New catalyst for phosphonylation of C=X electrophiles

Article abstract of DOI:10.1080/00397911.2010.542602

Pyridinium perchlorate is found to be an efficient and recyclable catalyst for the reaction of trialkyl phosphites with various C=X electrophiles (aldehydes, ketones, ketophosphonates, imines, isocyanates, isothiocyanates, activated alkenes) to afford cor

Full text of DOI:10.1080/00397911.2010.542602

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New Catalyst for Phosphonylation of C˭X
Electrophiles
Oleg I. Kolodiazhnyi a & Olga O. Kolodiazhna a
a Institute of Bioorganic Chemistry and Petrol Chemistry, National
Academy of Sciences, Kyiv, Ukraine
Accepted author version posted online: 17 Nov 2011.Published
online: 03 Feb 2012.
To cite this article: Oleg I. Kolodiazhnyi & Olga O. Kolodiazhna (2012): New Catalyst for
Phosphonylation of C˭X Electrophiles, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 42:11, 1637-1649
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Synthetic Communications1, 42: 1637–1649, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.542602
=
NEW CATALYST FOR PHOSPHONYLATION OF C X
ELECTROPHILES
Oleg I. Kolodiazhnyi and Olga O. Kolodiazhna
Institute of Bioorganic Chemistry and Petrol Chemistry, National Academy
of Sciences, Kyiv, Ukraine
GRAPHICAL ABSTRACT
Abstract Pyridinium perchlorate is found to be an efficient and recyclable catalyst for the
=
reaction of trialkyl phosphites with various C X electrophiles (aldehydes, ketones, keto-
phosphonates, imines, isocyanates, isothiocyanates, activated alkenes) to afford corre-
sponding a-substituted phosphonates in good yields. The main advantages of the new
catalyst is strong activity, accessibility, good yields of products, and gentle conditions of
reaction.
Keywords a-Aminophosphonates; bisphosphonates; catalysis; a-hydroxyphosphonates;
pyridinium perchlorate
INTRODUCTION
Synthesis of functionalized phosphonates has attracted great attention because
of their biological activity.[1–3] They act as peptide mimics, haptenes of catalytic anti-
bodies, antibiotics and pharmaceuticals, herbicides, and enzyme inhibitors.[4] There
are two main pathways for the synthesis of a-functionalized phosphonates: the reac-
=
tion of dialkyl phosphites with nonsaturated electrophiles C X in the presence of
Brønsted bases or Lewis acids (Abramov reaction,[5,6] Kabachnik–Fields reac-
tion,[7,8] and Pudovik reaction[9,10]) and the reaction of trialkyl phosphites with alde-
hydes or imines in the presence of Lewis acids.[7,11] However, in spite of their
potential utility, these methods typically suffer from one or more disadvantages such
as poor activity of dialkyl phosphites to ketones and ketimines. The reactions
Received November 3, 2010.
Address correspondence to Oleg I. Kolodiazhnyi, Institute of Bioorganic Chemistry and Petrol
Chemistry, National Academy of Sciences, Murmanska 1, Kyiv 02094, Ukraine. E-mail: olegkol321@
rambler.ru
1637

1638
O. I. KOLODIAZHNYI AND O. O. KOLODIAZHNA
proceed with formation of various impurities formed under the effect of alkaline
catalysts (phosphonate-phosphatic rearrangement,[11] retro-Abramov reaction,[12]
and others). Besides, Lewis acids used as catalysts are moisture sensitive and require
specialized handling and tedious workup.
RESULTS AND DISCUSSION
In the present article, we propose the pyridinium perchlorate as a new, efficient,
=
=
and universal catalyst for the phosphonylation of C X electrophiles (X O, S, NR,
CR2), by trialkyl phosphites (Scheme 1, Table 1). To our knowledge, this is the first
case when ammonium or pyridinium salt catalyzes the reaction of trialkyl phosphites
with electrophiles.[13]
In all cases, the reactions proceeded smoothly under solvent-free conditions or
in a methylene chloride solution at room temperature to afford a-substituted phos-
phonates without undesired side products.[14] The pyridinium perchlorate increases
the rate of reaction; however, it is not consumed by the reaction itself. It can be iso-
lated from a reaction mixture and reused, and no significant decrease in its activity
was noticed.
We have recently reported that pyridinium halogenides ([C5H5NH]þHlgꢀ,
=
Hlg ¼ I, Br, Cl) activate the reaction of trialkyl phosphites with C X electro-
philes.[15] However the pyridinium halogenides are reagents, because they are con-
sumed in the course of reaction, whereas the pyridinium perchlorate is a catalyst.
Scheme 2 explains the catalytic action of pyridinium perchlorate.
The nucleophilic attack of triethyl phosphite on the electron-deficient carbon
=
of C X group leads to the formation of betaine A, which reacts with pyridinium per-
chlorate to afford the alkoxyphosphonium perchlorate C and pyridine. Salt C is
unstable and decomposes with the formation of phosphonate D, alkene, and per-
chloric acid, which reacts with pyridine to regenerate the pyridinium perchlorate.
The quasiphosphonium intermediate B forming from pyridinium halogenides
decomposes with formation of EtHlg. The pyridinium perchlorate more actively
=
Scheme 1. Phosphonylation of C X electrophiles.
Table 1. Effect of anion nature in pyridinium salts on the reaction of triethylphosphite with cyclohexa-
none
[C5H5NH]þXꢀ
X
Cl
X
Br
X
I
ClO4
5
=
=
=
6
=
X
Reaction time (h)
Temperature (ꢁC)
Yield (%)
12
35
55
12
35
70
25
85
25
92

