2Cl групи з утворенням піроліну, що містить дифлуорометильований амінофосфонатний залишок. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2022-06-30 Article Article application/pdf https://bioorganica.com.ua/index.php/journal/article/view/17 10.15407/bioorganica2022.01.101 Ukrainica Bioorganica Acta; Vol. 17 No. 1 (2022): Ukrainica Bioorganica Acta; 101-104 Ukrainica Bioorganica Acta; Том 17 № 1 (2022): Ukrainica Bioorganica Acta; 101-104 1814-9766 1814-9758 10.15407/bioorganica2022.01 en https://bioorganica.com.ua/index.php/journal/article/view/17/22 Copyright (c) 2022 Yulia V. Rassukana, Ivanna P. Yelenich, Petro P. Onysʹko https://creativecommons.org/licenses/by/4.0 |
| spellingShingle | імінофосфонати реакція аза-Генрі ціанування енаміни флуороалкіл Rassukana, Yulia V. Yelenich, Ivanna P. Onysʹko, Petro P. Флуоровані NH-імінофосфонати в синтезі біологічно важливих похідних α-амінофосфонових кислот |
| title | Флуоровані NH-імінофосфонати в синтезі біологічно важливих похідних α-амінофосфонових кислот |
| title_alt | Fluorinated NH-iminophosphonates in synthesis of biorelevant α-aminophosphonic acids derivatives |
| title_full | Флуоровані NH-імінофосфонати в синтезі біологічно важливих похідних α-амінофосфонових кислот |
| title_fullStr | Флуоровані NH-імінофосфонати в синтезі біологічно важливих похідних α-амінофосфонових кислот |
| title_full_unstemmed | Флуоровані NH-імінофосфонати в синтезі біологічно важливих похідних α-амінофосфонових кислот |
| title_short | Флуоровані NH-імінофосфонати в синтезі біологічно важливих похідних α-амінофосфонових кислот |
| title_sort | флуоровані nh-імінофосфонати в синтезі біологічно важливих похідних α-амінофосфонових кислот |
| topic | імінофосфонати реакція аза-Генрі ціанування енаміни флуороалкіл |
| topic_facet | iminophosphonates aza-Henry reaction cyanation enamines fluoroalkyl імінофосфонати реакція аза-Генрі ціанування енаміни флуороалкіл |
| url | https://bioorganica.com.ua/index.php/journal/article/view/17 |
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