NEW CATALYST FOR PHOSPHONYLATION
1639
Scheme 2. Possible mechanism of catalysis by pyridinium perchlorate.
=
initiates the reaction of trialkylphosphites with C X electrophiles than pyridinium
halogenides. Utilization of pyridinium perchlorate instead of pyridinium halogenides
considerably increases the reaction rate and increases yields (Table 1).
Pyridinium perchlorate can be easily prepared by reaction of pyridine with per-
chloric acid in a water solution. It is poorly soluble in water and can be easily filtered
off as crystalline matter. After drying in a vacuum exsiccator, the pyridinium per-
chlorate is ready for utilization.
We give some typical examples of syntheses demonstrating the high effective-
ness of pyridinium perchlorate as catalyst for the reaction of trialkylphosphites with
=
C X electrophiles (Scheme 3). Highly active catalysts allows to phosphonylate some
low-active electrophiles, which are impossible to convert into phosphonates by
known methods. The results are summarized in Table 2.
A number of aldehydes, including aromatic, aliphatic, and unsaturated alde-
hydes, underwent reactions with trialkyl phosphites in the presence of pyridinium
perchlorate to afford the corresponding a-hydroxy-phosphonates 1–7 in good yields.
The reaction is exothermic and should be performed at cooling to 0 ꢁC or below. The
formation of undesired side products was not observed. Only an insignificant
=
Scheme 3. Reaction of C X electrophiles with (RO)3P catalyzed by pyridinium perchlorate.

1640
O. I. KOLODIAZHNYI AND O. O. KOLODIAZHNA
þ
1
2
3
ꢀ
Table 2 Reaction conditions: (R O)3P þR R C X þ ½C5H5NHꢂ ClO4 ! ðR1OÞ2PðOÞCðXHÞR2R3
=
Compound R1
R2
R3
X
Temp. (ꢁC) Time (h) Yield (%)a
1
2
Et
H
O
0–20
0–20
2
2
88
89
Me
H
H
O
O
3b
Me
0 ꢀ 20
2
85
4
5
Et
Et
H
H
O
O
0–20
0–20
4
4
90
90
6
7
Et
Et
H
H
O
O
0–20
0–20
2
2
90
90
8
9
Et
Et
Et
3-F3CC6H4
4-t-BuC6H4
3,4-(MeO)2C6H3
Me
Me
Et
O
O
O
25
25
50
6
12
12
80
70
80
10
11
Et
O
25
4
85
12
13
Et
Et
O
O
25
25
4
85
70
(EtO)2P(O)
(EtO)2P(O)
H
10
14
15
Et
Et
O
25
30
6
75
60
PhN
12
16
17
18
19
Me
Et
Ph
Ph
H
H
BnN
CHNO2
28
12
6
71
65
90
80
0–20
0–20
0–20
=
C
Et
Et
PrN
O
S
2
=
CH2 ¼ CHCH2N
C
2
aYields of purified products are shown.
b4:1 mixture of diastereoisomers as calculated from the 1H and 31P NMR (dP 23.03; 22.02 ppm) spectra
of the crude product.
impurity of dialkyl phosphites is formed in some cases; however, it can be removed
easily under vacuum to provide spectroscopically pure hydroxyphosphonates 1–7.
The pyridinium perchlotate initiates the reaction of triethyl phosphite with ketones,

NEW CATALYST FOR PHOSPHONYLATION
1641
Scheme 4. Synthesis of bisphosphonate (S)-14.
which normally produces poor yields of hydroxyphosphonates in the reaction with
dialkyl phosphites because of their intrinsic lower reactivity. Because of the high
catalytic activity of pyridinium perchlorate, the reaction of trialkyl phosphites with
ketones proceeded under gentle conditions in good yields of corresponding hydroxy-
phosphonates 8–14.
In the presence of pyridinium perchlorate, ketophosphonates react readily with
trialkyl phosphites in methylene chloride at room temperature or at cooling to 0 ꢁC
with formation of 1-hydroxy-1,1-bis-phosphonates 13 and 14.[15,16] The reaction
is completed during several hours to afford in good yields the hydroxy-
bisphosphonates 13 and 14, bearing terpene or aminoacid residues. For example,
the chiral bisphosphonate (S)-14 was prepared starting from chloride N-Moc-L-
proline 20 (Scheme 4).
The chloride N-Moc-L-proline 20 reacts easily with triethyl phosphite to fur-
nish the chiral ketophosphonate (S)-21, which was purified by vacuum distillation
and then converted in good yield into bisphosphonates (S)-14 by reaction with
triethyl phosphite in the presence of pyridinium perchlorate.
The reaction of ðEtOÞ3P=½PyHꢂþClOꢀ4 with imines leads to the formation of
aminophosphonates 15 and 16 under soft conditions (Table 2).[17] The reaction pro-
ceeds at 0 ꢁC, more easily than the Kabachnik–Fields reaction of benzylbenzaldimine
with diethyl phosphite, wþhich ends only by heating to 140 ꢁC for several hours.
The ðEtOÞ3P=½PyHꢂ ClOꢀ4 phosphonylates also ketimines, which are hard to
reach by other methods (Table 2).[18]
Pyridinium perchlorate initiates the reaction of nitrostyrene with trialkyl
phosphites in methylene chloride solution at 0 ꢁC to afford the b-nitro-a-phenyl-
ethylphosphonates 17 in gooþd yields.[19]
In the presence of ½PyHꢂ ClOꢀ4 , triethyl phosphite phosphonylate readily isocya-
nates and isothiocyanates at 0 ꢁC in a solution of methylene chloride to convert them
into carbamoylphosphonate 18[6] or thiacarbamoylphosphonate 19 in good yields.
CONCLUSION
In summary, pyridinium perchlorate is a new and efficient catalyst for the reac-
=
tion of trialkyl phosphites with C X electrophiles. Utilization of pyridinium per-
chlorate allows phosphonylation of aldehydes, ketones, aldimines, ketimines,
ketophosphonates, and certain alkenes with formation of functionalized phospho-
nates. Pyridinium perchlorate is stable, easy to handle, recoverable by simple

1642
O. I. KOLODIAZHNYI AND O. O. KOLODIAZHNA
filtration, and recyclable. The advantages of this procedure are operational sim-
plicity, wide substrate scope, and good yields of products. In many cases, pyridinium
perchlorate allows us to obtain functionalized phosphonates, which are impossible to
prepare by known methods. We believe that the method utilizing pyridinium per-
chlorate presents a practical alternative to existing procedures for the synthesis of
a-functionalized phosphonates.
EXPERIMENTAL
1H, 19 F, and 31P NMR spectra were obtained on a Varian VXR-300 spec-
trometer at 300, 198, and 81 MHz, respectively. 1H, 13C, and 31P NMR spectra were
recorded on a Bruker DRX-500 Avance Spectrometer at 500.1, 125.8, and
202.45 MHz, respectively. Thin-layer chromatography (TLC) was performed on
aluminum-backed silica-gel TLC plates (250-mm layer) with ultraviolet visualiza-
tion. All solvents were purified using standard methods; diethyl phosphite, dimethyl
phosphite, aldehydes, ketones, amines, and aniline were purchased from Aldrich or
Acros Organics and used without further purification.
=
Addition of Trialkyl Phosphites to C X Compounds Under
Solvent-Free Conditions (General Procedure)
=
Pyridinium perchlorate (ꢃ0.005 mol) was added to a mixture of C X com-
pounds (0.01 mol) and trialkyl phosphite (0.01 mol) at cooling to 0 ꢁC, and the mix-
ture was stirred for the indicated time as shown in Table 1. Then the reaction mixture
was dissolved in methylene chloride or diethyl ether and filtered to give ꢃ0.0049 mol
of used catalyst. The solvent was removed under reduced pressure. The residue was
used without special purification or distilled under vacuum, crystallized, or chroma-
tographed on a column with silica gel.
=
Addition of Trialkyl Phosphites to C X Compounds in Solvent
(General Procedure)
=
Pyridinium perchlorate (ꢃ0.005 mol) was added to a solution of C X com-
pound (0.01 mol) and trialkyl phosphite (0.01 mol) at 0 ꢁC, and the reaction mixture
was stirred for the indicated time and temperature as shown in Table 1. Then the
mixture was filtered, evaporated, and diluted with diethyl ether to give after filtration
ꢃ0.0049 mol of used catalyst. The solvent was evaporated under reduced pressure,
and the residue was purified by distillation under vacuum, crystallized, or chromato-
graphed on a column with silica gel.
Recyclability of Catalyst
The pyridinium perchlorate used in the experiment was washed with diethyl
ether and dried under vacuum. Then the recovered pyridinium perchlorate
(ꢃ0.005 mol) was added to the mixture of triethyl phosphite (0.01 mol) and benzal-
dehyde (0.01 mole) at cooling to 0 ꢁC, and the reaction mixture was stirred ꢃ2 h at
room temperature. The catalyst was separated, and the residue was distilled under

NEW CATALYST FOR PHOSPHONYLATION
1643
vacuum to give the phosphonate 1 in 85% yield, bp 160 ꢁC (0.05 mmHg), mp 83 ꢁC.
White solid.
1H NMR (300 MHz, CDCl3): d ¼ 1.14–1.27 (m, 6H), 3.94–4.08 (m, 4H), 5.00 (d,
J ¼ 11.0 Hz, 1H), 7.25–7.37 (m, 3H), 7.46–7.49 (m, 2H). 13C NMR (125.74 MHz,
CDCl3): d ¼ 16.40, 28.50, 33.01, 35.10, 62.00 (d, J ¼ 8); 64.05 (d, J ¼ 160). 31P
NMR (80.95 MHz, CDCl3): d ¼ 21.69.
Analogously, the reaction of triethyl phosphite with cyclohexanone in the pres-
ence of recycled pyridinium perchlorate afforded the phosphonate 11.
Yield 85%, bp 120 ꢁC (0.08 mmHg), mp 61–63 ꢁC.[15] 1H NMR (500 MHz,
CDCl3): d ¼ 1.30 (t, 6H, J ¼ 7.2, CH3CH2), 1.52 (m, 2H, CH2), 1.66 (m, 4H,
CH2), 1.87 (m, 4H, CH2), 3.60 (br, 1H, OH), 4.16 (dq, 4H, J ¼ 7, J ¼ 8, OCH2).
13C NMR (125.74 MHz, CDCl3): d ¼ 16.45 (d, J ¼ 6.25), 20.20 (d, J ¼ 11.5), 25.37;
31.51 (d, J ¼ 2.5, CH2), 62.51 (d, J ¼ 7.5, OCH2), 70.95 (d, J ¼ 147.5, PC). 31P
NMR (80.95 MHz, CDCl3): d 26.9.
Diethyl 1-Hydroxy N-tert-Butoxycarbonyl-3-aminopropyl-
Phosphonate (1)
1
Colorless oil, bp 160 ꢁC (0.008 mmHg). H NMR (500 MHz, CDCl3): d ¼ 1.34
(t, 6H, J ¼ 7 Hz, CH3), 1.44 [s, 9H, (CH3)3C], 1.89 (m, 2H, CH2), 3.23 (m, 1H,
NCH2), 3.46 (m, 1H, NCH2), 3.96 (m, 1H, PCH), 4.18 (m, OCH2), 5.1 (br, 1H,
OH). 13C NMR (125.74 MHz, CDCl3): d ¼ 16.4, 28.5, 33, 35, 62 (d, J ¼ 8 Hz); 64
(d, J ¼ 160 Hz). 31P NMR (80.95 MHz, CDCl3): d ¼ 25.7. Anal. calcd. for
C12H26NO6P: N, 4.50, P 9.95. Found: N 4.55, P 9.81.
Dimethyl (1,3-Benzodioxol-5-yl)-hydroxymethylphosphonic Acid (2)
Colorless solid, mp 91 ꢁC (CHCl3=hexane). 1H NMR (300 MHz, CDCl3):
d ¼ 3.7 (d, J ¼ 15 Hz, CH3O), 5.36 (d, J ¼ 10 Hz, HCH), 5.91 (s, 3H, CH2O2),
7.2–7.4 (m, C6H3). 13C NMR (125.74 MHz, CDCl3): d ¼ 53 (d, J ¼ 28 Hz), 70 (d,
165 Hz), 101.1, 107.9 (d, J ¼ 21 Hz), 120, 130, 147.48, 147.68. 31P NMR
(80.95 MHz, CDCl3): dP ¼ 28. Calcd. for C10H13O6P: C, 46.16; H, 5.04. Found: C,
46.34; H, 5.21.
Dimethyl (S,R)-2-N-Boc-pyrolidine(hydroxy)methyl-phosphonate
(3)[16]
To 0.01 mol of trimethyl phosphite at ꢀ10 ꢁC were added 0.01 mol of N-Boc-
prolynale and 0.01 mol of pyridinium bromide. The reaction mixture was stirred
5 h at ꢀ10 ꢁC, 2 h at 0 ꢁC, and 1 h at rt. The reaction mixture was diluted with diethyl
ether and filtered, and the residue was evaporated. Yield 95%, mixture of (S,R) and
(S,S)-diastereomeres in ratio of 4:1. 31P NMR (CDCl3), d, ppm 26.9 and 26.3. The
product was purified by column chromatography on silica gel (EtOAc–hexane, 1:3),
recrystallized in a ꢀ20 ꢁC mixture of chloroform–hexane and then in hexane and
resulted in pure (S,R)-diastereomer.
1
Mp 79 ꢁC, [a]D ꢀ 60 (c 2, CHCl3). H NMR (300 MHz, CDCl3): d ¼ 1.42 (s,
9H), 1.8–2.3 (m, 4H), 3.2 (m, 1H), 3.7–3.8 (m, 2H), 3.7 (d, 6H, J ¼ 10 Hz), 4.1 (m,

1644
O. I. KOLODIAZHNYI AND O. O. KOLODIAZHNA
1H). 13C NMR (125.74 MHz, CDCl3): d ¼ 24.5, 28.5, 28.8, 47.5, 53.0 (d, J ¼ 6.9),
59.0, 73.5 (d, J ¼ 158.8), 81.5, 159. 31P NMR (80.95 MHz, CDCl3): dP ¼ 26.9.
Diethyl Hydroxy[6-methyl-4-(4-methylpent-3-enyl)cyclohex-3-en-1-
yl]methyl-Phosphonate (4)
Yield 80%. The product was purified by column chromatography on silica gel
(EtOAc–hexane, 1:3) to afford the desired phosphonate. Colorless oil, bp 180 ꢁC
1
(0.08 mmHg). H NMR (500 MHz, CDCl3): d ¼ 0.99 (d, 3H, J ¼ 6 Hz), 1.33 (t, 6H
J ¼ 7 Hz), 1.6 (s, 3H), 1.87 (s 3H), 1.91–2.22 (m, 10H), 3.51 (br, 1H), 4.17 (m, 5H,
J ¼ 7 Hz, J ¼ 8 Hz), 6.28 (s, 1H), 5.32 (m, 2H). 13C NMR (125.74 MHz, CDCl3):
d ¼ 8.87, 16.28, 17.3, 25.4, 25.78, 27.01, 27.08, 29.96, 32.15, 33.69 (d, J ¼ 150 Hz),
42.8, 61.81 (d, J ¼ 6 Hz), 120.6, 123.9, 130.8, 135.59. 31P NMR (80.95 MHz, CDCl3:
dP ¼ 26.6. Anal. calcd. for C18H33O4P: C, 62.77; H, 9.66; P, 8.99. Found: C, 62.58; H,
9.55; P, 8.80.
Diethyl Hydroxy(3,8,8-trimethyl-1,2,3,4,5,6,7,8-octahydro-
naphthalene-2-yl) Methylphosphonate (5)
Yield 80%, colorless solid, bp 190 ꢁC (0.1 mmHg), mp 107–110 ꢁC (hexane).
1H NMR (500 MHz, CDCl3): d ¼ 0.957 (d, 3H, J 6), 0.975 (s, 6H), 1.34 (t, 6H,
J ¼ 7 Hz), 1.43 (m, 2H), 1.6 (m, 4H), 1.8 (m, 2H), 1.9 (m, 1H), 2.0 (m, 1H), 2.19
(m, 2H), 2.91 (br, 1H), 4.2 (m, 5H). 13C NMR (125.74 MHz, CDCl3): d ¼ 16.4,
19.27, 19.99, 24.87, 27.02, 27.07, 28.1, 28.97, 32.89, 33.73, 39.5, 48.9, 62.17 (d,
J ¼ 6 Hz), 62.17, 70.88 (d, J ¼ 160 Hz), 127.2, 133.61. 31P NMR (80.95 MHz,
CDCl3): d ¼ 25.63. Anal. calcd. for C18H33O4P: C, 62.77; H, 9.66; P, 8.99. Found:
C, 62.53; H, 9.54; P, 9.19.
Diethyl (2E)-1-Hydroxy-3,7-dimethyl-2,6-octadienyl-phosphonate (6)
1
Yield 80%, bp 135 ꢁC (0.08 mm Hg). H NMR (300 MHz, CDCl3): d ¼ 1.28
(t, JHH ¼ 7 Hz), 1.29 (t, JHH ¼ 7 Hz), 1.61 (s, 3H), 1.69 (s, 3H); 2.1 (br, 4H), 4.12
(m, 4H), 4.52 (dd, 1H, JHH ¼ 9 Hz, JHP ¼ 9 Hz), 5.12 (br, 1H), 5.36 (br, 1H). 13C
NMR (125.74 MHz, CDCl3): d ¼ 16.4, 17.0, 17.6, 25.60, 26.7, 37.90, 37.9, 61.7,
61.8, 65.1, 66.1, 119.1, 124.0, 131.7, 138.8. 31P NMR (80.95 MHz, CDCl3):
d ¼ 24.19. Anal. calcd. for C14H27O4P: C, 57.92; H, 9.37. Found: C, 57.99;
H, 9.49.
Diethyl (SP,R/RP,R)-(6E)-1-Hydroxy-3,7-dimethyl-2,6-octenyl-
phosphonate (7)
Yield 80%, bp 145–150 ꢁC (0.08 mmHg). Mixture of (SpR=RpR)-diastereomers.
1H NMR (300 MHz, CDCl3), d ¼ 0.96 (d, 3H, J ¼ 7 Hz), 1.29 (t, 3H, J ¼ 7 Hz), 1.30
(t, 3H, J ¼ 7 Hz), 1.58 (s, 3H), 1.65 (s, 3H), 1.83 (m, 2H), 1.96 (m, 2H), 3.82 (m, 1H),
4.09 (m, 4H), 5.07 (t, 1H, J ¼ 7 Hz), 5.7 (br, 1H). 13C NMR (125.74 MHz, CDCl3):
(SpR) d ¼ 16.45, 16.49, 17.6, 20.25, 25.19, 25.52, 25.65, 28.30 d (J ¼ 12 Hz), 35.75,
38.11, 62.51 d (J ¼ 7.5 Hz), 62.64 d (J ¼ 6 Hz), 65.59 d (J ¼ 158 Hz), 124.70, 131.09;

NEW CATALYST FOR PHOSPHONYLATION
1645
(RpR) d ¼ 16.45, 16.49, 18.35, 20.25, 25.19, 25.52, 25.65, 29.0 (d, J ¼ 12 Hz), 37.80,
38.56, 62.51 (d, J ¼ 7.5 Hz), 62.64 (d, J 6 Hz), 66.06 (d, J ¼ 157 Hz), 124.72,
131.13. 31P NMR (202.45 MHz, CDCl3): d ¼ 26.50, 26.54. Anal. calcd. for
C14H29O4P: P, 10.59. Found: P, 10.69.
Diethyl 1-Hydroxy-1-(3-trifluoromethylphenyl)ethylphosphonate (8)
Yield 80%. Purified by crystallization in hexane. Colorless crystalline, mp
1
125–128 ꢁC. H NMR (500 MHz, CDCl3): d ¼ 1.24 (t, 6H, J ¼ 7 Hz), 1.83 (d, 3H,
J ¼ 15.6 Hz), 4.04 (m, 2H), 4.12 (m, 2H), 4.66 (br, 1H), 7.44–7.9 (m, 4H). 13C
NMR (125.74 MHz, CDCl3): d ¼ 16.17, 26.33, 63.5 (d, J ¼ 94 Hz), 73.5 (d,
J ¼ 161 Hz), 127 (q, J ¼ 271 Hz), 123.1, 123.88, 128.16, 130.01, 130.27, 143.00. 19 F
NMR (196 MHz, CDCl3): d ¼ ꢀ57.67. 31P NMR (202.45 MHz, CDCl3): dP ¼ 25.3
(d, J ¼ 8 Hz). Anal. calcd. for C13H18F3O4P: C, 47.86; H, 5.56; P, 9.49. Found: C,
47.55; H, 5.50; P, 9.65.
Diethyl 1-Hydroxy-1-(4-tert-butylphenyl)ethylphosphonate (9)
1
Yield 80%. Colorless crystalline, mp 84–86 ꢁC (hexane). H NMR (500 MHz,
CDCl3): d ¼ 1.15 (t, 3H, J ¼ 7 Hz) 1.17 (t, 3H, CH3 J ¼ 7 Hz), 1.24 (s, 9H), 1.8 (d,
J ¼ 14.5 Hz), 3.93 (m, 2H, OCH2), 4.07 (m, 2H, OCH2), 7.3–7.5 (m, 4H, C6H4).
13C NMR (125.74 MHz, CDCl3): d ¼ 16.35, 25.83, 31.34, 34.44, 63.26 (d, J ¼ 16 Hz);
73.4 (d, J ¼ 158 Hz), 124.9, 125.55 (d, J ¼ 4 Hz), 137.88, 150.24. 31P NMR
(80.95 MHz, CDCl3): d ¼ 26.0. Anal. calcd. for C16H27O4P: C, 61.13; H, 8.66; P,
9.85. Found: C, 61.01; H, 8.75; P, 9.65.
Diethyl [1-(3,4-Dimethoxyphenyl)-1-hydroxypropyl]phosphonate (10)
Purified by column chromatography on silica gel (EtOAc–hexane 1:3). Color-
less oil, Rf 0.33. Yield 60%. 1H NMR (300 MHz, CDCl3): d ¼ 0.77 (t, 3H,
J ¼ 7.2 Hz), 1.15 (t, 3H, J ¼ 7 Hz), 1.27 (t, 3H, J ¼ 7 Hz), 2.13 (dq, 1H, J ¼ 7 Hz,
J ¼ 8 Hz), 2.24 (dq, 1H, J ¼ 7 Hz, J ¼ 8 Hz), 3.87 (s, 3H), 3.89 (s, 3H), 4.1 (m, 4H);
6.9–7.5 (m, 3H). 13C NMR (125.74 MHz, CDCl3): d ¼ 9.09, 16.45, 27.82, 55.97,
62.35, 71.93, 72.94, 114.35, 116.59, 123.85, 125.3, 150.31, 151.02. 31P NMR
(80.95 MHz, CDCl3): d ¼ 24.3. Anal. calcd. for C15H25O6P: C, 54.21; H, 7.58%.
Found: C, 54.16; H, 7.54%.
Diethyl 1-Hydroxycyclohexylphosphonate (11)
Yield 80%, bp 120 ꢁC (0.1 mmHg), mp 71–73 ꢁC (hexane). 1H NMR (300 MHz,
CDCl3): d ¼ 1.3 (t, 6H, J 7.2 Hz), 1.52 (m, 2H), 1.66 (m, 4H), 1.87 (m, 4H), 3.6 (br,
1H), 4.16 (dq, 4H, J 7 Hz, J 8 Hz). 13C NMR (125.74 MHz, CDCl3): d ¼ 16.45 (d, J
6.25 Hz), 20.22 (d, J 11.5 Hz), 25.37; 31.5 (d, J 2.5 Hz), 62.5 (d, J 7.5 Hz), 70.95 (d, J
147.5 Hz). 31P NMR (80.95 MHz, CDCl3): dP ¼ 26.93. Anal. calcd. for C10H21O4P:
C, 50.84; H, 8.96; P, 13.11. Found: C, 50.62; H, 8.91; P, 13.09.

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O. I. KOLODIAZHNYI AND O. O. KOLODIAZHNA
Diethyl 4-Hydroxy(tetrahydro-2,2-dimethyl-2H-pyran-4-yl)
phosphonate (12)
1
Yield 80%, bp 130–135 ꢁC (0.08 mmHg), mp 72–75 ꢁC. H NMR (300 MHz,
CDCl3): d ¼ 1.19 (s, 3H), 1.43 (s, 3H), 1.64–19 (m, 4H), 3.65 (m, 2H), 3.95 (br, 1H),
3.65 (m, 1H), 4.05 (m, 1H), 4.15 (dq, 4H, J ¼ 7 Hz, J ¼ 8 Hz). 13C NMR
(125.74 MHz, CDCl3): d ¼ 16.45, 24.29, 31.909, 32.61, 39.87, 56.1 (d, J ¼ 12.5); 62.8
(d, J ¼ 8.5 Hz), 63.0 (d, J ¼ 7.5 Hz), 70 (d, J ¼ 183.5 Hz), 70.57. 31P NMR
(80.95 MHz, CDCl3): dP ¼ 23.6. Anal. calcd. for C11H23O5P: P, 11.63. Found: P, 11.63.
Tetraethyl (E)-1-Hydroxy-3,7-dimethylocta-2,6-diene-1,1-
diyldiphosphonate (13)[20]
The product was purified by column chromatography on silica gel (EtOAc–
hexane, 50:50) to afford the desired phosphonate. Yield 65%, oil. 1H NMR
(300 MHz, CDCl3): d ¼ 1.27 (t, 6H, J 7 Hz), 1.28 (t, 6H, J 7 Hz), 1.6 (s, 3H), 1.63
(s, 3H), 1.8 (d, 3H, JHH 8 Hz), 2.0 (m, 4H), 4.21 (m, 8H), 4.8 (m, 1H), 5.1 (t, 1H,
JHH 7 Hz). 13C NMR (125.74 MHz, CDCl3): d ¼ 16.21, 16.41, 17.59, 17.81, 25.61,
26.87, 36.9, 60.93, 64.53, 67.83, 71.13, 115.5, 124.03, 131.67, 139.77. 31P NMR
(80.95 MHz, CDCl3): d ¼ 23.3. Anal. calcd. for C18H36O7P2: C, 50.70; H, 8.51; P,
14.53. Found: C, 50.45; H, 8.41; P, 14.40.
Bis(diethoxyphosphinyl)hydroxymethyl-N-(methoxycarbonyl)-1-
pyrrolidine (14)
1
20
Rf 0.15 (EtAc=MeOH=C6H12 ¼ 1:1:1). ½aꢂD ꢀ 59 (c 3.5, CHCl3). H NMR
(500 MHz, CDCl3): d ¼ 1.37 (m, 12H), 1.68 (m, 1H), 1.91 (m, 1H), 2.37 and 2.65
(m, 2H, CH2), 3.39 (m, 2H), 3.75 (s, 3H), 4.3 (m, 8H); 4.4 (m, 1H). 13C NMR
(125.74 MHz, CDCl3): d ¼ 16.3, 23.63, 29.50, 47.69, 53.18, 63.07, 63.23, 63.29,
63.50, 64.05 (t, J 62, CHN), 79.3 (t, J 153), 159.4. MS APCI, m=z (M þ 1): 432.3
(calcd. M 431.3). 31P-(1H) NMR (202.45 MHz, CDCl3), d ¼ 21.72, 21.57, 20.94,
20.80 (rotamers and magnetic nonequivalence).
Dimethyl Phenyl[1-methyl[(benzyl)amino]methylphosphonate (15)[18]
1
Yield 70%, mp 60 ꢁC. H NMR (300 MHz, CDCl3): d ¼ 1.4 (d, 3H, J ¼ 7 Hz),
3.51 (m, 1H, NH), 3.79 (d, 3H, J ¼ 11.8 Hz), 3.83 (d, 3H, J ¼ 10.1 Hz), 5.2 (d, 1H,
J ¼ 24 Hz), 6.8–7.28 (m, 5H), 7.3 (d, 2H, J ¼ 8.5 Hz), 7.5 (d, J ¼ 8.5 Hz, 2H). 13C
NMR (125.74 MHz, CDCl3): d ¼ 16 (d, CH3), 56.1 (d, J ¼ 7.0 Hz), 56.2 (d, J ¼ 6.8 Hz),
57.2 (d, J ¼ 150 Hz), 114.3, 120.0, 128.2 (d, J ¼ 5.8 Hz), 128.4 (d, J ¼ 3.1 Hz), 130.1,
131.2, 140.0, 146.6 (d, J 14.5 Hz). 31P NMR (80.95 MHz, CDCl3): dP, 24. Anal. calcd.
for C17H22NO3P: C, 63.94; H, 6.94; N, 4.39. Found: C, 63.81; H, 6.92; N, 4.47.
Diethyl (2E)-1-Anilino-3,7-dimethylocta-2,6-dienylphosphonate (16)[19]
The product was purified by column chromatography on silica gel. Oil. Yield
50%. 1H NMR (300 MHz, CDCl3): d ¼ 1.27–1.17 (m, 6H), 1.49 (s, 3H), 1.54 (s, 3H),

NEW CATALYST FOR PHOSPHONYLATION
1647
1.61 (s, 3H), 1.72–1.71 (m, 2H), 2.06–1.97 (m, 2H), 3.97–4.15 (m, 4H), 4.38 (dd, 1H,
J ¼ 20.7 Hz, J ¼ 9.4 Hz), 4.95–5.12 (m, 2H), 6.54–7.13 (m, 5H). 13C NMR
(125.74 MHz, CDCl3): d ¼ 16.4, 16.5, 17.1, 17.7, 25.6, 26.2, 39.6, 50.6 (d,
J ¼ 158.5 Hz), 62.8 (d, J ¼ 7.3), 63.1 (d, J ¼ 6.6 Hz), 113.9, 118.4, 119.9, 123.6,
129.1, 131.8, 141.6, 146.8. 31P NMR (80.95 MHz, CDCl3): d ¼ 28.4. Anal. calcd.
for C20H32NO3P: N, 3.83; P, 8.48. Found: N, 3.72; P, 8.58.
Diethyl (2-Nitro-1-phenyl)ethylphosphonate (17)[20]
Yield 70%, mp 65 ꢁC (hexane). 13C NMR (125.74 MHz, CDCl3): d ¼ 16.2,
37.46, 37.94, 61.74, 78.35, 127.3, 128, 128.9, 133.7. 31P NMR (80.95 MHz, CDCl3):
d ¼ 28.0. Anal. calcd. for C12H18NO5P: N, 4.96; P, 10.71. Found: N, 4.88; P, 10.78.
Diethyl (Propylamino)carbonylphosphonate (18)
1
Yield 90%, Colorless oil, bp 100–110 ꢁC (0.08 mmHg). H NMR (300 MHz,
CDCl3): d ¼ 0.87 (t, 3H, J ¼ 7.5 Hz), 1.3 (t, 6H, J ¼ 7 Hz), 1.51 (m, 2H), 3.2 (q,
4H, J ¼ 7 Hz), 4.15 (m, 4H), 7.34 (br, 1H). 13C NMR (125.74 MHz, CDCl3):
d ¼ 11.2 (d, J ¼ 8), 16.15 (d, J ¼ 15 Hz), 22.6; 40.98, 64.15 (d, J ¼ 8 Hz); 165 (d,
J ¼ 221 Hz). 31P NMR (80.95 MHz, CDCl3): d ¼ ꢀ0.71. Anal. calcd. for
C8H18NO4P: N, 6.28; P, 13.88. Found: N, 6.40; P, 13.68.
Diethyl (Allylamino)thiocarbonylphosphonate (19)
1
Yellowish liquid. Yield 80%, bp 120 ꢁC (0.08 mmHg). H NMR (300 MHz,
CDCl3): d ¼ 1.36 (t, 6H, J 7), 4.08–4.3 (m, 6H); 5.27 (dd, 1H, J ¼ 6 Hz, J ¼ 1 Hz);
5.31 (dd, 1H, J ¼ 12.5 Hz, J ¼ 1 Hz), 5.91, ddt, 1H, J ¼ 17 Hz, J ¼ 10.2 Hz, J ¼ 6 Hz),
9.27 (br, 1H). 13C NMR (125.74 MHz, CDCl3): d ¼ 16.24 (d, J 10 Hz), 42.4 (d, J
9 Hz), 63 (d, J ¼ 6 Hz); 119, 130.7, 193 (d, J ¼ 155). 31P NMR (80.95 MHz, CDCl3):
d ¼ ꢀ1.7. Anal. calcd. for C8H16NO3PS: N, 5.90; P, 13.05. Found: N, 5.88; P,
13.37.
Diethyl N-(Methoxycarbonyl)-1-pyrrolidineketophosphonate (21)
To 0.02 mol of N-Moc-L-proline chloride 20 was added 0.04 mol of triethyl
phosphite at ꢀ20 ꢁC. Then the temperature was raised to room temperature, and
the reaction mixture was left for 2 h. After that the mixture was distilled under vac-
uum. Yield 85%, bp 140 ꢁC (0.08 mmHg). Colorless liquid. ½aD ꢀ 44 (c 2, CHCl3).
20
1H NMR (500 MHz, CDCl3): d ¼ 1.37 (m, 6H), 1.9 (m, 2H), 2.2 (m, 2H); 2.2 (m, 2H),
3.59 s, 3.71 s (3H, CH2), 4.24 m (3H, OCH2), 4.81 m, 4.87 m (1H, CHN). 13C NMR
(125.74 MHz, CDCl3): d ¼ 17.8, 28.89, 29.31, 29.53, 30.63, 46.39, 46.90, 52.21, 52.27,
63.30, 63.35, 63.55, 63.61, 154.25, 155.04, 208.8 (d, J 157.5 Hz), 208.6 (d, J 160 Hz).
31P NMR (202.45 MHz, CDCl3): dP ¼ ꢀ2.98 and ꢀ2.78 (rotamers). Anal. calcd. for
C11H20NO6P: N, 4.78; P, 10.56. Found: N, 4.61; P, 10.67.

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O. I. KOLODIAZHNYI AND O. O. KOLODIAZHNA
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